|
Robert Harrington is owner of
the company PED-O-JET, maker of the military jet guns used on the troops. During
a meeting with the FDA, VA and others, he states the jet injectors are safe,
because the gun was wiped off after each injection.
Quote
MR. HARRINGTON:
Not necessarily. It was used by the Army for 35 years and it was always wiped.
Never had an issue. Good tracking system. And there's nothing recorded in the
world that says that it wasn't wiped. It's in a study that was presented using
a method that isn't approved, it was not wiped and it said oh, we can
contaminate 31 out of 100.
This
is supporting evidence- If the jet gun was not wiped off
before it's use on you, add it to your claim.
www.fda.gov/ohrms/dockets/ac/99/transcpt/3527t1.rtf
SHDEPARTMENT OF HEALTH AND HUMAN
SERVICES
PUBLIC HEALTH ADMINISTRATION,
FOOD AND DRUG ADMINISTRATION
GENERAL HOSPITAL & PERSONAL USE
DEVICES PANEL
OPEN SESSION
Monday, August 2, 1999
8:43 a.m.
Food and Drug Administration
9200 Corporate Boulevard, Room
020B
Rockville, Maryland
C O N T E N T S
PAGE
Welcome and Introductory Remarks
Martha T. O'Lone, Executive Secretary
4
Dr. Charles E. Edmiston, Chairman
6
Post-Market Surveillance
Larry Kessler
8
Y2K Information
Charles Ho
17
Issue: Guidance for Review of Protected Sharps
Systems
FDA Presentation
Tim Ulatowski, Director DDIGD -
23
Overview
Irene Naveau, Reviewer, Sharps
26
Injury Prevention Guidance
Lireka P. Joseph, Director OHIP
36
Presentations by Users of Protected Sharps
Systems
Dr. June Fisher - Trauma Foundation,
41
San Francisco General Hospital
Toni Hughes, AORN
55
Mary Alexander, INS
57
Susan Wilburn, ANA
61
Open Public Hearing
73
Panel Discussion/Recommendation
84
Afternoon Session
141
Issue: Guidance Development for Jet Infectors
FDA Presentation
Tim Ulatowski, Director DIDGD
142
Capt. Von Nakayama, Reviewer
145
CDC Presentation
Dr. Bruce Weniger
153
Presentation by Industry
Glenn Austin, PATH
173
Bob Harrington, ANFIM
186
Open Public Hearing
203
Open Committee Discussion/Panel Summary
210
and Recommendations
P R O C E E D I N G S
WELCOME AND INTRODUCTORY REMARKS
MS. O'LONE: Good morning. Welcome to
the General Hospital and Personal Use Devices Panel for the open session. Thank
you for coming. If you have not signed in for this meeting, please do so.
I am Martha O'Lone, the executive
secretary of the General Hospital and Personal Use Devices Advisory Panel. And
before we have panel introductions and turn this portion of the meeting over to
the panel, I have two items of business that I have to read into the record.
The first is a conflict of interest
statement. It goes like this. The following announcement addresses conflict of
interest issues associated with this meeting and is made part of the record, to
preclude even the appearance of any impropriety. To determine if any conflict
existed, the agency reviewed the submitted agenda and all financial interests
were reported by the panel participants.
The conflict of interest statutes
prohibit special government employees from participating in matters that could
affect their or their employer's financial interests. However, the agency has
determined that participation of certain members and consultants, the need for
whose services out-weighs the potential conflict of interest involved, is in the
best interest of the government.
Full waivers have been granted for Dr.
William Rutala and Ms. Marcia Ryder for their interest in firms that could
potentially be affected by the panel's decisions. The waivers permit them to
participate in all matters before the panel. Copies of these waivers may be
obtained from the agency's Freedom of Information Office, Room 12A-15 of the
Parklawn Building.
In the event that the discussions involve
any other products or firms not already on the agenda for which an FDA
participant has a financial interest, the participant should excuse him or
herself from such involvement and their exclusion will be noted for the record.
With respect to all other participants,
we ask, in the interest of fairness, that all persons making statements or
presentations disclose any current or previous financial involvement with any
firm whose products they may wish to comment upon.
And the second item of business is
appointment to temporary voting status. Pursuant to the authority granted under
the Medical Devices Advisory Committee Charter dated October 27, 1990, as
amended on April 20, 1995 and October 10, 1997, I appoint the following person
as a voting member of the General Hospital and Personal Uses Devices Panel for
the duration of the panel meeting on August 2, 1999. In addition, the following
person will act as panel chair for August 2, 1999, and that's Charles E.
Edmiston, Ph.D.
For the record, this person is a special
government employee and is either a consultant to this panel or consultant or
voting member of another panel under the Medical Devices Advisory Committee. He
has undergone the customary conflict of interest review. He has reviewed the
material to be considered at this meeting. And it's signed David W. Feigal,
Jr., M.D., director, Center for Devices and Radiological Health on the 21st of
July 1999.
And the only other piece of business is
that the future tentative date of this panel would be potentially November 16
for this year. We don't have any other dates set aside at this time as
tentative dates. And to find out if we're having upcoming meetings, the phone
number of the hotline is 800/741-8138 and the code is 12520. That helps to get
right to the General Hospital Panel to determine if there are any new messages
on that line.
I'll now turn the meeting over to Dr.
Edmiston and we will begin the open session of the 34th General Hospital and
Personal Use Devices Panel meeting at this time. I'll introduce him. He is an
associate professor of surgery at the Medical College of Wisconsin and has been
a consultant to our panel for quite some time and thank you very much for acting
as chair today.
DR. EDMISTON: Thank you very much.
At this time I'd like the rest of the
panel members to introduce themselves, starting with my colleague on my right.
DR. FOWLER: Dr. Joe Fowler, a
dermatologist at the University of Louisville, Louisville, Kentucky.
MS. RYDER: Marcia Ryder. I'm a nurse
consultant in vascular access and a doctoral candidate at the University of
California at San Francisco in the Department of Physiological Nursing.
DR. RUTALA: Bill Rutala. I'm director
of hospital epidemiology, occupational health and safety at the University of
North Carolina Hospitals and professor in the School of Medicine.
MR. PALOMARES: Salvodore Palomares,
manager of regulatory affairs at ICU Medical.
MR. DACEY: Robert Dacey, consumer
representative from Boulder and Longmont, Colorado.
MR. ULATOWSKI: Tim Ulatowski, director
of Division of Dental, Infection Control and General Hospital Devices, FDA.
DR. EDMISTON: Thank you very much.
Now at this time I'd like to invite Mr.
Larry Kessler from the FDA to give us an update in postmarketing surveillance.
POST MARKET SURVEILLANCE
MR. KESSLER: Good morning. I want to
thank Dr. Edmiston and Martha O'Lone for having me here. Let me tell you how
this little presentation happened.
About two years ago Dr. Alper asked me,
as the director of the Office of Surveillance and Biometrics in the Center for
Devices and Radiological Health, to talk a little about postmarket surveillance
in front of a meeting of the entire panel chairs in this very room. At the end
of that meeting, the panel chairs asked that we give such presentations to all
the panels, to give you our perspective on postmarket surveillance, because you
will see postmarket surveillance issues from time to time, even in your
premarket review.
I'm going to give you our perspective on
how these relate to some of the work that we think you can play a very important
role in helping us with the FDA mission.
In the next 10 to 15 minutes I'll
describe a few methods of device postmarket evaluation at the Center, present
challenges in accomplishing postmarket evaluation, and describe the pivotal role
that advisory panels can play in postmarket evaluation of medical products.
This schematic is a fairly brief overview
of the way in which we generally perceive our overall role at FDA. From the
left-hand side of the chart here--this is a time chart basically--design
modification happened basically at industry and with the clinical community and
patients telling industry what new products they need, what clinical needs need
to be met.
FDA gets more and more involved as we
travel from design modification through testing and clinical testing to review.
On the right-hand side of the chart you'll see, under the postmarket evaluation
part of this, at least five different mechanisms we have at our disposal to help
evaluate and monitor products as they live and breathe on the market. We have
the Medical Device Reporting Program and two postmarket surveillance
authorities--Section 522 in the postapproval or PMA authority. I'll talk about
these three in some detail.
I won't today, because of time, talk
about our epidemiology program or the large field inspection force we have
running out of ORA with our contacts through the Office of Compliance, but they
are a very critical part of postmarket evaluation. I just won't get to talk
about them today.
While we're doing review and after we do
postmarket evaluation, the FDA should have constant contact with the clinical
community to find out what's going on and to communicate our findings and
problems, something we need to improve on. One of the ways in which we do
contact the clinical community is our contact with advisory panels, and I'll say
a little bit about how postmarket evaluation and advisory panel work should
meet.
Well, why bother with any of this at
all? Well, because there are a series of questions that we find often need to
be asked in the postmarket period. First and most obvious is long-term safety.
A number of products that reach the market do so on the basis of fairly modest
or short-term studies. Rather than wait for long-term studies to prove complete
safety or effectiveness, some products will make it to the market where we will
not have complete long-term data.
This may be particularly true in terms of
long-term implantables, where we would hesitate to wait, say, 10 years, which is
what we might want to see for certain kinds of implantable performance, and we
don't want to do clinical trials that last for 10 years, so we'll let something
on the market based on a shorter period of time data and then look at it later.
Other important questions come up often
in the postmarket period. For example, performance of device in community
practice. Often you will see products for review that are done in carefully
designed clinical trials but products then move to community practice and we
won't see the same effects and we will often see different patterns of adverse
events that you will see in the premarket review.
Sometimes effects of changes in user
setting are important in product evaluation. For example, a larger number of
products than ever before are leaving the hospital doors and winding up in
out-patient clinics and at the bedside at home. Some of those products need
professional training to be used properly and we get adverse events on a daily
basis that show serious injuries, illness and death from products that went from
the hospital to home either without adequate training or labeling or other kinds
of problems that can be sometimes avoided.
I'll talk for just a minute about the
Medical Device Reporting Program because a number of people who know a bit about
FDA and postmarket evaluation think MDR is where our postmarket evaluation
begins and ends, and that's not the case at all but it is one of our most
important programs.
Since 1984, manufacturers must by law
report deaths and serious injuries as well as malfunctions or near incidents to
FDA. Since 1990 with the Safe Medical Devices Act, all user facilities--every
hospital, nursing home, ambulance, surgi-center--must report deaths to the FDA
and serious injuries to manufacturers.
Unfortunately, the User Facility
Reporting Program in the country does not work nearly as well as it should. The
number of reports we get per year from manufacturers is roughly in the 80,000 to
100,000 range and only 5 percent of those reports of our total MDR system come
from user facilities.
Beginning about 1992 we were receiving
over 100,000 reports of adverse events each year. Information should include
device specifics--the event description, event date, patient
characteristics--with which we could see if there's a potential problem that
needs rectifying in the postmarket period. Unfortunately, reporting in the MDR
program is often very limited--limited information. It sometimes provides
critical signals to FDA but sometimes we miss things because the information is
poor.
Part of this comes from the unfortunate
litigious environment that we all practice in. Often we'll hear manufacturers
around this room tell you the reason our data are limited is when they call a
hospital after a hospital has told them that their device may be involved in a
death or serious injury, the hospital will say, "That's all I can tell you. My
lawyers tell me to give you no other information."
Part of this has to do with the vast
number of reports which are associated with use error, and hospitals are nervous
about reporting out of their facility problems where their users may not have
read the instructions, may not have followed the instructions so carefully or
chosen to use products in ways that the manufacturer did not initially intend.
But we do get a lot of mileage out of the
100,000 reports we get per year and here are some examples of things that
reflect adverse event reports and actions taken prompted by the MDR program,
related to products that involve this panel.
For example, we get directed inspections
of a manufacturer this year for blood leukocyte filters and hypotension and
released a public health advisory related to leukocyte filtration.
We've done product recalls in the past
few years. In fact, one explosion of an infusion pump puzzled one of our
analysts. We had outstanding collaboration from our Office of Science and
Technology staff, who looked into the problem with us, and eventually convinced
the manufacturer to do massive, 15,000 pump recall and reservicing.
In the recent past infusion pumps have
presented a lot of problems with free flow and we put out patient notifications
about this problem. This problem continues with a lot of pumps and we do all we
can to try to minimize the problems that we see in free flow with infusion
pumps, but it's a constant problem.
I want to talk for just a couple of
minutes about these two authorities because this is where you as panel members
can be most influential and helpful to the FDA.
Postmarket study authorities--there are
two of them that we can invoke. One is postmarket surveillance Section 522 and
the other is the Postapproval authority. Section 522 was originally mandated in
SMDA '90 and changed in FDAMA '97. And the changes were to reduce some of the
scope of the original 522 act.
Postapproval refers to PMA products only
and is also sometimes called condition of approval studies. Section 522 covers
only Class II or III products whose failure may present a public health
problem. The language in the statute is more specific but this is the basic
essence of that language.
We see both authorities as a complement
to the premarket role of the FDA and the role that you play.
The criteria that we use for postmarket
surveillance study in the requirements for manufacturers are whether we can
figure out what the critical public health question is, and it can result from
for-cause situations, new or expanded conditions of use or other reasons. We
have to consider whether other post-market strategies, such as the MDR program,
give us enough information without requiring manufacturers to do additional
study on their product in the postmarket period. And we have to consider
practicality and feasibility of the conduct of studies.
We also try to figure out how will the
data be used? And I'll come to that in just a minute.
Postmarket surveillance studies have a
wide variety of approaches. Our early foray into postmarket, earlier in this
decade, was heavily weighted toward studies at the bottom end of the more
rigorous type--randomized trials or case control studies. However, recent
guidance that we've published this year on postmarket surveillance studies
suggests that we will be expanding the kind of approach that we would require
manufacturers to apply, including detailed review of complaint history or the
literature or nonclinical testing of the device, to help us resolve potential
postmarket problems.
But postmarket studies are challenging.
First of all, the rapid evolution of technology makes studies obsolete. It is
indeed wonderful that the medical device community revises their products on
almost a weekly basis but it makes a postmarket study a particular challenge
because by the time a study protocol is approved, fielded, data are collected
and analyzed, it is often the case that the product is no longer marketed. So
is it still relevant? It makes it a challenge.
Second, in truth, there's a lack of
incentives for the industry. It is a rare situation where a postmarket study is
going to give great good news to a company, so they're not excited about doing
these, frankly.
There's also a lack of interest in the
clinical community. Very few postmarket studies are sexy enough to be
publishable, like the premarket stuff with the hot new technologies. So that
presents a big challenge.
But by far we think the biggest challenge
that we have faced, both in postapproval studies and in Section 522, is a lack
of a clearly specified public health question. What are we going to do with the
data once it arrives? Are you going to suggest a relabeling? Are you going to
suggest expanded or restricted indications for use? Would you consider advising
us of a product recall?
If one of those actions doesn't occur to
you and you're just interested in the question, then it probably isn't a good
candidate for a postapproval or postmarket study. But if you can help us with a
clearly specified public health question and what you think you might do with
the answer to that question, it'll help us formulate the appropriate protocol
and hold the manufacturer responsible to conduct that protocol and bring results
here back to the panel, which we rarely have done.
So that's my challenge for you. When
considering a postmarket study, whether postapproval or 522, and that's an issue
that we can work out at FDA and you needn't be concerned with, please ensure
that the question you're asking is of primary importance, help specify that
question and note the clinical or regulatory relevance of answering the
question. What will we do with the data? That'll help us formulate the
question; it'll motivate the company; it'll motivate the clinical community to
contribute data, answering the question; it'll help us address potentially
important postmarket surveillance problems.
The 100,000 events that we get every year
represent thousands of deaths and scores of thousands of serious injuries that
occur because of medical devices sometimes being used improperly, being handled
improperly or sometimes failing. Our job is to try and minimize that and we
hope you'll help us in that mission.
Thank you very much. I'd be glad to take
any questions.
DR. EDMISTON: I think in the interest of
time, we're going to move on. Thank you very much, Mr. Kessler.
Our next presenter will be Mr. Charles
Ho, who will give us a presentation on Y2K.
Y2K INFORMATION
MR. HO: Good morning. I'm Charles Ho.
It is my honor to be here to talk before the General Hospital and Personal Use
Devices Panel to discuss with you the year 2000 problem.
Yes, medical devices are subject to the
year 2000 problem. Susceptible devices can be found in the microprocessor or
PC-controlled products, software applications, device interfaces to databases
and recordkeeping systems and also in embedded chips for date display or
recording.
What is the year 2000 problem? It's the
failure of a computer system to properly process a display face due to
representing the year using only two digits or other date-related problems, such
as failure to recognize the leap year. For example, list of confusion between
the 2000 and 1900.
An example of a year 2000 failure. A
chemical in a clinical laboratory test has an expiration date in the year 2000.
However, the testing device reads this date as a in the year 1900 and did not
allow the test to proceed, since the testing device thought the chemical was out
of date.
So how do we define the year 2000
compliance? For the purpose of a database, year 2000 compliant means, with
respect to medical devices and scientific laboratory equipment, that the product
accurately processes and stores date/time data, including but not limited to
calculating, comparing, displaying, recording and sequencing operations
involving date/time data during, from, into and between the 20th and 21st
centuries and the years 1999 and 2000, including correct processing of leap year
data.
So what is the FDA requesting of the
panel? Please provide us with advice regarding problematic devices from the
panel's domain of expertise. Please identify types of devices which because of
their use of dates, could present risks to patients if not addressed. Please
provide suggestions to CDRH regarding actions to reduce risks from year 2000
problems.
What has the FDA done regarding the year
2000 problem? Since 1996 we have made internal assessments of potential impact
and vulnerable devices. In June 1997 we sent a notification letter to
manufacturers to advise them of the problem. FDA will address the year 2000
problem in premarket reviews. New submissions are not required for repairs
which are only date-related. Repairs/updates before impact will not be
classified as recalls.
In addition, we are also participating in
the Biomedical Equipment Working Group. This is a group of federal users of
devices and scientific equipment. The work group is chaired by the Department
of Health and Human Services. We send a consolidated request for information in
January 1998. We think that the public and the private health care
organizations have the same information needs.
We established a website in the spring of
1998. We sent out a guidance on FDA expectations in June of 1998.
The address of the FDA product database
can be found at www.fda.gov. Please select the year 2000 item.
The Biomedical Equipment Database. This
is an FDA-operated World Wide Website. The data are provided voluntarily by the
manufacturers. It is a certification by the manufacturers. The data are
continually updated, searchable and downloadable.
What does the project database show us?
Well, many companies have not yet reported. Presumably assessments are still in
progress. Most noncompliant products involve date display or date recordings.
They usually record date-stamping.
A limited number of products have
significant operational problems, such as the problem of the expiration date
that I talked to you about. PC-based problems and PC-type problems, such as
recording and date-stamping.
Manufacturers are providing a number of
solutions, such as software upgrade, patches or complete replacements.
Major additional letters to
manufacturers. In January 21, 1998 we sent out a letter on the year 2000 impact
on biomedical equipment. This was followed by the June 29 and September 2, 1998
letters. Then September 21, 1998 we sent a letter on manufacturing process
concerns. May 26, 1999 we sent a guidance on MDR reporting. June 18, 1999 we
sent out a year 2000 readiness survey.
Major additional communications to health
facilities and consumers. December 29, 1998 we sent a letter on computer date
problems on medical devices on January 1, 1999. This is about the rollover from
1998 to 1999. May 26, 1999 we sent a guidance on MDR reporting. And most
recently, on July 16, 1999 we sent out a Y2K planning.
The future CDRH/FDA activities. We have
already established a Biomedical Equipment Clearinghouse. We are expanding the
database to include complaint as well as noncompliant devices. We are
continuing to do outreach communications with industry, clinicians and
consumers. We are pursuing rigorous action on products which present
significant risk. We increased inspectional emphasis on Y2K.
Health care facilities. We recommend
that health care facilities do the following. Inventory and assess devices
used; obtain information on device status; test devices for Y2K compliance;
check interconnected or networked devices; check device information system
connections; plan for or develop workarounds, upgrades or replacements; and
finally, develop contingency plans.
If you have any comment, please give your
comments to the panel executive secretary or to Dr. Tom Shope at the address
listed. You can also send comments to him via e-mail at Tbs@cdrh.fda.gov.
DR. EDMISTON: Thank you very much, Mr.
Ho.
At this time we'll move into the main
presentations but before we do that from the FDA I'd like to make a statement.
The charges of this panel today are
twofold. This morning we're going to discuss guidance for review of
needleless systems and this afternoon we're going to
discuss and make recommendations to the FDA for guidance in the development of
jet injectors. That will be the focus of today's presentations. We will try to
keep on task and try and keep on time. These are two extremely important areas
that need to be discussed.
I also want to point out again that
anyone who comes to the podium, please speak directly into the microphone.
Identify yourself and your affiliation.
For those members in the audience,
representatives from industry and from private organizations, we would like you
to state not only your name and affiliation but we wish you would also state
what, if any, financial interest you may have in the medical device industries.
At this time I would like to ask Mr. Tim
Ulatowski, the division director for Dental, Infection Control and General
Hospital and Personal Use Devices, to provide an overview of this morning's
topic.
ISSUE: GUIDANCE FOR REVIEW OF
PROTECTED SHARPS SYSTEMS
FDA PRESENTATION
MR. ULATOWSKI: Thank you, Mr. Chairman,
and welcome to the panel. Thank you for taking the time out of your busy
schedules to come in and have this discussion with us today about these
important devices.
There's somewhat of a misnomer in the
agenda this morning. We're discussing protected sharps devices, not
needleless systems per se.
But at any rate, today's discussion is a
somewhat different panel session for a panel session. Usually we discuss
premarket submissions, premarket approval applications, investigational
applications in closed session or sometimes premarket notifications, so-called
510(k)s. But today we're having a discussion about guidance documents, either
current ones or future ones, and there will be no voting today, as there usually
is when we talk about a premarket submission.
We are talking about different devices
from the morning to the afternoon, somewhat different--protected sharps devices
in the morning and jet injectors in the afternoon. Certainly they're somewhat
different but they're related in terms of the problems they're trying to
address.
In the morning session we are revisiting
our 1996 guidance on protected sharps and what we intend to do is to update the
guidance based upon your comments and post it under our new good guidance
practice procedure, which came into effect a couple of years ago.
Now we're not here to discuss worker
safety policy or current events that are driving an interest in protected sharps
per se. That's certainly an important issue. We're here to talk about a
guidance document and how to update that guidance document to the benefit of the
agency.
This guidance we're talking about does
not address some devices that fall under the aspect of worker protection, sharps
containers and some other devices. We are talking about primarily protected
syringe devices, but there are many other devices that come under the purview of
our guidance that we'll be discussing today.
As I was considering having this as a
discussion item, I think one of my concerns, my critical concerns was as we move
forward with clearing products, as FDA moves forward and people are relying upon
our clearances across the country, we want to make our evaluations of these
devices certainly up to date and pertinent, relevant to what's going on today in
terms of what people think we ought to be doing in terms of product evaluations.
I think some people out there think we
get products and we're fidgeting with them and testing them on ourselves, trying
to stick ourselves and what-not. We don't really do that. We do get samples
and we do fiddle with them, as we are engineers and nurses and what-not and
physicians, and we love to fiddle with things, but primarily our focus is upon
the documentation contained in the documents and the testing that's done by the
manufacturers or the people they bring in to evaluate the products or to whom
they send products for evaluation.
I'm primarily concerned about the
clinical survey aspect in our guidance document as we discuss things this
morning. I know that there's various organizations and institutions who have
their own surveys for their purchasing purposes or whatever, and each has its
own scheme of questions and answers and approaches and how many products are
tested and what controls are run.
I think there's a place for everyone
doing their own thing to a certain extent but as far as FDA's purposes, I want
to try and reconcile some of those differences in approaches and see where we
need to be doing perhaps a more comprehensive job in some cases and where we can
leave some other evaluations as people feel it's necessary in their own
institutions.
So that's my reflections today and Irene
Naveau is going to bring us up to date in a little more detail on the guidance
document.
DR. EDMISTON: While we're waiting let me
ask Mr. Ulatowski one question. Do you prefer that in the course of this
morning that when we refer to these systems we refer to them as protected sharps
systems? Would you prefer that?
MR. ULATOWSKI: I think that's more
generally the scope. There are some needleless or
blunted needle-type systems but more generally it's protected sharps.
DR. EDMISTON: Fine. Thank you.
MS. NAVEAU: Good morning. The guidance
document under discussion this morning is entitled Supplementary Guidance on the
Content of Premarket Notification Submissions for Medical Devices with Sharps
Injury Prevention Features. The document is intended to assist manufacturers,
distributors or importers in preparing 510(k) submissions for medical devices or
accessories with sharps injury prevention features, as well as to facilitate the
510(k) review in a consistent manner.
I plan to include in my discussion today
a brief background of the existing guidance document, as well as a review of
working definitions of those types of medical devices to which this guidance
document pertains. The desirable performance characteristics of these devices
will be identified. Elements of the guidance document will be addressed and
then a brief summary.
Finally, I'd like to present a list of
questions that were previously submitted to the panel to review for subsequent
discussion and recommendation.
The earliest medical device with a sharps
injury prevention feature was reviewed in 1984 as an accessory to an IV
administration set. In 1985 a shielded syringe was reviewed.
Since that time, the General Hospital
Devices Branch has reviewed over 225 sharps injury devices with safety
protective features, with the largest number of devices reviewed in 1991 and
1992 and in 1996 and 1997.
It should be noted here that other
divisions in the Office of Device Evaluation also review various medical devices
with safety features. Therefore a comprehensive list of these devices is not
currently available.
In 1994 a supplementary guidance
document, the precursor of the guidance for review today, was presented to
panel. At the conclusion of that particular panel meeting, we acknowledged the
comments and recommendations of the panel, as well as the public, specific to
the performance data section and sample size recommendations for studies being
conducted. The revised draft supplement guidance in effect today has been used
by the agency and industry since March 1995.
The guidance document is used in our
review for various types of safety devices and include the blunt or blunted
needles of stainless steel or a plastic material, the prepierced septum devices
of various configurations, reflux valves, which are sometimes referred to as
bidirectional valves, vial adapters, those devices that provide
needleless access to a drug vial for reconstituting
and withdrawing medication, retractable needles, shields and guards associated
with syringes, and recessed needles.
These devices are integral components of
an existing device or may be marketed alone. For example, a reflux valve can be
marketed alone for use as a heparin lock type of device used in conjunction with
an IV catheter, an IV administration set or a syringe.
What are we talking about when we refer
to devices with safety features? There are any number of definitions for
devices with safety features but for our purposes today I'd like to read two
working definitions of these devices.
A medical device with a sharps injury
prevention feature is a device designed with a component or attachment, either
active or passive, that protects the user from a sharps injury.
Sharps injury prevention features are
found in devices such as but not limited to piston syringes, hypodermic single
lumen needles, IV administration sets, intravascular catheters, vacuum tube
holders, as well as blood collection devices.
These features can be a component of a
finished device, such as a sheathed or shielded syringe, while some safety
feature products are marketed separately as accessories that are attached to
devices by the user at the time of use.
For regulatory purposes, accessories to a
device are classified in the same class as the devices to which they are
assembled.
The second definition: a
needleless system is one that provides repeated
access to a patient's vascular system without the use of sharps. Fluid flow
through the system may be unidirectional or bidirectional, with the latter
allowing the user to administer or withdraw fluids or medications.
An example would be a prepierced septum
and blunt canula. With this type of septum, a blunt canula connected to a
syringe or secondary IV administration set can be inserted into the prepierced
septum on a Y site of an IV administration set, an adaptor or other secondary IV
or extension set.
Another example is a valve connector,
sometimes referred to as a reflux valve. It prevents fluid flow through the
device in either direction when not activated. However, when a male or mating
lower connector is inserted into the prepierced septum at the end of the valve's
housing, the valve is activated in various ways, depending on the valve
configuration. This activation opens the fluid flow pathway for the infusion of
IV solutions or medications and for the withdrawal of blood samples.
In the next two slides I've listed a
number of desirable performance characteristics that we believe should be
considered by industry in conducting their simulated clinical and actual
clinical studies in the evaluation of safety devices. Evaluation of these
characteristics may require actual use of the device and by targeting questions
to health care workers who may or may not have had any experience with the
device.
These characteristics can usually be
assessed with visual inspection of the device or by simple manipulation of the
mechanism and should include: hospital personnel are shielded from the needle
before, during and after disposal. The protective mechanism can be used equally
well, regardless of hand preference or for hand size, for that matter. If
additional steps to the usual procedure are necessary to activate the protective
mechanism, they would be few. And they do not interfere with the usual
nonprotected procedure.
It is not necessary for the user to place
either hand near the needle during a procedure and the hands should remain
behind the needle at all times.
In addition, the protective shield or
retracted needle reliably locks securely into place with little effort. The
protective mechanism is designed in such a way that the user is always aware of
its status; that is, whether or not the device is engaged or locked into place.
The design of the protective mechanism
allows appropriate visualization during device use. The user is not exposed to
the needle during disassembly and the mechanism is compatible with the sharps
disposal system used in the facility.
In September 1998 OSHA published a
request for comments from a number of health care organizations related to
occupational exposure to blood-borne pathogens due to percutaneous injury. The
FDA responded by submitting the preceding list of desirable performance
characteristics that are found in the guidance document.
Five similar performance characteristics
were listed in OSHA's recent executive summary as suggestions from researchers
for selecting safer medical devices. However, it has not yet been determined
how OSHA will incorporate these suggestions in their revised standard.
This may be an opportunity for FDA to
meet with OSHA and consolidate recommendations regarding the characteristics of
devices with injury prevention features.
