0116_Supporting Statement_2021

0116_Supporting Statement_2021.pdf

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

OMB: 0910-0116

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UNITED STATES FOOD & DRUG ADMINISTRATION
Current Good Manufacturing Practice (GMP) and Related Regulations for Blood and Blood
Components; and Requirements for Donation Testing, Donor Notification, and “Lookback”
OMB Control No. 0910-0116 – Revision
SUPPORTING STATEMENT – Part A: Justification
Terms of Clearance: We address OMB’s terms of clearance in Question 1, below.
1. Circumstances Making the Collection of Information Necessary
This information collection supports implementation of Food and Drug Administration (FDA,
us or we) 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) of the PHS act 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 (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.
To implement these statutory provisions, regulations have been codified at 21 CFR part 606 –
Current Good Manufacturing Practice for Blood and Blood Components; 21 CFR part 610 –
General Biological Products Standards; 21 CFR part 630 – Requirements for Blood and Blood
Components Intended For Transfusion or For Further Manufacturing Use; and 21 CFR part
640 – Additional Standards for Human Blood and Blood Products. The regulations establish
quality standard requirements applicable to blood and blood products including information
collection provisions. See Appendix A of this document for a summary list of provisions
covered by this information collection.

Description of Respondents: 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).
ASSOCIATED GUIDANCE:
We revised the information collection to reference the following guidance documents, which
were developed consistent with our Good Guidance Practice regulations in 21 CFR part 10.115
that provide for public comment at any time:
The 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) 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). Information collection discussed in the guidance is currently approved under
OMB control no. 0910-0862. The guidance is available for download from our website at:
https://www.fda.gov/media/119376/download. The guidance recommends disclosing nonABO/Rh(D) historical antigen typing results on a tie-tag or directly on the container label. We
assume such disclosures are usual and customary for blood establishments and estimate no
burden for the information collection, however for efficiency of agency operations we are
consolidating our accounting for the related activities into one information collection.
Accordingly, we request OMB approval of the information collection provisions found in the
applicable regulations and associated guidance, as discussed in this supporting statement.
2. Purpose and Use of the Information Collection
The CGMP regulations for human blood and blood components (part 606) and related
regulations (parts 610, 630, and 640) 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

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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.
Consistent with the regulations, records maintained shall be made readily available for
authorized inspection. FDA is authorized to inspect these records under section 704 of the
FD&C Act (21 U.S.C. 374) (and its enforcement section under section 301(f) of the FD&C
Act (21 U.S.C. 331(f)). We use the information to help determine compliance with regulatory
requirements established to ensure the safety and efficacy of the covered products. The thirdparty disclosure requirements identify the 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 of certain information that may require immediate corrective action.
FDA allows the use or shipment prior to test results of human blood or blood components
under two circumstances: appropriately documented medical emergency situations or for
further manufacturing use as approved in writing by FDA. Use or shipment prior to test
results may occur, provided the consignee is notified that test results are not available, the
tests for evidence of infection due to relevant transfusion-transmitted infections are
performed as soon as possible after release or shipment, and the results are provided promptly
to the consignee. The regulations require an establishment to document the emergency
release or shipment of blood or blood components prior to completion of testing. If the
establishment ships blood or blood components for further manufacturing use prior to
completion of testing, the establishment must obtain prior approval from FDA. In either
instance, the establishment must complete testing as soon as possible thereafter, and must
notify the consignee of test results as soon as they are available. Prior approval is necessary
to help ensure that an establishment is following proper procedures in shipping potentially
infectious blood and blood components for further manufacturing use. Without this
information, FDA could not monitor industry procedures and discharge its statutory
responsibility for protecting the nation’s health.
The donor notification process is intended to prevent further donations from donors who have
been deferred for positive test results for markers of certain relevant transfusion-transmitted
infections as prescribed in § 610.41 or for failing to satisfy the donor eligibility criteria under
§§ 630.10 and 630.15 prior to collection. Deferred donors are informed of: (1) The reason for
the decision; (2) the types of donation that the donor should not donate in the future, if
appropriate; (3) the results of the tests for evidence of infection due to relevant transfusiontransmitted infections that were the basis for deferral, if applicable; and (4) information
concerning medical follow-up and counseling. By having this information, the deferred donor
may make informed decisions as to his or her medical welfare.

