[Federal Register Volume 61, Number 78 (Monday, April 22, 1996)]
[Proposed Rules]
[Pages 17807-17812]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-9734]
Federal Register / Vol. 61, No. 78 / Monday, April 22, 1996 /
Proposed Rules
[[Page 17807]]
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Parts 201 and 331
[Docket No. 95N-0254]
RIN 0910-AA63
Labeling of Orally Ingested Over-the-Counter Drug Products
Containing Calcium, Magnesium, and Potassium
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice of proposed rulemaking.
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SUMMARY: The Food and Drug Administration (FDA) is proposing to amend
the general labeling provisions for over-the-counter (OTC) drug
products to require that the labeling of all OTC drug products intended
for oral ingestion include the calcium content per dosage unit when the
product contains 20 milligrams (mg) or more per single dose; a warning
statement that persons with kidney stones and persons on a calcium-
restricted diet should not take the product unless directed by a doctor
when the product contains more than 3.2 grams (g) of calcium in the
labeled maximum daily dose; the magnesium content per dosage unit when
the product contains 8 mg or more per single dose; a warning statement
that persons with kidney disease and persons on a magnesium-restricted
diet should not take the product unless directed by a doctor if the
product contains more than 600 mg magnesium in the labeled maximum
daily dose; the potassium content per dosage unit when the product
contains 5 mg or more per single dose; and a warning statement that
persons with kidney disease and persons on a potassium-restricted diet
should not take the product unless directed by a doctor if the product
contains more than 975 mg potassium in the labeled maximum daily dose.
The agency is proposing that the calcium, magnesium, and potassium
content be labeled in mg per dosage unit, rounded to the nearest whole
number. FDA is issuing this notice of proposed rulemaking in order to
provide uniform calcium, magnesium, and potassium content and warning
labeling for all OTC drug products intended for oral ingestion whether
marketed under an OTC drug monograph, an approved application, or no
application.
DATES: Written comments by July 22, 1996. Written comments on the
agency's economic impact determination by July 22, 1996. The agency is
proposing that any final rule based on this proposal be effective 12
months after the date of its publication in the Federal Register.
ADDRESSES: Submit written comments to the Dockets Management Branch
(HFA-305), Food and Drug Administration, 12420 Parklawn Dr., rm. 1-23,
Rockville, MD 20857.
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
A. Calcium
In the advance notice of proposed rulemaking for OTC antacid drug
products (38 FR 8714 at 8718, April 5, 1973), the Advisory Review Panel
on OTC Antacid Drug Products (Antacid Panel) concluded that calcium
carbonate is safe when taken in a dosage of not more than 160
milliequivalents (mEq) of calcium (8 g calcium carbonate) per day. The
Antacid Panel stated that hypercalcuria in response to calcium
ingestion is not rare in the population and the danger of renal stone
formation has to be considered in determining the intake of calcium-
containing antacids.
The maximum daily dose for calcium carbonate or calcium phosphate
in Sec. 331.11(d) (21 CFR 331.11(d)) of the antacid monograph is 160
mEq (e.g., 3.2 g calcium). This amount of calcium is contained in 8.0 g
calcium carbonate, 18.7 g monobasic calcium phosphate, and 8.3 g
tribasic calcium phosphate. The warning in Sec. 331.30(c)(1) (21 CFR
331.30(c)(1)) states: ``Do not take more than (maximum recommended
daily dosage
* * *) in a 24-hour period, or use the maximum dosage of this product
for more than 2 weeks, except under the advice and supervision of a
physician.''
In the advance notice of proposed rulemaking for OTC digestive aid
drug products (47 FR 454 at 469, January 5, 1982), the Advisory Review
Panel on OTC Miscellaneous Internal Drug Products (Miscellaneous
Internal Panel) stated that adverse reactions associated with calcium
carbonate, including alkalosis, hypercalcemia, acid rebound, milk-
alkali syndrome, and constipation, usually occur with ingestion of
larger than recommended doses and/or with chronic ingestion. The
Miscellaneous Internal Panel stated that some antacids decrease the
effectiveness of many other drugs. The Miscellaneous Internal Panel
recommended the following labeling for drug products containing calcium
carbonate: (1) ``If you are taking other drugs, consult your physician
as this drug may interfere with their effectiveness,'' and (2) ``Do not
take for longer than 2 weeks or in greater than recommended amounts,
except on the advice of a physician.'' However, these warnings were
never finalized because no calcium salt attained monograph status as an
active ingredient for use as an OTC digestive aid drug product.
