[Federal Register Volume 85, Number 50 (Friday, March 13, 2020)]
[Notices]
[Pages 14682-14684]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-05103]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2001-D-0007 (formerly Docket No. 2001D-0221)]


Biological Product Deviation Reporting for Blood and Plasma 
Establishments; Guidance for Industry; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

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SUMMARY: The Food and Drug Administration (FDA, Agency, or we) is 
announcing the availability of a revised final guidance entitled 
``Biological Product Deviation Reporting for Blood and Plasma 
Establishments; Guidance for Industry.'' The final guidance document 
provides blood and plasma establishments with revised recommendations 
related to biological product deviation (BPD) reporting. The guidance 
is intended to assist blood and plasma establishments in determining 
when a report is required, who submits the report, what information to 
submit in the report, the timeframe for reporting, and how to submit 
the report. The revised guidance explains that we do not consider post 
donation information (PDI) events to require BPD reports. The revised 
guidance also contains other technical updates and editorial revisions 
to improve clarity and provide a more streamlined document. For the 
purposes of this guidance, ``blood and plasma establishment'' includes 
licensed manufacturers of blood and blood components, including Source 
Plasma, unlicensed registered blood establishments, and transfusion 
services. The guidance announced in this notice supersedes the document 
entitled ``Guidance for Industry: Biological Product Deviation 
Reporting for Blood and Plasma Establishments,'' dated October 2006.

DATES: The Agency is soliciting public comment, but is implementing 
this guidance immediately, because the Agency has determined that prior 
public participation is not feasible or appropriate. Submit either 
electronic or written comments on Agency guidances at any time. The 
announcement of the guidance is published in the Federal Register on 
March 13, 2020.

ADDRESSES: You may submit either electronic or written comments on 
Agency guidances at any time as follows:

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

[[Page 14683]]

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-2001-D-0007 for ``Biological Product Deviation Reporting for Blood 
and Plasma Establishments; Guidance for Industry.'' Received comments 
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.
     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 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.
    You may submit comments on any guidance at any time (see 21 CFR 
10.115(g)(5)).
    Submit written requests for single copies of the final guidance to 
the Office of Communication, Outreach, and Development, Center for 
Biologics Evaluation and Research, Food and Drug Administration, 10903 
New Hampshire Ave., Bldg. 71, Rm. 3128, Silver Spring, MD 20993-0002. 
Send one self-addressed adhesive label to assist that office in 
processing your requests. See the SUPPLEMENTARY INFORMATION section for 
electronic access to guidance document.

FOR FURTHER INFORMATION CONTACT: Tami Belouin, Center for Biologics 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 71, Rm. 7301, Silver Spring, MD 20993-0002, 240-
402-7911.

SUPPLEMENTARY INFORMATION: 

I. Background

    FDA is announcing the availability of a revised document entitled 
``Biological Product Deviation Reporting for Blood and Plasma 
Establishments; Guidance for Industry.'' The final guidance document 
provides blood and plasma establishments with revised recommendations 
related to BPD reporting. The guidance is intended to assist blood and 
plasma establishments in determining when a report is required, who 
submits the report, what information to submit in the report, the 
timeframe for reporting, and how to submit the report. The revised 
guidance explains that we do not consider PDI events to require BPD 
reports. The revised guidance also contains other technical updates and 
editorial revisions to improve clarity and provide a more streamlined 
document. For the purposes of this guidance, ``blood and plasma 
establishment'' includes licensed manufacturers of blood and blood 
components, including Source Plasma, unlicensed registered blood 
establishments, and transfusion services. The guidance announced in 
this notice supersedes the document entitled ``Guidance for Industry: 
Biological Product Deviation Reporting for Blood and Plasma 
Establishments,'' dated October 2006.
    FDA is also announcing the withdrawal of two obsolete memoranda to 
blood establishments entitled ``Responsibilities of Blood 
Establishments Related to Errors and Accidents in the Manufacture of 
Blood and Blood Components,'' issued March 20, 1991, and ``Guidance 
Regarding Post Donation Information Reports,'' issued December 10, 
1993.
    The revised guidance explains that we do not consider PDI events to 
require BPD reports under Sec.  606.171 (21 CFR 606.171) because these 
events are no longer unexpected or unforeseeable based on 18 years of 
data, which show that more than 18,000 reports of PDI events have been 
submitted to FDA each fiscal year (FY) for the past 18 years.
    Every year, the Center for Biologics Evaluation and Research (CBER) 
receives thousands of BPD reports of events associated with 
manufacturing, to include testing, processing, packing, labeling, or 
storage, or with the holding or distribution of both licensed and 
unlicensed blood or blood components, including Source Plasma. Such an 
event is reportable under Sec.  606.171 if certain criteria are met, 
including that the event either: (1) Represents a deviation from 
current good manufacturing practice (CGMP), applicable regulations, 
applicable standards, or established specification that may affect the 
safety, purity, or potency of the product; or (2) represents an 
unexpected or unforeseeable event that may affect the safety, purity, 
or potency of the product. The Agency's BPD reporting program is one of 
the post-market surveillance tools that CBER uses to monitor blood 
manufacturing and to detect potential blood safety issues.
    One type of BPD report received by FDA from blood establishments 
involves PDI events. PDI includes information that a donor, or other 
reliable source, provides to a blood establishment following a donation 
(e.g., at a subsequent donation) that would have resulted in donor 
deferral had it been known by the establishment at the time of 
donation. In these situations, the relevant donor screening questions 
were asked at the original donation, but the donor did not provide the 
information at that time.
    In the Federal Register of November 7, 2000 (65 FR 66635), FDA 
issued a final rule to amend the regulations for biological product 
deviation reporting. In the October 2006 guidance, ``Biological Product 
Deviation Reporting for Blood and Plasma Establishments,'' FDA 
explained that it considered PDI events to be ``unexpected or

