[Federal Register Volume 62, Number 44 (Thursday, March 6, 1997)]
[Proposed Rules]
[Pages 10242-10247]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-5495]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 2
[Docket No. 97N-0023]
RIN 0910-AA99
Chlorofluorocarbon Propellants in Self-Pressurized Containers;
Determinations That Uses Are No Longer Essential; Request for Comments
AGENCY: Food and Drug Administration, HHS.
ACTION: Advance notice of proposed rulemaking.
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SUMMARY: The Food and Drug Administration (FDA) is seeking public
comment on the policy it is considering for adoption on making and
implementing determinations that uses of chlorofluorocarbons (CFC's)
currently designated essential will no longer be deemed essential under
the Clean Air Act due to the availability of safe and effective medical
product technology that does not use CFC's. 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. The agency is taking this
action because it is responsible for determining which products
containing CFC's or other ozone-depleting substances are an essential
use under the Clean Air Act. FDA is soliciting comments on this policy
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 treatment alternatives and by curtailing the release
of ozone-depleting substances.
DATES: Written comments by May 5, 1997.
ADDRESSES: Submit written comments to the Dockets Management Branch
(HFA-305), Food and Drug Administration, 12420 Parklawn Dr., rm. 1-23,
Rockville, MD 20857.
FOR FURTHER INFORMATION CONTACT: Wayne H. Mitchell, Center for Drug
Evaluation and Research (HFD-7), Food and Drug Administration, 7500
Standish Pl., Rockville, MD 20855, 301-594-2041.
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 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. 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 FDA 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 that would not be obtainable
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 the provisions of section 610 of the
Clean Air Act (42 U.S.C. 7671i) 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 EPA 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 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).
Production of ozone-depleting substances 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 CFC's in the United States was generally banned as of
January 1, 1996. To receive permission to manufacture CFC's in the
United States after the phaseout date, manufacturers must obtain an
exemption from the phaseout 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 CFC's manufactured after the phaseout date in
medical devices (as
[[Page 10243]]
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 phaseout of the production of
CFC's, drug manufacturers are developing or have developed alternatives
to MDI's and other self-pressurized drug dosage forms that do not
contain ozone-depleting substances. Examples of these alternative
dosage forms are MDI's that use such non-ozone-depleting substances as
propellants and dry-powder inhalers (DPI's). FDA has recently approved
the first CFC-free MDI, 3M Pharmaceuticals Inc.'s albuterol sulfate
product, Proventil HFA; although a determination has not yet
been made on whether this product is a technically feasible alternative
to the use of CFC's, this approval gives the subject matter of this
advance notice of proposed rulemaking (ANPRM) a particular timeliness.
The current or future availability of ``technically feasible
alternatives to the use of a [CFC]'' may mean that the existing listing
of a use in Sec. 2.125(e) would no longer reflect current conditions.
It is with this situation in mind that FDA is publishing this ANPRM
regarding agency determinations that certain uses of ozone-depleting
substances are no longer essential.
FDA has determined that it would be most productive to set out the
following tentative policy on the elimination of essential uses in an
ANPRM. The agency believes that providing an opportunity for the
fullest public participation at the earliest possible stage in the
agency decisionmaking process in this matter is appropriate to assist
FDA in striking an appropriate balance that will best protect the
public health, both by ensuring the availability of an adequate number
of treatment alternatives and by curtailing the release of ozone-
depleting substances. In striking this balance, FDA intends to assess a
number of factors and is interested in public comment on them. In
establishing its policy on the elimination of essential uses, FDA will
assess the potential beneficial effects of reducing CFC emissions from
drug products broadly, based on the amount of CFC emissions that would
be avoided, the stratospheric ozone depletion that would be averted,
and the resulting decline in incidence of UV-B-related adverse human
health effects, including human cancers and cataracts. FDA will also
assess the beneficial public health effects of continued availability
of CFC-containing drug products broadly, based on the availability,
safety, and efficacy of alternatives, in full consideration of
differences in patients' medical circumstances, physiological
sensitivity, and acceptability of use, among others. FDA is
specifically soliciting comments on how it should develop information
to assist in striking this balance and how it should further balance
the need for timely action. FDA also believes that there is adequate
time to publish an ANPRM and respond to comments but will endeavor to
complete this rulemaking process in a timely fashion. Because the first
potential technically feasible alternatives are just now coming on the
market, it will take a significant amount of time for manufacturers to
collect and present the postmarketing safety and patient acceptance
data that the agency will need to determine if the products are, in
fact, technically feasible alternatives (see section II.B. of this
document).
