ndac december 14, 2007 1 nonprescription drugs advisory committee meeting silver spring, maryland...
TRANSCRIPT
NDAC December 14, 20071
Nonprescription Drugs Advisory Committee MeetingSilver Spring, MarylandDecember 14, 2007
Mary S. Robinson, MSDivision of Nonprescription Regulation DevelopmentOffice of Nonprescription Products
OTC Drug Review History of Phenylephrine
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OTC Drug Review Initiated January 1972
Over 800 active ingredients in marketed OTC drug products
FDA divided these ingredients into 26 therapeutic categories
FDA determined that the review would be a three step process
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OTC Drug Review Process Step 1
Advisory Review Panel’s (Panel) review and evaluation of the data
Publication Advanced Notice of Proposed Rulemaking (ANPR)
Step 2 FDA’s tentative review of Panel report and evaluation of
comments submitted to ANPR Publication Tentative Final Monograph (TFM) in the form of
a proposed rule
Step 3 FDA’s review of updated literature and comments submitted
in response to the TFM Publication Final Monograph (FM) to establish regulation in
the Code of Federal Regulations
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Panel Review and ANPR The Advisory Review Panel on over-the-counter
(OTC) Cold, Cough, Allergy, Bronchodilator and Antiasthmatic Products
The panel defined nasal decongestants as agents that reduce nasal congestion in patients with acute or chronic rhinitis
Administered topically as drops, sprays or inhaled vapors or orally in a solid or liquid dosage forms
Phenylephrine hydrochloride (PEH) and pseudoephedrine were the only active ingredients considered as both oral and nasal decongestants
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Charge to the Panel
The Panel was charged with: Making recommendations based on their experience and
the available data to establish conditions of use with respect to dosing, directions, warnings and in some cases testing and final formulations
Applying effectiveness standards in accordance with 21 CFR § 330.10(a)(4)(ii)
Effectiveness means a reasonable expectation that, in a significant proportion of the target population, the pharmacological effect of the drug, when used under adequate directions for use and warnings against unsafe use, will provide clinically significant relief of the type claimed
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Panel Recommendations
Categorized Ingredients Category I – Generally recognized as safe and
effective (GRASE) for the claimed therapeutic indication
Category II – Not generally recognized as safe and effective (NGRASE) for the claimed therapeutic indication
Category III – Insufficient data to determine safety and effectiveness
PEH was classified as Category I (GRASE) at a dose of 10 mg every 4 hours not to exceed 60 mg in 24 hours
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ANPR
A public comment period follows to allow interested person to submit comments, objections, new data and requests for hearings
ANPR Publication
September 1976
Upon conclusion of the Panel deliberations, the agency published a report of the unaltered
conclusions and recommendations of the Panel
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FDA reviewed: ANPR recommendations Public comment submitted in response to ANPR New data and scientific literature (if any)
One comment questioned Panel’s finding of effectiveness of PEH Based on heterogeneity of the findings among the
studies and overall strength of the findings
Tentative Final Monograph
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TFM PublicationJanuary 1985
TFM
FDA concluded that evidence was sufficient based on the studies information on clinical use marketing experience the Panel’s expertise
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Final MonographAugust 1994
FM
Manufacturers are given an effective date at which time their drug product must be in compliance with the monograph.
No additional comments were received about PEH
Promulgated regulation that establish standard for labeling to be used in an OTC therapeutic drug category.
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Phenylephrine Hydrochloride
Active ingredient Phenylephrine HCl Purpose Nasal decongestant
Uses temporarily relieves nasal congestion due to the common
cold, hay fever or other upper respiratory allergies temporarily relieves sinus congestion and pressure
Directions take 10 mg every 4 hours do not take more than 6 doses in 24 hours
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Can amend monograph with submission of a Citizen Petition (CP), per 21 CFR 10.30
CP submitted March 2002 requested that PEB in effervescent dosage form be GRASE Nonmonograph in FM
CP contained Domestic and global marketing history data Pharmacokinetic data
PEH and PEB have comparable bioavailability profiles
Monograph amended to allow for PEB in effervescent dosage form PR published November 2004 FR published August 2006
Phenylephrine Bitartrate (PEB)
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Other Nasal Decongestants in Final Monograph
Oral Phenylephrine hydrochloride Pseudoephedrine hydrochloride Pseudoephedrine sulfate
Topical Ephedrine Ephedrine hydrochloride Ephedrine sulfate Naphazoline hydrochloride Oxymetazoline hydrochloride Phenylephrine hydrochloride Propylhexedrine Xylometazoline hydrochloride
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Current CP Submission
The petition states that: PEH at the dose of 10 mg every 4 hours is not
effective PEB at the dose of 15.6 mg every 4 hours is not
effective The petition requests that:
the maximum dose of PEH and PEB be increased FDA require additional studies to validate that a 25-
mg dose of PEH is more efficacious than 10-mg dose of phenylephrine and is as safe.
No new data were submitted in the CP