[Federal Register Volume 86, Number 120 (Friday, June 25, 2021)]
[Notices]
[Pages 33713-33716]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2021-13575]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2017-N-6931]


Agency Information Collection Activities; Submission for Office 
of Management and Budget Review; Comment Request; Current Good 
Manufacturing Practices and Related Regulations for Blood and Blood 
Components; and Requirements for Donation Testing, Donor Notification, 
and ``Lookback''

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA, Agency, or we) is 
announcing that a proposed collection of information has been submitted 
to the Office of Management and Budget (OMB) for review and clearance 
under the Paperwork Reduction Act of 1995.

DATES: Submit written comments (including recommendations) on the 
collection of information by July 26, 2021.

ADDRESSES: To ensure that comments on the information collection are 
received, OMB recommends that written comments be submitted to https://www.reginfo.gov/public/do/PRAMain. Find this particular information 
collection by selecting ``Currently under Review--Open for Public 
Comments'' or by using the search function. The OMB control number for 
this information collection is 0910-0116. Also, include the FDA docket 
number found in brackets in the heading of this document.

FOR FURTHER INFORMATION CONTACT: Amber Sanford, Office of Operations, 
Food and Drug Administration, Three White Flint North, 10A-12M, 11601 
Landsdown St., North Bethesda, MD 20852, 301-796-8867, 
PRAStaff@fda.hhs.gov.

SUPPLEMENTARY INFORMATION: In compliance with 44 U.S.C. 3507, FDA has 
submitted the following proposed collection of information to OMB for 
review and clearance.

Current Good Manufacturing Practices and Related Regulations for Blood 
and Blood Components; and Requirements for Donation Testing, Donor 
Notification, and ``Lookback''

OMB Control Number 0910-0116--Revision

    This information collection supports Agency regulations and 
associated guidance. All blood and blood components introduced or 
delivered for introduction into interstate commerce are subject to 
section 351(a) of the Public Health Service Act (PHS Act) (42 U.S.C. 
262(a)). Section 351(a) requires that manufacturers of biological 
products, which include blood and blood components intended for further 
manufacturing into products, have a license, issued upon a 
demonstration that the product is safe, pure, and potent and that the 
manufacturing establishment meets all applicable standards, including 
those prescribed in the FDA regulations designed to ensure the 
continued safety, purity, and potency of the product. In addition, 
under section 361 of the PHS Act (42 U.S.C. 264), by delegation from 
the Secretary of Health and Human Services, FDA may make and enforce 
regulations necessary to prevent the introduction, transmission, or 
spread of communicable diseases from foreign countries into the States 
or possessions, or from one State or possession into any other State or 
possession.
    Section 351(j) of the PHS Act states that the Federal Food, Drug, 
and Cosmetic Act (FD&C Act) also applies to biological products. Blood 
and blood components for transfusion or for further manufacturing into 
products are drugs, as that term is defined in section 201(g)(1) of the 
FD&C Act (21 U.S.C. 321(g)(1)). Because blood and blood components are 
drugs under the FD&C Act, blood and plasma establishments must comply 
with the provisions and related regulatory scheme of the FD&C Act. For 
example, under section 501 of the FD&C Act (21 U.S.C. 351), drugs are 
deemed ``adulterated'' if the methods used in their manufacturing, 
processing, packing, or holding do not conform to current good 
manufacturing practice (CGMP) and related regulations.
    The CGMP regulations (part 606) (21 CFR part 606) and related 
regulations implement FDA's statutory authority to ensure the safety, 
purity, and potency of blood and blood components. The public health 
objective in testing human blood donations for evidence of relevant 
transfusion-transmitted infections and in notifying donors is to 
prevent the transmission of relevant transfusion-transmitted 
infections. For example, the ``lookback'' requirements are intended to 
help ensure the continued safety of the blood supply by providing 
necessary information to consignees of blood and blood components and 
appropriate notification of recipients of blood components that are at 
increased risk for transmitting human immunodeficiency virus (HIV) or 
hepatitis C virus (HCV) infection.

