[Federal Register: April 20, 2005 (Volume 70, Number 75)]
[Page 20571-20573]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]



Food and Drug Administration

[Docket No. 2004N-0469]

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 May 20, 

ADDRESSES: OMB is still experiencing significant delays in the regular 
mail, including first class and express mail, and messenger deliveries 
are not being accepted. To ensure that comments on the information 
collection are received, OMB recommends that written

[[Page 20572]]

comments be faxed to the Office of Information and Regulatory Affairs, 
OMB, Attn: Fumie Yokota, Desk Officer for FDA, FAX: 202-395-6974.

FOR FURTHER INFORMATION CONTACT: Jonna Capezzuto, Office of Management 
Programs (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 that 
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 the licensed 
manufacturer 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 and 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 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 Sec.  600.80(c)(1)(i) 
at quarterly intervals, for 3 years from the date of issuance of the 
biologics 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 
requires the licensed manufacturer to submit information about the 
quantity of the product distributed under the biologics license, 
including the quantity distributed to distributors at an interval of 
every 6 months. The semiannual distribution report informs FDA of the 
quantity, certain lot numbers, labeled date of expiration, the number 
of doses, and date of release. Under Sec.  600.90, a licensed 
manufacturer may submit a waiver request that applies to the licensed 
manufacturer under Sec.  Sec.  600.80 and 600.81. A waiver request 
submitted under Sec.  600.90 must be submitted with supporting 
    Manufacturers of biological products for human use must keep 
records of each step in the manufacture and distribution of products 
including the 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 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 collection of information are manufacturers of 
biological products. In table 1 of this document, the number of 
respondents is based on the estimated number of manufacturers that 
submitted the required information to FDA in fiscal year (FY) 2002 and 
2003. Based on information obtained from the Center for Biologics 
Evaluation and Research's (CBER's) database system, there were 90 
licensed biologics manufacturers. This number excludes those 
manufacturers who produce blood and blood components and in-vitro 
diagnostic licensed products because these products are specifically 
exempt from the regulations under Sec.  600.80(k). The total annual 
responses are based on the average estimated number of submissions 
received annually by FDA for FY 2002 and 2003. However, not all 
manufacturers have submissions in a given year and some may have 
multiple submissions. There were an estimated 15,126 15-day alert 
reports, 6,550 periodic reports, and 323 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 an average of five waiver requests for FY 
2002 and 2003 under Sec.  600.90, all of which were approved for 
exemption of the AER requirements. The hours per response are based on 
FDA's 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 November 3, 2004 (69 FR 64069), FDA 
published a 60-day notice requesting public comment on the information 
collection provisions. No comments were received.

[[Page 20573]]

                                 Table 1.--Estimated Annual Reporting Burden\1\
                         No. of        Annual Frequency     Total Annual        Hours per
  21 CFR Section      Respondents        per Response        Responses          Respondent        Total Hours
600.80(c)(1) and                  90             168.07             15,126                  1             15,126
600.80(c)(2)                      90              72.78              6,550                 28            183,400
600.81                            90               3.59                323                  1                355
600.90                             5                  1                  5                  1                  5
Total                                                                                                    198,886
\1\ There are no capital costs or operating and maintenance costs associated with this collection of

                               Table 2.--Estimated Annual Recordkeeping Burden\1\
                        No. of        Annual Frequency      Total Annual        Hours per
 21 CFR Section     Recordkeepers        per Record           Records          Recordkeeper       Total Hours
600.12                          116               57.16              6,630                 32            212,160
600.12(b)(2)                    320                6.12              1,958                 24             46,992
600.80(i)                        90              394.27             35,484                  1             35,484
Total                                                                                                    294,636
\1\There are no capital costs or operating and maintenance costs associated with this collection of information.

    Dated: April 13, 2005.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 05-7824 Filed 4-19-05; 8:45 am]