[Federal Register Volume 61, Number 27 (Thursday, February 8, 1996)]
[Rules and Regulations]
[Pages 4822-4823]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-2666]
[[Page 4821]]
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Part III
Department of Health and Human Services
_______________________________________________________________________
Food and Drug Administration
_______________________________________________________________________
21 CFR Part 331
Antacid Drug Products for Over-the-Counter Human Use; Amendment of
Antacid Monograph; Final Rule
Federal Register / Vol. 61, No. 27 / Thursday, February 8, 1996 /
Rules and Regulations
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[[Page 4822]]
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 331
[Docket No. 88N-0327]
RIN 0905-AA06
Antacid Drug Products for Over-the-Counter Human Use; Amendment
of Antacid Monograph
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
that amends the monograph for over-the-counter (OTC) antacid drug
products by deleting parts of the testing procedures in subpart C. This
final rule is part of the ongoing review of OTC drug products conducted
by FDA. Also, this final rule is part of the Administration's
``Reinventing Government'' initiative which seeks to streamline
government and to ease the burden on regulated industry and consumers.
EFFECTIVE DATE: February 10, 1997.
FOR FURTHER INFORMATION CONTACT: William E. Gilbertson, Center for Drug
Evaluation and Research (HFD-105), Food and Drug Administration, 5600
Fishers Lane, Rockville, MD 20857, 301-827-2304.
SUPPLEMENTARY INFORMATION:
-I. Background
-In the Federal Register of June 4, 1974 (39 FR 19862), FDA issued
a final monograph for OTC antacid drug products (21 CFR part 331) that
included procedures for testing antacid drug products. An acid
neutralizing capacity test is described in Sec. 331.26. When the final
monograph was issued in 1974, the United States Pharmacopeia (USP) did
not include an acid neutralizing capacity test. However, in 1980 an
acid neutralizing capacity test was included in the USP (Ref. 1). That
test is substantially the same as the test found in the final monograph
for OTC antacid drug products. Several revisions in the USP acid
neutralizing capacity test have been made since 1980 to increase the
accuracy and utility of the test. The current USP 23/National Formulary
(N.F.) 18 acid neutralizing capacity test (Ref. 2) differs from the
agency's antacid monograph testing procedures, which have not been
revised.
-The FDA recommended disintegration test method (in Sec. 331.24)
and the methods in current USP 23/N.F. 18 monographs for antacid
tablets also have some differences. Current USP 23/N.F. 18 procedures
include tests for powder and suspension dosage forms and for products
having an acid neutralizing capacity greater than 25 milliequivalents
(meq) of acid, as well as a more detailed sample preparation procedure
for capsule dosage forms.
-In the Federal Register of September 23, 1993 (58 FR 49826), the
agency issued a notice of proposed rulemaking to amend the final
monograph for OTC antacid drug products to delete parts of the testing
procedures in subpart C, as discussed above in this document. The
agency discussed the differences between its antacid monograph
standards and those in the USP. The agency mentioned that it could
amend its antacid monograph to be consistent with the USP, but opted to
delete portions of its monograph testing procedures and refer to the
USP procedures for determination of the antacid product's acid
neutralizing capacity in place thereof. The agency noted that USP
procedures do not include a ``preliminary antacid test'' (as contained
in Sec. 331.25 of the antacid monograph) or a procedure for the
``determination of percent contribution of active ingredients'' in a
combination antacid drug product (as contained in Sec. 331.21 of the
antacid monograph). The agency does not consider the ``preliminary
antacid test'' as essential to the determination of a product's acid
neutralizing capacity. However, manufacturers may elect to continue to
use this test as a preliminary screening procedure. The agency stated
that it was retaining Sec. 331.21 (``determination of percent
contribution of active ingredients'') in the monograph (redesignated as
Sec. 331.20) so that a procedure will be available for making that
determination. No comments were received in response to the agency's
proposed changes in the antacid monograph.
References
(1) ``United States Pharmacopeia XX--National Formulary XV,''
United States Pharmacopeial Convention, Inc., Rockville, MD, p. 912,
1980.
(2) ``United States Pharmacopeia 23--National Formulary 18,''
United States Pharmacopeial Convention, Inc., Rockville, MD, pp. 54-
55 and 1791-1793, 1994.
II. The Agency's Final Conclusions on the Amendment to the
Monograph for OTC Antacid Drug Products
-In the proposal, the agency referred to the acid neutralizing
capacity test procedures in USP XXII/N.F. XVII. Since the proposal was
published, USP 23/N.F. 18 became official on January 1, 1995. The test
procedures in both editions of the USP are the same. Therefore, the
agency is referencing USP 23/N.F. 18 in this final rule.
