[Federal Register Volume 76, Number 77 (Thursday, April 21, 2011)]
[Pages 22401-22404]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2011-9651]



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.


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 (AER) for licensed biological products, 
and general records associated with the manufacture and distribution of 
biological products.

[[Page 22402]]

DATES: Submit either written or electronic comments on the collection 
of information by June 20, 2011.

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:  Juanmanuel Vilela, Office of 
Information Management, Food and Drug Administration, 1350 Piccard Dr., 
PI50-400B, Rockville, MD 20850, 301-796-7651, [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)--

    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 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 the AERS system 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 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., fifty thousand 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 
    Manufacturers of biological products for human use must keep 
records of each step in the manufacture and distribution of a product 
including any

[[Page 22403]]

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.
    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. Under table 1 of this document, 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) 
2010. Based on information obtained from the FDA's database system, 
there were 108 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 2010. There were an 
estimated 86,583 15-day Alert reports, 57,300 periodic reports, and 349 
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 21 requests for 
waivers under Sec.  600.90, of which 19 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 No. 0910-0291.
    FDA estimates the burden of this collection of information as 

                                 Table 1--Estimated Annual Reporting Burden \1\
                                                     Number of                    Average burden
         21 CFR section              Number of     responses per   Total annual    per  response    Total hours
                                    respondents     respondent       responses      (in hours)
600.80(c)(1) and 600.80(e)......             108          801.69          86,583               1          86,583
600.80(c)(2)....................             108          530.55          57,300              28       1,604,400
600.81..........................             108            3.23             349               1             349
600.90..........................              21               1              21               1              21
    Total.......................  ..............  ..............  ..............  ..............       1,691,353
\1\ There are no capital costs or operating and maintenance costs associated with this collection of

    Under table 2 of this document, 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 304 
licensed manufacturers of biological products in FY 2010. However, the 
number of recordkeepers listed for Sec.  600.12(a) through (e) 
excluding (b)(2) is estimated to be 131. 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 
No. 0910-0116. The total annual records is based on the annual average 
of lots released in FY 2010 (6,752), number of recalls made (1,881), 
and total number of adverse experience reports received (143,883) in FY 
2010. 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\
                                                                                  Average burden
                                     Number of       Number of     Total annual         per
         21 CFR section            recordkeepers    records per       records      recordkeeping    Total hours
                                                   recordkeeper                     (in hours)
600.12 \2\......................             131           51.54           6,752              32         216,064
600.12 (b)(2)...................             304            6.19           1,881              24          45,144
600.80(c)(1) and 600.80(i)......             108        1,332.25         143,883               1         143,883
    Total.......................  ..............  ..............  ..............  ..............         405,091
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
\2\ The recordkeeping requirements in Sec.   610.18(b) are included in the estimate for Sec.   600.12.

[[Page 22404]]

    Dated: April 15, 2011.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2011-9651 Filed 4-20-11; 8:45 am]