This is the final report of the Advisory Committee for
Pharmaceutical Science meeting held on
http://www.fda.gov/ohrms/dockets/ac/cder05.html#PharmScience
All external requests should be submitted to the Freedom of
Information office.
____________________________________________________________________________________
The
Advisory Committee for Pharmaceutical Science of the Food and Drug
Administration, Center for Drug Evaluation and Research, met on
Advisory Committee for Pharmaceutical Science Members (voting):
Charles L. Cooney, Ph.D., Patrick
P. DeLuca, Ph.D., Michael S. Korczynski, Ph.D., Kenneth Morris, Ph.D., Cynthia
R.D. Selassie, Ph.D., Marc Swadener, Ed.D.,
Advisory Committee for Pharmaceutical Science Consultants (voting):
Carol Gloff, Ph.D., Thomas Layloff, Ph.D., Arthur H. Kibbe, Ph.D., Marvin C. Meyer, Ph.D.,
Industry Representative (non-voting):
Paul H. Fackler, Ph.D., Gerald Migliaccio
FDA Guest Speakers:
Lucinda Buhse, Ph.D., Kathleen A. Clouse, Ph.D., Jerry Collins, Ph.D., Ajaz
Hussain, Ph.D., Robert Lionberger, Ph.D., Mehul Mehta, Ph.D., Robert O’Neill,
Ph.D., Vibhakar Shah, Ph.D., Keith Webber, Ph.D., Helen Winkle, Lawrence Yu, Ph.D.
FDA Participants:
Gary Buehler, R.Ph.
Open Public Hearing
Speakers:
May 3, 2005: Will Brown, USP
May 4, 2005: None
These summary minutes for the May 3 and 4, 2005 of the Advisory Committee for Pharmaceutical Science of the Food and Drug Administration were approved on ____May 20, 2005____________.
I certify that I attended the May 3 and 4, 2005, meeting of the Advisory Committee for Pharmaceutical Science of the Food and Drug Administration meeting and that these minutes accurately reflect what transpired.
________//S//____________________ ________//S//____________________
Hilda F. Scharen, M.S. Charles L.Cooney, Ph.D.
Executive Secretary Chair
On
.
Charles
L. Cooney, Ph.D. (Committee Chair), called the meeting to order at
Day 1:
Introduction to Meeting Helen Winkle
OPS
Update Director,
Office of Pharmaceutical Science
Welcome and Opening Remarks Charles Cooney, Ph.D.
Chair,
ACPS
Establishing Drug Release or
Dissolution Specifications
(1)
Topic Introduction Ajaz Hussain, Ph.D.
Deputy Director, OPS
(2) Dissolution Measurement
System: Lucinda Buhse, Ph.D.
Office of Testing and Research (OTR), OPS
Break
(3)
Overview of Current Guidance Documents and Mehul
Mehta, Ph.D.
Decision
process: Biopharmaceutics Section Director,
Division of Pharm. Evaluation I,
Office of Clinical Pharmacology and
Biopharmaceutics
(4) Establishing Dissolution
Specifications: Vibhakar
Shah, Ph.D.
Current Practice (CMC) Chemist, Division of
New Drug Chemistry II
Office
of New Drug Chemistry
Lunch
Open Public Hearing
Establishing Drug Release or
Dissolution Specifications
(5) Factors Impacting Drug Dissolution and
Absorption:
(6) Summary of Tactical Plan Ajaz
Hussain, Ph.D.
Break
Committee Discussions and
Recommendations
Subcommittee Reports
Clinical Pharmacology Subcommittee Jürgen Venitz, M.D., Ph.D.
(via teleconference) Chair,
Clinical Pharmacology Subcommittee
The meeting was
adjourned at approximately
Charles
L. Cooney, Ph.D. (Committee Chair), called the meeting to order at
Day 2:
Parametric Tolerance
Interval Test Robert O'Neill, Ph.D.
for Dose Content Uniformity Director, Office of Biostatistics (
Pharmacoepidemiology and Statistical Science
Current update on the Working Group
Quality-by-Design and Pharmaceutical Equivalence
(1) Topic Introduction Ajaz
Hussain, Ph.D.
(2) Using Product Development Information to Ajaz Hussain Ph.D.
Extend Biopharmaceutics
Classification
System-based Biowaviers
Break
(3) Using Product Development Information to
Address
the Challenge of Highly-variable Drugs
(4) Using
Product Development Information to Robert
Lionberger, Ph.D.
