13590 Federal Register / Vol. 60, No. 48 / Monday, March 13, 1995 / Rules and Regulations

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

21 CFR Part 328

[Docket No. 93N–0107]

Over-the-Counter Drug Products

Intended for Oral Ingestion that

Contain Alcohol

AGENCY: Food and Drug Administration,

HHS.

ACTION: Final rule.

SUMMARY: The Food and Drug

Administration (FDA) is issuing a final

rule establishing a maximum

concentration limit for alcohol (ethyl

alcohol) as an inactive ingredient in

over-the-counter (OTC) drug products

intended for oral ingestion (0.5 percent

alcohol for children under 6 years of

age, 5 percent alcohol for children 6 to

under 12 years of age, and 10 percent

alcohol for anyone 12 years of age and

over). This final rule also requires that

the alcohol content be stated

prominently and conspicuously on the

principal display (front) panel of

product labeling. FDA is issuing this

final rule after considering

recommendations from its

Nonprescription Drugs Advisory

Committee (NDAC) and public

comments on the agency’s notice of

proposed rulemaking. This final rule

defers action on alcohol limits for

Aromatic Cascara Fluidextract, Cascara

Sagrada Fluidextract, and orally

ingested OTC homeopathic drug

products.

EFFECTIVE DATE: March 13, 1996.

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: In the

Federal Register of October 21, 1993 (58

FR 54466), the agency proposed

maximum concentration limits for

alcohol as an inactive ingredient in OTC

drug products intended for oral

ingestion. The proposed limits were 0.5

percent alcohol for children under 6

years of age, 5 percent alcohol for

children 6 to under 12 years of age, and

10 percent alcohol for anyone 12 years

of age and over. In addition, the agency

proposed that the alcohol content be

stated prominently and conspicuously

on the principal display (front) panel of

product labeling, and that the labeling

term ‘‘alcohol-free’’ mean that the

product contains no alcohol at all.

These proposals were based on NDAC’s

recommendations.

In response to the proposal, seven

drug manufacturers, four professional

organizations, four drug manufacturers

associations, and two consumers

submitted comments. Copies of the

comments are on public display in the

Dockets Management Branch (HFA–

305), Food and Drug Administration,

rm. 1–23, 12420 Parklawn Dr.,

Rockville, MD 20857.

I. The Agency’s Conclusions on the

Comments

A. General Comments

1. Several comments expressed their

support for the alcohol content

limitations proposed by the agency and

placement of the alcohol content on the

front (principal) display panel. The

comments stated that prominent and

conspicuous labeling will enhance and

guide the public in making an informed

decision when purchasing products.

2. Two comments urged FDA and

industry to find alternatives to alcohol

so that eventually alcohol can be

eliminated from OTC drug products

entirely. One comment, from a

manufacturer of nonalcoholic OTC drug

products, suggested that the agency

codify its policy of encouragement of

the lowest amount of alcohol necessary

for pharmaceutical purposes. The

comment stated that this could be done

by amending proposed § 328.10 to

include new paragraph (f) as follows:

(f) Any manufacturer of OTC drug products

shall use, within reasonable time of it

becoming known, any formulary technique or

technology commercially available at

adoption of this rule or which may later

become available and would optimally

reduce or eliminate the use of alcohol in its

OTC product(s).

The agency appreciates the

comments’ concerns and strongly

encourages the further development of

safe alternatives to alcohol. However,

the agency believes that it is

unnecessary to codify its policy of

‘‘encouragement,’’ as suggested by one

comment. The agency’s statements in

the preamble to the proposal and the

agency’s action in implementing alcohol

concentration limits adequately reflect

the agency’s policy to reduce the

amount of alcohol in OTC drug

products.

3. One comment requested that FDA

adopt a timetable for implementation of

the new alcohol content limitations for

orally ingested OTC drug products that

is consistent with the timetable in the

voluntary program proposed by the

Nonprescription Drugs Manufacturers

Association (NDMA). That program

calls for NDMA member companies

with affected products to implement the

new limitations ‘‘as soon as

practicable.’’ The goal for reformulating

and labeling the 5- and 10-percent

alcohol limitations was November 1993.

The goal for reformulating and labeling

of alcohol-free OTC drug products was

December 1994. Both dates were for

factory shipment of reformulated

products.

The agency stated in its proposed rule

(58 FR 54466) that the final rule would

become effective 12 months after the

date of its publication in the Federal

Register. Thus, the effective date for

implementing this final rule will go

beyond the December 1994 date

proposed by NDMA to complete the

implementation of its voluntary

program and should present no

problems timewise to NDMA member

companies.

4. One comment contended that the

alcohol content regulation should

pertain solely to orally ingested

products covered by OTC drug

monographs. The comment stated that

OTC drug monographs represent a menu

of ingredients that represent an

essentially known set of products from

a formulation standpoint, while OTC

drug products under new drug

applications (NDA’s) usually represent

novel OTC formulations that may

require special considerations regarding

product specifications. The comment

added that formulatory flexibility is

especially needed in the future for

prescription-to-OTC switch products

under NDA’s.

The agency disagrees with the

comment. The intent of the regulation is

to limit the alcohol content of all OTC

drug products intended for oral

ingestion, regardless whether marketed

under an OTC drug monograph(s) or an

NDA (which also includes abbreviated

applications). The regulation provides

an exemption procedure in § 328.10(e).

Appropriate cause, such as a specific

solubility or manufacturing problem,

must be adequately documented. This

procedure applies equally to products

marketed under an OTC drug

monograph(s) or an NDA. Therefore, the

agency finds no basis to limit the

regulation solely to products covered by

OTC drug monographs.

5. One comment asserted that the

proposed rule should be withdrawn

because there are no data to support a

10-percent alcohol limit for orally

ingested OTC drug products intended

for adults. The comment contended that

the 10-percent maximum alcohol

concentration for adults was based

solely on scientific opinion, but without

scientific data to support the opinion.

The comment argued that requiring
Federal Register / Vol. 60, No. 48 / Monday, March 13, 1995 / Rules and Regulations 13591

manufacturers to apply for an

exemption to exceed the 10-percent

alcohol content limit is unwarranted

because the agency has not shown that

such products are dangerous.

The agency disagrees with the

comment. A number of safety issues

related to higher alcohol concentrations

were discussed at the NDAC meeting

held on December 17, 1992. NDAC

discussed development of lactic

acidosis (with hypoglycemia occurring

in some people) in acute alcohol

intoxication, sensitivity and tolerance to

alcohol, cutaneous vasodilation,

withdrawal syndrome, fetal alcohol

syndrome, interaction with drugs, etc.

(See 58 FR 54466 at 54467 to 54468.)

NDAC considered that alcohol displays

zero order pharmacokinetics once a

threshold concentration is exceeded.

This means that blood alcohol

concentrations are not proportional to

the amount ingested. Thus, a small

increase in the amount ingested may

lead to a large increase in the blood

alcohol concentration. It therefore is

much easier to attain intoxicating blood

levels of alcohol, because less alcohol

needs to be ingested to do so.

The agency believes that there are

sufficient scientific data to support the

10-percent alcohol limit for orally

ingested OTC drug products intended

for adults and that the petition

procedure in § 328.10(e) is appropriate

if there is a need to request an

exemption.

6. One comment claimed that

requiring child-resistant (CR) packaging

would be more helpful in preventing

accidental overdose in children than the

alcohol content limitations proposed by

the agency. The comment noted that the

Consumer Product Safety Commission

(CPSC) is currently considering

development of a regulation to require

CR packaging for mouthwashes

containing greater than five percent

alcohol. The comment mentioned that

in response to the continuing problem

of tampering with OTC drug products

formulated as two-piece hard gelatin

capsules, FDA had not proposed to

simply ban gelatin capsules but rather

‘‘balanced the value of the hard capsule

dosage form to consumers against its

continued vulnerability to malicious

tampering’’ and proposed to strengthen

its tamper-resistant packaging regulation

(59 FR 2542 at 2543, January 18, 1994).

The agency believes that CR

packaging could play a role in

preventing toxic effects in infants and

young children from accidental

ingestion of alcohol-containing OTC

drug products. However, CR packaging

alone would not prevent adolescents

and adults from intentionally ingesting

OTC drug products for their alcohol

content or prevent young children and

adolescents from ingesting undesirable

levels of alcohol from normal doses of

alcohol-containing OTC drug products.

Because prevention of accidental

overdose in children is not the primary

purpose of this regulation, the agency is

finalizing the regulation as proposed.

The agency discussed the issue of CR

packaging in the OTC cough-cold

combinations tentative final monograph

(53 FR 30522 at 30527, August 12,

1988), and stated that the authority to

require CR packaging rests with the

CPSC under the Poison Prevention

Packaging Act of 1970. FDA is aware

that the CPSC has published a proposed

rule (59 FR 24386, May 11, 1994) to

require CR packaging for mouthwash

products containing 3 grams (g) or more

of alcohol. FDA is not aware of any

CPSC consideration of CR packaging for

alcohol-containing OTC drug products

intended for oral ingestion.

7. One comment questioned why

small amounts of alcohol ingested in

OTC drug products are considered

harmful when one to two ounces (oz) of

alcohol per day are recommended for

cardiovascular health in adults.

The agency acknowledges that small

amounts of alcohol are not harmful for

most adults. However, for some people

even small amounts of alcohol could be

harmful (see section I.A., comments 5

and 6). Those individuals will avoid

alcoholic beverages but may not avoid

OTC drug products because of

unawareness of their alcohol content.

The agency concludes that the potential

benefit alcohol may have for

cardiovascular health in some adults

does not justify the unnecessary use of

alcohol in OTC drug products, when

this use may be harmful to some

individuals.

8. One comment contended that

eliminating alcohol from products

intended for use by children and

younger adolescents will not entirely

address the problem posed by

adolescents who purchase OTC drug

products intended for use by adults in

order to obtain psychoactive effects

from the alcohol.

The agency acknowledges that the

final regulation will not entirely

eliminate the potential for adults and

adolescents intentionally to misuse OTC

drug products for their alcohol content.

The prevention of intentional misuse,

however, is not the primary

consideration of this regulation.

However, by reducing the amount of

alcohol that can be consumed from OTC

drug products, the agency believes that

this regulation will discourage and

reduce intentional misuse.

9. One comment requested that the

agency have NDAC review the safety of

synthetic alcohols (glycols) as a phase II

followup to its initial ‘‘alcohol’’ work.

The agency notes that the comment

offered no data or reasons to support its

request. The agency is not aware of any

current safety problems surrounding the

use of glycols as inactive ingredients in

OTC drug products that would warrant

review at this time.

B. Comments on Labeling of OTC Drug

Products Intended for Oral Ingestion

that Contain Alcohol

10. Two comments objected to the

requirement in proposed § 328.50(b)

that the product’s alcohol content

appear on the principal display panel

(PDP). The comments indicated that the

PDP is for the purpose of product

recognition and was not designed to

carry all important information about

safe product use, contending that the

product information panel (PIP) was

intended to provide this information.

The comments stated that section 502(e)

of the Federal Food, Drug, and Cosmetic

Act (the act) (21 U.S.C. 352(e)) allows

the alcohol content to appear anywhere

on the OTC label. The comments

mentioned that it has been industry

practice to place the alcohol content in

the PIP under the inactive ingredients

section. The comments indicated that

when consumers question product

content, they logically turn to the

ingredient listing on the PIP. The

comments added that alcohol content

information on the PDP would

overemphasize and detract from the PIP.

One comment argued that including an

alcohol content statement would

inevitably decrease the

‘‘conspicuousness’’ and prominence of

other language currently required on the

PDP. The other comment argued that it

is important to use the PDP for its

specialized marketing purposes

(product recognition, e.g., product

name, statement of identity, and net

contents) and to use the PIP for

consistent consumer usage of OTC drug

labeling (e.g., ingredients, warnings, and

directions) for all the various OTC drug

categories. The comment added that a

low alcohol content is not of any greater

importance than other warnings

currently required on OTC drug

products intended for oral ingestion.

The comment mentioned that

consumers with a personal interest in

the product’s alcohol content will be

self-motivated to read the PIP for the

disclosed alcohol content. The

comments noted that a number of other

related important warnings (e.g., the

aspartame warning for phenylketonurics

on food products, the sodium content
13592 Federal Register / Vol. 60, No. 48 / Monday, March 13, 1995 / Rules and Regulations

warnings, and the FD&C Yellow No. 5

warnings in 21 CFR 201.20 for certain

drugs) are not required to appear on the

PDP, but may appear on the PIP.

One comment also stated that there is

no demonstrable evidence of a serious

public health hazard resulting from the

presence of alcohol in OTC drug

products. The comment argued that the

use of the PDP to disclose alcohol

content would create, by regulation, a

negative perception of alcohol, which is

unwarranted scientifically. The

comment concluded that no data are

available to suggest that the current

labeling regulations are ineffective in

informing consumers who want to know

the alcohol content of OTC drug

products.

The agency disagrees with the

comments. While no specific data are

available to demonstrate consumer

confusion, the agency believes

consumers need to be able to readily

determine the alcohol content of OTC

drug products at the time of purchase.

The agency is aware that consumers do

not necessarily read all labeling at the

time of purchase. Prominent and

conspicuous labeling of the alcohol

content on the PDP will help consumers

to make an informed decision at the

time of purchase. This information is

extremely important for consumers who

wish to avoid or limit alcohol ingestion,

such as a recovering alcoholic or a

parent of a young child. The agency

acknowledges that the act allows the

alcohol content of a product to appear

anywhere on the OTC label. However,

the agency believes that the new alcohol

labeling requirements should prove

more effective in bringing this

information to consumers’ attention.

The agency concludes that a few words

describing the alcohol content (e.g.,

‘‘contains 5% alcohol,’’ ‘‘5% alcohol’’)

on the PDP would not significantly

decrease label readability or alter the

prominence of additional information

currently required on the PDP. At this

time, many manufacturers already

voluntarily include related labeling to

inform consumers that a product is

‘‘alcohol free.’’ To facilitate product

comparison and to better provide

consumers with information needed to

make an informed decision, the agency

is requiring a product’s alcohol content

to appear on the PDP. The agency is not

aware of any significant safety problems

with other inactive ingredients in OTC

drug products that would warrant

information about the ingredients on the

PDP.

11. One comment expressed support

for the agency’s proposal that allows use

of the term ‘‘alcohol free’’ only on those

OTC drug products that contain no

alcohol. Two comments objected to the

proposal in § 328.50(e) that the term

‘‘alcohol free’’ mean zero percent

alcohol. The comments requested that a

de minimus level of alcohol be allowed

in OTC drug products in order to permit

some variability in the sensitivity of the

methods of analysis and detection,

especially due to the presence of alcohol

moieties from natural flavors that are

often used in OTC drug products. One

comment argued that, due to the

practicalities of pharmaceutical

formulation, a de minimus level of 0.5

percent alcohol being labeled as

‘‘alcohol free’’ would allow

manufacturers to use available alcoholcontaining flavors in OTC drug

formulations to provide essentially

‘‘alcohol-free’’ palatable formulations to

consumers who want to avoid alcohol.

The comment indicated that the terms

‘‘sugar free’’ (≤ 0.5 g), ‘‘sodium free’’ (≤

5 mg), and ‘‘fat free’’ (≤ 0.5 g), may be

applied to dietary supplements and

foods (21 CFR 101.60(c)(1), 101.61(b)(1),

and 101.62(b)(1)). The comment

contended that this precedent

acknowledges that a total absence of

these components from certain foods is

unlikely and difficult to achieve from

the standpoint of product preparation.

The comment concluded that this

approach should carry over to an

alcohol-free claim for OTC drug

products.

The agency disagrees with the

comments and believes that the term

‘‘alcohol free’’ should mean no (0

percent) alcohol in a product. The

agency acknowledges that the total

elimination of certain food components

(fat, sugar, sodium) from foods is

unlikely and difficult to achieve. Small

amounts of these components, when

present in foods, are dietarily

insignificant. However, the agency

believes that these circumstances do not

apply to alcohol in OTC drug products.

Restricting use of the term ‘‘alcohol

free’’ to products that contain no (0

percent) alcohol within the limits of

current technology (Ref. 1) in no way

limits manufacturers’ ability to produce

low alcohol OTC drug products.

However, it does provide important and

truthful labeling to consumers who may

be interested in total avoidance of

alcohol for personal, religious, or

medical reasons. Consumers who want

to purchase a product with no alcohol

should be assured that the product does,

in fact, contain no alcohol. Individuals

taking an alcohol-deterrent medication,

such as disulfiram, could suffer

untoward reactions from ingesting a

drug product labeled as ‘‘alcohol free’’

when it actually contains a small

amount of alcohol (even up to 0.5

percent). Alcohol free products can be

achieved, because a significant number

of OTC drug products have already been

reformulated with no alcohol.

Therefore, the agency is finalizing

§ 328.50(e) as proposed.

The agency will use a gas-liquid

chromatographic method (Ref. 1) to

analyze products for their alcohol

content. A copy of this method has been

placed in the Dockets Management

Branch (address above). The agency

invites comments on this test method.

Reference

(1) Santos, J., ‘‘Limit of Alcohol Test,’’ draft

of unpublished procedure, in OTC Vol.

260002, Docket No. 93N–0107, Dockets

Management Branch.

12. One comment requested that the

agency phase in the labeling

requirements as they apply to

homeopathic drug products over a

period of 3 years. The comment

contended that changing the labels on

such a large number of preparations

would require tremendous effort and

expense. The comment added that this

relabeling could not reasonably be

achieved within the proposed 12-month

period. Another comment complained

that the agency is allowing

manufacturers only 1 year to

reformulate their products when it is

impossible to achieve and prove a stable

product formula in less than 3 years.

The comment added that there may be

no studies on the safety of increasing

the amounts of alternative preservatives,

while alcohol has a long history of

safety.

The agency disagrees with the

comments and finds no basis to grant a

3-year phase in period for this

regulation. The comments offered no

documentation to support that 3 years is

necessary for product reformulation or

relabeling. The agency feels that 1 year

from the date of the final rule is

sufficient for manufacturers to

reformulate and relabel their products.

One year has been the standard time

provided for reformulation and

relabeling throughout most of the OTC

drug review. This timeframe has proven

satisfactory for the vast majority of

reformulations and relabelings that have

resulted from the OTC drug review.

Relabeling needed for homeopathic drug

products to label the alcohol content on

the principal display panel can be

accomplished by the use of ‘‘stick-on’’

labels, if necessary.

The agency recognizes that

manufacturers have already had 1 year

since the proposal was published to

conduct stability studies on products

that will need to be reformulated. They

will have 1 more year to complete these
Federal Register / Vol. 60, No. 48 / Monday, March 13, 1995 / Rules and Regulations 13593

studies before this final rule becomes

effective. Further, manufacturers may

request an extension for either

relabeling or reformulating their

products provided that they can justify

and document their need.

C. Comments on Specific OTC Drug

Products Containing Alcohol

13. One comment questioned whether

the proposed regulations are intended to

apply to homeopathic drug products.

The comment noted that the preamble

of the proposed rule stated that ‘‘these

regulations would apply to OTC drug

products regulated under the

monograph system (21 CFR parts 330 to

358), and those approved under new

drug applications’’ (58 FR 54466 at

54469). Referring to Compliance Policy

Guide 7132.15 (homeopathic drugs)

(Ref. 1) and the Federal Register

announcement excluding OTC

homeopathic drug products from the

OTC drug review (37 FR 9464 at 9466,

May 11, 1972), the comment mentioned

that homeopathic drug products are not

regulated under OTC drug monographs,

nor are they subject to NDAs. The

comment requested the agency to clarify

this ambiguity.

The discussion in the preamble of the

proposed rule about products regulated

under the monograph system and NDA’s

was an illustrative example following a

general statement that alcohol

limitations and related labeling

requirements apply to all OTC drug

products intended for oral ingestion. It

was the agency’s intent that the

proposed regulation apply to all drugs

sold without a prescription. While

homeopathic drugs are neither regulated

under the monograph system nor

subject to NDA’s, they are still regulated

as drugs under the act. The safety

considerations surrounding alcohol

apply equally to all OTC drug products.

Accordingly, homeopathic drug

products are subject to the final

regulation and must meet all of the

labeling requirements in § 328.50.

However, because the regulation may

conflict with alcohol content

specifications set forth in the

Homeopathic Pharmacopeia of the

United States (see section I.C., comment

15), the agency is temporarily

exempting orally ingested homeopathic

drug products from the alcohol

percentage limitations in § 328.10(b),

(c), and (d) until this issue is resolved.

Reference

(1) FDA, Compliance Policy Guide

7132.15, May 31, 1988, copy in OTC Vol.

260002, Docket No. 93N–0107, Dockets

Management Branch.

14. Two comments stated that the

proposed regulation conflicts with the

alcohol content specifications set forth

in the Homeopathic Pharmacopoeia of

the United States. Several comments

argued that for solubility, stability, and

preservative purposes, there is no

substitute for alcohol in homeopathic

drug products. Three of the comments

added that alcohol is also essential in

aiding the absorption of homeopathic

medicines. The comments stated that ‘‘if

dilutions containing preservatives other

than alcohol are used by a process of

alternate serial dilution and

dynaminization to prepare higher

potencies, for example using a 3X

formula to make a 6X, the preservatives

would be potentized as well as the

remedy in the homeopathic manner.’’

The comments added that the

physiological activity of

homeopathically potentized

preservatives is unknown and

unpredictable, and no data exist to

assist the homeopathic community in

predicting the therapeutic effect on the

user. Two comments mentioned that

chemical preservatives have been

identified increasingly as a source of

undesired side effects, including

allergies. One comment stated that the

proposed alcohol restrictions would

mean giving up all of the

pharmaceutical, technical, and medical

experience for homeopathic drug

products. Another comment claimed

that a therapeutic re-evaluation of

homeopathic remedies would be

necessary. Several comments claimed

that alcohol in homeopathic drug

products does not pose a risk to adults

or children because of the small volume

of alcohol present in a standard

homeopathic drug dose (standard adult

dose is generally 10 drops, 5 drops for

children, approximately .25 to .5 mL)

and the small package volume of

alcohol containing homeopathic drug

products (usually ≤ 4 oz). One comment

stated that because the proposed alcohol

content labeling focuses on percent

alcohol content rather than total alcohol

content per dose, consumers will avoid

homeopathic drug products on the

mistaken assumption that a high percent

alcohol content reflects a high level of

alcohol intake. Several comments

asserted that the new regulation would

have a significant ‘‘negative’’ economic

impact on the homeopathic industry.

The comments stated that a full-line

homeopathic drug manufacturer makes

dosage forms using over 1,000 active

ingredients, and to reformulate, test,

repackage, and relabel all homeopathic

drug products would be very costly and

time consuming. Further, having to

apply for an exemption for each

individual dosage form would be

impracticable, time-consuming, and

expensive for both manufacturers and

FDA. Two comments asserted that

subjecting homeopathic drug products

to the new alcohol limitations would

cause their removal from the market.

One comment contended that to

proceed with a rulemaking that has the

effect of destroying an entire industry

without the support of an economic

impact analysis would contravene

regulatory requirements.

The agency does not have sufficient

data or information to determine

whether orally ingested homeopathic

drug products can be reformulated with

10 percent alcohol or less. Due to the

manner in which homeopathic drug

products are manufactured, the agency

will not make a decision concerning the

appropriate alcohol content of these

products until it obtains the necessary

data and information on how these

products are manufactured and why

they need such high levels of alcohol for

product formulation. Rather than delay

publication of this final rule, the agency

will temporarily exempt orally ingested

homeopathic drug products from the

alcohol percentage limitations in

§ 328.10(b), (c), and (d). The agency will

publish its decision concerning the

appropriate alcohol content for orally

ingested homeopathic drug products in

a future issue of the Federal Register.

15. One comment suggested it would

be more cost effective for industry and

FDA to exempt herbal drugs that

contain more than 50 percent herbal

products on a weight to volume (w/v)

basis, rather than require individual

exemptions for herbal drug products

that contain more than 10 percent

alcohol by necessity.

The agency disagrees with the

comment. The purpose of § 328.10 (e) is

to exempt OTC drug products for which

no alternatives to alcohol exist. The

comment submitted no evidence to

support why all herbal drug products

that contain 50 percent (w/v) herbal

ingredients should be automatically

exempt.

16. One comment stated that the OTC

drug product Aromatic Cascara

Fluidextract, which contains 18 to 20

percent alcohol, cannot be formulated at

lower alcohol concentrations because of

its susceptibility to microbial

contamination. The comment added

that if the product were reformulated to

10 percent alcohol or less, it would not

be within the specifications set forth in

the United States Pharmacopeia

(U.S.P.).

The comment is correct in stating that

if Aromatic Cascara Fluidextract were
13594 Federal Register / Vol. 60, No. 48 / Monday, March 13, 1995 / Rules and Regulations

reformulated to 10 percent alcohol or

less, it would not be within the

specifications set forth in the U.S.P.

Aromatic Cascara Fluidextract and

Cascara Sagrada Fluidextract both

contain between 18 and 20 percent

alcohol (Ref. 1). The comment did not

provide any data to substantiate that

microbial contamination would occur if

Aromatic Cascara Fluidextract were to

be formulated at lower alcohol

concentrations. Thus, the agency does

not have sufficient data or information

to determine whether Aromatic Cascara

Fluidextract or Cascara Sagrada

Fluidextract can be formulated with less

alcohol.

The agency is currently working with

the United States Pharmacopeial

Convention (U.S.P.C.) to ascertain if a

lower alcohol concentration can be

used. Rather than delay publication of

this final rule, the agency will

temporary exempt Aromatic Cascara

Fluidextract and Cascara Sagrada

Fluidextract from the requirements in

§ 328.10(b), (c), and (d). The agency will

publish its decision concerning the

appropriate alcohol content for

Aromatic Cascara Fluidextract and

Cascara Sagrada Fluidextract in a future

issue of the Federal Register.

Reference

(1) The United States Pharmacopeia 23—

The National Formulary 18, United States

Pharmacopeial Convention, Inc., Rockville,

MD, pp. 282, 1994.

II. The Agency’s Final Conclusions on

OTC Drug Products Intended for Oral

Ingestion that Contain Alcohol

The agency is issuing a final rule

establishing the following limits on the

concentrations of alcohol as an inactive

ingredient in OTC drug products

intended for oral ingestion: (1) 10

percent alcohol for products labeled for

use by adults and children 12 years of

age and over, (2) 5 percent alcohol for

products labeled for use by children 6

to under 12 years of age, and (3) 0.5

percent alcohol for products labeled for

use by children under 6 years of age.

Further, the agency strongly

recommends that OTC drug products for

oral ingestion not contain any more than

the minimum amount of alcohol

necessary for use as a solvent,

preservative, flavor (to enhance taste), or

any other pharmaceutical purpose.

The agency concludes that the term

‘‘alcohol free’’ should mean no (0

percent) alcohol in a product. This

requirement will assure consumers who

want to purchase an OTC drug product

with out alcohol that the product, in

fact, contains no alcohol. The agency

has determined that the alcohol content

information should appear prominently

and conspicuously on the principal

display panel of the OTC drug product.

This requirement is consistent with

section 502(c) of the act (21 U.S.C.

352(c)). Further, because section 502(e)

of the act requires that the quantity,

kind, and proportion of alcohol be

stated on a drug product’s label, the

alcohol content will also need to appear

on the immediate container label when

that container (e.g., a glass bottle) is

marketed in another retail package, e.g.,

an outer box. This dual labeling of

alcohol content will be beneficial

should a consumer discard the outer

package.

In accordance with the provisions

found in § 328.10(e), the agency is

temporarily exempting Aromatic

Cascara Fluidextract, Cascara Sagrada

Fluidextract, and orally ingested OTC

homeopathic drug products from the

requirements in § 328.10(b), (c), and (d).

Additional information is needed about

the formulations of these specific

products. Rather than delay publication

of this final rule to resolve the

outstanding issues, the agency is

temporarily exempting these products

from some of the requirements. The

agency will publish its decision

concerning the appropriate alcohol

content for Aromatic Cascara

Fluidextract, Cascara Sagrada

Fluidextract, and orally ingested

homeopathic drug products in a future

issue of the Federal Register. In the

interim, these products must meet the

labeling requirements in § 328.50.

III. Analysis of Impacts

An analysis of the cost and benefits of

this regulation, conducted under

Executive Order 12291, was discussed

in the proposed rule (58 FR 54466 at

54470). Several comments concerning

the reformulating, testing, repackaging,

and relabeling of homeopathic drug

products were received in response to

the agency’s request for specific

comment on the economic impact of

this rulemaking. The agency is

temporarily exempting orally ingested

homeopathic drug products from the

requirements in § 328.10(b), (c), and (d)

of this rulemaking. Therefore, no

reformulation or testing will be

necessary at this time. Any comments

concerning a significant economic

impact on reformulating or testing of

orally ingested homeopathic drug

products will be addressed in a future

issue of the Federal Register.

Homeopathic drug products will be

subject to relabeling and repackaging, if

necessary, in the same manner as other

OTC drug products that contain alcohol

and which are affected by this final rule.

The burden on all products will be the

same--the standard 1 year for relabeling

to be done.

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, thus, 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. Within the OTC drug product

marketplace, the agency is not aware of

a significant number of products that

would be affected due to their alcohol

content as an inactive ingredient.

Products that would be affected consist

of a limited number of OTC liquid

cough-cold, internal analgesic, laxative,

and homeopathic drug products. The

effect on orally ingested homeopathic

drug products is discussed above, and

these products have a partial exemption

from the 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.

IV. Environmental Impact

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 328

Drugs, Labeling, Alcohol.

Therefore, under the Federal Food,

Drug, and Cosmetic Act andunder

authority delegated to the Commissioner

of Food and Drugs, chapter I of title 21

of the Code of Federal Regulations is

amended as follows:

1. Part 328 is added to read as follows:
Federal Register / Vol. 60, No. 48 / Monday, March 13, 1995 / Rules and Regulations 13595

PART 328—OVER-THE-COUNTER

DRUG PRODUCTS INTENDED FOR

ORAL INGESTION THAT CONTAIN

ALCOHOL

Subpart A—General Provisions

Sec.

328.1 Scope.

328.3 Definitions.

Subpart B—Ingredients

328.10 Alcohol.

Subpart C—Labeling

328.50 Principal display panel of all OTC

drug products intended for oral ingestion

that contain alcohol.

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

505, 701 of the Federal Food, Drug, and

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

353, 355, 371).

Subpart A—General Provisions

§ 328.1 Scope.

Reference in this part to regulatory

sections of the Code of Federal

Regulations are to chapter I of title 21

unless otherwise noted.

§ 328.3 Definitions.

As used in this part:

(a) Alcohol means the substance

known as ethanol, ethyl alcohol, or

Alcohol, USP.

(b) Inactive ingredient means any

component of a product other than an

active ingredient as defined in

§ 210.3(b)(7) of this chapter.

Subpart B—Ingredients

§ 328.10 Alcohol.

(a) Any over-the-counter (OTC) drug

product intended for oral ingestion shall

not contain alcohol as an inactive

ingredient in concentrations that exceed

those established in this part, unless a

specific exemption, as provided in

paragraph (e) or (f) of this section, has

been approved.

(b) For any OTC drug product

intended for oral ingestion and labeled

for use by adults and children 12 years

of age and over, the amount of alcohol

in the product shall not exceed 10

percent.

(c) For any OTC drug product

intended for oral ingestion and labeled

for use by children 6 to under 12 years

of age, the amount of alcohol in the

product shall not exceed 5 percent.

(d) For any OTC drug product

intended for oral ingestion and labeled

for use by children under 6 years of age,

the amount of alcohol in the product

shall not exceed 0.5 percent.

(e) The Food and Drug Administration

will grant an exemption from

paragraphs (b), (c), and (d) of this

section where appropriate, upon

petition under the provisions of § 10.30

of this chapter. Appropriate cause, such

as a specific solubility or manufacturing

problem, must be adequately

documented in the petition. Decisions

with respect to requests for exemption

shall be maintained in a permanent file

for public review by the Dockets

Management Branch (HFA–305), Food

and Drug Administration, rm. 1–23,

12420 Parklawn Dr., Rockville, MD

20857.

(f) The following drugs are

temporarily exempt from the provisions

of paragraphs (b), (c), and (d) of this

section:

(1) Aromatic Cascara Fluidextract.

(2) Cascara Sagrada Fluidextract.

(3) Orally ingested homeopathic drug

products.

Subpart C—Labeling

§ 328.50 Principal display panel of all OTC

drug products intended for oral ingestion

that contain alcohol.

(a) The amount (percentage) of

alcohol present in a product shall be

stated in terms of percent volume of

absolute alcohol at 60 °F (15.56 °C) in

accordance with § 201.10(d)(2) of this

chapter.

(b) A statement expressing the amount

(percentage) of alcohol present in a

product shall appear prominently and

conspicuously on the ‘‘principal display

panel,’’ as defined in § 201.60 of this

chapter. For products whose principal

display panel is on the immediate

container label and that are not

marketed in another retail package (e.g.,

an outer box), the statement of the

percentage of alcohol present in the

product shall appear prominently and

conspicuously on the ‘‘principal display

panel’’ of the immediate container label.

(c) For products whose principal

display panel is on the retail package

and the retail package is not the

immediate container, the statement of

the percentage of alcohol present in the

product shall also appear on the

immediate container label; it may

appear anywhere on that label in accord

with section 502(e) of the Federal Food,

Drug, and Cosmetic Act.

(d) The statement expressing the

amount (percentage) of alcohol present

in the product shall be in a size

reasonably related to the most

prominent printed matter on the panel

or label on which it appears, and shall

be in lines generally parallel to the base

on which the package rests as it is

designed to be displayed.

(e) For a product to state in its

labeling that it is ‘‘alcohol free,’’ it must

contain no alcohol (0 percent).

(f) For any OTC drug product

intended for oral ingestion containing

over 5 percent alcohol and labeled for

use by adults and children 12 years of

age and over, the labeling shall contain

the following statement in the directions

section: ‘‘Consult a physician for use in

children under 12 years of age.’’

(g) For any OTC drug product

intended for oral ingestion containing

over 0.5 percent alcohol and labeled for

use by children ages 6 to under 12 years

of age, the labeling shall contain the

following statement in the directions

section: ‘‘Consult a physician for use in

children under 6 years of age.’’

(h) When the direction regarding age

in paragraph (e) or (f) of this section

differs from an age-limiting direction

contained in any OTC drug monograph

in this chapter, the direction containing

the more stringent age limitation shall

be used.

Dated: March 1, 1995,

William K. Hubbard,

Acting Deputy Commissioner for Policy.

[FR Doc. 95–6128 Filed 3–10–95; 8:45 am]

BILLING CODE 4160–01–F