Atypical Actives
PDA-FDA Conference
March 9-10, 2011
David R. Schoneker
Email: dschoneker@colorcon.com
www.ipecamericas.org
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What is an Atypical Active?
• A chemical that is normally produced for use as
an excipient, food additive or an industrial
product that a customer decides to use
(typically without the maker’s knowledge) as an
API in a drug product (ie; OTCs… but not
always!)
• Usually NOT the maker’s intended market for
the material so the manufacturing process and
controls are NOT typically designed to meet API
GMPs (ICH Q7) – Excipient or Food GMPs used
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What is an Atypical Active?
• Usually a very small market for the
material compared to the normal uses
• Typically, prices and margins are low
compared to standard APIs
• Seen by most suppliers as a liability risk
with little business benefit
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API (Q7) GMPs vs Excipient GMPs
• Due to the nature of the manufacturing
processes and distribution channels, it
would be very difficult and costly to try
to use API (Q7) GMPs when manufacturing
Atypical Actives
• The costs rarely would be justified from a
business perspective due to the profit
margins and market size
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IPEC – Initial Concepts for
Atypical Actives
• GMPs aligned with the IPEC-PQG Excipient GMPs
should be acceptable
• Some additional technical considerations may
need to be addressed; Examples:
– Better understanding of specific composition and potential
variability
– Tighter specifications on critical properties where needed
– Improved understanding of stability but not the same level of
stability studies as required for standard APIs
– Stronger change control and customer notification procedures
• These are technical requirements, not a higher
level of GMP
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Atypical Actives Workshop Program
• Overview of the Issue – Maker’s & User’s
Perspectives
• Regulatory Perspectives – FDA & EMA
• Liability and Legal Issues
• Impact on Users and Makers of Uncertainty
• Case Studies – Real-Life Examples
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Atypical Actives Workshop Program
• Breakout Working Groups & Reports
– Technical Considerations – what appropriate
controls need to be considered for an
excipient that is used as an API?
– Regulatory Considerations – How can
industry and regulators work together to
resolve legislative and regulatory barriers to
embrace a science and risk based approach?
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Total Excipient Control (TEC)
Tools for Managing Excipient Quality
The Next Decade for IPEC
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What is TEC and how to combine
TEC Elements
• IPEC’s first attempt at pulling together the
various guidelines into an integrated structure
was the development of the Excipient
Qualification guideline
• Provided overall guidance on how to use a
number of the related IPEC guidelines to build a
credible excipient qualification program from
both the makers and the users perspective.
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What is TEC and how to combine
TEC Elements
• As IPEC moves into our third decade we now
want to take this concept even further and
work towards the development of a system of
Total Excipient Control (TEC)
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What is TEC and how to combine
TEC Elements
• TEC will utilize all of the existing IPEC
guidelines, programs and proposals to build an
overall control system
• TEC covers the controls needed from the time
an excipient manufacturer thinks of marketing
a chemical as an excipient to the
pharmaceutical industry to the time the patient
takes the drug product containing the
excipient.
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What is TEC and how to combine
TEC Elements
• We will determine where there may be gaps in
our current toolkit and develop appropriate
guidance or programs to establish Total
Excipient Control.
• IPEC’s challenge for the future!!!
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The Building Blocks have been
developed in the last 20 Years!!
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TEC will finish things off and Add
the Roof
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The House that IPEC Built!!
Patient
Safety
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