[Federal Register Volume 69, Number 187 (Tuesday, September 28, 2004)]
[Notices]
[Pages 57943-57945]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-21624]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2004N-0367]


Cumulative List of Exceptions and Alternative Procedures Approved 
by the Director of the Center for Biologics Evaluation and Research

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability a cumulative list of exceptions and alternative procedures 
to requirements regarding blood, blood components, and blood products 
that have been approved by the Director of the Center for Biologics 
Evaluation and Research (CBER). Also, FDA is announcing that this list 
is posted on the Internet and it will be periodically updated.

ADDRESSES: Copies of the cumulative list of exceptions and alternative 
procedures are available from the Division of Dockets Management (HFA-
305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852, and the Office of Communication, Training and 
Manufacturers Assistance (HFM-40), Food and Drug Administration, suite 
200 N, 1401 Rockville Pike, Rockville, MD 20852-1448, 1-800-835-4709 or 
301-827-1800. See the SUPPLEMENTARY INFORMATION section for electronic 
access to the cumulative list of exceptions and alternative procedures.

FOR FURTHER INFORMATION CONTACT: Nathaniel L. Geary, Center for 
Biologics Evaluation and Research (HFM-17), Food and Drug 
Administration, suite 200N, 1401 Rockville Pike, Rockville, MD 20852-
1448, 301-827-6210.

SUPPLEMENTARY INFORMATION:

I. Background

    The Director of CBER has approved exceptions or alternative 
procedures that have been requested by blood establishments under Sec.  
640.120 (21 CFR 640.120). Section 640.120 grants the Director authority 
to approve exceptions or alternatives to any requirement in subchapter 
F (Biologics) of chapter I, parts 600 through 680 (21 CFR parts 600 
through 680) regarding blood, blood components, or blood products.
    FDA is announcing publication of a cumulative list of exceptions 
and alternative procedures to requirements regarding blood, blood 
components, and blood products that have been approved by the Director 
of CBER. Also, FDA is announcing that this list is posted on the 
Internet and it will be periodically updated.

II. List of Approved Exceptions and Alternative Procedures (Sec.  
640.120(b))

Sec.  600.15(a)
     Allow use of autologous units that were transported in a 
shipping container without ice and exposed to temperatures of 10.0 
[deg]C to 10.5 [deg]C for 10 minutes.
Sec.  606.60(b)
     Calibrate digital thermometer according to the schedule 
recommended by manufacturer, instead of monthly as required by 
regulation.
Sec.  606.65(e)
     Deviate from manufacturer's instructions to use the Gen-
Probe Procleix HIV-1/HCV Assay and Roche COBAS Ampliscreen HIV-1 and 
HCV nucleic acid tests on whole blood, red blood cells (RBC), 
platelets, source leukocytes, therapeutic exchange plasma, and 
recovered plasma intended for further manufacturing.
     Deviate from manufacturer's instruction to use samples 
containing up to 200 milligrams (mg)/deciliters (dL) hemoglobin or 800 
mg/dL triglycerides in the following assays: Abbott HIV AB HIV-1/HIV-2, 
(rDNA) EIA (LN3A77), Ortho Hepatitis B Core Antibody, Ortho Hepatitis B 
Surface Antigen ELISA System 2, and Roche Alanine Aminotransferase.
     Deviate from manufacturer's instruction to use an 
alternate testing algorithm for confirming repeatedly reactive HIV-1 
p24 antigen test results. Specifically, a licensed HIV-1 single unit 
Nucleic Acid Test will be performed in place of the HIV-1 p24 antigen 
neutralization test and the results used for donor notification and 
counseling and recipient tracing.
     Deviate from manufacturer's instructions to test donor 
specimens that were initially reactive using Ortho HbsAg System 3, in 
duplicate using Genetic Systems HbsAg EIA 3.0 (shaker method). If 
either or both of the donor samples test reactive using Genetic Systems 
HbsAg EIA 3.0 (shaker method), the donor specimen will be tested using 
Genetic Systems HbsAg Confirmatory 3.0 (shaker method).
Sec.  606.121
     Use of full face green labels for autologous use only 
units.
     Use of black print for all statements on container labels 
(omit use of statements in red print.) (Regulation revised--variance 
request no longer needed.)
     Use of ``Autologous'' on label in lieu of ``Paid'' or 
``Volunteer''
     Omit special labeling from RBC with positive antibody 
screens that are suspended in additive solution, if the supernatant of 
the additive solution was tested using approved methods and found to be 
negative for unexpected antibodies.
     Place ABO/Rh label and ``Donor Untested'' on group and 
type label position.
     Print the anticoagulant name after the proper product name 
instead of preceding it. (Done for ISBT 128 labels.)
Sec.  606.122(m)
     Extend the storage time of thawed Fresh Frozen Plasma 
(FFP) at 1 to 6 [deg]C to 24 hours, instead of 6 hours.
Sec.  606.151
     Omit performing a minor side crossmatch on RBC prepared in 
additive solutions that have not been screened for unexpected 
antibodies.
     Use of a computer (electronic) crossmatch instead of a 
major side crossmatch. (Regulation revised--variance request no longer 
needed.)
     Use of a type and screen procedure as an alternative 
method for the antiglobulin crossmatch. (Regulation revised--variance 
request no longer needed.)
     Allow use of a recipient sample up to 72 hours old for 
pre-transfusion testing. (Regulation revised--variance request no 
longer needed.)
Sec.  610.40
     Ship source leukocytes to the manufacturer before 
infectious disease testing has been completed, provided the product is 
labeled that testing is not complete and stored in quarantine until the 
manufacturer has received the test results. (Regulation revised--
variance request no longer needed.)
     Ship autologous blood unit to another establishment 
without testing unit for communicable disease agents. Testing performed 
on sample drawn on subsequent donation.
     Ship autologous blood unit to another establishment for 
processing and labeling and return to collecting facility without 
testing unit for communicable disease agents, provided neither facility 
has a crossover policy.
     Allow shipment under quarantine of untested source plasma 
labeled as

