Preliminary Program - American Association of Pharmaceutical ...

75
2009 AAPS Annual Meeting and Exposition
AAPS Pharmacokinetics, Pharmacodynamics and Drug Metabolism (PPDM) Programming
Clinical Pharmacology Rationale of First Time
in Human Dosing Study
Waldemar Radziszewski, M.D.
Merck and Co., Inc.
Regulatory Insight and Experience of First Time
in Human Dosing Studies
Mehul Mehta, Ph.D., invited
U.S. Food and Drug Administration
9:00 am – 11:00 am
Predicting Oral Drug Absorption:
Fiction and Facts
Roundtable
Finding a safe and effective compound amongst the
hoards of available chemical moieties is challenging
and costly. To bring a single drug to market may
take years, cost hundreds of millions of dollars, and
generally require testing in thousands of human
subjects. Most drug candidates never make it as far
as human testing and many that do are rejected for
various reasons. In an effort to minimize time and
costs of drug discovery and creation, pharmaceutical
manufacturers have produced numerous screening
techniques to identify the drug candidates most
likely to take them to market. Some of these
tests are aimed at drug absorption, distribution,
metabolism, and elimination (ADME). Others
are aimed at the effectiveness of drugs. In silico
methods (i.e. computer models) are the fastest and
one of the most efficient means for screening large
numbers of drugs for oral absorption. For drugs
that have survived the screening process, in silico
methods continue to play an important role. This
session will review models for predicting oral drug
absorption.
Moderators
Lawrence X. Yu, Ph.D.
U.S. Food and Drug Administration
Tycho Heimbach, Ph.D., M.S.
Novartis
Mechanistic Approaches to Predicting Oral
Drug Absorption
Gordon Amidon, Ph.D.
University of Michigan
Roles of Oral Drug Absorption and Exposure
Prediction in Drug Development
Tycho Heimbach, Ph.D., M.S.
Novartis
Roles of Oral Drug Absorption Prediction in
Regulatory Review
Robert Lionberger, Ph.D.
U.S. Food and Drug Administration
9:00 am – 11:00 am
Evaluating Fit-for-Purpose Models:
Consensus or Controversy
Roundtable
Disease/PK/PD/Trial Models are now being
increasingly used to aid decisions in industry,
hospital, and regulatory settings. It is generally
agreed that the adequacy of a model should be
judged mainly based on its intended application.
While modeling zealots continue to debate on
what term best fits the process of evaluating model
adequacy (model validation, model evaluation, etc.)
the more critical issue is the lack of consensus on
what constitutes an adequate model for a specific
application. The objective of this roundtable is to
debate on the appropriateness of models frequently
used in 3 areas of drug development; models
derived from in vitro, preclinical and literature
(study-level) data on competitors to inform decisions
in preclinical and clinical development, models
used to select doses for Phase 3 testing, and models
used for regulatory decisions, specifically to derive
labeling statements. The overarching question
is, what are the minimally acceptable statistical,
biological, and predictive (S, B, P) properties of
such models? To encourage an interactive session
on specific items, panel presentations will focus on
the following scenarios of model application. First,
intended application using exposure-response
models for efficacy and safety to design a dose
response study to find optimal dose(s) for Phase
3 testing. What are minimally acceptable S/B/P
properties for such models? What visual and
statistical tools would you use to judge model
adequacy? Second, intended application benchmark
the magnitude of efficacy of your compound relative
to competitors based on literature data to make a
go/no-go decision. What are minimally acceptable
S/B/P properties for such a model that combines
subject level data for your compound with study
level data with competitors? What visual and
statistical tools would you use to judge model
adequacy? Finally, intended application labeling
statement to include the estimated magnitude of
mean change in PK/efficacy/safety under conditions
of an interacting agent or in a special population.
What are minimally acceptable S/B/P properties for
such models? What visual and statistical tools would
you use to judge model adequacy?
Moderator
Sriram Krishnaswami, Ph.D.
Pfizer Global Research & Development
A Pharmacologist’s View
Nick Holford, M.D., M.S.
University of Auckland
A Statistician’s View
Kenneth Kowalski, M.S.
A2PG
A Regulator’s View
Yaning Wang, Ph.D., invited
U.S. Food and Drug Administration
OPEN FORUM
1:30 pm – 5:00 pm
An Evolution or Revolution in Drug
Metabolism: When, Where, Why,
What, How?
AAPS Pharmacokinetics, Pharmacodynamics
and Drug Metabolism (PPDM) Open Forum
An additional fee is required to attend this open forum
The critical aspects and fundamentals for
understanding the metabolism of new drugs are in
continual change driven by technological innovation,
regulatory expectations and the ubiquitous
pressures of logistics, timing, and cost. Because of
the diversity of different platforms and development
programs, it is impossible to adopt a “one-size-fitsall”
strategy for metabolism studies. Every molecule
has unique characteristics and the development
process represents complex and difficult challenges
that pivot around the drug’s potency, efficacy, safety,
toxicity, metabolic pathways and routes of excretion.
Even greater challenges are poised on the horizon
as human genomics and a deeper understanding
of the impact of metabolic enzyme and transporter
systems magnify the potential research complexity
for metabolism studies. Technology is friend and
foe providing incredible tools that facilitate greater
sensitivity for metabolite identification but creating
the difficult challenge of putting a meaningful
perspective on the findings and observations.
The questions that encapsulate drug metabolism
studies are numerous and often escape any simple
answer. At the PPDM Open Forum participants will
discuss various aspects of the design, conduct
and regulatory utility of mass balance and drug
metabolism studies. Among the issues to be
debated and discussed are: When is it best to
perform human metabolism studies? Where will
the greater understanding of human genomics
take the next generation of metabolism studies?
Why should samples be pooled or not and is there
an optimal approach? What exactly is a “major”
metabolite? How can 14C-tracer multiple dose study
be conducted most efficiently and should they be?