[[Page 33714]]

    The information collection requirements in the CGMP, donation 
testing, donor notification, and ``lookback'' regulations provide FDA 
with the necessary information to perform its duty to ensure the 
safety, purity, and potency of blood and blood components. These 
requirements establish accountability and traceability in the 
processing and handling of blood and blood components and enable FDA to 
perform meaningful inspections.
    The recordkeeping requirements serve preventive and remedial 
purposes. The third-party disclosure requirements identify various 
blood and blood components and important properties of the product, 
demonstrate that the CGMP requirements have been met, and facilitate 
the tracing of a product back to its original source. The reporting 
requirements inform FDA's Center for Biologics Evaluation and Research 
of certain information that may require immediate corrective action.
    Respondents to this collection of information are licensed and 
unlicensed blood establishments that collect blood and blood 
components, including Source Plasma and Source Leukocytes, inspected by 
FDA, and transfusion services inspected by Centers for Medicare and 
Medicaid Services (CMS). Based on submission data, there are 
approximately 864 licensed Source Plasma establishments and 
approximately 1,789 licensed blood collection establishments, for an 
estimated total of 2,653 (864 + 1,789) licensed blood collection 
establishments. Also, there are an estimated total of 817 unlicensed, 
registered blood collection establishments for an approximate total of 
3,470 collection establishments (864 + 1,789 + 817 = 3,470 
establishments). Of these establishments, approximately 856 perform 
plateletpheresis (777) and leukapheresis (79). These establishments 
annually collect approximately 73.7 million units of Whole Blood and 
blood components, including Source Plasma and Source Leukocytes, and 
are required to follow FDA ``lookback'' procedures. In addition, there 
are another estimated 4,961 establishments that fall under the Clinical 
Laboratory Improvement Amendments of 1988 (CLIA) (formerly referred to 
as facilities approved for Medicare reimbursement) that transfuse blood 
and blood components.
    The following reporting and recordkeeping estimates are based on 
information provided by industry, CMS, and our experience with the 
information collection. We estimate 53.5 million donations of Source 
Plasma from approximately 2.5 million donors and estimate 12.3 million 
donations of Whole Blood and apheresis Red Blood Cells, including an 
estimated 10,000 (approximately 0.081 percent of 12.3 million) 
autologous donations, from 9 million donors. Assuming each autologous 
donor makes an average of 1.1 donations, we estimate there are 9,090 
autologous donors (10,000 autologous/1.1 average donations).
    We estimate 0.53 percent (56,000 / 10,654,000) of the 77,000 
donations that are donated specifically for the use of an identified 
recipient would be tested under the dedicated donors' testing 
provisions in Sec.  610.40(c)(1)(ii) (21 CFR 610.40(c)(1)(ii)).
    Under Sec.  610.40(g)(2) and (h)(2)(ii)(A), Source Leukocytes, a 
licensed product that is used in the manufacture of interferon, which 
requires rapid preparation from blood, is currently shipped prior to 
completion of testing for evidence of relevant transfusion-transmitted 
infections. Shipments of Source Leukocytes are approved under a 
biologics license application and each shipment does not have to be 
reported to the Agency. Based on a review of data, FDA receives less 
than one application per year from manufacturers of Source Leukocytes; 
however, we estimate one annually for this analysis.
    Also according to Agency data, there are approximately 15 licensed 
manufacturers that ship known reactive human blood or blood components 
