10242 Federal Register / Vol. 62, No. 44 / Thursday, March 6, 1997 / Proposed Rules

compliance approved for AD 86–07–02 are

considered approved as alternative methods

of compliance for this AD.

Note 3: Information concerning the

existence of approved alternative methods of

compliance with this AD, if any, may be

obtained from the Brussels Aircraft

Certification Division.

(g) All persons affected by this directive

may obtain copies of the documents referred

to herein upon request to Fairey Hydraulics

Limited, Claverham, Bristol, England; or

Pilatus Britten-Norman Limited, Bembridge,

Isle of Wight, United Kingdom PO35 5PR, as

applicable; or may examine these documents

at the FAA, Central Region, Office of the

Assistant Chief Counsel, Room 1558, 601 E.

12th Street, Kansas City, Missouri 64106.

(h) This amendment revises AD 86–07–02,

Amendment 39–5382.

Issued in Kansas City, Missouri, on

February 25, 1997.

Michael Gallagher,

Manager, Small Airplane Directorate, Aircraft

Certification Service.

[FR Doc. 97–5491 Filed 3–5–97; 8:45 am]

BILLING CODE 4910–13–U

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.

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 FDAregulated 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 § 2.125 (21 CFR 2.125), any

food, drug, device, or cosmetic in a selfpressurized 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

§ 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 § 2.125(e). Under § 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

§ 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
Federal Register / Vol. 62, No. 44 / Thursday, March 6, 1997 / Proposed Rules 10243

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.’’

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 ozonedepleting substances. Examples of these

alternative dosage forms are MDI’s that

use such non-ozone-depleting

substances as propellants and drypowder 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 § 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-Brelated 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 § 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 § 2.125(e).

2. Drug Products That Are No Longer

Being Marketed

Several of the essential uses listed in

§ 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 § 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 § 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 moiety1 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 essentialuse product. Many of the drug products

marketed under § 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 metereddose corticosteroid human drugs for oral

inhalation and metered-dose short-
10244 Federal Register / Vol. 62, No. 44 / Thursday, March 6, 1997 / Proposed Rules

2The 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.

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.

FDA has tentatively determined that

all drugs currently marketed under

§ 2.125(e)(2) should be considered to be

members of the therapeutic class

‘‘metered-dose corticosteroid2 human

drugs for oral inhalation.’’ These drugs

contain the following active moieties:

• beclomethasone

• dexamethasone

• flunisolide

• fluticasone

• triamcinolone

FDA has tentatively determined that

drugs containing the following active

moieties currently marketed under

§ 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 essentialuse 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
Federal Register / Vol. 62, No. 44 / Thursday, March 6, 1997 / Proposed Rules 10245

3The 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 § 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.

4Single-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.

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

• 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’s4 and MDI’s that do

not contain CFC’s. Continuing changes

in technology may give FDA reason to

revisit this tentative determination.

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
10246 Federal Register / Vol. 62, No. 44 / Thursday, March 6, 1997 / Proposed Rules

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 § 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 § 2.125(e) to eliminate

essential uses that cover an entire class

of drugs, such as current § 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 § 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 ozonedepleting 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.
Federal Register / Vol. 62, No. 44 / Thursday, March 6, 1997 / Proposed Rules 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

DEPARTMENT OF HOUSING AND

URBAN DEVELOPMENT

24 CFR Chapter I

[Docket No. FR–4170–N–07]

Native American Housing Assistance

and Self-Determination Negotiated

Rulemaking Committee; Meetings

AGENCY: Office of the Assistant

Secretary for Public and Indian

Housing, HUD.

ACTION: Notice of Negotiated

Rulemaking Committee Meetings.

SUMMARY: This notice announces three

series of negotiated rulemaking

meetings sponsored by HUD to develop

the regulations necessary to carry out

the Native American Housing

Assistance and Self-Determination Act

of 1996 (NAHASDA) (Pub. L. 104–330,

approved October 26, 1996).

DATES: The meetings will be held on:

1. March 20, 21, 22, 24, 25, 26, and

27, 1997.

2. April 8, 9, 10, and 11, 1997.

3. April 24, 25, 26, 28, 29, 30, and

May 1, 1997.

The meetings will begin at

approximately 9:00 am and end at

approximately 5:00 pm on each day,

local time.

ADDRESS: The meetings will be held at

the Cheyenne Mountain Conference

Resort, 325 Broadmoor Valley Road,

Colorado Springs, CO 8096; telephone

(719) 576–4600 or 1–800–588–6532; fax

(719) 576–4711 (With the exception of

the ‘‘800’’ telephone number, these are

not toll-free numbers).

