Document ID: FDA-2011-N-0231-0005
Agency: fda
Document Type: Notice
Title: Agency Information Collection Activities; Proposed Collection;
Comment Request; Adverse Experience Reporting for Licensed
Biological Products; and General Records
Posted Date: 2014-04-07T04:00Z

[Federal Register Volume 79, Number 66 (Monday, April 7, 2014)]
[Notices]
[Pages 19097-19099]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2014-07711]

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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) is announcing an 
opportunity for public comment on the proposed collection of certain 
information by the Agency. Under the Paperwork Reduction Act of 1995 
(the 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 (AERS) 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 June 6, 2014.

ADDRESSES: Submit electronic comments on the collection of information 
to http://www.regulations.gov. Submit written comments on the 
collection of information to the Division of Dockets Management (HFA-
305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, 
Rockville, MD 20852. All comments should be identified with the 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, 1350 Piccard Dr., PI50-400B, Rockville, 
MD 20850, PRAStaff@fda.hhs.gov.

SUPPLEMENTARY INFORMATION: Under the PRA (44 U.S.C. 3501-3520), 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 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. The primary purpose of FDA's AER system 
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 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

[[Page 19098]]

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 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.
    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:

[[Page 19099]]

                                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
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: April 1, 2014.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2014-07711 Filed 4-4-14; 8:45 am]
BILLING CODE 4160-01-P