The performance characteristics on the
previous two slides are listed in this table. They were compared with those
characteristics outlined in the evaluation forms the three other organizations
use; that is, the Service Employees International Union, the SEIU, from their
guide In Preventing Needle Stick Injuries in 1998; the New York State Department
of Health, the NYSDOH, from their study of needle stick prevention devices in
March of 1992; and the Training for the Development of Innovative Control
Technologies, the TDICT, from their Safety Feature Evaluation Form found on
their website.
The results of this comparison indicate
that similar evaluations are being used by these organizations and in most cases
concur with our characteristics. For instance, we all agree that the user
should be protected from needle stick injury before, during and after use, that
the safety feature may be activated with either hand, and the user be able to
visualize the fluid and the fluid level during preparation and use.
We have included a statement indicating
that the device with safety features should be compatible with the sharps
disposal system in the facility. The statement may be included in their
evaluations, but it was not evident in the material that I had access to.
The guidance document does not include a
list of targeted questions, as do these organizations, but it does contain
recommendations to industry regarding their report forms that would include this
information.
Apart from the section that addresses
appropriate device description and labeling, much of the guidance is directed to
device specification and performance test specific to sharps injury prevention.
What it does not address are sharps containers which are addressed in their own
guidance document and needle recappers.
In essence, the guidance provides
overview information to applicants to aid in the analysis of performance
characteristics of these devices and contains recommended types of tests that
can be performed. Again only recommendations are suggested to industry.
Therefore the document does contain a checklist or a to-do list for
manufacturers to follow.
In this document we refer to five main
types of performance testing for devices with sharps injury prevention
features. Those include bench testing, biocompatibility data, preclinical,
simulated clinical and actual clinical studies.
The guidance also contains factors that
should be considered before conducting a simulated clinical or actual clinical
study; for example, how a device is equivalent to other similar devices, and
microbiological issues.
Typically,
needleless systems present a contamination concern addressed with simulated
testing in a microbial challenge test, whereas the sharps devices present a
needle stick concern addressed with simulated clinical and actual clinical study
data.
In summary, we have established that the
1994 revised draft guidance document has served as a working document for FDA
reviewers and industry alike for the past five years. The document includes
recommendations to industry, especially related to design features and
performance characteristics that should be included in their studies prior to
510(k) submission.
Several types of surveys are in progress
by industry during their preparation in introducing their safety devices into
the marketplace and by organizations dedicated to the protection of health care
workers and others that use devices with protective features.
In light of public health issues that
have arisen and emerging new technology, we are revisiting our document. We
recognize that it may need revision for the following reasons: for consistency
in our reviews and to assist the manufacturer in assembling scientific
information, especially microbiological and performance data to determine
substantial equivalence. There may be other areas in the guidance, as well,
which you may offer your suggestions for change.
I'd like to read now the following
questions that were previously submitted to the panel. I understand that the
questions will then be considered separately for discussion and recommendation.
Number one, "Our current guidance
document allows sponsors to perform either a simulated clinical use study or an
actual clinical use study to evaluate the performance of the sharps injury
prevention feature. In most cases, sponsors have provided information from
simulated clinical studies. When would it be appropriate for FDA to consider
data from actual clinical use versus simulated clinical use?
"Are there minimum criteria in terms of
sample size, independence of the evaluators and number of sites that FDA could
consider for both the simulated clinical and actual clinical use studies?
"In addition to the survey format, are
there any other methods that the FDA should consider when evaluating the
performance of these types of devices?
"Are the evaluation criteria listed in
the guidance document appropriate and inclusive?
"How could the results of these
evaluations be presented to users? Should the results be included in the
labeling?"
And two, "Currently sponsors submitting
applications for needleless access devices are asked
to demonstrate that their device is substantially equivalent by providing
nonclinical bench data to demonstrate that their device does not increase the
risk of microbial contamination of the fluid pathway, validation of the cleaning
method, and instructions for use. What additional types of information should
be considered for our premarket review?"
Three, "What mechanism does the panel
recommend to the FDA to increase user awareness of the safe use of these
devices?"
And four, "Is there a need for
educational programs for the use of sharps injury prevention devices? If so,
what content should be included in the educational programs to encourage the
safe and effective use of these devices?"
And five, "Are there other areas of the
guidance document that should be revised?" Thank you.
DR. EDMISTON: Thank you very much.
Do the members of the panel have any
questions for Ms. Naveau?
[No response.]
DR. EDMISTON: That being the case, I'd
like to invite to the podium Dr. Joseph, director of the Office of Health and
Industries Program at the FDA.
DR. JOSEPH: I'll say good morning while
we get ready and we appreciate your being here and thanks to the division for
including us today.
As was stated, I'm Dr. Joseph, the
director of the Office of Health and Industry Program in the Center. The office
has several activities in which we engage on behalf of the Center, one of which
is outreach and educational activities.
What I'm going to talk about today is a
little bit about to put our educational activities in a context. I think it's
really important to briefly review what our mandate is in terms of the FDA
mandate relative to devices. And because there are other sister agencies who
also, as Irene said, have an interest in this area, I thought we'd briefly take
a little snapshot of what OSHA's mandate is and see how we can blend our
activities and then get your advice on that.
Okay. The mandate of the FDA in terms of
medical devices is to really focus on our regulatory activities on the product
features and product aspects, and that's again to ensure the safety and
effectiveness of those devices. So we pretty much look at the labeling
requirements, the performance test methodology, good manufacturing practices and
quality systems.
Whereas the Occupational Safety and
Health Administration has a deep interest in sharps injury prevention devices,
as well, and from their mandate you can see that they're tasked with ensuring
that workplace conditions are safe and healthful for employees, and they do this
by enforcing their standards developed under their act, as well as collaborating
with the states to ensure that those conditions are met and providing research,
information, education, training in occupational safety and health.
And as Irene said, recently OSHA issued
their request for information and comments on a number of items to reassess
their blood-borne pathogen standard. They asked specifically for information on
16 items. I've just listed three here, which has sort of some interesting
possible overlap with where our interests are, and that's in training and
education in the safe use of medical devices and any effect on reducing injury
rates and the impact on the delivery of patient
care.
But we've, as I said, we do have a role
and there are things we can do. Irene mentioned we cleared in excess of 200
devices with some sharps injury prevention features. We have cosponsored
several meetings with CDC, OSHA, NIOSH, NIH and the most recent one was last
August relative to the prevention of transmission of blood-borne pathogens.
We have issued three safety alerts or
notices, all of which went to the health care community, two of which pertained
to recommendations on the safe use of safety prevention technology relative to
administration sets, and most recently, the one we issued in February of this
year, on capillary tubes. I think that was probably the first alert that we
issued that was jointly sponsored by OSHA, NIOSH and ourselves.
We've also issued eight guidance
documents on injury prevention aspects, of which three were directly related to
sharps prevention devices, the primary one being the one that you'll be
discussing the morning; the other two are supplementary to it.
Irene mentioned we responded to the OSHA
request for information by providing them with the human factors desirable
performance characteristics that we look for and feel would assist and go a long
way in preventing any injuries.
And I failed to mention under the safety
alerts that we also are currently developing a new notification on use of
devices with sharps injury protection features and we're just now trying to
determine the direction or if those will be interval notices.
But we've also been planning an
educational teleconference with several federal agencies on sharps injury
prevention activities and devices. We've been communicating with OSHA in trying
to determine if they're willing to take the lead in this venture and we
certainly are willing to collaborate with them on that.
And as Irene read to you, there are three
questions that we would appreciate response from you as guidance for the future,
since the office has been tasked with doing some additional educational or
outreach activities and before moving too much further along, we thought it
would be helpful if we could get your guidance on the mechanism that the panel
could recommend for us to increase user awareness of the safe use of devices.
If indeed there is a need for educational
programs for use of sharps injury prevention devices, should you respond in the
affirmative to that, then what should the content be included in those programs
that would encourage the safe and effective use of those devices?
And in the interest of being very brief,
that's all I'll say this morning. And I look forward to whatever information or
guidance you can provide us. Thank you.
DR. EDMISTON: Thank you very much.
Are there any questions from the panel
members for Dr. Joseph?
[No response.]
PRESENTATIONS BY USERS OF
PROTECTED SHARPS SYSTEMS
DR. EDMISTON: That being the case, we're
going to move on to our presenters, the users of protective sharps systems.
Before I do that, I'd like to reiterate
again when you come to the podium, please speak clearly into the microphone.
Also it's very important for you to identify the organization you're part of.
We need to know what, if any, financial interest you may have in the medical
device community.
And I should also emphasize that we're
trying to run a tight schedule today because we're going to have some
significant discussion regarding this particular guidance documentation. I want
to encourage our next presenters to limit their comments to 15 minutes.
The first person I'd like to call to the
podium at this time is Dr. June Fisher, who's a clinical associate professor of
medicine at the University of California and is director of training and
development for innovative controls and technology. Dr. Fisher.
DR. FISHER: I would like to make the
comment that I am thankful for the invitation to speak here today and that I
really am very excited to see that the FDA is addressing the issue of health car
worker health and safety.
I know there's a mythology out in the
general community that there's an oppositional thing between patient safety and
health care worker safety and I know that in institutions these are weighed. I
think that this has been proven repeatedly that this is an erroneous approach to
patient care.
As a clinician, that is my primary
concern but I do know that the health care worker who has a safe environment can
provide much better care. The most obvious example is if you think about in
terms of back injuries. I do not want to be lifted in a hospital but if I had
to be there, by somebody who has had a back injury and is not supplied with the
appropriate devices to lift people.
I think that this certainly goes for the
needle stick area and I really welcome this kind of--the FDA is vigorously
approaching the issue of health care worker safety in their desire to improve
patient safety.
I am not going to talk specifically about
needleless systems. It'll be a little bit more of
an overview, which will be consistent with some of the presentations that went a
little earlier.
[Pause.]
I have a lectureship in engineering but I
must say that I'm totally baffled when we have anything like this. I think it's
every speaker's nightmare to not have your slides available. Since your time is
a little pressed, I will try to speak a little extemporaneously and then
hopefully the slides will be projected.
The Training for Development of
Innovative Control Technology is a program that was started in 1989 and has been
funded for almost 10 years by the National Institute of Occupational Safety and
Health and it's a program that brings together product designers, industrial
hygienists and users. And most of my discussion will be really based on
user-driven technology.
You're going to have to bear with me.
They were organized.
This is our logo for our slide. I hope
I'll have a few more minutes.
DR. EDMISTON: Of course you will.
DR. FISHER: As all presentations that I
do around this topic, I always use this dedication slide. This is a group of
health care workers who--the first group are still alive and the bottom group
are people who have died from occupational exposure to blood.
I have to make the point that these are
all in one city. And when I do speak around the country, I hear from many
people that probably the same numbers do exist, so that as important as the CDC
numbers have been, most of us feel that these numbers are very, very limited.
And I don't have time to discuss that, so we have to remember that there is a
real human face and there are serious outcomes for this.
I was asked to talk a little bit by
people earlier today so I put this slide in. Coming from California, we have a
particular circumstance that we now have legislation mandating the use of safer
devices, which will change the whole direction in California and will have
impact or already has had impact nationally.
We have the blood-borne pathogen
standard, which is OSHA. We have a Cal/OSHA standard now, which is working
under an emergency order, which mandates the use of engineering controls. If
this is not passed by the board, the emergency standard will continue so that
this will be in effect regardless of what--in California we have a political
board. The assumption is that they will pass this.
There's legislation in Tennessee,
Maryland and I think in 20 other states--somebody may speak for that--and
there's federal legislation pending on it. So we have, although we don't want
to deal with the political issues, we do have a political driving force.
As I said, our project is a project that
brings together the industrial hygienists, product designers and health care
workers. And, as far as I know, this is unique for any area in health care.
And I would certainly recommend that this kind of collaboration exist for many
areas in device development.
I do know, as an aside, because I have a
lectureship in engineering, I have 48 product designers usually a year running
around the hospital and there are major, major issues that need to be addressed,
not just in these devices, that could be improved by bringing together the user
and the product designers.
Why bring the health care workers to it?
This is from a modification of Warren Estrine from HEMAS because they have a
familiarity with new existing devices, the knowledge of the medical device
procedure and protocol and an understanding of the environment in which the
devices will be used and intimacy with the concerns of the actual user and an
advocacy that goes on.
The manufacturers do try to have this but
in my only experience with them, they really don't fully understand the line
user. I suppose the best example is when I was a resident at Stanford. The
hospital was built by talking to the chiefs of medicine. The building didn't
work, and it was the first instance we made it very clear that you have to go to
the person who's doing the job.
Our project involves a large group of
institutions and this is an old slide and it can be expanded now because we have
national involvement with both dental areas and with some of the other hospitals
in the country.
This slide, and it's upside down and it's
supposed to go later--it's showing you when we do simulation studies. I think
we'll have to forego that.
Our methods developed our review of data
on needle stick injuries, an appraisal of the health care workers who are doing
the observational studies, failure analysis of devices. And I really want to
emphasize that that is very important, to do failure analysis and simulation
studies with the devices and joint brain-storming sessions and multi-center
health care worker testing.
One of our first things we did was to
provide a tool for health care workers to assess devices and you got some of
that when the chart was presented before. If there's a consistency with the
SEIU it's because they adapted their devices from ours, so I wouldn't say that
independently this occurred.
And we have now 14 devices where we have
the tools--I don't know if I can focus this any better--and you can get these
tools on our web page, which give guidance to the health care worker in
evaluating the device. And I chose the one for
needleless systems for IV connectors today.
The interesting thing about these
devices, I'm not going to go over the specifics within 15 minutes but we can
provide you with those, all of them. I don't know Martha, if you were able to
get that off the web. We could provide that for the committee. I have a copy
here.
These were the first written criteria for
now 14 types of safety devices. They provided a means for involving health care
workers and most of these have been validated in multiple institutions. This is
an old slide. The 14 are now in the 1999 AHA document.
And while they were originally used for a
tool for health care worker evaluation and selection, it became the industry
benchmarks. So it is very important to develop these criteria that are
user-based because it does drive the industry.
That was the surprise to us, a picture
showing--this is when our team was living down in the emergency room. Here is a
product designer actually who is now trying to do laboratory failure analysis of
the device. This is a picture--actually the woman in white is a product
designer, industrial hygienist and nurse who is guiding another nurse in testing
of the devices, using the criteria sheets.
One of the things that we did is also we
do design evaluation courses for nurses. When you're talking about education,
this is one of the things that actually we want to include. We're hoping now to
be able to develop a program with the American Nurses Association where we will
hope to develop 400 master trainers around the country so that we could
emphasize the training.
Training is essential. When the question
was asked for health care workers, you cannot just coldly go in. This is one of
the slides for our course. We're not expecting the nurses to be product
designers but we were trying to help them develop a language so they could talk
to product designers and manufacturers in a constructive way.
The importance of it is that out of this
course, not only did they learn something but we learned a lot. And what we got
out of that course was a user-based performance standard for design evaluation
selection of medical devices.
And a performance standard is different
than benchmarks and it should not stifle innovation. We were very aware that
the manufacturers have to have that kind of freedom where they can develop new
devices.
We are still in the early stages of
development. It should be user patient-based. You give a framework for
evaluation. And we need a national task force to develop consensus on
performance standards and this is one of the things that I was talking about
with Tim for a long time, that if the FDA could take the lead in promoting this
kind of census, it may not be something that you can do yourself but if you
develop that national consensus, that will be furthering things.
And performance standards versus criteria
performance are generalized. It's procedure-based and encompasses the product
life cycle versus the point of use only. Before, I was talking about the
specific criteria.
It's a rather extensive document. We can
also give you copies of that that can be made, but these are the areas that they
cover. Obviously patient care and quality care came first. User safety, user
fit and satisfaction, we felt, came before patient fit and satisfaction. And
product life cycle, which we're talking about sharps boxes, administrator's fit
and satisfaction.
One of the other things that came out of
there was the issue of scenarios, which you call simulation and we're calling
them scenarios. It's the ability of the actual user to test-drive new products
and it approximates real-life situations and it draws attention to unforeseen
difficulties. It's a very systematic way of doing that.
These are the variables that we
identified and that impacted on the use. Some of them may sound silly to you.
Why lighting? Well, that's labeling and packaging. Noise? Why noise, people
ask us, because a lot of the engagement of the devices depends on sound. And
crowding, condition of hands, visibility. Some of these, I think, are included
in your document, also. So we feel these are the variables to be considered for
the sharps devices.
And here is the way we rank them. You
choose what is applicable to your clinical situation and then develop the
device. This chart shows how you put them all together.
And, as an aside, I just have to say we
tested that at UCSF and I think the system works because a door was open in the
room when we were doing the simulation and one of the nurses was acting as a
patient who was having some difficulties and the intern ran in and said, "Can I
help you?" So I knew that we had a good scenario. We just closed the door.
What came out of that is that we needed a
user-based design and that users should be involved from the very beginning of
need-finding and they should be involved throughout the whole process. Rarely
are they. This is really the process that goes on. If you don't believe me you
don't have to, but we've gone to manufacturers who've all told us this is, in
reality, what happens. And we would push that the user be involved from the
beginning.
One of the other things I just want to
put in, what we really are aiming for is to have the PEST. That is passive,
easy, simple and throughout. That's the summary of what we think is desirable
in a device.
I would like to go over briefly the
overheads. I have to apologize for the overheads because they're handwritten.
There was a power failure as I was trying to use my computer and I couldn't wait
any longer because I had a plane waiting for me. As a physician, my handwriting
is not very good but I think you can read that.
These are the recommendations for FDA, to
participate in the promotion of primary prevention of occupational exposure to
blood. I know that there's a lot of emphasis and there should be and people do
get stuck but I think we have to think about primary prevention so we don't even
have to think about post-exposure treatment.
The first thing, some of these are very
specific and some are more general. One is labeling of all sharps devices. At
present, the only sharps devices that are labeled are those that have the safety
feature. We believe that the ones with nonsafety features need to be labeled,
also, and they clearly need to be labeled.
There are going to be instances where you
have to use a standard sharp device but you should be very aware that it is a
standard sharp device, so we think that they should all be labeled. They should
not be treated differently.
I think it's interesting that previous
speakers from FDA brought this up, to actively solicit device failure inadequacy
from end users. I think you may have to redefine things. I don't want to think
about death or serious injury. I think any needle stick, and we have probably
900,000, should be analyzed and FDA should be having their handle on. I'm not
asking you to look at all 900,000 but that there should be more awareness of
what's going on there.
There should be promotion of criteria for
systematic pilot-testing of market-available devices. I didn't talk about that
because of the time but what I presented before, we consider are just screening
tests. That pilot testing systematically is a very urgent issue. And from my
experience, both in my institutions that I've been in and now I've been in many
institutions talking around the country, pilot testing is--at best I could call
it a joke.
Generally you give the device to people
and you come back two months later and ask them, "Did you like it or you didn't
like it?" That is not pilot testing. There needs to be a very systematic
approach to doing it and to actively collecting the data.
And I think if there were criteria for
this that you would be getting better pilot testing and actively collect failure
inadequacy data obtained from pilot test. If you had good pilot tests, that
would really give you postmarket data that is really not available now. So
we're recommending that there really be an emphasis on the pilot testing.
And there should be expanded requirements
for simulation testing. From what I can gather, the simulation testing is left
to the manufacturer to define what they are and I think that that causes a great
deal of variability. There should be standards. I'm not saying that you
specifically say you have to do this and this and this, but put the benchmarks
out there, the standards for the variables to be included in that testing.
And to require, before you even do the
testing, a user-based work task analysis. Define what variables you want in
that test. If you're going to go in the emergency room and you're going to use
some standards that you devised for the out-patient department, that doesn't
give you much detail. Or if you just bring a group of people together that
doesn't represent the spectrum of work and say, "Well, try this," and sit in the
room, which has no clinical bearing at all, so I think that you should have
user-based work task analyses and require testing for failure.
That sounds very strange but in our own
experience if you just go to a naive health care worker, they know what their
problems are but they don't know how to look at it. They're so grateful that
you have a new device that they say, "Oh, it's fine." And you look at them and
you say, "That is fine?" So they have to understand how to go to failure, to do
all those mistakes.
Our trained users will throw things on
the floor, will do bad practice because they know that's what they have to look
at, because that's what you're going to get in reality. And to require the
inclusion of trained users in the testing process. This is why we're excited
about our collaboration with the ANA, to train these kinds of resources around
the country, but I think that should be required by the FDA in your simulation
testing, that you've had some trained users who can foresee.
And my last slide is that our performance
standards and our criteria and some discussion scenarios are all available on
our website, which is here. Thank you for allowing me to speak. I think I've
covered the 15 minutes.
DR. EDMISTON: You're right on time,
believe it or not. You're right on time.
Are there any questions from the panel
for Dr. Fisher?
[No response.]
DR. EDMISTON: Dr. Fisher, I have one
question. When you use the word "pilot," are you referring to bench testing or
to simulated clinical testing?
DR. FISHER: No, I'm actually--thank you
for asking that. I think they should be bench-tested. I think there should be
evaluation before you even do a simulation, at least for the evaluation. For
the manufacturers, they should then go to simulation.
And then the pilot testing is actually
postmarket pilot testing by the institutions. And I think most places say they
do that. They're going to decide if they're going to buy a device or not and
they bring it on the unit and look at it.
DR. EDMISTON: So you're defining pilot
testing really as product evaluation within the institution.
DR. FISHER: Yes. And I think that
that's a very valuable area that FDA could use for a postmarket details without
having to wait for the death, which may come a year later. So I think that that
data could be extremely valuable.
DR. EDMISTON: Well, thank you very much.
Our next presenter is Ms. Toni Hughes, a
perioperative nurse who is representing the Association of Operating Room
Nurses.
MS. HUGHES: Good morning. Thank you for
the opportunity to submit a statement on behalf of AORN to this Federal Drug
Administration advisory panel.
My name is Toni Hughes. I'm a registered
nurse with a bachelors of science degree in nursing and a certification in
operating room nursing. I'm a perioperative nurse at Anne Arundel Medical
Center in Annapolis, Maryland. I have been a perioperative nurse for 19 years
and a surgical department manager for the past two, a member of AORN since
1981. I was the chair of the AORN National Practices Committee from 1998 to
1999 and am an active member of the Maryland Nurses Association and the American
Nurses Association.
Organized in 1949 with a current
membership of 43,000, AORN, the Association of Perioperative Nurses, is the
professional organization of perioperative registered nurses, whose mission is
to promote quality patient care for providing its members with education,
standards, services and representation.
AORN supports the development and use of
products, such as safe needle devices, to prevent unnecessary exposures of
perioperative personnel to hazardous blood-borne infections. Perioperative
nurses are acutely aware of the potential dangers associated with use of needles
and other sharps in caring for perioperative patients. Although only 13 percent
of the sharp injuries in the operating room are due to hollow bore needles,
needle stick injuries are even more significant risks than the preoperative and
postoperative patient care arenas.
Eighty percent of all blood-borne
exposures are the result of needle stick injuries. One study has found that a
needle stick injury prevention strategy eliminating 100 percent of needle sticks
and not costing more than 36 percent of the cost of needle devices would not
increase overall costs.
As participants in product evaluation and
purchasing teams, perioperative nurses recognize the complex challenges
encountered when trying to identify the most effective and affordable products
available.
As health care employers begin to
acknowledge the hazards and risks associated with direct
delivery of health care services and begin to seek safe needle devices for
workers, manufacturing standards should be established to ensure that truly safe
and effective devices are available in the marketplace. The FDA's role in
supporting the development and manufacturing of high quality, safe, affordable
and effective devices is critical to achieving a truly safe working evidence.
AORN supports the FDA's efforts in collaboration with manufacturers and users to
build a safer health care working environment.
DR. EDMISTON: Thank you very much.
Does the panel have any questions for Ms.
Hughes?
[No response.]
DR. EDMISTON: In that case, thank you
very much.
Our next presenter will be Ms. Mary
Alexander, who is the past president of the Intravenous Nurses Society.
MS. ALEXANDER: Good morning. I'd also
like to thank the panel for allowing INS to make a statement.
My name is Mary Alexander. I'm the chief
executive officer of the other INS, with the Intravenous Nurses Society. We're
a national nonprofit member organization that was founded in 1973. INS is the
largest organization for the IV specialty and exists to promote excellence in
intravenous nursing through standards of practice, education, public awareness
and research. The organization's ultimate goal is to ensure that patients
receive safe, high quality, cost-effective nursing care.
The Intravenous Nurses Certification
Corporation is also affiliated with INS. However, it is a separate corporation
established in 1983 to ensure the clinical competency of intravenous nurses.
INCC achieves this goal by administering certification exam and recertification
programs.
A registered nurse who passes the
certification exam and meets the experience criterion receives the certified
registered nurse intravenous credential. This credential is maintained by
continuing to practice the IV specialty and completing continuing education
requirements or retaking the exam.
INCC exists to benefit and protect the
public through assessment, validation and documentation of the clinical
eligibility and continued competency of nurses delivering intravenous therapy in
all practice settings.
INS understands the inherent dangers
involved in administering IV therapy. Vascular access devices, needles and
sharps are fundamental to the practice of IV therapy. INS members are the
frontline health care workers who provide IV therapy to patients in a variety of
practice settings, which are now extending beyond the acute care setting and
including but not limited to the home, physicians' offices, skilled nursing
facilities, subacute facilities and ambulatory infusion centers. As well as our
members, more practitioners are involved and their competency and skill levels
differ widely.
INS supports engineering and work
practice controls that eliminate or minimize exposure of the health care worker
to blood-borne pathogens. In 1997 INS wrote a position paper on safety products
which appeared in the Journal of Intravenous Nursing.
INS supports research and development
activities on IV products and medical products and devices to improve patient
care and protect the health care worker, education and compliance with commonly
accepted principles of infection control and basic practices, choice of products
based on engineering design that accomplishes the prevention of transmission of
blood-borne pathogens and improvement in patient outcomes, safety and risk
management based on professional responsibility and clinical standards of
practice, and blood collection design characteristics which result in effective
safety device, which include the elimination of the need for the clinician's
hands to be placed in front of a sharp needle tip, integration onto the device's
design and not an accessory, activation before disassembly in that it remains in
effect after disposal, and simplicity in utilization, preferably a passive
system.
Requiring all health care facilities to
use needleless systems and sharps with engineered
protections, such as retractable needles, and instituting training and education
in the use of safer medical devices provides an effective means of preventing
percutaneous exposure incidents and reducing the needle stick injuries each
year.
INS contends the best way to reduce the
risk of accidental needle sticks to health care workers is through ongoing
education, training and competency testing, use of vascular access devices that
minimize the risk of needle stick injuries, in compliance with OSHA's
blood-borne pathogen standards.
Frontline health care workers should not
have to risk their lives while saving the lives of their patients. INS applauds
and supports your efforts to positively impact health care worker safety. Thank
you.
DR. EDMISTON: Thank you, Ms. Alexander.
Are there any questions from the panel
members?
[No response.]
DR. EDMISTON: Thank you.
Our final presenter will be Susan
Wilburn, the president of the American Nurses Association, who will address the
panel.
MS. WILBURN: Good morning. Thank you
very much. It's a pleasure to be with you here today and thank you for taking a
look at this issue that is of critical importance to the American Nurses
Association and the two and a half million registered nurses around the country
that we represent.
My name is Susan Wilburn and I'm the
senior specialist for occupational safety and health at the American Nurses
Association, so my work is to work with you to protect nurses from needle stick
injuries and the subsequent illness and death, as Dr. Fisher described. And I
wanted to start today to talk a little bit about our members and the impact in
recent years of needle stick injuries on their lives.
The American Nurses Association is the
professional association representing nurses in the United States with our
200,000 members and as the professional association, we develop the code of
ethics for nurses; we establish standards of practice; we develop standards for
certification and certification testing of basic nurses and nurses in specialty
practice, including advanced registered nurse-practitioners. And as the largest
union representing nurses in the country, we also, in 28 states across the
country, represent nurses for the purposes of collective bargaining and the
advancement of the economic and general welfare of registered nurses. And my
role as the occupational safety and health specialist falls in all of those
areas.
Our members are all too often the victims
of needle stick injuries. This nurse, Linda Arnold, that many of you may have
had the opportunity to hear from and have known about over the past four years,
had a needle stick injury after she finished an IV insertion of a patient with
AIDS. Linda is a nurse from Lancaster, Pennsylvania, a small community
hospital, and most people in that community not only were unaware that the
community had any patients with AIDS but the first time they learned about it
was when one of their own, a very young nurse who, at the time of her needle
stick was 23 years old and had only just come out of nursing school about three
years prior when she had her needle stick injury.
As a result of her needle stick injury,
she did develop HIV and subsequently AIDS; in fact, in very short order. And as
a result of her injury, Linda did a great deal of research on her own, working
in collaboration with ANA, with a number of other organizations, including SEIU,
and worked with the International Center at Charlottesville, Virginia for Health
Care Worker Safety.
Linda decided that she wanted to start an
organization that would prevent, for all nurses, what had happened to her and
the tragedy for her family. She founded in 1996 the National Campaign for
Health Care Worker Safety. And part of the goal of her campaign was to get
institutions around the country to implement and use safer needle stick devices,
as well as to educate nurses and other health care workers about the importance
of working together with their employer to evaluate, select and implement these
safer devices.
But one result or lack of result during
the many years of Linda's work, as well as work for many years by a number of
us, even following the FDA advisory in 1992 about IV
needleless systems, is that this is data from November '98 from the
American Hospital Association consultant, Gina Pugliese, that across the
country, the percentage of use of safer needle devices is abysmally small. You
can see the largest use of safer devices in needleless
IV access, and most of us believe that it is not coincidental that this has
occurred in the years ensuing since the FDA advisory in 1992.
But for hypodermic needles and syringes,
the most common use of injections, there's less than 10 percent of the hospitals
around the country, as of last November, had implemented safer devices.
November was immediately following the California legislation and then
subsequent to November, last spring there's been a number of other states.