FOR FURTHER INFORMATION CONTACT:

Dominic Nessi, Deputy Assistant

Secretary for Native American

Programs, Department of Housing and

Urban Development, 1999 Broadway,

Suite 3390, Denver, CO; telephone (303)

675–1600 (voice) or 1–800–877–8339

(TTY for speech or hearing impaired

individuals) (With the exception of the

‘‘800’’ number, these are not toll-free

numbers).

SUPPLEMENTARY INFORMATION: The

Secretary of HUD has established the

Native American Housing Assistance &

Self-Determination Negotiated

Rulemaking Committee (Committee) to

negotiate and develop a proposed rule

implementing NAHASDA. HUD will

hold three series of meetings during

March and April 1997 in Colorado

Springs, Colorado to discuss the

regulatory implementation of

NAHASDA. The meetings will be held

on the following dates:

1. March 20, 21, 22, 24, 25, 26, and

27, 1997.

2. April 8, 9, 10, and 11, 1997.

3. April 24, 25, 26, 28, 29, 30, and

May 1, 1997.

The agenda planned for the meetings

includes: (1) the development of

regulatory language by workgroups; (2)

discussion and approval of the draft

regulatory language by the full

Committee; and (3) other agenda items

which may be agreed upon by the

Committee.

The meetings will be open to the

public without advance registration.

Public attendance may be limited to the

space available. Members of the public

may make statements during the

meeting, to the extent time permits, and

file written statements with the

Committee for its consideration. Written

statements should be submitted to the

address listed in the FOR FURTHER

INFORMATION section of this notice.

Summaries of Committee meetings will

be available for public inspection and

copying at the same address.

The location and dates of any future

meetings will be published in the

Federal Register. HUD will make every

effort to publish such notice at least 15

calendar days prior to each meeting.

Dated: March 3, 1997.

Kevin Emanuel Marchman,

Acting Assistant Secretary for Public and

Indian Housing.

[FR Doc. 97–5564 Filed 3–5–97; 8:45 am]

BILLING CODE 4210–33–P

DEPARTMENT OF THE INTERIOR

Minerals Management Service

30 CFR Parts 202 and 206

RIN 1010–AB57

Amendments to Gas Valuation

Regulations for Indian Leases

AGENCY: Minerals Management Service,

Interior.

ACTION: Notice of meeting and reopening

of public comment period.

SUMMARY: The Minerals Management

Service (MMS) is reopening the public

comment period for a proposed rule

published in the Federal Register on

September 23, 1996, 61 FR 49894,

amending its regulations governing the

valuation for royalty purposes of natural

gas produced from Indian leases.

DATES: Comments must be submitted on

or before April 4, 1997. The committee

meeting will be on March 26, 1997.

ADDRESSES: MMS will hold a meeting of

the Indian Gas Valuation Negotiated

rulemaking committee on March 26,

1997, in the conference room at: Golden

Hill Office Complex, 12600 West Colfax

Avenue, Suite B200, Golden, Colorado.

Written comments, suggestions, or

objections regarding this proposed

amendment should be sent to the

following addresses. For comments sent

via the U.S. Postal Service use: Minerals

Management Service, Royalty

Management Program, Rules and

Publications Staff, P.O. Box 25165, MS

3101, Denver, Colorado 80225–0165.

For comments via courier or overnight

delivery service use: Minerals

Management Service, Royalty

Management Program, Rules and

Publications Staff, MS 3101, Building

85, Denver Federal Center, Room A–

212, Denver, Colorado 80225–0165.

FOR FURTHER INFORMATION CONTACT:

David S. Guzy, Chief, Rules and

Publications Staff, phone (303) 231–

3432, FAX (303) 231–3194, e-Mail

DavidlGuzy@smtp.mms.gov.

FOR FURTHER INFORMATION CONTACT:

David S. Guzy, Chief, Rules and

Procedures Staff, at (303) 231–3432.

I. SUPPLEMENTARY INFORMATION:

Background

On September 23, 1996, MMS

published a notice of proposed

rulemaking in the Federal Register (61

FR 49894) to amend the valuation

regulations for gas production from

Indian leases. The framework for the

proposed rule was the product of an

Indian Gas Valuation Negotiated

Rulemaking Committee. The proposed

rulemaking provided for a 60-day

comment period, which ended

November 22, 1996, and was extended

to December 3, 1996, by a Federal

Register Notice (61 FR 59849, November

25, 1996). during the public comment

period MMS received 13 written

comments: 7 responses from industry, 4

from industry trade groups or

associations, 1 from an Indian tribe, and

1 from an Indian agency. A public

hearing was held in Oklahoma City,

Oklahoma, on October 23, 1996.

II. Comments on Proposed Rule

MMS proposed to revise the current

regulations regarding the valuation of

gas production from Indian leases to

accomplish the following:

• To ensure that Indian mineral

lessors receive the maximum revenues

from mineral resources on their land

consistent with the Secretary of the