Over-the-Counter Drug Products Containing Analgesic/Antipyretic Active Ingredients for Internal Use; Required Alcohol Warning; Final Rule; Compliance Date

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 201

[Docket No. 77N-094W]

Over-the-Counter Drug Products Containing Analgesic/Antipyretic

Active Ingredients for Internal Use; Required Alcohol Warning; Final

Rule; Compliance Date

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule; compliance date.

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SUMMARY: The Food and Drug Administration (FDA) is establishing a

compliance date of October 22, 1999, for the regulation that published

in the Federal Register of October 23, 1998 (63 FR 56789). The

regulation established warning statements that advise consumers with a

history of heavy alcohol use to consult a physician for advice about

the use of OTC internal analgesic/antipyretic drug products. The

compliance date applies to all affected OTC drug products, whether

marketed with or without an approved application. FDA is taking this

action in response to correspondence and a citizen petition requesting

more time to relabel these products.

DATES: 21 CFR 201.322, published on October 23, 1998 (63 FR 56789), is

effective April 23, 1999; but compliance is not required until October

22, 1999.

FOR FURTHER INFORMATION CONTACT: Gerald M. Rachanow, Center for Drug

Evaluation and Research (HFD-560), Food and Drug Administration, 5600

Fishers Lane, Rockville, MD 20857, 301-827-2307.

SUPPLEMENTARY INFORMATION:

I. Background

In the Federal Register of November 14, 1997 (62 FR 61041), FDA

published a proposed amendment of part 201 (21 CFR part 201) to

establish alcohol warnings for all OTC drug products labeled for adult

use containing internal analgesic/antipyretic active ingredients. The

agency stated that it may change the wording of the proposed warnings

or not require them as a result of comments filed in response to the

proposal. Because it wished to encourage the voluntary use of the

proposed warning statements, the agency advised that manufacturers

would be given ample time after publication of a final rule to use up

any labeling printed in conformance with the proposal (62 FR 61041 at

61052).

In the Federal Register of October 23, 1998 (63 FR 56789), FDA

issued a final rule amending part 201 and establishing in Sec. 201.322

a required alcohol warning for OTC drug products containing internal

analgesic/antipyretic active ingredients. The final rule requires

manufacturers to add certain new warnings for any OTC drug product,

labeled for adult use, containing any internal analgesic/antipyretic

active ingredients (including, but not limited to, acetaminophen,

aspirin, carbaspirin calcium, choline salicylate, ibuprofen,

ketoprofen, magnesium salicylate, naproxen sodium, and sodium

salicylate) alone or in combination and marketed with or without an

approved application. The wording of the warnings in the final rule was

different than the wording in the proposal. The final rule specified an

effective date of April 23, 1999, for any OTC drug product subject to

this section.

II. Summary of Comments Received

In response to the final rule, the agency received several comments

(Ref. 1) and a citizen petition (Ref. 2) requesting more time to

implement the new required alcohol warnings and a mechanism by which

manufacturers may petition the agency for a variance or extension of

time to comply with the regulation's 6-month implementation date. The

comments were submitted by several large manufacturers of brand name

OTC internal analgesic/antipyretic drug products and a manufacturer of

a large number of private label OTC internal analgesic/antipyretic drug

products. The comments stated that relabeling procedures generally take

longer than the 6 months provided for in the final rule and that the

companies simply lack the needed manpower and equipment to comply by

April 23, 1999.

The comments added that the implementation period for the new rule

must ensure that label integrity is not compromised or done

haphazardly. The comments stated that 6 months is an insufficient

period of time for a number of companies to accomplish the relabeling,

and the short timeframe does not promote emphasis on labeling integrity

and good manufacturing practice compliance. All of the comments

expressed concern that numerous products could become unavailable and

estimated significant loss of inventory if required to implement the

labeling change by April 23, 1999.

One comment requested permission to use up all existing supplies of

labeling that contain the precise alcohol warning contained in an

agency letter dated March 14, 1996 (Ref. 3). Another

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comment, submitted by a manufacturer, stated that it would implement

the new alcohol warnings by the effective date and that other affected

companies should also be required to meet that date (Ref. 4).

The agency held a public meeting on January 20, 1999 (Ref. 5), to

hear the views of interested parties regarding the implementation date

of the rule. At this meeting, one large private label manufacturer of

internal analgesic/antipyretic drug products stated that it would not

be able to meet the April 23, 1999, implementation date, and that if

the deadline were not extended a real possibility existed that there

would be a national shortage of certain products that it manufactures.

