[Federal Register Volume 73, Number 96 (Friday, May 16, 2008)]
[Pages 28486-28488]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E8-11057]



Food and Drug Administration

[Docket No. FDA-2008-N-0073]

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 June 
16, 2008.

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: 202-395-6974, or e-mailed to [email protected]. 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 

FOR FURTHER INFORMATION CONTACT: Jonna Capezzuto, Office of the Chief 
Information Officer (HFA-250), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-827-4659.

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--(OMB Control Number 0910-0308)--Extension

    Under the Public Health Service Act (42 U.S.C. 262), FDA is 
required to ensure the marketing of only those biological products 
which are safe and effective. FDA must, therefore, be informed of all 
adverse experiences occasioned by the use of licensed biological 
products. 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 flag 
potentially serious safety problems with licensed biological products, 
focusing especially on newly licensed 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. Reports are obtained from a variety of sources, including 
patients, physicians, foreign regulatory agencies, and clinical 
investigators. Information derived from the AER system contributes 
directly to increased public health protection because such information 
enables FDA to recommend important changes to the product's labeling 
(such as adding a new warning), to initiate removal of a biological 
product from the market when necessary, and to assure the manufacturer 
has taken adequate corrective action if necessary.
    The regulation in Sec.  600.80(c)(1) requires licensed 
manufacturers to report each adverse experience that is both serious 
and unexpected, whether

[[Page 28487]]

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 are known as postmarketing 15-day Alert reports. 
Section 600.80(c)(1) also requires licensed manufacturers to submit any 
followup reports within 15-calendar days of receipt of new information 
or as requested by FDA.
    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 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 will 
be submitted annually because 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 semiannual 
distribution reports provide FDA with important information about 
products distributed under biologics licenses, including the quantity, 
certain lot numbers, labeled date of expiration, number of dosage 
units, and date of release. Under Sec.  600.90, a licensed manufacturer 
may submit a waiver request for any requirements that applies to the 
licensed manufacturer under 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, concurrently with the 
performance of each step that all records of each step in the 
manufacture and distribution of a product be made and 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, manufacturers 
must maintain records of sterilization of equipment and supplies, 
animal necropsy records, and records in cases of divided manufacturing 
of a product. Section 600.12(b)(2) requires manufacturers to maintain 
complete records pertaining to the recall from distribution of any 
    Respondents to this collection of information are manufacturers of 
biological products. Under table 1 of this document, the number of 
respondents is based on the estimated number of manufacturers that 
submitted the required information to the Center for Biologics 
Evaluation and Research and Center for Drug Evaluation and Research, 
FDA, in fiscal year (FY) 2006. Based on information obtained from FDA's 
database system, there were 88 licensed biologics manufacturers. This 
number excludes those manufacturers who produce blood and blood 
components and in-vitro diagnostic licensed products, because Sec.  
600.80(k) specifically exempts manufacturers of these products from 
adverse experience reporting requirements. The total annual responses 
are based on the estimated number of submissions received annually by 
FDA in FY 2006. However, not all manufacturers have submissions in a 
given year and some may have multiple submissions. There were an 
estimated 23,835 15-day Alert reports, 21,872 periodic reports, and 179 
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 6 requests for 
waiver under Sec.  600.90, all of which 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.
    In the Federal Register of February 15, 2008 (73 FR 8881), FDA 
published a 60-day notice requesting public comment on the information 
collection provisions. No comments were received.

                                 Table 1.--Estimated Annual Reporting Burden\1\
                      No. of         Annual Frequency       Total Annual        Hours per
21 CFR Section     Respondents         per Response          Responses           Response         Total Hours
600.80(c)(1)                   88                270.85             23,835                  1             23,835
 and 600.80(e)
600.80(c)(2)                   88                248.55             21,872                 28            612,416
600.81                         88                  2.03                179                  1                179
600.90                          6                  1                     6                  1                  6
Total                                                                                                    636,436
\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 303 
licensed manufacturers of biological products in FY 2006. However, the 
number of recordkeepers listed for Sec.  600.12(a) through (e) 
excluding (b)(2) is estimated to be 112. This number excludes 
manufacturers of blood and blood components because their burden hours 
for recordkeeping have been reported under 21 CFR 606.160 in OMB 
control no. 0910-0116. The total annual records is based on the annual 
average of lots released (5,291), number of recalls made (1,841), and 
total number of adverse experience reports received (45,707) in FY 
2006. The hours per record are based on FDA experience.
    FDA estimates the burden of this recordkeeping as follows:

[[Page 28488]]

                               Table 2.--Estimated Annual Recordkeeping Burden\1\
                      No. Of         Annual Frequency       Total Annual
21 CFR Section    Recordkeepers      per Recordkeeping        Records       Hours per  Record     Total Hours
600.12                        112                 47.24              5,291                 32            169,312
600.12(b)(2)                  303                  6.08              1,841                 24             44,184
600.80(i)                      88                519.40             45,707                  1             45,707
Total                                                                                                    259,203
\1\ There are no capital costs or operating and maintenance costs associated with this collection of

    Dated: May 13, 2008.
Jeffrey Shuren,
Associate Commissioner for Policy and Planning.
[FR Doc. E8-11057 Filed 5-15-08; 8:45 am]