II. Proposed Policy
FDA has tentatively determined that certain uses of CFC's, listed
in Sec. 2.125(e) as essential, can no longer be considered to be
essential. FDA is considering proposing to remove these uses from the
list of essential uses in a rulemaking to be initiated soon. Uses no
longer considered essential are discussed in section II.A. of this
document. FDA also expects that certain uses still considered to be
essential will cease to be considered essential as new technology
develops. Section II.B. of this document describes the policy that FDA
has tentatively determined will be used in making determinations that
these uses of CFC's are no longer essential. FDA has worked closely
with EPA in developing the following policy and this ANPRM reflects
those discussions. This policy will also be the subject of a notice of
proposed rulemaking to incorporate the policy into FDA regulations.
A. Listed Uses That Are No Longer Considered Essential
1. Metered-Dose Steroid Human Drugs for Nasal Inhalation
Steroid human drugs for nasal inhalation are currently available
using metering atomizing pumps rather than nasal MDI's. The
availability of such products as Beconase AQ and
Vancenase AQ (beclomethasone dipropionate monohydrate),
Nasarel and Nasalide (flunisolide),
Flonase (fluticasone propionate), and Nasacort AQ
(triamcinolone acetonide), and the widespread patient acceptance of
these products, indicate to FDA that using CFC's in metered-dose
steroid human drugs for nasal inhalation can no longer be considered to
be essential and FDA has tentatively determined to remove the use from
Sec. 2.125(e).
2. Drug Products That Are No Longer Being Marketed
Several of the essential uses listed in Sec. 2.125(e) exempt only a
single approved drug product and, in a few cases, that drug product is
no longer being marketed (or is no longer being marketed in a
formulation containing CFC's). FDA has tentatively determined that an
essential use for which no drug product is currently being marketed
should no longer be considered to be essential. The absence of a demand
for the product sufficient for even one company to market it is highly
indicative that the use is not essential. Therefore, FDA has
tentatively determined to remove the following uses from Sec. 2.125(e):
Polymyxin B sulfate-bacitracin zinc-neomycin sulfate soluble antibiotic
powder without excipients, for topical use on humans; and contraceptive
vaginal foams for human use.
B. Criteria for Determination That a Use Is No Longer Essential
1. Therapeutic Classes
In evaluating petitions submitted under Sec. 2.125(f) requesting
that a new use be listed as essential, FDA has not required a showing
that technically feasible non-CFC alternatives to a product contain the
same active ingredient or active moiety\1\ as the drug product that
would be the subject of the proposed essential use. Thus, if other drug
products, containing other active moieties, are available for treatment
of the same condition, they may be considered technically feasible
alternatives to the proposed essential-use product. Many of the drug
products marketed under Sec. 2.125 are pharmacologically closely
related, are indicated for the treatment of the same conditions, and
may be considered to be treatment alternatives. In evaluating whether a
use remains essential, FDA believes that it is appropriate to evaluate
these treatment alternatives together as a therapeutic class. In this
regard, FDA has tentatively determined that metered-dose corticosteroid
human drugs for oral inhalation and metered-dose short-
[[Page 10244]]
acting adrenergic bronchodilator human drugs for oral inhalation are
appropriate therapeutic classes for essential-use determinations. The
determination of whether drug products that are not members of either
therapeutic class represent essential uses of CFC's will be made under
the criteria set out in section II.B.2. of this document.
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\1\ 21 CFR 314.108(a) defines active moiety as meaning ``the
molecule or ion, excluding those appended portions of the molecule
that cause the drug to be an ester, salt (including a salt with
hydrogen or coordination bonds), or other noncovalent derivative
(such as a complex, chelate, or clathrate) of the molecule,
responsible for the physiological or pharmacological action of the
drug substance.''
