[Federal Register Volume 85, Number 170 (Tuesday, September 1, 2020)]
[Notices]
[Pages 54385-54388]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-19239]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2011-N-0231]


Agency Information Collection Activities: Proposed Collection; 
Comment Request; Adverse Experience Reporting for Licensed Biological 
Products; and General Records

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA or Agency) 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 the proposed extension of the collection of 
information concerning requirements relating to FDA's Adverse 
Experience Reporting System (FAERS) for licensed biological products, 
and general records associated with the manufacture and distribution of 
biological products.

DATES: Submit either electronic or written comments on the collection 
of information by November 2, 2020.

ADDRESSES: You may submit comments as follows. Please note that late, 
untimely filed comments will not be

[[Page 54386]]

considered. Electronic comments must be submitted on or before November 
2, 2020. The https://www.regulations.gov electronic filing system will 
accept comments until 11:59 p.m. Eastern Time at the end of November 2, 
2020. 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-2011-N-0231 for ``Adverse Experience Reporting for Licensed 
Biological Products; and General Records.'' 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 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: Domini Bean, Office of Operations, 
Food and Drug Administration, Three White Flint North, 10A-45, 11601 
Landsdown St., North Bethesda, MD 20852, 301-796-5733, 
[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.

Adverse Experience Reporting For Licensed Biological Products; and 
General Records--21 CFR Part 600

OMB Control Number 0910-0308--Extension

    Under the Public Health Service Act (42 U.S.C. 262), FDA may only 
approve a biologics license application for a biological product that 
is safe, pure, and potent. When a biological product is approved and 
enters the market, the product is introduced to a larger patient 
population in settings different from clinical trials. New information 
generated during the postmarketing period offers further insight into 
the benefits and risks of the product, and evaluation of this 
information is important to ensure its safe use. FDA issued the Adverse 
Experience Reporting (AER) requirements in part 600 (21 CFR part 600) 
to enable FDA to take actions necessary for the protection of the 
public health in response to reports of adverse experiences related to 
licensed biological products. The primary purpose of FDA's FAERS is to 
identify potentially serious safety problems with licensed biological 
products. Although premarket testing discloses a general safety profile 
of a biological product's comparatively

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common adverse effects, the larger and more diverse patient populations 
exposed to the licensed biological product provides the opportunity to 
collect information on rare, latent, and long-term effects. In 
addition, production and/or distribution problems have contaminated 
biological products in the past. AER reports are obtained from a 
variety of sources, including manufacturers, patients, physicians, 
foreign regulatory agencies, and clinical investigators. Identification 
of new and unexpected safety issues through the analysis of the data in 
FAERS contributes directly to increased public health protection. For 
example, evaluation of these safety issues enables FDA to take focused 
regulatory action. Such action may include, but is not limited to, 
important changes to the product's labeling (such as adding a new 
warning), coordination with manufacturers to ensure adequate corrective 
action is taken, and removal of a biological product from the market 
when necessary.
    Section 600.80(c)(1) requires licensed manufacturers or any person 
whose name appears on the label of a licensed biological product to 
report each adverse experience that is both serious and unexpected, 
whether foreign or domestic, as soon as possible but in no case later 
than 15 calendar days of initial receipt of the information by the 
licensed manufacturer. These reports are known as postmarketing 15-day 
Alert reports. This section also requires licensed manufacturers to 
submit any followup reports within 15 calendar days of receipt of new 
information or as requested by FDA, and if additional information is 
not obtainable, to maintain records of the unsuccessful steps taken to 
seek additional information. In addition, this section requires that a 
person who submits an adverse action report to the licensed 
manufacturer, rather than to FDA, maintain a record of this action. 
Section 600.80(e) requires licensed manufacturers to submit a 15-day 
Alert report for an adverse experience obtained from a postmarketing 
clinical study only if the licensed manufacturer concludes that there 
is a reasonable possibility that the product caused the adverse 
experience. Section 600.80(c)(2) requires licensed manufacturers to 
report each adverse experience not reported in a postmarketing 15-day 
Alert report at quarterly intervals, for 3 years from the date of 
issuance of the biologics license, and then at annual intervals. The 
majority of these periodic reports are submitted annually, since a 
large percentage of currently licensed biological products have been 
licensed longer than 3 years. Section 600.80(k) requires licensed 
manufacturers to maintain for a period of 10 years records of all 
adverse experiences known to the licensed manufacturer, including raw 
data and any correspondence relating to the adverse experiences. 
Section 600.81 requires licensed manufacturers to submit, at an 
interval of every 6 months, information about the quantity of the 
product distributed under the biologics license, including the quantity 
distributed to distributors. These distribution reports provide FDA 
with important information about products distributed under biologics 
licenses, including the quantity, certain lot numbers, labeled date of 
expiration, the fill lot numbers for the total number of dosage units 
of each strength or potency distributed (e.g., 50,000 per 10-milliliter 
vials), and date of release. FDA may require the licensed manufacturer 
to submit distribution reports under this section at times other than 
every 6 months. Under Sec.  600.82(a), an applicant of a biological 
product or blood and blood component must notify FDA of a permanent 
discontinuance of manufacture or an interruption in manufacturing or 
disruption in supply, as applicable. Under Sec. Sec.  600.80(h)(2) and 
600.81(b)(2), a licensed manufacturer may request a temporary waiver 
for the requirements under Sec. Sec.  600.80(h)(1) and 600.80(b)(1), 
respectively. Requests for waivers must be submitted in accordance with 
Sec.  600.90. Under Sec.  600.90, a licensed manufacturer may submit a 
waiver request for any requirements that apply to the licensed 
manufacturer under Sec. Sec.  600.80 and 600.81. A waiver request 
submitted under Sec.  600.90 must include supporting documentation.
    Manufacturers of biological products for human use must keep 
records of each step in the manufacture and distribution of a product, 
including any recalls. These recordkeeping requirements serve 
preventative and remedial purposes by establishing accountability and 
traceability in the manufacture and distribution of products. These 
requirements also enable FDA to perform meaningful inspections. Section 
600.12 requires, among other things, that records be made concurrently 
with the performance of each step in the manufacture and distribution 
of products. These records must be retained for no less than 5 years 
after the records of manufacture have been completed or 6 months after 
the latest expiration date for the individual product, whichever 
represents a later date. In addition, under Sec.  600.12, manufacturers 
must maintain records relating to the sterilization of equipment and 
supplies, animal necropsy records, and records in cases of divided 
manufacturing responsibility with respect to a product. Under Sec.  
600.12(b)(2), manufacturers are also required to maintain complete 
records pertaining to the recall from distribution of any product. 
Furthermore, Sec.  610.18(b) (21 CFR 610.18(b)) requires, in part, that 
the results of all periodic tests for verification of cultures and 
determination of freedom from extraneous organisms be recorded and 
retained. The recordkeeping requirements for 21 CFR 610.12(g), 
610.13(a)(2), 610.18(d), 680.2(f) and 680.3(f) are approved under OMB 
control number 0910-0139.
    Respondents to this collection of information include manufacturers 
of biological products (including blood and blood components) and any 
person whose name appears on the label of a licensed biological 
product. In table 1, the number of respondents is based on the 
estimated number of manufacturers that are subject to those regulations 
or that submitted the required information to the Center for Biologics 
Evaluation and Research and Center for Drugs Evaluation and Research, 
FDA, in fiscal year (FY) 2019. Based on information obtained from the 
FDA's database system, there were 103 manufacturers of biological 
products. This number excludes those manufacturers who produce Whole 
Blood, components of Whole Blood, or in-vitro diagnostic licensed 
products, because of the exemption under Sec.  600.80(m). The total 
annual responses are based on the number of submissions received by FDA 
in FY 2019. There were an estimated 169,334 15-day Alert reports, 
184,265 periodic reports, and 789 lot distribution reports submitted to 
FDA. The number of 15-day Alert reports for postmarketing studies under 
Sec.  600.80(e) is included in the total number of 15-day Alert 
reports. FDA received 63 requests from 40 manufacturers for waivers 
under Sec.  600.90 (including Sec. Sec.  600.80(h)(2) and 
600.81(b)(2)), of which 61 were granted. The hours per response are 
based on FDA experience. The burden hours required to complete the 
MedWatch Form (Form FDA 3500A) for Sec.  600.80(c)(1), (e), and (f) are 
reported under OMB control number 0910-0291.
    FDA estimates the burden of this collection of information as 
follows:

