Document ID: FDA-2011-N-0231-0009
Agency: fda
Document Type: Notice
Title: Agency Information Collection Activities; Submission for Office of Management and Budget Review; Adverse Experience Reporting for Licensed Biological Products; and General Records
Posted Date: 2018-01-08T05:00Z

[Federal Register Volume 83, Number 5 (Monday, January 8, 2018)]
[Notices]
[Pages 819-821]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-00095]

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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; 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: Fax written comments on the collection of information by 
February 7, 2018.

ADDRESSES: To ensure that comments on the information collection are 
received, OMB recommends that written comments be faxed to the Office 
of Information and Regulatory Affairs,

[[Page 820]]

OMB, Attn: FDA Desk Officer, Fax: 202-395-7285, or emailed to 
[email protected]. All comments should be identified with the 
OMB control number 0910-0308. Also include the FDA docket number found 
in brackets in the heading of this document.

FOR FURTHER INFORMATION CONTACT: Ila S. Mizrachi, Office of Operations, 
Food and Drug Administration, Three White Flint North, 10A-12M, 11601 
Landsdown St., North Bethesda, MD 20852, 301-796-7726, 
[email protected].

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 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 AERS 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. 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 AERS 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.  600.80(h)(1) and (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

[[Page 821]]

retained. The recordkeeping requirements for Sec. Sec.  610.12(g), 
610.13(a)(2), 610.18(d), 21 CFR 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) 2016. Based on information obtained from the 
FDA's database system, there were 93 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 2016. There were an estimated 125,371 15-day Alert reports, 
180,580 periodic reports, and 677 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 81 requests from 40 manufacturers for waivers 
under Sec.  600.90 (including Sec. Sec.  600.80(h)(2) and 
600.81(b)(2)), of which 79 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 July 18, 2017 (82 FR 32836), FDA 
published a 60-day notice requesting public comment on the proposed 
collection of information. No comments were received.
    FDA estimates the burden of this collection of information as 
follows:

                                                     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 (in     Total hours
                                                              respondents         respondent         responses            hours)
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600.80(c)(1), 600.80(d), and 600.80(e); postmarketing 15-                 93           1,348.07            125,371                  1            125,371
 day Alert reports.......................................
600.82; notification of discontinuance or interruption in                 18               1.61                 29                  2                 58
 manufacturing...........................................
600.80(c)(2); periodic adverse experience reports........                 93           1,941.72            180,580                 28          5,056,240
600.81 Distribution Reports..............................                 93               7.28                677                  1                677
600.80(h)(2), 600.81(b)(2), and 600.90; waiver requests..                 40               2.03                 81                  1                 81
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    Total................................................  .................  .................  .................  .................          5,182,427
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.

    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 263 licensed 
manufacturers of biological products in FY 2016. However, the number of 
recordkeepers listed for Sec.  600.12(a) through (e) excluding (b)(2) 
is estimated to be 114. 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 
2016 (7,198), number of recalls made (575), and total number of adverse 
experience reports received (305,951) in FY 2016. 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            recordkeepers    records per       records      recordkeeper     Total hours
                                                   recordkeeper                     (in hours)
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600.12 \2\; maintenance of                   114           63.14           7,198              32         230,336
 records........................
600.12(b)(2); recall records....             263            2.19             575              24          13,800
600.80(c)(1) and 600.80(k)......              93        3,289.79         305,951               1         305,951
                                 -------------------------------------------------------------------------------
    Total.......................  ..............  ..............  ..............  ..............         550,087
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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. Because of an increase in the number of AER reports 
we have received during the past 3years, we have increased our 
reporting and recordkeeping burden estimates.

    Dated: January 2, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-00095 Filed 1-5-18; 8:45 am]
 BILLING CODE 4164-01-P