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3. Use of Improved Information Technology and Burden Reduction
The regulations do not prescribe specific means by which respondents must fulfill the
information collection requirements. Establishments may use and we recommend utilization
of computer and electronic information technology. Computers may be used for emailing
reports to FDA. Notification of consignees can be accomplished by e-mail, phone, fax, or
mail. There are no technical obstacles for electronic reporting of the applicable information
to FDA. FDA continues to pursue methods of applying technology to reduce burden to the
respondents of its information collection as limited resources permit.
4. Efforts to Identify Duplication and Use of Similar Information
We are unaware of duplicative information collection. Although GMP or quality system (QS)
regulations appear in several parts of Title 21 (Food and Drugs) of the CFR, this information
collection covers provisions applicable to blood and blood products as described under 21
CFR parts 606, 630, and 640 and associated guidance, as discussed in this supporting
statement.
5. Impact on Small Businesses or Other Small Entities
The public health protection requirements underlying the information collection apply to all
respondents; however, we believe they impose no undue burden on small entities. At the same
time, we assist small businesses in complying with agency requirements through CBER’s
Office of Communication, Outreach and Development (OCOD) and through the scientific and
administrative staffs within the agency. We also provide a Small Business Guide on our
website at http://www.fda.gov/ForIndustry/SmallBusinessAssistance/default.htm.
6. Consequences of Collecting the Information Less Frequently
The information collection schedule is consistent with statutory and agency requirements
established to promote and protect the public health. There are no technical or legal obstacles
to reducing the burden.
7. Special Circumstances Relating to the Guidelines of 5 CFR 1320.5
There are no special circumstances associated with this information collection.
8. Comments in Response to the Federal Register Notice and Efforts to Consult Outside
the Agency
In accordance with 5 CFR 1320.8(d), FDA published a 60-day notice for public comment in
the Federal Register of February 22, 2021 (86 FR 10582). No comments were received in
response to the notice.

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9. Explanation of Any Payment or Gift to Respondents
There are no incentives, payments or gifts associated with this information collection.
10. Assurance of Confidentiality Provided to Respondents
In preparing this supporting statement, we consulted our Privacy Office to ensure appropriate
identification and handling of information collected. Although personally identifiable
information (PII) is collected, it is collected in the context of the subject individuals’
professional capacity and the FDA-related work performed for their employer (e.g., point of
contact). Specifically, the ICR collects PII in the context of fatality reports; requests for
approval to ship or use donations that have a reactive screening tests for a relevant transfusiontransmitted infection; and requests for requalification of deferred donors. Consistent with 21
CFR 606.170(b) PII submitted pertaining to (Donor or recipient fatality reporting) includes
name, title, telephone number with area code, and fax number (if available), facility's name,
mailing address, and FDA registration number (if applicable). Donor information provided
can also include name, age and sex of the deceased; date, time, and cause or suspected cause
of death (brief description of event); and whether an autopsy was or will be performed.
Consistent with 21 CFR 610.40(g)(2) (Application for approval to ship) PII is submitted with
a written application and may include name, address, telephone number, email address and fax
number. PII submitted under 610.41(b) (Request for requalification of a donor) is contact
information submitted with a written request, that might include name, address, telephone
number, email address and fax number. PII submitted consistent with 610.40(h)(2)(ii)(A)
(Application for approval for shipment or use) is contact information submitted with a written
application, that might include name, address, telephone number, email address and fax
number. PII submitted consistent with 630.35(b) (Request for requalification of a donor) is
contact information submitted with a written request, that might include name, address,
telephone number, email address and fax number. Through appropriate guidance, FDA
limited submission fields and minimized the PII collected to protect the privacy of the
individuals.
The confidentiality of information received by FDA is consistent with the Freedom of
Information Act (FOIA) and FDA’s published regulations of “Public Information” under 21
CFR part 20. After an FDA investigator completes a routine inspection of a blood or blood
component manufacturing establishment, the completed report with the results of the
inspection becomes public information, available under the FOIA. However, certain
information, such as donor and patient names, for example, is deleted from any information
released by FDA under the FOIA and FDA regulations. Manufacturers of human blood and
blood components are not required to reveal any proprietary information or trade secrets to
achieve compliance with the provisions.

