[Federal Register: December 31, 2003 (Volume 68, Number 250)]
[Notices]
[Page 75572-75574]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr31de03-99]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 2003N-0268]
Agency Information Collection Activities; Submission for Office
of Management and Budget Review; Comment Request; Biological Products:
Reporting of Biological Product Deviations in Manufacturing
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
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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 January
30, 2004.
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 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: JonnaLynn P. 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.
Biological Products: Reporting of Biological Product Deviations in
Manufacturing--(OMB Control Number 0910-0458)--Extension
Under section 351 of the Public Health Service Act (42 U.S.C. 262),
all biological products, including human blood and blood components,
offered for sale in interstate commerce must be licensed and meet
standards designed to ensure the continued safety, purity, and potency
of such products. In addition, section 501 of the Federal Food, Drug,
and Cosmetic Act (the act) (21 U.S.C. 351) provides that drugs and
devices (including human blood and blood components) are adulterated if
they do not conform with current good manufacturing practice (CGMP)
assuring that they meet the requirements of the act. All establishments
manufacturing human blood and blood components are required to register
with FDA, and comply with the CGMP regulations for human blood and
blood components (parts 211 and 606 (21 CFR parts 211 and 606)).
Transfusion services are required under 42 CFR 493.1273(a) to comply
with part 606 and 21 CFR part 640 as they pertain to the performance of
manufacturing activities. FDA regards biological product deviation
reporting to be an essential tool in its directive to protect public
health by establishing and maintaining surveillance programs that
provide timely and useful information. Section 600.14 (21 CFR 600.14)
requires the licensed manufacturer who holds the biological product
license, for other than human blood and blood components, and who had
control over the product when the deviation occurred, to report to the
Center for Biologics Evaluation and Research (CBER) as soon as possible
but not to exceed 45 calendar days after acquiring information
reasonably suggesting that a reportable event has occurred. Section
606.171 requires a licensed manufacturer of human blood and blood
components, including Source Plasma; an unlicensed registered blood
establishment; or a transfusion service who had control over the
product when the deviation occurred, to report to CBER as soon as
possible but not to exceed 45 calendar days after acquiring information
reasonably suggesting that a reportable event has occurred. Respondents
to this collection of information are the licensed manufacturers of
biological products other than human blood and blood components,
unlicensed registered blood establishments, and transfusion services.
Based on information from CBER's databases for fiscal year (FY) 2002,
there were 115 licensed manufacturers of biological products other than
human blood and blood components, 207 licensed manufacturers of human
blood and blood components, including Source Plasma, and 2,800
unlicensed registered blood establishments and 3,221 transfusion
services. However, not all manufacturers or establishments may have any
submissions in a given year and some may have multiple submissions. In
the same FY, CBER's database also showed that the licensed
manufacturers of biological products other than human blood and blood
components submitted 476 biological product deviation reports (BPDRs)
under Sec. 600.14, the licensed manufacturers of human blood and blood
components, including Source Plasma submitted 27,000 BPDRs under Sec.
606.171, and the unlicensed registered blood establishments and
transfusion services submitted a total of 6,446 BPDRs. The number of
total annual responses is based on the number of BPDRs CBER received in
FY 2002. The rate of submission is not expected to change significantly
in the next few years. Based on information from industry, the
estimated average time to complete a deviation report is 2 hours. The
availability of the standardized report FDA Form 3486, and the ability
to submit this report electronically further streamlines the report
submission process. Activities such as investigating, changing standard
operating procedures (SOPs) or processes, and followup are currently
required under parts 211 (approved under OMB control numbers 0910-0139
[[Page 75573]]
and 0910-0353), 606 (approved under OMB control number 0910-0116), and
820 (21 CFR part 820) (approved under OMB control number 0910-0073)
and, therefore, are not included in the burden calculation for the
separate requirement of submitting a deviation report to FDA.
In the Federal Register of June 30, 2003 (68 FR 38712), FDA
published a 60-day notice requesting public comment on the information
collection provisions. We received two comments.
In response to whether the proposed collection of information is
necessary, comment one stated that we should harmonize the biological
product deviation reporting requirements (Sec. 600.14) with the NDA
field alert reports under 21 CFR 314.81(b)(1) and, therefore, revoke
Sec. 600.14. The comment stated the adoption of the new drug
application (NDA) field alert regulations for all biologics would
streamline compliance activities, and facilitate and align the recent
transfer of biotechnology products from CBER to the Center for Drug
Evaluation and Research (CDER). The comment also stated that revocation
of Sec. 600.14 would reduce the reporting burden while continuing to
support the industry in making good, risk based quality decisions.