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FDA has tentatively determined that all drugs currently marketed
under Sec. 2.125(e)(2) should be considered to be members of the
therapeutic class ``metered-dose corticosteroid\2\ human drugs for
oral inhalation.'' These drugs contain the following active moieties:
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\2\ The active ingredients in all drug products currently
marketed under the essential use for metered-dose steroid human
drugs for oral inhalation are members of the subclass of substances
known as corticosteroids. FDA has tentatively determined that it
would be more accurate to use the more specific term corticosteroids
rather than the more general term steroids to describe the
therapeutic class.
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beclomethasone
dexamethasone
flunisolide
fluticasone
triamcinolone
FDA has tentatively determined that drugs containing the following
active moieties currently marketed under Sec. 2.125(e)(3) should be
considered to be members of the therapeutic class ``metered-dose short-
acting adrenergic bronchodilator human drugs for oral inhalation'':
albuterol
bitolterol
isoetharine
isoproterenol
metaproterenol
pirbuterol
terbutaline
Adrenergic bronchodilator drug products containing the active
moiety salmeterol are not included in the therapeutic class because of
the longer duration of action and different indication of usage of
salmeterol as compared to metered-dose short-acting adrenergic
bronchodilator human drugs for oral inhalation. Adrenergic
bronchodilator drug products containing the active moiety epinephrine
are also not included in the class because epinephrine is the only
active moiety used in drug products sold over-the-counter (OTC). These
OTC drug products are available to patients who may not have access to
prescription drugs. Therefore, FDA has tentatively determined that
prescription drug products should not be considered as alternatives to
drug products containing epinephrine. The determination of whether a
drug product containing salmeterol or epinephrine constitutes an
essential use would be considered under the criteria for an individual
active moiety discussed in section II.B.2. of this document.
The use of CFC's in any drug product that is a member of a
therapeutic class described above would no longer be considered
essential if, for each therapeutic class:
1. Three distinct alternative products, representing at least two
different active moieties, are being marketed, with the same route of
delivery, for the same indication, and with approximately the same
level of convenience of use as the products containing CFC's. At least
two of the three alternative products must be MDI's.
2. Adequate supplies and production capacity exist for the
alternative products to meet the needs of the population indicated for
the therapeutic class.
3. At least 1 year of postmarketing use data for each product are
available. There should be persuasive evidence of patient acceptance in
the United States of each of the alternative products.
4. There is no persuasive evidence to rebut a presumption that all
significant patient subpopulations are served by the alternative
products.
FDA believes that making essential-use determinations for an entire
class of closely related drug products will expedite the elimination of
drug products that release ozone-depleting substances. FDA recognizes
that there may be limited incentives to develop alternative products
containing every active moiety currently marketed under essential-use
exemptions. By eliminating the essential use by therapeutic class, FDA
will ensure that these drugs do not remain on the market longer than
necessary.
FDA also hopes that the knowledge that the essential use covering a
given product may be eliminated, even though no alternative product
exists containing the same active moiety as that product, may provide
added incentive for the manufacturer of that product to develop an
alternative product containing the same active moiety. In addition, the
agency believes that requiring multiple alternative drug products
containing multiple active moieties should ensure that all significant
patient populations have safe and effective alternatives to CFC-
containing drug products.
A discussion of the application of these criteria can be found in
section II.B.3 of this document.
Under the proposed policy being considered for elimination of the
essential-use status of the therapeutic classes, the essential-use
status for individual members of a therapeutic class would only be
eliminated when the essential-use status for the therapeutic class as a
whole is eliminated. FDA recognizes that this approach may allow the
essential-use status of an individual member of a therapeutic class to
be retained despite the marketing of one or more technically feasible
alternatives containing the same active moiety, pending elimination of
the essential-use status for the therapeutic class as a whole. In
addition to the policy FDA is considering for elimination of the
essential-use status of the therapeutic classes described above, FDA is
considering a policy for elimination of the essential-use status of
individual members of a therapeutic class in advance of elimination of
the essential-use status for the therapeutic class as a whole. Under
this proposed policy, the essential-use status of an active moiety
within a therapeutic class would be eliminated when one alternative
product that contains the same active moiety is being marketed. All
other elements of the policy regarding therapeutic classes would apply,
including: The alternative product is delivered by the same route of
administration, for the same indication, and with approximately the
same level of convenience of use; there are adequate supplies and
production capacity; at least 1 year of postmarketing use data are
available; and there is no persuasive evidence to rebut a presumption
that all significant patient subpopulations using that active moiety
are served by the alternative product. Therapeutic classes would still
be evaluated under the proposed therapeutic class policy, and
alternative products used in the evaluation of the essential-use status
of a member of the therapeutic class under the proposed additional
policy would also be used in the evaluation of the class as a whole.
