Cold, Cough, Allergy, Bronchodilator, and Antiasthmatic Drug Products for Over-the-Counter Human Use; OTC Nasal Decongestant Drug Products; Partial Stay of Final Rule; Enforcement Policy

[[Page 9570]]

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 310

[Docket No. 76N-052N]

RIN 0910-AA01

Cold, Cough, Allergy, Bronchodilator, and Antiasthmatic Drug

Products for Over-the-Counter Human Use; OTC Nasal Decongestant Drug

Products; Partial Stay of Final Rule; Enforcement Policy

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule; partial stay of regulation; enforcement policy.

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SUMMARY: The Food and Drug Administration (FDA) is staying part of a

final rule that established that certain over-the-counter (OTC) nasal

decongestant drug products are not generally recognized as safe and

effective and are misbranded. This action is being taken in response to

a citizen petition for a stay of enforcement of regulatory action

against OTC nasal decongestant drug products containing the active

ingredient l-desoxyephedrine. The agency is also providing labeling

requirements for OTC topical nasal decongestant drug products

containing l-desoxyephedrine. This action is part of the ongoing review

of OTC drug products conducted by FDA.

DATES: This partial stay is effective August 31, 1995. On or after

September 9, 1996, no OTC drug product containing l-desoxyephedrine may

be initially introduced or initially delivered for introduction into

interstate commerce unless its labeling conforms to the conditions of

this partial stay.

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

In the Federal Register of August 23, 1994 (59 FR 43386), the

agency published a final rule in the form of a final monograph

establishing conditions under which OTC nasal decongestant drug

products are generally recognized as safe and effective. The final

monograph did not include l-desoxyephedrine as a nasal decongestant

active ingredient. The final rule listed l-desoxyephedrine in

Sec. 310.545(a)(6)(ii)(B) (21 CFR 310.545(a)(6)(ii)(B)) as not

generally recognized as safe and effective. L-desoxyephedrine was

declared nonmonograph because it was not currently standardized and

characterized for quality and purity in an official compendium, i.e.,

the United States Pharmacopeia (USP)/National Formulary (NF) (59 FR

43386 at 43408). The agency stated in the final rule that OTC drug

products containing l-desoxyephedrine as a topical nasal decongestant

active ingredient were new drugs under section 201(p) of the Federal

Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 321(p)). The

effective date of the final rule was August 23, 1995. To be marketed,

OTC topical nasal decongestant drug products containing l-

desoxyephedrine would require an application or abbreviated application

approved under section 505 of the act (21 U.S.C. 355) and part 314 (21

CFR part 314). In the absence of an approved application, OTC topical

nasal decongestant drug products containing l-desoxyephedrine would be

misbranded under section 502 of the act (21 U.S.C. 352). The agency

also stated that should interested parties develop appropriate

standards that are included in the USP, the nasal decongestant final

monograph would be amended to include l-desoxyephedrine as a topical

nasal decongestant active ingredient. The agency reserved 21 CFR

341.20(b)(1) of the final monograph for OTC nasal decongestant drug

products for possible future inclusion of l-desoxyephedrine as a

topical nasal decongestant active ingredient.

Subsequently, a citizen petition (Ref. 1) requested that the

agency defer the effective date of Sec. 310.545(a)(6)(ii)(B) as it

applies to l-desoxyephedrine (topical) until December 31, 1996. The

petitioner stated that it had forwarded a draft compendial monograph

(Ref. 2) for 1-desoxyephedrine to the USP in late July 1995. The

petition stated that USP expects to publish a proposed monograph for

public comment in the November/December 1995 issue of Pharmacopeial

Forum, and expects the resulting monograph to become official with

publication of USP23/NF18 Supplement No. 5, on November 15, 1996. The

petition stated that USP, as a practical matter, will have concluded to

adopt the monograph for l-desoxyephedrine well before November 15,

1996, and will have given notice of that conclusion in its

Pharmacopeial Forum Interim Revision Announcement. The petitioner

stated its belief that the agency should have ample time to initiate

its process to amend the nasal decongestant final monograph by the end

of 1996.

The agency was subsequently informed that the ingredient might

become official in the USP in November 1996 or May 1997 (Ref. 3). On

August 31, 1995, the agency stated its intent to stay the effective

date for l-desoxyephedrine in the list of active ingredients in

Sec. 310.545(a)(6)(ii)(B) until December 31, 1996, to permit time for

USP processing to include the ingredient in a compendial monograph

(Ref. 4). At this time, the agency is staying the entry for ``l-

desoxyephedrine (topical)'' in Sec. 310.545(a)(6)(ii)(B) until further

notice. When l-desoxyephedrine becomes official in the USP, the final

monograph for OTC nasal decongestant drug products will be amended to

include the ingredient and Sec. 310.545(a)(6)(ii)(B) will be revised

accordingly.

