Document ID: FDA-2011-N-0231-0013
Agency: fda
Document Type: Notice
Title: Agency Information Collection Activities; Submission for Office of Management and Budget Review;
Comment Request; Adverse Experience Reporting for Licensed Biological Products; and General Records
Posted Date: 2021-02-23T05:00Z

[Federal Register Volume 86, Number 34 (Tuesday, February 23, 2021)]
[Notices]
[Pages 10975-10977]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2021-03541]

[[Page 10975]]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

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

Agency Information Collection Activities; Submission for Office 
of Management and Budget Review; 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 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 March 25, 2021.

ADDRESSES: To ensure that comments on the information collection are 
received, OMB recommends that written comments be submitted to https://www.reginfo.gov/public/do/PRAMain. 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 0910-0308. 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, 
PRAStaff@fda.hhs.gov.

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.

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 its Adverse 
Experience Reporting System (FAERS) 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 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 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.
    FAERS 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.

[[Page 10976]]

    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, 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 the 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.
    In the Federal Register of September 1, 2020 (85 FR 54385), we 
published a 60-day notice requesting public comment on the proposed 
collection of information. One comment was received but was not 
responsive to the information collection topics solicited.
    We estimate the burden of the collection of information as follows:

                                  Table 1--Estimated Annual Reporting Burden 1
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                                                                                      Average
                                     Number of       Number of     Total annual     burden per
         21 CFR section             respondents    responses per     responses     response  (in    Total hours
                                                    respondent                        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 (FAERS).....
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.

                                Table 2--Estimated Annual Recordkeeping Burden 1
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                                                                                      Average
                                     Number of       Number of     Total annual     burden 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) and 600.80(k);                  103           3,433         353,599               1         353,599
 FAERS records..................
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[[Page 10977]]

 
    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 FAERS reports submitted to 
FDA and the associated recordkeeping with these reports.

    Dated: February 16, 2021.
Lauren K. Roth,
Acting Principal Associate Commissioner for Policy.
[FR Doc. 2021-03541 Filed 2-22-21; 8:45 am]
BILLING CODE 4164-01-P