So this number will be increasing rapidly
and there also with come with it a need from the FDA and the other organizations
responsible for worker health and safety, as well as consumer health and safety,
to assist these institutions as they implement their new regulations to be able
to provide education to employees and to choose the right devices.
Another of our members, Karen Daley, who
is the president of the Massachusetts Nurses Association, had a sharps injury
last summer. And I know that you're not talking about sharps injury
containers; however, if the needle that was in the sharps container that stuck
Karen--she was working in the emergency room, she was working on the day shift,
she had taken care of a patient and had administered a medication, had taken the
sharp that she was using, put it in the sharps container and in the top of the
sharps container the previous needle that had been dropped had not dropped down
into the box. It was a mailbox kind of drop container where the weight of the
sharp itself is supposed to drop that sharp down below.
It did not do that and even though in the
previous five months the nurses in Karen's institution, who are represented by
the Mass. Nurses Association for collective bargaining, had repeatedly gone to
the employer and labor-management committees and said, "Get rid of this
container; it's not safe," well, the day after Karen got her diagnosis of HIV
and hepatitis C, all of those sharps containers were removed, but too late for
Karen.
What happened is as she dropped her sharp
in, there was a needle already in the top. She got stuck about a millimeter and
a half into her index finger. And nine months later--and most of you know that
six months following a needle stick injury, 95 percent of all seroconversion to
HIV will occur. With coinfection with hepatitis C, that seroconversion can be
extended. And I just heard of another nurse in the last month that it was 11
months before she came back with a positive HIV test.
Karen Daley is a tremendous leader within
the American Nurses Association and you can barely imagine the devastating
effect its had on our entire organization. And the way we all learned about
Karen's illness was because the Massachusetts Nurses Association had introduced
legislation in the State of Massachusetts to require safer needle stick devices
and Karen, on the day they introduced the legislation last spring, spoke on the
steps of the State House and her story was featured in the front page of the
Boston Globe.
Now the issue here is not sharps
containers. The issue is that if the device that was used by the nurse or
whoever had used the device previous to Karen had a blunting, retractable or
sheathed feature, Karen wouldn't have been stuck.
And I think what's happened is that even
though I live in Seattle, I'm less familiar with Power Point than I am with
WordPerfect presentations and I think this is what happened in the translation
to Power Point.
I wanted to just mention quickly the
hazards to health care workers and the kind of situation that nurses and health
care workers face on a daily basis in the institution.
We are subject to various biological
hazards. You can see HIV, hepatitis B, hepatitis C, tuberculosis and many
others.
Chemical agents, and ANA has had a great
privilege to work over the past few years with the FDA on the issue of latex
allergy and the teleconference a year and a half ago on that subject. Another
chemical hazard to health care workers, glutaraldehyde, ethylene oxide.
Ergonomic hazards--back and upper
extremities.
Physical agents like sound and radiation.
And then what has been lumped together in
the category of psychosocial hazards are stress, violence, shift work, shift
rotation.
So it's not just needle stick injuries
that we need to worry about.
Health care workers, with occupationally
acquired HIV, Dr. Fisher mentioned the CDC data for confirmed cases of the HIV
virus from a needle stick or other blood-borne exposure. As of December '97
there were 54 documented cases and 132 possible cases that didn't meet all the
criteria but are very likely to be occupationally acquired HIV.
And as Dr. Fisher mentioned, with the
number of cases you saw just from one hospital in California and the fact that
in March of this year I learned about two nurses, Karen Daley and one other who
I'll mention in a minute, who were notified that they had become infected with
both HIV and hepatitis C, two in one month, all of us that are involved in this
field of occupational safety and health believe that these estimates are very,
very low.
And if you take prevalence data from the
CDC and from the Hospital Association, who has said that 16,000 of the 800,000
to 1 million needle stick injuries per year, 16,000 of those are needle stick
injuries from patients with HIV, and then you add onto that the .03
seroconversion rate, that will bring you to a number of between 10 to 35
occupationally acquired HIV infections per year. And with only 54 since 1985,
we know that this is an underestimation.
I also wanted to note that of the 54
documented cases, 87 percent were from percutaneous injuries and 89 percent from
hollow bore needles, so we can hone down the area of the greatest risk.
Then the risk from these needle stick
injuries. I mentioned HIV .03 or 1 in 300 risk, but the risk from a needle
stick injury sustained from a patient infected with either hepatitis B or
hepatitis C is so much greater. And as a result of the blood-borne pathogen
standard that was implemented in 1991, we have reduced the death rate from
hepatitis B from thousands per year to a negligible, less than 10 per year, as a
result of the requirement for immunization.
The problem with hepatitis C though, is
that there is neither an immunization nor at this point a reliable cure.
The data is all across the map in terms
of hepatitis C. We at the American Nurses Association believe that we have only
begun to see the needle stick injuries that have seroconverted to hepatitis C.
We know that there is as long as a 10-year lag time between infection to illness
and we know that it was only in the last year, in 1998, that the CDC began to
recommend that health care workers be tested for hepatitis C following a needle
stick injury. So that we don't know how many people have developed hepatitis C
and we're going to be seeing this tidal wave over the next number of years.
This was a scan that didn't work. I'll
go on.
Now when we talk about needle stick
injuries, of course we need to find out whether there is a way that we can
reduce the number of needle stick injuries, and this is a slide that
demonstrates the data from the CDC case controlled study from '93 to '95 in
Minnesota, New York and California. That's the starred percentages.
For butterfly or wing steel needles there
was a 23 percent reduction in needle stick injuries following the implementation
of safety butterflies, a 76 percent reduction with blunt needles, and a 66
percent reduction in needle stick injuries with a hinged recap IV needle. And
the last 84 percent reduction from IV safety catheters is data from the
University of Virginia Charlottesville trial. So we know that there is great
benefit from the implementation of safety devices.
ANA's recommendations to the FDA and in
general to institutions as we look at safer devices are to incorporate user
training and in-use testing by users and evaluation by health care workers to
implement safer devices.
Our main goal is to remove all barriers
to implementation. And as many of you know, we've been working in a coalition
to pass the Pete Stark legislation which would require the implementation of
safer needle stick devices on a federal level, as we've been working state by
state.
There are some folks that say that there
should be no unsafe devices on the market, that every device that is on the
market should have a sharps injury prevention feature. We know as nurses that
there are uses for what are less safe devices or unsafe devices.
And I have a question for you, for the
panel, and the question in general is do we need a supplemental premarket review
for devices with sharps injury prevention features or should all devices undergo
the same kind of testing and that any device that increases the risk of needle
stick injury to either the health care worker or, of course, to the family
member who is at home taking care of that patient and may be administering
diabetes, may be administering some other medication at home, that any device
that is being used by any consumer or any health care worker should be a safer
device?
And as Dr. Fisher mentioned, we have
begun a process to develop experts across the country in device evaluation and
selection and our first training will be in Massachusetts since, of course, the
state is very, very eager for this not to happen to any other nurse, and that
will be in November.
And last comment, the family at home
that's taking care of the patient, I talked to a nurse the other day in
Wisconsin about the issues related to needle stick injuries and she said, "Well,
you know, the other day I walked"--pediatric nurse--"I walked into a patient's
room and there was a baby in the bed that had a needle stuck in its stomach."
This was a syringe that had been inadvertently left in the baby's bed and the
child had picked it up, as children do, to play with it and when the nurse came
in to observe the child, this was a syringe stuck in the baby. And we know that
you will join with ANA in wanting that not to happen to any baby but also not to
happen to any other health care worker, either. Thank you.
DR. EDMISTON: Thank you, Ms. Wilburn.
Are there any questions by panel
members? Yes, Dr. Rutala.
DR. RUTALA: Yes, I have one question.
You mentioned some data from Gina Pugliese November 1998 where there was some
market data where health care institutions were not implementing various
engineering controls.
Certain professional organizations have
believed that engineering controls should be implemented when there is a
demonstration of efficacy; that is, actual clinical efficacy. And certainly
we've heard this morning that these devices should be safe and efficacious. How
do you feel about the issue of actual clinical efficacy versus simulated
efficacy testing?
MS. WILBURN: In the questions I noted
that most of the manufacturers have been doing simulated testing instead of
actual testing and we believe that not only should it be actual testing but it
should be actual testing with an educated group of trainers who, like the group
that Dr. Fisher has worked with, can really put a device through its paces and
not just be thrilled with a new bell and whistle that is much better than what
we've had before.
I also wanted to add that Dr. Kessler
earlier was talking about the use of medical device reporting and we've learned
at ANA how unsatisfactory medical device reporting has been for incidents that
occur to health care workers. When I've gone around the country to talk to
nurses about medical device reporting, specifically about the issue of latex
allergy, they say, "Well, we know all about MedWatch. We know that we're
supposed to use it when there's a patient incident. We are unaware that it
applies to health care workers."
So there needs to be an additional
education and advisories from the FDA to reinforce to end users that it is not
only the consumer or the patient but it's the user of the device that should be
reporting an incident.
DR. EDMISTON: Thank you very much.
I want to thank our four presenters.
This ends our formal scheduled presentation portion of the morning.
Before we move on to the open public
hearing session, Martha O'Lone has a statement she needs to read.
OPEN PUBLIC HEARING
MS. O'LONE: Actually this is part of the
open public hearing. I have two statements that I promised if people were not
able to attend that I would read into the record for them.
The first is from the Department of
Health Services Sharps Injury Control Program at the State of California, from
Dr. Cone and Martha Davis. They said, "Since we may not be able to attend the
meeting, would you please accept and read into the minutes the following
comments?
"Recent legislation in California,
AB1208, added Labor Code Section 144.7 that required the Division of
Occupational Safety and Health, Cal/OSHA, to revise the blood-borne pathogen
standard. The revised standard requires California health care workers to use
needles with engineered sharps injury protection and
needleless systems to reduce the risk of sharps injury and potential
transmission of blood-borne diseases.
"In addition to the requirement for a
revised standard, Labor Code Section 144.7 also directed Cal/OSHA and the
California Department of Health Services to jointly compile a list of
needleless systems and needle devices with
engineered sharps injury protection to assist employers in complying with these
new requirements. "Within the California Department of Health Services, the
Sharps Injury Control Program has proceeded in the development of this list. We
make no claims to evaluating devices placed on this list.
"Now that other states have passed
similar legislation, the impact and importance of this California safety device
list increases. As the FDA is a federal organization which approves medical
devices and associated safety claims and labeling, it is our hope that the FDA
will take the lead and establish a process which standardizes the product safety
claims across all states with similar legislation.
"In developing the list, we requested the
assistance of the FDA in identifying needles with engineered sharps injury
protection and needleless systems. We were told
that the FDA could not provide a complete list of FDA-approved needles with
engineered sharps injury protection and needleless
systems. We could, however, begin to develop our list by searching the
Releasable 510(k) database for antistick syringe, which has a product code
80meg.
Only a small subset of devices making
safety claims are available with "meg" codes. As of July 6, 1999, there were
only 17 products listed with the product code "meg." We are aware of piston
syringes not on the "meg" list that are available on the market that make safety
claims. We also understand that there are not similar anti-stick or safety
device codes for blood-drawing devices, for needleless
intravascular administration set, safety catheters, for safety lancets, for
blunted surgical needles or for hemodialysis needles.
Please provide a way for us to identify
safety products. You may wish to consider providing a way to search the
Releasable 510(k) database for engineered safety products in all categories
mentioned above or consider new product codes specific to identify needle
devices with engineered safety component. Alternatively, once safety claims are
approved by FDA, could FDA maintain a list of these safety needle products?
"Additionally, we would like to know what
are the criteria, if any, for making safety claims, above that of 'not
significantly different from existing products.'
"The following comments refer
specifically to the Supplementary Guidance on the Content of Premarket
Notification 510(k) Submissions for Medical Devices with Sharps Injury
Prevention Features.
"Currently a device manufacturer of a
piston syringe makes the following safety claim: 'Once sealed, works like a
built-in portable sharps container' and provides 'sharps container savings. Can
eliminate the need for containers in patient rooms.'
"Are these claims reviewed when the FDA
reviews a product as a medical device with sharps injury prevention features?
The Supplementary Guidance on the Content of Premarket Notification 510(k)
Submissions for Medical Devices with Sharps Injury Prevention Features should
incorporate specific safety criteria for what constitutes a safe sharps disposal
container.
"Lastly, to protect the safety of our
health care providers, FDA should make readily available results from Medical
Device Reporting System that is device-specific. We encourage product users to
report to FDA MedWatch on injuries involving device failures with potential for
blood-borne pathogen exposure. It is important to know which devices have had
failures resulting in injuries and the frequency of occurrence. Users of
products need to know the risk associated with each device. We would like to
see FDA prescribe specific test methods to assess safety performance of a needle
safety device or other medical device product that manufacturer claim will be
'safer' to use than a 'standard device.' How safe is safer and what are the
risks associated with a 'standard device?'"
It ends with "Thank you for allowing us
to submit comments."
DR. EDMISTON: Thank you very much.
MS. O'LONE: And we have one more. The
second one that I have is from a manufacturing firm and our purpose is to go
over some things to add to the guidance, and this goes through actual line
deletions, so it may not make as much sense if I read all this comment on the
second page, but I'll begin with their first page and then try to address what
they've listed as revisions. Those would be addressed also as written comments
in the draft that goes out in the Federal Register in the future.
This is from Biomedical Disposal. It was
written by Cathryn Cambria, who's the director of regulatory affairs and quality
assurance. Its subject is suggested changes to the guidance document.
"In developing these comments we were
guided by the belief that this guidance document should reflect changes in
technology, regulations, and the marketplace since March 1995 when this guidance
document was issued; allow and encourage new technology as it becomes available;
and include clarifications to avoid potential misconceptions. Separately,
making the guidance document for needle destruction units available via the
Internet would additionally help reduce confusion."
They have on here, "Biomedical Disposal
is a private company located in Atlanta, Georgia, which markets products
designed to make the health care workplace safer. Specific products for needle
safety include the SharpX, a FDA-approved needle destruction unit." And they
state that they also recently acquired a patient for safety syringe technology.
Their main comment that they made that
I'll share now, in the interest of time, is that they felt that the guidance
should be amended to say that it's for the review of 510(k)s for devices with
built-in sharps injury prevention features, and also to reiterate that there is
a separate guidance document for needle destruction units.
And that's the end of the comments that
they have that are pertinent to read at this time.
Well, now that we are in the open public
hearing portion of this meeting, let me read a statement. This next half hour
or so will be available for members of the public who would like to address the
panel. Please raise your hand so we can determine the number of speakers that
are present who may be interested in addressing this panel.
I am aware at this time that we have a
representative from the Service Employees International Union. Could you raise
your hand please?
Do we have any other individuals who
would like to address this panel? Could you please come forward? One more? We
have two individuals. Could you come forward, please, state your name, your
affiliation?
MS. GOODENOUGH: Good morning. My name
is Laurie Goodenough. I'm a registered nurse and a member of Local 200A,
Service Employees International Union, AFL-CIO. Service Employees International
Union has 1.3 million members, including 675,000 health care workers. It's the
nation's largest organization representing the interests and concerns of our
nation's caregivers.
SEIU has been a leader in fighting to
protect our members from a wide range of workplace hazards they face. In 1986
SEIU originally petitioned OSHA for the blood-borne pathogen standard that was
eventually completed in 1991. Understanding the important role of FDA regarding
the safety and efficacy of needles and other sharps, in 1991 we petitioned FDA
to better regulate conventional needles and other sharps which can
occupationally transmit hepatitis and HIV.
While FDA largely denied our 1991
petition, the agency has cleared well over 200 safer devices with integrated
safety features. Unfortunately, however, fewer than 15 percent of needles and
other sharps purchased by health care facilities today use these potentially
life-saving devices. Most health care workers have never seen these safer
products. In other instances, lack of proper training has led to resistance to
adoption of safer products by the health care workers themselves.
On behalf of SEIU, I offer our experience
on what we have found to be the critical elements necessary to achieve success
at the work site level during the conversion from conventional to safer needles
and other safer sharps.
Education and training must be
coordinated with the manufacturer of the device and the education staff of the
facility before the device is put into use.
Training must be mandatory for all staff
using the new device.
Training should include a review of the
manufacturer's written program, as well as a video program, on the use of the
device for the initial training and ongoing training.
There must be assurance that the
manufacturer's representatives have clinical experience and are available
on-site or on-call for 24-hour coverage during the initial implementation and
use of the new device.
There must be an opportunity for a
performance test on the new device, including three return demonstrations; at
least one return demonstration conducted with the manufacturer's representative
and at least one return demonstration conducted with the facility's educational
services coordinator.
There must be allowance for extended
training for workers who fail initial performance tests or are uncomfortable
with the new device.
There must be follow-up testing within a
30-day period on the implementation and use of the new device.
Education must include a review of the
risk of exposures to blood-borne diseases from needle stick injuries and how
these injuries can be prevented through the use of control technology.
Education must be provided on OSHA
blood-borne pathogen standards that require the use of feasible safer devices.
Education must be provided and
disincentives removed on how to report a needle stick injury.
There must be the provision of easy,
visual reference material--an example would be a poster--that can be posted
throughout a facility that can provide key points on the use of the safer
control technology.
As a part of any effective program to
implement safer devices, there must be an ongoing monitoring of surveillance
data regarding needle stick injuries before and after introduction of the new
control technology.
Thank you for this opportunity to suggest
actions by FDA to stem this epidemic of 600,000 to 1 million needle stick
injuries which affect our nation's health care workers each year.
DR. EDMISTON: Thank you. Before you go,
are there any questions from the members of the panel?
MS. GOODENOUGH: You mentioned our book
as part of this checklist and I didn't know if I can offer you one of these to
add to--
MS. O'LONE: We have that as a resource
already.
MS. GOODENOUGH: Okay, thank you.
DR. EDMISTON: Thank you very much.
Could the second speaker come forward
please and identify herself?
MS. DUCMAN: Thank you very much. My
name is Kathryn Ducman. I'm a registered nurse and the director of clinical
services with Retractable Technologies Incorporated. We are the manufacturers
of safety medical devices. We have a retractable syringe, Vanish Point syringe
that has been on the market since 1997, as well as a blood collection device
that has been on the market since September of 1998.
I appreciate the opportunity to speak and
certainly am in great agreement with the previous speakers. I again would like
to reiterate that all devices with the potential for sharps injury and/or
blood-borne pathogen exposure undergo the same rigorous testing and standards
that safety devices must go through, so that frontline health care workers are
protected from those injuries.
I also would like to see some type of
criteria that assesses the length of exposure that these safety devices do
protect health care workers from. I think there's an enormous difference
between a device that offers instantaneous or in-patient safety as compared to
those that must be activated manually outside the patient, which does create an
exposure to that sharps injury. So in-patient versus out-of-patient and the
length of exposure is a criteria that certainly needs to be included in that.
Also safety post-assembly of any safety
product needs to be looked at quite stringently. Blood collection devices pose
an enormous risk to health care workers because they are large bore hollow
needles filled with blood. Many, many of the safety devices on the market, once
disassembled, present a nonsafe contaminated needle on the back end phlebotomy
needle that is not addressed in any of the labeling. So once that is
disassembled, they are exposed to a risk.
Also some criteria for the products that
are on the market and have had some history if they are creating sharps injuries
because of their design, and looking at that criteria that would go back and
assess them accurately.
Thank you very much for the opportunity
to speak.
DR. EDMISTON: Thank you very much.
Are there any questions from the panel?
[No response.]
DR. EDMISTON: Thank you.
Is there anyone else in the audience who
was not scheduled or is interested in making a presentation to this panel?
[No response.]
DR. EDMISTON: If not, at this time I'd
like to close the open public hearing and take a break. Let's meet back here at
the top of the hour, 11:00.
[Recess.]
PANEL DISCUSSION/RECOMMENDATION
DR. EDMISTON: Thank you for coming back
promptly. At this time the panel will address the questions that have been
presented. We will discuss these questions in detail and make recommendations
to the FDA.
It is possible during the discussion of
these questions that we may ask for assistance from members of the FDA, OSHA or
NIOSH, who I suspect are still available in the audience.
Could we get the first question up on the
screen, please?
I should also point up before we get
started that we are not voting today, although I may poll the panel members to
arrive at a consensus for the recommendations which we will be giving to the
FDA.
I will read the first question. "Our
current guidance document allows sponsors to perform either a simulated clinical
use study or an actual clinical use study to evaluate the performance of the
sharps injury prevention feature. In most cases, sponsors have provided
information from a simulated clinical study."
Question one: "When would it be
appropriate for FDA to consider data from actual clinical use or simulated
clinical use trials?"
I'd like to open this up to the panel for
discussion. Dr. Rutala.
DR. RUTALA: I'll begin by commenting
that I believe that the demonstration of actual clinical efficacy should be
required for any claim, suggestion or hint that a device will reduce sharp
injuries. That is, if a manufacturer claims, suggests or hints that a product
or a device will reduce sharp injuries, then I believe that clinical efficacy
data should be required.
The manufacturer should first perform
simulated use studies. If the device fails that, additional testing is
unnecessary. However, all devices should be tested under clinical conditions.
In all such cases, a comparative group
must also be studied in order to determine efficacy; that is, the added benefit
from the new device. For example, the frequency of injuries from a blunted
suture needle should be compared to similar surgeries using standard sharp
needles. The usual guidelines for study design should be followed, such as
adequate power, objective outcome measures and randomization.
If a manufacturer is going to claim the
device will reduce needle stick injuries, then this claim must be verified in
actual clinical studies. For example, a self-sheathing IV needle device should
be tested using pigskin by an IV technician. However, lack of injury in this
simulation may not predict lack of injury when used by ordinary personnel on
live, moving patients.
So in summary, if there is a hint, claim
or suggestion that a device will reduce sharp injuries, I believe that not only
should the manufacturer do simulated use tests but also actual clinical use
studies.
DR. EDMISTON: Marcia, do you have any
comments?
MS. RYDER: I am in complete agreement
with Dr. Rutala's offerings. The only thing I would add in regard to the actual
clinical study would be the suggestion that not only would these devices be
incorporated into health care worker review but also those devices that are used
by patients and nonprofessional people also be included in those trials.
DR. EDMISTON: Mr. Palomares?
MR. PALOMARES: Personally, seeing how
the products are used, I don't think it would be feasible to actually conduct
clinical studies. You're talking about very low effect size--not effect size
but incident rate here. And to actually conduct a study along this nature to
develop the information to determine whether it's beneficial or not, basically
like was said earlier, the technology just overrides it. By the time the study
is done, there's already new technology available and that product is nearly
obsolete.
DR. EDMISTON: But for instance, if a
claim is made that the device will prevent infection or prevent contamination of
a line or device, that really needs to be validated; don't you agree?
MR. PALOMARES: I agree with that and
what I think needs to be done is that there should be a standardized protocol to
follow. Right now manufacturers are left open to determine the protocol, the
sample size, the challenge organism for a needleless
system on microbial challenges. And at that, the FDA doesn't have an adequate
benchmark to say did this product perform as good as its predicate?
And really that's what we're here to talk
about. Is it as good or better than what was previously on the market, to get
it cleared?
DR. EDMISTON: Mr. Dacey.
MR. DACEY: I have to, from a consumer
perspective, agree with Dr. Rutala. I'm especially concerned when a product
works down the line to where it's in the hand of the consumer or
consumer-patient. I was joking earlier that I've self-administered insulin for
20 years and I've stuck myself I can't count the number of times inadvertently,
but it's my own needle.
But I did a little research with our
local hospital--I serve on the ethics committee--just to get their perspective
in a generalized way around this subject. Again from a consumer perspective it
was a case of I didn't know a problem existed until I started asking questions.
And I was very impressed with the hospital's response in that they had been
tracking these sharps stick incidents and knew what the costs were and I was
very impressed with the problems that they were confronted with in this. Then I
tried to project that down into home care and it got to be pretty awesome. So I
definitely favor more actual clinical use study.
And one of the comments I got from the
staff people was that they felt at the mercy of manufacturers, that they didn't
have a role in the product design. That resonated over and over again.
DR. EDMISTON: Dr. Fowler.
DR. FOWLER: I agree entirely with Dr.
Rutala. I think we might have to make a distinction of the idea of simulated
studies versus clinical use studies, however, in that the type of study that Dr.
Fisher described earlier, to me is essentially very close to a clinical use
study and that sort of study certainly may well be valuable. A controlled
situation using humans rather than artificial limbs or animal testing or what
have you, that sort of evaluation I think in some situations certainly would be
a valid clinical use study.
I also agree and understand the
difficulty in performing open-ended long-term studies without proper guidance,
so I think there should be criteria developed to specify the types of work that
needs to be done on a particular product under those controlled conditions.
DR. EDMISTON: I think one of the
concerns that I have, and if someone from the FDA could jump in and give me some
assistance on this, in terms of the 510(k) submission, a device that's submitted
to the FDA, even if it's an invasive device, that device is significantly
dissimilar or similar to previously marketed devices. That has a major impact,
does it not, on how it's perceived by the FDA?
MR. ULATOWSKI: That's true. There's two
primary methods of getting to the market and all the devices that have been
cleared, I believe, have been cleared through our 510(k) process, which is a
determination that the product is as safe and effective as a legally marketed
product already out there that is also subject to the 510(k) process.
That has its benefits and its problems.
The benefit is in some cases if the product is sufficiently similar to one
that's already legally marketed, in fact identical in some cases, one can rely
upon certain what we call descriptive information--dimension specifications,
certain bench specifications--to clear the product, and only go to other tests
as necessary to evaluate differences.
The down side is we've been working with
a technology here for 15 years plus, perhaps, where the earlier technology may
not be the best thing on the block but yet it remains substantially equivalent
and legal. And I think one purpose of the guidance and the discussion today
from the public and from the panel is to kind of draw a line in the sand, to say
these are the features that are appropriate, these are the ways one should
evaluate them. And those that would by some chance get some older technologies
that don't meet these expectations really should fall by the wayside now.
I'm giving a long answer but the short
answer is our process constrains us in some respects.
DR. EDMISTON: There's no doubt that
failure of a device can, in part, be documented by benchwork that occurs in the
laboratory. The issue that Dr. Fisher brought up, postmarket evaluation, we
really don't know what's going to happen to these devices once they get out into
the public, the public domain. We see that with anti-infectives. We see that
with a variety of compounds that within the clinical trial period of numerous
patients we find no adverse effects; it's when the compound or the device is out
in the hands of the public that we do see these problems.
So I think we need to separate this
postmarketing and I don't want to forget about it; I want to come back to it. I
really think the postmarketing surveillance part of it is extremely important.
Going back to Dr. Rutala's statements, I
am also in line with his comments concerning these devices, especially these
devices representing new technologies. And many of these devices do represent
new technologies. And to adequately demonstrate that these devices are safe,
there's no doubt that simulated studies can demonstrate that within a very
defined environment.
What I'd like to do is that as we move
through this, let's try and arrive at a consensus on each question rather than
going back to them all at the end.
Martha, could you read the very first
response that Dr. Rutala gave us?
MS. O'LONE: Well, I know that you
started out with some information about clinical efficacy. I didn't quite get
every word. I might ask Dr. Rutala--did you have your remarks prepared?
DR. RUTALA: Yes, I do. I can give you a
copy of them.
MS. O'LONE: If you would like me to read
them, I can do that.
DR. RUTALA: Or I can just reiterate--
DR. EDMISTON: We're particularly
interested in the first two sentences.
DR. RUTALA: That's exactly what I was
going to repeat. My comment was the demonstration of clinical efficacy should
be required for any claim, suggestion or hint that a device will reduce sharp
injuries. If a product does not make a claim, suggestion or hint, then a
clinical use study may not be necessary, but a clinical use efficacy study would
be required for any claim, suggestion or hint that a device will reduce sharp
injuries.
DR. EDMISTON: Is there any comment from
the panel? We're talking about claims specifically that are made with these
devices that may impact on patient care or health care professional caregiving.
Yes?
MR. PALOMARES: How would you capture
that data? When you talk about--
DR. EDMISTON: Actually, Dr. Rutala
answered three questions in his commentary. I think the issue that's at hand
here is that devices that make specific claims--anti-infectives that make
specific claims, they're approved for indications. And while these may not be
approved for indications, the broad indication is that they're safe devices,
that if a specific claim is made, that needs to be validated for the consumer
and for the health care professional.
So should the panel be in agreement to
enter in Dr. Rutala's first two sentences or two and a half sentences as a
response to question number one?
MR. PALOMARES: I believe in the guidance
document it talks about devices that don't--let's say, for example, don't have a
needle in it. It could still say it's for the prevention of needle sticks,
since it does not have it; it's passively performing that function.
DR. EDMISTON: Well, if you make a
specific claim, I think it still falls under that purview.
MR. PALOMARES: I would not agree with
that. I understand that the panel is trying to make what's best and safe for
the general public--
DR. EDMISTON: I think you just answered
that, in terms of the safety perspective, that it would be prudent if the claim
is made with that device, to enter into some type of clinical evaluation.
Let me summarize this first question,
then, the response to this first question. Clinical use efficacy studies should
be required for any specific claim regarding sharps injury protection features.
All right?
The next question, "Are there minimum
criteria in terms of sample size, independence of the evaluators, number of
sites, et cetera that the FDA could consider for both the simulated clinical and
actual clinical use studies?"
Mr. Palomares, I'll let you speak first.
MR. PALOMARES: Well, understanding if we
are going to go in the direction of having clinical studies, how do you
determine--
DR. EDMISTON: Correct me if I'm wrong
from the FDA. We're just making recommendations.
MR. ULATOWSKI: That's right. You're
providing recommendations and we'll think about what you said in total.
MR. PALOMARES: That's fair.
DR. EDMISTON: There will also be an
opportunity for written comments, both from the private sector and the public
sector.
MR. PALOMARES: What are you deeming as
an acceptable sample size? As well as what level of improvement in safety are
you looking for if we make claims along these lines?
