20162 Federal Register / Vol. 60, No. 78 / Monday, April 24, 1995 / Rules and Regulations

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

21 CFR Part 310

[Docket No. 79N–0379]

RIN 0905–AA06

Exocrine Pancreatic Insufficiency Drug

Products for Over-The-Counter Human

Use

AGENCY: Food and Drug Administration,

HHS.

ACTION: Final rule.

SUMMARY: The Food and Drug

Administration (FDA) is issuing a final

rule establishing that over-the-counter

(OTC) exocrine pancreatic insufficiency

drug products (drug products used to

treat pancreatic enzyme deficiency) are

not generally recognized as safe and

effective and are misbranded. FDA is

issuing this final rule after considering

public comments on the agency’s notice

of proposed rulemaking and all new

information on OTC exocrine pancreatic

insufficiency drug products that has

come to the agency’s attention. This

final rule is part of the ongoing review

of OTC drug products conducted by

FDA.

EFFECTIVE DATE: October 24, 1995.

FOR FURTHER INFORMATION CONTACT:

William E. Gilbertson, Center for Drug

Evaluation and Research (HFD–810),

Food and Drug Administration, 5600

Fishers Lane, Rockville, MD 20857,

301–594–5000.

SUPPLEMENTARY INFORMATION:

I. Background

In the Federal Register of December

21, 1979 (44 FR 75666), FDA published,

under § 330.10(a)(6) (21 CFR

330.10(a)(6)), an advance notice of

proposed rulemaking to establish a

monograph for OTC exocrine pancreatic

insufficiency drug products, together

with the recommendations of the

Advisory Review Panel on OTC

Miscellaneous Internal Drug Products

(the Panel), which was the advisory

review panel responsible for evaluating

data on the active ingredients in this

drug class. Interested persons were

invited to submit comments by April 21,

1980. Reply comments in response to

comments filed in the initial comment

period could be submitted by May 21,

1980.

In accordance with § 330.10(a)(10),

the data and information considered by

the Panel were placed on public display

in the Dockets Management Branch

(HFA–305), Food and Drug

Administration, rm. 1–23, 12420

Parklawn Dr., Rockville, MD 20857,

after deletion of a small amount of trade

secret information. Only five comments

were submitted in response to the

publication of the advance notice of

proposed rulemaking.

The agency’s proposed regulation, in

the form of a tentative final monograph,

for OTC exocrine pancreatic

insufficiency drug products was

published in the Federal Register of

November 8, 1985 (50 FR 46594). That

proposal constituted FDA’s tentative

adoption of the Panel’s conclusions and

recommendations on OTC exocrine

pancreatic insufficiency drug products

as modified on the basis of the

comments received and the agency’s

independent evaluation of the Panel’s

report and information available at that

time. In that document, the agency

accepted the Panel’s recommendation

that exocrine pancreatic insufficiency

drug products be available as OTC drug

products and proposed the conditions

under which these drug products would

be generally recognized as safe and

effective and not misbranded. Interested

persons were invited to file by January

7, 1986, written comments, objections,

or requests for oral hearing before the

Commissioner of Food and Drugs (the

Commissioner) regarding the proposal,

and by March 10, 1986, to file

comments on the agency’s economic

impact determination. New data could

have been submitted until November 10,

1986, and comments on the new data

until January 8, 1987.

New information submitted in

response to the tentative final

monograph caused the agency to

reconsider the approach proposed in

that document. In vivo and in vitro

studies of various commercial

pancreatic enzyme preparations had

demonstrated variations in lipase

activity and release rates among the

products. These variations in pancreatic

extract drug products occurred both

among various dosage forms and among

products from different manufacturers

of the same dosage form. In addition,

problems had been reported with

pancreatic extract products

manufactured as tablets with enteric

coatings and as encapsulated entericcoated microspheres. As a result of the

wide range of enzyme activity in these

products, the variety of dosage forms

marketed, and the apparent uneven

quality of the enteric coatings among

pancreatic extract drug products,

instances of underdosing and

overdosing with pancreatic extract

products have occurred. The agency

determined that preclearance of each

product in order to standardize enzyme

bioactivity was necessary to avoid

serious safety problems resulting from

too little or too much enzyme

supplementation. The agency

tentatively concluded that an OTC drug

monograph would not be sufficient to

adequately regulate these drug products.

