[Title 21 CFR G]
[Code of Federal Regulations (annual edition) - April 1, 1996 Edition]
[Title 21 - FOOD AND DRUGS]
[Chapter I - FOOD AND DRUG ADMINISTRATION,]
[Subchapter F - BIOLOGICS]
[Part 640 - ADDITIONAL STANDARDS FOR HUMAN BLOOD AND BLOOD PRODUCTS]
[Subpart G - Source Plasma]
[From the U.S. Government Publishing Office]
21
FOOD AND DRUGS
7
1996-04-01
1996-04-01
false
Source Plasma
G
Subpart G
FOOD AND DRUGS
FOOD AND DRUG ADMINISTRATION,
BIOLOGICS
ADDITIONAL STANDARDS FOR HUMAN BLOOD AND BLOOD PRODUCTS
Subpart G--Source Plasma
Sec. 640.60 Source Plasma.
The proper name of the product shall be Source Plasma. The product
is defined as the fluid portion of human blood collected by
plasmapheresis and intended as source material for further manufacturing
use. The definition excludes single donor plasma products intended for
intravenous use.
[41 FR 10768, Mar. 12, 1976, as amended at 50 FR 4140, Jan. 29, 1985]
Sec. 640.61 Informed consent.
The written consent of a prospective donor shall be obtained after a
qualified licensed physician has explained the hazards of the procedure
to the prospective donor. The explanation shall include the risks of a
hemolytic transfusion reaction if he is given the cells of another
donor, and the hazards involved if he is hyperimmunized. The explanation
shall consist of such disclosure and be made in such a manner that
intelligent and informed consent
[[Page 131]]
be given and that a clear opportunity to refuse is presented.
Sec. 640.62 Medical supervision.
A qualified licensed physician shall be on the premises when donor
suitability is being determined, immunizations are being made, whole
blood is being collected, and red blood cells are being returned to the
donor.
Sec. 640.63 Suitability of donor.
(a) Method of determining. The suitability of a donor for Source
Plasma shall be determined by a qualified licensed physician or by
persons under his supervision and trained in determining donor
suitability. Such determination shall be made on the day of collection
from the donor by means of a medical history, tests, and such physical
examination as appears necessary to the qualified licensed physician.
(b) Initial medical examinations. (1) Each donor shall be examined
by a qualified licensed physician on the day of the first donation or no
more than 1 week before the first donation and at subsequent intervals
of no longer than 1 year.
(2)(i) A donor who is to be immunized for the production of high-
titer plasma shall be examined by a qualified licensed physician. The
medical examination shall be performed within no more than 1 week before
the first immunization injection. The medical examination for
plasmapheresis need not be repeated, if the first donation occurs within
3 weeks after the first injection.
(ii) A donor who is an active participant in a plasmapheresis
program, and has been examined in accordance with paragraph (b)(1) of
this section, need not be reexamined before immunization for the
production of high-titer plasma.
(3) Each donor shall be certified to be in good health by the
examining physician. The certification of good health shall be on a form
supplied by the licensed establishment and shall indicate that the
certification applies to the suitability of the individual to be a
plasmapheresis donor and, when applicable, an immunized donor.
(c) Qualification of donor. Donors shall be in good health on the
day of donation, as indicated in part by:
(1) Normal temperature;
(2) Demonstration that systolic and diastolic blood pressures are
within normal limits, unless the examining physician is satisfied that
an individual with blood pressures outside these limits is an otherwise
qualified donor under the provisions of this section;
(3) A blood hemoglobin level of no less than 12.5 grams of
hemoglobin per 100 milliliters of blood;
(4) A normal pulse rate;
(5) A total serum protein of no less than 6.0 grams per 100
milliliters of serum;
(6) Weight, which shall be at least 110 pounds;
(7) Freedom from acute respiratory diseases;
(8) Freedom from any infectious skin disease at the site of
phlebotomy and from any such disease generalized to such an extent as to
create a risk of contamination of the plasma;
(9) Freedom from any disease, other than malaria, transmissible by
blood transfusion, insofar as can be determined by history and
examinations indicated in this section;
(10) Freedom of the arms and forearms from skin punctures or scars
indicative of addiction to self-injected narcotics;
(11) Freedom from a history of viral hepatitis;
(12) Freedom from a history of close contact within six months of
donation with an individual having viral hepatitis;
(13) Freedom from a history of having received, within six months,
human blood or any derivative of human blood which the Food and Drug
Administration has advised the licensed establishment is a possible
source of viral hepatitis, except for specific immunization performed in
accordance with Sec. 640.66 of this part.
