[Federal Register Volume 80, Number 124 (Monday, June 29, 2015)]
[Proposed Rules]
[Pages 36937-36939]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-15902]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 2

[Docket No. FDA-2015-N-1355]


Use of Ozone-Depleting Substances; Request for Comment Concerning 
Essential-Use Designations

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice and request for public comment.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is seeking 
public comment on whether the uses of ozone-depleting substances 
(ODSs), including chlorofluorocarbons (CFCs), in certain FDA-regulated 
products currently designated essential are no longer essential under 
the Clean Air Act due to the availability of alternatives that do not 
use CFCs or because the products are no longer being marketed. 
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 CFCs in pressurized dispensers. FDA 
is seeking public comment because it is responsible for determining 
which FDA-regulated products that release CFCs or other ODSs are 
essential uses under the Clean Air Act. FDA is soliciting comments to 
assist the Agency in striking an appropriate balance that will best 
protect the public health, both by ensuring the availability of an 
adequate number of alternatives and by curtailing the release of ODSs.

DATES: Submit written or electronic comments by August 28, 2015.

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ADDRESSES: You may submit comments by any of the following methods:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments.

Written Submissions

    Submit written submissions in the following ways:
     Mail/Hand delivery/Courier (for paper submissions): 
Division of Dockets Management (HFA-305), Food and Drug Administration, 
5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
    Instructions: All submissions received must include the Docket 
No(s). ([INSERT]). All comments received may be posted without change 
to http://www.regulations.gov, including any personal information 
provided. For additional information on submitting comments, see the 
``Comments'' heading of the SUPPLEMENTARY INFORMATION section of this 
document.
    Docket: For access to the docket to read background documents or 
comments received, go to http://www.regulations.gov and insert the 
docket number(s), found in brackets in the heading of this document, 
into the ``Search'' box and follow the prompts and/or go to the 
Division of Dockets Management, 5630 Fishers Lane, Rm. 1061, Rockville, 
MD 20852.

FOR FURTHER INFORMATION CONTACT: Daniel Orr, Center for Drug Evaluation 
and Research, Food and Drug Administration, 10903 New Hampshire Ave., 
Bldg. 51, Rm. 6246, Silver Spring, MD 20993, 240-402-0979, 
[email protected].

SUPPLEMENTARY INFORMATION: 

I. Background

    Any drug, device, cosmetic, or food contained in an aerosol product 
or other pressurized dispenser that releases a CFC or other ODS 
propellant is not an essential use of the ODS under the Clean Air Act 
except as provided in 21 CFR 2.125(c) and (e). This prohibition is 
based on scientific research indicating that CFCs reduce the amount of 
ozone in the stratosphere and thereby increase the amount of 
ultraviolet radiation reaching the Earth. An increase in ultraviolet 
radiation will increase the incidence of skin cancer, and produce other 
adverse effects of unknown magnitude on humans, animals, and plants. 
Sections 2.125(c) and (e) provide exemptions for essential uses of ODSs 
for certain products containing ODS propellants that FDA determines 
provide unique health benefits that would not be available without the 
use of a CFC.
    EPA regulations implementing the provisions of section 610 of the 
Clean Air Act (42 U.S.C. 7671i) contain a general ban on the use of 
CFCs in pressurized dispensers, such as metered-dose inhalers (MDIs) 
(40 CFR 82.64(c) and 82.66(d)). These EPA regulations exempt from the 
general ban ``medical devices'' that FDA considers essential and that 
are listed in 21 CFR 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 FD&C Act), diagnostic product, drug (as defined in the FD&C Act), 
and drug delivery system, if such device, diagnostic product, drug, or 
drug delivery system uses a class I or class II ODS 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, diagnostic 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 
CFCs, 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 (see 40 CFR part 82, appendix B to subpart A).
    Production of ODSs is being phased out worldwide under the terms of 
the Montreal Protocol on Substances that Deplete the Ozone Layer 
(Montreal Protocol), Sept. 16, 1987, S. Treaty Doc. No. 10, 100th 
Cong., 1st sess., 26 I.L.M. 1541 (1987). In accordance with the 
provisions of the Montreal Protocol, under authority of Title VI of the 
Clean Air Act (section 601 et seq.), manufacture of ODSs, including 
CFCs, in the United States was banned generally as of January 1, 1996. 
To receive permission to manufacture CFCs in the United States after 
the phase-out date, manufacturers must obtain an exemption from the 
phase-out requirements from the Parties to the Montreal Protocol. 
Procedures for securing an essential-use exemption under the Montreal 
Protocol are described in the most recent request by EPA for 
applications for exemptions (60 FR 54349, October 23, 1995). Firms that 
wish to use CFCs manufactured after the phase-out date in medical 
devices (as defined in section 601(8) of the Clean Air Act) covered 
under section 610 of the Clean Air Act must receive exemptions for 
essential uses under the Montreal Protocol.
    Faced with the statutorily mandated phase-out of the production of 
CFCs, drug manufacturers have developed alternatives to MDIs and other 
self-pressurized drug dosage forms that do not contain ODSs. Examples 
of these alternative dosage forms are MDIs that use non-ODSs as 
propellants and dry-powder inhalers. The current and future 
availability of technically feasible alternatives to the use of a CFC 
may mean that the existing listing of an essential use in 21 CFR 
2.125(e) no longer reflects current conditions. It is with this 
situation in mind that FDA is seeking public comment regarding the 
Agency's consideration of whether certain uses of ODSs are no longer 
essential.
    FDA is soliciting comments to assist the Agency in striking an 
appropriate balance that will best protect the public health by 
ensuring the availability of an adequate number of treatment 
alternatives and by curtailing the release of ODSs.