The agency discussed these problems in

the Federal Register of July 15, 1991 (56

FR 32282 at 32286 and 32287).

In that notice, FDA proposed to

classify OTC drug products to treat

exocrine pancreatic insufficiency as not

generally recognized as safe and

effective, as being misbranded, and as

new drugs within the meaning of

section 201(p) of the Federal Food,

Drug, and Cosmetic Act (the act) (21

U.S.C. 321(p)). FDA proposed to amend

part 310, subpart E by adding new

§ 310.543 (21 CFR 310.543) for OTC

exocrine pancreatic insufficiency drug

products. The agency also withdrew its

proposed rule (part 357, subpart E)

issued on November 8, 1985. Interested

persons were invited to file by

November 12, 1991, written comments,

objections, or requests for oral hearing

on the proposed regulation before the

Commissioner, and to file comments on

the agency’s economic impact

determination by November 12, 1991.

Final agency action occurs with the

publication of this final rule on OTC

exocrine pancreatic insufficiency drug

products.

In the Federal Register of March 11,

1992 (57 FR 8586), the agency reopened

the administrative record and

announced that a workshop would be

held on April 23, 1992, to discuss

testing procedures that will be required

as part of new drug applications

(NDA’s) for all exocrine pancreatic

insufficiency drug products. Relevant

data and notice of participation were to

be submitted by April 10, 1992. The

administrative record remained open

until July 23, 1992, to receive comments

regarding matters raised at the

workshop.

In response to the announcement of

the workshop, eight notices of

participation and three comments were

submitted. Copies of the comments,

notices received, and information

coming to the agency’s attention after

the workshop are also on public display

in the Dockets Management Branch

(address above). At the conclusion of

the workshop, manufacturers were

encouraged to arrange pre-NDA

meetings with agency personnel so that

NDA submissions could proceed as

quickly as possible (Ref. 1).

This final rule amends part 310 to

include drug products containing

ingredients for the treatment of exocrine

pancreatic insufficiency by adding new
Federal Register / Vol. 60, No. 78 / Monday, April 24, 1995 / Rules and Regulations 20163

§ 310.543 to subpart E. The inclusion of

OTC exocrine pancreatic insufficiency

drug products in part 310 follows FDA’s

established policy for regulations in

which there are no monograph

conditions. (See, e.g., §§ 310.510,

310.519, 310.525, 310.526, 310.532,

310.533, 310.534, and 310.546.) It is the

agency’s intent that exocrine pancreatic

insufficiency drug products be marketed

by prescription only. However, if, in the

future, any ingredient is determined to

be generally recognized as safe and

effective for use in an OTC exocrine

pancreatic insufficiency drug product,

the agency will promulgate an

appropriate regulation at that time.

FDA no longer uses the terms

‘‘Category I’’ (generally recognized as

safe and effective and not misbranded),

‘‘Category II’’ (not generally recognized

as safe and effective or misbranded),

and ‘‘Category III’’ (available data are

insufficient to classify as safe and

effective, and further testing is required)

at the final rule stage. In place of

Category I, the term ‘‘monograph

conditions’’ is used; in place of Category

II or III, the term ‘‘nonmonograph

conditions’’ is used.

In the proposed rule for OTC exocrine

pancreatic insufficiency drug products

(56 FR 32282 at 32283), the agency

advised that the final rule for these drug

products would be effective 6 months

after the date of its publication in the

Federal Register. Therefore, on or after

October 24, 1995, no OTC drug products

that are subject to this final rule may be

initially introduced or initially

delivered for introduction into interstate

commerce unless they are the subject of

an approved application. The agency is

unaware of any OTC exocrine

pancreatic insufficiency drug products

that are the subject of an approved

application. Any such drug product in

interstate commerce after the effective

date of this final rule that is not in

compliance with the regulation is

subject to regulatory action.

In response to the proposed rule on

OTC exocrine pancreatic insufficiency

drug products, five drug manufacturers,

one foundation, and three individuals

submitted comments. Copies of the

comments received and any additional

information that has come to the

agency’s attention since publication of

the proposed rule are on public display

in the Dockets Management Branch

(address above).

Reference

(1) Comment No. MM1, Docket No. 79N–

0379, Dockets Management Branch.