(d) General. Any donor who, in the opinion of the interviewer,
appears to be under the influence of any drug, alcohol, or for any
reason does not appear to be providing reliable answers to medical
history questions, shall not be considered a suitable donor.
(e) Failure to return red blood cells. Any donor who has not had the
red blood cells returned from a unit of
[[Page 132]]
blood collected during a plasmapheresis procedure or who has been a
donor of a unit of whole blood shall not be subjected to plasmapheresis
for a period of 8 weeks, unless:
(1) The donor has been examined by a qualified licensed physician
and certified by the physician to be acceptable for further
plasmapheresis before expiration of the 8-week period;
(2) The donor possesses an antibody that is (i) transitory, (ii) of
a highly unusual or infrequent specificity, or (iii) of an unusually
high titer; and
(3) The special characteristics of the antibody and the need for
plasmapheresing the donor are documented.
[38 FR 32089, Nov. 20, 1973, as amended at 41 FR 10768, Mar. 12, 1976;
43 FR 9805, Mar. 10, 1978; 43 FR 12311, Mar. 24, 1978; 46 FR 57480, Nov.
24, 1981; 50 FR 4140, Jan. 29, 1985]
Sec. 640.64 Collection of blood for Source Plasma.
(a) Supervision. All blood for the collection of Source Plasma shall
be drawn from the donor by a qualified licensed physician or by persons
under his supervision trained in the procedure.
(b) Blood containers. Blood containers and donor sets shall be
pyrogen-free, sterile and identified by lot number. The amount of
anticoagulant required for the quantity of blood to be collected shall
be in the blood container when it is sterilized.
(c) The anticoagulant solution. The anticoagulant solution shall be
sterile and pyrogen-free. One of the following formulas shall be used in
the indicated volumes, except that a different formula may be used for
plasma for manufacture into noninjectable products if prior written
approval is obtained from the Director of the Center for Biologics
Evaluation and Research at the time of licensing or in the form of a
supplement to the Source Plasma product license.
(1) Anticoagulant citrate dextrose solution (ACD).
Tri-sodium citrate (Na3C6H5O72H2O).
Citric acid (C6H8O7H2O)........ 8.0 grams.
Dextrose (C6H12O6H2O).................... 24.5 grams.
Water for injection (U.S.P.) to make..... 1,000 milliliters.
Volume per 100 milliliters blood......... 15 milliliters.
(2) Anticoagulant citrate phosphate dextrose solution (CPD).
Tri-sodium citrate (Na3C6H5O72H2O).
Citric acid (C6H8OH2O)......... 3.27 grams.
Dextrose (C6H12O6H2O).................... 25.5 grams.
Monobasic sodium phosphate (NaH2PO4H2O).
Water for injection (U.S.P.) to make..... 1,000 milliliters.
Volume per 100 milliliters blood......... 14 milliliters.
(3) Anticoagulant sodium citrate solution.
Tri-sodium citrate (Na3C6H5O72H2O).
Water for injection (U.S.P.) to make..... 1,000 milliliters.
Volume per 100 milliliters of blood...... 10 milliliters.
(d) Donor identification. Each unit of blood and plasma shall be so
marked or identified by number or other symbol so as to relate it
directly to the donor.
(e) Prevention of contamination of the blood and plasma. The skin of
the donor at the site of phlebotomy shall be prepared thoroughly and
carefully by a method that gives maximum assurance of a sterile
container of blood. The blood shall be collected, the plasma separated,
and the cells returned to the donor by aseptic methods in a sterile
system which may be closed, or may be vented if the vent protects the
blood cells and plasma against contamination.
[38 FR 32089, Nov. 20, 1973; 39 FR 13632, Apr. 16, 1974, as amended at
41 FR 10768, Mar. 12, 1976; 49 FR 23834, June 8, 1984; 50 FR 4140, Jan.
29, 1985; 55 FR 11013, Mar. 26, 1990; 59 FR 49351, Sept. 28, 1994]
Sec. 640.65 Plasmapheresis.
