[Federal Register: December 26, 2000 (Volume 65, Number 248)]
[Notices]               
[Page 81528-81530]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr26de00-67]                         

=======================================================================
-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 00N-1502]

 
Agency Information Collection Activities; Submission for OMB 
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 the 
proposed collection of information listed below has been submitted to 
the Office of Management and Budget (OMB) for review and clearance 
under the Paperwork Reduction Act of 1995.

DATES: Submit written comments on the collection of information by 
January 25, 2001.

ADDRESSES: Submit written comments on the collection of information to 
the Office of Information and Regulatory Affairs, OMB, New Executive 
Office Bldg., 725 17th St. NW., rm. 10235, Washington, DC 20503, Attn: 
Wendy Taylor, Desk Officer for FDA.

FOR FURTHER INFORMATION CONTACT: JonnaLynn P. Capezzuto, Office of 
Information Resources Management (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.

[[Page 81529]]

Adverse Experience Reporting for Licensed Biological Products; and 
General Records--21 CFR 600.12 and Part 600 Subpart D (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 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 new 
drug'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 ensure the 
manufacturer has taken adequate corrective action if necessary.
    Section 600.80(c)(1) (21 CFR 600.80(c)(1)) requires the licensed 
manufacturer to report each adverse experience that is both serious and 
unexpected, regardless of source, as soon as possible but in any case 
within 15 working days of initial receipt of the information. Section 
600.80(e) requires licensed manufacturers to submit a 15-day alert 
report 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 the licensed manufacturer to report each 
adverse experience not reported under paragraph (c)(1) at quarterly 
intervals, for 3 years from the date of issuance of the product 
license, and then at annual intervals. The majority of the periodic 
reports will be submitted annually since a large percentage of the 
current licensed biological products have been licensed longer than 3 
years. Section 600.80(i) requires the licensed manufacturer 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 (21 CFR 600.81) 
requires the licensed manufacturer to submit information about the 
quantity of the product distributed under the product license, 
including the quantity distributed to distributors at an interval of 
every 6 months. The semiannual distribution report informs FDA of the 
quantity, the lot number, and the dosage of different products. Section 
600.90 (21 CFR 600.90) requires a licensed manufacturer to submit a 
waiver request with supporting documentation when asking for waiving 
the requirement that applies to them under Secs. 600.80 and 600.81.
    Manufacturers of biological products for human use must keep 
records of each step in the manufacture and distribution of products 
including recalls of the product. The recordkeeping requirements serve 
preventative and remedial purposes. These requirements establish 
accountability and traceability in the manufacture and distribution of 
products, and enable FDA to perform meaningful inspections.
    Section 600.12 (21 CFR 600.12) requires 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, 
records of sterilization of equipment and supplies, animal necropsy 
records, and records in cases of divided manufacturing of a product are 
required to be maintained. Section 600.12(b)(2) requires complete 
records to be maintained pertaining to the recall from distribution of 
any product.
    Respondents to this information collection are manufacturers of 
biological products. In fiscal year (FY) 99 there were approximately 79 
licensed manufacturers. This number excludes those manufacturers who 
produce blood and blood components and in vitro diagnostic licensed 
products because they are specifically exempt from the regulations. 
However, not all manufacturers may have any submissions in a given year 
and some may have multiple submissions. FDA received four waiver 
requests under Sec. 600.90, of which one was approved for exemption of 
the AER requirements. In FY 99, there were an estimated 3,662 15-day 
alert reports, 13,238 periodic reports, and 502 distribution reports 
submitted to FDA. The number of 15-day alert reports for postmarketing 
studies as stated in Sec. 600.80(e) was minimal and is included in the 
total number of 15-day alert reports. 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 September 25, 2000 (65 FR 57612), the 
agency requested comments on the proposed collection of information. No 
significant comments were received.

                                 Table 1.--Estimated Annual Reporting Burden\1\
----------------------------------------------------------------------------------------------------------------
   21 CFR                                Annual Frequency    Total Annual
  Section        No. of Respondents        per Response       Responses      Hours per Response    Total Hours
----------------------------------------------------------------------------------------------------------------
600.80(c)(1                         78              46.95            3,662                    1            3,662
 ) and (e)
600.80(c)(2                         78             169.72           13,238                    1           13,238
 )
600.81                              78                6.4              502                    1              502
600.90                               4                  1                4                    1                4
¬¬¬¬¬¬¬¬¬¬¬¬
----------------------------------------------------------------------------------------------------------------
\1\There are no capital costs or operating and maintenance costs associated with this collection of information.

    There are approximately 343 licensed manufacturers of biological 
products. However, the number of recordkeepers listed for 
Sec. 600.12(a) through (e) excluding paragraph (b)(2) is estimated to 
be 111. This number excludes

[[Page 81530]]

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 recordkeeping burden is based on the number of lots 
released (6,446), the number of recalls made (1,176), and the total 
number of AER reports received (16,900) for FY 99. 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\
----------------------------------------------------------------------------------------------------------------
   21 CFR                                Annual Frequency    Total Annual        Hours per
  Section       No. of Recordkeepers     of Recordkeeping      Records          Recordkeeper       Total Hours
----------------------------------------------------------------------------------------------------------------
600.12                             111               58.1            6,446                   32          206,272
600.12(b)(2                        343                3.4            1,176                   24           28,224
 )
600.80(i)                           79             213.92           16,900                    1           16,900
¬¬¬¬¬¬¬¬¬¬¬¬
----------------------------------------------------------------------------------------------------------------
\1\There are no capital costs or operating and maintenance costs associated with this collection of information.


    Dated: December 18, 2000.
Margaret M. Dotzel,
Associate Commissioner for Policy.
[FR Doc. 00-32783 Filed 12-22-00; 8:45 am]
BILLING CODE: 4160-01-S