[Printable PDF]
[Federal Register: February 1, 2002 (Volume 67, Number 22)]
[Rules and Regulations]
[Page 4904-4907]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr01fe02-9]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Parts 10, 201, 250, 290, 310, 329, 341, 361, 369, 606, and
610
[Docket No. 00N-0086]
Amendment of Regulations Regarding Certain Label Statements on
Prescription Drugs
AGENCY: Food and Drug Administration, HHS.
ACTION: Final rule.
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SUMMARY: The Food and Drug Administration (FDA) is amending its
regulations concerning certain statements that have been required on
the labels of prescription drugs generally and on certain narcotic or
hypnotic (habit-forming) drugs. The agency is taking this action in
accordance with provisions of the Food and Drug Administration
Modernization Act of 1997 (Modernization Act).
DATES: This rule is effective April 2, 2002.
FOR FURTHER INFORMATION CONTACT:
For information regarding human drugs: Jerry Phillips, Center for
Drug Evaluation and Research (HFD-400), Food and Drug Administration,
5600 Fishers Lane, Rockville, MD 20857, 301-827-3246.
For information regarding biologics: Robert A. Yetter, Center for
Biologics Evaluation and Research (HFM-10), Food and Drug
Administration, 1401 Rockville Pike, Rockville, MD 20852-1448, 301-827-
0373.
SUPPLEMENTARY INFORMATION:
I. Background
On November 21, 1997, the Modernization Act (Public Law 105-115)
was signed into law. Section 126 of the Modernization Act amended
section 503(b)(4) of the Federal Food, Drug, and Cosmetic Act (the act)
(21 U.S.C. 353(b)(4)) to require, at a minimum, that, prior to
dispensing, the label of prescription drugs bear the symbol ``Rx only''
instead of the statement ``Caution: Federal law prohibits dispensing
without prescription.'' The new label statement may be printed as
either ``Rx only'' or `` only.'' Section 126 of the Modernization
Act also repealed section 502(d) of the act (21 U.S.C. 352(d)), which
provided that a drug or device containing certain enumerated narcotic
or hypnotic (habit-forming) substances or their derivatives was
misbranded unless its label bore the name and quantity of the substance
and the statement ``Warning--May be habit forming.'' In the Federal
Register of April 21, 2000 (65 FR 21378), FDA proposed amending its
regulations to implement these provisions of the Modernization Act.
II. Highlights of the Final Rule
The agency is finalizing without change the regulatory provisions
of the proposed rule.
The final rule amends parts 10, 201, 250, 310, 329, 361,
606, and 610 (21 CFR parts 10, 201, 250, 310, 329, 361, 606, and 610)
by removing the requirement that prescription drugs be labeled with
``Caution: Federal law prohibits dispensing without prescription'' and
adding in its place a requirement that prescription drugs be labeled
with ``Rx only'' or `` only.''
The final rule amends parts 201 and 369 (21 CFR part 369)
by removing the requirement that certain habit-forming drugs bear the
statement ``Warning--May be habit forming.''
The final rule removes part 329, Habit-Forming Drugs.
The final rule amends part 290 (21 CFR part 290) by adding
new Secs. 290.1 and 290.2. Section 290.1 is being added to make clear
the agency's determination that a drug that is a controlled substance
listed in schedule II, III, IV, or V of the Federal Controlled
Substances Act (CSA) or implementing regulations must, unless otherwise
determined by the agency, be dispensed by prescription only as required
by section 503(b)(1) of the act. Section 290.2 retains the exemption
from the prescription-dispensing requirement in Sec. 329.20 for small
amounts of codeine in combination with other nonnarcotic active
medicinal ingredients.
III. Comments on the Proposed Rule
The agency received three comments from pharmaceutical companies
and one comment from an association of pharmacists.
(1). All four comments concerned the appearance of the ``Rx only''
statement on the label. In the proposed rule, the symbol appeared
in bold because of type-setting limitations. FDA did not want to create
the impression that it was proposing to require the symbol to
appear in bold. In an attempt at clarification, a footnote was included
in the proposed rule stating: ``The symbol appears in bold in this
document because of type-setting limitations, however, it should not be
bolded when used on the product's label'' (65 FR 21378). Two comments
objected to this apparent prohibition against the use of bolding,
noting that the implementing guidance discussed in section IV of this
document did not prescribe whether or not the symbol or the Rx
only statement generally should appear in bold. FDA agrees with these
comments. The symbol and the Rx only statement may be printed in
bold or in regular type.