(a) Procedure-general. The plasmapheresis procedure is a procedure
in which, during a single visit to the establishment, blood is removed
from a donor, the plasma separated from the formed elements, and at
least the red blood cells returned to the donor. This procedure shall be
described in detail in the product license application.
(b) Procedures-specific requirements. The plasmapheresis procedure
shall meet the following requirements:
(1)(i) A sample of blood shall be drawn from each donor on the day
of the first medical examination or plasmapheresis, whichever comes
first and at least every 4 months thereafter by a qualified licensed
physician or by persons under his supervision and trained in such
procedure. A serologic test for
[[Page 133]]
syphilis, a total plasma or serum protein determination, and a plasma or
serum protein electrophoresis or quantitative immuno-diffusion test or
an equivalent test to determine immunoglobulin composition of the plasma
or serum shall be performed on the sample.
(ii) A repeat donor who does not return for plasmapheresis at the
time the 4-month sample is due to be collected may be plasmapheresed on
the day he appears: Provided, That no longer than 6 months has elapsed
since the last sample was collected, and the physician on the premises
approves the plasmapheresis procedure and so indicates by signing the
donor's record before such procedure is performed. The sample for the 4-
month tests shall be collected on the day of the donor's return.
(iii) A repeat donor from whom the plasmapheresis center is unable
to obtain a sample for testing as prescribed in paragraph (b)(1)(i) of
this section for a total period exceeding 6 months shall be processed as
a new donor.
(2)(i) The accumulated laboratory data, including tracings, if any,
of the plasma or serum protein electrophoresis pattern, the calculated
values of each component, and the collection records shall be reviewed
by a qualified licensed physician within 21 days after the sample is
drawn to determine whether or not the donor may continue in the program.
The review shall be signed by the reviewing physician. If the protein
composition is not within normal limits established by the testing
laboratory, or if the total protein is less than 6.0 grams per 100
milliliters of samples, the donor shall be removed from the program
until these values return to normal.
(ii) A donor with a reactive serologic test for syphilis shall not
be plasmapheresed again until the donor's serum is tested and found to
be nonreactive to a serologic test for syphilis, except as provided in
paragraph (b)(2) (iii) and (iv) of this section.
(iii) A donor whose serum is determined to have a biologic false-
positive reaction to a serologic test for syphilis may be
plasmapheresed: Provided, That the donor's file identifies the serologic
test for syphilis and results used to confirm the biologic false-
positive reaction and indicates that the physician on the premises has
determined the false-positive reaction is not the result of an
underlying disorder that would disqualify the donor from participation
in the plasmapheresis program. If the serologic test for syphilis is
performed at a facility other than the plasmapheresis center, all
applicable provisions of Sec. 640.71 shall be met.
(iv) A donor with a reactive serologic test for syphilis may be
plasmapheresed only to obtain plasma to be used for further
manufacturing into control serum for the serologic test for syphilis:
Provided, That the physician on the premises approves the donation, the
donor's file contains a signed statement from a physician or clinic
establishing that treatment for syphilis has been initiated and that
continuance in the plasmapheresis program will not interfere with or
jeopardize the treatment of the syphilitic donor.
(3) A donor identification system shall be established that
positively identifies each donor and relates such donor directly to his
blood and its components as well as to his accumulated records and
laboratory data. Such system shall include either a photograph of each
donor which shall be used on each visit to confirm the donor's identity,
or some other method that provides equal or greater assurance of
positively identifying the donor.
(4) The amount of whole blood, not including anticoagulant, removed
from a donor during a plasmapheresis procedure or in any 48-hour period
shall not exceed 1,000 milliliters unless the donor's weight is 175
pounds or greater, in which case the amount of whole blood, not
including anticoagulant, removed from the donor during a plasmapheresis
procedure or in any 48-hour period shall not exceed 1,200 milliliters.
(5) The amount of whole blood, not including anticoagulant, removed
from a donor within a seven-day period shall not exceed 2,000
milliliters unless the donor's weight is 175 pounds or greater, in which
case the amount of whole blood, not including anticoagulant, removed
from the donor during a seven-day period shall not exceed 2,400
milliliters.