[[Page 57944]]

tested negative, to warehouse operated by another manufacturer for 
storage until testing is completed.
     Reinstate one donor with nondiscriminated results (NDR) on 
the Procleix HIV-1/HCV assay provided the donor tests negative for HIV 
RNA and HCV RNA using the Procleix Discriminatory assays and anti-HIV 
1/2 using Genetic Systems EIA.
     Allow shipment under quarantine of source plasma before 
completion of PCR testing, and labeled as pending NAT, to another 
licensed manufacturer who will cull and destroy NAT reactive units 
under a contractual arrangement with the source plasma manufacturer.
     Allow shipment under quarantine of source plasma that is 
labeled as negative/nonreactive for infectious diseases before 
completion of the infectious disease tests, to a contract off-site 
storage facility not operating under a U.S. license. source plasma 
manufacturer will cull and destroy reactive units according to their 
standard procedures.
Sec.  610.53
     Extend CPD and CP2D liquid plasma expiration date to 42 
days when stored at 1 to 6 [deg]C.
     Allow use of 53 vials of deglycerolized immunogen RBC that 
were exposed to temperatures from 6 to 8 [deg]C for up to 3 hours.
Sec.  640.3
     Allow whole blood collection from autologous donors who 
don't meet donor suitability requirements.
     Allow whole blood collection from donors with a history of 
hepatitis before age 11. (Regulation revised--variance request no 
longer needed.)
     Allow 4-week intervals between FFP donations when it is 
collected as a by-product of a plateletpheresis procedure.
     Allow individuals with hereditary hemochromatosis to 
donate blood and blood components more frequently than every 8 weeks 
without examination or certification of health by physician at time of 
donation and to be exempt from placing special labeling about the 
donor's disease on the blood components.
     Allow post-donation requalification after day of donation 
of donors who used an outdated vCJD donor questionnaire.
Sec. Sec.  640.4(h) and 640.11(a)
     Allow use of whole blood and RBC that have been exposed to 
temperatures up to 11.5 [deg]C for 4.5 hours or 17 [deg]C for 2 hours 
and 15 minutes, provided that the safety, purity, and potency were not 
affected.
Sec.  640.5
     Allow syphilis testing to be performed on 27 donors on a 
substitute sample drawn after day of donation.
     Allow specimens used for NAT assay to be collected up to 
24 hours prior to the collection of heparinized whole blood units.
Sec.  640.11(a)
     Allow use of RBC and RBC Leukocyte-Reduced that were 
stored at 1 [deg]C to -3 [deg]C for up to 4 hours, provided each unit 
was examined for hemolysis before distribution.
     Allow use of RBC that were exposed to temperatures between 
6 [deg]C and 10.5 [deg]C for up to 4.75 hours, provided each unit was 
examined for hemolysis before distribution.
Sec.  640.23(b)
     Allow ABO and Rh testing on plateletpheresis donors to be 
performed every 90 days.
Sec.  640.32(b)
     Relabel FFP collected by apheresis as recovered plasma 
prior to expiration of the original product. (Done to manage FFP 
inventory collected during periods of increased risk for West Nile 
Virus.)
Sec.  640.34
     Allow use of A and AB FFP that was warmed to -4 [deg]C 
over an 18-hour time period, provided that safety, purity, and potency 
were not affected and the consignee is notified of the temperature 
deviation. Relabeling or shortening of the expiration date is not 
required.
     Allow plasma manufactured from whole blood to be frozen 
within 24 hours after phlebotomy. Blood component must be labeled as 
``PLASMA Frozen within 24 hours after Phlebotomy.''
     Allow use of 45 units of FFP that were exposed to 
temperatures between -6 [deg]C and -18 [deg]C for a total of 4.5 hours, 
provided the blood components remained frozen during the whole time 
period.
     Allow distribution of 1,201 units of FFP and 395 units of 
Plasma Cryoprecipitate Reduced that were exposed to temperatures 
between -16.4 [deg]C and -18 [deg]C for a total of 1.5 hours, provided 
