Over-the-Counter
(OTC) Drug
Products
Introduction to Drug
Law and Regulation:
OTC Monograph System
Debra S. Dunne, R.Ph., Esq.
Partner | SHB Philadelphia |
[email protected] Regulation of OTC Drug Products
• OTC drugs play increasingly vital role in America’s
healthcare system
• More than 80 therapeutic categories of OTC drugs
• More than 300,000 OTC drug products marketed,
encompassing about 800 active ingredients
2
OTC Drugs: Generally Safe and
Effective for Use by the General Public
• The product has an acceptable safety margin (benefits
outweigh the risks)
• Potential for misuse and abuse is low
• Consumer can use them for self-diagnosed conditions
• Drug can be adequately labeled
• HCPs are not needed for the safe and effective use of the
product
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Regulatory Pathways for Marketing
OTC Drugs
• OTC Drug Monograph
• Identifies specific requirements for a class of drug products
• If product complies, manufacturer does not need FDA approval before
marketing
• New Drug Application
• Rx-to-OTC Switch
• Full Switch (NDA supplement)
• Partial Switch (new NDA)
• Direct to OTC
• NDA Deviation (330.11)
• Generic (ANDA)
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Requirements For All OTC Drug
Products
Manufacturing and Good
Standards for safety and
Manufacturing Practice
efficacy
Inspections
All OTC Drugs
Labeling under
Advertising Regulations
21 CFR 201.66
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NDA Process vs Monograph Process
NDA Process Monograph Process
Drug-product specific Active ingred/drug category specific
Pre-approval required Pre-approval not required
Clinical studies and user fees may be Clinical studies may not be necessary
necessary and no user fees
Review process is proprietary Notice and comment process is public
Approved labeling is unique to your Labeling is the same for all similar
drug drugs
Possible marketing exclusivity No marketing exclusivity
Approved NDA is license to market Final monograph is open to anyone
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OTC Drug Review: Regulatory History
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The OTC Drug Review- Inception of
Monograph Process
• Process began in early 1970s
• Offshoot of Drug Efficacy Study Implementation (DESI) for pre-1962
NDA-approved drugs
• FDA assembled expert panels to review active ingredients
and claims
• Panels to develop standards, “monographs”, to set out the
conditions under which OTC drugs would be considered
GRASE and not misbranded
• Final monographs published in CFR
8
Three phase process
Proposed Rule
Advanced Notice of Final Rule
Proposed
Tentative Final
Rulemaking (ANPR) Final Monograph
Monograph (TFM)
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Public Rulemaking Process: Phase 1
• FDA “call for data” from industry
• Expert panel reviews data submitted, develops
recommendations to FDA
• Panel report covers active ingredients, labeling requirements, excluded
conditions
• Classification of active ingredients and other conditions
• Category I-GRASE
• Category II- affirmatively not GRASE
• Category III- insufficient evidence for I or II
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Public Rulemaking Process: Phase 2
• Panel report published in Federal Register with a
“proposed monograph”
• “Advanced notice of proposed rulemaking”
• Agency seeks comment from public
• FDA reviews comments and any new data
• Agency publishes “tentative final monograph”
• TFM is a “proposed regulation”
• Sets forth active ingredients, indications, warnings,
and directions (Category I)
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Public Rule Making Process: Phase 3
• Agency again reviews comments, objections and new
data
• Final order issued (“final regulation”) setting forth
requirements
• Monographs typically effective 1 year after publication
• Non-compliant products then subject to regulatory action
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What is included in an OTC Drug
Monograph
• Monographs include:
• Listing of active ingredients that are GRASE
• Specific labeling requirements for indications, directions for use,
and warnings
• Finished formulations testing if appropriate
• Dosage forms (in some cases) and doseage strength
• Requirements designed to ensure that the product is
used in the manner for which it is GRASE and is
not misbranded
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Monograph Does Not Include
• Monographs do not include:
• Data requirements to establish safety and effectiveness
• Requirements to establish “material time” or “material extent” of
marketing
• Listing of permitted inactive ingredients
• Specific requirements for OTC packaging
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Mechanism to Amend OTC Monograph
• FDA may amend a monograph on its own initiative (21
C.F.R. 330.10(a)(12)(i)
• Interested party may submit petition requesting
amendment
• Citizen Petition
• Time and Extent Application
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Mechanism to Amend OTC Monograph:
Citizen Petition
• 21 CFR 10.30
• Can be used to amend OTC drug monograph at any
stage
• Limited to pre-1975 marketing conditions
• “conditions”: active ingredient, dosage form, indication, etc.
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Mechanism to Amend OTC Monograph:
Time and Extension Application (TEA)
• 21 CFR 330.14 (Effective in 2002)
• Can be used to amend OTC drug monograph for products
marketed:
• Under an approved NDA after OTC Drug Review began
• Outside the US
• Meets “material time” and “material extent” requirements
of 21 CFR 330.14(b)
• At least 5 continuous years in the same country
• 10s of millions of doseage units sold
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Do You Have Questions About:
• OTC Monograph Process
• Marketing During Monograph Development
• Marketing With a Final Monograph
• OTC Labeling
• Adverse Event Reporting
• Enforcement Actions
• Rx to OTC Switch
• NSURE
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PLEASE CONTACT
Debra S. Dunne, R.Ph., Esq.
Partner | SHB Philadelphia
[email protected] 19
Over-the-Counter
(OTC) Drug
Products
Introduction to Drug
Law and Regulation:
OTC Monograph System
Debra S. Dunne, R.Ph., Esq.
Partner | SHB Philadelphia |
[email protected]