[Federal Register Volume 65, Number 2 (Tuesday, January 4, 2000)]
[Proposed Rules]
[Pages 256-258]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-76]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 216
[Docket No. 99N-4490]
Additions to the List of Drug Products That Have Been Withdrawn
or Removed From the Market for Reasons of Safety or Effectiveness
AGENCY: Food and Drug Administration, HHS.
ACTION: Proposed rule.
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SUMMARY: The Food and Drug Administration (FDA) is proposing to amend
its regulations to add two drug products to the list of drug products
that may not be used for pharmacy compounding under the exemptions
provided by the Federal Food, Drug, and Cosmetic Act (the act) because
they have had their approval withdrawn or were removed from the market
because the drug product or its components have been found to be unsafe
or not effective.
DATES: Written comments must be received on or before March 20, 2000.
ADDRESSES: Submit written comments to the Dockets Management Branch
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061,
Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT: Wayne H. Mitchell, Center for Drug
Evaluation and Research (HFD-7), Food and Drug Administration, 5600
Fishers Lane, Rockville, MD 20857, 301-594-2041.
SUPPLEMENTARY INFORMATION:
I. Background
President Clinton signed the Food and Drug Administration
Modernization Act (Public Law 105-115) into law on November 21, 1997.
One of the issues addressed in the legislation is the applicability of
the act to the practice of pharmacy compounding. Compounding involves a
process whereby a pharmacist or physician combines, mixes, or alters
ingredients to create a customized medication for an individual
patient. Section 127 of the Modernization Act, which adds section 503A
to the act (21 U.S.C. 353a), describes the circumstances under which
compounded drugs qualify for exemptions from certain adulteration,
misbranding, and new drug provisions of the act (i.e., sections
501(a)(2)(B), 502(f)(1), and 505 of the act (21 U.S.C. 351(a)(2)(B),
352(f)(1), and 355)).
Section 503A of the act contains several conditions that must be
satisfied for pharmacy compounding to qualify for the exemptions. One
of the conditions is that the licensed pharmacist or licensed physician
does not ``compound a drug product that appears on a list published by
the Secretary in the Federal Register of drug products that have been
withdrawn or removed from the market because such drug products or
components of such drug products have been found to be unsafe or not
effective.''
II. Rulemaking to Establish the List
In the Federal Register of October 8, 1998 (63 FR 54082), we
proposed the original list of drug products that have had their
approval withdrawn or were removed from the market because the drug
product or its components have been found to be unsafe or not
effective. We published the original list as a final rule in the
Federal Register of March 8, 1999 (64 FR 10944). You may wish to read
these documents for additional information about the list. The two
Federal Register documents may be found on the Center for Drug
Evaluation and Research's website at http://www.fda.gov/cder/pharmcomp/
default.htm or the Government Printing Office's website at http://
www.access.gpo.gov/su__docs/aces/aces140.html.
The list was codified as Sec. 216.24 of Title 21 in the Code of
Federal Regulations (CFR) (21 CFR 216.24). This is the first time we
have proposed to amend the list.
III. Description of this Proposed Rule
We are proposing that the drug products described below be added to
[[Page 257]]
the list of drug products that have had their approval withdrawn or
were removed from the market because the drug product or its components
have been found to be unsafe or not effective. Compounding a drug
product that appears on the list is not covered by the exemption
provided in section 503A(a) of the act, and it may be subject to
enforcement action under sections 501(a)(2)(B), 502(f)(1), and 505
(among other applicable provisions) of the act.
Aminopyrine: All drug products containing aminopyrine. Drug
products containing aminopyrine were used as an analgesic and an
antipyretic. Aminopyrine caused agranulocytosis, a condition
characterized by a decrease in the number of certain white blood cells
and lesions on the mucous membrane and skin. Some of the cases of
agranulocytosis were fatal. In 1964, we declared drug products
containing aminopyrine to be new drugs. We invited new drug
applications (NDA's) for these drug products, but only for use as an
antipyretic in serious situations where other safer drugs could not be
used (see 21 CFR 201.311 (42 FR 53954, October 4, 1977)). We received
no NDA's for drug products containing aminopyrine, and those unapproved
drug products were removed from the market by their manufacturers (see
42 FR 53954).
Astemizole: All drug products containing astemizole. Astemizole
tablets were marketed under the trade name Hismanal and were indicated
for the relief of symptoms associated with seasonal allergic rhinitis
and chronic idiopathic urticaria. We approved the NDA for astemizole
tablets in December 1988. Within a few years of the approval, it was
learned that low-level overdosages of astemizole were resulting in
life-threatening heart arrhythmias. Patients with liver dysfunction or
who were taking other drugs that interfered with the metabolization of
astemizole were also found to be at risk of serious cardiac adverse
events while taking astemizole. The manufacturer of astemizole tablets,
the only astemizole drug product, removed the product from the market
on June 18, 1999. We published a notice in the Federal Register of
August 23, 1999 (64 FR 45973), announcing our determination that
astemizole tablets were withdrawn from the market for safety reasons.
