[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]]
_______________________________________________________________________
Part X
Department of Health and Human Services
_______________________________________________________________________
Food and Drug Administration
_______________________________________________________________________
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
=======================================================================
-----------------------------------------------------------------------
[[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.
-----------------------------------------------------------------------
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'' ( 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 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 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
