[Federal Register Volume 61, Number 69 (Tuesday, April 9, 1996)]
[Rules and Regulations]
[Pages 15699-15700]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-8826]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 2
[Docket No. 92P-0403]
Chlorofluorocarbon Propellants in Self-Pressurized Containers;
Addition to List of Essential Uses
AGENCY: Food and Drug Administration, HHS.
ACTION: Final rule.
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SUMMARY: The Food and Drug Administration (FDA) has granted the
petition of Boehringer Ingelheim Pharmaceuticals, Inc. (BIPI), to add
metered-dose albuterol sulfate and ipratropium bromide in combination
for oral inhalation to the list of products containing a
chlorofluorocarbon (CFC) propellant for an essential use. Essential use
products are exempt from FDA's ban on the use of CFC propellants in
FDA-regulated products and the Environmental Protection Agency's
(EPA's) ban on the use of CFC's in pressurized dispensers. This
document amends FDA's regulations governing use of CFC's to include
metered-dose albuterol sulfate and ipratropium bromide in combination
for oral inhalation as an essential use.
EFFECTIVE DATE: April 9, 1996.
FOR FURTHER INFORMATION CONTACT: Wayne H. Mitchell, Center for Drug
Evaluation and Research (HFD-097), Food and Drug Administration, 7500
Standish Pl., Rockville, MD 20855, 301-594-1049.
SUPPLEMENTARY INFORMATION:
I. Background
In response to a citizen petition submitted by BIPI, in the Federal
Register of October 17, 1995 (60 FR 53725), FDA published a proposed
rule to amend 1A2.125 (21 CFR 2.125) to add metered-dose albuterol
sulfate and ipratropium bromide in combination for oral inhalation to
the list of productscontaining a CFC propellant for an essential use.
Under 1A2.125, any food, drug, device, or cosmetic in a self-
pressurized container that contains a CFC propellant for a nonessential
use is adulterated or misbranded, or both, under the Federal Food,
Drug, and Cosmetic Act. This prohibition is based on scientific
research indicating that CFC's may reduce the amount of ozone in the
stratosphere and thereby increase the amount of ultraviolet radiation
reaching the earth. An increase in ultraviolet radiation may increase
the incidence of skin cancer, change the climate, and produce other
adverse effects of unknown magnitude on humans, animals, and plants.
Section 2.125(d) exempts from the adulteration and misbranding
provisions of 1A2.125(c) certain products containing CFC propellants
thatFDA determines provide unique health benefits that would not be
available without the use of a CFC. These products are referred to in
the regulation as essential uses of CFC's and are listed in 1A2.125(e).
Under 1A2.125(f), any person may petition the agency to request
additions to the list of uses considered essential. To demonstrate that
the use of a CFC is essential, the petition must be supported by an
adequate showing that: (1) There are no technically feasible
alternatives to the use of a CFC in the product; (2) the product
provides a substantial health, environmental, or other public benefit
unobtainable without the use of the CFC; and (3) the use does not
involve a significant release of CFC's into the atmosphere or, if it
does, the release is warranted by the consequence if the use were not
permitted.
EPA regulations implementing provisions of the Clean Air Act
contain a general ban on the use of CFC's in pressurized dispensers,
such as metered-dose inhalers (MDI's) (40 CFR 82.64(c) and 82.66(d)).
These regulations exempt from the general ban ``medical devices'' that
FDA considers essential and that are listed in 1A2.125(e). Section
601(8) of the Clean Air Act (42 U.S.C. 7671(8)) defines ``medical
device'' as any device (as defined in the Federal Food, Drug, and
Cosmetic Act), diagnostic product, drug (as defined in the Federal
Food, Drug, and Cosmetic Act), and drug delivery system, if such
device, product, drug, or drug delivery system uses a class I or class
II ozone-depleting substance for which no safe and effective
alternative has been developed (and where necessary, approved by the
Commissioner of Food and Drugs (the Commissioner)); and if such device,
product, drug, or drug delivery system has, after notice and
opportunity for public comment, been approved and determined to be
essential by the Commissioner in consultation with the Administrator of
EPA (the Administrator). Class I substances include CFC's, halons,
carbon tetrachloride, methyl chloroform, methyl bromide, and other
chemicals not relevant to this document (see 40 CFR part 82, appendix A
to subpart A). Class II substances include hydrochlorofluorocarbons
(HCFC's)(see 40 CFR part 82, appendix B to subpart A).
II. Petition Received by FDA
BIPI submitted a petition under 1A2.125(f) and 21 CFR part 10
requesting an addition to the list of CFC uses considered essential.
The petition is on file under the docket number found in brackets in
the heading of this document and may be seen in the Dockets Management
Branch (HFA-305), Food and Drug Administration, 12420 Parklawn Dr., rm.