B. Magnesium
In the advance notice of proposed rulemaking for OTC antacid drug
products (38 FR 8714 at 8719), the Antacid Panel stated that in normal
renal function it is difficult to reach excessive magnesium blood
levels via the oral route, because magnesium enters and leaves the
cells rapidly. However, the Antacid Panel stated that hypermagnesemia
toxicity may occur in renal dysfunction and therefore a warning is
necessary. The Antacid Panel concluded that for those products in which
the maximal daily dose exceeds 50 mEq of magnesium, the labeling should
state: ``Do not use this product if you have kidney disease except
under the advice and supervision of a physician.''
In the final monograph for OTC antacid drug products (39 FR 19862
at 19868, June 6, 1974), the agency noted that at some of its early
meetings the Antacid Panel initially considered 150 mEq per day of
magnesium as the level for requiring a warning, but upon
reconsideration reduced the amount to 50 mEq. The Antacid Panel gave
several reasons for lowering this level: (1) The normal individual
consumes from 20 to 40 mEq of magnesium per day and about one-third of
that amount is absorbed into the body; (2) if a person is taking a
magnesium-containing antacid, approximately 15 to 30 percent of that
magnesium is absorbed, and (3) if a person does not have normal renal
function, it is possible to have hypermagnesemia toxicity, i.e., the
level of magnesium in the body may reach a toxic level.
The final monograph for OTC antacid drug products includes a
warning in Sec. 331.30(c)(4) for products containing more than 50 mEq
of magnesium in the recommended daily dosage, which states: ``Do not
use this product except under the advice and supervision of a physician
if you have kidney disease.'' Although persons with normal renal
function can easily tolerate more than 50 mEq of magnesium a day, the
agency included this warning in the monograph because large doses of an
antacid could present a serious problem for
[[Page 17808]]
individuals with reduced renal function.
In the advance notice of proposed rulemaking for OTC laxative drug
products (56 FR 12902 at 12905, March 21, 1975), the Advisory Review
Panel on OTC Laxative, Antidiarrheal, Emetic, and Antiemetic Drug
Products (Laxative Panel) stated that OTC laxative drug products
containing more than 50 mEq (600 mg) magnesium in the maximum
recommended daily dose should include a warning which states that
people with kidney disease should not use the product except under the
advice and supervision of a physician. In the Federal Register of
January 15, 1985 (50 FR 2124 at 2153), the agency published a tentative
final monograph for OTC laxative drug products that included the
warning recommended by the Laxative Panel. This rulemaking has not been
completed at this time.
In the advance notice of proposed rulemaking for OTC digestive aid
drug products (47 FR 454 at 471), the Miscellaneous Internal Panel
stated that high serum magnesium levels may result from magnesium
ingestion by persons with kidney damage. The Miscellaneous Internal
Panel agreed with the Antacid Panel that a warning statement should be
present on any magnesium hydroxide preparation (47 FR 470) and on any
magnesium trisilicate preparation (47 FR 471) for which the maximal
daily dose exceeds 50 mEq (600 mg) of magnesium. The Miscellaneous
Internal Panel also stated that magnesium hydroxide has the potential
for drug interactions with certain anticoagulants and antibiotics.
Similarly, the Miscellaneous Internal Panel noted that magnesium
trisilicate absorbs various alkaloids and antibiotics in vitro.
However, this warning was never finalized because no magnesium salt
attained monograph status as an active ingredient for use as an OTC
digestive aid drug product.