under Sec.  610.40(h)(2)(ii)(C) and (D). We estimate each manufacturer 
would ship an average of 1 unit of human blood or blood components per 
month (12 per year) that would require two labels: One as reactive for 
the appropriate screening test under Sec.  610.40(h)(2)(ii)(C) and the 
other stating the exempted use specifically approved by FDA under Sec.  
610.40(h)(2)(ii)(D).
    Based on information received from industry, we estimate 7,500 
donations that test reactive by a screening test for syphilis and are 
determined to be biological false positives by additional testing 
annually. These units would be labeled according to Sec.  
610.40(h)(2)(vi).
    Human blood or a blood component with a reactive screening test, as 
a component of a medical device, is an integral part of the medical 
device; e.g., a positive control for an in vitro diagnostic testing 
kit. It is the usual and customary business practice for manufacturers 
to include on the container label a warning statement indicating that 
the product was manufactured from a donation found to be reactive for 
the identified relevant transfusion-transmitted infection(s). In 
addition, on the rare occasion when a human blood or blood component 
with a reactive screening test is the only component available for a 
medical device that does not require a reactive component, then a 
warning statement must be affixed to the medical device. To account for 
this rare occasion under Sec.  610.42(a) (21 CFR 610.42(a)), we 
estimate that the warning statement would be necessary no more than 
once a year.
    We estimate 3,100 repeat donors will test reactive on a screening 
test for HIV. We assume an average of three components was made from 
each donation. Under Sec.  610.46(a)(1)(ii)(B) and (a)(3) (21 CFR 
610.46(a)(1)(ii)(B) and (b)(3)), this estimate results in 9,300 (3,100 
x 3) notifications of the HIV screening test results to consignees by 
collecting establishments for the purpose of quarantining affected 
blood and blood components, and another 9,300 (3,100 x 3) notifications 
to consignees of subsequent test results.
    We estimate 4,961 consignees will be required under Sec.  
610.46(b)(3) to notify transfusion recipients, their legal 
representatives, or physicians of record an average of 0.35 times per 
year resulting in a total number of 1,755 (585 confirmed positive 
repeat donors x 3) notifications. Also, under Sec.  610.46(b)(3), we 
estimate and include the time to gather test results and records for 
each recipient and to accommodate multiple attempts to contact the 
recipient.
    Furthermore, we estimate 6,800 repeat donors per year would test 
reactive for antibody to HCV. Under Sec. Sec.  610.47(a)(1)(ii)(B) and 
(a)(3) (21 CFR 610.47(a)(1)(ii)(B) and (a)(3)), collecting 
establishments would notify the consignee two times for each of the 
20,400 (6,800 x 3 components) components prepared from these donations: 
Once for quarantine purposes and again with additional HCV test results 
for a total of 40,800 (2 x 20,400) notifications as an annual ongoing 
burden. Under Sec.  610.47(b)(3), we assume 4,961 consignees notify 
approximately 2,050 recipients or their physicians of record annually.
    Based on industry estimates, approximately 18.15 percent of 
approximately 14,018,000 million potential donors (2,544,000 donors) 
who come to donate annually are determined not to be eligible for 
donation prior to collection because of failure to satisfy eligibility 
criteria. It is the usual and customary business practice of 
approximately 2,606 (1,789 + 817) blood collecting establishments to 
notify onsite and to explain why the donor is determined not to be 
suitable for donating. Based on such available information, we estimate 
that two-thirds (1,737) of the 2,606 blood collecting