IV. Environmental Impact
The agency has determined under 21 CFR 25.30(h) 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.
V. Analysis of Impacts
We have examined the impacts of the proposed rule under Executive
Order 12866, the Regulatory Flexibility Act (5 U.S.C 601-612), and the
Unfunded Mandates Reform Act of 1995 (Public Law 104-4). 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). Executive Order 12866
classifies a rule as significant if it meets any one of a number of
specified conditions, including having an annual effect on the economy
of $100 million or adversely affecting in a material way a sector of
the economy, competition, or jobs, or if it raises novel legal or
policy issues. As discussed below, the agency believes that this
proposed rule is consistent with the regulatory philosophy and
principles identified in the Executive Order. In addition, the proposed
rule is not a significant regulatory action as defined by the Executive
Order and so is not subject to review under the Executive Order.
The agency has not estimated any compliance costs or loss of sales
due to this proposed rule because it prohibits pharmacy compounding of
only those drug products that have already been withdrawn or removed
from the market. Although the agency is not aware of any routine use of
these drug products in pharmacy compounding, the agency invites the
submission of comments on this issue and solicits current compounding
usage data for these drug products.
Unless an agency certifies that a rule will not have a significant
economic impact on a substantial number of small entities, the
Regulatory Flexibility Act requires agencies to analyze regulatory
options to minimize any significant economic impact of a regulation on
small entities. The agency is taking this action to comply with section
503A of the act. This provision specifically directs us to develop a
list of drug products that have been withdrawn or removed from the
market because such products or components have been found to be unsafe
or not effective. Any drug product on this list will not qualify for
the pharmacy compounding exemptions under section 503A of the act.
The drug products that are proposed to be added to the this list
were manufactured by several different pharmaceutical firms, some of
which may have qualified under the Small Business Administration (SBA)
regulations (those with less than 750 employees) as small businesses.
However, since the list only includes drug products that have already
been withdrawn or removed from the market for safety or efficacy
concerns, this proposal will not negatively impact these small
businesses. Moreover, no compliance costs are estimated for any of
these small pharmaceutical firms because they are not the subject of
this rule and are not expected to realize any further loss of sales due
to this proposal. Further, the SBA guidelines limit the definition of
small drug stores or pharmacies to those that have less than $5.0
million in sales. Again, the pharmacies that qualify as small
businesses are not expected to incur any compliance costs or loss of
sales due to this regulation because the products have already been
withdrawn or removed from the market, and the agency believes that
these drugs would be compounded only very rarely, if ever. Therefore,
we certify that this rule will not have a significant economic impact
on a substantial number of small entities.
Section 202 of the Unfunded Mandates Reform Act requires that
agencies prepare an assessment of anticipated costs and benefits before
proposing any expenditure by State, local, and tribal governments, in
the aggregate, or by the private sector of $100 million (adjusted
annually for inflation) in any one year. The publication of the list of
products withdrawn or removed from the market because they were found
to be unsafe or ineffective will not result in expenditures of funds by
State, local, and tribal governments or the private sector in excess of
$100 million annually. Because the agency does not estimate any annual
expenditures due to the proposed rule, we are not required to perform a
cost/benefit analysis according to the Unfunded Mandates Reform Act.
VI. Paperwork Reduction Act of 1995
We tentatively conclude that this proposed 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.
VII. Request for Comments
Interested persons may, on or before March 20, 2000, submit to the
Dockets
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Management Branch (address above) written comments regarding this
proposal. Two copies of any comments are to be submitted, except that
individuals may submit one copy. Comments are to be identified with the
docket number found in brackets in the heading of this document.
Received comments may be seen in the office above between 9 a.m. and 4
p.m., Monday through Friday.
List of Subjects in 21 CFR Part 216
Drugs, Pharmacy compounding, Prescription drugs.
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, it is
proposed that 21 CFR part 216 be amended as follows:
PART 216--PHARMACY COMPOUNDING
1. The authority citation for 21 CFR part 216 continues to read as
follows:
Authority: 21 U.S.C. 351, 352, 353a, 355, and 371.
2. Amend Sec. 216.24 by adding alphabetically to the list of drug
products ``Aminopyrine'' and ``Astemizole'' to read as follows:
Sec. 216.24 Drug products withdrawn or removed from the market for
reasons of safety or effectiveness.
* * * * *
Aminopyrine: All drug products containing aminopyrine.
Astemizole: All drug products containing astemizole.
* * * * *
Dated: December 10, 1999.
Margaret M. Dotzel,
Acting Associate Commissioner for Policy.
[FR Doc. 00-76 Filed 1-3-00; 8:45 am]
BILLING CODE 4160-01-F