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11. Justification for Sensitive Questions
Establishments as part of the donation screening process for blood collection must ask
questions of a sensitive nature. These questions are used to evaluate the suitability of a donor.
Donors not meeting certain criteria are deferred from donating. This information is necessary
to help prevent the transmission of communicable diseases and protect public health. These
records are maintained by the establishment and may be reviewed by FDA during an
inspection.
12. Estimates of Annualized Burden Hours and Costs
12a. Annualized Hour Burden Estimate
Table 1.--Estimated Annual Reporting Burden1,2
21 CFR Section; Activity No. of
No. of
Total
Respondents Responses per
Annual
Respondent
Responses
606.170(b)2 ; Donor or
81
1
81
recipient fatality reporting
610.40(g)(2); Application 1
1
1
for approval to ship
610.41(b); Request for
2,653
0.0094
25
requalification of donor
610.40(h)(2)(ii)(A);
1
1
1
Application for approval
for shipment or use
630.35(b); Request for
2,653
0.00113
3
requalification of donor
Total

Average
Burden per
Response
20

Total
Hours

1

1

7

175

1

1

7

21

1,620

1,818

1

There are no capital costs or operating and maintenance costs associated with this collection of information.
2
The reporting requirement in § 640.73, which addresses the reporting of fatal donor reactions, is included in the estimate
for § 606.170(b).

Table 2 – Estimated Annual Recordkeeping Burden 1
21 CFR Section; Activity

No. of
Recordkeepers
4225

No. of
Records per
Recordkeeper
1

Total
Annual
Records
422

Average
Total
Burden per
Hours
Recordkeeping
24
10,128

606.100(b)2 ; Maintenance of
SOPs
606.100(c); Records of
investigations
606.110(a)3 ; Documentation
donor’s health permits
plateletpheresis or
leukapheresis
606.151(e); Records of
emergency transfusions

4225

10

4,220

1

4,220

436

1

43

0.5
(30 min.)

22

4225

12

5,064

0.08
(5 min.)

405

6

21 CFR Section; Activity
606.1604 ; Records of
collection, processing,
compatibility testing,
storage, and distribution of
each unit of blood and blood
components
606.160(b)(1)(viii); HIV
consignee notification

No. of
Recordkeepers
4225

No. of
Total
Average
Total
Records per
Annual
Burden per
Hours
Recordkeeper Records
Recordkeeping
907.583
383,000
0.75 287,250
(45 min.)

1,789

10.4533

18,701

4,961

3.6537

18,126

1,789

22.8060

40,800

4,961

8.2241

40,800

HIV recipient notification

4,961

0.3538

1,755

HCV recipient notification

4,961

0.4132

2,050

606.160(b)(1)(ix); Donor
notification records
606.160(b)(1)(xi); Physician
notification records
606.165; Distribution and
receipt records
606.170(a); Adverse reaction
records
610.40(g)(1);
Documentation of medical
emergency
630.15(a)(1)(ii)(B);
Documentation required for
dedicated donation
630.20(c); Documentation of
exceptional medical need

3,470

757.380

2,628,109

1,789

0.2286

409

4225

907.583

383,000

4225

12

5,064

3,470

1

3,470

0.5
(30 min.)