the blood components remained frozen during the whole time period.
Sec. Sec.  640.34 and 640.54(a)
     Allow distribution of 1,235 units of FFP and 963 units of 
Plasma Cryoprecipitate Reduced and prepare Cryoprecipitated AHF from 
1,531 units Cryoprecipitate rich plasma that were exposed to 
temperatures between -11.8 [deg]C and -18 [deg]C for a total of 5.5 
hours, provided the blood components remained frozen during the whole 
time period.
Sec. Sec.  640.61, 640.62, and 640.63
     Permit trained staff to explain the hazards of 
plasmapheresis and obtain informed consent.
     Allow physician substitutes to perform some of the duties 
of a physician (i.e., physical examinations of source plasma donors) 
and to approve physician substitute training programs.
Sec.  640.63
     Draw one donor with a rare RBC antibody who was Anti-HCV 
positive.
     Draw a donor with IgM Anti-HAV with a disease state 
program approval.
     Allow plasmapheresis of an asymptomatic donor with a 
history of Lyme Disease, provided product is labeled that it was 
collected from donor with a history of Lyme Disease.
     Allow a donor with a slightly abnormal Serum Protein 
Electrophoresis (SPE) to donate for an Infant Botulism Program.
     Allow individuals with childhood history of hepatitis at 
age 10 or younger to donate. (Regulation revised-variance request no 
longer needed.)
     Allow source plasma to be collected from a specific anti-e 
donor whose weight fluctuates between 108 and 112 pounds (lbs) to 
donate, provided the weight does not drop below 108 lbs at time of 
donation and donor meets all other eligibility requirements.
Sec.  640.65
     Allow an infrequent plasmapheresis program in source 
plasma facilities. Donors may donate without a physical examination or 
SPE.
     Allow collection of source plasma from anti-HCV reactive 
donors with elevated SPE results (no more than 25 percent over normal 
limits established by testing lab), provided the donor's personal 
physician has given written approval.
Sec.  640.66
     Allow a physician substitute to schedule Tetanus Toxoid 
injections and review responses of donors immunized with licensed 
vaccines. The center physician must still do weekly evaluation of 
records.
Sec.  640.76
     Allow source plasma exposed to more than one episode of 
storage temperature fluctuations warmer than -20 [deg]C and colder than 
-5 [deg]C for less than 72 total hours to not be relabeled as ``Source 
Plasma, Salvaged,'' provided the plasma was not allowed to thaw and the 
consignee is notified of the temperature deviations.
     Allow a revised procedure for labeling shipments of Source 
Plasma, Salvaged. Instead of labeling each unit, the facility may mark 
``Source Plasma, Salvaged'' on the shipping cartons and packing slips.
     Allow 600 liters of source plasma stored at temperatures 
ranging from

[[Page 57945]]

-20 [deg]C to +19 [deg]C for 3 1/2 hours to be relabeled as ``Source 
Plasma, Salvaged.''
     Allow 53 units of source plasma intended for further 
manufacture into injectable products, that were stored at 14 [deg]C to 
be relabeled for further manufacture into noninjectable products, 
provided that label states that it was stored at 14 [deg]C.
Sec. Sec.  660.22 and 660.28
     Use FTA-ABS methodology as an alternative procedure to 
quantitative RPR testing on samples with a qualitative reactive RPR 
test for syphilis.
     Use an alternate procedure to perform FDA required tests 
for lot release action on bulk product prior to filling final 
containers for RBC antigen phenotyping reagents and Anti-Human Globulin 
reagents.
Sec.  660.28
     Allow the use of existing labels for blood grouping 
reagents, pending reprinting of corrected labels.

III. Electronic Access

    Persons with access to the Internet may obtain the cumulative list 
of exceptions and alternative procedures at http://www.fda.gov/cber/blood/exceptions.htm.

    Dated: September 20, 2004.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 04-21624 Filed 9-27-04; 8:45 am]
BILLING CODE 4160-01-S