Transcript FDA-CHPA Joint Presentation

CHPA Guidelines on Stability Testing of
OTC Monograph Drug Products
Karen L. Lucas
Pfizer Consumer Healthcare
Patricia Werschulz
BMS Worldwide Consumer
36th Annual ASQ-FDC/FDA Conference
June 23, 2005
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Overview
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Background
Who and What is the CHPA Stability
Working Group (SWG)?
What are we trying to fix in the OTC World?
Risks vs. Benefits of Having a Guideline
Where are we today & What’s next?
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Background
• In August 2002, CHPA was approached by a member
company to obtain support in addressing FDA’s lack
of guidance on stability testing requirements for OTC
Monograph Drug Products.
• As a starting point toward further dialogue with both
the agency and industry, the development of a draft
stability guideline document was proposed.
• In May 2003, CHPA granted approval to form the
Stability Working Group (SWG).
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Stability Working Group Members
•Karen L. Lucas, Pfizer Consumer Healthcare - Chairperson
•Patricia Werschulz, Bristol-Myers Squibb
•Jeffrey Needels, Novartis Consumer Health
•David Wiggins, Schering Plough
•Judy Lee, Purdue Pharma
•Bruce Henning, Bayer Healthcare Consumer Care
•Jane Cai, Johnson & Johnson Consumer
•Eleanor Freeman, McNeil Consumer
•Mary W. Seibel, Procter & Gamble Health Care
•Tony Psihoules, Colgate-Palmolive
•Bill Van Meter, Perrigo
•Frederick Razzaghi, CHPA - Facilitator
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A Need was Identified……..
SWG’s Goal
Prior
to this CHPA guideline, the non-prescription industry
did not have directly applicable stability testing guidance for
OTC monograph drug products not regulated by an
NDA/ANDA.
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Historically, non-prescription drug companies developed
their stability testing programs based upon their best
interpretation and practical application of the most current
FDA guidance for new drug products.
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A Need was Identified……
SWG’s Goal (cont’d)
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Because of the unique requirements associated with new
OTC drug products, the direct application of the FDA
guidance is frequently inappropriate and impractical.
Drug products with an OTC monograph will typically be
well characterized with a:
– significant body of information
– well known safety profile
– long history of use in multiple dosage forms.
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For this reason, the OTC Industry (under the CHPA) is
proposing this guideline for non-prescription (OTC) drug
products not regulated by an NDA/ANDA.
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A Need was Identified…….
SWG’s Goal (cont’d)
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SWG’s Goal:
– To create an OTC Stability Guideline in order to
establish science-based best practices and minimum
requirements for the development and launch of
OTC Monograph Drug Products in the U.S. (that
are not regulated by an NDA/ANDA).
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We Recognized The Problem…..
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Rx World (NCEs):
 ICH Q1A and FDA (3 batches, LT & ACC, 12 months data)
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Generic World (NCEs with experience):
 1987 and draft 1998 FDA Stability Guidelines
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OTCs (extensive experience, good safety record, Monograph Drugs):
 The existing FDA stability references applicable to OTC monograph
products (e.g.. the Joel Davis "Dating Game" memo from 1978, and
FDA Inspector Technical Guide ITG-41 from 1985) are somewhat
dated. Something more recent is preferable in order to justify the
OTC Industry's approach to stability testing.
 Current practice is for companies to use ICH Q1A. Q1A is the most
recent guidance that has been developed. It represents the most
conservative set of stability requirements. Clearly, OTCs do not
require as much testing, and in practice, companies are not strictly
following ICH.
Bottom Line:
The NCE requirements ASQ-FDA
are excessive!
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What are we trying to fix???
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We recognize that there are a number of
Warning Letters & Recalls for inadequate
and/or no established Stability Programs
within OTC Companies.
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This guidance will help CHPA Member
Companies develop adequate Stability
Programs and reach a “higher state” of
compliance.
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Warning Letters & Recalls
(1997 – 2003)
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Warning Letters to OTC Companies:
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Failure to establish a written Stability Program – 33
Failure to follow written Stability Program – 19
No data available to support labeled expiration -11
Inadequate Stability Program - 10
Methods not stability indicating - 3
Recalls by OTC Companies:
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Data does not support labeled expiration – 6
Failed dissolution – 5
Sub-potency (stability failure) – 4
Other stability failure – 3
Non-uniformity in potency results – 1
Degradation failure - 1
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Risks to Industry
(Having a Guidance)
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We may provide a starting point for FDA to use to
over-regulate the OTC Industry.
May decrease flexibility of some individual CHPA
Member Companies not already meeting minimum
standards.
Uncertainty about Industry acceptance.
This would only be ONE part of FDA’s “Quality
System”.
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Benefits to Industry
(Having a Guidance)
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Helps us to minimize the Regulatory Burden:
– lower the Regulatory Risk through science – use our
knowledge and experience to base decisions!
– Reduces risk especially for CHPA member-companies
that do not have an established Stability Program!
– Self-regulation works to advantage of Government,
Industry & Consumer!
– Helps to avoid / minimize Over-Regulation.
– In alignment with FDA’s cGMPs for the 21st Century
Initiative: A Risk-Based Approach!
Science-based Risk Management: we can use science &
knowledge to base decisions.
Creates a “Level Playing Field” for everyone.
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Benefits to Industry
(Having a Guidance)….cont’d
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Gives us the opportunity to reduce the amount of stability
testing required prior to launch in the US.
Reduce “Time-to-Market”/ Satisfies a Business Need:
– Allows business units to plan better (Increase
Efficiency).
– Provides companies a “fast-track” option for
development of OTCs.
– Allows flexibility to reduce or eliminate testing under
specific circumstances.