[[Page 134]]
(6) No more than 500 milliliters of whole blood shall be removed
from a donor at one time, unless the donor's weight is 175 pounds or
greater, in which case no more than 600 milliliters of whole blood shall
be removed from the donor at one time.
(7) The plasma shall be separated from the red blood cells
immediately after blood collection. The maximum feasible volume of red
blood cells shall be returned to the donor before another unit is
collected.
[38 FR 32089, Nov. 20, 1973, as amended at 41 FR 10769, Mar. 12, 1976]
Sec. 640.66 Immunization of donors.
If specific immunization of a donor is to be performed, the
selection and scheduling of the injection of the antigen, and the
evaluation of each donor's clinical response, shall be by a qualified
licensed physician or physicians. The administration of the antigen may
be performed by a licensed physician or a trained person under his
supervision. Any material used for immunization shall be either a
product licensed under section 351 of the Public Health Service Act for
such purpose or one specifically approved by the Director, Center for
Biologics Evaluation and Research, Food and Drug Administration.
Immunization procedures shall be on file at each plasmapheresis center
where immunizations are performed.
[38 FR 32089, Nov. 20, 1973, as amended at 49 FR 23834, June 8, 1984; 55
FR 11013, Mar. 26, 1990]
Sec. 640.67 Laboratory tests.
(a) Hepatitis B surface antigen. Each unit of Source Plasma shall be
nonreactive to a test for hepatitis B surface antigen as prescribed in
Secs. 610.40 and 610.41 of this chapter, except insofar as permitted in
Sec. 610.40(d)(1) and (d)(2) of this chapter.
(b) Antibody to HIV. Each unit of Source Plasma shall be negative by
a test for antibody to HIV as prescribed in Sec. 610.45 of this chapter,
except as provided in Sec. 610.45(c) of this chapter.
[53 FR 117, Jan. 5, 1988, as amended at 57 FR 10814, Mar. 31, 1992]
Sec. 640.68 Processing.
(a) Sterile system. All administration and transfer sets inserted
into blood containers used for processing Source Plasma intended for
manufacturing into injectable or noninjectable products and all interior
surfaces of plasma containers used for processing Source Plasma intended
for manufacturing into injectable products shall be sterile, pyrogen-
free, nontoxic, and compatible with the contents under normal conditions
of use. Only Sodium Chloride Injection USP shall be used as a red blood
cell diluent. If the method of separation of the plasma intended for
injectable products involves a system in which an airway must be
inserted into the plasma container, the airway shall be sterile and
constructed so as to exclude microorganisms and maintain a sterile
system.
(b) Final containers. Final containers used for Source Plasma,
whether integrally attached or separated from the original blood
container, shall not be entered prior to issuance for any purpose except
for filling with the plasma. Such containers shall be uncolored and
hermetically sealed, and shall permit clear visibility of the contents.
Final containers and their components shall not interact with the plasma
contents under conditions of storage and use so as to alter the safety,
quality, purity, or potency of the plasma and shall provide adequate
protection against external factors that may cause deterioration or
contamination. Prior to filling, the final container shall be marked or
identified by number or other symbol which will relate it directly to
the donor.
(c) Preservative. Source Plasma shall not contain a preservative.
[38 FR 32089, Nov. 20, 1973, as amended at 41 FR 10769, Mar. 12, 1976;
50 FR 4140, Jan. 29, 1985]
Sec. 640.69 General requirements.
(a) Pooling. Two units of Source Plasma from the same donor may be
pooled if such units are collected during one plasmapheresis procedure:
Provided, That the pooling is done by a procedure that does not
introduce a risk of contamination of the red blood cells and, for plasma
intended for injectable
[[Page 135]]
products, gives maximum assurance of a sterile container of plasma.
(1) The pooling of plasma from two or more donors is not permitted
in the manufacture of Source Plasma intended for manufacturing into
injectable products.
(2) The pooling of plasma from two or more donors by the
manufacturer of Source Plasma intended for manufacturing into
noninjectable products is permitted: Provided, That the plasma from two
or more donors is pooled after the plasma has been removed from the red
blood cells, and after the red blood cell containers are sealed.