C. Potassium
In the advance notice of proposed rulemaking for OTC antacid drug
products (38 FR 8714 at 8719), the Antacid Panel stated that
hyperkalemia is rare for normal persons who can easily tolerate the
potassium content of antacid drug products. The Antacid Panel
concluded, however, that potassium can accumulate in the body of
persons with impaired renal function and exert toxic effects. The
Antacid Panel recommended the following warning for products containing
more than 25 mEq (975 mg) potassium in the maximum recommended daily
dose: ``Do not use this product if you have kidney disease except under
the advice and supervision of a physician.'' This warning appears in
Sec. 331.30(c)(6) of the antacid final monograph, slightly rephrased to
read: ``Do not use this product except under the advice and supervision
of a physician if you have kidney disease.''
In the advance notice of proposed rulemaking (56 FR 12902 at
12905), the Laxative Panel recommended that if a laxative product
contains more than 25 mEq (975 mg) of potassium in the maximum
recommended daily dose, the labeling should advise consumers with
kidney disease not to use the product except under the advice and
supervision of a physician. The agency is aware that some effervescent
laxative drug products contain significant amounts of potassium as
inactive ingredients. The Laxative Panel recommended that the inactive
ingredients be listed (with or without the amounts) for OTC laxative
drug products and that the availability of sodium, potassium, and
magnesium in the maximum recommended daily dose be stated in the
labeling. The Laxative Panel noted that certain inactive ingredients
(including calcium hydroxide and potassium carbonate) are added to some
laxative preparations to enhance their formulation or to contribute to
the effervescent qualities.
In the tentative final monograph for OTC laxative drug products (50
FR 2124 at 2153), the agency agreed with the Laxative Panel's
recommendation and proposed the following warning for those products
containing more than 975 mg potassium in the maximum recommended daily
dose: ``Do not use this product if you have kidney disease unless
directed by a doctor.'' This rulemaking has not been completed at this
time.
D. Rulemaking for Sodium Labeling of OTC Drug Products
The agency has already addressed sodium labeling in a final rule
published elsewhere in this issue of the Federal Register. That rule
amends the general labeling provisions for OTC drug products to include
sodium labeling and provides for across-the-board uniform sodium
content and warning labeling for all OTC drug products intended for
oral ingestion. New Sec. 201.64 requires sodium content labeling of all
products containing 5 mg or more sodium per single recommended dose and
requires that products containing more than 140 mg sodium per maximum
recommended daily dose be labeled with a general warning that states:
``Do not use this product if you are on a sodium-restricted diet unless
directed by a doctor.'' Section 201.64 also provides for the voluntary
use of certain descriptive terms (``sodium free,'' ``very low sodium,''
and ``low sodium''). These descriptive terms are the same terms used to
describe sodium content in food labeling.
Sodium content is expressed in mg per single dosage unit (e.g.,
tablet, teaspoonful), rounded-off to the nearest whole number, and
includes the total amount of sodium regardless of the source (both
active and inactive ingredients). OTC drug products ``intended for oral
ingestion'' also include gum and lozenge dosage forms, but do not
include dentifrices, mouthwashes, or mouth rinses. Because some OTC
drug products not intended for oral administration can contain very
high levels of sodium that may be absorbed from both active and
inactive ingredients, the agency has asked for comments from interested
individuals on whether the final rule should be amended to include
sodium labeling for OTC rectal, vaginal, dentifrice, mouthwash, and
mouth rinse drug products. The agency will address this subject in a
future issue of the Federal Register.
Two comments received to the tentative final monograph for OTC
laxative drug products contended that sodium labeling of OTC laxative
and other drug products should be consistent with FDA's food labeling
terminology. The comments stated that food products already bear FDA
terminology and the food terminology will become the dominant system.
Thus, other mandatory FDA labeling systems should be made consistent
with that system. The agency has used this approach in the final rule
for sodium labeling of OTC drug products published elsewhere in this
issue of the Federal Register.
E. Food Labeling Regulations
FDA regulations for food products address calcium and magnesium
labeling. Section 101.9 (21 CFR 101.9) requires the labeling of food
products to declare the content, as a percent of the Reference Daily
Intake (RDI), of calcium, iron, vitamin C, and vitamin E. Other
vitamins and minerals for which a RDI has been established, including
magnesium, may be listed voluntarily, unless they are added as a
nutrient supplement or a claim is made about them, in which case they
must be declared.