1,735

1,789

1

1,789

1

1,789

1,789

1

1,789

1

1,789

606.160(b)(1)(viii); HCV
consignee notification

0.17
3,179
(10 min.)
0.17
3,081
(10 min.)
0.17
6,936
(10 min.)
0.17
6,936
(10 min.)
0.17
298
(10 min.)
0.17
349
(10 min.)
0.05 131,405
(3 min.)
0.05
20.5
(3 min.)
0.08 30,640
(5 min.)
1
5,064

Total
495,247
There are no capital costs or operating and maintenance costs associated with this collection of information.
2
The recordkeeping requirements in §§ 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 § 606.100(b).
3
The recordkeeping requirements in § 640.27(b), which address the maintenance of donor health records for the
plateletpheresis, are included in the estimate for § 606.110(a).
4
The recordkeeping requirements in §§ 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 § 606.160.
5
Five percent of establishments that fall under CLIA that transfuse blood and components and FDA-registered blood
establishments (0.05 × 4,961 + 3,470 = 422).
6
Five percent of plateletpheresis and leukapheresis establishments (0.05 × 856 = 43).
1

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Table 3.--Estimated Annual Third-Party Disclosure Burden1
21 CFR Section; Activity
No. of
No. of
Total
Average
Total
Respondents Disclosures Annual
Burden
Hours
per
Disclosures per
Respondent
Disclosure
606.145(c); Notification of bacterial
4,961
0.2822
1,400
0.02
28
contamination of platelets
(90
seconds)
606.170(a); Reports of transfusion
4222
12
5,064
0.5
2,532
reaction
(30 min.)
610.40(c)(1)(ii); Labeling of
3,470
0.0395
137
0.08
11
donation dedicated to single recipient
(5 min.)
610.40(h)(2)(ii)(C) and (D);
15
12
180
0.2
36
Labeling of reactive blood and blood
(12 min.)
components
610.40(h)(2)(vi); Labeling of
3,470
2.1614
7,500
0.08
600
reactive blood and blood components
(5 min.)
610.42(a); Warning statement for
1
1
1
1
1
medical devices
610.46(a)(1)(ii)(B); Notification to
1,789
5.1984
9,300
0.17
1,581
consignees to quarantine (HIV
(10 min.)
“lookback”)
610.46(a)(3); Notification to
1,789
5.1984
9,300
0.17
1,581
consignees of further testing
(10 min.)
610.46(b)(3); Notification to
4,961
0.3528
1,750
1
1,750
recipients
610.47(a)(1)(ii)(B); Notification to
1,789
11.4030
20,400
0.17
3,468
consignees to quarantine (HCV
(10 min.)
“lookback”)
610.47(a)(3); Notification to
1,789
11.4030
20,400
0.17
3,468
consignees of further testing
(10 min.)
610.47(b)(3); Notification to
4,961
0.4132
2,050
1
2,050
recipients
630.40(a); Notification of donors
869
975.834
848,000
0.08 67,840
determined not to be eligible for
(5 min.)
donation
630.40(a); Notification of donors
133
6.323
841
1.5
1,262
deferred based on reactive test
results
630.40(d)(1); Notification to
89
2.247
200
1
200
physician of autologous donor
Total
86,408
1

There are no capital costs or operating and maintenance costs associated with this collection of information.
Five percent of establishments that fall under CLIA that transfuse blood and components and FDA-registered blood
establishments (0.05 × 4,961 + 3,470 = 422).