(b) Storage. Immediately after filling, plasma intended for
manufacturing into injectable products shall be stored at a temperature
not warmer than --20 deg. C., except for plasma collected as provided in
Sec. 640.74. Plasma intended for manufacturing into noninjectable
products may be stored at temperatures appropriate for the intended use
of the final product, provided these temperatures are included in the
Source Plasma license application.
(c) Inspection. Source Plasma intended for manufacturing into
injectable products shall be inspected for evidence of thawing at the
time of issuance, except that inspection of individual plasma containers
need not be made if the records of continuous monitoring of the storage
temperature establish that the temperature remained at --20 deg. C or
colder. If there is evidence that the storage temperature has not been
maintained at --20 deg. C or colder, the plasma may be relabeled and
issued as provided in Sec. 640.76(a).
(d) Pilot samples. If pilot samples are provided, they shall meet
the following standards:
(1) Prior to filling, all pilot samples shall be marked or
identified so as to relate them directly to the donor of that unit of
plasma.
(2) All pilot samples shall be filled at the time the final product
is prepared by the person who prepares the final product.
(3) All pilot samples shall be representative of the contents of the
final product.
(4) All pilot samples shall be collected in a manner that does not
contaminate the contents of the final container.
[38 FR 32089, Nov. 20, 1973, as amended at 41 FR 10769, Mar. 12, 1976;
41 FR 14367, Apr. 5, 1976; 50 FR 4140, Jan. 29, 1985]
Sec. 640.70 Labeling.
(a) In addition to the labeling requirements of Sec. 610.62 of this
chapter, and in lieu of the requirements in Secs. 606.121, 610.60, and
610.61 of this chapter, the following information shall appear on the
label affixed to each container of Source Plasma:
(1) The proper name of the product.
(2) The statement ``Caution: For Manufacturing Use Only'' for
products intended for further manufacturing into injectable products, or
the statement, ``Caution: For Use In Manufacturing Noninjectable
Products Only'', for products intended for further manufacturing into
noninjectable products. The statement shall follow the proper name in
the same size and type of print as the proper name.
(3) The statement ``Store at --20 deg. C. or colder'': Provided,
That where plasma is intended for manufacturing into noninjectable
products, this statement may be omitted if replaced by a statement of
the temperature appropriate for the final product to be prepared from
the plasma.
(4) The total volume or weight of plasma and total quantity and type
of anticoagulant used.
(5) The donor number or individual bleed number, or both. If plasma
is pooled from two or more donors, either all donor numbers, all bleed
numbers, or a pool number that is traceable to each individual unit
comprising the pool.
(6) The expiration date of the plasma. If plasma intended for
manufacturing into noninjectable products is pooled from two or more
donors the expiration date is determined from the collection date of the
oldest unit in the pool, and the pooling records shall show the
collection date for each unit constituting the pool.
(7) A statement as to whether the plasma was collected from normal
donors or from immunized donors. In the case of immunized donors, the
label shall state the immunizing antigen.
[[Page 136]]
(8) The test for hepatitis B surface antigen used for the results,
or the statement ``Nonreactive for HBsAg by FDA required test''.
(9) When plasma collected from a donor is reactive for the serologic
test for syphilis, a statement that the plasma is reactive and must be
used only for the manufacturing of positive control reagents for the
serologic test for syphilis.
(10) Name, address, and license number of the manufacturer.
(11) The statement ``Negative by a test for antibody to HIV'', or
equivalent statement.
(b) Source Plasma diverted for Source Plasma Salvaged shall be
relabeled ``Source Plasma Salvaged'' as prescribed in Sec. 640.76.
Immediately following the proper name of the product, the labeling shall
conspicuously state as applicable, ``STORAGE TEMPERATURE EXCEEDED --
20 deg. C'' or ``SHIPPING TEMPERATURE EXCEEDED --5 deg. C''.
[41 FR 10770, Mar. 12, 1976, as amended at 41 FR 27034, July 1, 1976; 41
FR 35062, Aug. 19, 1976; 47 FR 30969, July 16, 1982; 50 FR 4140, Jan.
29, 1985; 50 FR 35471, Aug. 30, 1985; 53 FR 117, Jan. 5, 1988]
Sec. 640.71 Manufacturing responsibility.
