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Link to original content: https://web.archive.org/web/20070929145513/http://www.fda.gov/ohrms/dockets/98fr/050902b.htm
[Federal Register: May 9, 2002 (Volume 67, Number 90)]
[Rules and Regulations]
[Page 31123-31125]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr09my02-6]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 310
[Docket No. 80N-0280]
RIN 0910-AA01
Status of Certain Additional Over-the-Counter Drug Category II
and III Active Ingredients
AGENCY: Food and Drug Administration, HHS.
ACTION: Final rule.
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SUMMARY: The Food and Drug Administration (FDA) is issuing a final rule
stating that a certain ingredient in over-the-counter (OTC) drug
products is not generally recognized as safe and effective or is
misbranded. FDA is issuing this final rule after considering the
reports and recommendations of various OTC drug advisory review panels
and public comments on proposed agency regulations. This final rule
addresses the ingredient octoxynol 9, considered in the rulemaking for
OTC vaginal contraceptive drug products. Based on the failure of
interested parties to submit new data or information to FDA under the
proposed regulation, the agency has determined that the presence of
this active ingredient in an OTC drug product would result in that drug
product not being generally recognized as safe and effective for its
intended use or would result in misbranding. This final rule is part of
FDA's ongoing OTC drug product review.
DATES: This regulation is effective November 5, 2002.
FOR FURTHER INFORMATION CONTACT: Helen Cothran, Center for Drug
Evaluation and Research (HFD-560), Food and Drug Administration, 5600
Fishers Lane, Rockville, MD 20857, 301-827-2222.
SUPPLEMENTARY INFORMATION:
I. Background
In the Federal Register of November 7, 1990 (55 FR 46914), FDA
published under Sec. 330.10(a)(7)(ii) (21 CFR 330.10(a)(7)(ii)) a final
rule on the status of certain OTC drug Category II and III active
ingredients. That final rule declared as not generally recognized as
safe and effective certain active ingredients that had been proposed as
nonmonograph (Category II or III) under the agency's OTC drug review.
The periods for submission of comments and new data following the
publication of a notice of proposed rulemaking had closed and no
significant comments or new data had been submitted to upgrade the
status of these ingredients. In each instance, a final rule for the
class of ingredients involved had not been published to date.
In the Federal Register of May 10, 1993 (58 FR 27636), FDA
published a final rule establishing that certain additional active
ingredients in OTC drug products are not generally recognized as safe
and effective or are misbranded. That final rule included active
ingredients from a number of OTC drug rulemakings that were not covered
by the November 7, 1990, final rule (see table I of the May 10, 1993,
final rule (58 FR 27636 at 27639 to 27641) for a list of OTC drug
rulemakings and active ingredients covered by that final rule).
In the proposed rulemaking for OTC vaginal contraceptive drug
products (45 FR 82014, December 12, 1980), the Advisory Review Panel on
OTC Contraceptives and Other Vaginal Drug Products (the Panel) placed
nonoxynol 9 and octoxynol 9 in Category I (safe and effective), placed
phenylmercuric acetate, phenylmercuric nitrate, and other compounds
containing mercury in Category II for safety, and placed dodecaethylene
glycol monolaurate (polyethylene glycol 600 monolaurate), laureth 10S,
and methoxypolyoxyethylene glycol 550 laurate in Category III for
efficacy. In the preamble to the Panel's report (45 FR 82014), the
agency stated that clinical trials of each product or final formulation
may be the only certain predictor of its effectiveness in humans. The
agency further stated that if clinical trials are necessary,
manufacturers may be required to submit a new drug application (NDA) or
supplement an existing NDA. The agency stated that it would announce
its decision in a separate Federal Register document or in the
tentative final order.
In the proposed rule for OTC vaginal contraceptive drug products
(60 FR 6892, February 3, 1995), the agency proposed that manufacturers
of OTC vaginal contraceptive drug products obtain approved applications
for marketing of their products. The agency took this action because
the evidence currently available shows that effectiveness of these
products is dependent upon the final formulation and clinical studies
in humans are needed to establish the effectiveness of the active
ingredients in OTC vaginal contraceptive drug products. Therefore, each
product must be tested in appropriate clinical trials under actual
conditions of use. FDA encouraged manufacturers to consult with the
agency regarding testing and the
[[Page 31124]]
submission of applications as soon as possible. In the proposed rule,
all of the ingredients evaluated by the Panel were considered
nonmonograph for reasons of safety and/or effectiveness.
