[Federal Register Volume 60, Number 200 (Tuesday, October 17, 1995)]
[Proposed Rules]
[Pages 53725-53726]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-25619]



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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: Proposed rule.

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SUMMARY: The Food and Drug Administration (FDA) is proposing to grant 
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 proposes to amend 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.

DATES: Written comments by November 16, 1995.
ADDRESSES: Submit written comments to the Dockets Management Branch 
(HFA-305), Food and Drug Administration, rm. 1-23, 12420 Parklawn Dr., 
Rockville, MD 20857.
FOR FURTHER INFORMATION CONTACT: Wayne H. Mitchell, Center for Drug 
Evaluation and Research (HFD-362), Food and Drug Administration, 7500 
Standish Pl., Rockville, MD 20855, 301-594-1049.

SUPPLEMENTARY INFORMATION:

I. Background

    Under Sec. 2.125 (21 CFR 2.125), 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 Sec. 2.125(c) certain 
products containing CFC propellants that FDA 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 Sec. 2.125(e).
    Under Sec. 2.125(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 Sec. 2.125(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 

[[Page 53726]]
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 Sec. 2.125(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 appearing in the 
heading of this document and may be seen in the Dockets Management 
Branch (address above). The petition requested that metered-dose 
albuterol sulfate and ipratropium bromide in combination for oral 
inhalation be included in Sec. 2.125(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. The petition 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 and ipratropium 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.

III. FDA'S Review of the Petition

    The agency has tentatively decided 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, 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 Sec. 2.125(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 a significant release of CFC's into the 
atmosphere. Therefore, FDA is proposing to amend Sec. 2.125(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 this document has been provided to the Administrator.

IV. Analysis of Impacts

    FDA has examined the impacts of the proposed 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 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 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 of this proposed rule will have on any small entities, the 
agency certifies that the proposed 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.

V. Opportunity for Comments

    Interested persons may, on or before November 16, 1995, submit to 
the Dockets 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 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, it is 
proposed that 21 CFR part 2 be 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: October 10, 1995.
William B. Schultz,
Deputy Commissioner for Policy.
[FR Doc. 95-25619 Filed 10-16-95; 8:45 am]
BILLING CODE 4160-01-F