(a) All steps in the manufacture of Source Plasma, including donor
examination, blood collection, plasmapheresis, laboratory testing,
labeling, storage, and issuing shall be performed by personnel of the
establishment licensed to manufacture Source Plasma, except that the
following tests may be performed by personnel of an establishment
licensed for blood or blood derivatives under section 351(a) of the
Public Health Service Act, or by a clinical laboratory that meets the
standards of the Clinical Laboratories Improvement Act of 1967 (CLIA)
(42 U.S.C. 263a): Provided, The establishment or the clinical laboratory
is qualified to perform the assigned test(s).
(1) The test for hepatitis B surface antigen.
(2) The total plasma or serum protein and the quantitative test for
plasma or serum proteins or for immunoglobulins.
(3) The serologic test for syphilis.
(4) A test for antibody to HIV.
(b) Such testing shall not be considered divided manufacturing,
which requires two product licenses for Source Plasma: Provided, That
(1) The results of such tests are maintained by the establishment
licensed for Source Plasma whereby such results may be reviewed by a
licensed physician as required in Sec. 640.65(b)(2) and by an authorized
representative of the Food and Drug Administration.
(2) The Source Plasma manufacturer has obtained a written agreement
that the testing laboratory will permit authorized representatives of
the Food and Drug Administration to inspect its testing procedures and
facilities during reasonable business hours.
(3) The testing laboratory will participate in any proficiency
testing programs undertaken by the Center for Biologics Evaluation and
Research, Food and Drug Administration.
[41 FR 10770, Mar. 12, 1976, as amended at 49 FR 23834, June 8, 1984; 50
FR 4140, Jan. 29, 1985; 53 FR 117, Jan. 5, 1988; 55 FR 11013, Mar. 26,
1990]
Sec. 640.72 Records.
(a) In addition to the recordkeeping requirements of this
subchapter, the following records shall be maintained:
(1) Documentation compiled every 3 months establishing that the
shipping temperature requirements of Sec. 600.15 of this title and
Sec. 640.74(b)(2) are being met for Source Plasma intended for
manufacture into injectable products.
(2) For each donor, a separate and complete record of all initial
and periodic examinations, tests, laboratory data, interviews, etc.,
undertaken pursuant to Secs. 640.63, 640.65, 640.66, and 640.67, except
that negative test results for hepatitis B surface antigen, negative
test results for antibody to HIV, and the volume or weight of plasma
withdrawn from a donor need not be kept on the individual donor record:
Provided, That such information is maintained on the premises of the
plasmapheresis center where the donor's plasma has been collected.
(3) The original or a clear copy of the donor's written consent for
participation in the plasmapheresis program or for immunization.
[[Page 137]]
(4) The certification of the donor's good health as prescribed in
Sec. 640.63(b)(3).
(5) If plasma that is reactive to a serologic test for syphilis is
issued as prescribed in Sec. 640.65(b)(2)(iv), the distribution records
shall indicate by number those units that are reactive.
(b) Each donor record must be directly cross-referenced to the
unit(s) of Source Plasma associated with the donor.
(c) If a repeat donor is rejected or a donor's plasma is found
unsuitable, the donor's record shall contain a full explanation for the
rejection.
(d) If a donor has a reaction while on the plasmapheresis premises,
or a donor reaction is reported to the center after the donor has left
the premises, the donor's record shall contain a full explanation of the
reaction, including the measures taken to assist the donor and the
outcome of the incident.
(Collection of information requirements approved by the Office of
Management and Budget under control number 0910-0227)
[41 FR 10770, Mar. 12, 1976, as amended at 50 FR 4140, Jan. 29, 1985; 53
FR 117, Jan. 5, 1988]
Sec. 640.73 Reporting of fatal donor reactions.
If a donor has a fatal reaction which, in any way, may be associated
with plasmapheresis the Director of the Center for Biologics Evaluation
and Research shall be notified by telephone as soon as possible. If the
facility is located outside of the continental United States,
notification by cable or telegram shall be acceptable.
[41 FR 10770, Mar. 12, 1976, as amended at 49 FR 23834, June 8, 1984; 55
FR 11013, Mar. 26, 1990]
Sec. 640.74 Modification of Source Plasma.
(a) Upon approval by the Director, Center for Biologics Evaluation
and Research, Food and Drug Administration, of a supplement to the
product license for Source Plasma, a manufacturer may prepare Source
Plasma as a liquid product for a licensed blood derivative manufacturer
who has indicated a need for a liquid product.