FDA requests public comment on these approaches, and other possible
approaches, for the elimination of the essential-use status of
individual members of the therapeutic classes and the therapeutic
classes as a whole.
2. Individual Active Moieties
In examining the essential-use status of drug products when FDA has
not already made a tentative determination that a currently listed
essential use can no longer be considered to be essential, or when the
drug is not a member of one of the therapeutic classes described in
section II.B.1. of this document, FDA will look at other drug products
containing the same active moiety as possible technically feasible
alternatives. The use of CFC's in any drug product that is not a member
of a
[[Page 10245]]
therapeutic class described in section II.B.1. of this document would
no longer be considered essential if:
1. One alternative product containing the same active moiety is
being marketed, delivered by the same route of administration, for the
same indication, and with approximately the same level of convenience
of use compared to the product containing CFC's.
2. Adequate supplies and production capacity exist to meet the
needs of the population indicated for the alternative drug product
containing the active moiety.
3. At least 1 year of postmarketing use data for the product are
available. There should be persuasive evidence of patient acceptance in
the United States of the alternative product.
4. There is no persuasive evidence to rebut a presumption that all
significant patient subpopulations are served by the alternative
product.
A discussion of the application of these criteria can be found in
section II.B.3. of this document.
Drug products marketed under the following current essential uses
would generally be evaluated under the above ``individual active
moieties'' criteria:
Metered-dose ergotamine tartrate drug products administered by
oral inhalation for use in humans.
Intrarectal hydrocortisone acetate for human use.
Anesthetic drugs for topical use on accessible mucous
membranes of humans where a cannula is used for application.
Metered-dose nitroglycerin human drugs administered to the
oral cavity.
Metered-dose cromolyn sodium human drugs administered by oral
inhalation.
Metered-dose ipratropium bromide for oral inhalation.
Metered-dose atropine sulfate aerosol human drugs administered
by oral inhalation.\3\
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\3\ The evaluation of the essential use status of drug products
containing atropine sulfate may be an exception to the application
of the criteria set out in section II.B. of this document. Drug
products containing atropine sulfate were never commercially
marketed under Sec. 2.125, but were manufactured for the U.S. Army
for use by armed services personnel. The unique status of this use
may require that other criteria be applied to it.
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Metered-dose nedocromil sodium human drugs administered by
oral inhalation.
Metered-dose ipratropium bromide and albuterol sulfate, in
combination, administered by oral inhalation for human use.
Sterile aerosol talc administered intrapleurally by
thoracoscopy for human use.
As discussed in section II.B.1. of this document, the essential-use
status of drugs containing the active moieties epinephrine and
salmeterol will also be evaluated under the ``individual active
moieties'' criteria.
FDA requests public comment on the appropriateness of potentially
eliminating such essential uses and criteria outlined here.
3. Discussion of Criteria
In arriving at the tentative criteria for evaluating the essential-
use status of the two therapeutic classes, FDA has kept in mind that
the MDI is the most widely accepted delivery system for administering
drugs by oral inhalation for the treatment of asthma and chronic
obstructive pulmonary disease. Physicians and patients value an MDI's
compact size and ease of use. Because these factors are important and
help ensure that patients receive appropriate medical treatment, FDA
would require that at least two of the alternative products be
available as an MDI. FDA is also aware that not all patients may
tolerate a given drug product. Accordingly, FDA has reached the
tentative conclusion that there must be products representing at least
two different active moieties before FDA will consider that there are
technically feasible alternatives to the therapeutic class. FDA is
proposing that there be three distinct drug products. FDA wishes to
ensure that there are substantial differences among the alternative
products in order to give patients a wide variety of therapeutic
options. Therefore, a drug product and a second generic drug product
that refers to the first drug product to gain approval, under section
505(j) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355(j)),
would not generally be considered to be two distinct drug products for
purposes of evaluating the essential-use status of the drug.
