Notice2023-00013

Agency Information Collection Activities; Submission for Office of Management and Budget Review; Comment Request; Biological Products: Reporting of Biological Product Deviations and Human Cells, Tissues, and Cellular and Tissue-Based Product Deviations in Manufacturing

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Metadata and text below are from the Federal Register, a public-domain U.S. government work. Always verify the official published version before relying on it for any legal matter.

Published
January 6, 2023

Issuing agencies

Health and Human Services DepartmentFood and Drug Administration

Abstract

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.

Full Text

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<title>Federal Register, Volume 88 Issue 4 (Friday, January 6, 2023)</title>
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[Federal Register Volume 88, Number 4 (Friday, January 6, 2023)]
[Notices]
[Pages 1074-1075]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2023-00013]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2009-N-0545]


Agency Information Collection Activities; Submission for Office 
of Management and Budget Review; Comment Request; Biological Products: 
Reporting of Biological Product Deviations and Human Cells, Tissues, 
and Cellular and Tissue-Based Product Deviations in Manufacturing

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 February 6, 2023.

ADDRESSES: To ensure that comments on the information collection are 
received, OMB recommends that written comments be submitted to <a href="https://www.reginfo.gov/public/do/PRAMain">https://www.reginfo.gov/public/do/PRAMain</a>. 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 0910-0458. Also include the FDA docket 
number found in brackets in the heading of this document.

FOR FURTHER INFORMATION CONTACT: Domini Bean, Office of Operations, 
Food and Drug Administration, Three White Flint North, 10A-12M, 11601 
Landsdown St., North Bethesda, MD 20852, 301-796-5733, 
<a href="/cdn-cgi/l/email-protection#4e1e1c0f1d3a2f28280e282a2f6026263d60292138"><span class="__cf_email__" data-cfemail="cf9f9d8e9cbbaea9a98fa9abaee1a7a7bce1a8a0b9">[email&#160;protected]</span></a>.

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.

Cellular and Tissue-Based Product Deviations in Manufacturing; Forms 
FDA 3486 and 3486A

OMB Control Number 0910-0458--Extension

    Under section 351 of the Public Health Service Act (PHS Act) (42 
U.S.C. 262), all biological products, including human blood and blood 
components, offered for sale in interstate commerce must be licensed 
and meet standards, including those prescribed in FDA regulations, 
designed to ensure the continued safety, purity, and potency of such 
products. In addition, under section 361 of the PHS Act (42 U.S.C. 
264), FDA may issue and enforce regulations necessary to prevent the 
introduction, transmission, or spread of communicable diseases between 
the States or possessions or from foreign countries into the States or 
possessions. Further, the Federal Food, Drug, and Cosmetic Act (FD&C 
Act) (21 U.S.C. 351) provides that drugs and devices (including human 
blood and blood components) are adulterated if they do not conform with 
current good manufacturing practice (CGMP) assuring that they meet the 
requirements of the FD&C Act. Establishments manufacturing biological 
products, including human blood and blood components, must comply with 
the applicable CGMP regulations (parts 211, 606, and 820 (21 CFR parts 
211, 606, and 820)) and current good tissue practice (CGTP) regulations 
(part 1271 (21 CFR part 1271)) as appropriate. FDA regards biological 
product deviation (BPD) reporting and human cells, tissues, and 
cellular and tissue-based product (HCT/P) deviation reporting to be an 
essential tool in its directive to protect public health by 
establishing and maintaining surveillance programs that provide timely 
and useful information.
    Section 600.14 (21 CFR 600.14), in brief, requires the manufacturer 
who holds the biological product license, for other than human blood 
and blood components, and who had control over a distributed product 
when the deviation occurred, to report to the Center for Biologics 
Evaluation and Research (CBER) or to the Center for Drug Evaluation and 
Research (CDER) as soon as possible but at a date not to exceed 45 
calendar days after acquiring information reasonably suggesting that a 
reportable event has occurred. Section 606.171 (21 CFR 606.171), in 
brief, requires licensed manufacturers of human blood and blood 
components, including Source Plasma, unlicensed registered blood 
establishments, and transfusion services, who had control over a 
distributed product when the deviation occurred, to report to CBER as 
soon as possible but at a date not to exceed 45 calendar days after 
acquiring information reasonably suggesting that a reportable event has 
occurred. Similarly, Sec.  1271.350(b) (21 CFR 1271.350(b)), in brief, 
requires HCT/P establishments that manufacture non-

