[Federal Register Volume 67, Number 22 (Friday, February 1, 2002)]
[Rules and Regulations]
[Pages 4904-4907]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-2548]


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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 ``Rx 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Act also repealed section 502(d) of the act (21 U.S.C. 352(d)), which 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 ``Rx 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 Rx symbol appeared 
in bold because of type-setting limitations. FDA did not want to create 
the impression that it was proposing to require the Rx symbol to 
appear in bold. In an attempt at clarification, a footnote was included 
in the proposed rule stating: ``The Rx 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 Rx symbol or the Rx 
only statement generally should appear in bold. FDA agrees with these 
comments. The Rx 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://www.fda. gov/cder/guidance/
index.htm or 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 
``Rx 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