[Federal Register Volume 65, Number 131 (Friday, July 7, 2000)]
[Notices]
[Page 42017]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-17197]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 83N-0118; DESI 6514]


Oral Prescription Drugs Offered for Relief of Symptoms of Cough, 
Cold, or Allergy; Drug Efficacy Study Implementation; Caramiphen 
Edisylate; Final Actions on Supplemental New Drug Applications

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) refuses to approve 
supplemental new drug applications (NDA's) for Tuss-Ornade Spansules 
and Liquid containing caramiphen edisylate and phenylpropanolamine 
hydrochloride. The basis for FDA's refusal to approve these products is 
that there is a lack of substantial evidence that caramiphen edisylate 
is effective.

DATES: Effective July 7, 2000.

ADDRESSES: Requests for applicability of this notice to a specific 
product should be identified with Docket No. 83N-0118 and reference 
number DESI 6514 and directed to the Division of Prescription Drug 
Compliance and Surveillance (HFD-330), Center for Drug Evaluation and 
Research, Food and Drug Administration, 7500 Standish Pl., Rockville, 
MD 20855.

FOR FURTHER INFORMATION CONTACT: David T. Read, Center for Drug 
Evaluation and Research (HFD-7), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-594-2041.

SUPPLEMENTARY INFORMATION: In a notice published in the Federal 
Register of February 9, 1973 (38 FR 4006), FDA classified the following 
drug products as less than effective for their labeled indications:
    1. NDA 12-903; Tuss-Ornade Spansules containing caramiphen 
edisylate 20 milligrams (mg), chlorpheniramine maleate 8 mg, 
phenylpropanolamine hydrochloride 50 mg, and isopropamide iodide 2.5 
mg; SmithKline Beecham Pharmaceuticals, P.O. Box 7929, Philadelphia, PA 
19101-7929 (SmithKline).
    2. NDA 13-068; Tuss-Ornade Liquid containing caramiphen edisylate 5 
mg, chlorpheniramine maleate 2 mg, phenylpropanolamine hydrochloride 15 
mg, and isopropamide iodide 0.75 mg; SmithKline.
    In a notice published in the Federal Register of December 14, 1973 
(38 FR 34481), FDA granted a temporary exemption from the time limits 
established for completing certain phases of the drug efficacy study 
implementation (DESI) program, for certain oral prescription drugs 
offered for relief of cough, cold, allergy, and related symptoms, 
including the aforementioned products. The exemption was granted 
because of the close relationship between drugs sold over the counter 
(OTC)--and thus subject to the ongoing OTC drug review (21 CFR part 
330)--and prescription drugs offered for relief of cough, cold, 
allergies, and related symptoms.
    In 1980 SmithKline submitted supplements proposing to reformulate 
the products listed above and marketed the following reformulated 
products pending a final determination of effectiveness:
    1. NDA 12-903; caramiphen edisylate 40 mg and phenylpropanolamine 
hydrochloride 25 mg.
    2. NDA 13-068; caramiphen edisylate 6.7 mg and phenylpropanolamine 
hydrochloride 12.5 mg.
    In 1976 the OTC drug review panel for cold, cough, allergy, 
bronchodilator, and antiasthmatic drugs concluded that there were no 
well-controlled, objective, clinical studies documenting the 
effectiveness of caramiphen edisylate as an antitussive (41 FR 38312, 
September 9, 1976). The OTC monograph on antitussives was finalized in 
1987 (52 FR 30042 at 30054, August 12, 1987).
    Because of the lack of evidence that caramiphen edisylate is an 
effective antitussive, the Director of what was then the National 
Center for Drugs and Biologics concluded that there was a lack of 
substantial evidence that Tuss-Ornade Spansules and Liquid, either as 
previously formulated or as proposed for reformulation, would have all 
the effects they purported or were represented to have under the 
conditions of use prescribed, recommended, or suggested in the 
labeling. The Director issued a notice of opportunity for hearing on 
two proposals: (1) To withdraw approval of the original formulations of 
Tuss-Ornade Spansules and Liquid, and (2) to refuse approval of the 
supplemental reformulations of the same products (48 FR 40322, 
September 6, 1983).
    Neither SmithKline nor any other interested party requested a 
hearing on the proposal to withdraw approval of the original 
formulations of Tuss-Ornade Spansules and Liquid; therefore, approval 
of the old formulations was withdrawn (49 FR 10707, March 22, 1984). 
However, in response to the agency's September 6, 1983, proposal to 
refuse to approve the reformulated products, SmithKline and National 
Pharmaceutical Manufacturing Company (National) requested hearings. 
SmithKline submitted data and information in support of its hearing 
request.
    FDA has reviewed these data and determined that there is not 
substantial evidence of the effectiveness of caramiphen edisylate. 
SmithKline and National no longer market the products named in their 
1983 hearing requests and have withdrawn those hearing requests.
    This notice applies to any drug product that is identical, related, 
or similar to the products named above and is not the subject of an 
approved NDA (21 CFR 310.6). Any person who wishes to determine whether 
a specific product is covered by this notice should write to the 
Division of Prescription Drug Compliance and Surveillance (address 
above).
    The Director of the Center for Drug Evaluation and Research, under 
section 505 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355) 
and under the authority delegated to her (21 CFR 5.70 and 5.82) finds 
that, on the basis of new information before her with respect to Tuss-
Ornade Spansules and Liquid, evaluated together with the evidence 
available to her when the applications were approved, there is a lack 
of substantial evidence that the products as proposed for reformulation 
will have the effect they purport or are represented to have under the 
conditions of use prescribed, recommended, or suggested in their 
labeling.
    Therefore, based on the foregoing finding, approvals and all the 
amendments and supplements thereto of NDA 12-903 and NDA 13-068 are 
withdrawn and refused effective July 7, 2000. Shipment in interstate 
commerce of the products listed above or of any identical, related, or 
similar product that is not the subject of an approved NDA will then be 
unlawful.

    Dated: June 20, 2000.
Janet Woodcock,
Director, Center for Drug Evaluation and Research.
[FR Doc. 00-17197 Filed 7-6-00; 8:45 am]
BILLING CODE 4160-01-F