(b) Source Plasma Liquid shall meet all standards of the frozen
Source Plasma except:
(1) Source Plasma Liquid shall be stored in nonleachable containers
so that the containers and their components will not interact with the
plasma contents under conditions of storage and use so as to alter the
safety, quality, purity, or potency of the plasma and shall provide
adequate protection against external factors that may cause
deterioration or contamination.
(2) Source Plasma Liquid shall be shipped, stored and labeled for
storage at a temperature of 10 deg.C. or colder. An exception to the
shipping or storage temperature shall be approved by the Director,
Center for Biologics Evaluation and Research, Food and Drug
Administration, based upon his receipt of substantial evidence to
support another temperature. Such evidence may be submitted by either
the product licensee of the Source Plasma Liquid or the manufacturer of
the final blood derivative product who has requested the Source Plasma
Liquid.
(3) The label for the Source Plasma Liquid shall be easily
distinguished from that of the frozen product. Color coding shall not be
used for this purpose.
(4) The label affixed to each container of Source Plasma Liquid
shall contain, in addition to the information required by Sec. 640.70(a)
but excluding Sec. 640.70(a)(3), the name of the manufacturer of the
final blood derivative product for whom it was prepared.
(5) Source Plasma Liquid shall be inspected immediately prior to
issuance. If the color or physical appearance is abnormal, or there is
any indication or suspicion of microbial contamination, the unit of
Source Plasma Liquid shall not be issued.
[38 FR 32089, Nov. 20, 1973. Redesignated and amended at 41 FR 10770,
Mar. 12, 1976; 49 FR 23834, June 8, 1984; 50 FR 4140, Jan. 29, 1985; 55
FR 11013, Mar. 26, 1990; 59 FR 49351, Sept. 28, 1994]
Sec. 640.76 Products stored or shipped at unacceptable temperatures.
(a) Storage temperature. (1) Except as provided in paragraph (a)(2)
of this section, Source Plasma intended for manufacture into injectable
products that
[[Page 138]]
is inadvertently exposed (i.e., an unforeseen occurrence in spite of
compliance with good manufacturing practice) to a storage temperature
warmer than -20 deg. C and colder than +10 deg. C may be issued only if
labeled as ``Source Plasma Salvaged.'' The label shall be revised before
issuance, and appropriate records shall be maintained identifying the
units involved, describing their disposition, and explaining fully the
conditions that caused the inadvertent temperature exposure.
(2) Source Plasma intended for manufacture into injectable products
that is exposed inadvertently (i.e., an unforeseen occurrence in spite
of compliance with good manufacturing practice) to one episode of
storage temperature fluctuation that is warmer than -20 deg. C and
colder than -5 deg. C for not more than 72 hours is exempt from the
labeling requirements of paragraph (a)(1) of this section, provided that
the plasma has been and remains frozen solid. Appropriate records shall
be maintained identifying the units involved, describing their
disposition, explaining fully the conditions that caused the inadvertent
temperature exposure, and documenting that the episode of temperature
elevation did not exceed 72 hours, that the temperature did not rise to
warmer than -5 deg. C in storage, and that the plasma remained frozen
solid throughout the period of elevated temperature. When requested,
copies of the records shall be provided to the plasma derivative
manufacturer.
(b) Shipping temperature. If Source Plasma for manufacture into
injectable products is exposed inadvertently (i.e., an unforeseen
occurrence in spite of compliance with good manufacturing practice) to a
shipping temperature warmer than -5 deg. C and colder than +10 deg. C,
the plasma derivative manufacturer shall label it ``Source Plasma
Salvaged.'' Appropriate records shall be maintained identifying the
units involved, describing their disposition, and explaining fully the
conditions that caused the inadvertent temperature exposure.
(c) Relabeling. If Source Plasma is required to be relabeled as
``Source Plasma Salvaged'' under paragraph (a)(1) or (b) of this
section, the person responsible for the relabeling shall cover the
original label with either (1) a complete new label containing the
appropriate information or (2) a partial label affixed to the original
label and containing the appropriate new information, which covers the
incorrect information regarding storage temperature.
[45 FR 80501, Dec. 5, 1980, as amended at 50 FR 4140, Jan. 29, 1985]