Quality By Design - A Generic

Industry Perspective
Edmund M. Fry
Vice President of Compliance
IVAX Corp.

Generic Pharmaceutical Association

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A shared vision of quality
GPhA supports the FDA CGMP initiative
 Generic drug manufacturing companies:
 Exist to make affordable drug therapies available to
all
 Companies, staff, volumes and revenues are
smaller
 It is completely appropriate that regulatory
requirements apply to all companies small and
large, as long as regulatory guidance provides
flexibility in recognition of more limited
resources at smaller firms

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What is Quality by Design?

“You can’t test quality into drug products” has

been heard for decades – so what’s new?
 It’s a culture - incorporates quality principles as well
as strong compliance function
 Incorporates risk assessment and management
 Refocuses attention and resources on what’s
important to the customer, i.e. the patients, health
professionals, payors and distribution chain

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Quality by Design

 Continuous improvement is a hallmark of

quality by design
 G. Taguchi on Robust Design: design changes
during manufacture can result in the last product
produced being different from the first product
 In pharmaceutical manufacturing, we don’t
want this – patients and physicians must count
on each batch of drug working just like the
batches that came before

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Quality by Design

In generic pharmaceutical
manufacturing, there are additional
constraints
 Fixed bioequivalence targets
 Regulatory requirements to duplicate
formulation of innovator drug
 Lack of access to innovator development
data

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The Changing Environment
Quality by Design Current Regulatory Situation

 Adequate resources for  Little guidance on adequate

quality: number, resources or qualifications
qualifications, etc.  Self-assessments not trusted
 Self-assessments play key  Annual product reviews
role instead of continuous
 Continuous analysis & analysis
improvement  Formidable barriers to
 Change management based change, including intimidating
on good science enforcement emphasis
 Focus on what’s important  Seldom admit that anything is
(risk management) not important; test everything

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Suggested actions

 Give credit for good performance

 Continue to reduce unnecessary supplements
 Continue to develop the Pharmaceutical
Inspectorate
 Reward process innovation
 Eliminate unnecessary testing requirements
 Address oversight of overseas API mfrs

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Give credit for good performance
Proven ability to operate in compliance should
result in reduced regulatory burden, e.g.
inspections and pre-approval review
requirements

 Factors considered by FDA in assigning inspections

(D. Horowitz, Sept. 10, ’03):
 Facility (e.g., compliance history)
 Product being manufactured at the facility
 Process used (e.g., process understanding)
 Generic pharmaceutical manufacturers must be rated
on the same basis as larger companies

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Continue to reduce pre-approval
supplements
Examples
 New manufacturing sites
 Post-approval changes for sterile
products

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Continue to develop the
Pharmaceutical Inspectorate
FDA is doing a good job of raising
technical competence of Investigators
 System-based inspections are a
meaningful approach
 Further opportunities exist to integrate
field activities with review activities;
integrated uniform training; delegation of
more decisions to field personnel

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Reward process innovation

 PAT holds promise; effort actually led by

FDA instead of industry
 Similar encouragement should be
provided for other advancing
technologies (e.g. advanced aseptic
processing)

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Eliminate unnecessary testing and
other requirements
 Prime example: sterility testing
 Blend uniformity testing

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Address oversight of overseas API
mfrs
 Use data from pharmaceutical
companies
 Support pooling audit information

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International Initiatives
Continue to include all affected parties in
policy-making initiatives
 Due to the nature of the generic
pharmaceutical industry, we may not have
equivalent numbers of senior-level technical
personnel who can dedicate substantial
extramural time to working with ICH and other
international activities
 However, that does not mean we can’t be at
the table

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Conclusion

 Quality by Design and the FDA CGMP

Initiative make excellent business and
scientific sense
 The generic pharmaceutical industry
welcomes the opportunity to work with
FDA

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