Support Establishing
Therapeutic Equivalence Chemist, OGD, OPS
of Topical Products
Lunch
Open Public Hearing
Quality-by-Design and Pharmaceutical Equivalence
(5)
Topic Introduction (Cont’d) Ajaz Hussain, Ph.D.
Committee Discussion and
Recommendations
Break
Criteria for Establishing a Working Group for
Review and Assessment of OPS Research Programs
(1) CBER Peer Review Process for Kathleen A. Clouse, Ph.D.
Researchers/Reviewers Acting
Director, Division of Monoclonal Antibodies, Office of Biotechnology Products
(OBP)
(2) CDER Peer Review Research Jerry Collins, Ph.D.
Director, Laboratory of Clinical Pharmacology,
Office of Testing and Research (OTR), OPS
Committee Discussion and
Recommendations
Conclusion and Summary
Remarks Ajaz Hussain, Ph.D.
Helen Winkle
Questions to the Committee:
Topic #1
Are the tactical steps outlined consistent with the QbD goals we seek
to achieve?
The Committee agreed with the outlined tactical steps and the members
felt that this is one additional step in moving towards Quality by Design while
moving to
Yes: 11
No: 24
Abstain: 0
What additional steps and/or changes would you recommend to improve
this plan?
The Committee emphasized it is important to think through the
implications this plan will have for the regulatory process. The members
expressed some desire that this plan helps move away from a “check the box”
process for reviewing and approval, and will enable continuous learning and
ultimately improve the process.
What additional scientific evidence is necessary to support the
development and implementation of this plan?
The members recognized the rational for the currently used release test
b y the FDA and emphasized it is important to keep in mind that the ultimate
point of the release test is the patient.. Finally,
the Committee felt it is important for the implementation plan to consider the
impact on both the regulator and the manufacturer.
The Committee added that it is essential to incorporate in its work an
adequate communication plan, to inform a broader community about the
implementation of the tactical plan.
General considerations for identifying and developing statistical
procedures
Any other specific recommendations
Prioritization
The members discussed the implications that exist with using the same
dissolution specifications for generic as for pharma. Also, some members
emphasized the difficult position the generic drug industry is in while trying
to comply with both FDA specifications and USP standards. The Committee agreed
that it is important to give particular attention to generic products, while
developing this strategy. Some member felt that this could be achieved by
revising the requirements and standards and submitting them to USP. However,
some members noted the long time required for a USP change and the financial
burden this places on industry.
Topic #2
How can pharmaceutical development
information help to extend the applications of BCS-based waiver of in vivo
studies for immediate release products?
How can pharmaceutical development
information be utilized to address the challenge of highly variable drugs?
Establishing therapeutic equivalence of
topical products?
The members felt that a better understanding
of the scenario of formulation design will lead to improved product quality
with reduced variability, which they agreed is the foundation of Quality by
Design. The Committee highlighted that it is a scientific hypothesis, which
will allow for clearer decision-making and ultimately, hopefully create more
flexibility.
In addition, the Committee added that the
implementation of Quality by Design will require for additional information on
the product development process, e.g. the Product Development Report. However,
the members emphasized it was important that while Industry shares additional
information, that this risk-based system reduces their burden and adds more relevancy to the questions asked, as well
as, reduces the number of approval cycles.
The members understood that FDA wants to use
the Product Development Report to: (1) extend BCS-based waiver for immediate
release products, (2) facilitate approval of Highly Variable Drugs, (3) facilitate pharmaceutical equivalence of topical products.
The Committee believes it is important to
add clarity on what information is needed and how additional information will
be used to establish bioavailability and bioequivalence. Additionally, the
members felt it was essential for the system to be receptive and advised there
was a need for FDA to work with both the reviewers and Industry to ensure and
educate them so that the new information provided will be used effectively.
Some members underlined the importance of
having the generic drug industry well engaged during the development phase of
the decision trees for the proposed hypothesis.
In conclusion, the Committee recommended
that FDA continue to address Quality by Design and define its use to facilitate
its use in the regulatory approval of drug products.
Topic #3
Does the ACPS support the creation of a
subcommittee under ACPS to develop the criteria and the process for review of
OPS research programs?
The members agreed with the concept of creating a
subcommittee under the Advisory Committee for Pharmaceutical Science in order to
review the Office of Pharmaceutical Science research programs. The Committee
unanimously endorsed the recommendation for the creation of this subcommittee under the main
Advisory Committee for Pharmaceutical Science.
Yes: 11
No: 24
Abstain: 0
The meeting was
adjourned at approximately