For most of the essential uses that would be evaluated under the
``individual active moieties'' criteria, there is only one product
being marketed under each essential use. Therefore, requiring the
availability of more than one alternative would appear to be
inadvisable.
Because of their larger size and relative lack of convenience of
use, FDA does not consider currently available nebulizers to be
technically feasible alternatives to MDI's. Currently available
delivery systems that FDA considers to be technically feasible
alternatives to MDI's using CFC's are multiple-dose DPI's\4\ and MDI's
that do not contain CFC's. Continuing changes in technology may give
FDA reason to revisit this tentative determination.
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\4\ Single-dose DPI's that are currently marketed in the United
States would not be considered technically feasible alternatives to
MDI's using CFC's. The agency has tentatively determined that these
single-dose DPI's do not approximate the convenience of MDI's
because patients must carry both the single-dose DPI device and a
supply of the drug. The patient must also load the device prior to
each use. The comparative inconvenience of single-dose DPI's does
not warrant their being considered technically feasible
alternatives. The agency also believes that these single-dose DPI's
have not shown adequate levels of patient acceptance.
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In evaluating whether adequate supplies and production capacity
exist for the alternative product or products to meet the needs of the
patient population indicated for drug products covered by an essential
use, FDA's analyses will be flexible, but with one overarching
principle: To ensure that there are no significant shortages of drug
product that could harm the public health of the United States. Factors
such as multiple production sites, to secure a steady supply if there
is an interruption at one site, would be considered favorably in this
regard.
In evaluating postmarketing use data and evidence of patient
acceptance under the third criterion, FDA anticipates that it may be
useful for sponsors of alternative products to conduct large
postmarketing studies, preferably in the U.S. clinical practice
setting, directly comparing their product which does not contain CFC's
to the CFC-containing product for which it would be considered an
alternative. It may also be possible for several sponsors to jointly
commission a large postmarketing clinical study of their common
products. In addition to the formal studies described above,
manufacturers of alternative products, or other persons requesting the
elimination of an essential use, may wish to submit to FDA a review of
postmarketing surveillance data from FDA's MEDWATCH program, the
spontaneous reporting systems of other countries, and all other
available postmarketing data after a potential alternative product has
been marketed in the United States for a period of 1 year. FDA has
tentatively concluded that foreign data would not be considered
acceptable as the sole evidence of patient acceptance, but these data
will be considered in addition to U.S. postmarketing use data in cases
where U.S. formulations and foreign formulations have been shown to be
the same or substantially similar. The term ``patient acceptance'' here
[[Page 10246]]
assumes that the alternative products have adequate safety,
tolerability, effectiveness, and compliance. Because information
regarding patient acceptance is not routinely captured by postmarketing
surveillance, such assessments should be incorporated into the proposed
formal clinical studies.
In evaluating the last criterion, that there is no persuasive
evidence to rebut a presumption that all significant patient
subpopulations are served by the alternative product, FDA believes that
there should be a strong presumption that, if the first three criteria
are met, then all relevant subpopulations will be adequately served by
alternative products. If FDA is not already in possession of evidence
indicating the presence of a subpopulation served only by a product
containing CFC's, then the burden of producing compelling scientific
evidence that there is a subpopulation served only by a product
containing CFC's would be placed on anyone opposing the determination
that a use is no longer essential.
C. Implementation
FDA currently intends to publish a notice of proposed rulemaking
after the comment period for this ANPRM closes. That proposed rule
would eliminate essential uses for steroid human drugs for nasal
inhalation and for drugs that are no longer marketed. The proposed rule
would also codify the criteria for elimination of essential uses
discussed in section II.B. of this document. FDA intends to use the
preamble of the proposed rule to respond to comments on this ANPRM.
As the criteria for eliminating essential uses are met, FDA will
propose elimination of essential uses for the appropriate therapeutic
classes or individual active moieties. FDA intends that such proposals
will be published and finalized in an expeditious manner.