2

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Based on current 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). 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.
Based on available information, we estimate 53.5 million donations of Source Plasma from 2.5
million donors and 12.3 million donations of Whole Blood and apheresis Red Blood Cells,
including approximately 10,000 (approximately 0.081 percent of 12.3 million) autologous
donations, from approximately 9 million donors. Assuming each autologous donor makes an
average of 1.1 donations, we estimate 9,090 autologous donors (10,000 autologous/1.1 average
donations). We assume 0.53 percent (56,000/10,654,000) of the 77,000 donations that are
donated specifically for the use of an identified recipient are tested under the dedicated donors
testing provisions in § 610.40(c)(1)(ii).
Under § 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 infection due to relevant transfusiontransmitted 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
information from CBER’s database system, FDA receives less than one application per year
from manufacturers of Source Leukocytes. However, for calculation purposes, FDA is
estimating one application annually.
According our data, there are approximately 15 licensed manufacturers that ship known
reactive human blood or blood components under §§ 610.40(h)(2)(ii)(C) and (D). FDA
estimates that each manufacturer would ship an estimated 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 § 610.40(h)(2)(ii)(C), and the other stating the exempted use
specifically approved by FDA under § 610.40(h)(2)(ii)(D).
Based on industry feedback, we estimate that 7,500 donations testing reactive by a screening
test for syphilis and are determined to be biological false positives by additional testing
annually. These units would be labeled accordingly (§ 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 usual and customary business practice for manufacturers to include on the container label
a warning statement 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

9

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
§ 610.42(a), we estimate that the warning statement would be necessary no more than once a
year.
We estimate that 3,100 repeat donors will test reactive on a screening test for HIV. We
assume an average of three components are made from each donation. Under
§ 610.46(a)(1)(ii)(B) and (a)(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 assume an average of 10 minutes per notification
of consignees is necessary for the information collection.
We estimate 4,961 consignees will be required under § 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 § 610.46(b)(3), FDA estimates and includes the time to gather test results and
records for each recipient and to accommodate multiple attempts to contact the recipient.
We estimate that 6,800 repeat donors per year would test reactive for antibody to HCV.
Under § 610.47(a)(1)(ii)(B) and 610.47(a)(3), collecting establishments would notify the
consignee 2 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) notifications as an annual ongoing burden. Under §
610.47(b)(3), we estimate that 4,961 consignees will notify 2,050 recipients or their physicians
of record annually.
Based on industry estimates, roughly 18.15 percent of 14,018,000 million potential donors
(2,544,000 donors) who come to donate annually are determined ineligible for donation prior
to collection. We assume it to be usual and customary business practice for the estimated
2,606 (1,789+817) blood collecting establishments to make notifications onsite and to explain
why the donor is determined to be ineligible. Based on available information, we estimate
two-thirds (1,737) of the 2,606 blood collecting establishments provided on site additional
information and counseling to a donor determined ineligible. Therefore, we estimate that only
one-third, or 869 of the 2,606 blood collection establishments would incur burden under
§ 630.40(a), to provide additional information and counseling to 848,000 (one-third of
2,544,000) ineligible donors.
We assume another 0.6 percent of 14,018,000 donors (84,108 donors) are deferred annually
based on test results. We estimate 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 (HBV), HCV, Human T-Lymphotropic Virus (HTLV), and syphilis as
usual and customary business practice. Thus, 5 percent of the 2,653 establishments (133)
collecting 1 percent (841) of the deferred donors (84,108) would notify donors under
§ 630.40(a). We consider it part of usual and customary business practice that collecting