(2). In the implementing guidance, FDA stated: ``The statement
should be prominent and conspicuous, as is required by section 502(c)
of the Act and 21 CFR 201.15.'' One comment suggested that
manufacturers should not be permitted to determine what placement on
the label is prominent and conspicuous. The comment asked that FDA
require that the Rx only statement appear on the main part of the label
and also that FDA establish a minimum font size for the Rx only
statement relative to the other text on the label.
FDA declines to adopt this suggestion. Section 502(c) of the act
provides that a drug or device is misbranded if a label statement
required by the act or FDA regulations * * * ``is not prominently
placed thereon with such conspicuousness (as compared with other words,
statements, designs, or devices, in the labeling) and in such terms as
to render it likely to be read and understood by the ordinary
individual under customary conditions of purchase and use.'' FDA's
regulation at Sec. 201.15 elaborates on specific factors that could
render a label statement not prominent and conspicuous. This regulation
applies to the Rx only statement, and thus requirements specific to the
Rx only statement are unnecessary.
(3). One comment objected to the agency's position, expressed in
the implementing guidance, that manufacturers are not prohibited from
using the ``Warning--May be habit forming'' statement. The
Modernization Act removed the requirement that the labels of habit-
forming drugs bear this statement, but did not prohibit use of the
statement. However, as explained in
[[Page 4905]]
the guidance, FDA believes that the habit-forming characteristics of a
drug product should be adequately described in the ``Drug Abuse and
Dependence'' section of the package insert and that further labeled
warnings are not necessary.
IV. Implementation
A guidance for industry entitled ``Implementation of Section 126 of
the Food and Drug Administration Modernization Act of 1997--Elimination
of Certain Labeling Requirements'' (63 FR 39100, July 21, 1998) is
available on the Internet at http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda. gov/cder/guidance/
index.htm or http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/cber/ guidelines.htm. The guidance
indicates that, for the time periods and under the circumstances stated
below, in the exercise of its enforcement discretion, FDA does not
intend to object if a sponsor does not comply with the new labeling
requirements of section 126 of the Modernization Act. The guidance
advises that FDA does not intend to object if sponsors of certain
currently approved products implement the new requirements of section
126 of the Modernization Act at the time of the next revision of their
labels, or by February 19, 2003, whichever comes first, and report
these minor changes in the next annual report. For pending (unapproved)
full or abbreviated applications received by the agency prior to
February 19, 1998, sponsors should comply with the new labeling
requirements by the time of the next revision of their labels or by
February 19, 2003, whichever comes first. The guidance also advises
that full or abbreviated applications received by FDA after February
19, 1998, should provide labels and labeling in compliance with the new
labeling requirements.
V. Environmental Impact
The agency has determined under 21 CFR 25.30(k) 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. Analysis of Impacts
FDA has examined the impacts of the final rule under Executive
Order 12866 and the Regulatory Flexibility Act (5 U.S.C. 601-612).
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. As described in section
IV of this document, the agency's guidance document explains that FDA
will exercise its enforcement discretion in a manner that will permit
companies to implement the required label changes at the time of the
next revision of their labels, or by February 19, 2003, whichever comes
first. Because almost all labels would typically be reprinted within
this timeframe, this enforcement strategy will eliminate any
significant costs that would otherwise be associated with the rule. As
a result, the final rule is not a significant regulatory action as
defined by the Executive order.
The Regulatory Flexibility Act requires agencies to analyze
regulatory options to minimize any significant impact of a rule on a
substantial number of small entities. The agency certifies that the
final rule would not have a significant impact on a substantial number
of small entities because the lengthy implementation period will allow
companies to make the necessary label changes during the normal course
of business. Therefore, under the Regulatory Flexibility Act, no
further analysis is required. Section 202(a) of the Unfunded Mandates
Reform Act (Public Law 104-4) requires that agencies prepare an
assessment of anticipated costs and benefits before proposing any rule
that may result in an expenditure by State, local, and tribal
governments, in the aggregate, or by the private sector, of $100
million or more in any one year (adjusted annually for inflation).
Because this rule does not impose any mandates on State, local, or
tribal governments, or the private sector that will result in an
expenditure of $100 million or more in any one year, FDA is not
required to perform a cost-benefit analysis under the Unfunded Mandates
Reform Act.