Section 101.9(c)(5) provides for the voluntary declaration of
potassium content in a labeled serving size. However, when a claim is
made about potassium, the declaration is mandatory and is placed on the
nutrition label
[[Page 17809]]
immediately following the sodium content. When the potassium content is
less than 5 mg per serving, the content is expressed as zero.
Vitamins and minerals, other than calcium, iron, vitamin C, and
vitamin E, present at less than 2 percent of the RDI are not required
to be declared in nutrition labeling but may be declared as zero or by
use of an asterisk referring to a footnote that states, ``Contains less
than 2% of the Daily Value of this (these) nutrient (nutrients)''
(Sec. 101.9(c)(8)(iii)). The RDI for calcium is 1,000 mg and for
magnesium is 400 mg (Sec. 101.9(c)(8)(iv)). Thus, for foods containing
less than 20 mg of calcium per serving, a declaration of zero is
required on the nutrition label. For foods containing less than 8 mg of
magnesium per serving, content declaration is not required (unless a
claim is made about the nutrient) or may be declared as zero or as less
than 2 percent of the Daily Value.
The regulations in Sec. 101.36(b)(3) (21 CFR 101.36(b)(3)) for
nutrition labeling of dietary supplements of vitamins and minerals
require that potassium be declared except when present in quantitative
amounts by weight that allow a declaration of zero.
The regulations for health claims related to calcium and
osteoporosis in Sec. 101.72(c)(2)(i)(E) (21 CFR 101.72(c)(2)(i)(E))
require the labeling of food products to state that a total dietary
intake greater than 2,000 mg of calcium has no further known benefit to
bone health. This requirement applies when the food or supplement
contains more than 400 mg of calcium per reference amount. A recently
published NIH Concensus Statement on optimal calcium intake states that
up to a total intake of 2,000 mg per day appears to be safe in most
individuals (``Optimal Calcium Intake,'' NIH Consensus Statement,
12(4):1-31, June 6-8, 1994).
II. The Agency's Tentative Conclusions on Labeling of Orally
Ingested OTC Drug Products Containing Calcium, Magnesium, and
Potassium
A. Basis for Rulemaking -
FDA believes that the public interest in, and the public health
consequences of, calcium, magnesium, and potassium intake have produced
a need for more informative and consistent labeling information for
these ingredients in OTC drug products. The agency believes certain
labeling requirements are needed to alert persons with renal failure,
kidney stones, or other conditions, and persons taking other
medications who wish to monitor their intake of calcium, magnesium, and
potassium. Consumers need to consider their intake from foods, dietary
supplements, and drugs. Therefore, the agency is proposing calcium,
magnesium, and potassium content and warning labeling for all OTC drug
products intended for oral ingestion that contain certain levels of
these ingredients (including both active and inactive ingredients).
B. Criteria for Content and Warning Labeling-
In order to establish uniform content declarations and warnings
relating to calcium, magnesium, and potassium for orally ingested OTC
drug products and to establish content labeling similar to that used in
food labeling, the agency is proposing to adopt: (1) 20 mg of calcium,
8 mg of magnesium, and 5 mg of potassium as the amount per single
recommended dose in an OTC drug product (which may involve one or more
dosage units, e.g., tablets, teaspoonsful, etc.) that requires a
content declaration; and (2) 3.2 g calcium, 600 mg magnesium, and 975
mg potassium as the amounts present in the maximum labeled daily dose
above which a warning is required. The agency is therefore proposing to
amend the general drug labeling provisions in part 201 (21 CFR part
201) to include these labeling requirements for OTC drug products
intended for oral ingestion.
The proposed levels for requiring content labeling are similar to
those used in food labeling. In contrast, the proposed levels for
requiring warnings are based on recommendations of FDA advisory review
panels in the early 1970's. The agency acknowledges that there may be
more recent scientific information to consider in setting requirements
for OTC drug product labeling. The agency specifically encourages
comment and data on this aspect of the proposal.