II. Listed Uses That May No Longer Be Considered Essential

    There are certain uses of CFCs currently listed in 21 CFR 2.125(e) 
as essential that may no longer be considered as essential. Section 
2.125(g) sets forth standards for determining whether the use of an ODS 
in a medical product is no longer essential. FDA is seeking public 
comment concerning whether the following uses should still be 
considered essential:

A. Sterile Aerosol Talc Administered Intrapleurally by Thoracoscopy for 
Human Use (21 CFR 2.125(e)(4)(ix))

    There is currently one sterile aerosol talc product containing ODSs 
which is approved for administration intrapleurally by thoracoscopy for 
human use for the treatment of recurrent malignant pleural effusion 
(MPE) in symptomatic patients. Under 21 CFR 2.125(g)(3), an essential-
use designation for individual active moieties marketed as ODS products 
and represented by one new drug application may no longer be essential 
if:
     At least one non-ODS product with the same active moiety 
is marketed with the same route of administration, for the same 
indication, and with approximately the same level of convenience of use 
as the ODS product containing that active moiety;
     Supplies and production capacity for the non-ODS 
product(s) exist or will exist at levels sufficient to meet patient 
need;

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     Adequate U.S. postmarketing-use data are available for the 
non-ODS product(s); and
     Patients who medically require the ODS product are 
adequately served by the non-ODS product(s) containing that active 
moiety and other available products (21 CFR 2.125(g)(3)).
    Sterile aerosol talc is currently marketed for intrapleural 
administration in two non-ODS formulations--powder and aerosol. Sterile 
aerosol talc is a powder formulation of talc available for intrapleural 
administration via chest tube. Sclerosol Intrapleural Aerosol (sterile 
talc powder) is an aerosol formulation which contains the propellant, 
hydrofluoroalkane (HFA) 134a and is approved for intrapleural 
administration. Sclerosol Intrapleural Alcohol, a form of aerosol 
sterile talc, is indicated for the treatment of recurrent MPE in 
symptomatic patients.
    The route of administration, indications, and level of convenience 
appear to be the same for the ODS and non-ODS formulations of sterile 
aerosol talc. Moreover, because production of non-ODS formulations are 
not limited by restrictions on the use of ODSs, the Agency believes 
that non-ODS formulations can be produced at greater quantities and 
have the potential to be more widely available than prior formulations 
that contained ODSs. In addition, there is adequate U.S. postmarketing-
use data indicating that the non-ODS products are available in 
sufficient quantities to serve the current patient population. For 
these reasons, we believe that patients may be adequately served by the 
non-ODS products containing sterile aerosol talc. Thus, FDA is seeking 
public comment concerning whether sterile aerosol talc administered 
intrapleurally by thoracoscopy for human use is no longer an essential 
use of ODSs described in 21 CFR 2.125(e).

B. Drug Products That Are No Longer Being Marketed

    Under 21 CFR 2.125(g)(1), an active moiety may no longer be an 
essential-use (21 CFR 2.125(e)) if it is no longer marketed in an 
approved ODS formulation. FDA believes failure to market indicates non-
essentiality because the absence of a demand sufficient for even one 
company to market the product is highly indicative that the use is not 
essential.
    FDA is seeking public comment as to whether metered-dose atropine 
sulfate aerosol human drugs administered by oral inhalation (21 CFR 
2.125(e)(4)(vi)) and anesthetic drugs for topical use on accessible 
mucous membranes of humans where a cannula is used for application (21 
CFR 2.125(e)(4)(iii)) are no longer essential uses as described at 21 
CFR 2.125(e). FDA has information that these products are not currently 
being marketed in an approved form that releases ODSs, and, under 21 
CFR 2.125(g)(1), they may no longer constitute an essential-use. 
Because these products are no longer being marketed, FDA does not 
believe that loss of essential use status would not result in any drugs 
being made unavailable to patients.

III. Comments

    Interested persons may submit either electronic comments regarding 
this document to http://www.regulations.gov or written comments to the 
Division of Dockets Management (see ADDRESSES). It is only necessary to 
send one set of comments. Identify comments with the docket number 
found in brackets in the heading of this document. Received comments 
may be seen in the Division of Dockets Management between 9 a.m. and 4 
p.m., Monday through Friday, and will be posted to the docket at http://www.regulations.gov.

    Dated: June 24, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-15902 Filed 6-26-15; 8:45 am]
 BILLING CODE 4164-01-P