II. The Agency’s Conclusions on the

Comments

1. Six comments (including the Cystic

Fibrosis Foundation and the American

Academy of Pediatrics) agreed with the

agency’s proposal that exocrine

pancreatic insufficiency drug products

should not be marketed OTC. Three

comments opposed the proposal. Two of

those comments stated that increased

costs to consumers would include a

physician’s fee and a higher markup

when sold by prescription. The third

comment indicated that these products

are currently reasonably priced as

nonprescription drugs.

The agency appreciates the support of

the six agreeing comments and is

finalizing its proposal that all exocrine

pancreatic insufficiency drug products

should be available only by a doctor’s

prescription. The agency stated in the

proposed rule that continuous physician

monitoring of patients appears to be one

of several important factors in the

increased survival rates for exocrine

pancreatic insufficiency patients (56 FR

32282 at 32285). Accordingly, such

collateral measures necessary to the use

of these drug products require that they

be available by prescription only, as

required by section 503(b)(1)(B) of the

act (21 U.S.C. 353(b)(1)(B)). The agency

acknowledges the cost concerns raised

by the three opposing comments.

However, as stated in the proposed rule

(56 FR 32282 at 32285), financial

considerations are not among the

statutory criteria for determining

whether a drug product should be

restricted to prescription status.

2. Two comments disagreed with the

agency’s proposal that NDA approval be

required for continued marketing of all

exocrine pancreatic insufficiency drug

products. One comment stated that the

proposal is inconsistent with the Panel’s

and the agency’s previous conclusion

that these products have been safely

used to treat exocrine pancreatic

insufficiency for many years (50 FR

46594 at 46597). The comment

contended that the July 15, 1991,

proposal did not contain any new

evidence showing that the initial

conclusion was erroneous. The

comment stated that the agency’s

concerns are based on a perceived

inability of patients to treat themselves

and mentioned that this problem could

be remedied by requiring these products

to be available by prescription, without

the need for an NDA for continued safe

and effective use. The comment

contended that an NDA requirement

would have a devastating effect on

patients who require these products for

survival, e.g., cystic fibrosis patients.

The comment surmised that most

manufacturers would withdraw their

exocrine pancreatic insufficiency drug

products from the market if an NDA

were required, primarily because of

NDA-associated costs. The comment

added that manufacturers would wait

until another manufacturer’s application

was approved so they could submit an

abbreviated NDA. A third comment

made a number of suggestions for the

bioactivity testing requirements, urged

that certain products that had been

extensively used and studied be granted

approval on the basis of published

reports and in vitro data, and contended

that placebo-controlled safety and

effectiveness studies in cystic fibrosis

patients are unethical.

The agency disagrees with the first

two comments. The agency’s position

on exocrine pancreatic insufficiency

drug products changed between 1985

and 1991. Based on variations in

formulations and dosage forms, e.g.,

encapsulated microsphere dosage forms,

in use in 1991, the agency determined

that final formulation effectiveness

testing and information on the product’s

formulation, manufacture, and quality

control procedures are necessary to

ensure that a company has the ability to

manufacture a proper, bioactive

formulation (56 FR 32282 at 32283).

Because there are no approved NDA’s

for any exocrine pancreatic

insufficiency drug products, the agency

has no information on the bioactivity of

these products. The agency notes that

even if all products were available only

by prescription, variances in bioactivity

of final formulations could pose safety

concerns. Additional information

(which an NDA would contain) is

needed to assure safe and effective use

of these products. Bioactivity must be

shown to correlate with the stated

potency of each proposed product,

particularly for newer formulations that

include microspheres and high potency

levels of the pancreatic enzymes.

The agency is not persuaded by the

comment’s suggestion that

manufacturers would not submit

applications for pancreatic enzyme

products and would wait until

abbreviated NDA’s were possible. The

agency acknowledges that a number of

manufacturers are currently seeking

NDA approval for their currently

marketed exocrine pancreatic

insufficiency drug products.

The agency has received a number of

reports of occurrences of stricture of the

colon in cystic fibrosis patients who had

taken higher potency pancreatic

enzymes in delayed release microtablets

and microspheres for varying numbers

of months prior to corrective surgery
20164 Federal Register / Vol. 60, No. 78 / Monday, April 24, 1995 / Rules and Regulations

(Refs. 1 through 8). The agency is

concerned that there may be a

relationship between the use of these

formulations and stricture of the colon.