In response to this proposed rule, the agency received no comments
or data relating to the safety and effectiveness of any of the Panel's
Category II or III ingredients. Therefore, in theFederal Register of
April 22, 1998 (63 FR 19799), the agency issued a final rule regarding
the nonmonograph status of these Category II and III ingredients. Based
on the absence of substantive comments in opposition to the agency's
proposed nonmonograph status for these ingredients, as well as the
failure of interested parties to submit new data or information to FDA
under the regulation, the agency determined that the presence of these
ingredients in an OTC drug product would result in the drug product not
being generally recognized as safe and effective or would result in
misbranding.
In response to the proposed rule, the agency was informed of
ongoing clinical trials involving nonoxynol 9 (Refs. 1, 2, and 3).
However, the agency is not aware of any clinical trials, nor have any
comments or data on octoxynol 9 been submitted to the agency since the
proposed rule. Accordingly, FDA concludes that octoxynol 9 has not been
shown to be generally recognized as safe and effective for its intended
use as a vaginal contraceptive and should be eliminated from OTC drug
products 6 months after the publication of this final rule in the
Federal Register, regardless of whether further testing is undertaken
to justify future use. Publication of this final rule does not preclude
a manufacturer's testing an ingredient. New, relevant data can be
submitted to the agency at a later date as the subject of a NDA that
may provide for prescription or OTC marketing status (see part 314 (21
CFR part 314)).
The monograph or new drug status of nonoxynol 9 will be addressed
after completion and analysis of the ongoing clinical trials. This
final rule for octoxynol 9 does not affect the current marketing status
of nonoxynol 9 as an OTC vaginal contraceptive.
II. The Agency's Final Conclusions on Certain OTC Drug Category II
and III Ingredients
For the reasons discussed in section I of this document, the agency
has determined that octoxynol 9 should be deemed not generally
recognized as safe and effective for OTC use before a final rule is
established for OTC vaginal contraceptive drug products. Accordingly,
any drug product containing octoxynol 9 and labeled for OTC use as a
vaginal contraceptive or spermicide will be considered nonmonograph and
misbranded under section 502 of the Federal Food, Drug, and Cosmetic
Act (the act) (21 U.S.C. 352) and a new drug under section 201(p) of
the act (21 U.S.C. 321(p)) for which an approved application under
section 505 of the act (21 U.S.C. 355) and part 314 of the regulations
is required for marketing. This applies to any OTC drug product
containing octoxynol 9 and labeled for use as a vaginal contraceptive
or vaginal spermicide that is initially introduced or initially
delivered for introduction into interstate commerce after the effective
date of this final rule. Further, any OTC drug product that was
previously initially introduced or initially delivered for introduction
into interstate commerce cannot be repackaged or relabeled after the
effective date of the rule. Manufacturers are encouraged to comply
voluntarily with the rule at the earliest possible date.
III. Analysis of Impacts
FDA has examined the impacts of the final rule under Executive
Order 12866, the Regulatory Flexibility Act (5 U.S.C. 601-612), and the
Unfunded Mandates Reform Act of 1995 (2 U.S.C. 1501 et seq.). Executive
Order 12866 directs agencies to assess all costs and benefits of
available regulatory alternatives and, when regulation is necessary, to
select regulatory approaches that maximize net benefits (including
potential economic, environmental, public health and safety, and other
advantages; distributive impacts; and equity). Under the Regulatory
Flexibility Act, if a rule has a significant impact on a substantial
number of small entities, an agency must analyze regulatory options
that would minimize any significant impact of the rule on small
entities. Section 202(a) of the Unfunded Mandates Reform Act requires
that agencies prepare a written statement of anticipated costs and
benefits before proposing any rule that may result in an expenditure in
any one year by State, local, and tribal governments, in the aggregate,
or by the private sector, of $100 million (adjusted annually for
inflation).
The agency concludes that this final rule is consistent with the
principles set out in the Executive order and in these two statutes.
Further, since this final rule is not expected to result in any 1-year
expenditure that would exceed $100 million adjusted for inflation, FDA
need not prepare additional analyses under the Unfunded Mandates Reform
Act.
The purpose of this final rule is to finalize the proposed
nonmonograph status of octoxynol 9 in order to expedite completion of
the OTC drug review. There are a limited number of products currently
marketed that will be affected by this rule. The agency's Drug Listing
System identifies two manufacturers of OTC vaginal contraceptive drug
products containing octoxynol 9, although there may be some additional
products that are not currently included in the agency's system. One
manufacturer markets four products and the other manufacturer markets
one product, for a total of five products. At least one of the
manufacturers is considered a small entity, using the U.S. Small
Business Administration designation for this industry (750 employees).