10

establishments notify an autologous donor’s referring physician of reactive test results
obtained during the donation process required under § 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 reactive test results
(200).
The recordkeeping table reflects the estimate that approximately 95 percent of the
recordkeepers, which collect 99 percent of the blood supply, have developed 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 § 606.160(b)(1)(ix), we estimate total annual records based on 2,544,000 donors
determined ineligible 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 § 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 4.5 percent of the 9,090 autologous donors (409) will be deferred
under § 610.41 which in turn will lead to the notification of their referring physicians.
Under § 610.41(b), we estimate 25 submissions for requalification of donors and assume there
would be only 3 notifications for requalification of donors under § 630.35(b), each requiring 7
hours for submission. FDA permits the shipment of untested or incompletely tested but
appropriately documented human blood or blood components in rare medical emergencies and
when appropriately documented (§ 610.40(g)(1)). We estimate recordkeeping under
§ 610.40(g)(1) to be minimal with one or fewer occurrences per year. We consider the
reporting of test results to the consignee in § 610.40(g) to be usual and customary business
practice of blood establishments. Our assumptions of the average burden per response (hours)
and the average burden for recordkeeping (hours) are based on our experience with the
collection and informal industry feedback.
The development of labels is a one-time burden. The container labels have been standardized
and are sold commercially. The label is only customized for the firm’s name and address. In
addition, the instruction circular is printed by major blood banking associations, the ARC,
AABB, and ABC, and are sold at minimal cost to the firms. The circulars are updated
annually usually due to new industry information. Therefore, we assume no burden is
incurred as the result of FDA labeling and disclosure regulations (§§ 606.121 and 606.122)
and Uniform Labeling of Blood and Blood Components using ISBT 128 (Industry Consensus
Standard for the Uniform Labeling of Blood and Blood Components Using ISTB 128.

11

12b. Annualized Cost Burden Estimate
The estimated annual cost to respondents is $42,593,529.
Activity

Total Burden Hours

Hourly Wage Rate

Reporting

1,818

$73

Total Respondent
Costs
$132,714

Recordkeeping

495,247

$73

$36,153,031

Disclosure

86,408

$73

$6,307,784

Total

$42,593,529

The cost is based on a pay rate of $48/hour for a medical technologist (MT), who is
responsible for recording donor, quarantine, testing, and disposition of information, notifying
consignees of test results, and has the training and skills to handle various recordkeeping
requirements. The cost estimate is also based on a supervisor, at a pay rate of $65/hour who is
responsible for updating SOPs, recording donor information, and notifying physicians of
recipients or recipients of test results, investigating, writing, and reporting a fatality, and a
Medical Director (MD), at a pay rate of $107/hour, who is responsible for updating SOPs,
recording donor information, and notifying physicians of recipients or recipients of test
results, investigating, writing, and reporting a fatality. These salary estimates include
recordkeeping, reporting, and disclosure requirements that are performed by the MT,
supervisor, or MD; the cost/hour includes the average salary of the three ($73). These salary
estimates include benefits but no overhead costs.
13. Estimates of Other Total Annual Costs to Respondents/Recordkeepers or Capital Costs
There are no capital, start-up, operating or maintenance costs associated with this information
collection.
14. Annualized Cost to the Federal Government
The estimated annualized cost to the Federal Government is $2,836,116. This estimate is
based on a FDA reviewer or investigator at an average grade scale of GS-12/5 ($56/hour),
who reviews the requests for approval submitted under §§ 610.40(g)(2) and
610.40(h)(2)(ii)(A), or performs biannual on-site inspections. The inspection cost includes
inspection of a facility, review of facility records, and report preparation. The cost is based on
1,327 inspections, since the 2,653 facilities are inspected biannually. The estimated cost is
also based on a GS-13/5 ($67/hour) Consumer Safety Officer who compiles, reviews, and
analyzes fatality reports. In Fiscal Year 2019, FDA received 81 fatality reports. These salary
estimates include benefits but no overhead costs.

12

Activity
Product Release Review
Inspection
Fatality Report Review
Total

Number of
Respondents
2
1, 237
81

Number of
Hours
1
40
12

Cost per
Hour
$56
$56
$67

Total Cost
$112
$2,770,880
$65,124
$2,836,116

15. Explanation for Program Changes or Adjustments
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. Also, for efficiency of
agency operations we have consolidated related information collection approved under 09100862 and will discontinue the latter collection upon OMB approval of this request.
16. Plans for Tabulation and Publication and Project Time Schedule
This information collected will not be published or tabulated.
17. Reason(s) Display of OMB Expiration Date is Inappropriate
FDA is not seeking approval to not display the expiration date for OMB approval.
18. Exceptions to Certification for Paperwork Reduction Act Submissions
There are no exceptions to the certification.

