The
Manufacturing Subcommittee of the Advisory Committee for Pharmaceutical Science
of the Food and Drug Administration, Center for Drug Evaluation and Research
met on
Manufacturing Subcommittee of the Advisory Committee for Pharmaceutical
Members (voting):
Patrick DeLuca, Ph.D. (ACPS),
Robert (
Judy Boehlert, Ph.D., Daniel Gold, Ph.D., Thomas Layloff, Jr., Ph.D., Garnet Peck, Ph.D., G.K. Raju, Ph.D., Nozer Singpurwalla, Ph.D.
Manufacturing Subcommittee of the Advisory Committee for Pharmaceutical
Science Consultants(voting):
Acting Industry Representative (non-voting):
Efraim Shek, Ph.D.
Guest Speakers:
Edmund Fry, Colin Gardner, Greg Guyer, Ph.D., Tobias Massa, Ph.D., Gerry Migliaccio, Kenneth Morris, Ph.D.
FDA Guest Speakers:
Joe Famulare, Ajaz Hussain, Ph.D., Norman Schmuff, Ph.D., Janet Woodcock, M.D.
FDA Participants:
Diana Koliatis
Open Public Hearing Speakers:
Robert Menson, Ph.D.
These summary minutes for the
I certify that I attended the
____________________________ ____________________________
Hilda Scharen, M.S. Judy
Boehlert, Ph.D.
Executive Secretary Chair
The
Committee discussed Quality by Design and its relationship to Risk-based
Regulatory Scrutiny. The members and the invited consultants were provided the
background material from the FDA prior to the meeting.
The
meeting was called to order at
Introduction Ajaz Hussain, Ph.D., FDA
Quality by Design and Risk-Based Scrutiny
Quality
for the 21st Century: Summary of FDA/PQRI Workshop Tobias
Massa, Ph.D., Eli Lilly &
Defining Quality of a Pharmaceutical Product Janet Woodcock, M.D., FDA
Components of “Quality by Design”: Performance Measurement G.K. Raju, Ph.D., MIT
Assessing Quality-by-Design: A CMC Review Perspective Norman Schmuff, Ph.D.
Proposals for Regulatory Assessment of
“Quality by Design”
Using Manufacturing Science and Risk Management principles Gerry Migliaccio, Pfizer Inc.
to achieve “Quality by Design”
Quality by Design – A Generic Industry Perspective Edmund Fry, IVAX Corp.
Risk –Based
Development for Quality by Design Kenneth
Morris, Ph.D.,
Regulatory Assessment of Quality by Design: A CGMP Perspective Joe Famulare, FDA
Quality by Design: Next Steps to Realize Opportunities Ajaz Hussain, FDA
Open Public Hearing
Committee Discussion and Recommendations
Quality by Design and Risk Based Regulatory Scrutiny
Designing Quality in Design Colin Gardner, Transform Pharmaceuticals Inc.
Use of Risk Management in Pharmaceutical Manufacturing Greg Guyer, Ph. D., Merck & Co., Inc.
Committee Discussion and Recommendations
Closing Remarks
Adjourn
Questions to the Committee:
1. Quality by Design:
· Articulate a clear description of the term quality by design
· Identify the type of information and knowledge most useful to assess quality by design
· Regulatory approach for assessment of pharmaceutical development knowledge to maximize its value without impacting drug development
The committee found general agreement that
Quality by Design is a dynamic active process that continues in the development
stages and post-approval of a product. The knowledge useful to assess Quality
by Design is the identification of stress relevance and the critical control
point, and robustness of these critical control points. The regulatory approach
for assessment is output oriented.
The committee recognized the clear advantage
of making progress in an existing system where the goal would be to have
creative incentives for a broader development context so that the companies do
it and communicate it to FDA.
For process development knowledge, it is
essential to first understand the boundaries and basic failure modes of this
process in terms of its safety and efficacy issues, and predictability issues.
They are the basis for the range of the variables and specifications. In making
product development formulation it is essential to understand variability,
manage variability, the critical process, and end point. The focus on
post-approval changes provides a flexible means to engage industry and enhance
collaboration. There was also agreement
that the issues discussed helped frame this view point and were consistent with
the PAT Guidance.
In summary, the committee agreed that the notion of
quality is self evident. They committee further defined quality by design as
being a systematic process of achieving desirable quality by a careful and
methodical scrutiny of all the attributes that go into characterizing quality,
from the inception of a product to its end use, involving all its stakeholders
(the patient, the manufacturer, the physician, and the regulator).
2. Relationship between Quality by Design & Risk Based Regulatory Scrutiny
In this
discussion we seek subcommittee recommendations on ways to link the concept of risk based regulatory scrutiny to quality by
design.
The
committee defined the concept as using process understanding as a means for
Quality by Design. In PAT, a
high level of process understanding was defined as being able to
understand the change and impact, and thereby the risk assessment, on the
process.
There was a general
agreement among the committee members that a less burdensome change management
system based on development information provided, as well as testing protocol
is needed to qualify change.
The committee concluded that the
post-approval change scenario offers a way forward to bring pharmaceutical
development information and to learn how to better utilize that information. It
was emphasized that pharmaceutical development reports are not only important
for post-approval changes. The committee felt this incoming information would
help in training FDA personnel, as well as starting to build a culture of
“information sharing” between FDA and industry.
In
summary, the committee felt that the Quality by Design and risk assessment
concepts would assist in the NDA review process and help alleviate fears of
delayed post-approval changes. The committee agrees that the current products being developed in
ICH guidance will be run in parallel to
the CDER’s efforts. The committee’s thought process and discussions were
consistent with the information contained in the Draft Process Analytical Technology(PAT) guidance and represented a good basis for
ICH deliberations.
The meeting was
adjourned at approximately