Document ID: FDA-2011-N-0231-0003
Agency: fda
Document Type: Notice
Title: Agency Information Collection Activities; Proposals, Submissions, and Approvals: Adverse Experience Reporting for Licensed Biological Products; and General Records
Posted Date: 2011-07-14T04:00Z

[Federal Register Volume 76, Number 135 (Thursday, July 14, 2011)]
[Notices]
[Pages 41504-41506]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2011-17675]

-----------------------------------------------------------------------

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.

-----------------------------------------------------------------------

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 August 
15, 2011.

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 e-mailed 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: Juanmanuel Vilela, Office of 
Information Management, Food and Drug Administration, 1350 Piccard Dr., 
PI50-400B, Rockville, MD 20850, 301-796-7651, 
juanmanuel.vilela@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 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 the 
AER 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

[[Page 41505]]

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., 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) (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 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 post marketing 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 number 0910-0291.
    In the Federal Register of April 21, 2011 (77 FR 22401), FDA 
published a 60-day notice requesting public comment on the proposed 
collection of information. No comments were received from the public.
    FDA estimates the burden of this collection of information as 
follows:

                                 Table 1--Estimated Annual Reporting Burden \1\
----------------------------------------------------------------------------------------------------------------
                                                     Number of                        Average
         21 CFR Section              Number of     responses per   Total annual     burden per      Total hours
                                    respondents     respondent       responses       response
----------------------------------------------------------------------------------------------------------------
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
  information.

    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 
number 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:

[[Page 41506]]

                               Table 2--Estimated Annual Recordkeeping Burden \1\
----------------------------------------------------------------------------------------------------------------
                                                     Number of                        Average
         21 CFR Section              Number of      records per    Total annual     burden per      Total hours
                                   recordkeepers   recordkeeper       records      recordkeeping
----------------------------------------------------------------------------------------------------------------
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
  information.
\2\ The recordkeeping requirements in Sec.   610.18(b) are included in the estimate for Sec.   600.12.

    Dated: July 8, 2011.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2011-17675 Filed 7-13-11; 8:45 am]
BILLING CODE 4160-01-P