13

Appendix A
The 0910-0116 information collection includes the following citations:
Citation
21 CFR 606.100(b)
SOPs

Type of Activity
Recordkeeping

21 CFR 606.100(c)
SOPs

Recordkeeping

21 CFR 606.110(a)
Records (Donor)

Recordkeeping

21 CFR 606.121
Labeling
21 CFR 606.122
Labeling
21 CFR 606.151(e)
SOPs

Disclosure

21 CFR 606.160
Records (General)

Recordkeeping

21 CFR
606.160(b)(1)(viii)
Records (General)
21 CFR
606.160(b)(1)(ix)
Records
(Notification)
21 CFR
606.160(b)(1)(xi)
Records
(Notification)
21 CFR 606.165
Records
21 CFR 606.170(a)
Adverse Reaction
Records and Report

Recordkeeping

21 CFR 606.170(b)
Fatality Report

Reporting

21 CFR
610.40(c)(1)(ii)
Labeling
21 CFR 610.40(g)(1)

Disclosure

Disclosure
Recordkeeping

Recordkeeping

Description
Requires that written standard operating procedures (SOPs) be maintained for all
steps to be followed in the collection, processing, compatibility testing, storage
and distribution of blood and blood components used for transfusion and further
manufacturing purposes.
Requires the review of all records pertinent to the lot or unit of blood prior to
release or distribution. Any unexplained discrepancy or the failure of a lot or
unit of final product to meet any of its specifications must be thoroughly
investigated, and the investigation, including conclusions and follow-up, must be
recorded.
Provides that the use of plateletpheresis and leukapheresis procedures to obtain a
product for a specific recipient may be at variance with the additional standards
for that specific product, if among other things, the physician certifies in writing
that the donor’s health permits plateletpheresis or leukapheresis.
Requires container label for blood and blood components (except Source
Plasma) by all blood establishments.
Requires an instruction circular to provide adequate directions for use, to be
available for distribution if the product is intended for transfusion.
Requires that SOPs for compatibility testing include procedures to expedite
transfusion in life-threatening emergencies; records of all such incidents must be
maintained, including complete documentation justifying the emergency action,
which must be signed by a physician.
Requires that legible and indelible contemporaneous records of each significant
step in the collection, processing, compatibility testing, storage, and distribution
of each unit of blood and blood components be made so that each unit can be
clearly traced and records be maintained for no less than 10 years.
Requires maintenance of records concerning quarantine, notification, testing and
disposition performed under the human immunodeficiency virus (HIV) and
hepatitis C virus (HCV) ‘‘lookback’’ provisions.
Requires a blood collection establishment to maintain records of notification of
donors deferred or determined not to be eligible for donation, including
appropriate follow-up.

Recordkeeping

Requires an establishment to maintain records of notification of the referring
physician of a deferred autologous donor, including appropriate follow-up.

Recordkeeping

Requires that distribution and receipt records be maintained to facilitate recalls,
if necessary.
Requires records to be maintained of any reports of complaints of adverse
reactions arising as a result of blood collection or transfusion. Each such report
must be thoroughly investigated, and a written report, including conclusions and
follow-up, must be prepared and maintained. When an investigation concludes
that the product caused the transfusion reaction, copies of all such written reports
must be forwarded to and maintained by the manufacturer or collecting facility.
Requires that facilities notify FDA’s Center for Biologics Evaluation and
Research (CBER) as soon as possible after confirming a complication of blood
collection or transfusion to be fatal. The collecting facility is to report donor
fatalities, and the compatibility testing facility is to report recipient fatalities.
The reporting facility also must submit a written report of the investigation
within 7 days after the fatality.
Requires that each donation dedicated to a single identified recipient be labeled
as required under § 606.121, and with a label containing the name and
identifying information of the recipient.
Requires an establishment to appropriately document a medical emergency for

