Version- 1995FDA/ORA Compliance
Program Guidance 7342.006 CHAPTER 42 - BLOOD AND BLOOD PRODUCTS
This
compliance
program
combines
and
replaces
the
compliance
programs
for
licensed
allergenics
(7345.001),
licensed
vaccines
(7345.002),
plasma
derivatives
(7342.006)
and
therapeutic
drugs
(7341.001).
This
program
represents
a
continuing
compliance
and
surveillance
activity
conducted
to
ensure
that
CBER-regulated
biological
drug
products
for
human
use
are
safe,
pure,
potent,
effective,
and
appropriately
labeled.
The
inspection
of a
facility
is
performed
to
ensure
that
manufacturers
are
making
products
that:
Meet the standards described in applicable provisions of the regulations. These include regulations in 21 CFR Parts 600, 601, 610, 640, 660, 680, and 1271, CGMP regulations in 21 CFR Part 200, 201, 210 and 211.
Meet any additional conditions of licensure in the approved Biologics License Application (BLA) and/or supplements, if manufacturing a licensed product, and other applicable standards.
ATTACHMENTS - Product Guidance
ATTACHMENT 1: FRACTIONATORS
Plasma Fractionation
Blood plasma contains a mixture of hundreds of
different kinds of proteins, only a few of which are of therapeutic
interest. To make plasma derivative products, plasma can be treated with a
variety of substances to separate the desired proteins from others, in a
process called fractionation. Fractionation of plasma, from pools often
derived from thousands of donors, was developed during World War II by
Cohn and co-workers at Harvard Medical School. Today, most plasma
derivative manufacturers use a modified Cohn method developed by Oncley
(Cohn-Oncley fractionation process) or further variants of this method,
that permit manufacture of additional products.
Fractionation by the Cohn-Oncley method relies on
precipitation of plasma proteins by a combination of cold alcohol (usually
ethanol)-water mixtures and adjustments of pH, ionic strength,
temperature, and protein concentration. Alternatively, some manufacturers
separate plasma derivatives by column chromatography using ion exchange,
gel filtration, or affinity methods, without alcohol. In all cases,
fractions of plasma are separated sequentially, with the product from one
step, such as the precipitate and/or supernatant, becoming the starting
material for the next step in the fractionation process. If each step is
not done properly, subsequent fractions can be adversely affected. Thus,
the integrity of each final product is dependent on all of the preceding
steps in the process.
After fractionation,
derivatives undergo further processing to purify and concentrate proteins
and to inactivate or remove (clearance) any bacterial or viral
contaminants. While early steps in the manufacturing process are not
performed aseptically, all final products are sterile. Types of
viral clearance include those steps that are part of the fractionation
process itself, e.g., pH4/pepsin or polyethylene glycol (PEG)
fractionation, or those steps that are deliberately added, e.g.,
solvent/detergent treatment or viral filtration. In some instances more
than one viral clearance step is used for a given product. Plasma
derivatives are similar to other biological products in that they are
protein-based and subject to denaturization at high temperatures. These
products are usually filled by using aseptic processing techniques, and
cannot be terminally sterilized, although in some instances they can be
heat-treated in the final container to effect viral or bacterial
inactivation.
A few plasma proteins may also be manufactured by
recombinant DNA methods.
Fractionation Products
Each plasma fraction is enriched in specific protein
components and is used for a different purpose. In the Cohn-Oncley method,
Fraction I contains mostly fibrinogen (not a licensed product), the main
protein component of blood clots. Fraction II+III has a high concentration
of immunoglobulins (antibodies). Some manufacturers use Fraction IV to
prepare licensed products; others consider it a by-product. Fraction IV-1
is the source material for Alpha-1-proteinase Inhibitor (Human); Fraction
IV-4+V is the source of Plasma Protein Fraction (Human). Fraction V is the
source of Albumin (Human). Most of these products, but not all are
intravenously administered. A description of some of the major plasma
derivatives follows:
Antihemophilic Factor (Human) (AHF, Factor VIII).
AHF protein, one component of the cryoprecipitate fraction of plasma, is
used to treat classical hemophilia (hemophilia A). Cryoprecipitate is the
solid material that remains after frozen plasma is thawed at a near
freezing temperature; it serves as the source of AHF. After the
cryoprecipitate dissolves upon warming, the AHF in it can be purified to a
high degree, subjected to various viral clearance procedures, and prepared
as a lyophilized concentrate. AHF is administered intravenously. NOTE:
Even though the clinically active ingredient is the same, AHF is not the
same product as Cryoprecipitated AHF, a single donor product prepared in
blood banks.
Factor IX Complex (Human) is adsorbed
from the plasma fraction remaining after cryoprecipitate removal. It is a
heat- or solvent/detergent-treated, lyophilized preparation containing
factors II, VII, IX, and X. It is administered intravenously for the
prevention and control of bleeding caused by Factor IX deficiency
(hemophilia B), and other coagulation disorders.
Coagulation Factor IX (Human) is a highly
purified factor IX product that contains negligible amounts of other
coagulation factors, and is used to treat hemophilia B.
Immune Globulin (Human) (IG) is a
solution of immunoglobulin G (IgG) indicated for prophylaxis of hepatitis
A, prevention or modification of measles (Rubeola), and for immunoglobulin
deficiency. It is administered intramuscularly.
Additional specific immune globulins for
intramuscular administration are obtained from donors whose plasma
contains selected high titer antibodies. Products are available for use in
the passive prophylaxis of varicella-zoster, tetanus, hepatitis B, rabies,
and other infections. Another product, Rho(D) Immune Globulin (Human), is
for the prevention of sensitization to the Rho(D) antigen and hemolytic
disease of the newborn. Some of the intramuscular immunoglobulin products
have been subjected to heat- or solvent/detergent-treatment.
Immune Globulin Intravenous (Human) (IGIV)
is a lyophilized preparation that contains intact, unmodified,
immunoglobulin. It is often stabilized with monosaccharide (sucrose,
glucose, or mannose) and/or Albumin (Human) or glycine. It is indicated
for patients with primary immunodeficiency, immune thrombocytopenia and
Kawasaki's disease. Additional specific IGIV products are also available
and used for such indications as prevention of hemolytic disease of the
newborn, or passive prophylaxis of cytomegalovirus or respiratory
syncytial virus. All IGIV products have been
subjected to viral inactivation/removal procedures by either fortuitous or
deliberate methods.
FDA/ORA Compliance
Program Guidance 7342.006
CHAPTER 42 - BLOOD AND BLOOD PRODUCTS
http://www.fda.gov/ora/cpgm/42_006.html
-
FDA Guide to
Inspections of
Blood Banks -
BloodBook,
Blood ...
Aug 30, 1985
... Refer to
Compliance
Program
7342.001,
Inspection of
License and
Unlicensed
... "Guideline
for Collection
of
Blood or
Blood Products
from Donors with
..... A
copy of the
chapter
concerning
biosafety level
2 precautions
can ...
FDA on the
internet at
http://www.fda.gov/ora/inspect_ref/igs/blood.html