DR. EDMISTON: I think if you read the
guidance documentation under statistical evaluation, they make a lucid argument
for the use of confidence intervals. And I think if you look at the confidence
intervals, if you had X number of devices in which you're testing in
multi-centers, and multi-centers could be two centers, with independent
investigators, because obviously you want to have as many users, as Dr. Fisher
indicated, as many users looking at these devices on the front end, that an N,
in my perspective, an N of 500 is not reasonable considering the number of these
devices that are used, even within a single institution.
Marcia, do you have any comments?
MS. RYDER: Well, certainly as
identified, I would agree in terms of the confidence interval perspective and
certainly, again because of the scope of the problem and numbers and spectrum of
users, that we certainly, as scientists, should require the scientific rigor
that is suggested in the document.
DR. EDMISTON: Dr. Rutala?
DR. RUTALA: Yes, I'm just going to refer
to possibly five minimum criteria that could be used in doing a clinical use
efficacy study.
One is that the body sites tested should
conform to the expected use of the device. For example, a peripheral IV should
be used on a patient's arm and hands.
Two is that the sample size should be
based on a clinically meaningful reduction in needle stick injuries. A
reasonable number might be greater than or equal to 10 percent reduction, but
that is debatable. The exact percent reduction should be reported in the
manufacturer's package insert.
Three, as with drugs, manufacturers
should provide data demonstrating efficacy and the study should be properly
performed or performed by impartial outside investigators. When observer bias
may influence results, observers should be masked as to the intervention.
Four, appropriate populations should be
studied. That is, the study should have internal and external validity.
And five, the device studied should be
the actual device to be sold, not a prototype to the device being sold.
DR. EDMISTON: Mr. Palomares, how does
that sound? Does that sound reasonable?
MR. PALOMARES: I agree that it should be
the final device. I know a lot of manufacturers try and use prototypes. It's
not the best way to do it. I believe most of them don't do that but I know
there are some that have done that.
I believe--can you repeat those?
DR. RUTALA: The first was the body sites
tested should conform to the expected use of the device.
MR. PALOMARES: I believe that's true.
DR. RUTALA: The second was sample size
should be based on clinically meaningful reduction in needle stick injuries. A
reasonable number might be greater than or equal to 10 percent reduction.
MR. PALOMARES: I'd agree until about the
10 percent.
DR. RUTALA: That is just a proposal.
DR. EDMISTON: Actually that's an
interesting argument. What we're talking about is the power, the power of
statistical tests.
If you're working on a urinary catheter
you're going to decrease the urinary infection rate, the nosocomial urinary
infection rate from 2 to 1.5 percent, that would involve thousands of patients.
However, as you determine what would be
an appropriate reduction--5, 10, 15 percent--impacting upon your power actually
decreases the number of individuals that you would need in your data pool.
I think it's reasonable, from my
perspective, that if you're going to manufacture a safe device, it should reduce
needle sticks and there should be some documentation of this.
Dr. Fowler?
DR. FOWLER: I agree. I think the
statistical methods, as you say, will require varying numbers of subjects,
depending on what you're trying to achieve and that is something I think that
might have to be a joint decision between the regulators and the industry or
manufacturer wanting to make a particular claim. Obviously, as you say, if you
want to claim your product is 10 percent better than what's out there, you have
to have a certain number of subjects in order to do that and that certainly can
be come up by any statistician.
I think the independence of the
evaluators is, of course, critical and I would also speak to the use of multiple
sites, whether that be at least two, perhaps more. Knowing that products of
this nature will be used in many, many different sites, having the testing done
at multiple sites. It would somewhat increase the variability of the users and
would be a more realistic assessment, I think, of the product in its final
environment.
DR. EDMISTON: Mr. Palomares and members
of the audience, I understand that when you're talking about reduction,
especially if you're making a claim for a device that it's equivalent to what's
already on the market, you may not be looking to demonstrate that the advantage
is there's a tenfold or a 10 percent reduction. You're looking for equivalence
because this is what you submitted to the FDA.
However, getting back to the earlier
statement that Dr. Rutala made, if you're going to make a specific claim, then
you're looking at more than likely having to provide a statistical argument for
that claim.
I don't think the FDA is going to hold us
to what we're saying in terms of a number because they realize the subtleties
that are involved here.
MR. ULATOWSKI: As we approached the
guidance document back in the mid-'90s, we understood that claims being made and
how one approaches clinical evaluation would be a very difficult situation. And
we indicated in our guidance that fundamentally everyone's making a baseline
claim that you're trying to provide a safe device that's going to help prevent
needle stick injuries.
And then beyond that, people may want to,
for whatever reason, want to make some other disease prevention claim or
something else that might incur additional requirements.
I think with the discussion I heard this
morning and from your response, although it's not a question, it's kind of the
coming together of the need for data and is it pre- or postmarket? And what are
the numbers?
I think in terms of numbers, if the idea
is it's preventing needle stick injuries, well, to be able to show that
statistically in a significant manner would, depending on your institution, may
require some big numbers. And we realize that, so we went to a survey, rather
than calling it a clinical study, with the type of traditional clinical end
points that one might see in studies, but rather look at a survey and a user
familiarity, user confidence sort of outcome, rather than hard and fast
incidence differences.
That may not be totally satisfactory and
it has not been, I think, for every institution because then they'd move to do
their own additional studies and collect more data in their own institution.
But I hear the interest in clinical information, in following up on claims being
made, and that's very helpful.
DR. EDMISTON: Let me tell you where I'm
coming from. When a new product comes into my institution, as it does into all
of our institutions, before we accept that product as part of our inventory we
go through our product evaluation committee and at some step there's evaluation
that occurs of that product.
I can tell you with the sharps issues
that quite often we don't have enough information to make that evaluation. So
it's been very difficult to get that information.
This is a very, very difficult issue in
terms of designing appropriate trials that encompass enough warm bodies so that
we can reach levels of significance, even within multi-center institutions. But
I think if specific claims are made--it may be best from the manufacturers'
perspective never to make a specific claim but if claims are made, this is going
to impact on our presentation or how we view that device.
So on one hand, if you're presenting a
device and you're saying it's equivalent to what's available but we're cheaper,
that's one issue. On the other hand, if you're stating we're equivalent but
we're going to reduce your nosocomial bloodstream infection rate, that's another
issue.
So I think you have to be very specific
from the manufacturing perspective what you're saying in the labeling.
So from that perspective, if the device
can be demonstrated to be equivalent to devices that are currently being
marketed and there's no significant change in technology, I think more than
likely we can defer to the historical data on that device. But if a specific
claim is made, then we need to be more probing in terms of what we expect in
terms of the data to evaluate that device as a health care professional or as a
consumer.
MR. ULATOWSKI: That clarification is
helpful. Thank you.
DR. EDMISTON: All right. Do we have
enough information? Yes, Marcia?
MS. RYDER: I just wanted to reiterate
the comment and concern that I made earlier in terms of the design of these
studies, the incorporation of patient users and not simply multi-center hospital
institutions in that evaluation. Is there some way we could interject a comment
in those recommendations?
DR. EDMISTON: You mean working with, for
instance, the phlebotomists?
MS. RYDER: To be very specific, home
care.
DR. EDMISTON: Oh, yes. That's a
difficult nut to crack right there, yes.
MS. RYDER: Because we need to be assured
that they're safe not only for professional users but, as we all know, that the
home care arena is huge in terms of patient users, as well.
DR. EDMISTON: I think the real problem
with home care, home care environment, is trying to document what occurs within
that environment and trying to develop a study where you can actually have the
appropriate controls and know what's going on in that environment. Home care is
a very, very difficult issue.
I think unless someone out there knows
something I don't, most of these devices are going to be evaluated, if they're
evaluated, in institutions that have health care professionals who are used to
using them and they will be the end users. But I think it would be tough to
deal with that home care issue, especially the way it's structured currently.
Any other comments or questions?
MR. DACEY: On that home care issue,
despite the fact that it is so terribly difficult and clearly the user, in
perhaps most cases, would be a non-health care professional, I too would like to
see some effort made, some diligent effort made to examine in a clinical
setting, and again I don't have expertise on how to do this, so that there is
some feedback statistically on what happens when these things are in the hands
of a person at home. Eventually some of them are going to be there.
DR. EDMISTON: One of the questions
that's going to come up is in terms of education and I think in terms of home
care, that's an area where we need to strengthen our education.
MR. DACEY: Absolutely.
DR. EDMISTON: We may be able to get
toward that issue by looking at it from the educational perspective.
MR. DACEY: I certainly can accept that.
MS. RYDER: I would just reiterate in
terms of your comment then, you're saying that we are going to be able to make
the huge assumption that professional workers, if we're able to demonstrate
safety and efficacy, that we can assume that it will also be safe for a patient
user. I think that's probably a huge leap but also I agree that the ability to
be able to study that in a home care environment would be very difficult but
it's something that is here and it's something that we're dealing with every day
as nurses, and even on the educational basis in talking about educating the
health care worker, but they also have to have the ability to educate the
patient. And that hasn't been really addressed, either.
DR. EDMISTON: Marcia, could we reach
some of those conclusions by doing more intensive surveying of that home care
environment?
MS. RYDER: That could be a start.
DR. EDMISTON: That may be it.
MS. RYDER: Through the home car
professionals.
DR. EDMISTON: Home care agency, to try
and assess precisely what is going on because you know and I know this is a very
aberrant environment at times. It's hard to get a handle on what exactly is
going on.
MS. RYDER: Well, of course, because we
certainly don't even know the scope of husicomial infections, as well as other
types of injury.
DR. EDMISTON: All right, Ms. O'Lone,
what have you come up with over there?
MS. O'LONE: Jeez. No, that's your job.
DR. EDMISTON: All right, this is my
job. This is what we have here. Bear with me for a second.
We should get Dr. Rutala to read his
third and fourth sentences. Could you read your third and fourth sentences? I
think you really hit on those areas. We will amend those sentences.
DR. RUTALA: I think we agreed on the
body sites tested--
DR. EDMISTON: Yes.
DR. RUTALA: --should conform to expected
use of the device.
DR. EDMISTON: Yes.
DR. RUTALA: I think the issue of a
reasonable number as it pertains to meaningful reduction was an issue but the
comment was sample size should be based on a clinically meaningful reduction in
needle stick injuries.
DR. EDMISTON: We're talking, in part,
about devices that are making a specific claim.
DR. RUTALA: That's correct. That's
correct. Very important distinction.
DR. EDMISTON: So devices that are
making--
DR. RUTALA: Not equivalency. A claim of
reducing needle stick injuries.
DR. EDMISTON: All devices, if they
involve puncture of some type, should be tested on appropriate tissues or
simulated tissues.
In terms of the sample size, if a
specific claim is made, then an appropriate sample size should be determined.
DR. RUTALA: That's correct.
DR. EDMISTON: I don't think we have to
determine that sample size.
DR. RUTALA: Or the percent reduction.
DR. EDMISTON: Or the percent reduction.
No, we don't.
DR. RUTALA: The third point was as with
drugs, manufacturers should provide data demonstrating efficacy and the study
should be properly performed or performed by impartial outside investigators.
The fourth point was appropriate
population should be studied. And the fifth is the device study should be the
actual device used.
DR. EDMISTON: Are we all fundamentally
in agreement with those principles?
[Nods from the panel members.]
DR. EDMISTON: And you indicated that you
wanted independent investigators, that it was appropriate to have independent
investigators and that there should be at least two or more sites involved in
the clinical evaluation of those devices in which a specific claim is made. Is
that what you're saying?
DR. RUTALA: I didn't say two or more
sites but I will accept that.
DR. EDMISTON: Actually Dr. Fowler said
that. Sorry about that.
Martha has indicated that it might be
appropriate to indicate what type of patient population or end user population
that we would be studying and I think based on our discussion that we'd have a
difficult time really--I have a difficult time and I'm not sure how the rest of
the committee feels, the panel feels, but in terms of providing some rational
way in which we can get to that home health care population, I think we can
agree that it would be appropriate for a manufacturer to develop a reasonable
protocol which then is available, farmed out to two or more investigators, who
can do the studies. I don't think that can be done per se for home care because
it's just not been studied very well in the past.
MR. ULATOWSKI: You raised a point to
consider and I think we can put our minds to it and get additional comment from
the public and maybe there's an approach to be taken there.
DR. EDMISTON: Let me at this time ask
Dr. Fisher, would she be willing to come to the podium and make a comment
specifically addressing this home health care population?
DR. FISHER: We are currently doing a
study with home health care and the problems are enormous but I think that
they're solvable.
One of the things we've actually done is
do a needle box for home health care because we found that it just didn't hold
in the situation.
As I was hearing the discussion I was
thinking again that if you have trained users, they can not only deal with the
issues for the health care worker and the home care but they can be the
resources for getting the other data.
I think we do have to separate the issues
into three components. One is the health care workers themselves being
exposed. Now, one of the issues that they brought up is that if the user, the
patient is going to use a nonsafety device and they have to demonstrate that,
that they can't use that safety device. They don't have a safety device in
demonstration, so that they have a loop that you have to think about.
And I know that there are issues and
costs, that you would want a diabetic not to have to buy the more expensive
devices but how are you going to demonstrate that for that person or the
lancets?
So you have that component. How can they
do that kind of teaching and demonstration if they're not using a safety
device? Hopefully the market will come down and we'll be able to have the
safety device but that's an issue.
When they do their own procedures, what
kind of technique? And I must say that I was rather staggered to find out what
people are doing in the home. What three years ago would have been done in an
ICU, at least in the Bay Area is now being done at home, so that there are very
complex procedures that are being done there.
The problem also that goes on in there is
that the patient may come home from the hospital with one device or one system,
certainly with a needleless system, and then the
whole thing has to be changed, so you have more complexities there.
Then the issue that of nonhealth care
people administering techniques. I do know in my own family that my young
nieces were administering to their 88-year-old father complex procedures because
they wanted to keep him at home. So I was somewhat staggered at what they were
using. So the protection of that, the nonhealth care worker provider.
And then the issue of the protection of
the patient, which may be different, as was pointed out before, having a stick
from yourself. It may be painful but it is another--you don't have the kind of
risk. So you're faced with that problem.
I would think that the examination of
this issue is of a high priority and there is virtually no data available. And
I think that that would be something that both in terms of FDA and the Health
and Human Services should be putting in quite a bit of resources to research
this area because it is the booming area and I think it presents an enormous
risk.
I think that the approach that we've
taken is applicable because we saw that. In fact, the pictures that you saw
about the design course was a design course for home health care providers.
DR. EDMISTON: Thank you, Dr. Fisher.
Could I have the speaker in the back,
please? Would you please identify yourself, please?
DR. FARRELL: I'm Dr. Farrell from CDER.
Seven months ago I left my hematology-oncology practice and I will tell you that
there is a CALGB protocol randomizing febrile neutropenic patients to home care
versus hospitalization and sometimes the administration of the second drug that
day is done by family members. I think home care studies have been done and are
successful.
DR. EDMISTON: Please identify yourself.
DR. WENIGER: Thank you. I am Bruce
Weniger from the National Immunization Program at CDC and I wanted to just
follow up on a point that Dr. Fisher mentioned about the absence of data.
I understand that the California sharps
safety legislation is going to require every hospital and clinic to maintain a
log of needle stick accidents, which I think is going to be very, very important
and useful. And yet if we use the analogy to the systems that we have for
monitoring adverse events of vaccines, we mandate that adverse events believed
to be associated with vaccines are reported to some central place, the
Vaccine Adverse Events Reporting System of FDA and
CDC.
But, at the same time, the FDA also
receives data from the manufacturers on the number of doses of vaccines in every
lot, so that they can put denominators under those numerators of adverse events.
So two issues to consider are should FDA
consider requiring the reporting of this information from those logs in some
way? And secondly, should FDA consider receiving from the manufacturers of this
safe needle or old needle devices the number of products within each lot
distributed in the United States so that they can eventually put denominators
under them and then compare the rates on a national basis of these accidents?
Thank you.
DR. EDMISTON: Thank you. I think your
comments really speak again to the postdischarge nature of this.
Let me see if I can encapsulate this a
bit and I want comments from the panel. Would it be appropriate for the panel
to recommend to the FDA that efforts be taken under way to investigate the
optimal means by which devices such as these can be studied in the home health
care environment and to start this as a discussion process with public comment,
comment from industry, but not per se make this as a mandate from this panel?
Is that appropriate?
[Nods from the panel members.]
DR. EDMISTON: Does FDA agree with that?
MR. ULATOWSKI: That's just fine with me
as far as the recommendation is concerned.
DR. EDMISTON: Okay. I think that takes
care of question number 2.
Question number 3, "In addition to the
survey format, are there any other methods that the FDA should consider when
evaluating the performance of these types of devices?"
I think I'll ask my colleague to my right
if he has any comments regarding that.
DR. FOWLER: Well, I think we've already
really spoken about that, the comment about the clinical use studies. I think
the survey format can provide good postmarketing data, which should probably be
looked at. And, in fact, a clinical use study may involve, to a greater or
lesser degree, a survey format.
DR. EDMISTON: When you talk about survey
format, you're talking about survey format from the end user, correct?
DR. FOWLER: Well, my understanding of a
survey format would yes, that the company, for instance, in a clinical study
would obtain the information from the end user of the product, yes.
DR. EDMISTON: Well, this is information
that would occur prior to marketing, so it doesn't really correspond to
postmarking, correct?
DR. FOWLER: I'm not sure it would
necessarily apply to one or the other. It could be both.
DR. EDMISTON: Marcia?
MS. RYDER: Could you repeat the
question?
DR. EDMISTON: "In addition to the survey
format, are there any other methods that the FDA should consider when evaluating
the performance of these types of devices?"
MS. RYDER: I concur. I believe we've
already covered that.
DR. EDMISTON: Let me just make one
interjection here. I think that the activities that we've seen today from Dr.
Fisher's group, from the Service Employees International Union, the surveys that
they've developed, these also might be appropriate for consideration on the part
of the FDA in looking at some of these guidance criteria.
There's a wealth of information that
these organizations have already developed and I think it would be appropriate
to at least look at this in developing future guidance documentation.
MR. ULATOWSKI: I think people put a lot
of time and effort to creating the sorts of reporting forms that are used today
and I'd be perfectly happy to entertain a 510(k) that had data submitted using
one of these mechanisms, these instruments, if you will.
So I applaud June and other of her
coworkers' efforts in this regard.
DR. EDMISTON: Mr. Dacey, do you have any
comments?
MR. DACEY: No further comment.
DR. EDMISTON: So I suspect what we would
actually propose is that in addition to the surveys currently in place, it would
be appropriate to incorporate data from TDICT, SEIU and what was the other
organization? The New York State? New York State Department of Health--these
types of vehicles as surveys.
Yes, Dr. Fisher?
DR. FISHER: As flattering and validating
of our work are those comments, I think we have to be realistic. We can't even
get people to report needle sticks. And I have some suspicions that surveys are
not going to--I would be encouraged but I'm not optimistic that we're going to
get that kind of data.
And I would like to suggest that we think
in more formalized outcomes. That was why I didn't go into the whole issue of
pilot testing because I didn't have enough time, but I think if you would
establish standards for pilot testing which could be done premarketing and that
we develop ways that we can easily get material.
One of the things we were talking about,
developing a little Palm Pilot type of thing so that you instantaneously can
enter in that you used the device, that the device was adequate or you have
maybe four or five different parameters that you can just--because otherwise in
an environment which Susan Wilburn described where people are very, very busy
and they're running around, you're just not going to get that data that we need
to get.
So there has to be attention directed to
formalized studies and that formalized studies have great specificity. In fact,
we submitted a graph and I don't know if it's going to be funded, to NIOSH or
not, to have a user-based design pilot study, to come up with a national agenda
where we poll people who are interested and develop some criteria for what pilot
testing should be, what should be included in pilot testing and, when you give
that, to test it with a group of users and with a control group, to see if you
can get better data and to have some kind of way that you can quickly get that
data, that you don't put a burden onto people who don't even have time for
reporting.
We did not bring this up but reporting
goes from 30 percent to 60 percent. No matter what efforts you make, you can't
get--the most common one, besides which some people are discouraged because in
some hospitals your pay, your merit pay will depend on whether you have a needle
stick or not, is "I don't have the time to do that."
So I think we have to be realistic and
try to--I'm not saying we shouldn't do it but we should be more creative in
trying to get that data.
DR. EDMISTON: I think your survey data,
even though you found limitations in it and we all recognize limitations in this
type of data, still is valuable in that it recognizes the problem and it
addresses the problem.
As Mr. Ulatowski indicated, there was a
lot of work involved in these studies and I think they're a valuable format. I
think that in terms of--when would you anticipate that this document would be
revised and available for public comment?
MR. ULATOWSKI: That's always a good
question. Probably sometime in the fall.
DR. EDMISTON: Yes, I think it would be
very difficult to implement the technology and the research methodology at this
stage, to try and address this particular issue.
DR. FISHER: I was giving that as a
perspective--
DR. EDMISTON: As a perspective. But my
feeling about this is that this probably won't be the last revision of this
document, that this is going to be an ongoing process until we essentially reach
a zero state.
So does the panel feel comfortable in
using the previous survey vehicles and also incorporating the work that's been
done by other agencies in surveys to assess the risk?
[Nods from the panel members.]
DR. EDMISTON: Okay.
Number 4, "Are the evaluation criteria
listed in the guidance document appropriate and inclusive?" Mr. Palomares?
MR. PALOMARES: I have no comment at this
time.
DR. EDMISTON: Let me get a little help
from the FDA. Can you review this particular aspect in terms of the evaluation
criteria? Off the top of your head.
MR. ULATOWSKI: Well, we showed a couple
of slides of elements of the guidance document in terms of the bench testing,
biocompatibility, preclinical, clinical, simulated and clinical.
The panel, though, is primarily
concerned--typically any panel that we bring here is concerned with the clinical
aspects of guidance documents and not the engineering aspects so much.
I think we have all seen some different
things presented or in front of us here and if there's one or two noteworthy
items that seems to be worth mentioning to us, then that would be acceptable to
us. I don't expect you to go down and try to catalogue, compare and contract
everything on those lists.
DR. EDMISTON: When I look at those
guidance documentation and evaluation criteria, as you go from bench to a full
blown clinical study, if indeed a clinical study is warranted, and in most cases
it probably won't be warranted, I think from an engineering perspective you hit
that from the bench studies and you can also hit that in the simulated studies,
too.
So my take on this is that the evaluation
criteria that are currently in place have been well conceived and documented and
we can fine-tune these in terms of the type of end users we're studying and
eventually with postmarketing types of surveillance. But I'm personally happy
with the evaluation criteria that are present in the document.
MS. RYDER: A question for you. Are the
current items in this document in compliance with AMMI and ISO standards today?
MR. ULATOWSKI: Well, there is no
specific standard that speaks to the safety features. There's discussion of
development of standards. There are standards for syringes and needles, those
types of things, but not for these additional features.
MS. RYDER: Okay. I was specifically
referring to the bench testing and the biocompatibility--
MR. ULATOWSKI: Oh, yes, there's adequate
standards with regard to biocompatibility and engineering tests that can be
applied in this instance.
I think one thing with a guidance
document, we try not to be too prescriptive in our guidance document on how one
may approach a certain area of interest. There may be more than one approach to
an engineering test, for example. I've heard comments about, well, you need to
provide a little more information and end points and criteria. There's pros and
cons to that. You don't want to box technology in. But I understand the need
for people to get more information sometimes.
DR. EDMISTON: Mr. Palomares?
MR. PALOMARES: To the degree of testing,
whether it's bench, simulated clinicals or clinicals, I agree and disagree with
the panel to a certain extent and I'll work with the panel here. However, one
thing as a manufacturer that we see is we want to be working off the same
playing ground. What I mean is on microbial challenges--
DR. EDMISTON: Could you speak into your
microphone, please?
MR. PALOMARES: Excuse me. With regard
to microbial challenges, right now most manufacturers use that as the benchmark
for getting a needleless system approved, because
that's what ODE has been asking for.
However, when you're looking at the
various tests that the manufacturers perform, you don't get a consistent
result. Sample size, challenge organism, number of activations, point of
use--all of those come into a factor of whether this product is safe and
effective.
I think from an industry standpoint,
we're looking for something more standardized. That way we can always give
something where ODE can review it and say this is an apples to applies
comparison and this product is equivalent or not equivalent to what's existing
on the market.
DR. EDMISTON: Well, that's an
appropriate comment and I think what we could propose is that the FDA entertain
the development of standardized testing protocol specifically in microbial
challenges so that you're right; your competition or whoever is not doing less
than you are to demonstrate the efficacy of your device.
Dr. Rutala?
DR. RUTALA: No questions.
DR. EDMISTON: So with the evaluation
criteria in place, we feel comfortable with the evaluation criteria, with the
caveat that the panel recommends that the FDA look at the development of
standardized testing protocols, specifically in microbial challenge protocols,
in comparing these devices. Inclusion.
Is the panel in agreement with this?
[Nods from the panel members.]
DR. EDMISTON: Thank you.
Final question for the first response.
"How could the results of these evaluations be presented to users? Included in
the labeling?" I think Dr. Rutala, that was his last two sentences. That's
also been echoed for the past half an hour by the various panel members.
Dr. Rutala?
DR. RUTALA: Let me make a couple of
other comments regarding labeling criteria that could be considered.
Of course, labeling should consider
intended use, as well as unimproved uses, training required for use,
disabilities which preclude use, potential dangers with using the device, and a
range of expected reductions in injuries compared to the standard device.
And, of course, we also talk about the
labeling issue as it pertains to demonstrating efficacy when there is a hint,
suggestion or claim of efficacy in reducing sharp injuries.
DR. EDMISTON: I think your last
statement, the expectation of reduction of injuries? There should be a
reasonable expectation?
DR. RUTALA: A range of expected
reduction.
DR. EDMISTON: A range of expected
reduction.
DR. RUTALA: Compared to standard
devices.
DR. EDMISTON: Compared to standard
devices.
DR. RUTALA: That's correct. Again we're
talking about the device that has a claim of efficacy.
DR. EDMISTON: And the benchmark for that
could be what's current in the literature.
DR. RUTALA: That's correct, or a
comparison with the standard products.
DR. EDMISTON: Do we have an OSHA
representative in the room? Could you come to the podium, please? I was told I
can't torture you.
Let me ask you a question because we all
deal with OSHA.
MR. ULATOWSKI: He needs to identify
himself.
MR. LANDKRON: I'm Kevin Landkron with
OSHA.
DR. EDMISTON: We understand what our
obligations are in terms of training our employees, whether they're full,
part-time or contract employees, as they come into our institution, especially
in terms of blood-borne pathogens.
Tell me how does OSHA perceive labeling
of equipment that we are using within the institution? Do you care about that
or are you moire interested in what we're doing on our end to ensure the
equipment is being used appropriately or safely?
MR. LANDKRON: As far as labeling of a
device, I wouldn't think that we would come into that per se. I can't answer
definitively. I know in blood-borne we have, as far as contaminated medical
equipment, we require that to be labeled. Sharps containers, we require those
to be labeled.
So we do have some labeling requirements,
but as far as the labeling of the device prior to it getting into the workplace,
I don't know what role we would play in that.
DR. EDMISTON: All right. So I think it
gets back almost to the first--very similar to the first question in that if a
claim is made, that claim needs to be documented in some capacity so that the
user is able to see that claim, either as an insert or through the educational
materials that are presented to him by the company.
Does that sound reasonable, Mr. Palomares?
MR. PALOMARES: It does sound
reasonable. Unfortunately, the perspective from industry is that your
directional insert that comes in with your case of product usually ends up on
the floor of central supply. It doesn't get to--
DR. EDMISTON: Oh, you're right. You're
right. You're right. You're right. There is an onus on the institution in
terms of ensuring that, but that's not the FDA's venue.
MR. PALOMARES: No, it's not.
DR. EDMISTON: That's why I brought up
the OSHA guy.
So you're right. Compliance is an
institutional issue, from our perspective. But you're in agreement that if
claims are made, or even if claims aren't made, if this is a technology that
requires education on the part of the handler, and virtually all of these
devices do, that this is clearly spelled out--it's reasonable to have this
clearly spelled out within the product, either as an insert or as a poster, as
Dr. Fisher has indicated, or some type of educational aid.
MR. PALOMARES: It is reasonable to
expect that, yes.
DR. EDMISTON: Does the panel have any
other comment?
DR. RUTALA: The only other comment that
I would make is that this question seems to go beyond just the efficacy issue
and I was wondering if we should consider other issues, such as intended uses,
unapproved uses, training required for use and disabilities which preclude use,
such as a sight-impaired person to use the device, or potential dangers with
using the device.
So beyond that issue of efficacy for a
device making a claim.
DR. EDMISTON: Since I'm one of those
individuals who's never read one of those inserts, explain to me. Is it clearly
defined in the inserts the intended use of the device?
MR. PALOMARES: The device usually has
its intended use on the directions for use or its package labeling. So it
states what it's used for.
DR. EDMISTON: Okay. I think in terms
of--well, within an institution in terms of visually impaired individuals, I
suspect the greater onus is placed upon the institution.
Marcia, how do you feel, in terms of the
education of that person?
MS. RYDER: Indeed, but once again it
goes that we need to begin thinking beyond the institution and into the home
care setting.
I believe, if I'm not mistaken and we can
certainly address this, that many of the things that Dr. Rutala detailed are
already part of requirements of labeling. Is that not true?
MR. ULATOWSKI: Well, there's labels for
products, syringes and that. A lot of the instructions for use that were
mentioned are not included because they're commonly understood sorts of
provisions.
But for safety devices, I would not
consider them commonly understood and would expect more information in labeling.
DR. EDMISTON: Yes? We have a volunteer
from the audience.