10923, Rockville, MD 20857. The petition requested that metered-dose
albuterol sulfate and ipratropium bromide in combination for oral
inhalation be included in 1A2.125(e) as an essential use of CFC's. The
petition contained a discussion supporting the position that there are
no technically feasible alternatives to the use of CFC's in the
product. It included information showing that no alternative delivery
systems (e.g., the dry powder inhaler) or other substitute propellants
(e.g., compressed gases) can dispense the drug for effective inhalation
therapy as safely and uniformly, in all situations, as CFC propellants.
Also, the petition stated that the product provides a substantial
health benefit that would not be obtainable without the use of CFC's.
In this regard, the petition contained information to support the use
of this product as a combination bronchodilator. The petition asserted
that metered-dose albuterol sulfate andipratropium bromide in
combination potentially reduces the amount of CFC's released into the
atmosphere attributable to patients using one MDI for the combination
product, rather than two MDI's, one for each of the two active
ingredients.
The agency has determined that, for some chronic obstructive
pulmonary disease patients, the use of metered-dose albuterol sulfate
and ipratropium bromide in combination provides a special benefit that
would be unavailable without the use of CFC's,
[[Page 15700]]
and that the use of the drugs in combination has the potential to
reduce the amount of CFC's released into the atmosphere. In this
regard, FDA notes that albuterol sulfate and ipratropium bromide are
currently listed separately (i.e., not in combination) in 1A2.125(e) as
essential uses of CFC's. Based on the evidence currently before it, FDA
also agrees that the use of a metered-dose delivery system for this
product does not involve asignificant release of CFC's into the
atmosphere. Therefore, FDA is amending 1A2.125(e) to include metered-
dose albuterol sulfate and ipratropium bromide in combination for oral
inhalation in the list of essential uses of CFC propellants.
A copy of the proposed rule was provided to the Administrator.
III. Comments on the Proposed Rule
Interested persons were given 30 days to comment on the proposed
rule. FDA received one comment regarding the proposed rule. The comment
pointed out that CFC-free MDI's for albuterol sulfate and other drugs
are generally expected to be developed and marketed in the near future,
and that the availability of alternative propellants will undercut the
factual basis for FDA's determination that the use of CFC's in MDI's is
medically necessary. The comment suggested that FDA's determination be
made conditionally, and that FDA reexamine the ``medical essentiality''
of the MDI if and when a CFC-free albuterol sulfate MDI is approved.
The comment also suggested that future rulemaking may be necessary to
provide for the transition between MDI's containing CFC's and CFC-free
MDI's.
FDA is aware of the development of CFC-free MDI's and shares the
comment's concerns that proper provision should be made for the
transition between MDI's containing CFC's and CFC-free MDI's. FDA,
working with EPA, is developing a policy on this matter at this time,
and anticipates that a rulemaking procedure may be necessary to
implement that policy. Section 2.125 does not provide for a
``conditional'' listing as an essential use and to provide for such a
``conditional'' listing in this rule would be beyond the scope of the
proposal. Any phase-out or reformulation requirement for MDI's
containing albuterol sulfate and ipratropium bromide in combination
undertaken because of the availability of alternative propellants will
be undertaken as part of a properly implemented general policy on the
elimination of CFC's from MDI's and other similar products.
IV. Analysis of Impacts
FDA has examined the impacts of the final rule under Executive
Order 12866 and the Regulatory Flexibility Act (Pub. L. 96-354).
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). The agency believes that
this final rule is consistent with the regulatory philosophy and
principles identified in the Executive Order. In addition, the final
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 Regulatory Flexibility Act requires agencies to analyze
regulatory options that would minimize any significant impact of a rule
on small entities. Because the agency is not aware of any adverse
impact this final rule will have on any small entities, the agency
certifies that the final rule will not have a significant economic
impact on a substantial number of small entities. Therefore, under the
Regulatory Flexibility Act, no further analysis is required.
List of Subjects in 21 CFR Part 2
Administrative practice and procedure, Cosmetics, Devices, Drugs,
Foods.
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, 21 CFR part
2 is amended as follows:
PART 2--GENERAL ADMINISTRATIVE RULINGS AND DECISIONS
1. The authority citation for 21 CFR part 2 continues to read as
follows:
Authority: Secs. 201, 301, 305, 402, 408, 409, 501, 502, 505,
507, 512, 601, 701, 702, 704 of the Federal Food, Drug, and Cosmetic
Act (21 U.S.C. 321, 331, 335, 342, 346a, 348, 351, 352, 355, 357,
360b, 361, 371, 372, 374); 15 U.S.C. 402, 409.
2. Section 2.125 is amended by adding new paragraph (e)(14) to read
as follows:
Sec. 2.125 Use of chlorofluorocarbon propellants in self-pressurized
containers.
* * * * *
(e) * * *
(14) Metered-dose ipratropium bromide and albuterol sulfate, in
combination, administered by oral inhalation for human use.
* * * * *
Dated: March 29, 1996.
William K. Hubbard,
Associate Commissioner for Policy Coordination.
[FR Doc. 96-8826 Filed 4-8-96; 8:45 am]
BILLING CODE 4160-01-F