[[Page 33715]]

establishments provided onsite additional information and counseling to 
a donor determined not to be eligible for donation as usual and 
customary business practice. Consequently, we estimate one-third, or 
869 of the 2,606 blood collecting establishments, would need to 
provide, under Sec.  630.40(a) (21 CFR 630.40(a)), additional 
information and onsite counseling to the estimated 848,000 (one-third 
of approximately 2,544,000) ineligible donors.
    We estimate another 0.6 percent of 14,018,000 potential donors 
(84,108 donors) are deferred annually based on test results. We assume 
95 percent of the establishments that collect 99 percent of the blood 
and blood components notify donors who have reactive test results for 
HIV, Hepatitis B Virus, HCV, Human T-Lymphotropic Virus, and syphilis 
as their usual and customary business practice. Consequently, 5 percent 
of the 2,653 licensed establishments (133) collecting 1 percent (841) 
of the deferred donors (84,108) would notify donors under Sec.  
630.40(a).
    As part of their usual and customary business practice, collecting 
establishments notify an autologous donor's referring physician of 
reactive test results obtained during the donation process required 
under Sec.  630.40(d)(1). However, we assume 5 percent of the 1,789 
blood collection establishments (89) may not notify the referring 
physicians of the estimated 2 percent of 10,000 autologous donors with 
the initial reactive test results (200) as their usual and customary 
business practice.
    We assume 95 percent of recordkeepers, which account for 99 percent 
of blood donations, have developed standard operating procedures (SOPs) 
as part of their customary and usual business practice. Establishments 
may minimize burdens associated with CGMP and related regulations by 
using model standards developed by industries' accreditation 
organizations. These accreditation organizations represent almost all 
registered blood establishments.
    Under Sec.  606.160(b)(1)(ix) (21 CFR 606.160(b)(1)(ix)), we assume 
a total number of annual records based on 2,544,000 ineligible donors 
and each of the estimated 2,628,108 (2,544,000 + 84,108) donors 
deferred based on reactive test results for evidence of infection 
because of relevant transfusion-transmitted infections. Under Sec.  
606.160(b)(1)(xi), only the 1,789 registered blood establishments 
collect autologous donations and, therefore, are required to notify 
referring physicians. We estimate that 4.5 percent of the 9,090 
autologous donors (409) will be deferred under Sec.  610.41 (21 CFR 
610.41), which in turn will lead to the notification of their referring 
physicians.
    Under Sec.  610.41(b), we estimate 25 submissions for 
requalification of donors each requiring 7 hours per submission. In 
addition, we assume that there would be only three notifications for 
requalification of donors under Sec.  630.35(b) (21 CFR 630.35(b)), 
which would also require 7 hours for each submission.
    FDA permits the shipment of untested or incompletely tested human 
blood or blood components in rare medical emergencies and when 
appropriately documented (Sec.  610.40(g)(1)). We estimate the 
recordkeeping under Sec.  610.40(g)(1) to be minimal with one or fewer 
occurrences per year. The reporting of test results to the consignee in 
Sec.  610.40(g) is part of the usual and customary business practice of 
blood establishments.
    In the Federal Register of February 22, 2021 (86 FR 10582), we 
published a 60-day notice requesting public comment on the proposed 
collection of information. No comments were received. On our own 
initiative, however, and for efficiency of Agency operations, we are 
revising the information collection to include and consolidate related 
information collection found in Agency guidance. The guidance documents 
were issued consistent with our good guidance practice regulations in 
21 CFR 10.115, which provide for public comment at any time.
    We are revising the information collection to reference the Agency 
guidance document entitled ``Bacterial Risk Control Strategies for 
Blood Collection Establishments and Transfusion Services to Enhance the 
Safety and Availability of Platelets for Transfusion'' (December 2020), 
which provides blood collection establishments and transfusion services 
with recommendations to control the risk of bacterial contamination of 
room temperature stored platelets intended for transfusion. The 
guidance is available for download from our website at: https://www.fda.gov/media/123448/download.
    The guidance recommends blood collection establishments notify 
transfusion services if a distributed platelet product is subsequently 
identified as positive for bacterial contamination and that blood 
establishments communicate to their consignees the type of storage 
container the platelets are stored in. We assume such notification is a 
usual and customary business practice for blood establishments and, 
therefore, estimate no burden estimate for the information collection.
    We also developed the guidance entitled ``Labeling of Red Blood 
Cell Units with Historical Antigen Typing Results'' (December 2018) to 
provide establishments that collect blood and blood components for 
transfusion with recommendations for labeling Red Blood Cell units with 
non-ABO/Rh(D) antigen typing results obtained from previous donations 
(historical antigen typing results). The guidance is available for 
download from our website at: https://www.fda.gov/media/119376/download.
    The guidance recommends disclosing non-ABO/Rh(D) historical antigen 
typing results on a tie-tag or directly on the container label. We 
assume such information disclosures would be usual and customary for 
blood establishments and, therefore, estimate no burden for the 
information collection, currently approved under OMB control number 
0910-0862.
    We estimate the burden of this collection of information as 
follows:

                                 Table 1--Estimated Annual Reporting Burden \1\
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                                                     Number of
    21 CFR section; activity         Number of     responses per   Total annual   Average burden    Total hours
                                    respondents     respondent       responses     per response
----------------------------------------------------------------------------------------------------------------
606.170(b); \2\ Donor or                      81               1              81              20           1,620
 recipient fatality reporting...
610.40(g)(2); Application for                  1               1               1               1               1
 approval to ship...............
610.41(b); Request for                     2,653          0.0094              25               7             175
 requalification of donor.......
610.40(h)(2)(ii)(A); Application               1               1               1               1               1
 for approval for shipment or
 use............................
630.35(b); Request for                     2,653         0.00113               3               7              21
 requalification of donor.......
                                 -------------------------------------------------------------------------------
    Total.......................  ..............  ..............  ..............  ..............           1,818
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.
\2\ The reporting requirement in Sec.   640.73, which addresses the reporting of fatal donor reactions, is
  included in the estimate for Sec.   606.170(b).


[[Page 33716]]


                                                   Table 2--Estimated Annual Recordkeeping Burden \1\
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                                                                   Number of
           21 CFR section; activity                Number of      records per    Total annual       Average burden per recordkeeping        Total hours
                                                 recordkeepers   recordkeeper       records
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606.100(b); \2\ Maintenance of SOPs...........         \5\ 422               1             422  24......................................          10,128
606.100(c); Records of investigations.........         \5\ 422              10           4,220  1.......................................           4,220
606.110(a); \3\ Documentation donor's health            \6\ 43               1              43  0.5 (30 minutes)........................              22
 permits plateletpheresis or leukapheresis.
606.151(e); Records of emergency transfusions.         \5\ 422              12           5,064  0.08 (5 minutes)........................             405
606.160; \4\ Records of collection,                    \5\ 422         907.583         383,000  0.75 (45 minutes).......................         287,250
 processing, compatibility testing, storage,
 and distribution of each unit of blood and
 blood components.
606.160(b)(1)(viii); HIV consignee                       1,789         10.4533          18,701  0.17 (10 minutes).......................           3,179
 notification.
                                                         4,961          3.6537          18,126  0.17 (10 minutes).......................           3,081
606.160(b)(1)(viii); HCV consignee                       1,789         22.8060          40,800  0.17 (10 minutes).......................           6,936
 notification.
                                                         4,961          8.2241          40,800  0.17 (10 minutes).......................           6,936
HIV recipient notification....................           4,961          0.3538           1,755  0.17 (10 minutes).......................             298
HCV recipient notification....................           4,961          0.4132           2,050  0.17 (10 minutes).......................             349
606.160(b)(1)(ix); Donor notification records.           3,470         757.380       2,628,109  0.05 (3 minutes)........................         131,405
606.160(b)(1)(xi); Physician notification                1,789          0.2286             409  0.05 (3 minutes)........................            20.5
 records.
606.165; Distribution and receipt records.....         \5\ 422         907.583         383,000  0.08 (5 minutes)........................          30,640
606.170(a); Adverse reaction records..........         \5\ 422              12           5,064  1.......................................           5,064
610.40(g)(1); Documentation of medical                   3,470               1           3,470  0.5 (30 minutes)........................           1,735
 emergency.
630.15(a)(1)(ii)(B); Documentation required              1,789               1           1,789  1.......................................           1,789
 for dedicated donation.
630.20(c); Documentation of exceptional                  1,789               1           1,789  1.......................................           1,789
 medical need.
                                               ---------------------------------------------------------------------------------------------------------
    Total.....................................  ..............  ..............  ..............  ........................................         495,247
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.
\2\ The recordkeeping requirements in Sec.  Sec.   606.171, 630.5(d), 630.10(c)(1) and (2), and 640.66, which address the maintenance of SOPs, are
  included in the estimate for Sec.   606.100(b).
\3\ The recordkeeping requirements in Sec.   640.27(b), which address the maintenance of donor health records for the plateletpheresis, are included in
  the estimate for Sec.   606.110(a).
\4\ The recordkeeping requirements in Sec.  Sec.   606.110(a)(2), 630.5(b)(1)(i), 630.10(f)(2) and (4), 630.10(g)(2)(i), 630.15(a)(1)(ii)(A) and (B),
  630.15(b)(2), (b)(7)(i) and (iii), 630.20(a) and (b), 640.21(e)(4), 640.25(b)(4) and (c)(1), 640.31(b), 640.33(b), 640.51(b), 640.53(b) and (c),
  640.56(b) and (d), 630.15(b)(2), 640.65(b)(2)(i), 640.65(b)(2)(i), 640.71(b)(1), 640.72, 640.73, and 640.76(a) and (b), which address the maintenance
  of various records are included in the estimate for Sec.   606.160.
\5\ Five percent of establishments that fall under CLIA that transfuse blood and components and FDA-registered blood establishments (0.05 x 4,961 +
  3,470 = 422).
\6\ Five percent of plateletpheresis and leukapheresis establishments (0.05 x 856 = 43).