C. Basis for Amount Requiring Content Labeling
1. Calcium and Magnesium Content-
As stated in section I.E. of this document, a serving of food
containing 20 mg or more of calcium requires a content declaration, and
a serving of food containing 8 mg or more of magnesium (if added as a
supplement or if a claim is made) requires a content declaration in the
nutrition labeling of foods. Thus, the agency is using 20 mg calcium
and 8 mg magnesium per single recommended dose as the amounts at which
OTC drug products should include content labeling for these
ingredients.
2. Potassium Content
As noted in section I.E. of this document, potassium labeling for
foods is optional unless a claim is made about the potassium content;
but, if declared, it is expressed in mg per serving for those foods
containing 5 mg or more. In Sec. 201.64(a) of the final rule for sodium
labeling of OTC drug products, the agency required a declaration of the
sodium content for all OTC drugs intended for oral ingestion if the
sodium content per single recommended dose is 5 mg or more. The agency
believes it is not necessary to declare potassium amounts below 5 mg
per dose. However, the agency believes it is appropriate to declare the
potassium content if the product contains 5 mg or more per single
recommended dose.
D. Basis for Amount Requiring Warning Statements
The agency believes that for uniformity in labeling, warnings
should be required across-the-board for calcium, magnesium, and
potassium for those OTC drug products intended for oral ingestion
containing a certain concentration of these ingredients.
1. Calcium Warning
Based on the current requirements in the monograph for OTC antacid
drug products and the recommendations of the Miscellaneous Internal
Panel (see section I.A. of this document), the agency is proposing to
require the following warning for all OTC drug products containing more
than 3.2 g calcium (equivalent to 8 g calcium carbonate) per labeled
maximum daily dose: ``Do not use this product if you have kidney stones
or if you are on a calcium-restricted diet unless directed by a
doctor.'' The NIH Consensus Statement on optimal calcium intake
suggests that a 2,000 mg total daily intake is safe, but it does not
give a definitive conclusion as to what level is unsafe. When the 3,200
mg daily dosage level, proposed as the level requiring a warning, is
added to the 1,000 mg recommended daily intake that may be included in
a person's diet, the resulting 4,200 mg daily intake is considerably
higher than the 2,000 mg level found to be safe in the NIH consensus
statement. The agency invites comments on whether the proposed 3.2 g
level requiring a warning should be lowered.
2. Magnesium Warning
The agency is proposing to require the following warning for all
OTC drug products that contain more than 600 mg magnesium per labeled
maximum daily dose: ``Do not use this product if you have kidney
disease or if you are on a
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magnesium-restricted diet unless directed by a doctor.'' This warning
is similar to the warning in Sec. 331.30(c)(4) of the final monograph
for OTC antacid drug products.
3. Potassium Warning
The agency is proposing to require the following warning for all
OTC drug products that contain more than 975 mg potassium per maximum
recommended dose: ``Do not use this product if you have kidney disease
or if you are on a potassium-restricted diet unless directed by a
doctor.'' This warning is similar to the warning in Sec. 331.30(c)(6)
of the final monograph for OTC antacid drug products.
E. Units of Measure-
The agency believes the units of measure, where possible, should be
similar for foods and drugs. The unit of measure in declaring the
content of these components in foods is mg or g per serving of food.
While a serving of food is not the same as a dosage of a drug, the
agency believes it is logical to declare the content in mg per dosage
unit of the drug and to require a content declaration if the ingredient
per dose (which could be contained in one or more active or inactive
ingredients and in one or more dosage units) is equal to the amount in
a serving of food that requires a declaration in the nutrition
labeling. This is similar to the agency's approach in the final rule
for sodium labeling of OTC drug products. Section 201.64(b) states:
``The sodium content shall be expressed in milligrams per dosage unit
and shall include the total amount of sodium regardless of the source,
i.e., from both active and inactive ingredients.''