MS. DUCMAN: Again my name is Kathryn
Ducman, registered nurse, director of clinical services with Retractable
Technologies.
My question on this issue pertains to
products already in use. As you mentioned, standard syringes that have such an
historical perspective implied uses but, for example, they are labeling as
nonreusable products when they are inherently reusable.
I direct you to remember that reusability
is certainly an issue of safety, whether that reuse is intentional or
inadvertent.
And when you put that in perspective with
the clinical situation, a very volatile and uncontrollable setting, to label
something as nonreusable might be physically impossible. And how will the FDA
regulations back-track and look at that issue in regard to standard products as
it does to safety products?
MR. ULATOWSKI: Well, that's a whole
other issue for another day, actually.
DR. EDMISTON: I think that takes on two
issues. First of all, we're talking about sharps instruments and the issue
today is not--
MR. ULATOWSKI: That's reuse of single
use only instruments and we're addressing that separately.
DR. EDMISTON: Right.
MR. ULATOWSKI: We do have a policy
forthcoming.
MS. DUCMAN: But as the reuse pertains to
sharps injuries. I mean reuse is either inadvertent or intentional and how can
you label something as don't reuse when it is inherently reusable, whether that
reuse is the inadvertent stick that occurs in an uncontrollable setting,
clinical setting, or an intentional use, which is often what is thought of in
opposition to sharps injuries?
MR. ULATOWSKI: I understand what you're
saying. It's somewhat outside the purview of exactly what we're talking about
today but your point is well noted and we are considering that aspect in terms
of safety with reusable products or single use only products.
MS. DUCMAN: Thank you.
DR. EDMISTON: So let me poll the panel.
In reference to Dr. Rutala's statement, your statement in terms of labeling, in
terms of the criteria for labeling, intended use must be thoroughly documented
and present on the insert and available for the user.
Also, how do we make this information
more presentable to the user? I would suspect that we could propose to the FDA
that we look at strategies either educational, tapes, because I know some of
these devices--I do look at the tapes--some of these devices do come with tapes,
that these types of educational tools are inherently valuable to our health care
professionals and we use them for in-services.
Is the FDA in agreement with that?
MR. ULATOWSKI: [Nods.]
DR. EDMISTON: Okay, let's move on to
question number 2. We have 20 minutes left and let's try and move along here.
This is the toughest part of the whole format and I think we'll move quite
rapidly now.
"Currently sponsors submitting
applications for needleless access devices--
intravenous systems that do not require the use of a needle--are asked to
demonstrate that their device is substantially equivalent by providing
nonclinical bench data to demonstrate that their device does not increase the
risk of microbial contamination of the fluid pathway, validation of the cleaning
method, and instructions for use. What additional type of information should be
considered for our premarket review?"
And this we've already addressed in terms
of the FDA should attempt to develop standardized testing protocols for
microbial contamination. Is the panel in agreement with that?
[Nods from the panel members.]
DR. EDMISTON: Number 3, "What mechanisms
does the panel recommend to the FDA to increase user awareness of the safe use
of these devices?"
Now let me ask the FDA on this. You're
proposing, the FDA is proposing that they would provide documentation to the
public in terms of the way in which these devices should be used, when they
should be used?
MR. ULATOWSKI: That's all part of it.
And perhaps Dr. Joseph would want to add to that.
DR. EDMISTON: Could Dr. Joseph give us a
brief synopsis.
DR. JOSEPH: As you say, that is indeed
part of the it but also we were thinking in terms of mechanisms, and you touched
on some of them--tapes, posters. You know, what vehicles would be most
effective to the users of these products that we would be able to get the
message to them?
And I think in terms of the message,
that's part of another question.
DR. EDMISTON: So we're proposing
multi-media type of documentation.
MR. ULATOWSKI: We haven't been as
broad-based as you're discussing now in our evaluations, but we incorporate an
expectation in regard to these aspects.
DR. EDMISTON: It always amazes me that
the OSHA guys never want to get involved in this part of it. I'm picking on
you; I'm sorry about that.
So how does the rest of the panel
perceive this? Let me ask Mr. Palomares first, representing industry.
MR. PALOMARES: Well, as a member of
industry, what we try to provide is adequate information such that a user
facility can train their personnel, whether that's adequate directions for use,
whether that's having a product specialist on site during the trials and
conversions period, whether it's tape, whether it's demonstrations. That all
does occur.
DR. EDMISTON: So you think anything that
would enhance the appropriate use of your devices, even on the part of the FDA,
to demonstrate how these devices should be used, that would be reasonable?
MR. PALOMARES: I think it already
occurs. I don't think it needs to be part of the regulatory process simply
because in order for a facility to take on this, they're asking the manufacturer
to provide this information. They're asking to train us, demonstrate how this
product is used, give us some support.
To have FDA now regulate and saying this
is adequate support or not, does it provide a benefit?
DR. EDMISTON: As part of your marketing
of these devices, you actually provide in-service for most of these devices,
correct?
MR. PALOMARES: That is correct.
DR. EDMISTON: Marcia, as a user, how do
you perceive that? Is the in-service usually appropriate? Is it comprehensive
enough?
MS. RYDER: For the most part, industry
does assume a large responsibility for doing that and in most good companies I
would have to say it's done pretty well. Otherwise if they don't educate
properly, their device doesn't work. So I think they do take a major step in
doing that.
Again back to the home care issue and the
end user, because the scope here is so huge, perhaps a suggestion to the FDA
would again consult with patient educators in terms of studying and look at
those mechanisms by which patients learn best and perhaps incorporate some of
those systems into the pieces that you develop.
DR. EDMISTON: Mr. Dacey, I haven't
forgotten you.
MR. DACEY: That's fine. You touched on
an area I only have 100,000 words on.
After years in the world of preparing
patient education materials and test-driving many, many formats and mediums and
also studying the whole world of marketing, in fact, I think it would behoove
the FDA to look at the private sector to see how they strive to influence
consumer decisions.
And I've even come to the point, after
all these years, of questioning the term "patient education." Are we really
educating or are we influencing? We're seeing shorter attention spans. We're
seeing, when you get into the younger generation, what I call Generation
Extreme, you see a whole different demographic profile.
So people, especially when you get into
self-care issues, when they have the need--they aren't even aware of these
issues until they are confronted with it in their personal lives. That is the
same with their families, who may be operating in the home care setting.
I think there is no well defined, totally
effective medium for communicating to all patients and to all caregivers the
information that you want to provide. I think you've got to almost customize
it. And very often it becomes essential to do it on a one-on-one basis.
My book shelf is crowded with
instructional videos, some of which I haven't even gotten around to seeing yet.
And now with the Internet and DVD and all the other stuff that's coming down the
pike so rapidly, all I can do is urge you to look at the private sector, find
out what they're using, what works, and consider, seriously consider customizing
communication to providers who are, in this case, self-care perhaps, and
consumers.
DR. EDMISTON: Dr. Fowler, do you have
any comments?
DR. FOWLER: I would suggest that FDA
leaves any requirements very, very broad-based. And while the concept of
requiring appropriate training and education I think is necessary, the specifics
of that training and education, I think, should be totally left up to the--I
think a recommendation should be that whatever appropriate training and
education vehicle the manufacturer chooses, if it appears appropriate to FDA,
would be allowable. I would think that overregulating or overspecifying
requirements in this area would not really be of any benefit.
DR. EDMISTON: Dr. Rutala?
DR. RUTALA: Yes, just two comments.
First, I do agree with the preceding comments but I would like to possibly allow
the panel to consider a variation of a couple of the comments.
First, the issue of training, user
training. I was wondering, like what is done for the OSHA blood-borne pathogen
rule, where there are certain criteria that must be met to essentially achieve
training on an annual basis, if there isn't some indication here for the FDA to
consider some minimal criteria as it pertains to user training, minimal criteria
such as how to use the device, the indications, the contraindications, the
hazards, the material incompatibility issues, things such as that.
I agree that that should not be very
prescriptive, it should be broad-based, but the criteria should possibly be
considered.
The second point is the issue of
competency testing of users. It's becoming very common now in health care to
recognize the need for competency testing. That is, we can train persons by
showing videos and by asking them to listen to a slide presentation but very
commonly, that does not result in a competent person, a person capable of
performing a task.
So there's more commonly now competency
testing to ensure that the person performs the task after hearing the user
training.
So the two points that I would like to
bring up are the issue of considering minimal criteria, and I don't know that we
decide what they are--we've addressed a few of them but minimal criteria for
user training of these needleless devices or
protective sharps.
And the second, when indicated,
competency training, so that it's not merely a matter of seeing it done but
actually performing it and ensuring that the person knows how to perform it
properly.
DR. EDMISTON: In reading through this,
it's obvious that 3 and 4 really run together. Let me read 4. "Is there a need
for educational programs for use of sharp injury prevention devices? If so,
what content should be included in educational programs to encourage the safe
and effective use of these devices?"
I think in terms of your comments that
the FDA's position should be that the information, the insert information
provided by industry should describe the intended use of the device in which it
should be appropriately used and also should address, as you've indicated, the
competency, the potential competency of those individuals who are using the
device.
Now in terms of how this information can
get across, I think there is some area of debate--whether it's part of an
in-service by your colleagues in the industry or is there some formal mechanism
by which the FDA puts together a series of educational tapes and then provides
those to the end user?
I don't know if that format needs to be
completely worked out but it sounds to me, from listening to Dr. Joseph, she is
addressing this particular area in terms of education. Is that correct?
DR. JOSEPH: That's correct.
DR. EDMISTON: I would like to say one
more thing. The home health care area is extremely important and it's come up
several times. And I think the level of sensitivity should be such that that
also should be an area of priority for the FDA.
DR. JOSEPH: We have certainly heard it.
MS. RYDER: Again one more comment in
regard to the home care area. I would suggest that one would be careful at how
those requirements are placed on the manufacturer or the institution in
educating the home care patient. And the reason for that is because we're all
very much aware of the reimbursement issues, which are getting much worse
instead of better.
So the time that nurses have to spend in
educating patients becomes less and less and less. And now we're suggesting
that--I'm suggesting that we be careful on where we put that responsibility.
DR. EDMISTON: I think this whole issue
of home health care is really a black box that's not going to be clearly defined
by this criteria document, but I think we need to be thinking about it in the
work that Dr. Joseph and Dr. Fisher and others in the audience are alluding to
needs to be considered, especially in future revisions of this documentation.
Is the FDA in agreement with our
comments?
MR. ULATOWSKI: [Nods.]
DR. EDMISTON: Number 5, "Are there other
areas of the guidance document that need to be revised?"
I keep hearing very clearly that we need
to have a mechanism for postmarketing surveillance. We've heard from Dr. Fisher
that pilot testing as she defines, which I really look upon as product testing
within the institution, is defined as postmarketing. She suggested there should
be a premarket-type pilot, and we've talked about that.
But in terms of this particular question,
I really feel there should be some mechanism in place to look at postmarketing
surveillance for these various devices.
Now will we get 100 percent compliance?
Unlikely. But I think this should be a consideration that is entertained by the
FDA.
Let me panel the panel.
MS. RYDER: No added comments.
DR. EDMISTON: Dr. Rutala?
DR. RUTALA: [Nods.].
DR. EDMISTON: Mr. Palomares?
MR. PALOMARES: [Nods.]
DR. EDMISTON: Mr. Dacey?
MR. DACEY: I agree.
DR. EDMISTON: Terrific. That was
painless.
Yes? We have a guest.
MS. WILBURN: Susan Wilburn from the
American Nurses Association.
I wanted to add an additional example of
information that's available, a database about device-specific injury rates.
That is a database called Epinet that is available from the University of
Virginia in Charlottesville that is complementary and incorporated in some ways
in the CDC database.
I wanted to reiterate what the doctor
from the CDC was talking about--the Cal/OSHA standard for needle stick reporting
will provide device-specific data and the medical reporting guidelines that have
been proposed and will be finalized this year, according to OSHA, also will
include a change in needle stick reporting.
So the federal OSHA blood-borne pathogen
standard will include all needle stick injury reporting, not just those needle
sticks that went on to cause an infection later.
DR. EDMISTON: Thank you very much. We
can't forget Jeanine Jacgertz's contribution to this field. That's an absolute
benchmark for many of these future studies.
MS. WILBURN: As you've been referring to
what's happened in the health care field in terms of downsizing and really
tightening up of budgets, one of the things I've heard in the last couple of
months from institutions related to manufacturer-provided education on new
devices is that I've had nursing administrators say that the manufacturers have
told them that they have to pay for that kind of education.
So I think that clarifying
recommendations for education for manufacturers is very important.
DR. EDMISTON: Does the panel have any
more recommendations or--oh, we have the OSHA fellow. She says round three.
MR. LANDKRON: Just very quickly, 3 and 4
are about educational programs and formats and things of that sort. We do have
training requirements in the standard. Dr. Rutala makes a good point, where we
spell out certain criteria that we expect to be met in that training.
DR. EDMISTON: I knew you guys were in
there somewhere. Thank you very much.
Are there any final comments from our
panel members?
[No response.]
DR. EDMISTON: If not, I'd like to ask
the FDA if we have addressed the questions sufficiently.
MR. ULATOWSKI: [Nods.]
DR. EDMISTON: If so, I will now close
this part of the meeting so that we can break for lunch. We will reconvene at
1:30. Thank you very much.
[Whereupon, at 12:30 p.m., the meeting
adjourned for lunch, to reconvene at 1:30 p.m. the same day.]
A F T E R N O O N S E S S I O N
[1:35 p.m.]
MS. O'LONE: I think we'll go ahead and
start for this afternoon, in the interest of being on time.
I'm Martha O'Lone. I'm the executive
secretary of the General Hospital and Personal Use Devices Panel and I'd again
like to welcome the audience to the afternoon portion of this meeting.
And again for the purposes of
transcription I will ask all persons addressing the panel to identify themselves
and their affiliation and if they have any interest or direct involvement in
medical devices.
I would now like to reintroduce the chair
for the panel, Dr. Charles Edmiston, who's here on my right. He's a professor
of surgery and he's also a hospital epidemiologist at Memorial Lutheran Hospital
at the Medical College of Wisconsin, Milwaukee, Wisconsin.
ISSUE: GUIDANCE DEVELOPMENT FOR
JET INFECTORS
DR. EDMISTON: Thank you very much.
We now would like to begin the afternoon
portion of the 34th General Hospital and Personal Use Device Panel. This
afternoon we're going to discuss guidance documentation for jet injectors.
And for those of you who were not in the
audience this morning I would like my colleagues on the panel to reintroduce
themselves, starting with my colleague on the right.
DR. FOWLER: Dr. Joe Fowler,
dermatologist, University of Louisville, Louisville, Kentucky.
DR. RUTALA: My name is Bill Rutala. I'm
director of hospital epidemiology, occupational health and safety at the
University of North Carolina Hospitals and professor in the Department of
Medicine.
MR. PALOMARES: I'm Salvodore Palomares.
I'm industry representative. I'm the manager of regulatory affairs for ICU
Medical.
MR. DACEY: Robert Dacey, consumer
representative from Boulder, Colorado.
MR. ULATOWSKI: Tim Ulatowski, director,
Division of Dental, Infection Control and General Hospital Devices, FDA.
DR. EDMISTON: And we have one more panel
member who is MIA, who I suspect will be here momentarily.
This is a great entrance.
MS. RYDER: I'm Marcia Ryder and I'm a
nurse consultant in vascular access and I'm a doctoral candidate at the
University of California San Francisco in the Department of Physiological
Nursing.
MS. O'LONE: Okay, and now we'll have Tim
Ulatowski, the division director for Dental, Infection Control and General
Hospital and Personal Use Device Division provide an overview on the topic for
this afternoon's session.
FDA PRESENTATION
MR. ULATOWSKI: Thanks again, Martha, and
welcome back to the panel for the afternoon session.
Like this morning, we are not doing a
premarket evaluation of any devices. Rather, we're having a discussion
regarding a technology and obtaining opinions and recommendations from the panel
on a particular type of device, generally called, for the afternoon, jet
injection technology, which has quite a long history in regard to the
fundamental technology, which I think will be touched upon, but also some
interesting new technologies coming along that fall within the general umbrella,
I'll call it, of jet injection technology.
Within this large grouping of current or
future products, we do have different types of injectors that a subsequent FDA
person will talk about, and delivery of different
products, FDA-regulated products by these injectors, both drugs and biologics.
This being a drug and biologics
delivery device, we are not alone in this Center in
the evaluation of these products, typically. When the need arises, we will
obtain the opinions of our drug or biologics centers on drug or biologic aspects
with the injectors. And in fact, some of the products that may be touched upon
today are, in fact, primarily regulated by our Center for Drugs and Center for
Biologics, those injectors that may be prefilled with a biologic or a drug when
it's sold to an end user.
There are some significant safety
concerns that you hear about with these products and a very great potential
future need for new technologies.
We intend to develop a guidance document
based upon what we hear today and what we have heard already in other forums. I
think there's a definite need for guidance in this area and we intend on moving
forward.
We also intend on incorporating as much
as possible any standards that might be created to address this technology, of
which there is some activity now.
As with this morning, I have a particular
interest as the director in regard to these products. We deal with quite a
range of manufacturers in the medical device area, from very large manufacturing
facilities with hundreds, even thousands of employees and regiments of people
who are in the regulatory affairs area down to very small operations who create
and develop and try to finance their operations.
And that's really the challenge in front
of us. As a center, we have to deal with both ends of the spectrum in the
device area. One of the critical areas that we have to deal with with this
technology is when clinical data are needed and providing some criteria along
those lines, of when more than just bench or engineering information is
necessary.
So we'll consider your recommendations,
comments, reflections today and those of the public and we intend on publishing
a guidance through our good guidance practice procedures, in which we post a
draft on the website and obtain public comment for a period of time and then we
finalize the document.
So without further ado, I'd like to
introduce Von Nakayama, Captain Nakayama, who will talk about this technology
from our perspective in a little more detail.
CAPT. NAKAYAMA: Thank you, Tim.
It's my pleasure to give you a background
on jet-injected devices. The terminology jet injector is, and I think Dr.
Weniger will discuss this in a little bit more detail, is under a little bit of
debate. Some people may prefer to call it needleless
injector systems or needle-free injector systems.
In any event, as I progress with my
overview, I'd like to remind you that this is a very important topic, although
it is quite pointless.
[Laughter.]
CAPT. NAKAYAMA: A jet injector is a
preamendment device that's an alternative means to administer a drug or
biologic. Jet injectors can be labeled for the specific administration of
specific compounds, such as insulin, or for general purpose use, such as IM
injections of vaccinations. Jet injectors are designed for personal use or
multi-patient use.
The prevalence of jet injector use may
increase due, in part, to increased public health awareness of needle stick
injuries, sharp disposal, reuse of single use needles, and the possible
cost-effectiveness of mass immunization programs.
Two things jumped out at me over the
weekend that I just want to interject here. Malaria infects 275 million people
a year. TB deaths account for 1.5 million deaths a year. Treatment of these
epidemics may be most effective, cost-effective, using jet injectors rather than
a traditional needle and syringe.
The classification of device. Currently
a jet injector is defined as a nonelectrically powered fluid injector and
classified in 21 CFR 880.5430. I will get to the definition on the next slide.
Jet injectors are Class II devices and subject to regulatory controls that are
identified in 21 CFR 860.3.
Part 21 CFR 880.5430, nonelectrically
powered fluid injector--the jet injector that we're talking about--is a device
used by health care providers to give a hypodermic injection by means of a high
velocity jet fluid. This fluid penetrates the surface of the skin and delivers
a fluid to the body.
As a Class II device, the jet injector is
subject to both general controls and special controls. General controls include
items such as registration and listing, reports and records, and conformance to
the general provisions of the Food and Drug and Cosmetic Act, such as
prohibitions against adulteration and misbranding.
There are special controls and the type
of special controls that may apply to Class II devices include performance
standards, postmarket surveillance, patient registries, development and
dissemination of guidelines, including guidelines for clinical data, and other
actions deemed appropriate by the agency.
Jet injectors themselves are complex and
have designs ranging from the relatively simple to highly sophisticated. There
are two broad categories based upon the intended user. The first is a personal
use device designed to be used by a single patient in the treatment of a disease
or health condition.
The second is for multiple patient use,
where the device is used by a health care provider, generally for public health
initiatives like immunization programs, and can be categorized into three
types: low, medium and high workload devices. High, medium and low workload
devices are terminologies recognized as developed through various CDC-sponsored
conferences on jet injector devices.
Jet injectors can be used to administer
different forms of a drug or biologic, including liquid doses, powered
formulations and coated particles. The dosing sites or target tissues can be
mucosal membranes, the skin, epidermis or dermis, subcutaneous tissue, and
intramuscular tissue.
The mechanism of action of a jet injector
is the acceleration of a drug or biologic using spring or compressed gasses to
high velocity that will deposit the drug or biologic into the tissue without any
part of the device penetrating the tissue. Jet injectors use nozzles instead of
needles and may have a single nozzle to inject a single injectate in a single
stream or an admixture in a single stream.
Multiple nozzle designs, on the other
hand, can inject a single injectate or admixture through several streams or
simultaneously inject several different injectates in one action.
There are several important review issues
in the evaluation of a jet injector for safety and effectiveness. The first is
the identification of an appropriate legally marketed device to which a jet
injector device can be compared. The CFR definition of a jet injector is--I'll
repeat it again--a device that injects fluids to the body through the skin. We
have used an elastic interpretation of "substantial equivalence" to include
injectors that inject solids--powders and particles--not only through the skin
but in some cases to the skin.
Advanced technologies, new medications
and emerging concepts of immunization may require rethinking of how the jet
injectors are to be reviewed and evaluated.
The second issue is that a jet injector
is reviewed in three distinct parts. One part is on the physical and mechanical
properties of the device--its physical specifications, materials of manufacture,
biological and chemical compatibility, cleaning, disinfecting and sterilizing of
the device, and the human factor issues that affect its proper use.
The second review concern on this
three-part review looks at the performance characteristics of the jet injector
and is an evaluation of the data that has been provided to establish the
performance specification of the device. Data may include nonclinical data,
such as bench testing for functionality, reliability and appropriate conditions
for use, and simulated use studies, or valid scientific data that comprise
evidence to support the safety and effectiveness of the device.
Valid scientific evidence is defined in
21 CFR 860.7(c)(2). That section also defines what valid scientific evidence is
not. And I have some slides for that if you want to review those items.
They're the last two slides in my presentation.
The third issue is the evaluation of the
jet injector as a combination project, a device with a drug or biologic
component. There can be questions as to whether a drug or biologic can be jet
injected and if the jet injection of that drug or biologic could cause a
physical change to the drug or biologic through incompatibility with the device
or denaturing of the drug or biologic when subjected to high pressures, high
velocity forces.
There's also a question as to whether or
not the drug or biologic will have stability issues when the drug or biologic is
incorporated as part of the device, either through a modification of the
original container closure system--the vial--or as it's put into the vial of the
device.
Then there's the issue of mutually
conforming labeling. Is the device labeling consistent with the drug and
biologic labeling, and vice versa? Are there possible conflicts that could
arise from the use of the device with the drug or the biologic? Most drugs and
biologics are labeled with the route of administration, such as subcutaneous,
intramuscular IV. The method of administration is generally not specified.
The development process of a drug or
biologic might have included dose administration only by needle and syringe.
These data may not be sufficient to conclude that the drug or biologic is
suitable for administration by jet injection.
This is of particular concern because of
the significant differences between a dose administered by a jet injector as
opposed to one that's been delivered by a needle and syringe. A jet injector,
for instance, uses nozzles instead of a hypodermic needle. The injection
pressures are high, with high velocities, whereas with the needle and syringe,
it's low finger pressure and slow flow.
A jet dose is all or none versus the dose
control that's available through a needle and syringe, including partial dosing.
A jet dose is dispersed. The analogy is
it's like a shotgun, compared to the concentrated dose, a single bullet, that is
evident from a needle and syringe injection.
The jet injector can involve multiple
tissue dosing versus single target tissue from needle and syringes. Various
dose forms can be administered through a jet injector. The needle and syringe
will inject a liquid.
There are also multiple fluid paths and
multiple drugs that can be administered in a single jet injection. The
concomitant dose is a single drug and fluid path.
I hope I haven't used my Andy Warhol 15
minutes, but this concludes my overview. You'll receive additional information
about jet injection devices from the speakers who will follow me but I hope that
this overview has provided you, the panel, with a foundation upon which to
consider the three questions which were mailed to you and on which guidance is
solicited.
The first item is, "What are the key
issues that should be considered in the premarket evaluation of jet injectors?"
Number 2, "What data could be appropriate
to address each of the above issues?"
And 3, "If and when clinical data are
appropriate, what are the panel's general recommendations regarding the form and
content of the studies to derive the clinical data?"
And while that's up, I think what I will
do is just flip through the next two slides to show you what, as you think about
clinical data, what valid scientific evidence comprises.
Well-controlled investigations, partially
controlled investigations--I can read that but you can read it as well as I
could.
And this is what they're not.
And with that, unless you have any
questions, I will defer to Bruce.
DR. EDMISTON: Thank you.
MS. O'LONE: And our next presenter is
Dr. Bruce Weniger from CDC, who will present on needle-free technology.
DR. WENIGER: My name is Bruce Weniger
and I'm with the National Immunization Program at the Centers for Disease
Control and Prevention.
I want to thank Martha O'Lone and the
other staff of the FDA for inviting this presentation. And there are hand-outs
of my slides on the table outside that were put out during the lunch hour.
In addition to the dangers of needle
stick injuries that were the subject of this morning's discussion, in much of
the world needles and syringes pose a serious threat due to their improper
recycling and reuse without proper sterilization.
WHO estimates that upwards of half the
injections in the developing world, including for vaccines, are unsterile and
thus unsafe, resulting in major burdens of iatrogenic disease and WHO estimates
in the world there have been 8 million infections caused in this manner for
hepatitis B, 2 million for hepatitis C and 75,000 HIV infections.
In addition to transmitting blood-borne
diseases, needles also pose obstacles to immunization, which is one of the most
cost-effective interventions to prevent disease. Just a decade ago in this
country, to fully vaccinate a child in accordance with the recommended
immunization schedule required only eight injections. Today is requires a
minimum of 14 injections, and this number will increase to 16 injections next
January when the oral polio vaccine is entirely
replaced by the injected polio vaccine.
And many wonderful new vaccines for
diseases not yet vaccine-preventable are in the
pipeline to be added to this schedule. But as those of you who have taken your
children for their vaccinations know, doctors and nurses are uncomfortable, as
well as parents and children themselves, administering multiple vaccines or
receiving multiple vaccines, as documented in various studies from which 20
percent to 80 percent of the respondents either objected or deferred some
vaccinations, which may result in costly repeat visits or even missed
protection.
We believe that needle-free injection
technology presents a practical solution to overcome this and the other
drawbacks of needles and syringes that I just mentioned.
Jet injectors are devices to administer
drugs by shooting through the skin a fine stream of liquid under high pressure
through a small orifice. The first commercial needle-free injector in the
United States was the Hypospray shown here, developed in the late 1940s, and
this first model was developed primarily to reduce needle phobia among diabetic
children.
Over the decade since that first
indication, a variety of other needle-free injectors targeted for insulin users
have been developed into a very small but established niche in the diabetes
market. Since insulin injectors are usually owned and used by only one patient,
there's little concern that some have permanent middle nozzles, as shown here in
this AdvantaJet.
More recently developed models for
insulin users, such as this Vitajet, have begun using disposable cartridges made
of clear plastic to hold the drug. To save on costs, such cartridges are often
reused up to several weeks by the same patient before replacement. This late
model Medi-Jector is another injector which uses a disposable cartridge.
Another recent entrant into this market
is the Injex, also with a disposable cartridge. It's smaller than the previous
injectors you saw because the heavy and sturdy spring cocking mechanism has been
off-loaded into a separate item.
Unlike the previous devices shown, this
J-Tip is unusual as a completely disposable single use only device. The user
loads the drug through the orifice, through this protective cap into the
chamber, and pressurized gas stored here drives the drug into the tissue.
Now let's turn away from devices oriented
to the insulin market, even though they also deliver other drugs subcutaneously,
as well. This Biojector 2000 is the first injector with a single use disposable
cartridge marketed for immunization and it also has other indications. It is
sold primarily to clinics and doctors, rather than to individual patients.
Another device still in research and
development is also aimed for use in immunization. The SensaJet is now
undergoing clinical vaccination studies in Cuba.
This Intraject device still in
development is similar to the J-Tip that you saw earlier in that it is
completely disposable and operates by a charge of pressurized nitrogen in here.
What is novel about this Intraject is that it contains a borosilicate glass
liner held within the plastic nozzle here. It will be prefilled at the factory
with vaccine or other medication.
Thus the Intraject steps beyond the realm
of a device and really represents the primary packing of a drug or biological.
Use of the more common glass liner instead of polypropalene may facilitate
satisfying packaging regulations.
This PenJet model, also in development,
is designed to administer drugs or vaccines in cartridges also prefilled by the
pharmaceutical company but unlike the Intraject you just saw, this injector
device would be reusable.
Another example of a prefilled
needle-free cartridge for use in a reasonable device was brought to an advanced
stage of development with several published clinical trials by Pasteur Merieux
Connaught. This Imule cartridge is about the same size and shape as a standard
unit dose vaccine vial.
Now almost all the previous devices I
showed you have the disadvantage of requiring the health worker or end user to
fill them by manually transferring the vaccine or
drug from another container. This is inconvenient, takes time, and often
expends a needle and syringe or some other transfer container.
CDC, WHO and PATH strongly believe that
the prefilling of a small, simple needle-free vaccine
cartridge that would serve as its own primary packaging would represent a
tremendous advance for immunization practice in both developing and developed
countries. The cartridge would be included in the
vaccine price, thus offsetting the cost of a standard vial.
