Quantitative Pharmacokinetic Methods for Dosimetry Determinations A Workshop

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Quantitative Pharmacokinetic Methods for
Dosimetry Determinations A Workshop

• The mission of this project is conduct a
  multi-sector workshop to identify how
  quantitative methods in pharmacokinetics can
  address improved toxicity test designs, dose
  selection issues, application to tier-based
  decision making, and better prediction of
  route-to-route differences in exposure

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Workshop Design Team

• Dr. James Bus (Acting Chair), Dow Chemical
  Company
• Dr. Melvin Andersen, CIIT
• Dr. Hugh Barton, U.S. EPA
• Dr. Janice Chambers (Sci Advisor), Mississippi
  State University
• Dr. Craig Farr, Arkema Inc.
• Dr. James Gibson (Sci Advisor), East Carolina
  State University
• Dr. David Jacobson-Kram, U.S. FDA
• Dr. Robert Lindenschmidt, Procter Gamble
• Dr. Ron Melnick, NIEHS
• Dr. James Sanders, sanofi-aventis
• Dr. Charles Timchalk, Batelle Northwest
• Mr. J. David Sandler, Staff
• Ms. Candice Hamilton, Staff

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Why is HESI undertaking this exercise?

• Rapid advances in analytical sciences and
  pharmacokinetic modeling position chemical safety
  evaluations to include earlier and more
  comprehensive PK evaluations that provide
  critical study design and interpretive
  information
• Regulatory initiatives present potential for
  increased animal tests (e.g., HPV, REACH) while
  others seek to reduce or refine these tests
  (e.g., European Cosmetic Directive, SAR)
• Exposure/dose information from human
  biomonitoring programs must be placed in context
  with dosimetry info from animal studies to
  understand potential for human risk

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Why is HESI undertaking this exercise?

• Likely rapid increase in availability of PK
  information and methodologies indicate that
  efforts must be made to mutually understand their
  potential application and value.
• Need to define and implement appropriately
  harmonized approaches

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The Workshop will identify

• Key partners industry, academia, government
• Critical research supporting proactive and
  rational role for use of pharmacokinetic data in
  design and interpretation of toxicology studies
• Opportunities to improve use of pharmacokinetic
  data in risk assessments, including evaluations
  of mode of action, interpreting biomonitoring
  results, and risks of low-dose exposures to
  mixtures

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Preliminary Design

• Full consideration of current HESI projects,
  i.e., Agricultural Chemical Safety Assessment,
  DNA Adducts, Biomarkers, others

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Logistics

• Workshop Design Team meeting at EPA NHEERL
  facilities in Research Triangle Park, January or
  February 2005, to finalize workshop plans
• Workshop to be held late 2005 in Research
  Triangle Park

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HESI Mapping Exercise
9
10
E
? (Aging World Population)
B
? (Obesity)
(Education of Public/Precautionary Principle) ?
HESI Revised Societal Challenges Map
C
? (Sensitive Subpopulations/Childrens Health)
A
D
? (Alternative Therapies)
2004
10
10
F

• ? (Exposure Inputs to Risk Assess./Regul.
• testing priorities)

A
(Sensitive Subpopulations)?
? (REACH, DSL)
I
G
P
? (Conservative Default Factors)
D
?(Data Quality Cluster)
(Mixtures/Coexposures ? Bio, tox, proof of
principle)
(Conservative Default Factors)?
(Transitioning New Science ? Into Regs and
Guidelines Validation)
H
J
HESI Revised Regulatory Challenges Map
L
(Mixtures/ Coexposures Empiricism)?
(Childrens Health Late-Life Outcomes)?
(Childrens Health PK, MOA)?
(REACH)?
B
M
C
E
N
? (Transitioning New Science Into Regs
Guidelines Flexibility to Reflect Science)
(New Tech ? Cluster)
(Exposure Inputs to Risk ? Assess/Regul.
conducting assmts, etc)
K
O
2004
? (Transitioning New Science into Regs and
Guidelines mapping intl process)
11
10
? (Environmental Toxicology)
? (Omics/bioinformatics)
(Sensitive Subpopulations, Evaluative Databases)
?
HESI Revised Scientific Challenges Map
(Predicting Idiosyncratic Reactions) ?
? (Sensitive Subpopulations, Safety
Factors/ Predictive Models)
? (Cancer Testing)
? (Toxicology of Mixtures)
2004
12
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HESI Scientific Projects Portfolio Development
Feb - New Projects Idd Input to Map
July Survey for Topics
Oct Mtg Survey culled Input to Map
Jan - New EI topics at Ann Mtg
Feb - New Projects Idd Input to Map
July Survey for Topics
Jan - New EI topics at Ann Mtg
EIC Timeline
PSSC Mapping Timeline
Mid-year Mtg w/input from Mbr Dvpt Comm Input
to EIC for October selection of topics for
presentation at Annual Meeting
Spring Conf Call Review HESI Portfolio
Consider EI proposals not selected for year
Update Map Provide topic specificity for EI
Survey
Spring Conf Call Review HESI Portfolio
Consider EI proposals not selected for year
Update Map Provide topic specificity for EI
Survey
Jan PSSC mtg w/Board at Annual Mtg
Jan PSSC mtg w/Board at Annual Mtg