F. Rounding to Whole Number
While the food labeling regulations allow for the content
declaration of certain ingredients (e.g., sodium and potassium) to be
labeled as ``zero'' up to a certain level (5 mg per serving)
(Sec. 101.9(c)(8)(i) and (c)(8)(ii)), the agency believes these
ingredients in drugs should not be labeled as zero content except when
the content is zero (based on rounding to the nearest whole number, as
in the regulation for sodium labeling of OTC drug products). As
discussed in the sodium labeling final rule, most OTC drug products are
manufactured and the concentration of ingredients can be strictly
controlled. Thus, the concentration of specific ingredients is expected
to be less variable in OTC drug products than in foods. For consistency
in labeling, the agency believes the labeling of these ingredients
should be expressed in mg per dosage unit rounded to the nearest whole
number for those products containing less than 1 g. For those products
containing 1 g or more per dosage unit, the content labeling may be
rounded to the nearest tenth of a g.
G. Implementation of Labeling Requirements
The agency encourages manufacturers to comply voluntarily with the
provisions of this proposed rule despite the fact that revisions in the
requirements may occur in the final rule in response to submitted
comments. Should any manufacturer choose to adopt the labeling
described in this proposed rule, and should any revisions occur in the
final rule, the agency will permit the use of existing stocks of labels
for those products labeled according to the proposed rule for a period
of 1 year following publication of the final rule.
Should this proposed amendment to part 201 relating to calcium,
magnesium, and potassium content and warning labeling of all OTC drug
products intended for oral ingestion be published as a final rule, then
the existing requirements relating to magnesium labeling in
Sec. 331.30(c)(4) and potassium labeling in Sec. 331.30(c)(5) of the
final monograph for OTC antacid drug products and the proposed labeling
requirements for magnesium and potassium being considered in other
ongoing OTC drug rulemakings will be deleted. The agency advises that
on or after 12 months after publication of a final rule any OTC drug
product subject to this rule that does not meet these labeling
requirements and that is initially introduced or initially delivered
for introduction into interstate commerce will be misbranded under
sections 201(n) and 502(a) and (f) of the Federal Food, Drug, and
Cosmetic Act (21 U.S.C. 321(n) and 352(a) and (f)).
III. Analysis of Impacts
FDA has examined the impacts of the proposed 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 proposed rule is consistent with the regulatory philosophy and
principles identified in the Executive Order. In addition, the proposed
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. Should this proposed rule become a final rule, one-
time label modification costs associated with changing product labels
would be incurred by some manufacturers. FDA estimates those costs to
total less than $500,000 for the entire industry. This projected cost
is based on estimates of the number of products that will be affected
by the proposed rule, the number of distinct label changes that will be
required, and the cost of printing new labels.
OTC antacid drug products are the primary products having a
significant number of orally administered active ingredients containing
calcium, magnesium, and potassium. The monograph for those products has
been in effect since 1974 and these products currently bear magnesium
and potassium warning labeling. For these products, the labeling change
would involve a slight change in wording, resulting only in a minor
cost to have a labeling revision printed. For those products containing
calcium, a new warning would be required in product labeling. In almost
all cases, this revision would be routinely done at the next labeling
printing so that minimal costs should be incurred. Manufacturers will
have up to 12 months after publication of a final rule in the Federal
Register to revise their product labeling. It is anticipated that most
antacid drug products would undergo a label printing within a 12-month
period. Products containing magnesium and potassium would need only
minor revisions, and products containing calcium would need to add some
new labeling.
Other OTC drug products (i.e., antidiarrheals, laxatives, and
internal analgesics) having one or a few calcium, magnesium, and
potassium-containing active ingredients that would be affected by
mandatory calcium, magnesium, and potassium labeling currently are not
required to bear the labeling recommended in this proposed rule. These
products would need to have new labels printed to incorporate the
labeling requirements of this rulemaking. These products will also need
to have new labeling printed in the future when the final monographs
for OTC antidiarrheal, laxative, and internal analgesic drug products
are published. This again involves one-time label modification costs.
For products that will be undergoing such labeling
[[Page 17811]]
changes, the incremental costs attributable to this rule for calcium,
magnesium, and potassium labeling would be negligible. A limited number
of OTC antidiarrheal, laxative, and internal analgesic drug products
contain calcium, magnesium, and potassium-containing active
ingredients.