We are working to promote a universal,
open standard and source for such cartridges to be available to all
pharmaceutical and jet gun manufacturers on an equal basis.
The universal standard for 33 millimeter
film cartridges has been a boon to both the makers of cameras and film. And the
VHS standard has been a boon to both movie studies and VCR manufacturers and
video rental stores. Similarly, a common standard for needle-free cartridges
ought to help the now-struggling cottage industry of jet injection manufacturers
while, at the same time, improving compliance with vaccination and thus
hopefully getting more vaccine used.
I would like now to focus on a different
category of jet injector--the high speed devices used for mass immunization
campaigns, controlling epidemics, and vaccinating large numbers of soldiers.
But first I'd like to credit Dr. Robert Hingson, who contributed so much to the
science and development of this field, including the early low workload models I
showed you earlier, as well as the high workload models to follow. Dr. Hingson
was a uniformed Public Health Service medical officer early in this career, like
many of those in the room here today. And this is the New York Times obituary
in 1966 of this father of jet injection.
The most common high workload device in
the world today is the Ped-O-Jet type device, which is being used here by Dr.
Hingson to immunize patients against polio and measles in Costa Rica in 1967.
That one campaign in that one small country immunized in one year over 800,000
persons.
Since the early 1950s, such high workload
devices have been used around the world to deliver hundreds of millions of
vaccinations, if not billions by now. For example, in the early 1990s Brazil
purchased 10,000 of these Ped-O-Jets and immunized 50 million children up to age
15 in mass campaigns to control measles.
In the last five decades, such devices
have been made by a variety of companies, such as these Hypospray trade name
devices. High workload devices usually accept multi-dose
vaccine vials and automatically refill an internal
injection chamber between each injection. They're often powered by foot pumps
or pressurized gas or electricity and springs and can vaccinate hundreds of
patients per hour. Here are some Dermo-Jet high speed models.
One distinguishing feature of existing
high workload devices is that they have reusable metal nozzles and internal
fluid pathways that are reused and not ordinarily sterilized between consecutive
patients.
Another common model is this Med-E-Jet
shown here. One Med-E-Jet device, however, was implicated in the first and to
date, only known case of blood-born disease transmission between patients.
Before getting into the issues raised by this, let me briefly review some
clinical aspects of jet injectors.
Over the years, a variety of medications,
such as those listed here, in addition to vaccines, have been reported in the
scientific literature to be successfully and safely delivered by jet injectors.
The published data for this are contained in a bibliography on needle-free
injection that we maintain and a somewhat mistaken website address. We're now
posting this bibliography to make it more convenient for people to obtain it and
we'll be periodically updating it. If you'll send me an email--my email address
is in the hand-out--I'll be glad to give you the current website address to get
that bibliography.
Focussing just on the immune response to
vaccines, jet injectors have usually been found to be as good as and often
better than the immune response achieved with traditional needles. There's no
good data on why this immune response is often enhanced but it may be due, if we
may speculate, to the somewhat different dispersion of the
vaccine compared to needle vaccination or perhaps
because some of the dose is always left in the skin, which is rich in
antigen-processing cells.
You can see here the wide variety of both
live and inactivated vaccines which have been successfully demonstrated
effective with needle-free injectors.
On the safety side, controlled clinical
studies of jet injectors have often found somewhat higher rates of local
reactions, both immediate and delayed, compared to needle and syringe.
The pain issue is not as carefully
studied and the results are mixed. Despite the claims of reduced pain in early
and often poorly controlled studies, I'm not yet convinced that they always have
less pain. In any case, it seems to depend on both the device and the
vaccine used.
Adjuvant vaccines more frequently seem to
provoke immediate pain compared to needle and syringe. Other local adverse
events include occasional blood at the injection site and rarely, laceration and
other traumatic injuries are reported, but probably no more commonly than with
needles.
Tissue deposition tends to be diffuse, in
a generally conical shape with the apex at the skin. The drug tends to follow
the path of least resistance, often glancing off muscle fascia, especially if
the angle of penetration is not perpendicular.
Where the drug ends up depends on a
variety of factors, as listed here, related to the device or to the operator or
to the patient. In actual reality, it's hard to predict precisely where a dose
is going to end up.
But is this really much more different
from with needles, in which a nurse must estimate the thickness of the patient's
fat for at least an IM injection and then decide how long a needle to use and
occasionally may misjudge the proper angle and depth of penetration?
The devices listed here in this bullet
have sufficient power for IM injection but it's not certain that they always
achieve it. But as long as the dose works empirically, does it really matter?
Good results have been found for several IM vaccines, even hepatitis B. And you
may recall that hepatitis B had a problem when it was being delivered with
needles in the gluteus. It was believed the lower seroconversion that was found
was due to the occasional deposition into fat and it wasn't really getting into
the muscle. And yet hepatitis B is documented to have high seroconversion rates
when delivered with jet injection.
This is an x-ray of a living human
biceps, comparing simultaneous intramuscular injection between a needle, which
is the upper contrast injection, and the Hypospray injector, the lower contrast
one, and you can see how the contrast appears to spread along the muscle fibers,
with perhaps the Hypospray dose spreading a bit faster. And by 45 minutes
later, most of both injections have diffused away.
This is more recent magnetic resonance
imaging of simultaneous subcutaneous injections in a living human thigh. The
needle dose in the upper left position of these four shots is the needle dose
and the jet injector dose is the one in the central right.
When the volunteer walked around between
the initial dose at 2 minutes here and here at 48 minutes, you can see that most
of the dose was gone but when the patient was immobilized, most of the doses
remained in place.
This cadaver injection photograph was
kindly shared with me by Weston Medical. It illustrates a somewhat conical and
diffuse distribution of the dye, which was injected from the center of the black
circle marked here on the skin. Note that it doesn't appear to penetrate the
underlying muscle, perhaps only 2 centimeters or so underneath the skin.
This illustration from the Lancet was
from injection of dye by a J-Tip device in vivo into breast tissue prior to a
mastectomy. In addition to coloring the fat below it, which is a bit difficult
to see, notice how well the blue dye diffused laterally and superficially to
permit its visualization through the skin.
Now the great variation in where jet
injector doses end up is revealed in this product brochure and the next slide
I'll show you for the Biojector 2000. Bioject varies the syringe size and thus
the orifice size as a means of achieving different depths of penetration. Based
on magnetic resonance imaging this data was obtained and it found that almost
one-third of the number 3 syringe here, only 29 percent of the injections went
into muscle or actually got into muscle, even though they were intended for
subcutaneous use.
Now let's look at the intramuscular
injections in the next slide, please. Here you see the various syringe sizes
intended for intramuscular injection and you can see that for only one-half to
two-thirds of the time did these various orifice sizes actually deposit their
dose intramuscularly. In other cases it was left on the surface of the muscle.
So once again I would ask if the clinical
results are good from controlled trials, does it really matter where the dose
ends up? I wonder if we had done similar studies of multiple IM injections with
needle and syringe, how often we would find that the intended target tissue was
missed.
Let us now return to the issue of the
safety of multiple use nozzle jet injectors. In the mid-1980s one Med-E-Jet
device, as I mentioned earlier, was documented to cause a hepatitis B outbreak
in California. Several dozen confirmed cases were identified who had received
multiple hormone injections in one weight loss clinic. There was no evidence of
problems in other branches of this chain of clinics using similar devices for
similar injections. As part of the investigation, CDC did laboratory testing of
the Med-E-Jet.
The Ped-O-Jet device, another device I
showed you, was also tested as a control and most of the results were reported
in this 1990 Archives of Internal Medicine article.
First, a chimpanzee carrier of hepatitis
B surface antigen was inoculated with both jet guns
and in several cases visible blood appeared at the injection site.
Nevertheless, when they looked at subsequent fluids ejected from that jet gun
into vials, they could not detect hepatitis B surface antigen.
These are close-ups of the nozzles of the
two devices, the Ped-O-Jet on the left and the one implicated in the outbreak on
the right.
After failing to detect contamination
with hepatitis B antigen in the downstream ejectates after injecting the
infected chimpanzee, they then intentionally contaminated each nozzle of the
device with infected serum, serum containing HBsAg, and then looked in
subsequent fluid ejected from that gun, as well as various parts of the gun.
After intentional contamination of the
nozzles of the two devices, the Ped-O-Jet and the Med-E-Jet, in both devices
hepatitis B antigen was detected in from 6 percent to 80 percent of the samples
of the next discharge into the vial. Swabbing, whether swabbing the vials or
not swabbing the vials, reduced but did not eliminate the contamination rates,
at least in the case of the Ped-O-Jet. It reduced it in the case of the Ped-O-Jet
but not in the Med-E-Jet.
Also in the Medi-E-Jet, the external
contamination somehow made its way into the nozzle interior, but this was not
found with the Ped-O-Jet.
Now despite these findings, the
California outbreak represents the only documented case of blood-borne disease
transmission from the use of jet guns, despite
hundreds of millions of injections delivered over five decades.
In deriving some hypothetical cut-offs
for how much blood or serum might transmit disease if transferred between
patients via jet gun, hepatitis B virus is a good agent to consider in a
conservative, worst case scenario because of its extremely high infectivity.
Needle stick accident surveillance indicates hepatitis B is 100 times more
infectious than HIV, for example.
Given chimp studies indicating that
carrier blood may contain 100 million chimpanzee infectious doses per
milliliter, this calculates to a theoretical single infectious dose of 10
picoliters of blood, and this is an extremely small volume that challenges
detection methodologies.
A few years ago the U.K. Public Health
Laboratory Service and the Global Program on Vaccines at WHO pioneered an animal
model to evaluate the safety of multiple use nozzle jet
guns. They used calves and developed an ELISA assay shown here using serum
albumen as a blood marker and diluted blood to generate various standard
calibration curves, as you see in the example illustrated here.
Now we at CDC are collaborating with the
University of Florida and Small Business Innovation Research Contractors to
duplicate and extend that model in both calves and pigs. We're discovering some
problematic nonlinear behavior of serum albumen at extremely low dilutions and
we're not getting this straight line you see here from the London study.
You can see here the overlap between
totally negative controls, the optical density of totally negative controls, and
some of the lower calibration positive controls. And this is hampering the
achievement of consistent results and good specificity close to the target of 10
picoliters, but we're hopeful that we can work this problem out.
This is a photograph from our injections
of anesthetized pigs in Florida. After various control specimens are collected,
including mock injections in the first boxes of this injection grid, 100 real
injections of phosphate-buffered saline are given in each series.
Immediately after these injections, the
next ejectate is fired into a specimen vial representing the fluid that would
have been injected into the next vaccinee in a typical use scenario. Despite
the assay problems that I mentioned, on at least some occasions among 100 or
more specimens, for each of several guns tested,
both in the U.K. and in Florida, we have detected contamination well above
currently levels that we would consider indeterminate or uninterpretable.
And now in 1994 a similar study in Brazil
used a procedure of using urine dipsticks to measure blood and they found an
alarming rate of from a little less than 1 percent to up to 6 percent positive
after routine vaccinations of human beings. And they observed that the health
workers were negligent in not swabbing the head of the device with alcohol
between each vaccinee.
Now various gun manufacturers are
planning engineering changes in these multiple use nozzle devices, such as
disposable spacers and covers, to see if they can pass this test. But our
biggest challenge is how to prove safety from negative results in such an
evaluation model.
If 100 consecutive specimens are clean,
what would happen on the 101st? Or if we had 1,000 consecutive injections that
were clean, can we be sure the 1,001st wouldn't be contaminated? And thus how
many samples are really going to be necessary to satisfy regulatory review?
As a result of the 1980s outbreak and
these recent lab tests, WHO policies over the last few years concerning multiple
use nozzles and reusable fluid path devices have become increasingly
restrictive. I won't take the time to read these policy statements because you
have them in the hand-out, but currently WHO does not recommend their use, even
for emergency campaigns where the use of conventional needles and syringes might
also impose some burden on unsafe injections in iatrogenic disease.
Now CDC currently still recommends
weighing the risks versus the benefits of using jet guns
versus needles and syringes which, as I mentioned, have their own risks.
However, the Department of Defense in 1997 withdrew these devices from their
routine use, despite their reliance on them for decades to immunize soldiers.
So now existing high workload jet
injectors are in a state of limbo. This means the world's population is more
vulnerable to the threat of pandemics and bioterrorism.
Now in 1976, upwards of 75 million
Americans were vaccinated with these devices in a short space of time in order
to protect them from the swine flu. But now with these devices in limbo, we
lack any alternatives means to quickly vaccinate large numbers of persons with
limited manpower.
And it is not a question of whether the
deadly 1918 swine influenza pandemic will recur but really a question of when it
will recur. The recent H5N1 fatal influenza cases in Hong Kong were perhaps a
warning of this vulnerability.
Let me conclude on my last slide here
with some key questions I hope will be addressed in today's discussion. First
consider needle-free injectors as simply drug delivery
devices sold empty. Should the device manufacturer be required to furnish data
on clinical efficacy for each and every medication that might possibly be
administered with them?
That might be a burdensome obstacle and
would be inconsistent with how new needles and syringes are licensed, perhaps.
Obviously if they're sold for diabetes
there ought to be clinical data on their use with insulin. If they're sold for
vaccines I could understand the need for perhaps some representative, a live
vaccine or an inactivated
vaccine, as markers for all the many possible vaccines.
Instead however, recognizing the public
health advantages of needle-free injection, the clinical data on efficacy and
safety for specific vaccines delivered by jet injector might properly be a part
of the license application for the biological because currently the
manufacturers really only provide data on vaccines delivered with needles.
However, for the device developers it
might be reasonable to require animal and clinical data on where the dose is
deposited and with how much variation. And this ultimately would leave to the
end user, the physician, to decide which drugs or vaccines are acceptable to use
in the device based on published data and ideally relevant information in the
drug labeling.
Second, let's consider the issue of
prefilling vaccine into cartridges at the
vaccine manufacturer that I mentioned earlier. Now
regardless of whether the cartridge is going to be of glass or new polypropalene,
routine stability and potency studies will be required, of course. But if the
same drug has already been licensed in similar material as the primary
packaging, such as prefilled syringes, could not the needle-free packaging
application refer back to that other data and avoid starting at square one in
the process of regulation?
And finally, let's ask if it would not be
reasonable in determining the safety and efficacy of common vaccines that were
prefilled into such cartridges to use relatively small clinical studies for
reatrogenicity and serologic response with jet injectors. And then bridge from
those studies to perhaps the large field trials that may have been conducted in
the past with needle and syringe and show comparable rates of immune response.
And finally, in terms of the issue of the
multiple use nozzle jet injectors that I mentioned earlier, what type of safety
evaluation should be applied for them? And how many negative results in an
animal model will demonstrate sufficient safety? No contaminations out of 100
shots or 500 shots or 1,000 shots or 10,000 shots, et cetera?
Now some might argue that such jet gun
designs are inherently unsafe if they use the same nozzles between patients, but
given the inherent risks of needles, is it fair to apply a zero risk standard to
jet injectors, regardless of the results of such safety testing? These are some
difficult questions to address. I do understand. Thank you very much.
MS. O'LONE: Thank you. Now we're going
to have some presentation by industry and professional organizations. And again
we're requesting that all persons making statements disclose whether they have
financial interests in any medical device company and also please state their
names as they come up to address the podium, and their affiliation.
PRESENTATION BY INDUSTRY
DR. EDMISTON: Our first presenter will
be Mr. Glenn Austin from PATH, which is the Program for Appropriate Technology
in Health.
MR. AUSTIN: Thank you. I'll start with
one of the first slides of my presentation telling you a little bit about my
affiliation and who PATH is.
Since I didn't know what else was going
to be covered, and this is a very diverse and complex set of issues, I prepared
about three presentations worth of information and I thought maybe the panel
could help me select what to emphasize here this afternoon.
I'm going to give you a little background
on PATH whether you want to hear it or not. We can cover some needle-free
fundamentals, which I think were already covered to a good extent and if you
don't need to really look at the dynamics of the needle-free injection or jet
injection, there's been some recent discussions with the ISO working group that
I could share with you on standardization and regulatory issues, talk a little
bit about variation among devices. I think Bruce has covered that and the
earlier FDA presenter covered that but there is some level of detail.
Also, we've done at PATH about 11 years
worth of functional and safety testing that might be of interest.
Are there areas that are of particular
interest to the panel?
DR. EDMISTON: Your ISO information would
be extremely interesting to this particular panel.
MR. AUSTIN: All right, we'll emphasize
that, then.
As you said, PATH is the Program for
Appropriate Technology in Health. We're actually not an industry
representative. We're a nonprofit, nongovernmental organization. We've been
around now about 22 years and we're an international organization with field
offices around the world.
However, we work very closely with
industry and with the public sector to try to ensure that products that
otherwise might not benefit underserved populations are made available. That's
our mission--to improve the health in underserved populations, especially women
and children in developing countries.
This is basically a reiteration of some
things that were covered very well by Bruce. There are many good reasons to be
considering needle-free injectors, especially reduction of sharps injury and
reducing the hazardous waste.
When you're talking about those
campaign-type injectors, it can lower the cost. The Ped-O-Jet style injector
has been the very lowest possible way to deliver vaccine
in developing countries for many, many years.
We also have a special interest in
eliminating unwanted reuse, and this is, as Bruce said, a very common problem in
developing countries.
I'm going to skip over some of these. I
don't want to give you whiplash here from going through the slides quickly but
we'll go through these rather quickly.
Jetstream quality is an important issue.
It can be measured. This diagram shows on the right side a laminar or coherent
flow and on the left side, a turbulent flow. And this gives you a photographic
representation of the kinds of differences you see in commercially available jet
injectors. I think this also represents a range that you would see in jet
injectors that have demonstrated good immune response or good response to the
drug delivery.
This is a simplified diagram addressing
what Bruce talked about in terms of the site and dispersion of the injectate
delivered by jet injectors. It depends a lot on the operator's pressure against
the skin and site selection and in the underlying tissue orientation. As you
can see, the jetstream in the upper left diagram, you can see the jetstream is
oblique to the muscle fascia. That's going to deposit over the fascia.
If it's normal to the fascia and there's
a shallow subcutaneous overlying tissue, it will typically penetrate the muscle
fascia. If it's deep subcutaneous tissue, you get a wide dispersion in the
fatty tissue. And, of course, the needle is going to deliver at the tip of the
needle primarily.
Also along the injection track in each
case it is depositing, as Bruce indicated.
Well, as was mentioned earlier, the world
of needle-free is expanding and I think it's going to expand beyond these
current uses because of reduced dose forms, the nonliquid forms that were
mentioned, which as far as I know are not in current commercial use, and a new
emphasis on intradermal or subdermal delivery
because of new findings for improved immune response, smaller, low energy
requirements for the devices themselves, and we're likely to see these first
bundled with new drugs. It's also a possible answer for simultaneous multiple
injections, which would reduce the number of immunization shots that a child
might have.
As I mentioned earlier, the ISO Standards
Working Group had their first discussion on June 3. This is an ad hoc group.
It's a spin-off of the Pen Injector Group that's been working for eight years to
develop standards for pen injectors.
If you're familiar with those, those have
a needle. They're self-contained. They're typically for the
delivery of insulin to diabetics. They're very
popular, much more popular in Europe than they are here in the States.
They did establish this working group and
time line. It has representation from ANFIM, which Bob Harrington will talk
about in a minute. And they are addressing sort of the typical starting point
of standards--the physical dimensional characteristics, safety and quality.
I don't think they're yet addressing all
of the aspects that are unique to jet injection, although I hear there's been
some follow-up discussions about the effect on the drug in terms of the sheer
and the high pressure exposure.
So what I'm going to do now is show you
slides that alternate between capsulizing what the ISO discussions consisted of
and then some of the pieces that might be missing from those discussions. I was
not there so I lifted these from the minutes.
The drug compartment could contain liquid
or powder. This might also be called a syringe or cartridge, depending on the
manufacturer. That can be single dose, multi-dose or refillable. It can be
disposable or reusable. It has to have some sort of power source, typically
spring, gas or compressed air. There's also patents
on ballistically driven jet injectors.
The nozzle can be either multi-use,
durable or disposable.
I think one of the things they missed in
the basics that is not present in the pen injector is the activation means or
the trigger that is used, and this has some safety implications.
I would add that some jet injectors are
being designed now with autodisposable features so that the nozzle or cartridge
cannot be reused. This is of particular interest, as I said, in developing
countries but maybe also here.
Hybrid devices have some reusable portion
of the fluid path but also have some disposable portion and this is to add a
margin of safety, and I'll talk a little bit more about that in a minute and
show you some cut-away views.
There's the distinction between prefilled,
as Dr. Weniger mentioned, and filling on site. If you fill on site, you then
incorporate another subsystem or another device to transfer the drug, and this
might be on board the injector, as in the case of the Ped-O-Jet or the campaign
injectors or it may be a separate component which is common to all of the
nonprefilled, hand-held devices that Bruce showed you.
There are considerations about the fluid
path, as well, particularly if you're considering contamination. How much of
the fluid path is reused? How much is exposed to potential blood being wicked
back up into the system after exposure to the nozzle face? And is the dose
adjustable or fixed?
ISO group captured the same safety
aspects that they had been using for pen injectors. So in fact you can see here
even from their transcript that they're still using pen injector, mostly having
to do with dose accuracy.
I think there's quite a few other safety
aspects that should be considered--freedom from cross-contamination, as Bruce
said, both blood-borne pathogens but also skin-borne pathogens and environmental
contamination, especially of a concern if you have an exposed drug or
vaccine transfer system that has a needle or sharp
that could be left on a table top or whatever. That portion of the fluid path
is not always considered.
There's also the consideration of when
the device is safe when used as directed, complaint versus noncompliant use. A
lot of the tests that were done in London and safety tests that were done in
Brazil were in a noncompliant mode. That is if you had visible blood on the
nozzle, the device would be reused or it would be sampled downstream for
contamination. And, of course, that would be noncompliant.
In fact, the Med-E-Jet Corporation has
just now changed their instructions and has sent out copies to all their
customers and to us, trying to find a safer way to use that device that was
implicated in the weight loss clinic hepatitis B outbreak. There is a
distinction there and that's something for the panel to consider.
I think that compliance can be assured
partially with good design, and that's something that can be tested,
particularly in the kinds of user tests that June Fisher was talking about.
Additional safety aspects. Unlike a pen
injector, if you accidently fire this, this can do some damage from several
inches away, so it's not something you'd want to accidently fire into the hands
or the eyes.
Some injectors that autodose from a vial
may occasionally provide a short dose. This could prevent adequate response to
the drug or vaccine.
Of course, any injector that causes more
bleeding and adds blood to the work environment can pose a risk. And poor
maintenance, such as leaving it soak in a mild disinfectant for too long, that
sort of thing, can lead to other infections.
ISO's initial statement about quality
aspects describes things like dose accuracy and then how durable the device is.
There are some other quality aspects that might be worth considering. The dose
accuracy, as set, is something that ISO is already considering directing
themselves toward.
The dose accuracy as delivered. In other
words, is all the dose delivered into the tissue or is some left on the surface
of the skin? This is something that we frequently observe with jet injection.
Not all jet injectors are able to deliver the entire dose into the tissue.
Efficacy. I think Bruce has already
addressed this very well. There's a very good history of efficacy in
commercially available jet injectors now.
Stream quality, as I mentioned, and pain
or bleeding rates, which may be something that could be addressed.
I'm going to talk about some variation in
the fundamental part of the jet injector, the part that's of most concern for
cross-contamination. This very simple diagram shows the fluid cartridge or
fluid container. This is the piston here. It's driven forward by some force.
These are the reaction forces or the pressure forces inside. Those arrows will
stay on subsequent diagrams. They're really just to show that this is a
pressure vessel during the use of this container. It's driven out the exit
orifice and this would be considered the nozzle face.
So there's another picture of that. The
items you see in red are now additional device components that become
incorporated, depending. These are all variants within reusable nozzles and
there's many different subflavors of this that are either in development or in
commercial devices.
The fluid path with autofill--this is
very common to campaign-style injectors--has an inlet that allows fluid to come
into this chamber, typically with a check valve, and then also a check valve at
the outlet, and this offers a potential sequestering site for contamination.
And there are injectors with this design that stay largely free from
contamination but it does complicate the fluid path. It does add something to
the fluid path.
There are a number of injector designs
where the nozzle front or face is disposable, but the rest of the fluid path is
reused. The piston and the cylinder walls, if they were to be exposed to
contamination, would then still be reused in subsequent shots.
And there's new designs now with a
space-backed nozzle and a protector shield in front where the jetstream actually
goes through the air and the protector shield is
meant to catch any contaminants and is the surface that is in contact with the
skin.
At first you might think that disposable
cartridges would be guaranteed safe because you're throwing it away and if you
throw the whole thing away, that's likely true, but there are different subsets
of this, as well.
The cartridge might have a reusable
piston so the drive rod and the piston face may be tied together and you throw
away the front portion only, so that piston can carry contamination to
subsequent patients.
Some designs have a soft plastic
cartridge that is not fully supported, so it has to be supported by a metal
outer shell that's depicted in red here. If that design allows the fluid to
pass very close to the shell opening--in other words, the orifice is near--then
you're going to have the same situation that was found with the Med-E-Jet. You
have sequestering sites there.
There's also partial cartridges with a
separate nozzle face and if that nozzle face were to be reused, obviously that's
a potential carrier for contamination.
User interface issues are very
important. Particularly in our constituency with low literacy users, the device
must be easy to learn to use and learn to use properly.
I think one of the most important things
is assuring compliance through good design. And if we're talking about
disposable cartridges, this new family of jet injectors, we want to watch out
that we're not introducing another means of contamination through handling.
This is one design actually that I was
involved in that if you were to reload the cartridge with bloody gloves, you'd
want to have an overcap over this, as an example. That's hands-on.
Getting back to the autodisposable
features, just like with the syringes, there's active versus passive. Obviously
whenever possible, passive is the preferred.
And then there's some kind of interaction
with the device. The device has to participate with the cartridge usually in
order to result in a disabled cartridge.
There are other standards that probably
at some point will need to be discussed about disposal, reuse. Is it
sterilizable or disinfectable, as most of the current campaign injectors are?
What are the methods used? How often is it done? Are there cold liquid
disinfectants allowed?
And then what is the wear life over
multiple uses, including exposure to things like steam sterilization and liquid
disinfectants?
Again there's the difference between a
prefilled unit dose, which does become a package, versus filling on site, which
then has to be compatible with some sort of intermediate filling mechanism.
I'm just going to show you a couple of
quick pictures. We've done developmental tests for about 11 years. They're not
meant to develop standards. They're not guaranteeing performance. However,
they give you a little bit of insight into the sort of dynamics that are going
on when a jet injection is given.
The three tests that I'll talk about are
a combination of target photography test, force test and penetration test.
Target test is very simple. We're
shooting through a thin piece of plastic and looking at the resulting hole. It
does tend to correlate, at least in our limited human and porcine studies, to
the trauma of the entry puncture hole and it does very strongly correlate to the
jetstream quality.
Again reviewing this picture, you can see
these would make quite large targets and we double up and do this photography
test because a substream like this is too weak to penetrate the target and that
would result rather than in a rough trauma at the entry or puncture wound, it
would result in undelivered injectate.
We also test the force. These nice neat
bell curves are not an exact representation of what's happening because the test
mechanism has some mass and it smooths out and slows down the bell curves.
However, as a comparative test, there's some value.
Mostly I wanted to show you this to show
you how wide a range efficacious injectors cover, more than a factor of 2 in
terms of peak force and length. This is all half-cc shots. This is all the
same volume.
We use a foam model that was developed
originally for training people to insert Norplant capsules as a test for
penetration. This shows the sort of thing we would observe with human subject
tests--a very small amount of residual fluid, a few drops, and this actually
depicts a running liquid down the arm. And this is the range that you would see
with human subjects, as well.
We tried to develop a gel penetration
test. It's become part of the nomenclature or discussions among the industry.
We're now recommending that this not be pursued until someone finds a gel that
actually simulates human tissue better. This is something we worked on for
nearly 10 years and have now abandoned.
I think that's my time, unless you'd like
me to discuss the safety tests. I think I should stop.
DR. EDMISTON: I think we're going to
move along.
Do the panel members have any questions
at all for Mr. Austin?
[No response.]
DR. EDMISTON: Thank you very much.
Our next speaker is Mr. Bob Harrington,
who is here to represent the Association of Needle Free Injector Manufacturers.
MR. HARRINGTON: Good afternoon to the
panel. I think I'm the last speaker so if you want to run early, you can run,
and if I keep you too late, boo at me or something.
I would like to thank Von and Dr. Weniger
and Glenn for talking about jet injection and giving you some background.
Unfortunately, they used probably most of my material so I'll be quite quick
through my slides and I will eliminate some that I already have prepared.
My first presentation today is about
ANFIM, the Association of Needle Free Injection Manufacturers. The second
presentation is about the Ped-O-Jet, since I was president of Vernitron and
currently owner and president of American Jet Injector, and I'll talk a little
bit about the truth and the myth of high workload injector contamination.
ANFIM was an association that was created
to promote an understanding and advancement of needle-free injection technology
through the world, to develop common standards that facilitate invention and
progress within the field of jet injection--needle-free injection, I should say.
We want to represent industry as a
unified group when dealing with regulators like yourselves, standard-setters,
government agencies and other organizations and the general public. We're
trying to disseminate information to the common benefit of all members.
We want to act as liaison between PHRMA
and IFPMA or the pharmaceutical equivalents of our organization.
There are four classes within our
organization: needle-free manufacturers, needle-free developers and related
industry members, such as pharmaceuticals or vaccine
manufacturers, and then observers from the public health community.
We have five board members that are
actually voting and two nonvoting board members: myself, Linda D'Antonio and
Valerie D'Antonio from DCI, John Lloyd, who is head of the Program for Expanded
Immunization at WHO, and Ralph Bitdinger from Becton Dickinson.