[[Page 14684]]

unforeseeable'' events for purposes of BPD reporting (see Sec.  
606.171(b)(1)(ii)). Accordingly, establishments have been submitting 
BPD reports regarding PDI that may affect the safety, purity, or 
potency of a distributed product. PDI events continue to be reported, 
and the numbers have increased over time. Reports of PDI events have 
consistently been the highest number of reports received from blood 
establishments, representing a significant burden to industry and FDA. 
For example, from FYs 2000 through 2017, FDA has received approximately 
18,000 to 40,000 PDI reports each year. The total number of PDI reports 
submitted by blood establishments in FY 2017 was 37,265 of 51,434 total 
BPD reports, representing approximately 72 percent of all BPD reports 
submitted by blood establishments. In reviewing the data for the past 
18 years, based on the extraordinarily high number of PDI reports, FDA 
has concluded that PDI events are no longer ``unexpected or 
unforeseeable,'' and will likely continue to occur. Because PDI events 
are no longer ``unexpected or unforeseeable,'' and also do not 
represent deviations from CGMP, applicable regulations, applicable 
standards, or established specifications, such events are not 
reportable under Sec.  606.171.
    FDA is issuing this guidance for immediate implementation in 
accordance with Sec.  10.115(g)(3) (21 CFR 10.115(g)(3)) without 
initially seeking prior comment because the Agency has determined that 
prior public participation is not feasible or appropriate (see Sec.  
10.115(g)(2)). Specifically, we made this determination because this 
guidance presents a less burdensome policy for reporting BPDs that is 
consistent with public health. It eliminates the reporting of PDI 
events as BPD reports because these reports are no longer unexpected or 
unforeseeable based on PDI data for the past 18 years, without 
compromising public health protections.
    This guidance is expected to significantly reduce the BPD reporting 
burden on industry and the burden on FDA to review these reports. Based 
on the above FY 2017 PDI data, FDA expects that the elimination of PDI 
reports will result in a 72 percent reduction in total BPD reports 
received (elimination of 37,265 of 51,434 total reports in FY 2017). 
FDA anticipates that this will substantially and proportionally reduce 
the blood industry's estimated annual reporting burden under Sec.  
606.171, which FDA recently estimated to be 92,384 total annual hours 
(84 FR 70979 at 70981; December 26, 2019). The revised recommendations 
are also consistent with public health.
    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. PDI events are not 
associated with deviations from CGMP or other requirements, and blood 
establishments generally have no control over information provided by 
donors or third parties subsequent to a donation. Eliminating PDI 
reports will enable blood establishments and FDA to prioritize 
resources on BPD reports that are more likely to inform corrective 
actions to protect the public health. Additionally, blood 
establishments are required to comply with applicable regulations 
regarding, among other things, establishing, maintaining, and following 
standard operating procedures (SOPs) (see Sec.  606.100(b) (21 CFR 
606.100(b)) and maintaining records (see Sec.  606.160 (21 CFR 
606.160)). FDA will continue to assess SOPs and records associated with 
PDI events during routine inspections of blood establishments. Thus, 
this revised guidance presents a less burdensome policy for reporting 
PDI events that is consistent with public health.
    This guidance is being issued consistent with FDA's good guidance 
practices regulation (Sec.  10.115). FDA is issuing this guidance for 
immediate implementation in accordance with Sec.  10.115(g)(3) without 
initially seeking prior comment because the Agency has determined that 
prior public participation is not feasible or appropriate. The guidance 
represents the current thinking of FDA on biological product deviation 
reporting for blood and plasma establishments. It does not establish 
any rights for any person and is not binding on FDA or the public. You 
can use an alternative approach if it satisfies the requirements of the 
applicable statutes and regulations.

II. Paperwork Reduction Act of 1995

    This guidance refers to previously approved FDA collections of 
information. These collections of information are subject to review by 
the Office of Management and Budget (OMB) under the Paperwork Reduction 
Act of 1995 (44 U.S.C. 3501-3521). The collections of information under 
Sec. Sec.  600.14 and 606.171 were approved under OMB control number 
0910-0458; the collections of information under Sec. Sec.  606.100 and 
606.160 were approved under OMB control number 0910-0116; the 
collections of information under 21 CFR 211.192 and 211.198 were 
approved under OMB control number 0910-0139; and the collections of 
information under 21 CFR 601.12 were approved under OMB control number 
0910-0338.

III. Electronic Access

    Persons with access to the internet may obtain the guidance at 
either https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics or https://www.regulations.gov.

    Dated: March 9, 2020.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2020-05103 Filed 3-12-20; 8:45 am]
 BILLING CODE 4164-01-P