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                                 Table 1--Estimated Annual Reporting Burden \1\
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                                                     Number of                    Average burden
         21 CFR section              Number of     responses per   Total annual     per response    Total hours
                                    respondents     respondent       responses      (in hours)
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600.80(c)(1), 600.80(d),                     103        1,644.02         169,334               1         169,334
 600.80(e); postmarketing 15-day
 Alert Reports..................
600.82; notification of                       21            1.67              35               2              70
 discontinuance or interruption
 in manufacturing...............
600.80(c)(2) periodic adverse                103        1,788.98         184,265              28       5,159,420
 experience reports.............
600.81; distribution reports....             117           6.744             789               1             789
600.80(h)(2), 600.81(b)(2),                   40           1.575              63               1              63
 600.90; waiver requests........
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    Total.......................  ..............  ..............  ..............  ..............       5,329,676
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\1\ There are no capital costs or operating and maintenance costs associated with the information collection.

    In table 2 the number of respondents is based on the number of 
manufacturers subject to those regulations. Based on information 
obtained from FDA's database system, there were 212 licensed 
manufacturers of biological products in FY 2019. However, the number of 
recordkeepers listed for Sec.  600.12(a) through (e), excluding (b)(2), 
is estimated to be 109. This number excludes manufacturers of blood and 
blood components because their burden hours for recordkeeping have been 
reported under Sec.  606.160 in OMB control number 0910-0116. The total 
annual records is based on the annual average of lots released in FY 
2019 (6,670), number of recalls made (735), and total number of adverse 
experience reports received (305,951) in FY 2019. The hours per record 
are based on FDA experience.
    FDA estimates the burden of this recordkeeping as follows:

                               Table 2--Estimated Annual Recordkeeping Burden \1\
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                                                                                  Average burden
                                     Number of       Number of     Total annual         per
    21 CFR section; activity       recordkeepers    records per       records      recordkeeper     Total hours
                                                   recordkeeper                     (in hours)
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600.12 \2\; maintenance of                   109           61.19           6,670              32         213,440
 Records........................
600.12(b)(2); recall records....             212           3,467             735              24          17,640
600.80(c)(1) & 600.80(k); AER                103           3,433         353,599               1         353,599
 records........................
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    Total.......................  ..............  ..............  ..............  ..............         584,679
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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.   610.18(b) are included in the estimate for Sec.   600.12.

    The burden for this information collection has changed since the 
last OMB approval. The reporting and recordkeeping burden has increased 
mostly due to an increase in the number of AER reports submitted to FDA 
and the associated recordkeeping with these reports.

    Dated: August 26, 2020.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2020-19239 Filed 8-31-20; 8:45 am]
BILLING CODE 4164-01-P