                                               Table 3--Estimated Annual Third-Party Disclosure Burden \1\
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                                                                  Number of
          21 CFR section; activity               Number of     disclosures per    Total annual        Average burden per disclosure         Total hours
                                                respondents       respondent      disclosures
--------------------------------------------------------------------------------------------------------------------------------------------------------
606.145(c); Notification of bacterial                   4,961           0.2822            1,400  0.02 (90 seconds)......................              28
 contamination of platelets.
606.170(a); Reports of transfusion reaction.          \2\ 422               12            5,064  0.5 (30 minutes).......................           2,532
610.40(c)(1)(ii); Labeling of donation                  3,470           0.0395              137  0.08 (5 minutes).......................              11
 dedicated to single recipient.
610.40(h)(2)(ii)(C) and (D); Labeling of                   15               12              180  0.2 (12 minutes).......................              36
 reactive blood and blood components.
610.40(h)(2)(vi); Labeling of reactive blood            3,470           2.1614            7,500  0.08 (5 minutes).......................             600
 and blood components.
610.42(a); Warning statement for medical                    1                1                1  1......................................               1
 devices.
610.46(a)(1)(ii)(B); Notification to                    1,789           5.1984            9,300  0.17 (10 minutes)......................           1,581
 consignees to quarantine (HIV ``lookback'').
610.46(a)(3); Notification to consignees of             1,789           5.1984            9,300  0.17 (10 minutes)......................           1,581
 further testing.
610.46(b)(3); Notification to recipients....            4,961           0.3528            1,750  1......................................           1,750
610.47(a)(1)(ii)(B); Notification to                    1,789          11.4030           20,400  0.17 (10 minutes)......................           3,468
 consignees to quarantine (HCV ``lookback'').
610.47(a)(3); Notification to consignees of             1,789          11.4030           20,400  0.17 (10 minutes)......................           3,468
 further testing.
610.47(b)(3); Notification to recipients....            4,961           0.4132            2,050  1......................................           2,050
630.40(a); Notification of donors determined              869          975.834          848,000  0.08 (5 minutes).......................          67,840
 not to be eligible for donation.
630.40(a); Notification of donors deferred                133            6.323              841  1.5....................................           1,262
 based on reactive test results.
630.40(d)(1); Notification to physician of                 89            2.247              200  1......................................             200
 autologous donor.
                                             -----------------------------------------------------------------------------------------------------------
    Total...................................  ...............  ...............  ...............  .......................................          86,408
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.
\2\ Five percent of establishments that fall under CLIA that transfuse blood and components and FDA-registered blood establishments (0.05 x 4,961 +
  3,470 = 422).

    We have adjusted our burden estimate for this information 
collection since last OMB review to reflect an overall increase of 
79,024 hours annually. We attribute this adjustment to an increase in 
the number of registered blood establishments over the last 3 years.

    Dated: June 21, 2021.
Lauren K. Roth,
Acting Principal Associate Commissioner for Policy.
[FR Doc. 2021-13575 Filed 6-24-21; 8:45 am]
BILLING CODE 4164-01-P