The agency is removing the following sections from ``Subpart C--
Testing Procedures'' in ``Part 331--Antacid Products for Over-the-
Counter (OTC) Human Use'': Secs. 331.20, 331.22, 331.23, 331.24,
331.25, and 331.26. The agency is redesignating Sec. 331.21 as
Sec. 331.20 and amending it to refer to the USP 23/N.F. 18 test
procedure in place of Sec. 331.26, which is being removed. The agency
is retaining Sec. 331.29 (``test modifications'') in case there is a
need for any manufacturer to petition for a test modification, is
redesignating this section as Sec. 331.21, and is amending it to
reference the USP 23/N.F. 18 test procedure. The agency is also
amending Secs. 331.10(a) and 331.80(a)(1) to refer to USP 23/N.F. 18.
-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
49826 at 49827). No comments were received in response to the agency's
request for specific comment on the economic impact of this rulemaking.
Executive Order 12291 has been superseded by Executive Order 12866.
-FDA has examined the impacts of this 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. Manufacturers of OTC antacid drug products should
not be affected by the deletion of certain testing procedures that have
already been incorporated into the USP/N.F. Accordingly, the agency
certifies that the final rule will not have a significant economic
impact on a substantial
[[Page 4823]]
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 331
-Labeling, Over-the-counter drugs.
-Therefore, under the Federal Food, Drug, and Cosmetic Act and
under authority delegated to the Commissioner of Food and Drugs, 21 CFR
part 331 is amended as follows:
-PART 331--ANTACID PRODUCTS FOR OVER-THE-COUNTER (OTC) HUMAN USE
-1. The authority citation for 21 CFR part 331 continues to read
as follows:
-Authority: Secs. 201, 501, 502, 503, 505, 510, 701 of the
Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321, 351, 352, 353,
355, 360, 371).
-2. Section 331.10 is amended by revising paragraph (a) to read as
follows:
Sec. 331.10 Antacid active ingredients.
-(a) The active antacid ingredients of the product consist of one
or more of the ingredients permitted in Sec. 331.11 within any maximum
daily dosage limit established, each ingredient is included at a level
that contributes at least 25 percent of the total acid neutralizing
capacity of the product, and the finished product contains at least 5
meq of acid neutralizing capacity as measured by the procedure provided
in the United States Pharmacopeia 23/National Formulary 18. The method
established in Sec. 331.20 shall be used to determine the percent
contribution of each antacid active ingredient.
*- *- *- *- *
Sec. 331.20 [Removed]
-3. Section 331.20 Apparatus and reagents is removed from subpart
C.
Sec. 331.21 [Redesignated as Sec. 331.20]
-4. Section 331.21 is redesignated as Sec. 331.20 and revised to
read as follows:
Sec. 331.20 Determination of percent contribution of active
ingredients.
-To determine the percent contribution of an antacid active
ingredient, place an accurately weighed amount of the antacid active
ingredient equal to the amount present in a unit dose of the product
into a 250-milliliter (mL) beaker. If wetting is desired, add not more
than 5 mL of alcohol (neutralized to an apparent pH of 3.5), and mix to
wet the sample thoroughly. Add 70 mL of water, and mix on a magnetic
stirrer at 30030 r.p.m. for 1 minute. Analyze the acid
neutralizing capacity of the sample according to the procedure provided
in the United States Pharmacopeia 23/National Formulary 18 and
calculate the percent contribution of the antacid active ingredient in
the total product as follows:
-Percent contribution = (Total meq. Antacid Active Ingredient
x100)/(Total meq. Antacid Product).
Sec. 331.22 [Removed]
-5. Section 331.22 Reagent standardization is removed.
Sec. 331.23 [Removed]
-6. Section 331.23 Temperature standardization is removed.
Sec. 331.24 [Removed]
-7. Section 331.24 Tablet disintegration test is removed.
Sec. 331.25 [Removed]
-8. Section 331.25 Preliminary antacid test is removed.
Sec. 331.26 [Removed]
-9. Section 331.26 Acid neutralizing capacity test is removed.
Sec. 331.29 [Redesignated as Sec. 331.21]
10. Section 331.29 is redesignated as Sec. 331.21 and revised to
read as follows:
Sec. 331.21 Test modifications.
-The formulation or mode of administration of certain products may
require a modification of the United States Pharmacopeia 23/National
Formulary 18 acid neutralizing capacity test. Any proposed modification
and the data to support it shall be submitted as a petition under the
rules established in Sec. 10.30 of this chapter. All information
submitted will be subject to the disclosure rules in part 20 of this
chapter.
-11. Section 331.80 is amended by revising paragraph (a)(1) to read
as follows:
Sec. 331.80 Professional labeling.
-(a) * * *
-(1) Shall contain the neutralizing capacity of the product as
calculated using the procedure set forth in United States Pharmacopeia
23/National Formulary 18 expressed in terms of the dosage recommended
per minimum time interval or, if the labeling recommends more than one
dosage, in terms of the minimum dosage recommended per minimum time
interval.
* * * * *
Dated: January 29, 1996.
William K. Hubbard,
Associate Commissioner for Policy Coordination.
[FR Doc. 96-2666 Filed 2-7-96; 8:45 am]
BILLING CODE 4160-01-F
