[Federal Register Volume 64, Number 46 (Wednesday, March 10, 1999)]
[Notices]
[Pages 11920-11922]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-5904]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 98N-0482]
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 (the PRA).
DATES: Submit written comments on the collection of information by
April 9, 1999.
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:
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 section 3507 of the PRA
(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--21 CFR
600.80, 600.81, and 600.90; and General Records--21 CFR 600.12 (OMB
Control Number 0910-0308)--Extension
Under the Federal Food, Drug, and Cosmetic Act (the act) (21
U.S.C. 201 et seq.) and the Public Health Service Act (42 U.S.C. 262
and 264), FDA is required to ensure the marketing of only those
biological products that are shown to be safe and effective. Under the
authority of section 301(e) of the act (21 U.S.C. 331(e)), FDA issued
regulations for adverse experience reports related to the use of
licensed biological products. FDA issued the adverse experience
reporting 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 adverse
experience reporting system flags 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
adverse experience reporting 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.
Manufacturers of biological products for human use must also keep
records of each step in the manufacture and distribution of products
including any 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.
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
[[Page 11921]]
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 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 (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.
In the Federal Register of July 10, 1998 (63 FR 37394), a 60-day
notice for public comment on the information collection provisions was
published. Two comments were received in response to the 60-day notice.
Both comments agreed there is practical value in this proposed
collection of information. However they questioned the estimate of the
annual responses and provided estimates of burden hours for
Sec. 600.80(c)(2). Based on these comments and further internal
research, the estimated annual reporting burden has been revised as
follows. A periodic report submitted under Sec. 600.80(c)(2) may
include one or more, even hundreds, of individual MedWatch and Vaccine
Adverse Event Reporting System (VAERS)-1 Forms. These forms are
attached to the report. The original estimate of periodic reports
(5,903) included the number of individual attached forms, whereas the
current estimate (1,129) reflects only the number of periodic reports
received regardless of the number of attachments. More than half of
these reports are monthly reports on plasma derivatives that should
take on the average 2 hours each to complete. The balance of the
reports are quarterly and annual reports that may each require an
average of 28 hours to prepare. 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. The VAERS-1 Form is exempt from
compliance with paperwork reduction requirements under the National
Childhood Vaccine Injury Act (42 U.S.C. 300aa-1) (section 321 of Pub.
L. 99-660).
Both comments questioned the statement that there are no capital,
operating, or maintenance costs associated with maintaining records of
adverse experience reports for 10 years. FDA believes there are no
maintenance costs associated with the storage/retention of records
because respondents already have the facilities and the infrastructure
for ongoing record retention, and that existing and emerging data
storage technology minimizes space and costs of long-term record
retention.
Both comments recommended ways to enhance the quality, utility,
and clarity of the information to be collected, and to minimize the
burden of the collection of information on the respondents. FDA is in
the process of revising its safety reporting and recordkeeping
regulations and will consider these comments in developing its
rulemaking. FDA has provided notice and requested comments on several
proposed rules. In the Federal Register of October 27, 1994 (59 FR
54046), FDA published a proposed rule to amend its postmarketing
expedited and periodic safety reporting requirements, as well as
others, to implement international standards and to facilitate the
reporting of adverse drug experiences. In the Federal Register of
October 27, 1997 (62 FR 52237), FDA published a final rule amending its
expedited safety reporting regulations to implement certain
recommendations in the International Conference on Harmonization of
Technical Requirements for Registration of Pharmaceuticals for Human
Use (ICH) E2A guidance on definitions and standards for expedited
reporting (58 FR 37408, July 9, 1993). At this time, the agency is
further considering recommendations in the ICH E2A guidance for
additional amendments to its postmarketing expedited safety reporting
regulations. With respect to the proposed amendments to the periodic
adverse drug experience reporting requirements in the proposal of
October 27, 1994, FDA has decided to repropose these amendments based
on recommendations in the ICH E2C guidance on periodic safety update
reports (62 FR 27470, May 19, 1997). In developing the reproposal, FDA
will also consider comments submitted in response to the proposed rule
of October 27, 1994, regarding periodic adverse experience reports. FDA
is also considering rulemaking concerning the electronic submission of
postmarketing expedited and periodic safety reports using standardized
medical terminology, data elements, and electronic transmission
standards recommended by ICH. The respondents to the collection of
information discussed here will, therefore, have further opportunity to
provide comment on these rulemaking initiatives.