VII. Paperwork Reduction Act of 1995
FDA concludes that this final rule does not require information
collections subject to review by the Office of Management and Budget
(OMB) under the Paperwork Reduction Act of 1995 (the PRA) (Public Law
104-13).
FDA is amending its labeling regulations by removing the
requirement that prescription drugs be labeled with ``Caution: Federal
law prohibits dispensing without prescription'' and adding a
requirement that prescription drugs be labeled with ``Rx only'' or
`` only.'' This labeling statement is not subject to review by OMB
because it is ``originally supplied by the Federal Government to the
recipient for the purpose of disclosure to the public'' (5 CFR
1320.3(c)(2)) and therefore does not constitute a ``collection of
information'' under the PRA.
VIII. Executive Order 13132: Federalism
FDA has analyzed this final rule in accordance with Executive Order
13132: Federalism. Executive Order 13132 requires Federal agencies to
carefully examine actions to determine if they contain policies that
have federalism implications or that preempt existing State law. As
defined in the Order, ``policies that have federalism implications''
refers to regulations, legislative comments or final legislation, and
other policy statements or actions that have substantial direct effects
on the States, on the relationship between the National Government and
the States or on the distribution of power and responsibilities among
the various levels of government.
This final rule revises FDA labeling regulations as required by the
Modernization Act. Because enforcement of these labeling provisions is
a Federal responsibility, there should be little, if any, impact from
this rule on the States, on the relationship between the National
Government and the States, or on the distribution of power and
responsibilities among the various levels of government. In addition,
FDA does not believe that this final rule preempts any existing State
law.
Accordingly, FDA has determined that this final rule does not
contain policies that have federalism implications.
List of Subjects
21 CFR Part 10
Administrative practice and procedure, News media.
21 CFR Part 201
Drugs, Labeling, Reporting and recordkeeping requirements.
21 CFR Part 250
Drugs.
21 CFR Parts 290 and 329
Drugs, Labeling.
21 CFR Part 310
Administrative practice and procedure, Drugs, Labeling, Medical
devices, Reporting and recordkeeping requirements.
[[Page 4906]]
21 CFR Part 341
Labeling, Over-the-counter drugs.
21 CFR Part 361
Medical research, Prescription drugs, Radiation protection.
21 CFR Part 369
Labeling, Medical devices, Over-the-counter drugs.
21 CFR Part 606
Blood, Labeling, Laboratories, Reporting and recordkeeping
requirements.
21 CFR Part 610
Biologics, Labeling, Reporting and recordkeeping requirements.
Therefore, under the Federal Food, Drug, and Cosmetic Act, the
Public Health Service Act, and the Food and Drug Administration
Modernization Act, and under authority delegated to the Commissioner of
Food and Drugs, chapter I of Title 21 is amended as follows:
PART 10--ADMINISTRATIVE PRACTICES AND PROCEDURES
1. The authority citation for 21 CFR part 10 continues to read as
follows:
Authority: 5 U.S.C. 551-558, 701-706; 15 U.S.C. 1451-1461; 21
U.S.C. 141-149, 321-397, 467f, 679, 821, 1034; 28 U.S.C. 2112; 42
U.S.C. 201, 262, 263b, 264.
Sec. 10.50 [Amended]
2. Section 10.50 Promulgation of regulations and orders after an
opportunity for a formal evidentiary public hearing is amended by
removing and reserving paragraph (c)(7).
PART 201--LABELING
3. The authority citation for 21 CFR part 201 continues to read as
follows:
Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 358, 360,
360b, 360gg-360ss, 371, 374, 379e; 42 U.S.C. 216, 241, 262, 264.
Sec. 201.10 [Amended]
4. Section 201.10 Drugs; statement of ingredients is amended in
paragraph (a) by removing the phrase ``as `Warning--May be habit
forming' ''.
5. Section 201.16 is revised to read as follows:
Sec. 201.16 Drugs; Spanish-language version of certain required
statements.
An increasing number of medications restricted to prescription use
only are being labeled solely in Spanish for distribution in the
Commonwealth of Puerto Rico where Spanish is the predominant language.
