Document ID: FDA-2009-N-0545-0003
Agency: fda
Document Type: Notice
Title: Agency Information Collection Activities; Proposed Collection; Comment Request; Biological Products: Reporting of Biological Product Deviations and Human Cells, Tissues, and Cellular and Tissue-Based Product Deviations in 
Manufacturing
Posted Date: 2022-06-17T04:00Z

[Federal Register Volume 87, Number 117 (Friday, June 17, 2022)]
[Notices]
[Pages 36512-36514]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-13086]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

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

Agency Information Collection Activities; Proposed Collection; 
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 an opportunity for public comment on the proposed collection 
of certain information by the Agency. Under the Paperwork Reduction Act 
of 1995 (PRA), Federal Agencies are required to publish notice in the 
Federal Register concerning each proposed collection of information, 
including each proposed extension of an existing collection of 
information, and to allow 60 days for public comment in response to the 
notice. This notice solicits comments on information collection 
requirements relating to the reporting of biological product deviations 
and human cells, tissues, and cellular and tissue-based product (HCT/P) 
deviations in manufacturing, and Forms FDA 3486 and 3486A.

DATES: Submit either electronic or written comments on the collection 
of information by August 16, 2022.

ADDRESSES: You may submit comments as follows. Please note that late, 
untimely filed comments will not be considered. The https://www.regulations.gov electronic filing system will accept comments until 
11:59 p.m. Eastern Time at the end of August 16, 2022. Comments 
received by mail/hand delivery/courier (for written/paper submissions) 
will be considered timely if they are postmarked or the delivery 
service acceptance receipt is on or before that date.

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to https://www.regulations.gov 
will be posted to the docket unchanged. Because your comment will be 
made public, you are solely responsible for ensuring that your comment 
does not include any confidential information that you or a third party 
may not wish to be posted, such as medical information, your or anyone 
else's Social Security number, or confidential business information, 
such as a manufacturing process. Please note that if you include your 
name, contact information, or other information that identifies you in 
the body of your comments, that information will be posted on https://www.regulations.gov.
     If you want to submit a comment with confidential 
information that you do not wish to be made available to the public, 
submit the comment as a written/paper submission and in the manner 
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand Delivery/Courier (for written/paper 
submissions): Dockets Management Staff (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Dockets 
Management Staff, FDA will post your comment, as well as any 
attachments, except for information submitted, marked and identified, 
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No. 
FDA-2009-N-0545 for ``Agency Information Collection Activities; 
Proposed Collection; Comment Request; Biological Products: Reporting of 
Biological Product Deviations and Human Cells, Tissues, and Cellular 
and Tissue-Based Deviations in Manufacturing; Forms FDA 3486 and 
3486A.'' Received comments, those filed in a timely manner (see 
ADDRESSES), will be placed in the docket and, except for those 
submitted as ``Confidential Submissions,'' publicly viewable at https://www.regulations.gov or at the Dockets Management Staff between 9 a.m. 
and 4 p.m., Monday through Friday, 240-402-7500.
     Confidential Submissions--To submit a comment with 
confidential information that you do not wish to be made publicly 
available, submit your comments only as a written/paper submission. You 
should submit two copies total. One copy will include the information 
you claim to be confidential with a heading or cover note that states 
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will 
review this copy, including the claimed confidential information, in 
its consideration of comments. The second copy, which will have the 
claimed confidential information redacted/blacked out, will be 
available for public viewing and posted on https://www.regulations.gov. 
Submit both copies to the Dockets Management Staff. If you do not wish 
your name and contact information to be made publicly available, you 
can provide this information on the cover sheet and not in the body of 
your comments and you must identify this information as 
``confidential.'' Any information marked as ``confidential'' will not 
be disclosed except in accordance with 21 CFR 10.20

[[Page 36513]]

and other applicable disclosure law. For more information about FDA's 
posting of comments to public dockets, see 80 FR 56469, September 18, 
2015, or access the information at: https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in 
the heading of this document, into the ``Search'' box and follow the 
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852, 240-402-7500.

FOR FURTHER INFORMATION CONTACT: JonnaLynn Capezzuto, Office of 
Operations, Food and Drug Administration, Three White Flint North, 10A-
12M, 11601 Landsdown St., North Bethesda, MD 20852, 301-796-3794, 
[email protected].

SUPPLEMENTARY INFORMATION: Under the PRA (44 U.S.C. 3501-3521), Federal 
Agencies must obtain approval from the Office of Management and Budget 
(OMB) for each collection of information they conduct or sponsor. 
``Collection of information'' is defined in 44 U.S.C. 3502(3) and 5 CFR 
1320.3(c) and includes Agency requests or requirements that members of 
the public submit reports, keep records, or provide information to a 
third party. Section 3506(c)(2)(A) of the PRA (44 U.S.C. 3506(c)(2)(A)) 
requires Federal Agencies to provide a 60-day notice in the Federal 
Register concerning each proposed collection of information, including 
each proposed extension of an existing collection of information, 
before submitting the collection to OMB for approval. To comply with 
this requirement, FDA is publishing notice of the proposed collection 
of information set forth in this document.
    With respect to the following collection of information, FDA 
invites comments on these topics: (1) whether the proposed collection 
of information is necessary for the proper performance of FDA's 
functions, including whether the information will have practical 
utility; (2) the accuracy of FDA's estimate of the burden of the 
proposed collection of information, including the validity of the 
methodology and assumptions used; (3) ways to enhance the quality, 
utility, and clarity of the information to be collected; and (4) ways 
to minimize the burden of the collection of information on respondents, 
including through the use of automated collection techniques, when 
appropriate, and other forms of information technology.

Biological Products: Reporting of Biological Product Deviations and 
Human Cells, Tissues, and 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 the 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 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-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

[[Page 36514]]

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 follow up 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.
    We estimate the burden of this collection of information as 
follows:

                                                     Table 1--Estimated Annual Reporting Burden \1\
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                                                                                             Number of                        Average
                21 CFR section; activity                   FDA form No.      Number of     responses per   Total annual     burden per      Total hours
                                                                            respondents     respondent       responses       response
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600.14; Reporting of product deviations by licensed                 3486             103           6.864             707               2           1,414
 manufacturers..........................................
606.171; Reporting of product deviations by licensed                3486           2,008           6.883          13,821               2          27,642
 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           110.5
                                                         -----------------------------------------------------------------------------------------------
    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: June 14, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022-13086 Filed 6-16-22; 8:45 am]
BILLING CODE 4164-01-P