The agency needs to evaluate

manufacturing information for these

formulations, which would be included

in an NDA.

The third comment’s suggested

bioactivity testing requirements, support

for approval of certain products, and

opposition to placebo-controlled studies

are outside the scope of this document.

The agency notes, however, that it is

widely believed that demonstration of

the fat digestive actions of various

preparations can be done in ethical

human studies. Inquiries relating to

these subjects should be directed to the

Division of Gastrointestinal and

Coagulation Drug Products (HFD–180),

Center for Drug Evaluation and

Research, Food and Drug

Administration, 5600 Fishers Lane,

Rockville, MD 20857, 301–443–0479.

References

(1) Cystic Fibrosis Foundation Results of a

Survey of 114 Cystic Fibrosis Care Centers in

United States, Patient Registry 1992 Annual

Data Report, Bethesda, MD, October 1993, in

OTC Vol. 17BFR, Docket No. 79N–0379,

Dockets Management Branch.

(2) Smyth, R. L. et al., ‘‘Strictures of

Ascending Colon in Cystic Fibrosis and HighStrength Pancreatic Enzymes,’’ Lancet,

343:85–86, 1994.

(3) Oades, P. J. et al., ‘‘Letter to the Editor,’’

Lancet, 343:109, 1994.

(4) Campbell, C. A., J. Forrest, and C.

Musgrove, ‘‘Letter to the Editor,’’ Lancet,

343:109, 1994.

(5) Briars, G. L. et al., ‘‘Letter to the

Editor,’’ Lancet, 343:600, 1994.

(6) Mahony, M. J., and M. Corcoran, ‘‘Letter

to the Editor,’’ Lancet, 343:599–600, 1994.

(7) Knabe, N. et al., ‘‘Letter to the Editor,’’

Lancet, 343:1230, 1994.

(8) Taylor, C. J., ‘‘Colonic Strictures in

Cystic Fibrosis,’’ Lancet, 343:615–616, 1994.

3. As an alternative to the NDA

process, one comment recommended

that a uniform convention be developed

for labeling exocrine pancreatic

insufficiency drug products to clearly

describe product potency. The comment

urged that labels include the expiration

date and rate of loss of potency, and

indicate that proprietary agents are not

generally equivalent.

The agency disagrees with the

comment’s alternative to the NDA

process. Uniform labeling to describe

product potency is important; however,

that alone will not ensure safety and

effectiveness of these products. The

comment’s labeling suggestions will be

considered, based on data considered in

applications, as NDA’s for these

products are approved. These issues are

outside of the scope of this rulemaking.

4. One comment urged the agency not

to issue a final rule for OTC exocrine

pancreatic insufficiency drug products

until NDA’s for these products have

been approved. Alternatively, the

comment asked that the agency

withdraw its proposal and request that

NDA’s be submitted for exocrine

pancreatic insufficiency drug products.

The comment contended that the latter

action would be similar to the agency’s

action in 1978 regarding potassium

iodide. The comment stated that either

approach would guarantee the

availability of these products to patients

who are benefitting from them.

The agency disagrees with both of the

comment’s suggestions. In the Federal

Register of December 15, 1978 (43 FR

58798), the agency published a notice

requesting submission of NDA’s for

potassium iodide in oral dosage forms

for use as a thyroid-blocking agent in a

radiation emergency. The Commissioner

concluded that potassium iodide was

safe and effective under certain

specified conditions of use. However,

the Commissioner did not conclude that

potassium iodide was generally

recognized as safe and effective (43 FR

58798 at 58799). Therefore, potassium

iodide was regarded as a new drug

requiring an approved NDA as a

condition of marketing.

Exocrine pancreatic insufficiency

drug products are a similar situation.

These products are safe and effective

under specified conditions of use, but

their bioactivity raises both safety and

effectiveness concerns that require

agency preclearance under NDA’s. The

agency sees no reason to withdraw its

proposal because the final rule resulting

from that proposal requires that an NDA

be submitted for any exocrine

pancreatic insufficiency drug product

marketed OTC. Manufacturers have

known since 1991 that an approved

NDA would be needed for continued

marketing of their product(s) on an OTC

basis. While this final rule affects

availability of these products when

marketed OTC, it does not affect

products marketed on a prescription

basis. The agency intends that exocrine

pancreatic insufficiency drug products

marketed by prescription also have an

approved NDA. All manufacturers of

prescription exocrine pancreatic

insufficiency drug products will need to

have an NDA for their product(s). The

agency will address this subject further

in a future issue of the Federal Register.