[[Page 1075]]

reproductive HCT/Ps described in Sec.  1271.10 (21 CFR 1271.10) to 
investigate and report to CBER all HCT/P deviations relating to a 
distributed HCT/P that relates to the core CGTP requirements, if the 
deviation occurred in the establishment's facility or in a facility 
that performed a manufacturing step for the establishment under 
contract, agreement or other arrangement. Form FDA 3486 is used to 
submit BPD reports and HCT/P deviation reports.
    Respondents to this collection of information are: (1) licensed 
manufacturers of biological products other than human blood and blood 
components, (2) licensed manufacturers of blood and blood components 
including Source Plasma, (3) unlicensed registered blood 
establishments, (4) transfusion services, and (5) establishments that 
manufacture non-reproductive HCT/Ps regulated solely under section 361 
of the PHS Act as described in Sec.  1271.10. The number of respondents 
and total annual responses are based on the BPD reports and HCT/P 
deviation reports FDA received in fiscal year (FY) 2021. The number of 
licensed manufacturers and total annual responses under Sec.  600.14 
include the estimates for BPD reports submitted to both CBER and CDER. 
Based on the information from industry, the estimated average time to 
complete a deviation report is 2 hours, which includes a minimal one-
time burden to create a user account for those reports submitted 
electronically. The availability of the standardized report form, Form 
FDA 3486, and the ability to submit this report electronically to CBER 
(CDER does not currently accept electronic filings) further streamlines 
the report submission process.
    CBER has developed a web-based addendum to Form FDA 3486 (Form FDA 
3486A) to provide additional information when a BPD report has been 
reviewed by FDA and evaluated as a possible recall. The additional 
information requested includes information not contained in the Form 
FDA 3486 such as: (1) distribution pattern; (2) method of consignee 
notification; (3) consignee(s) of products for further manufacture; (4) 
additional product information; (5) updated product disposition; and 
(6) industry recall contacts. This information is requested by CBER 
through email notification to the submitter of the BPD report. This 
information is used by CBER for recall classification purposes. CBER 
estimates that 3 percent of the total BPD reports submitted to CBER 
would need additional information submitted in the addendum. CBER 
further estimates that it would take between 10 and 20 minutes to 
complete the addendum. For calculation purposes, CBER is using 15 
minutes.
    Activities such as investigating, changing standard operating 
procedures or processes, and followup are currently required under 
parts 211 (approved under OMB control number 0910-0139), 606 (approved 
under OMB control number 0910-0116), 820 (approved under OMB control 
number 0910-0073), and 1271 (approved under OMB control number 0910-
0543) and, therefore, are not included in the burden calculation for 
the separate requirement of submitting a deviation report to FDA.
    In the Federal Register of June 17, 2022 (87 FR 36512), we 
published a 60-day notice soliciting comment on the proposed collection 
of information. No comments were received.
    We estimate the burden of this collection of information as 
follows:

                                                     Table 1--Estimated Annual Reporting Burden \1\
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                                                                              Number of       Total
           21 CFR section; activity              FDA form     Number of     responses per    annual          Average burden per response         Total
                                                   No.       respondents     respondent     responses                                            hours
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600.14; Reporting of product deviations by           3486             103           6.864         707  2.....................................      1,414
 licensed manufacturers.
606.171; Reporting of product deviations by          3486           2,008           6.883      13,821  2.....................................     27,642
 licensed manufacturers, unlicensed registered
 blood establishments, and transfusion
 services.
1271.350(b); HCT/P deviations.................       3486              80           2.575         206  2.....................................        412
Web-based Addendum............................  \2\ 3486A              66            6.69         442  0.25 (15 minutes).....................      110.5
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    Total.....................................  .........  ..............  ..............      15,176  ......................................   29,578.5
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.
\2\ Three percent of the number of respondents ((2,008 + 103 + 80) x 0.03 = 66) and total annual responses to CBER ((13,821 + 707 + 206) x 0.03 = 442).

    Our estimated burden for the information collection reflects an 
overall decrease of approximately 65,014 hours and a corresponding 
decrease of 34,152 responses. We attribute this adjustment to a 
decrease in the number of deviation reports we received in FY 2021 from 
licensed manufacturers and unlicensed registered blood establishments 
under Sec.  606.171. This is likely due to our issuance of the revised 
guidance document entitled ``Biological Product Deviation Reporting for 
Blood and Plasma Establishments'' (85 FR 14682, March 13, 2020), which 
provided blood and plasma establishments with revised recommendations 
related to BPD reporting. The revised guidance provided a less 
burdensome policy for reporting BPDs that is consistent with public 
health and eliminated the reporting of post donation information (PDI) 
events as BPD reports because these reports were no longer unexpected 
or unforeseeable. Given the substantial number of PDI reports FDA has 
received, the Agency is aware that these events occur, and the 
submission of additional PDI reports to FDA is unlikely to facilitate 
the identification of manufacturing or safety issues.

    Dated: January 3, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023-00013 Filed 1-5-23; 8:45 am]
BILLING CODE 4164-01-P


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