The NDA field alert regulations (approved under OMB control number
0910-0001) are applicable only to those products that are approved for
marketing under the provisions of part 314 (21 CFR part 314) (including
those few products that CBER regulates even though they were approved
under the NDA provisions of part 314). The NDA field alert regulations
do not apply to biological drug products subject to licensing under the
Public Health Service (PHS) Act, including licensed products that CDER
now regulates. FDA has harmonized a number of regulations for certain
biotechnology products where products regulated as biological products
subject to licensure are similar to products subject to regulation as
new drugs (see 65 FR 66621 at 66625, November 7, 2000). The products
recently transferred from CBER to CDER are still regulated as
biological products under the PHS Act. However, we recently stated in
our CBER Web site that the biological product deviation reports for
those transferred products are now to be sent to CDER. CBER will
continue to monitor and assess its biological product deviation
reporting program. If the level of reporting or the needs of the agency
change, FDA will consider whether to harmonize its reporting
requirements. The comment's suggestion that FDA adopt the NDA field
alert regulations in Sec. 314.81(b)(1) and revoke Sec. 600.14 seeks a
regulatory change that is outside the scope of FDA's current request
for OMB renewal of the information collection in the existing
regulations. Consequently, we decline to adopt the comment's
recommendations.
Comment two, in response to the necessity of the proposed
regulation, recommended revisions to the regulation regarding the
submission of reports regarding post-donation information, and argued
that only a small percentage of those reports were forwarded to
District Offices for further investigation and that the reporting
burden has resulted in little tangible outcome. FDA uses those reports
for reasons other than initiating further investigation or product
recalls. For example, some reports of post-donation information
revealed to FDA that the manufacturers had flaws in their donor
screening procedures, which FDA communicated to the companies. In
addition, information from biological product deviation reports has
been valuable to FDA in crafting guidances for industry that improve
product quality and reduce manufacturing problems generally. However,
we will continue to monitor and assess our biological product deviation
reporting program, including the review of these type of reports.
Consequently, we decline to adopt the comment's recommendations at this
time.
In response to FDA's burden estimate, comment one questioned the
estimated hours per response to submit a report to FDA and stated that
FDA's estimate did not factor in the time to completely process the
report. The comment provided an estimation of burden hours to submit a
report 10 times FDA's estimate. In addition, the comment stated that
additional time is required to update SOPs associated with the
regulation and to perform ongoing training.
Based on comments received in response to the burden hours
published in the proposed rule of September 23, 1997 (62 FR 49642), FDA
revised the burden hours (hours per response) in the final rule (65 FR
66621 at 66632, November 7, 2000) to the current estimate. In response
to the comments on the proposed rule, we stated the revised estimate
was based in part on information from industry representatives about
typical procedures, and the availability of a standardized report form.
Activities such as investigating, changing SOPs or processes, and
followup are required under parts 211, 606, and 820, and therefore, are
not included in the burden estimate for the separate requirement of
submitting to FDA a biological product deviation report. In the final
rule, we estimated the hours as a one-time burden, in part, for
establishing and making adjustments to SOPs and staff training.
Continuance of these activities would be considered as part of normal
business practice or covered by other regulations. We, therefore,
decline to revise the burden hours.
Comment two questioned FDA's estimate that the rate of submissions
was not expected to change significantly in the next few years. The
comment stated that there was a large increase in the number of reports
from the previous year.
We realize that the number of reports increased in the first couple
of years after issuance of the final rule as industry adjusted to the
new reporting requirements. However, we expect the numbers of reports
to level off after this adjustment period, and therefore, we estimate
that the rate of submission will not significantly increase in the next
few years. If the number of reports significantly increases
unexpectedly in the next few years, we will adjust the estimates at the
next interval for approval of the information collection. Consequently,
we decline to revise the estimates at this time.
In response to ways of minimizing the collection burden, comment
one stated that we should notify manufacturers when a report is
submitted that is not deemed to meet the threshold for reporting. The
comment also stated that firms are not comfortable with filing
submissions electronically because there are inadequate safeguards to
ensure against false reports.
For reports submitted electronically, we notify the manufacturer of
those reports that do not meet the threshold for reporting. For those
submitted in hard copy, we notify the manufacturer if a trend of a
particular type of unnecessary report is detected. We currently have an
approximate rate of 45 percent of reports submitted electronically with
the majority being submitted by the blood industry. Because the system
is designed with a user name and password that is associated with the
establishment, we believe there are adequate safeguards for submitting
the information electronically.
Comment two responded to ways of minimizing the collection burden
by recommending that post-donation information be reported in summary
format not to exceed annually. Although, as mentioned previously, FDA
has made valuable use of
[[Page 75574]]
promptly-reported post-donation information, we will continue to
monitor and assess our biological product deviation reporting program
and make adjustments accordingly.
FDA estimates the burden of this collection of information as
follows:
Table 1.--Estimated Annual Reporting Burden\1\
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Annual Frequency Total Annual Hours per
21 CFR Section Form No. No. of Respondents per Response Responses Response Total Hours
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600.14 3,486 115 4.1 476 2 952
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606.171\2\ 3,486 207 130.4 27,000 2 54,000
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606.171\3\ 3,486 6,021 1.1 6,446 2 12,892
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Total 67,844
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
\2\ Licensed manufacturers of human blood and blood components, including Source Plasma.
\3\ Unlicensed registered blood establishments and transfusion services (2,800 + 3,221 = 6,021).
Dated: December 16, 2003.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 03-32160 Filed 12-30-03; 8:45 am]
BILLING CODE 4160-01-S