We have two liaisons to the board, one
from Center for Disease Control, Dr. Weniger, and the other is Pat Cricenti from
FDA Center for Devices and Radiological Health.
I'm here to talk a little bit today as an
industry about regulatory fairness. According to Congress, a vibrant and
growing small business sector is critical to creating jobs in a dynamic
economy. Small businesses, however, bear a disproportionate share of regulatory
costs and burdens.
According to reputable sources, there are
about 12 billion vaccine injections in the world
each year on an annual basis. The needle industry is made up of multinational
million dollar if not billion dollar corporations with tens of thousands of
employees. Unsaid, however, is they have significant dollars available for PR
and lobbying efforts.
The needle-free industry, on the other
hand, is made up of small businesses with less than $10 million in sales and
less than 50 employees. So we need to have some regulatory fairness here as a
small business.
Why is ANFIM here? Because we want to
deserve a federal regulatory enforcement process that is reasonable and
predictable. We want a common sense to problem-solving and a strong voice in
the federal regulatory process.
Congress has mandated that small
businesses should have this by passing Public Law 104 to 121 or known as SBREFA,
the Small Business Regulatory Enforcement Fairness Act. This act makes certain
that small business have a voice that will be heard by the FDA or other federal
agencies as they go through the rule-making process. It gives small business
expanded opportunities to challenge a federal agency's final regulatory
decision.
The bill makes the Small Business
Administration, the SBA, responsible for giving us the tools to do that.
According to Congress, these boards will shoulder much of the responsibility for
making regulatory fairness a more integral part of government.
There are six aspects of this regulation
and I will not read them to you. I'll just paraphrase the top. It's regulatory
compliance simplification. It should be comprehensive; it should be in plain
English.
Equal access to justice. If we go to
court and challenge an agency that has made regulations that we think are
unfair, we are able to have court and attorney fees returned to us.
There's a congressional review process.
Congress is authorized to review each major rule promulgated by any agency
before it becomes regulation.
There's enforcement reform. Within one
year of a new regulation, the FDA shall establish a policy for reduction and, in
some circumstances, the waiver of civil penalties for violations by small
businesses.
There's an advocacy review panel.
There's an oversight of regulatory enforcement. All of these things are part of
the law and we're just asking please that they take effect on regulations within
the needle-free industry because we are a cottage industry.
Under judicial review and a new act, the
RFA, Regulatory Flexibility Act, we have an opportunity to seek review of
federal agencies' compliance with the law through the SBA if you fail to meet
the required analysis and disclosure obligations. We can ask the chief counsel
to file a friend-of-the-court brief on our behalf, appealing any ruling or
violation of RFA by a federal agency.
My basic message under the ANFIM message
is simple. The children of the world need needle-free injection products. The
entire world and the environment we live in need needle-free injection products.
We, the citizens of the developed world,
have an obligation to the less fortunate inhabitants of the developing world.
We cannot continue to pollute, contaminate and infect the developing world by a
policy which recommends disposable needles, all the time knowing that they
routinely are reused dirty or are improperly disposed of.
ANFIM and the FDA perhaps have two
choices. The FDA can either allow this technology and our industry to grow,
prosper and flourish by providing reasonable direction, guidance and support or
create a burdensome bureaucracy that unnecessarily overregulates needle-free
products, with the end result of potentially forcing all of my member companies
out of business.
Three questions deserve answering in this
process. Are new regulations economically justified? Are the safety issues
associated with needle-free products real or perceived? Do needle-free products
really require regulations? If we have the answer to those three questions, I
think we have a significant step forward.
We must remember that in hundreds of
millions of injections by jet injectors, there has only been one documented case
of a contamination in the entire world, yet as the result of reused, dirty or
improperly disposed of needles there have been millions of unsuspecting and
undeserving children throughout the world that have been needlessly infected
with hepatitis or HIV.
Okay, that ends my ANFIM presentation and
I will change hats here and become an entrepreneur and a businessman and a
member of the industry community.
As I said, my name is Bob Harrington.
I'm president and CEO of American Jet Injector. It's an entrepreneurial company
that began in 1995. Prior to forming Am-O-Jet I was president and CEO of
Vernitron Medical Products. Vernitron, together with Walter Reed Army Hospital,
developed and patented the most widely used high workload jet injector device in
the world, known as the Ped-O-Jet.
Today Am-O-Jet, a company that I formed,
manufactures under FDA 510 approval two high workload jet injectors. One is a
foot-powered and one is an electric-powered.
A brief history of the Ped-O-Jet.
Researched and developed from mid-1950s to 1965. Released for military field
use circa 1965.
There are prior immunization programs of
note. My numbers are conservative by nature in the terms of what they really
did.
The US DOD, from 1965 to 1980, did 35
years of continuous service, to include the Vietnam and the Gulf War build-up,
on 20 to 40 million military personnel, which each were injected on multiple
times.
CDC, WHO and U.S. AID sponsored the
smallpox eradication program, 50 to 100 million people around the world.
Swine flu in 1976, according to Dr.
Weniger, did 75 million injections. Conservatively, I was 20 to 50.
The Brazilian African meningitis program
in 1988-1998 did 80 million injections in 60 days. The Brazilian measles
eradication program did somewhere between 60 and 80 million in 60 days.
Numerous CDC, U.S. AID, WHO--name is
all--sponsored routine vaccination and/or emergency epidemic immunization
programs over the last 30 years--100 to 500 million injections.
Conservatively there are more than a half
a billion, roughly, shots in the world, all without a reported contamination.
We've talked about the CDC MMWR article
in 1986. Thirty-one cases were confirmed with the Med-E-Jet. Unreported in the
CDC MMWR article was that the other injector tested, the Ped-O-Jet, the leading
injector in the world, in all cases tested negative for any traces of
hepatitis. And if you go to the article you can see it on page 375, line 21.
What has happened as a result of that one
contamination is the axiom that says that all injectors are unsafe. Since there
has been one reported contamination of a jet injector, it is theoretically
possible to contaminate all jet injectors.
As a result of the MMWR article and the
Med-E-Jet contamination, the Journal of the AMA, Newsweek and Middle East Health
all reported this contamination, saying that prior to it, jet injection had been
considered a safe method of inoculation.
WHO and their policy--Dr. Henderson came
out with a policy that said we are strongly recommending that jet injectors
should not be used if alternative methods are available. He further explained
that in the past, jet injectors were always used for mass immunization programs
when large numbers of people needed to have quick inoculation.
Ironically, he added in the same press
release, "For such emergencies, however, we are still saying that jet injectors
should continue to be used."
"All jet injectors should be used only as
a last resort for mass immunization epidemics until studies under way at Centers
for Disease Control show whether a design of a jet injector needs
modification." Very quickly, after eight or ten or 12 years since that time,
the policy remains in effect today with very, very minor modifications.
The problem is that CDC had no
opportunity or no plan to go further with any hepatitis evaluations. They were
very content with the fact that the leading jet injector was not and could not
be contaminated in their previously run hepatitis positive chimpanzee
experiments.
The myth continues in 1996 when WHO and
Public Health Laboratory in Kings College do a study. They tried to simulate
the infection of hepatitis in calves in a scenario.
The first information coming out of the
study said all but one injector was shown to be easily contaminated when
evaluated. They developed a new optically read ELISA assay, 10 to the minus 9,
designed to simulate hepatitis.
The net result of this PHL testing was
issued in a work in progress report 1998 was to reaffirm the theory that high
workload jet injectors, those with reusable fluid paths and reusable nozzles,
were easily contaminated and therefore not acceptable.
All the time, however, WHO continues to
recommend an enlightened policy of one needle/one shot, utilizing disposable
needles and/or an autodestruct needle, knowing full well that they are used
dirty in 70-90 percent of the developing world, that the developing world simply
can't afford autodestruct syringes and that the resulting sharps from either
type are improperly disposed of and routinely left unprotected on the street or
in a dump to easily infect unsuspecting men, women and children.
The facts of this whole scenario say that
the contamination study has not been replicated at an independent laboratory;
nor has it been subject to any peer review.
In an ongoing CDC public-funded SBIR
phase 1 research project that Dr. Weniger talked about, my company, Am-O-Jet,
the University of Florida, Kings College and an independent U.S. laboratory, we
think that the findings of this WHO study are seriously flawed. I'm not as
tactful as the public health community because I'm paying the bills on this one
and I do not see the replication of the data.
Of importance and for the record for the
FDA when we start looking at these studies that people begin to make up and say,
"This should be the standard," it is not one of the three approved tests for FDA
for hepatitis. The test method may not be scientifically valid. And there is
no indication that this test method will be acceptable to the FDA for any future
device submission.
The myth continues. In a steering
committee on jet injection in Geneva, Glenn Austin from PATH gave a report on
its ballistic gel testing, replicating skin and depth penetration in
contamination with ballistic gels. It described an experimental process and its
report said that the Ped-o-Jet could be easily contaminated as a result of back
pressure or splashback when fired into ballistic gel.
Subsequently, WHO issued a report and
this report was used by Keystone Industries, the purchaser of the Ped-O-Jet
assets and trademarks out of a bankruptcy sale in 1995, as the basis to write a
letter to the Department of Defense informing them that the product Ped-O-Jet
was unsafe, could easily be contaminated, and that Keystone no longer would be
responsible for the safety and efficacy of the product if it continued to be
used by the government. The direct result of this letter was an immediate ban
of all high workload jet injectors by the U.S. Department of Defense.
Recently, PATH's endorsement of this
ballistic gel model has been removed. However, one of the companies in the room
here with us today did independent testing and unlike skin, the ballistic gel
model demonstrated little or no ability to absorb fluid, often fractured and
artificially produced a fluid rebound, all leading to the erroneous conclusion
that splashback was inherent to a jet injector and produced contamination.
So where are we? Recently I was asked by
CDC to moderate a panel at the National Immunization Conference in Dallas. The
discussion was lively and it certainly centered around everything that we've
talked about this morning--needle sticks and there probably is a technology that
could help the industry immensely at this time.
An individual came up to me and said that
he had spent about 40 years in public health, had been part of the CDC smallpox
elimination program, had been part of the swine flu epidemic, and during his
career he had supervised or personally administered millions of doses of
vaccine with jet guns,
the Ped-O-Jet, and never once did he observe blood on the nozzle.
At first glance, the WHO stance he talked
about--one needle/one shot--would appear to be an enlightened policy, one that
could have a profound effect on reducing the spread of blood-borne pathogens in
the world. However, when one leaves the safe havens of Geneva, Atlanta or the
capital city of a developing nation, this enlightened policy assumes a far more
frightening face.
It is my estimate, and this is a direct
quote from him, this well intentioned WHO policy, one needle/one shot, is very
likely responsible for the spread of blood-borne pathogens to millions--is it 30
million, 50 million, 10 million?--millions of undeserving women and children in
the world.
Continued responsible use of high
workload jet injectors, on the other hand, would have resulted in a handful, if
any, infections.
Until there is clear scientific evidence
indicating jet injectors in the spread of disease, I believe that these devices
are the best alternatives for all mass immunization programs. Jet injectors are
far safer than available needle technologies for both the recipient and the
giver of vaccines alike.
Why do we need high workload injectors?
They're economic. They're about a penney a shot. They're efficient. A high
speed jet injector can do 1,000 people an hour if it has to. They're flexible.
They can be used by nonphysicians or nurses, by normal, well trained health
employees.
They have no hard currency value. If you
bring a program into the Third World and you have 5 million doses and 5 million
needles, about 90 percent of the needles don't make it because they're hard
currency on the street to be sold.
They're kind to our environment. They
have no disposal issues. There's no power required and they have no needle
sticks involved with them.
When should you use them? Pandemics,
epidemics, national immunization programs, special eradication programs,
military readiness and CBW response teams.
What is the future of Am-O-Jet's high
workload injectors? We believe in a traditional reusable nozzle, reusable work
path. We're continuing the production of that model.
However, we're tired of fighting the
battle and we're trying to develop some products, as my colleagues in ANFIM.
We're developing a new inexpensive low workload jet injector, something that
costs $300 and lasts 30,000 to 50,000 shots, again at a penny apiece. A new
disposal nozzle so that there is a pathway that's interrupted. A new
autodestruct disposable nozzle because in the developing world, if it's
disposable they continue to use it. It needs to autodestruct. And we're also
working on, like other people, a self-contained prefilled disposable
vaccine capsule. All able to fit the existing
injectors in the world and the new injectors.
Over the last 10 years, the following
have occurred: the fabrication, development and reinforcement of
misinformation, the creation of innuendo and assumption, all connoting jet
injectors are unsafe injections, an almost mystical transition of the
information from innuendo to scientific fact. The premise that high workload
jet injectors are unsafe and easily contaminated has not been proven.
Life is not without risk. I was a
military pilot in the 1960s. I went through flight school and two of my
classmates were killed in training. That was acceptable. I flew in Asia as a
military pilot and a variety of people were killed; that was an acceptable risk
again. And more dangerous than all of that, I drove on the beltway this morning
to get here and there's an acceptable risk of driving on the beltway.
We do not live in a world where all
medical devices or all medical procedures are risk-free. Many have inherent
risks, yet they are recommended, accepted and used on a daily basis. Vaccines,
by their very nature, have inherent risks.
There are several questions that we need
to ask ourselves. Is there a real risk of disease transmission with jet
injection? If there is, how great is that risk? What percentage of those
inoculated might have a chance to receive blood-borne pathogens? I'm not saying
there is, but if there were, what is it? What would be an acceptable level of
risk? Is risk-free, 100 percent chance of no infection, the only alternative?
Why are these questions very important to
all of us? Because we live in a world that's changing. If an epidemic were to
break out, perhaps something like meningococcal meningitis, where the fatality
rate was estimated to be 20 to 25 percent of those infected, tens of thousands
of people have to be inoculated quickly. Why options are there other than high
workload injectors? What would be an acceptable risk in this case?
If a pandemic were to come out of the Far
East, perhaps like bird flu of last year where the fatality rate was estimated
at 35 to 40 percent and millions of people--CDC estimated they'd have to do 250
million Americans in approximately 60 days--what options are available other
than high workload injectors? What would be an acceptable level of risk at a 35
to 40 percent fatality level?
If a CBW attack were to come to pass with
a fatality rate on one of the cocktails that they're talking about--anthrax,
smallpox and something else--estimated to be 90 to 95 percent of those infected
and millions of people--11 million people in the city of New York--would have to
be inoculated very quickly, perhaps within hours, what options are there other
than high workload jet injectors? What would be an acceptable level of risk in
this case?
I come to you with two hats. The first
is ANFIM. We'd like you to be fair and reasonable to our small manufacturers.
I come to you as a manufacturer personally and say there's a great deal of
innuendo and misinformation in the world that talks about jet injectors. We are
not being treated as fairly as needle companies, which have a variety of issues
that go unaddressed. We're being asked to be treated fairly. We're being asked
to accept what is a risk and how much is there? And I thank you for your time.
DR. EDMISTON: Thank you, Mr. Harrington.
As always, the script is changing. We
deleted one of our speakers, who represents the user side of this industry.
I'd like to call to the podium Deborah
Wexler, M.D., the Immunization Action Coalition. Dr. Wexler, please.
[No response.]
DR. EDMISTON: Is Dr. Wexler in the
audience?
[No response.]
DR. EDMISTON: So we didn't miss her.
At this time we will take a 10-minute
break. Let's come back by 10 after 3.
[Recess.]
DR. EDMISTON: I think we should finish
up this afternoon's session.
OPEN PUBLIC HEARING
DR. EDMISTON: At this time I'd like to
open the meeting for the open public hearing. Any member of the public may
address the panel during this open public period. Please limit your remarks.
Also I remind the speaker, if we have any
speakers, to approach the microphone, speak clearly into the microphone and
identify your affiliation and indicate if and what type of financial interest
you may have in this industry.
Do we have any speakers? We have two,
yes. Dr. Fisher?
DR. FISHER: I'm not going to talk about
the merits of jet injectors but I would raise the question that if you're going
to evaluate--if you consider those factors that I, as an occupational health
physician, have to raise, and that is the factor of what is the outcome of a
health care worker when you're doing 1,000 an hour, and if it's not properly
designed, the potential for musculoskeletal things is great.
And the other question I have is around
the issue of if there is any spray, if you have certain components, what effect
is that going to have, is aerosolization have on the provider? Because it may
be a small amount but if you're there all day, then it may be a cumulative dose.
So those are factors that should be
perhaps accounted for when you're giving approval.
DR. EDMISTON: Thank you very much.
MS. DUCMAN: Just real briefly, again my
name is Kathryn Ducman with Retractable Technologies.
I just would like to point out, in
contradiction to the previous presentation, not all needle and syringe
manufacturers are multi-million dollar corporations. Most of the new
technologies that are coming out are comprised of small, innovative businesses
out in the marketplace.
Some new technologies can make
one-shot/one-dose feasible, not to negate the value of jet injections but there
are technologies that do have an automated retraction that allows shots to be
given safely, efficiently and are absolutely nonreusable in that regard.
I think it is a dangerous concept to look
at an acceptable level of risk. As Susan Wilburn put so well, with some of the
emerging infectious diseases, such as hepatitis C, we weren't even testing those
until quite recently. So the idea of a contamination path, there are issues out
there that haven't even been delved into and it may be over the next one to two
decades before we see the effects of the past, how that has affected health care
workers.
Thank you very much.
DR. EDMISTON: Thank you very much.
Do we have any further speakers? Yes,
come forward to the microphone.
MR. ANTHONY: Thank you. I'm Bud Anthony
from the Biologics Consulting Group and I am a clinical consultant for
vaccine development.
I'd like to ask a question of one of the
speakers, if this is an appropriate time.
DR. EDMISTON: Yes, it is.
MR. ANTHONY: It's for Mr. Austin.
Glenn, in connection with Bruce's remarks
about using a jet injector with multi capabilities, that is, to deliver multiple
vaccines, has it been demonstrated or is it possible to demonstrate that the
individual vaccines do or do not mix within the tissues, end up in the same
tissue pocket, if you will? Or is it possible to demonstrate that they remain
separate or that they may commingle?
MR. AUSTIN: I'm not aware of any studies
that have been done.
MR. ANTHONY: Is it technically possible
to answer that question?
MR. AUSTIN: Yes.
MR. ANTHONY: Thank you.
DR. EDMISTON: Do we have any additional
questions for the speakers? Dr. Rutala.
DR. RUTALA: I had a question for Dr.
Weniger. The data that was presented in the MMWR from 1986 where there is the
one case of hepatitis B transmission, I was wondering was the jet injector used
as directed? That is, was there compliance with the manufacturer's use
directions?
And then if there was, could it be
modified such that the mechanism of transmission could be circumvented or
corrected?
MR. WENIGER: I believe it was used
according to direction and all these manufacturers do recommend swabbing of the
head after each shot to remove any serum or blood that might be on it.
The problem, as I alluded to in my talk,
is that there are occasions when health care workers are negligent and they
don't remember to do that, and that was the case in Brazil.
One of the hypotheses about the Med-E-Jet
was that the nozzle actually consists of an internal pin surrounded by a sleeve,
leaving basically a potential gap for capillary action to wick fluid from the
skin back into the device, which would not necessarily be removed by swab, and
that's still a hypothesis.
So I guess the issue that you're raising
is how can we minimize health care worker negligence or lack of attentiveness to
following manufacturers' directions? How can we make such devices so-called
failsafe? And I think it's an important question.
That's why in putting out contracts for
the development of a new generation of devices using disposable cartridges,
thinking about the developing world problem, we have encouraged people to figure
out ways to make sure that once it's used, it cannot be reused, even
intentionally, in places where they might want to save on costs, by having
somehow damaged or the piston gets locked into the bottom of the cartridge at
the end of the injection or some other way that it can only be used once.
DR. RUTALA: I guess just a follow-up. I
certainly agree with the comment that there's no such thing as absolute safety,
but obviously we always try to minimize risk and minimize disease transmission.
Do you believe it is possible to develop
a jet injector that would eliminate the risk that was seen in the one case of
hepatitis B transmission?
MR. WENIGER: Are you referring to a
multiple use nozzle--
DR. RUTALA: That's correct.
DR. WENIGER: Metal nozzle?
DR. RUTALA: That's correct.
DR. WENIGER: I think it's possible but I
think the challenge is to develop a methodology to evaluate that, to convince
ourselves of it. I think, and this is my own unofficial personal opinion, that
a more promising line of development is to just go the disposable route and
figure out some way to make a disposable cartridge work in a high speed gun, and
then we have the best of both worlds and we can avoid this uncharted territory
we're now in, trying to develop a model to measure extremely small quantities of
blood that might theoretically transmit these infections.
DR. RUTALA: Thank you.
DR. EDMISTON: Mr. Harrington, I believe
you had a comment? Come forward, please.
MR. HARRINGTON: The term "acceptable
risk" is not one that I coined but one that Dr. Margolis, head of the Hepatitis
Branch, CDC, coined at a meeting held by Dr. Weniger at CDC and his question
was, "Tell me what the risk of transmission is and if I know the mortality rate
and my risk is very little for hepatitis transfer, I can deal with treating
adult hepatitis but I can save millions of people from dying from the disease."
So I'm not suggesting there is a risk of
transmission but his concept was what is an acceptable risk if the mortality
rate is so much higher?
DR. EDMISTON: I think we had one more
individual in the back. Please identify yourself.
MR. SOLERNO: I'm Larry Solerno. I'm
director of operations for Retractable Technologies.
I will agree with Mr. Harrington on the
point that small business that is doing the innovative work, when they're trying
to get their 510(k)s and things passed, is on a very limited budget, that
excessive clinical trials or things that make the cost of--we were talking
earlier about prototype or devices that were used, if it takes $10 million to
get out of the prototype stage into a process where a company can put a device
before they get their 510(k), it's going to help kill the innovative research
that the National Institutes of Health and things are putting forward in the
process.
DR. EDMISTON: Thank you.
Are there any further comments or
questions?
[No response.]
OPEN COMMITTEE DISCUSSION/
PANEL SUMMARY RECOMMENDATION
DR. EDMISTON: I believe at this time we
will move into the open committee discussion with recommendations. I should
point out that at 4:00 we're going to lose approximately half our panel, so I
suggest that we move expeditiously through this.
And I would propose that we would combine
questions 1 and 2. "In general, what are the key issues that should be
considered in the premarket evaluation of jet injectors? And what data should
be appropriate to address each of these above issues?"
Let me get the ball rolling by suggesting
the following. I think it's obvious, whether we're talking about a disposable
or reusable device, there's an issue of safety and we have to have some way to
evaluate safety, be that bench testing, engineering controls, and I think that's
prudent.
We also need to ascertain dose accuracy.
We also need to ascertain labeling. If the injector comes prefilled, there has
to be some indication of labeling on that. Shelf life.
And I think as was brought out in the
earlier presentation, the issue of ISO standards I think are significant and I
would suggest that the FDA be very interested in the development of standards
for this industry as it evolves.
I think Mr. Harrington's concerns voice
one side of the equation but I think what's very important is that as a
technology in this area emerges in which children will be able to give
themselves injections at school or a variety of individuals who'll be able to
give themselves injections in atypical health care environments, there must be
some way that we can provide a watchdog area of expertise for these devices.
Having said that, I want now to poll my
panel members and see what their interests may be and concerns regarding these
two questions.
Ms. Ryder.
MS. RYDER: Well, I guess one of the
issues that came to mind as I heard the presentations and the huge numbers of
patients who have received injections by this method, and it was also pointed
out that we're only beginning to understand some of the emerging communicable
diseases, that what type of surveillance has been done on this to determine
indeed whether there were any resultant infections or transmissible diseases.
In other words, did the infections occur but we just didn't know it? And is
anybody actually measuring resultant infections from all of these injections?
DR. EDMISTON: Dr. Rutala?
DR. RUTALA: I just have a few comments.
I thought the presentations were excellent and I really appreciate the
information that was provided to us.
I have a number of questions or have
prepared a number of questions or a number of comments as far as studies not
having heard the presentations, but I'm going to comment on a few things,
realizing that some of these questions have been answered.
When I consider jet injectors, certainly
we have to consider efficacy issues and when we consider vaccines, we have to
consider things such as seroconversion rates and geometric mean titers. And, of
course, that, I think, has been answered.
I didn't hear any reference to geometric
mean titers and whether jet injectors provide the same geometric mean titers,
but everything else that was mentioned regarding the use of that product seemed
to be very comparable.
As far as drugs, of course, we have to
consider pharmokinetics--half-life, excretion, time to peak level, peak
time--and, of course, that needs to be considered by the manufacturers.
Side effects, of course. There has to be
consideration of the side effects of administration, such as abscessing,
bleeding, induration, erythema, superficial papules. And, of course, that can
be accomplished and I think it already has been accomplished, according to the
presentations, by randomized trials with frequency and type of complications
recorded. So I believe that's been addressed.
Of course, nosocomial infection risk is
very important in risk of disease transmission. That has been addressed. It
appears that there is at least one case of evidence of transmission.
Of course, as was mentioned by Marcia,
there's always a concern if there's not an active surveillance system or if
there's not some in vitro studies that demonstrate the absence of transmission,
what the true prevalence of transmission or the real incidence of transmission
is.
As far as
delivery amount, our chair has already mentioned the
delivery amount. Contamination has been mentioned. Those studies can be
done both in vitro and in vivo.
Contraindications. Of course we have to
evaluate the efficacy and safety in groups most at risk for failure or injury.
Those are some of the issues that
immediately come to mind.
DR. EDMISTON: Mr. Palomares?
MR. PALOMARES: I just want to remind the
panel that this product has already been classified as a Class II device, such
that it's supposed to be regulated by general controls, as well as some
performance standards if they're established.
So we have to really look at the safety
and effectiveness of this product, as well as the risks and benefits that the
products do provide here. There's a lot of data here, some of them established,
some of them not so. We have to look through that carefully.
DR. EDMISTON: As a potential use, Mr.
Dacey?
MR. DACEY: I'm going to offer what I
would call a very generalized overview, speaking as a consumer. That is I want
to go back to the definition of the word "medicine." As I understand it and
have been using it, medicine is a science-based remedy.
Ultimately, every consumer, every
patient, despite all the hype and all the stuff that goes on in the marketplace,
must at some level place its trust and faith in the science and not in the most
effective marketing strategy and salesmanship.
So as a consumer, I have to trust each of
you as scientists to do what is not only best but what is right because I don't
know, as a consumer. I'm not that much of a scientist.
DR. EDMISTON: Mr. Ulatowski?
MR. ULATOWSKI: Could I defer comment
until I hear from the other side?
DR. EDMISTON: Dr. Fowler?
DR. FOWLER: I think the presenters were
most interesting and enlightening and there are a number of questions certainly
brought to mind.
I wonder if one way to consider some of
these issues might be to divide to some degree, although I realize there's a lot
of overlap but to divide the projected use and the type of product--to divide
our thinking by the type of use or product.
For instance, we've heard very little
about the insulin injector that an individual subject or patient might use, and
perhaps many of the concerns for that product are not at all the concerns that
we're hearing much more about as far as the general vaccination uses.
And then a third section, which would
seem to me to perhaps be the most important one for further thought would be the
use of these types of products for medications to replace individual needle
injection in a hospital setting or in a facility setting or in a doctor's office
or dental office setting, to replace the use of needles and thereby to help
reduce the risk of needle stick injury.
And so in looking at that issue, as Dr.
Rutala mentioned a bit, I think there are a number of issues about drug
stability and where the dose is delivered. With a vaccination maybe it's great
to have a little more in the skin so the Langerhans cells can get to it and
enhance your reactivity, but with some other medication that you don't want
there, that might be a drawback. And I think that seems to me to be an area
where this type of product might have great promise but has certain concerns
that are not present in either of the other two areas.
DR. EDMISTON: Mr. Ulatowski?
MR. ULATOWSKI: Very quickly, I think
I've heard pieces of what FDA came here to find out in terms of how to approach
the evaluation of these products and I've seen a couple of overheads from Bruce
and others on an approach.
I guess our concern, as I said
originally, primarily is in terms of the clinical data. Whenever you say
clinical data it kind of scares half the population of manufacturers.
We want to be very careful in when we're
looking for data above and beyond the engineering types of bench tests. What's
the clinical question? You're heard that from Larry Kessler this morning.
What's the clinical question that we need to ask and get data on to answer, that
we don't otherwise have information on from the published literature, from
documented experience?
Von talked about valid scientific
evidence. What is out there in terms of valid scientific evidence to support
the safety and performance of jet injectors and the powder injectors and others,
for delivery of the products for which they are
labeled, intended for use?
And it's a time right now, as we develop
this guidance, to look at what we have in hand in terms of valid scientific
evidence and to say to ourselves, these claims are acceptable because the data
is there and it is as follows, for certain antibiotics, for certain drugs, for
certain vaccines. But to permit a broad indication for use, for
delivery of drugs or vaccines, I think that's an
area that we have to be very careful about and be data-driven.
So it's a time to look at the data.
We're primarily concerned with clinical information now that we're looking at.
And I heard from Dr. Rutala about the information in terms of drug and
vaccine information, taking that into account, in
terms of the Class II nature of the product, which allows us a lot of
flexibility for these kinds of products in terms of how we approach these
devices, and about dividing up these products. Not every type of product
necessarily needs the same amount of data. And, of course, being data-driven.
DR. EDMISTON: I think we can clear this
up fairly quickly. If you look at the first two questions, I think the issue of
safety relative to the engineering, there has to be some engineering controls
built into these devices, especially these new innovative devices which can be
used by a variety of end users, both adults and children. And I suspect these
devices will also find their way probably in the Third World at some time in the
future, as the costs come down.
That kind of testing is relatively easy.
Also validating dosing. The science is well established in terms of the unit
volume that's delivered and the pharmacokinetics has been well developed in
other studies.