Recordkeeping
and Disclosure

Recordkeeping

14

Records (Medical
Emergency)
21 CFR 610.40(g)(2)
Approval Request

Reporting

21 CFR
610.40(h)(2)(ii)(A)
Approval Request

Reporting

21 CFR
610.40(h)(2)(ii)(C)
and (h)(2)(ii)(D)
Labeling
21 CFR
610.40(h)(2)(vi)
Labeling
21 CFR 610.42(a)
Labeling

Disclosure

21 CFR
610.46(a)(1)(ii)(B)
and
610.47(a)(1)(ii)(B)
Consignee
Notification
21 CFR 610.46(a)(3)
and 610.47(a)(3)
Consignee
Notification
21 CFR 610.46(b)(3)
and 610.47(b)(3)
Recipient or
Physician
Notification

Disclosure

21 CFR 630.6(a)
Donor Notification

Disclosure

21 CFR 630.6(d)(1)
Physician
Notification

Disclosure

Disclosure

Disclosure

Disclosure

Disclosure

the release of human blood or blood components prior to completion of required
testing.
Requires an establishment to obtain written approval from FDA to ship human
blood or blood components for further manufacturing use prior to completion of
testing for evidence of infection due to certain communicable disease agents.
Requires an establishment to obtain written approval from FDA to use or ship
certain human blood or blood components found to be reactive by a screening
test for evidence of certain communicable disease agent(s) or collected from a
donor with a record of a reactive screening test.
Require an establishment to label certain reactive human blood and blood
components with the appropriate screening test results, and, if they are intended
for further manufacturing use into injectable products, include a statement on the
label indicating the exempted use specifically approved by FDA.
Requires each donation of human blood or blood components, excluding Source
Plasma, that tests reactive by a screening test for syphilis and is determined to be
a biological false positive to be labeled with both test results.
Requires a warning statement, “indicating that the product was manufactured
from a donation found to be reactive by a screening test for evidence of infection
due to the identified communicable agent(s)” in the labeling for medical devices
containing human blood or a blood component found to be reactive by a
screening test for evidence of infection due to a communicable disease agent(s)
or syphilis.
Require a collecting establishment, within 3 calendar days of the donor testing
reactive by an HIV or HCV screening test or the collecting establishment
becoming aware of other reliable test results or information, to, among other
things, notify consignees to quarantine all identified previously collected in-date
blood and blood components.
Require a collecting establishment, within 45 calendar days of the donor testing
reactive by an HIV or HCV screening test, to, among other things, notify
consignees of supplemental test results, or the results of a reactive screening test
if there is no available supplemental test that is approved for such use by FDA.
Require consignees to establish, maintain, and follow an appropriate system for
performing HIV and HCV ‘‘lookback’’ when notified by the collecting
establishment that they have received blood and blood components previously
collected from donors who later tested reactive for evidence of HIV or HCV
infection, or when the collecting establishment is made aware of other reliable
test results or information indicating evidence of HIV or HCV infection in a
donor. This provision for a system requires the consignee to follow SOPs for,
among other things, notifying transfusion recipients of blood and blood
components, or the recipient's physician of record or legal representative, when
such action is indicated by the results of the supplemental (additional, more
specific) tests or a reactive screening test if there is no available supplemental
test that is approved for such use by FDA, or if under an investigational new
drug application (IND) or an investigational device exemption (IDE), is
exempted for such use by FDA.
Also, require the consignee to make reasonable attempts to perform the
notification within 12 weeks of receipt of the supplemental test result or receipt
of a reactive screening test result when there is no available supplemental test
that is approved for such use by FDA, or if under an IND or IDE, is exempted
for such use by FDA.
Requires an establishment to make reasonable attempts to notify any donor who
has been deferred as required by § 610.41, or who has been determined not to be
eligible as a donor.
Requires an establishment to provide certain information to the referring
physician of an autologous donor who is deferred based on the results of tests as
described in § 610.41.

15


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