Document ID: FDA-2011-N-0231-0007
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: 2014-10-29T04:00Z

[Federal Register Volume 79, Number 209 (Wednesday, October 29, 2014)]
[Notices]
[Pages 64392-64394]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2014-25637]

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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) 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 
November 28, 2014.

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, OMB, Attn: FDA Desk Officer, 
FAX: 202-395-7285, or emailed to oira_submission@omb.eop.gov. 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: FDA PRA Staff, Office of Operations, 
Food and Drug Administration, 8455 Colesville Rd., COLE-14526, Silver 
Spring, MD 20993-0002, 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 (PHS) 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 insure 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.\1\
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    \1\ Please note that throughout the regulations referenced in 
relation to these information collections, licensed biological 
products refers to biologics licensed under any provision of section 
351 of the PHS Act.
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    The primary purpose of FDA's AER system is to identify potentially 
serious safety problems with licensed biological products. Although the 
premarket approval process is meant to disclose 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 follow-up 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 a 
person who submits an adverse action report to the licensed 
manufacturer, rather than FDA, to 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(i) 
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

[[Page 64393]]

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.  600.90, 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 must 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) requires, in part, that the 
results of all periodic tests for verification of cultures and 
determination of freedom from extraneous organisms be recorded and 
maintained. The recordkeeping requirements for Sec. Sec.  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 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) 2013. Based on 
information obtained from FDA's database system, there were 131 
licensed biologics manufacturers. This number excludes those 
manufacturers who produce Whole Blood or components of Whole Blood and 
in vitro diagnostic licensed products, because of the exemption under 
Sec.  600.80(k). The total annual responses are based on the number of 
submissions received by FDA in FY 2013. There were an estimated 92,470 
15-day Alert reports, 132,667 periodic reports, and 334 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 64 requests from 
35 manufacturers for waivers under Sec.  600.90, of which 63 were 
granted. The hours per response are based on FDA experience. The burden 
hours required to complete the MedWatch Form for Sec.  600.80(c)(1), 
(e), and (f) are reported under OMB control number 0910-0291.
    In the Federal Register of April 7, 2014 (79 FR 19097), FDA 
published a 60-day notice requesting public comment on the proposed 
collection of information. FDA received one comment; however, this 
comment did not address the information collection.
    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
         21 CFR section              Number of     responses per   Total annual     burden per      Total hours
                                    respondents     respondent       responses       response
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600.80(c)(1) and 600.80(e)......             131          705.88          92,470               1          92,470
600.80(c)(2)....................             131        1,012.73         132,667              28       3,714,676
600.81..........................             131            2.55             334               1             334
600.90..........................              35            1.83              64               1              64
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    Total.......................  ..............  ..............  ..............  ..............       3,807,544
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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 334 licensed 
manufacturers of biological products in FY 2013. However, the number of 
recordkeepers listed for Sec.  600.12(a) through (e) excluding (b)(2) 
is estimated to be 164. 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 
2013 (6,887), number of recalls made (1,679), and total number of 
adverse experience reports received (225,137) in FY 2013. 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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                                                     Number of                        Average
         21 CFR section              Number of      records per    Total annual     burden per      Total hours
                                   recordkeepers   recordkeeper       records      recordkeeping
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600.12 \2\......................             164           41.99           6,887              32         220,384
600.12(b)(2)....................             334            5.03           1,679              24          40,296

[[Page 64394]]

 
600.80(c)(1) and 600.80(i)......             131        1,718.60         225,137               1         225,137
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    Total.......................  ..............  ..............  ..............  ..............         485,817
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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.

    Dated: October 23, 2014.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2014-25637 Filed 10-28-14; 8:45 am]
BILLING CODE 4164-01-P