FDA is aware that the proposed policy contained in this ANPRM is,
to a certain degree, predicated on the assumption that drug
manufacturers are aggressively developing alternatives to products
containing CFC's. If this assumption is less than fully met, FDA
recognizes that it may have to take an even more active role in
encouraging the development of technically feasible alternatives.
Furthermore, FDA contemplates reexamining the effectiveness of the
policy set out in this ANPRM 1 to 3 years after the publication of the
first final rule implementing the policy set out in this ANPRM. If this
reexamination reveals that alternatives to CFC's are not being
aggressively developed, FDA will consider eliminating essential uses
where manufacturers of drug products covered by those uses have not
demonstrated due diligence in developing alternative products.
D. Analysis of Impacts
FDA is required to examine the impacts of its proposed rules under
Executive Order 12866 and the Regulatory Flexibility Act (5 U.S.C. 601-
612). 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 Regulatory
Flexibility Act requires agencies to analyze regulatory options if the
proposed rule is expected to have a significant impact on a substantial
number of small entities. FDA is soliciting information and data to
help it examine the impacts that a proposed rule based on this advance
notice would have. In order to help the agency prepare these analysis,
FDA requests comments on the following impact questions:
1. Are the incentives discussed in the ANPRM adequate to spur the
needed market innovation? Are there alternative means of introducing
appropriate market incentives?
2. Assuming that an alternative product is approved for marketing,
what is the estimated cost of obtaining postmarketing data supporting
the new product as a technologically feasible alternative? How much
time would be necessary? What other costs should the agency consider?
3. How much would it cost to obtain the data including the
postmarketing study discussed in the ANPRM? How much would it cost to
obtain the data excluding such a postmarketing study? What are the
components of this estimate (e.g., person-hours, contract dollars,
etc.)?
4. How much time should be allowed for phasing out a CFC-containing
product no longer considered essential?
5. Are there other alternative policies that the agency should
consider that would achieve the stated goals and be less burdensome to
patients that use these products and/or to the industry that provides
the products?
III. Other Rulemaking Proceedings Regarding CFC's
In the very near future, FDA intends to propose a rule regarding
criteria to be applied in agency determinations to add new essential
uses to Sec. 2.125(e). The agency is not soliciting comments on this
separate rulemaking proceeding, and is only mentioning the matter here
to provide a more complete picture of FDA's current plans regarding the
regulation of CFC-containing drug products. FDA does not intend to
respond to any comments regarding this issue at this time; those
persons wishing to comment on this issue should wait until the proposed
rule is published.
Consistent with the phaseout provisions of the Clean Air Act, the
proposed rule regarding the addition of new essential uses will provide
new and substantially more stringent criteria for determining that a
use is essential. Specific criteria will be proposed for both
investigational drugs and commercially marketed drugs.
FDA currently intends that this proposed rule will provide a
restructuring of Sec. 2.125(e) to eliminate essential uses that cover
an entire class of drugs, such as current Sec. 2.125(e)(3) ``metered-
dose adrenergic bronchodilator human drugs for oral inhalation.'' In
their place, FDA will propose to list the use of every active moiety
currently marketed under the current class essential use. This will
mean that an individual wishing to market, for example, an adrenergic
bronchodilator where the active moiety is not listed will need to
petition FDA to amend Sec. 2.125(e) to add the use of the active
moiety.
The proposed rule would also eliminate out-of-date transitional
provisions, and make other similar nonsubstantive housekeeping changes.
The agency has determined to go directly to a proposed rule on
these provisions of the agency's policy, rather than requesting comment
on them in this or another ANPRM, in order to accelerate consideration
of the new more stringent criteria for determining when new uses are
essential. FDA believes that as the agency will soon be eliminating
essential uses, it would be a waste of scarce agency resources, as well
as inconsistent with the general policy favoring the phase out of
ozone-depleting substances, to create new essential uses unless an
extraordinary showing of public benefit can be made.
Interested persons may, on or before May 5, 1997, submit to the
Dockets Management Branch (address above) written comments regarding
this ANPRM. 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.
[[Page 10247]]
Dated: February 28, 1997.
William B. Schultz,
Deputy Commissioner for Policy
[FR Doc. 97-5495 Filed 3-5-97; 8:45 am]
BILLING CODE 4160-01-F