Another manufacturer at the meeting stated that it would be able to

comply by the implementation date.

III. The Agency's Response

As stated in the final rule, the agency considers the lack of

sufficient alcohol warnings to be a significant public health issue.

However, additional information (Refs. 6 through 11) that the agency

has obtained since publication of the final rule suggests that the

agency may have underestimated the number of individual label changes

that some manufacturers will have to make. This information also

indicates that there may be a significantly greater disparity in the

effect of the required labeling upon manufacturers than originally

anticipated. For these reasons, FDA now believes that the original 6-

month implementation period would not provide adequate time for many

manufacturers of affected products to relabel a significant number of

their products and that strict adherence to the April 23, 1999,

effective date might result in short-term shortages of some of these

important OTC drug products, which are widely used by many consumers.

Consequently, the agency believes that establishing a compliance date

for the regulation, until October 22, 1999, will provide sufficient

time for industry to implement the labeling revisions required for

these OTC internal analgesic/antipyretic drug products.

The agency does not believe that there should be an open-ended

period, as one comment requested, to use up existing supplies of

labeling that contain an alcohol warning that was implemented

voluntarily in response to an agency letter dated March 14, 1996 (Ref.

3). Rather, FDA believes that there should be a date certain after

which all products initially introduced or initially delivered for

introduction into interstate commerce contain the new warnings.

Further, because of the importance of the alcohol warnings, the agency

continues to encourage all affected manufacturers to bring their

labeling into compliance with the final rule as promptly as possible.

Because this document merely establishes a compliance date, FDA

finds that notice and comment procedures are unnecessary and not in the

public interest (5 U.S.C. 553(b) and (d)). Moreover, because of the

need for the agency to publish this document before the original April

23, 1999, effective date, notice and comment rulemaking would be

impracticable for this document.

IV. Analysis of Impacts

The economic impact of the final regulation was discussed in the

final rule (63 FR 56789 at 56798 to 56799). This document will provide

additional time for companies to relabel affected products and will

reduce label obsolescence, as there will be additional time to use up

more existing labeling. Thus, setting a compliance date of October 22,

1999, should reduce the economic impact on industry significantly.

FDA has examined the impacts of this final rule (establishment of

the compliance date) 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 set

out in the Executive Order. The final rule is not a significant

regulatory action as defined by the Executive Order and so 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. This final rule sets a compliance date, which will

provide manufacturers additional time to use up existing product

labeling. Accordingly, the agency certifies that the final 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.

V. Paperwork Reduction Act of 1995

FDA concludes that the labeling requirements 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

labeling 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)).

VI. Environmental Impact

The agency has determined under 21 CFR 25.31(c) 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.

VII. References

The following references are on display in the Dockets Management

Branch (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm.

1061, Rockville, MD 20852, and may be seen by interested parties

between 9 a.m. and 4 p.m., Monday through Friday.

1. Comment Nos. C20, C21, and C22, Docket No. 77N-094W, Dockets

Management Branch.

2. Comment No. CP1, Docket No. 77N-094W, Dockets Management

Branch.

3. Letter from D. Bowen, FDA, to R. Soller, Nonprescription Drug

Manufacturers Association, Coded LET2, Docket No. 77N-094W, Dockets

Management Branch.

4. Comment No. C19, Docket No. 77N-094W, Dockets Management

Branch.

5. Comment No. MM, Docket No. 77N-094W, Dockets Management

Branch.

6. Letter from K. Rothschild, FDA, to D. Jespersen, Perrigo,

coded LET3, Docket No. 77N-094W, Dockets Management Branch.

7. Letter from K. Rothschild, FDA, to H. McCain, Whitehall-

Robins, coded LET4, Docket No. 77N-094W, Dockets Management Branch.

8. Comment No. C23, Docket No. 77N-094W, Dockets Management

Branch.

9. Comment No. C24, Docket No. 77N-094W, Dockets Management

Branch.

10. Letter from K. Rothschild, FDA, to H. McCain, Whitehall-

Robins, coded LET5, Docket No. 77N-094W, Dockets Management Branch.

11. Comment No. C25, Docket No. 77N-094W, Dockets Management

Branch.

Dated: March 11, 1999.

William K. Hubbard,

Acting Deputy Commissioner for Policy.

[FR Doc. 99-6447 Filed 3-12-99; 12:40 pm]

BILLING CODE 4160-01-F