– Allows flexibility to use smaller scale batches.
Creates an “Identity” for the uniqueness of the OTC
Industry.
Every company is essentially at risk because ICH Q1A
does NOT apply to OTCs!
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Our “Targeted State”
(What we would like to see):
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Clear stability requirements.
Elimination of Non-Value Added (NVA) activities.
Demystify stability requirements for non-technical
people.
Ability to plan more accurately & reliably.
Leverage to simplify our complex / inefficient
approach.
Zero adverse impact on “time-to-market”.
Science-based Risk Management!
Bottom Line:
 “Allow science to run our Stability Programs”. OTCs have more
experience, history, safety.
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How Did We Get To…
Where We Are Today?
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A Voluntary Alternative Method for doing OTC Monograph
Drug Product Stability was posted on the CHPA Website for
Industry comments through June 18, 2004.
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We had asked CHPA member-companies to look at their
internal procedures and comment where the discrepancies were
against the proposed guideline.
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6 CHPA member-companies responded with feedback /
comments.
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Published as a a CHPA Voluntary Guideline (along with
Industry comments) as of 10/8/04.
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Objectives of the Guideline
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To define the minimum stability data
package to support the commercial
distribution of OTC monograph drug
products in the United States per climatic
zone II. The stability data package will
be based on development stability
studies. These studies will be used to
establish the tentative expiration dating
period and label storage statement for
the OTC monograph drug product.
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Objectives of the Guideline
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This guideline recognizes that a
significant body of scientific
information may exist for OTC drug
products. Alternative approaches
may be used when they are
scientifically justified.
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Scope of the Guideline
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This guideline applies specifically to OTC
monograph drug product stability.
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This guideline does not currently seek to
cover the stability testing of:
– Non-prescription drug products regulated
by an NDA/ANDA
– Drug substances
– Drug products used in clinical trials
– Marketed product stability
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Scope of the Guideline
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Additionally, this guideline is not applicable
to:
– Specific details of the sampling and testing
for particular dosage forms in their
proposed container closures
– Safety studies
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Details of the Guideline
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SELECTION OF BATCHES
– Data should be available on at least one primary
batch of the drug product. Additional primary
batches may be necessary for new product
formulations and instances where no similar
formulations exist.
– Same formulation / same container closure system
as proposed for marketing.
– Manufacturing process should simulate that to be
applied to production batches and should provide
product of the same quality and meeting the same
specification as that intended for marketing.
– Batch(es) should be at least pilot scale (1/10
Production Scale); a scientific rationale may be
used to justify a smaller batch size.
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Details of the Guideline
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TESTING FREQUENCY
– The frequency of testing should be designed in
order to adequately determine the stability profile
for the drug product - typically 0, 3, 6, 12, and 24
months, and annually thereafter through the
proposed shelf-life. Other time points (such as 9,
18, 30 months) may also be appropriate.
– When the drug product fails to meet the
established shelf-life criteria at the accelerated
storage condition (such as 40C/75%RH),
alternative accelerated conditions may be used to
insure that at minimum, some acceptable
accelerated data is available to show that the
product can withstand the typical excursions
experienced in the distribution chain once the
product is marketed.
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Details of the Guideline (cont’d)
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STORAGE CONDITIONS
– GENERAL CASE:
Long Term 25 ± 2°C / 60 ± 5% RH
 Accelerated 40 ± 2°C / 75 ± 5% RH
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– DRUG PRODUCTS PACKAGED IN SEMIPERMEABLE CONTAINERS:
Long Term 25 ± 2°C / 40 ± 5% RH
 Accelerated 40 ± 2°C / NMT 25% ± 5% RH
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Details of the Guideline (cont’d)
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EVALUATION OF STABILITY DATA:
– A scientific approach should be adopted in the
presentation and evaluation of stability
information for establishing a tentative expiry
period. The scientific assessment should include
the results from physical, chemical and
microbiological data on the dosage form as well as
a “body of knowledge” which may consist of:
 Results from research and development
batches on similar or closely related
formulations.
 Results from research and development
batches on similar or closely related marketed
products.
 Data published in the literature, as well as
results from the specific stability study.
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Details of the Guideline (cont’d)
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EVALUATION OF STABILITY DATA:
– When the data from an accelerated
stability study remains within established
limits, while maintaining potency, a
tentative expiry period can be assigned
prior to marketing the product.
– A 24-month expiry period may be assigned
upon successful completion of three months
accelerated testing.
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Details of the Guideline (cont’d)
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EVALUATION OF STABILITY DATA:
– Using sound scientific judgment, shorter expiry
periods may be assigned based on less than three
months of accelerated testing and longer tentative
expiry periods may be justified using extended
periods of accelerated testing.
– Any longer tentative expiry period or extension of
an expiration dating period should be made based
on the previous histories of similar products,
sound scientific judgment, calculations using the
Arrhenius equation, all with appropriate
documentation.
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Why Follow this Alternative Approach?
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The OTC Industry plays a role in the overall
healthcare of the nation. This Guideline would help
us create an identity for the uniqueness of the OTC
Industry. Alternatives to adopting a “Voluntary
Standard” would include following the cumbersome
ICH stability requirements or wait for the FDA to
develop such a Guideline on this topic.
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We all participate in this business and benefit from it,
therefore we all should at least have a minimum
standard to continue to put quality OTC products on
the market for consumers.
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Where We Would Like to Go From
Here?
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Continue to engage in or share our information with
the Industry via conferences, meetings, etc.
Phase II – The Stability Working Group has
commenced activities to update the Guideline to
include changes to marketed OTC Monograph
Drug Products.
Revisit the Guideline at the CHPA Executive Level
if FDA endorsement is ever sought.
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Thank You For Attending!
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