What you're really talking about is the
third question, and that question is, "If and when clinical data are
appropriate, what are the panel's general recommendations regarding the form and
content of the studies?" Am I correct?
MR. ULATOWSKI: I think that's the
biggest point of concern of the industry.
DR. EDMISTON: So, in essence, we've
answered questions 1 and 2 and we're now going to move to question 3.
MR. ULATOWSKI: Taking stock of what
we've heard today in total, I think a lot of points have been covered.
DR. EDMISTON: I think for questions 1
and 2, what the panel may want to consider as a recommendation, and I'll poll
the panel, is that there should be an effort on the part of industry to provide
engineering controls documenting the safety of these devices, and that type of
documentation can be derived from bench data, from laboratory data.
MR. PALOMARES: I'll concur with that.
DR. EDMISTON: We're in agreement with
that?
Now let me ask you one more question as
the FDA liaison here. The drug side of it, how closely do you work with your
colleagues on the drug side of it to validate that that dose going in there is
the appropriate dose for that injector?
MR. ULATOWSKI: Well, there's the rub.
We have an historical context here in terms of jet injectors that we want to
provide--be fair to the manufacturers in regard to what's been permitted in the
past but let's all get firmly footed in the data and then move on from that
point as to what we need from now on in regard to additional claims for
additional drugs, for example.
DR. EDMISTON: So as new drugs come to
the market and as they're delivered by this type of technology, will that
evaluated separately?
MR. ULATOWSKI: That's evaluated in
harmony with our drug evaluation center. If we see a drug product that has not
been in the labeling before, we'll send that for a consult review to our drug
evaluation group.
DR. EDMISTON: That's not really a 510--
MR. ULATOWSKI: Yes, it may still be.
DR. EDMISTON: It still may be a 510(k)?
MR. ULATOWSKI: Mm-hmm. Comparing one
jet injector to another is difficult sometimes. One does not know whether the
performance characteristics will end up providing equivalent doses to the
desired site. There's insufficient data showing ranges of parameters that are
acceptable for various types of drugs. So it's a case by case basis sometimes
that we ask our questions.
DR. EDMISTON: Let me ask Dr. Weniger of
the CDC to go to the podium. I'd like to ask him a question relative to
vaccines. When you've looked at various devices, this issue of dose accuracy
between devices, what is your interpretation based on your experience?
MR. WENIGER: Well, I'm not privy to any
dose accuracy studies that may have been submitted for devices already on the
market. I haven't collected all the 510(k)s and maybe I can do that some day.
I guess my sense is that it would be
reasonable to request device manufacturers to provide that information but I
guess my recommendation would be that we not try to be too rigid about it
because clearly when needles and syringes are used and the nurse is measuring
the 1.0 ml dose or the half cc dose, there's probably 5 to 10 percent variation
right then and there. So I think we ought to have some flexibility around the
nominal dose in that regard.
If I can just comment a little bit about
the Catch-22, I think that we have in this situation where the drug
manufacturers and the vaccine manufacturers don't
have an incentive to do the additional clinical studies of their products with
jet injectors because it's such a tiny market.
On the other hand, the device manufacturers,
this cottage industry, cannot afford to do the studies on each and every
possible drug that might go into them, and they are held back by the lack of
market demand for these devices because until the manufacturers are going to
prefill the drugs or the vaccines into cartridges to eliminate that filling
step, they're very inconvenient for the end users. So there's this chicken-egg
phenomenon. Neither the chicken exists nor the egg exists and it's hard to get
them started. That's why we're trying to promote prefilling, to help overcome
that.
But the challenge will be, and I think
this is where public health agencies can help and universities can help and NIH
grantees can help, to develop clinical data on the use of a jet injector with
vaccines A, B, C and D and new vaccines that are coming along, like for example
hemophilus. There to date has never been a study of hemophilus
vaccine administered with a jet gun.
If we can provide that kind of data,
perhaps not under an I&D but at least get it into the literature, maybe this
will help a manufacturer of a device to say this has been shown to be effective
with this type of a gun.
Did that answer your question? I'm not
sure I completely answered it.
DR. EDMISTON: I don't believe there is
an answer.
Do any of the panel members have any
questions for Dr. Weniger?
[No response.]
DR. EDMISTON: I think at a minimum, we
should have some assurance that there is sufficient dose available in these
devices, so there has to be some labeling criteria as to when the dose was put
it, what's the shelf life of that. And I suspect that's already in place to
some extent, isn't it?
DR. WENIGER: Well, I think we're sort of
talking about two quite separate issues. One is the issue of jet injectors as
simply delivery devices, like needles and syringes.
And the other is if we can convince manufacturers to prefill into cartridges to
go into jet guns, then we have to deal with all the
potency and stability and compatibility with the plastic questions and the shelf
life in that, and I think that's quite reasonable and that burden ought to be on
the vaccine manufacturer who proposes to put them in
and we need to create enough incentives to encourage the manufacturers to do
that.
DR. EDMISTON: Do you anticipate that
will occur in the foreseeable future?
DR. WENIGER: Well, like I say, until we
can develop enough demand for needle-free devices, guns
that physicians and hospitals can buy, I don't see the manufacturers seeing a
large enough market to justify doing the studies on the several hundred patients
that might be necessary to develop the serologic assays or the bioavailability
studies.
DR. EDMISTON: So from your perspective
the real issue here is the safety and engineering designs of these devices.
DR. WENIGER: No, actually I think that's
a side issue relevant primarily to the multiple use nozzle devices. I think the
existing devices that have disposable cartridges, I don't see any inherent
problems with them. They've passed 510(k)s and they get their insulin in and
they get a number of other devices in and the side effects, although slightly
increased, are not unreasonable.
DR. EDMISTON: So you don't think it
would really be necessary for them to provide documentation, or at least bench
documentation, on the efficacy or the engineering characteristics of their--
DR. WENIGER: No, I think any device,
whether a disposable cartridge or a multiple use cartridge, ought to demonstrate
that it gets into the tissue that it states it goes into, whether it's
subcutaneous or not, and to provide either human studies with radioisotopes and
nuclear magnetic resonance imaging, which is not invasive and doesn't expose you
to x-rays--those techniques are there--to do cadaver studies or animal studies
to show that it gets in where it states it gets in.
The challenge, though, is that if someone
wants to use an IM vaccine in a device that only a
third of the time or less delivers IM, we now have an off-label--well, not an
off-label but sort of a conflict situation. There may be clinical data that
says you can use a jet gun for this product, even though it doesn't get into the
nominal compartment that's stated in the manufacturer's label for that
vaccine, but it works. So there's little incentive
to get the manufacturers to do some additional studies to show that jet
injection subcutaneously will work just as well as needle and syringe IM.
DR. EDMISTON: Well, that issue really is
a prevalent issue in health care, especially in anti-infectives and other types
of biologics, the off-label use. You'll never be able to address that per se.
DR. WENIGER: But I guess what I'm
hearing from the manufacturers is they want to bring today, 1999, not 1995, to
the FDA an application or a 510(k) for a device and they can show it gets
subcutaneously but then they want to be able to market it for the following six
vaccines or maybe vaccines in general and I'm hearing the requirement for proof.
Now we have some information in the
literature that they can use smallpox vaccine, they
can use measles vaccine, they can use a variety of
vaccines, but what about the practitioner who wants to use it for a
vaccine that doesn't have that data yet, like
hemophilus influenza, for example? How can they label this device, well, you
can use it for some vaccines but not all? Do you want them to specify--
MR. ULATOWSKI: And that's a problem.
It's the mutually conforming labeling, we call it as bureaucrats, making sure
the vaccine is labeled to be delivered by that
particular method of delivery.
It's an issue that's in front of our
Biologics Center right now, as far as how they're going to approach this issue
with jet injectors. But I certainly would want to rely upon what we've already
cleared and permitted in the past to continue, but to be watchful for additional
uses until some data comes forward, more data comes forward that says everything
is very similar in terms of delivery aspects from
one method to another, and I don't think that data is there. It's probably
going to be a product by product, vaccine by
vaccine issue in many cases.
We have a representative from Biologics
here who's going to consider what's been said today and you've already heard
from Norm Baylor at a couple of conferences where his concerns have been voiced
in regard to this.
We've had examples, for example, a device
coming forward that delivers a dose but doesn't match a dose of any drug in the
PDR. So you ask, "Well, what drug exactly do you intend on delivering by this
injector?" It turns out to be something like a product looking for a use, which
isn't good thinking. You're trying to provide a product that's going to deliver
a therapeutic or prophylactic, in terms of drugs, dose to the patient.
There have been many other cases where
it's not been very well thought out exactly what the product is and what it's
intended to deliver and we're seeing that more and more, I think, in my
division.
DR. EDMISTON: Well, let me try this
again, and I need my panel's help on this, that in devices that present
themselves to the FDA, if those devices are deemed significantly the same or
similar to devices on the market--
MR. ULATOWSKI: We're looking at a
grandfathered situation for many products still.
DR. EDMISTON: It's the FDA's call as to
whether or not additional data is required.
MR. ULATOWSKI: That's correct.
DR. EDMISTON: However, devices which
represent new technology, innovative technology, I think those devices--
MR. ULATOWSKI: Additional data.
DR. EDMISTON: Additional data, bench
data, engineering data, that would be appropriate. Adding to that the intended
use of the device in terms of the serum, the vaccination, anti-infective,
whatever is going to be delivered, can that be documented? Can the manufacturer
document that the effective therapeutic dose is delivered by that device?
MR. ULATOWSKI: By those parameters?
DR. EDMISTON: Right.
MR. ULATOWSKI: By the specifications.
Maybe not even that device necessarily.
DR. EDMISTON: Does to panel agree with
that?
[Nods from panel members.]
DR. EDMISTON: Now let's get to the area
of the clinical. I'd like to refer to the slide that Dr. Weniger presented on
the regulatory issues for jet injectors, which I think is a very nice slide
because it summarizes some of the issues that we're looking at.
For instance, needle-free injectors as
empty drug delivery devices. Do you require
clinical data on all drugs or only representative ones which the end user might
administer? And I want you to help me with this as I go through it.
Your tactile recommendation there is
probably no, and can you tell me why?
DR. WENIGER: No, actually that probably
refers to the more extreme proposition, which was to require you to have
clinical data prepared by the device manufacturer for every possible drug that a
physician might put into that device, and obviously the answer is no.
I think there may be some reasonable
balance in terms of selecting, and I use the example for a new jet injector that
comes along that doesn't have a predicate, to ask for some clinical data on a
representative live vaccine, representative
inactivated vaccine, perhaps one that has a good
serologic correlate so you can get an answer with 100 patients or 200 patients
and not have to do a field trial of 10,000 patients. I think that might be a
reasonable balance, to ask for that for a new device.
DR. EDMISTON: Then you state to require
animal and clinical data demonstrating compartments for doses deposited. We
discussed that already. Is the appropriate drug being delivered in the
appropriate area? Or demonstrate equivalence to proven devices. You said
maybe.
I think the FDA is well positioned to
make that decision in terms of equivalent devices because though I've looked at
devices similar to that in the past, in terms of whether or not that drug is
being delivered into that department, that is a key issue and my concern is
again what is the dose that's in there and is all that dose getting to the site
of action?
Now that could be onerous because we know
pharmacokinetic studies are very costly. I don't think this committee has to
recommend any number, but I think there has to be some basic clinical studies
conducted, especially on those products, as you mentioned, the new vaccines that
have not been tested in these devices before.
What are the comments from the panel?
Marcia?
MS. RYDER: I would concur.
DR. RUTALA: I agree.
MR. PALOMARES: Usually I've seen where
you're talking about dose deliveries; it usually falls on the onus of the
pharmaceutical manufacturer, not on the medical device. There are some drugs
that you have to look at and determine is it compatible with this product, but
not determine if I use vaccine A, does it get into
the appropriate dosage.
DR. EDMISTON: I think the issue would be
if you used a cartridge but that device only delivered half the dose, that would
be a concern, correct?
DR. WENIGER: Yes, and I think obviously
there ought to be data in the licensure of that product that states that when
the nominal dose is a half cc it delivers a half cc plus or minus some
reasonable variation. So that would be solved in terms of the required animal
or human data to demonstrate that in the license phase, but that's really
separate from efficacy of the drug or the vaccine
achieving its intended use.
MR. PALOMARES: Well, maybe Mr. Ulatowski
can help us here. When you have prepackaged combination on device-drugs, does
it usually go through CDER or ERH?
MR. ULATOWSKI: As I mentioned up front,
if it's a prepackaged, prefilled vial, it's evaluated by our biologics or drug
component, rather than by devices. We'll evaluate a jet injector that's applied
without a drug product or biologic product, as sold.
DR. EDMISTON: See, dose accuracy will
have impact on efficacy, so there has to be some way, at least on the front end,
for the user to be confident that he's getting an accurate level of that dose,
at a minimum. It may or may not be efficacious, depending on what he's
delivering, but you want to be assured that you're getting that basic dose.
Under those circumstances I think the FDA would want to have clinical data.
MR. ULATOWSKI: Yes, I think maybe our
biologics rep, if they're here, would want to comment. I think she does want to
comment.
DR. CHANDLER: I'm Donna Chandler. I'm
here from the Center for Biologics Office of Vaccines. I'm deputy director of
the Division of Vaccines and Related Products Applications.
I think part of this has to do with the
grey area and the case by case sorts of language that we always run up against
with biologics.
I think when we approve vaccines, for the
most part we're looking at approving essentially up through the packaging.
That's part of the labeling and would be part of the licensure application. For
example, we would look for stability studies showing that the
vaccine is compatible with the labeling, with the
packaging. And normally we'd be thinking in terms of referring to our device
colleagues for the device that was going to actually deliver that particular
product.
Now when we start to think about a jet
injector, we're starting to get across issues that are going to be important to
both of the centers.
I happened to be looking through some
labeling recently for something else and came across the fact that certain
multi-dose vials are approved for use with jet injectors but when you start to
talk about cartridges that are going to be used with a jet injector prefilled,
we would expect data, probably clinical data, to show that any change in
delivery system would give--you'd still assure the
safety and efficacy.
For a
vaccine
we're primarily looking at immunogenicity. And oftentimes when there's changes
such as in a regimen or a route of administration, we would look for clinical
studies, head to head, the proposed change versus the standard of care or what
is already approved.
DR. EDMISTON: Because of the intimacy of
your interest and this panel's interest, would you feel that it would be
appropriate that the recommendation is that the dose accuracy and efficacy be
linked, especially for new vaccines?
DR. CHANDLER: Well, by efficacy we
probably wouldn't expect a large scale field trial. I mean that would be
overkill. But we use oftentimes immunogenicity as a surrogate in many, many
cases for vaccines, and that's not the equivalent of a study. I mean clearly
you have to have immunogenicity studies or immunogenicity assays well in place
and potency assays for the approval of a product.
So immunogenicity, clinical
immunogenicity data and potency, either in vitro or animal studies, would be
appropriate. Does that answer your question?
DR. EDMISTON: But you feel that the
issue of dose accuracy is extremely important for these devices?
DR. CHANDLER: Well, probably not so
much--I mean it's not going to be quite as important for vaccines. It's going
to be much more important for drugs, I would think, because your response to a
vaccine is going to be--it's going to be somewhat
variable. The immune response to a vaccine is
oftentimes much more variable than, say, the pharmacokinetic response to a drug.
DR. EDMISTON: So you differentiate
between one of these devices being used to vaccine
someone against measles, as opposed to one of these devices being used to
deliver a dose of insulin to a diabetic?
DR. CHANDLER: Yeah, I would think so.
But again it's a matter of data.
Well, let me go back. I think that we
would generally expect to have at least stability data and maybe even some
clinical data for the use of prefilled syringes, and I think that's about as
close as we get to what you all are talking about now.
DR. EDMISTON: Is the onus, though, on
the manufacturer of the jet injector at that point for prefilled syringes or
vials?
DR. CHANDLER: No, that's part of the
vaccine's license. In other words, when we approve
the vaccine we approve the final package. Again
that's why I say this jet injector is getting into a grey area. I think it's
going to require cooperation and collaboration between the two centers and
probably between the two manufacturers.
DR. EDMISTON: So what I'm hearing, what
we know currently about vaccination is that the dose accuracy is less of a
concern than it would be for other biologic agents if we go into anti-infectives,
liposomal compounds or other biologics of that type.
DR. CHANDLER: Right, but that might well
be balanced by or counterbalanced by the concern for the site of
delivery, for muscular versus subcutaneous or
intradermal.
DR. EDMISTON: So the FDA should have
wide latitude then, in terms of evaluating what type of clinical data they would
need relative to whether it's a new technology and a new application of that
technology--the delivery of anti-infectives or
delivery of other biological entities like insulin.
DR. CHANDLER: Right. I would think that
a question could be we have experience with a vaccine,
for example, the hemophilus vaccine, that's been
given--an approved vaccine given by a specific
regimen using approved devices.
And if we would be involved, and this is
just sort of a personal viewpoint and not having had a chance to be involved in
previous discussions but I would think that if somebody came to us and said, "We
now have a cartridge that we would like to evaluate that we would like to have
approved and we'd like to add that to our labeling for a hemophilus
vaccine," we would like to see data to show that
that hemophilus vaccine delivered by that cartridge
and jet injector system is--that that vaccine is as
equivalently immunogenic as the needle and syringe method.
DR. EDMISTON: Thank you.
MR. PALOMARES: But who is the onus on
again? Excuse me but who's the onus on? Is it going to be on the
pharmaceutical or biologics or is it on the device manufacturer?
DR. CHANDLER: Well, that's going to have
to be worked out between the manufacturers, I think. And then probably it's
going to need further discussion.
DR. EDMISTON: I can see where there is a
lot of data available on immunizations with these devices and there is virtually
nothing available on other biologics in terms of both the pharmacology and
possibly even the efficacy, but it's indelibly linked to whether or not the
correct amount of the drug is being delivered to the patient.
So I think it's going to be on a case by
case basis as to whether or not the device is being used for an old application
or is it being used for a new application.
Dr. Weniger?
DR. WENIGER: Yes, just to follow up on
that point, I think clearly this issue is more important with nonvaccine
pharmaceuticals because the immune response has so many factors that affect it
and it's usually either protected or not protected and there's a fair amount of
overkill. There's probably more antigen in most vaccines than a patient needs
to be protected.
But I would ask what is the current
requirement for dose accuracy for a manufacturer of a simple needle and
syringe? Do they have to provide data that 100 nurses measuring up a half cc
dose accurately deliver that dose and a variation above and below that dose?
Because if you don't require that for
needle and syringe manufacturers--it seems you ought to apply the same
requirement for jet injectors. If there's a plus or minus 5 percent on the
nominal dose that's read in the indicator, if that's applied for one, it should
be applied for the other because my guess is there's a lot of dose variation,
high dose variations with needles and syringes.
DR. EDMISTON: The only problem is you
can see the dose in a syringe.
DR. WENIGER: Well, I think most of jet
guns--
DR. EDMISTON: Can you see it in the jet
injector?
DR. WENIGER: In the ones that have
disposable cartridges, the goal and I think the ideal is that you can always see
the dose in there. And if it's prefilled at the factory, it's--
DR. EDMISTON: So you can determine
whether or not the entire dose was delivered.
DR. WENIGER: Yes, you should be able to
see that it reaches the right marker on the--if it's a syringe and I have a
sample, I can show you afterwards. If it's a cartridge, the end user who fills
it usually has the gradations to mark the amount, such as a syringe. Then at
the end of an injection you can see that the plunger has gone all the way down.
Now, of course, some of it might leak out
on the skin in some cases, so that can occur.
DR. EDMISTON: So it's a very difficult
issue to thrash out. From the perspective of the manufacturer, one could say
the efficacy isn't really in my ballpark. The efficacy is in the ballpark of
the pharmaceutical company.
MR. ULATOWSKI: Well, we have cleared a
lot of products that say a lot of things about drugs and vaccines and before we
go any further down that path we want to make sure that we're clearing products
appropriately with their intended use labels and not extrapolating or extending
ourselves beyond the data.
DR. EDMISTON: But you said that. This
is the second or third time you've said that, so I think this is a key that
you're trying to get me to pick up on. It always takes at least three times.
The device--
MR. ULATOWSKI: I had a bat here. I was
trying to get your attention.
DR. EDMISTON: The device's intended use
should be clearly defined.
MR. ULATOWSKI: Yes.
DR. EDMISTON: Clearly defined. So a
recommendation from this panel would be that the intent of the device, its use,
clinical use, is clearly defined.
Now the issue of where there is a concern
for clinical studies, I think it was very well demonstrated that there are other
ways of getting around clinical studies. But again the issue is I'm not sure
that's the purview of the manufacturer. More the requirement of the
pharmaceutical company.
Am I off-base on this or do you think--
MR. ULATOWSKI: Well, if the jet injector
manufacturer wants to list a specific drug, then he or she is in a bind by
having to provide the data showing it's efficacious with that drug. If there's
no data, then there can be no claim, and that data can come from historical
information, experience of use, that valid scientific evidence I spoke of.
DR. EDMISTON: So there will have to be
minimal efforts on their part.
MR. ULATOWSKI: Yes.
DR. EDMISTON: To demonstrate some type
of efficacy.
MR. ULATOWSKI: And I think we might even
construct some sort of labeling that would be acceptable for jet injectors based
upon the historical information now available.
DR. EDMISTON: And it's unlikely that
we're going to need the types of studies involved in randomized double-blinded
type studies with these devices.
MR. ULATOWSKI: Well, I would hope they
would be incorporated into evaluations of drugs when the drugs are being
studied.
DR. EDMISTON: Yes. So it makes a rather
simplistic evaluation.
Any comments from the panel?
[No response.]
DR. EDMISTON: Now you're taking notes
back there so you can tell me if I'm misspeaking on this, but I think in terms
of the first and second questions, we felt that in devices that are similar to
devices that have been approved by the FDA in the past, that the FDA has wide
latitude to determine whether or not there's a similar or dissimilarity between
these devices.
If these devices, as a result of being
new and emerging technologies, and there's very little historical data
available, then the FDA is probably within its right to request bench
engineering-type data to demonstrate the safety of these devices.
In terms of the clinical trial, it would
be important for the manufacturer to document what these devices are going to be
used for. And if they do that, then there is some level of onus to determine
whether or not there is an efficacy for the utilization of this device.
I think it's unclear how that efficacy is
going to be determined but I believe it gives wide latitude to the agency, plus
in consultation with the manufacturers, to come to some consensus on this.
Would that be an appropriate
interpretation?
MR. ULATOWSKI: I think that's fine, yes.
DR. EDMISTON: Dr. Weniger, would you
concur with that?
DR. WENIGER: Yes.
DR. EDMISTON: Are there any other
questions by panel members?
[No response.]
DR. EDMISTON: Members of the audience?
Yes.
MS. RYDER: Were you finished with number
3, as well?
DR. EDMISTON: I thought I was. Go ahead
and jump in there.
MS. RYDER: I just was questioning
whether we addressed the issue of transmission of infectious diseases among
devices, how they would demonstrate that.
DR. EDMISTON: Let me defer to Dr.
Weniger on this. Can you jump in here and give us a little bit of help?
DR. WENIGER: Well, I was looking at the
guidance document for the morning discussion that talked about how many sharps
engineered devices need to be tested without a failure of either a needle stick
or a failure of the device that might have resulted in needle stick, and they
came up with a guidance of 500 and they showed the statistics for the confidence
limits around 100, 500 and 1,000 and so forth.
Having some kind of guidance like that to
help us in doing these studies with the pigs and the cows I think would be
helpful. It'll tell us what the ground rules are for this effort and if zero
shots out of 500 is reasonable, zero out of 1,000, I think that might be
realistic.
Beyond 1,000 it becomes a bit burdensome,
so it would be nice to have some feedback that if you shoot in some model that
you believe can detect the lowest infectious dose, what number would satisfy you
that you'd let your daughter or son have an injection with one of these devices.
DR. EDMISTON: Now we're talking about a
preclinical model, correct?
DR. WENIGER: Yes, this is animal
studies. Actually the Brazilians have actually done a human one in which they
injected infected carriers of hepatitis B and then put the subsequent injections
into vials and then sterilized the device before the next subject in that study,
so there was no danger of cross-contamination, but the results are not yet in on
that. But that's a very difficult--
DR. EDMISTON: Now what you'd propose,
for instance, if there were 500 consecutive injections, at that point the device
is taken apart or at that point the device is evaluated to determine if there's
any contamination?
DR. WENIGER: What I would say is you'd
give an injection to the animal and then the next injection would go into a vial
and you would search for quantities of blood from that animal and if you find
any quantities above your cut-off, you would say that was a potential
contamination event. And the question is how many of those pairs--animal-vial,
animal-vial--would be needed in which you resulted in no episodes of a
contamination event that would satisfy the regulatory review. That's the
difficult question.
What is the magic denominator? Zero out
of 500 or zero out of 1,000 or zero out of 100 or zero out of 10,000? I don't
want to put a number before I'd like to hear what number people might think
would be reasonable.
DR. EDMISTON: Fortunately, I don't think
we have to determine that. I think there's probably enough statistical
knowledge at the FDA to figure that out, correct?
MR. ULATOWSKI: Yeah, I would just
quickly premise the thought, though, that what comes up front is a design
process to minimize the potential. Like the one product that was implicated
with some problems, you could test that till you're blue in the face; you're
still going to have a problem because of the fundamental design flaw with the
product.
So assuming you've done all the right
stuff up front in design controls, then the tests are confirmatory. Otherwise,
I mean there's the premise here that you can't test quality until product.
You're designing quality and then confirming and validating that at the tail
end.
DR. EDMISTON: Keeping in mind also
there's at this point no standard methodology for defining contamination per se,
other than the study that was presented and showed how contamination was
determined, but there's no standard methodologies available within the industry.
DR. WENIGER: And we have to remember
that these models have not been corroborated or validated with some kind of a
gold standard. And I think the point that Ms. Ryder made about the fact that
maybe our surveillance systems over the last 40 years have not been sensitive
enough to pick up those rare transmissions that might have occurred. Then once
again we have to balance this desire to reduce risk to a bare minimum with the
existing risk that we know half the injections in the world today are unsafe and
causing literally millions of cases of hepatitis B from needles and syringes.
So we need to have a level playing field
between these new devices and the classic needle and syringe.
MS. RYDER: I think I just wanted to feel
comfortable that there was some issues addressed in terms of an obvious design
flaw that was picked up in the past, that that would have some level of control
in the future.
DR. EDMISTON: There's probably two ways
of looking at this. One is to do what we did in the morning session and look at
a postmarketing surveillance of these devices, pick it up on the back end. Or
recommend that the FDA investigate the possibility of developing standardized
methodology to determine contamination within these devices.
I think probably doing postmarketing
surveillance will allow you to pick it up on the back end. However, what is the
level of risk you're willing to accept?
So I would recommend the following, that
the FDA look at potential models for looking at cross-contamination of these
devices, at the same type develop the mentality for doing postmarketing
surveillance on these devices once they're out there and being used by the
public.
Would that be a reasonable
recommendation?
[Nods from panel members.]
MR. ULATOWSKI: Noted.
DR. EDMISTON: Does that address any more
concerns? Oh, yes.
MR. HARRINGTON: There is one caveat from
industry. You've heard this morning that one of the things on needle stick
devices was following manufacturers' directions, an explicit training program.
What we're asked for in the jet injection business and in the testing protocols
is a worst-case scenario: we do nothing, we allow it to contaminate and we ask
how clean you are.
So the question deserves to be answered:
are you going to follow the manufacturer's directions or is it always a
worst-case scenario?
DR. WENIGER: I think he's implying that
the health worker doesn't swab the nozzle, for example.
DR. EDMISTON: Right.
MR. HARRINGTON: No, I'm implying that in
the test to prove safety and efficacy, are we going to follow the manufacturer's
directions? Are we going to try to keep a clean product between patients? Or
do we automatically assume that it has to be nothing on it? We need to know
what that is, one way or the other.
Certainly there is a demonstrated
improvement on sterility and cleaning when CDC swabbed the nozzles.
So if a manufacturer says you need to do
this and such to my product between patients, if you don't do that, we're
responsible for it being dirty, or is the test going to be implied that it's
always going to be dirty? We need to have an answer to that question, is my
response.
DR. EDMISTON: Well, the recommendations
that the manufacturer would make for the device I assume would be prudent and
appropriate for those devices.
MR. HARRINGTON: But they have not been
followed in all the tests in the world to date.
MR. PALOMARES: Yeah, but the data that
you're generating would have to follow your protocol. Why wouldn't you promote
your product and why wouldn't you study your product unless it's following your
method?
MR. HARRINGTON: I absolutely agree. My
point is that WHO is ignoring those and testing it to a different level than the
manufacturer--
DR. EDMISTON: Well, we can't deal with
WHO issues in this meeting. We can only deal with what would be appropriate for
the FDA.
MR. ULATOWSKI: Well, I'd have to say
that yeah, you follow labeling but the labeling has to reflect actual use
conditions, real life conditions. And if you're disregarding some common event
or occurrence or some aspect of the environment, then the labeling is not quite
correct, either.
MR. PALOMARES: But then you should put
that in your warnings.
DR. EDMISTON: See, your device, for the
most part, the devices that you've been talking about, for the most part, that
device is going to be used by health care workers with some minimal level of
training.
MR.
HARRINGTON:
Not necessarily. It was used by the Army for 35 years and it was always wiped.
Never had an issue. Good tracking system. And there's nothing recorded in the
world that says that it wasn't wiped. It's in a study that was presented using
a method that isn't approved, it was not wiped and it said oh, we can
contaminate 31 out of 100.
MR. ULATOWSKI: You want to come up to
the mike? Because that's not getting transcribed.
DR. EDMISTON: Do you want to do that
again?
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