[Federal Register Volume 65, Number 69 (Monday, April 10, 2000)]
[Proposed Rules]
[Pages 18934-18938]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-8737]


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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: Proposed rule.

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SUMMARY: The Food and Drug Administration (FDA) is proposing to

[[Page 18935]]

amend its regulations to require the labels of prescription drugs to 
bear the statement ``only'' instead of the statement ``Caution: Federal 
law prohibits dispensing without prescription'' and to remove the 
requirement that certain habit-forming drugs bear the statement 
``Warning--May be habit forming.'' The agency is also proposing to add 
a new section to the regulations to make clear that these habit-forming 
drugs must be dispensed by prescription only. The agency is taking this 
action to implement changes made by the Food and Drug Administration 
Modernization Act of 1997 (FDAMA).

DATES: Submit written comments by June 26, 2000.

ADDRESSES: Submit written comments to the Dockets Management Branch 
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852.

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. The Modernization Act

    On November 21, 1997, President Clinton signed into law the 
Modernization Act (Public Law 105-115). 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 ``Rxonly'' 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.''\1\ 
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.''
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    \1\ 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.
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II. Description of the Proposed Rule

    The proposed rule would amend 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 proposed rule would amend 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 proposed rule would remove part 329. Part 329 was issued under 
repealed section 502(d) of the act. Section 329.1 designates as habit-
forming certain derivatives of the habit-forming substances listed in 
section 502(d) of the act. Section 329.10 elaborates on the labeling 
requirement of section 502(d) of the act.
    Section 329.20 exempts certain habit-forming drugs from the 
prescription-dispensing requirements of the act. This section has not 
been substantively revised in more than 30 years. It is now out of 
date. Except as discussed elsewhere in this section, none of the drug 
ingredients listed as exempt in Sec. 329.20 are currently marketed 
over-the-counter (OTC) or have any legal basis to be marketed OTC.
    The proposed rule would amend 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 503(b)(1) provides that a drug 
that ``because of its toxicity or other potentiality for harmful 
effect, or the method of its use, or the collateral measures necessary 
to its use,'' or a drug which ``is limited by an approved application 
under section 505 of the act to use under the professional supervision 
of a practitioner licensed by law to administer such drug,'' shall be 
dispensed only upon a prescription of a practitioner licensed by law to 
administer such drug. Generally, a drug that meets the criteria for 
control under Schedule II, III, IV, or V of the CSA (see 21 U.S.C. 812) 
would also meet the standard for prescription dispensing under section 
503(b)(1) of the act. Drugs included in Schedule I of the CSA cannot be 
lawfully marketed in the United States.
    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. Small 
amounts of codeine in combination with other nonnarcotic active 
medicinal ingredients, for example, cough syrup with codeine, may be 
marketed OTC under a final monograph for cold and cough products. (See 
Sec. 341.14 (21 CFR 341.14)). For the reason stated above, no other 
exemptions are warranted at this time for the other narcotic drugs 
listed in Sec. 329.20(a). Also, an exemption under Sec. 290.2 is not 
needed for the chlorobutanol preparations described in Sec. 329.20 
because chlorobutanol is not a scheduled substance under the CSA. The 
epinephrine product described in Sec. 329.20(c) cannot be lawfully 
marketed at this time.
    The proposed rule would also revise Sec. 341.14 to refer to the 
exemption at Sec. 290.2, rather than Sec. 329.20 which is being 
removed.

III. 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 in this 
section, 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 a sponsor of a currently 
approved product implements the new requirements of section 126 of the 
Modernization Act at the time of the next revision of its labels, or by 
February 19, 2003, whichever comes first, and reports 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

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compliance with the new labeling requirements.

IV. Environmental Impact

    The agency has determined under 21 CFR 25.30(h) through (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.

V. Analysis of Impacts

    FDA has examined the impacts of the proposed rule under Executive 
Order 12866 and the Regulatory Flexibility Act (5 U.S.C. 601-612), and 
the Unfunded Mandates Reform Act of 1995 (Public Law 104-4). 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. 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 proposed rule is not a 
significant action as defined by the Executive Order.
    The Regulatory Flexibility Act requires agencies to analyze 
regulatory options to minimize any significant impact on a substantial 
number of small entities. The agency certifies that the proposed rule 
would not have a significant impact on a substantial number of small 
entities because the 5-year 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. The Unfunded Mandates Reform Act (in section 202) 
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.

VI. Paperwork Reduction Act of 1995

    FDA tentatively concludes that this proposed rule contains no 
collections of information. Therefore, clearance by the Office of 
Management and Budget (OMB) under the Paperwork Reduction Act of 1995 
(Public Law 104-13) is not required. The revised labeling information 
is supplied by the Modernization Act (changing ``Caution: Federal law 
prohibits dispensing without prescription'' to `` only'' or `` 
only''). According to 5 CFR 1320.3(c)(2), the public disclosure of 
information originally supplied by the Federal Government to the 
recipient for the purpose of disclosure to the public is not considered 
a collection of information.

VII. Request for Comments

    Interested persons may, on or before June 26, 2000, submit to the 
Dockets Management Branch (address above) written comments regarding 
this proposal. Two copies of any 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. Received comments may be seen in the office above between 9 
a.m. and 4 p.m., Monday through Friday.

VIII. Proposed Effective Date

    FDA proposes that any final rule that may issue based on this 
proposal become effective 60 days after publication of the final rule. 
For information on implementation, see the discussion in section III of 
this document.

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.

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, and the 
Food and Drug Administration Modernization Act, and under authority 
delegated to the Commissioner of Food and Drugs, it is proposed that 
chapter I of Title 21 be amended as follows:

PART 10--ADMINISTRATIVE PRACTICES AND PROCEDURES

    1. The authority citation for 21 CFR part 10 is revised 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

[[Page 18937]]

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 ``SoAE1lamente 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 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 
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 introductory text, first sentence, by 
removing the phrase `` `Caution: Federal law prohibits dispensing 
without prescription' '' and 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 250.100Amyl nitrite 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 adding in its place the phrase ``statement `Rx only.' ''.


Sec. 250.101  [Amended]

    12. Section 250.101Amphetamine 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 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 by removing the phrase `` `Caution: 
Federal law prohibits dispensing without prescription.' '' from the 
last sentence and 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 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 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 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 adding in its place the 
phrase ``statement `Rx only,' '' and in paragraph (c)(4)(i) by removing 
the phrase ``prescription legend'' and 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 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 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 adding 
in its place ``Sec. 290.2''.

[[Page 18938]]

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 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 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 adding in its place the phrase `` `Rx 
only' ''.

    Dated: March 31, 2000.
Margaret M. Dotzel,
Acting Associate Commissioner for Policy.
[FR Doc. 00-8737 Filed 4-7-00; 8:45 am]
BILLING CODE 4160-01-F