Description of Respondents: Respondents to this collection of
information are manufacturers of biological products.
Reporting Burden: The total number of respondents in the chart, is
based upon information submitted to FDA in fiscal year (FY) 1996, which
shows that 69 licensed manufacturers (excluding 3 manufacturers who
received waivers from Adverse Event Reporting (AER) requirements,
produced 242 licensed biological products. The 69 licensed
manufacturers excludes those manufacturers who only produce blood and
blood components or in vitro diagnostic licensed products and are
exempt from the AER regulations. In FY 1996, licensed manufacturers
submitted approximately 1,616 15-day alert reports under
Sec. 600.80(c)(1) and (e); 1,129 periodic reports under
Sec. 600.80(c)(2); and 464 distribution reports under Sec. 600.81. The
MedWatch Form that is used to submit the information provided under
Sec. 600.80(c)(1), (e), and (f) has received approval under OMB Control
No. 0910-0291.
Table 1.--Estimated Annual Reporting Burden1
----------------------------------------------------------------------------------------------------------------
Annual
21 CFR Section No. of Frequency per Total Annual Hours per Total Hours
Respondents Response Responses Response
----------------------------------------------------------------------------------------------------------------
600.80(c)(1) and (e) 69 23.4 1,616 1 1,616
600.80(c)(2) 69 16.4 1,129 28 31,612
[[Page 11922]]
600.81 69 6.7 464 1 464
600.90 3 1 3 1 3
Total 33,695
----------------------------------------------------------------------------------------------------------------
\1\There are no capital costs or operation and maintenance costs associated with this collection of information.
Recordkeeping Burden: There are approximately 391 licensed
manufacturers of biological products. The number of recordkeepers under
Sec. 600.12(a), (c), (d), and (e) is estimated to be 102. That number
excludes the 189 manufacturers of blood and blood components whose
recordkeeping is conducted under 21 CFR 606.160, which is approved
under OMB Control No. 0910-0116. FDA expects that the total number of
AER records kept by the respondent will parallel the total number of
reports submitted to FDA. The total number of annual records,
therefore, is based on reporting information provided to FDA by
manufacturers. Based on FY 1996 data, the total annual records are
estimated as follows: Under Sec. 600.12(a), (c), (d), and (e), the
number of lots released was 9,027; under Sec. 600.12(b)(2), the number
of recalls was 710; and under Sec. 600.80(i), the total number of AER
reports received was 2,745. Based on FDA's experience, the agency
estimates that the total number of hours per recordkeeper under
Sec. 600.12(a), (c), (d), and (e) would be 32 hours per lot multiplied
by 88.5 lot records on the average per recordkeeper, totaling 2,832
hours; the total number of hours per recordkeeper under
Sec. 600.12(b)(2) would be 24 hours per recall multiplied by 1.8
recalls on the average per recordkeeper, totaling 43 hours; and the
total number of hours per recordkeeper under Sec. 600.80(i) would be 1
hour per report multiplied by 39.8 AER records on the average per
recordkeeper, totaling 40 hours.
Table 2.--Estimated Annual Recordkeeping Burden1
----------------------------------------------------------------------------------------------------------------
Annual
21 CFR Section No. of Frequency per Total Annual Hours per Total Hours
Recordkeepers Recordkeeping Records Recordkeeper
----------------------------------------------------------------------------------------------------------------
600.12(a), (c), (d) and (e) 102 88.5 9,027 2,832 288,864
600.12(b)(2) 391 1.8 710 43 16,813
600.80(i) 69 39.8 2,745 40 2,760
Total 308,437
----------------------------------------------------------------------------------------------------------------
\1\There are no capital costs or operation and maintenance costs associated with this collection of information.
Dated: March 4, 1999.
William K. Hubbard,
Acting Deputy Commissioner for Policy.
[FR Doc. 99-5904 Filed 3-9-99; 8:45 am]
BILLING CODE 4160-01-F