During the stay period, the following labeling requirements will

be in effect for topical nasal decongestant drug products containing l-

desoxyephedrine:

1. The statement of identity should follow Sec. 341.80(a) (21 CFR

341.80(a)) of the final monograph for OTC nasal decongestant drug

products (59 FR 43386 at 43409).

2. The indications should follow Sec. 341.80(b) of the final

monograph for OTC nasal decongestant drug products (59 FR 43386 at

43409 and 43410).

3. The warnings should follow Sec. 341.80(c)(2)(i) of the final

monograph for OTC nasal decongestant drug products (59 FR 43386 at

43410). In addition, the following warnings are required: ``Do not use

this product for more than 7 days. Use only as directed. Frequent or

prolonged use may cause nasal congestion to recur or worsen. If

symptoms persist, consult a doctor.''

4. The directions are for a product that must deliver 0.04 to 0.150

milligram of l-desoxyephedrine in each 800 milliliters of air. Adults

and children 12 years of age and over: Two inhalations in each nostril

not more often than every 2 hours. Children 6 to under 12 years of age

(with adult supervision): One inhalation in each nostril not more often

than every 2 hours. Children under 6 years of age: Consult a doctor.

5. Other required statements should follow Sec. 341.80(d)(viii)(A)

and (d)(viii)(B).

As part of the conditions of this stay of action, the agency has

determined that manufacturers of OTC topical nasal decongestant drug

products containing l-desoxyephedrine should implement this labeling

within 6 months of the publication of this partial stay. Therefore, on

or after September 9,

[[Page 9571]]

1996, no OTC drug product that is subject to this partial stay of the

final rule for OTC nasal decongestant drug products may be initially

introduced or initially delivered for introduction into interstate

commerce unless its labeling conforms to the conditions of this partial

stay. Further, any OTC drug product subject to this partial stay that

is repackaged or relabeled after the date of publication of this

partial stay must be in compliance with the partial stay regardless of

the date the product was initially introduced or initially delivered

for introduction into interstate commerce. Manufacturers are encouraged

to comply voluntarily with this partial stay at the earliest possible

date.

This partial stay of action applies only to l-desoxyephedrine in

OTC topical nasal decongestant drug products and not to any other nasal

decongestant active ingredient included under

Sec. 310.545(a)(6)(ii)(B).

II. References

The following references are on display in the Dockets Management

Branch (HFA-305), Food and Drug Administration, 12420 Parklawn Dr., rm.

1-23, Rockville, MD 20857, and may be seen by interested persons

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

(1) Comment No. CP1, Docket No. 95P-0245, Dockets Management

Branch.

(2) Draft Compendial Monograph, in Comment No. CP1, Docket No.

95P-0245, Dockets Management Branch.

(3) Memorandum of telephone conversation between M. T. Benson,

FDA, ---and T. Cecil, United States Pharmacopeial Convention, Inc.,

coded as MT1, Docket No. 95P-0245, Dockets Management Branch.

(4) Letter from W. E. Gilbertson, FDA, to S. Rexinger, Leiner

Health ---Products, and E. Lambert, Covington & Burling, coded as

LET1, Docket No. --95P-0245, Dockets Management Branch.

III. Paperwork Reduction Act of 1995

FDA concludes that the labeling requirements discussed 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)).----

List of Subjects in 21 CFR Part 310

Administrative practice and procedure, Drugs, Labeling, Medical

devices, Reporting and recordkeeping requirements.

Therefore, under the Federal Food, Drug, and Cosmetic Act and

under authority delegated to the Commissioner of Food and Drugs, 21 CFR

part 310 is amended as follows:

PART 310--NEW DRUGS

1. The authority citation for 21 CFR part 310 continues to read as

follows:

-Authority: Secs. 201, 301, 501, 502, 503, 505, 506, 507, 512-

516, 520, 601(a), 701, 704, 705, 721 of the Federal Food, Drug, and

Cosmetic Act (21 U.S.C. 321, 331, 351, 352, 353, 355, 356, 357,

360b-360f, 360j, 361(a), 371, 374, 375, 379e); secs. 215, 301,

302(a), 351, 354-360F of the Public Health Service Act (42 U.S.C.

216, 241, 242(a), 262, 263b-263n).

Sec. 310.545 [Partial stay]

2. In Sec. 310.545 Drug products containing certain active

ingredients offered over-the-counter (OTC) for certain uses in

paragraph (a)(6)(ii)(B), the entry for ``l-desoxyephedrine (topical)''

is stayed until further notice.

Dated: February 22, 1996.

William K. Hubbard,

Associate Commissioner for Policy Coordination.

[FR Doc. 96-5444 Filed 3-7-96; 8:45 am]

BILLING CODE 4160-01-F