III. The Agency’s Final Conclusions on

OTC Exocrine Pancreatic Insufficiency

Drug Products

A number of pancreatic enzyme drug

products are currently marketed OTC,

and other products are marketed by

prescription. Some of the prescription

products are encapsulated enteric

coated microsphere dosage forms. None

of these pancreatic enzyme drug

products have approved applications,

i.e, none have been precleared for

marketing by FDA. Some products are

produced by different manufacturers

and contain the same active

ingredient(s); however, these products

have shown significant differences in

bioavailability. The agency finds that

these differences raise a potential for

serious risk to patients using these

products.

Based on all available evidence, the

agency has determined that the

bioavailability of pancreatic enzymes is

dependent on the process used to

manufacture the drug products.

Information on this process is not

addressed by an OTC drug monograph.

Therefore, the agency has determined

that the safe and effective use of these

enzymes for treating exocrine pancreatic

insufficiency cannot be regulated

adequately by an OTC drug monograph.

In this final rule, the agency is declaring

that all exocrine pancreatic

insufficiency drug products (whether

currently marketed on an OTC or

prescription basis) are new drugs for

which approved applications will be

required for marketing.

In the Federal Register of November

7, 1990 (55 FR 46914), the agency

published a final rule in part 310

establishing that certain active

ingredients that had been under

consideration in a number of OTC drug

rulemaking proceedings were not

generally recognized as safe and

effective. That final rule was effective

on May 7, 1991, and included in

§ 310.545(a)(9) the ingredient

hemicellulase, which had been

previously considered under this

rulemaking for OTC exocrine pancreatic

insufficiency drug products. In order to

avoid duplication in listing OTC

exocrine pancreatic insufficiency active

ingredients in more than one regulation,

and for ease in locating these

ingredients in the Code of Federal

Regulations, the agency is listing all of

these ingredients in a single regulation

in new § 310.543 entitled ‘‘Drug

products containing active ingredients

offered over-the-counter (OTC) for

human use in exocrine pancreatic

insufficiency.’’ Accordingly, the

ingredient hemicellulase, currently

listed in § 310.545(a)(9) is now being

listed in § 310.543(d), and

§ 310.545(a)(9) is being removed and

reserved. The ingredients pancreatin

and pancrelipase, covered by this final

rule, are being listed in § 310.543(e).
Federal Register / Vol. 60, No. 78 / Monday, April 24, 1995 / Rules and Regulations 20165

IV. Analysis of Impacts

An analysis of the costs and benefits

of this regulation, conducted under

Executive Order 12291 was discussed in

the proposed rule (56 FR 32282 at

32289). Comments received were

discussed in part II of this final rule.

Executive Order 12291 has been

superseded by Executive Order 12866.

FDA has examined the impacts of the

final rule under Executive Order 12866

and the Regulatory Flexibility Act (Pub.

L. 96–354). Executive Order 12866

directs agencies to assess all costs and

benefits of available regulatory

alternatives and, when regulation is

necessary, to select regulatory

approaches that maximize net benefits

(including potential economic,

environmental, public health and safety,

and other advantages; distributive

impacts; and equity). The agency

believes that this final rule is consistent

with the regulatory philosophy and

principles identified in the Executive

Order. In addition, the final rule is not

a significant regulatory action as defined

by the Executive Order and, so, is not

subject to review under the Executive

Order.

The Regulatory Flexibility Act

requires agencies to analyze regulatory

options that would minimize any

significant impact of a rule on small

entities. This final rule will result in the

removal of all drug products containing

the ingredients pancreatin and

pancrelipase from the OTC marketplace.

However, only a limited number of OTC

drug products are marketed in this

manner and are affected by this final

rule. Accordingly, the agency certifies

that the final rule will not have a

significant economic impact on a

substantial number of small entities.

Therefore, under the Regulatory

Flexibility Act, no further analysis is

required.

The agency has determined under 21

CFR 25.24(c)(6) that this action is of a

type that does not individually or

cumulatively have a significant effect on

the human environment. Therefore,

neither an environmental assessment

nor an environmental impact statement

is required.

List of Subjects in 21 CFR Part 310

Administrative practice and

procedure, Drugs, Labeling, Medical

devices, Reporting and recordkeeping

requirements.

Therefore, under the Federal Food,

Drug, and Cosmetic Act and under

authority delegated to the Commissioner

of Food and Drugs, 21 CFR part 310 is

amended as follows:

PART 310—NEW DRUGS

1. The authority citation for 21 CFR

part 310 continues to read as follows:

Authority: Secs. 201, 301, 501, 502, 503,

505, 506, 507, 512–516, 520, 601(a), 701, 704,

705, 721 of the Federal Food, Drug, and

Cosmetic Act (21 U.S.C. 321, 331, 351, 352,

353, 355, 356, 357, 360b–360f, 360j, 361(a),

371, 374, 375, 379(e); secs. 215, 301, 302(a),

351, 354–360F of the Public Health Service

Act (42 U.S.C. 216, 241, 242(a), 262, 263b–

263n).

2. New § 310.543 is added to subpart

E to read as follows:

§ 310.543 Drug products containing active

ingredients offered over-the-counter (OTC)

for human use in exocrine pancreatic

insufficiency.

(a) Hemicellulase, pancreatin, and

pancrelipase have been present as

ingredients in exocrine pancreatic

insufficiency drug products. Pancreatin

and pancrelipase are composed of

enzymes: amylase, trypsin (protease),

and lipase. Significant differences have

been shown in the bioavailability of

marketed exocrine pancreatic

insufficiency drug products produced

by different manufacturers. These

differences raise a potential for serious

risk to patients using these drug

products. The bioavailability of

pancreatic enzymes is dependent on the

process used to manufacture the drug

products. Information on this process is

not included in an OTC drug

monograph. Therefore, the safe and

effective use of these enzymes for

treating exocrine pancreatic

insufficiency cannot be regulated

adequately by an OTC drug monograph.

Information on the product’s

formulation, manufacture, quality

control procedures, and final

formulation effectiveness testing are

necessary in an approved application to

ensure that a company has the ability to

manufacture a proper bioactive

formulation. In addition, continuous

physician monitoring of patients who

take these drug products is a collateral

measure necessary to the safe and

effective use of these enzymes, causing

such products to be available by

prescription only.

(b) Any drug product that is labeled,

represented, or promoted for OTC use in

the treatment of exocrine pancreatic

insufficiency is regarded as a new drug

within the meaning of section 201(p) of

the Federal Food, Drug, and Cosmetic

Act (the act), for which an approved

application under section 505 of the act

and part 314 of this chapter is required

for marketing. In the absence of an

approved application, such product is

also misbranded under section 502 of

the act.

(c) Clinical investigations designed to

obtain evidence that any drug product

labeled, represented, or promoted for

OTC use in the treatment of exocrine

pancreatic insufficiency is safe and

effective for the purpose intended must

comply with the requirements and

procedures governing the use of

investigational new drugs set forth in

part 312 of this chapter.

(d) After May 7, 1991, any such OTC

drug product that contains

hemicellulase initially introduced or

initially delivered for introduction into

interstate commerce that is not in

compliance with this section is subject

to regulatory action.

(e) After October 24, 1995, any such

OTC drug product that contains

pancreatin or pancrelipase initially

introduced or initially delivered for

introduction into interstate commerce

that is not in compliance with this

section is subject to regulatory action.

§ 310.545 [Amended]

3. Section 310.545 Drug products

containing certain active ingredients

offered over-the-counter (OTC) for

certain uses is amended by removing

and reserving paragraph (a)(9), and by

revising paragraph (d)(1) to read as

follows:

§ 310.545 Drug products containing

certain active ingredients offered over-thecounter (OTC) for certain uses.

(d) * * *

(1) May 7, 1991, for products subject

to paragraphs (a)(1) through (a)(4),

(a)(6)(i)(A), (a)(6)(ii)(A), (a)(7) (except as

covered by paragraph (d)(3) of this

section), (a)(8)(i), (a)(10)(i) through

(a)(10)(iii), (a)(12)(i) through (a)(12)(iv),

and (a)(14) through (a)(18)(i) of this

section.

* * * * *

Dated: April 13, 1995.

William K. Hubbard,

Acting Deputy Commissioner for Policy.

[FR Doc. 95–10078 Filed 4–21–95; 8:45 am]

BILLING CODE 4160–01–F