Such labeling is authorized under Sec. 201.15(c). One required warning,
the wording of which is fixed by law in the English language, could be
translated in various ways, from literal translation to loose
interpretation. The statutory nature of this warning requires that the
translation convey the meaning properly to avoid confusion and dilution
of the purpose of the warning. Section 503(b)(4) of the Federal Food,
Drug, and Cosmetic Act requires, at a minimum, that the label bear the
statement ``Rx only.'' The Spanish-language version of this must be
``Solamente Rx''.
Sec. 201.100 [Amended]
6. Section 201.100 Prescription drugs for human use is amended in
paragraph (b)(1) by removing the phrase `` `Caution: Federal law
prohibits dispensing without prescription' '' and by adding in its
place the phrase `` `Rx only' ''.
Sec. 201.120 [Amended]
7. Section 201.120 Prescription chemicals and other prescription
components is amended in paragraph (b)(2) by removing the phrase ``
`Caution: Federal law prohibits dispensing without prescription' '' and
by adding in its place the phrase `` `Rx only' ''.
Sec. 201.122 [Amended]
8. Section 201.122 Drugs for processing, repacking, or
manufacturing is amended in the first sentence of the introductory text
by removing the phrase `` `Caution: Federal law prohibits dispensing
without prescription' '' and by adding in its place the phrase `` `Rx
only' ''.
Sec. 201.306 [Amended]
9. Section 201.306 Potassium salt preparations intended for oral
ingestion by man is amended in paragraph (b)(1) by removing the word
``caution''.
PART 250--SPECIAL REQUIREMENTS FOR SPECIFIC HUMAN DRUGS
10. The authority citation for 21 CFR part 250 continues to read as
follows:
Authority: 21 U.S.C. 321, 336, 342, 352, 353, 355, 361(a),
362(a) and (c), 371, 375(b).
Sec. 250.100 [Amended]
11. Section 250.100 Amyl nitrate inhalant as a prescription drug
for human use is amended in paragraph (b) by removing the phrase
``legend `Caution: Federal law prohibits dispensing without
prescription.' '' and by adding in its place the phrase ``statement `Rx
only.' ''.
Sec. 250.101 [Amended]
12. Section 250.101 Amphetamine and methamphetamine inhalers
regarded as prescription drugs is amended in paragraph (b) by removing
the phrase ``legend `Caution: Federal law prohibits dispensing without
prescription.' '' and by adding in its place the phrase ``statement `Rx
only.' ''.
Sec. 250.105 [Amended]
13. Section 250.105 Gelsemium-containing preparations regarded as
prescription drugs is amended in the last sentence by removing the
phrase `` `Caution: Federal law prohibits dispensing without
prescription.' '' and by adding in its place the phrase `` `Rx only.'
''.
Sec. 250.108 [Amended]
14. Section 250.108 Potassium permanganate preparations as
prescription drugs is amended in paragraph (c)(1) by removing the
phrase ``legend, `Caution: Federal law prohibits dispensing without
prescription.' '' and by adding in its place the phrase ``statement `Rx
only.' '' and in paragraph (c)(2) by removing the phrase ``, `Caution:
Federal law prohibits dispensing without prescription.' '' and by
adding in its place the phrase `` `Rx only.' ''.
Sec. 250.201 [Amended]
15. Section 250.201 Preparations for the treatment of pernicious
anemia is amended in paragraph (d) by removing the phrase ``legend
`Caution--Federal law prohibits dispensing without prescription.' ''
and by adding in its place the phrase ``statement `Rx only.' ''.
Sec. 250.250 [Amended]
16. Section 250.250 Hexachlorophene, as a component of drug and
cosmetic products is amended in the last sentence of paragraph (c)(1)
by removing the phrase ``legend `Caution: Federal law prohibits
dispensing without a prescription,' '' and by adding in its place the
phrase ``statement `Rx only,' '' and in paragraph (c)(4)(i) by removing
the phrase ``prescription legend'' and by adding in its place the
phrase ``statement `Rx only' ''.
PART 290--CONTROLLED DRUGS
17. The authority citation for 21 CFR part 290 continues to read as
follows:
Authority: 21 U.S.C. 352, 353, 355, 371.
18. Section 290.1 is added to subpart A to read as follows:
Sec. 290.1 Controlled substances.
Any drug that is a controlled substance listed in schedule II, III,
IV, or V of the Federal Controlled Substances Act or implementing
regulations must be dispensed by prescription only as required by
section 503(b)(1) of the
[[Page 4907]]
Federal Food, Drug, and Cosmetic Act unless specifically exempted in
Sec. 290.2.
