[Federal Register Volume 79, Number 66 (Monday, April 7, 2014)]
[Notices]
[Pages 19097-19099]
From the Federal Register Online via the Government Publishing 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, [email protected].
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