Accordingly, the agency certifies that the proposed rule will not
have a significant economic impact on a substantial number of small
entities. Therefore, under the Regulatory Flexibility Act, no further
analysis is required.
The agency invites public comment regarding any substantial or
significant economic impact that this rulemaking would have on OTC drug
products intended for oral ingestion. Types of impact may include, but
are not limited to, costs associated with relabeling, repackaging, or
reformulating. Comments regarding the impact of this rulemaking on OTC
drug products should be --accompanied by appropriate documentation. A
period of 90 days from the date of publication of this proposed
rulemaking in the Federal Register will be provided for comments on
this subject to be developed and submitted. The agency will evaluate
any comments and supporting data that are received and will reassess
the economic impact of this rulemaking in the preamble to the final
rule.
IV. Paperwork Reduction Act of 1995
FDA tentatively concludes that the labeling requirements proposed
in this document are not subject to review by the Office of Management
and Budget because they do not constitute a ``collection of
information'' under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501
et seq.). Rather, the proposed warning statements are a ``public
disclosure of information originally supplied by the Federal government
to the recipient for the purpose of disclosure to the public'' (5 CFR
1320.3(c)(2)). The calcium, magnesium, and potassium content per dosage
unit is product formulation information that manufacturers have on hand
as part of their usual and customary business practice.
V. 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.
VI. Request for Comments
Interested persons may, on or before July 22, 1996, submit to the
Dockets Management Branch (address above) written comments regarding
this proposal. Written comments on the agency's economic impact
determination may be submitted on or before July 22, 1996. Three copies
of all comments are to be submitted, except that individuals may submit
one copy. Comments are to be identified with the docket number found in
brackets in the heading of this document and may be accompanied by a
supporting memorandum or brief. Received comments may be seen in the
office above between 9 a.m. and 4 p.m., Monday through Friday.
List of Subjects
21 CFR Part 201
Drugs, Labeling, Reporting and recordkeeping requirements.
21 CFR Part 331
Labeling, Over-the-counter drugs.
Therefore, under the Federal Food, Drug, and Cosmetic Act, it is
proposed that title 21 of the Code of Federal Regulations be amended in
parts 201 and 331 as follows:
PART 201--LABELING
1. The authority citation for 21 CFR part 201 continues to read as
follows:
Authority: Secs. 201, 301, 501, 502, 503, 505, 506, 507, 508,
510, 512, 530-542, 701, 704, 721 of the Federal Food, Drug, and
Cosmetic Act (21 U.S.C. 321, 331, 351, 352, 353, 355, 356, 357, 358,
360, 360b, 360gg-360ss, 371, 374, 379e); secs. 215, 301, 351, 361 of
the Public Health Service Act (42 U.S.C. 216, 241, 262, 264).
2. New Sec. 201.70 is added to subpart C to read as follows:
Sec. 201.70 Calcium labeling.
(a) The labeling of over-the-counter (OTC) drug products intended
for oral ingestion shall contain the calcium content per dosage unit
(e.g., tablet, teaspoonful) if the calcium content of a single
recommended dose of the product (which may be one or more dosage units)
is 20 milligrams or more. OTC drug products intended for oral ingestion
include gum and lozenge dosage forms, but do not include dentifrices,
mouthwashes, or mouth rinses.
(b) The calcium content shall be expressed in milligrams or grams
per dosage unit and shall include the total amount of calcium
regardless of the source, i.e., from both active and inactive
ingredients. If less than 1 gram, milligrams should be used. The
calcium content shall be rounded-off to the nearest whole number in
milligrams (or tenth of a gram if over 1 gram) and shall be listed on a
separate line after the heading ``Calcium Content'' as the last
sentence in the ingredients section.
(c) The labeling of OTC drug products intended for oral ingestion
shall contain the following warning under the heading ``Warning'' (or
``Warnings'' if it appears with additional warning statements) if the
amount of calcium present in the labeled maximum daily dose of the
product is more than 3.2 grams: ``Do not use this product if you have
kidney stones or if you are on a calcium-restricted diet unless
directed by a doctor.''
(d) Any product subject to this paragraph that is not labeled as
required by this paragraph and that is initially introduced or
initially delivered for introduction into interstate commerce after
(date 1 year after publication of the final rule), is misbranded under
sections 201(n) and 502(a) and (f) of the Federal Food, Drug, and
Cosmetic Act.
3. New Sec. 201.71 is added to subpart C to read as follows:
Sec. 201.71 Magnesium labeling.
(a) The labeling of over-the-counter (OTC) drug products intended
for oral ingestion shall contain the magnesium content per dosage unit
(e.g., tablet, teaspoonful) if the magnesium content of a single
recommended dose of the product (which may be one or more dosage units)
is 8 milligrams or more. OTC drug products intended for oral ingestion
include gum and lozenge dosage forms, but do not include dentifrices,
mouthwashes, or mouth rinses.
(b) The magnesium content shall be expressed in milligrams or grams
per dosage unit and shall include the total amount of magnesium
regardless of the source, i.e., from both active and inactive
ingredients. If less than 1 gram, milligrams should be used. The
magnesium content shall be rounded-off to the nearest whole number in
milligrams (or tenth of a gram if over 1 gram) and shall be listed on a
separate line after the heading ``Magnesium Content'' as the last
sentence in the ingredients section.
(c) The labeling of OTC drug products intended for oral ingestion
shall contain the following warning under the heading ``Warning'' (or
``Warnings'' if it appears with additional warning statements) if the
amount of magnesium present in the labeled maximum daily dose of the
product is more than 600 milligrams: ``Do not use this product if
[[Page 17812]]
you have kidney disease or if you are on a magnesium-restricted diet
unless directed by a doctor.''
(d) Any product subject to this paragraph that is not labeled as
required by this paragraph and that is initially introduced or
initially delivered for introduction into interstate commerce after
(date 1 year after publication of the final rule), is misbranded under
sections 201(n) and 502(a) and (f) of the Federal Food, Drug, and
Cosmetic Act.
4. New Sec. 201.72 is added to subpart C to read as follows:
Sec. 201.72 Potassium labeling.
(a) The labeling of over-the-counter (OTC) drug products intended
for oral ingestion shall contain the potassium content per dosage unit
(e.g., tablet, teaspoonful) if the potassium content of a single
recommended dose of the product (which may be one or more dosage units)
is 5 milligrams or more. OTC drug products intended for oral ingestion
include gum and lozenge dosage forms, but do not include dentifrices,
mouthwashes, or mouth rinses.
(b) The potassium content shall be expressed in milligrams or grams
per dosage unit and shall include the total amount of potassium
regardless of the source, i.e., from both active and inactive
ingredients. If less than 1 gram, miligrams should be used. The
potassium content shall be rounded-off to the nearest whole number in
milligrams (or tenth of a gram if over 1 gram) and shall be listed on a
separate line after the heading ``Potassium Content'' as the last
statement in the ingredients section.
(c) The labeling of OTC drug products intended for oral ingestion
shall contain the following warning under the heading ``Warning'' (or
``Warnings'' if it appears with additional warning statements) if the
amount of potassium present in the labeled maximum daily dose of the
product is more than 975 milligrams: ``Do not use this product if you
have kidney disease or if you are on a potassium-restricted diet unless
directed by a doctor.''
(d) Any product subject to this paragraph that is not labeled as
required by this paragraph and that is initially introduced or
initially delivered for introduction into interstate commerce after
(date 1 year after publication of the final rule), is misbranded under
sections 201(n) and 502(a) and (f) of the Federal Food, Drug, and
Cosmetic Act.
PART 331--ANTACID PRODUCTS FOR OVER-THE-COUNTER (OTC) HUMAN USE
5. 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).
Sec. 331.30 [Amended]
6. Section 331.30 Labeling of antacid products is amended by
removing paragraphs (c)(4) and (c)(5) and by redesignating paragraph
(c)(6) as paragraph (c)(4).
Dated: March 30, 1996.
William K. Hubbard,
Associate Commissioner for Policy Coordination.
[FR Doc. 96-9734 Filed 4-19-96; 8:45 am]
BILLING CODE 4160-01-F