19. Section 290.2 is added to subpart A to read as follows:
Sec. 290.2 Exemption from prescription requirements.
The prescription-dispensing requirements of section 503(b)(1) of
the Federal Food, Drug, and Cosmetic Act are not necessary for the
protection of the public health with respect to a compound, mixture, or
preparation containing not more than 200 milligrams of codeine per 100
milliliters or per 100 grams that also includes one or more nonnarcotic
active medicinal ingredients in sufficient proportion to confer upon
the compound, mixture, or preparation valuable medicinal qualities
other than those possessed by codeine alone.
PART 310--NEW DRUGS
20. The authority citation for 21 CFR part 310 continues to read as
follows:
Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 360b-360f,
360j, 361(a), 371, 374, 375, 379e; 42 U.S.C. 216, 241, 242(a), 262,
263b-263n.
Sec. 310.103 [Amended]
21. Section 310.103 New drug substances intended for
hypersensitivity testing is amended in paragraph (a)(3)(i) by removing
the phrase `` `Caution: Federal law prohibits dispensing without a
prescription' '' and by adding in its place the phrase `` `Rx only' ''.
PART 329--HABIT FORMING DRUGS
22. Part 329 is removed.
PART 341--COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC
DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE
23. The authority citation for 21 CFR part 341 continues to read as
follows:
Authority: 21 U.S.C. 321, 351, 352, 353, 355, 360, 371.
Sec. 341.14 [Amended]
24. Section 341.14 Antitussive active ingredients is amended in
paragraph (a)(2) by removing ``Secs. 329.20(a) and 341.40'' and by
adding in its place ``Sec. 290.2''.
PART 361--PRESCRIPTION DRUGS FOR HUMAN USE GENERALLY RECOGNIZED AS
SAFE AND EFFECTIVE AND NOT MISBRANDED: DRUGS USED IN RESEARCH
25. The authority citation for 21 CFR part 361 continues to read as
follows:
Authority: 21 U.S.C. 321, 351, 352, 353, 355, 371; 42 U.S.C.
262.
Sec. 361.1 [Amended]
26. Section 361.1 Radioactive drugs for certain research uses is
amended in paragraph (f)(1) by removing the phrase `` `Caution: Federal
law prohibits dispensing without prescription' '' and by adding in its
place the phrase `` `Rx only' ''.
PART 369--INTERPRETATIVE STATEMENTS RE WARNINGS ON DRUGS AND
DEVICES FOR OVER-THE-COUNTER SALE
27. The authority citation for 21 CFR part 369 continues to read as
follows:
Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 371.
Sec. 369.22 [Removed]
28. Section 369.22 is removed.
PART 606--CURRENT GOOD MANUFACTURING PRACTICE FOR BLOOD AND BLOOD
COMPONENTS
29. The authority citation for 21 CFR part 606 continues to read as
follows:
Authority: 21 U.S.C. 321, 331, 351, 352, 355, 360, 360j, 371,
374; 42 U.S.C. 216, 262, 263a, 264.
30. Section 606.121 is amended by revising paragraph (c)(8)(i) to
read as follows:
Sec. 606.121 Container label.
* * * * *
(c) * * *
(8) * * *
(i) ``Rx only.''
* * * * *
PART 610--GENERAL BIOLOGICAL PRODUCTS STANDARDS
31. The authority citation for 21 CFR part 610 continues to read as
follows:
Authority: 21 U.S.C. 321, 351, 352, 353, 355, 360, 371; 42
U.S.C. 216, 262, 263, 263a, 264.
Sec. 610.60 [Amended]
32. Section 610.60 Container label is amended in paragraph (a)(6)
by removing the phrase `` `Caution: Federal law prohibits dispensing
without prescription,' '' and by adding in its place the phrase `` `Rx
only' ''.
Sec. 610.61 [Amended]
33. Section 610.61 Package label is amended in paragraph (s) by
removing the phrase `` `Caution: Federal law prohibits dispensing
without prescription,' '' and by adding in its place the phrase `` `Rx
only' ''.
Dated: January 28, 2002.
Margaret M. Dotzel,
Associate Commissioner for Policy.
[FR Doc. 02-2548 Filed 1-31-02; 8:45 am]
BILLING CODE 4160-01-S