Manufacturers of these products will no longer be able to market
products containing octoxynol 9 after the effective date of this final
rule. One of the manufacturers of octoxynol 9 also produces products
that contain nonoxynol 9, which is currently being tested in clinical
trials. Other manufacturers will be able to reformulate vaginal
contraceptive drug products that contain octoxynol 9 and continue to
market them with nonoxynol 9, pending completion of the final rule for
these products. The agency estimates the cost of reformulation and
relabeling to range from $100,000 to $500,000 per product. Using the
midpoint of the cost estimate implies total costs up to $1.5 million.
However, the agency believes the total costs will be smaller because
all currently marketed products may not be reformulated. The
manufacturers have known since the publication of the proposed rule in
the Federal Register of February 3, 1995, that if adequate data from
clinical trials were not submitted to support safety and effectiveness,
cessation of marketing of the current products would be required when
the final rule is published. Generally, when safety is not a concern,
manufacturers will continue to market products that they know will
become nonmonograph for as long as legally possible to maximize their
profits for that product line.
The agency considered but rejected not acting on this ingredient in
advance of the completion of the final rule on OTC vaginal
contraceptive drug products. The ongoing clinical trials involving
nonoxynol 9 are not expected to be completed for a period of time.
However, safety and effectiveness have not been established for
octoxynol 9 and
[[Page 31125]]
no testing is currently being done. Therefore, the agency concludes
that consumers will benefit from the early removal from the marketplace
of products containing octoxynol 9.
Because so few small firms will be affected, the agency certifies
that there will not be a significant economic impact on a substantial
number of small firms.
IV. Paperwork Reduction Act of 1995
This final rule contains no collections of information. Therefore,
clearance by the Office of Management and Budget under the Paperwork
Reduction Act of 1995 is not required.
V. Environmental Impact
The agency has determined under 21 CFR 25.31(a) that this action is
of a type that does not individually or cumulatively have a significant
effect on the human environment. Therefore, neither an environmental
assessment nor an environmental impact statement is required.
VI. Federalism
FDA has analyzed this final rule in accordance with the principles
set forth in Executive Order 13132. FDA has determined that the rule
does not contain policies that have substantial direct effects on the
States, on the relationship between the National Government and the
States, or on the distribution of power and responsibilities among the
various levels of government. Accordingly, the agency has concluded
that the rule does not contain policies that have federalism
implications as defined in the Executive order and, consequently, a
federalism summary impact statement is not required.
VII. References
The following references are on display in the Dockets Management
Branch (address above) under Docket No. 80N-0280 and may be seen by
interested persons between 9 a.m. and 4 p.m., Monday through Friday.
1. FDA, Transcript of Joint Meeting of the Nonprescription
Drugs, Reproductive Health Drugs, Anti-Infective Drugs and Antiviral
Drugs Advisory Committees, November 22, 1996, pp. 86-99, in OTC Vol.
11ATFM2.
2. Letter from D. L. Bowen, FDA, to R. W. Soller,
Nonprescription Drug Manufacturers Association, coded LET 6.
3. Letter from D. L. Bowen, FDA, to R. W. Soller,
Nonprescription Drug Manufacturers Association, coded LET 7.
List of Subjects in 21 CFR Part 310
Administrative practice and procedure, Drugs, Labeling, Medical
devices, Reporting and recordkeeping requirements.
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, 21 CFR part
310 is amended as follows:
PART 310--NEW DRUGS
1. The authority citation for 21 CFR part 310 continues to read as
follows:
Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 360b-360f,
360j, 361(a), 371, 374, 375, 379e; 42 U.S.C. 216, 241, 242(a), 262,
263b-263n.
2. Section 310.545 is amended by adding a paragraph heading
(a)(28)(i) after the existing paragraph heading, by adding paragraphs
(a)(28)(ii) and (d)(36), by revising paragraph (d)(28), and by adding
and reserving paragraphs (d)(34) and (d)(35) to read as follows:
Sec. 310.545 Drug products containing certain active ingredients
offered over-the-counter (OTC) for certain uses.
(a) * * *
(28) Vaginal contraceptive drug products--(i) Approved as of
October 22, 1998. * * *
(ii) Approved as of November 5, 2002.
Octoxynol 9
* * * * *
(d) * * *
(28) October 22, 1998, for products subject to paragraphs (a)(27)
and (a)(28)(i) of this section.
* * * * *
(34) [Reserved]
(35) [Reserved]
(36) November 5, 2002, for products subject to paragraph
(a)(28)(ii) of this section.
Dated: April 29, 2002.
Margaret M. Dotzel,
Associate Commissioner for Policy.
[FR Doc. 02-11511 Filed 5-8-02; 8:45 am]
BILLING CODE 4160-01-S