Program - Society of Toxicology

44 th Annual Meeting
and ToxExpo
Continuing Education
INTERNATIONAL HARMONIZATION OF TECHNICAL
REQUIREMENTS FOR CONDUCTING NON-CLINICAL SAFETY
STUDIES OF HUMAN PHARMACEUTICALS: GUIDELINES, CASE
STUDIES, AND CHALLENGES
AM 07 (REPEATS AS PM 13)
BASIC
Chairperson(s): Rakesh Dixit, Merck Research Laboratories, West Point, PA.
Endorsed by:
Carcinogenesis SS*
Regulatory & Safety Evaluation SS
Risk Assessment SS
The International Conference on Harmonization of Technical Requirements for
Registration of Pharmaceuticals for Human Use (ICH) was established in 1990
to standardize and harmonize technical requirements for the world-wide
marketing approval of human pharmaceuticals. The six party ICH comprises the
regulatory agencies and research-based pharmaceutical industrial organizations
from three major geographical areas, the United States, the European Union and
the Japan. The major goals of the ICH process are to minimize unique regional
requirements, reduce the duplication of non-clinical toxicology and clinical
testing requirements, and to accelerate the global development, registration and
marketing of human pharmaceuticals in a cost-effective manner. Under Safety
topics (non-clinical safety), 15 major guidelines have been harmonized and
implemented through three major global regulatory agencies. These include
guidelines on technical requirements for genotoxicity, toxicity, carcinogenicity,
reproductive and development toxicity, biotechnology safety, toxicokinetics,
safety pharmacology and joint safety and efficacy. This course is designed to
provide a thorough understanding of the rationale behind ICH guidelines and
the utility of the ICH guidelines in accelerating and global harmonization of
safety evaluation of pharmaceuticals. The presentations will also highlight case
studies with detailed examples, and experience in conducting non-clinical ICH
safety studies. The presentations will also discuss the challenges, and problems
encountered due to the differences in the interpretation, and the acceptance of
the ICH Guidelines by the practicing regulatory organizations, reviewers and the
traditional practices of specific geographical areas.
• Guidelines on Genotoxicity Testing: Case Studies, Study Interpretation
and Challenges, Sheila Galloway, Merck Research Laboratories, West
Point, PA.
• Developmental and Reproductive Toxicology Testing: Case Studies
Study Interpretation and Challenges, Maureen Fesuton, Sanofi-
Synthelabo, PA.
• Chronic Toxicity, Carcinogenicity and Toxicokinetics Guidelines: Case
Studies and Challenges, Rakesh Dixit, Merck Research Laboratories,
West Point, PA.
• U.S. FDA’s Experience and Guidance Related to ICH Safety
Guidelines, David Jacobson-Kram, U.S. FDA, Rockville, MD.
MALE REPRODUCTIVE HAZARD IDENTIFICATION AND RISK
ASSESSMENT IN PHARMACEUTICAL DEVELOPMENT (WHAT DO
YOU DO NOW THAT YOU HAVE A SIGNAL?)
PM 08
ADVANCED
Chairperson(s): Michael W. Conner, Theravance, Inc., South San Francisco,
CA and Robert E. Chapin, Pfizer, Inc., Groton, CT.
Endorsed by:
Reproductive and Developmental Toxicology SS
Regulatory and Safety Evaluation SS
Toxicologic & Exploratory Pathology SS
In the preclinical development of pharmaceuticals, there are numerous opportunities
to observe effects on the male reproductive system. There are relevant
endpoints in both routine repeated-dose toxicity studies and in the developmental
and reproductive toxicity studies. In recent years methods for
identification of male reproductive injury have expanded well beyond the traditional
endpoints of fecundity in rodent fertility studies and routine microscopic
examination of testes in repeated-dose and reproductive toxicity studies. There
is an expectation, for instance, that pathologists will examine testes with knowledge
of and reference to the stages of the seminiferous epithelium. Assessment
of number, motility and frequency of morphological abnormalities in epidydimal
sperm has become routine in rodent fertility studies. Recently, some
emphasis has also been placed on identification of biomarkers for testicular
injury. The next steps following identification of a signal are ill defined. The
purpose of this continuing education course is to address what types of signals
are commonly observed and to present a rationale for interpreting these data
with regard to risk assessment for volunteers and patients. The speakers in this
course will place an emphasis on case studies and will provide their proposals
for subsequent preclinical and/or clinical investigations. We will deal with the
issue of reversible vs. irreversible injury, and review the latest data on the differences
between these two. We will hear case reports on investigative mechanistic
studies and when they are best pursued, and the course will close with a review
of the considerations that should be addressed when risk-assessing male reproductive
findings.
• Early Signal Identification, Dianne Creasy, Huntingdon Life Sciences,
East Millstone, NJ.
• