[Federal Register Volume 60, Number 48 (Monday, March 13, 1995)]
[Rules and Regulations]
[Pages 13590-13595]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-6128]




[[Page 13589]]

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Part X





Department of Health and Human Services





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Food and Drug Administration



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21 CFR Part 328



Over-the-Counter Drug Products Intended for Oral Ingestion That Contain 
Alcohol; Final Rule

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


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.

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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 Sec. 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 Sec. 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 
[[Page 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 
Sec. 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 
Sec. 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 
[[Page 13592]] 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 
Sec. 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 alcohol-containing 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'' (<ls-thn-eq> 0.5 g), ``sodium 
free'' (<ls-thn-eq> 5 mg), and ``fat free'' (<ls-thn-eq> 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 Sec. 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 [[Page 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 
Sec. 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 Sec. 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 <ls-thn-eq> 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 
Sec. 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 Sec. 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 [[Page 13594]] 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 
Sec. 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 Sec. 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 Sec. 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 
Sec. 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 Sec. 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: [[Page 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


Sec. 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.

Sec. 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 Sec. 210.3(b)(7) of this chapter.

Subpart B--Ingredients


Sec. 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 Sec. 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


Sec. 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  deg.F 
(15.56  deg.C) in accordance with Sec. 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 Sec. 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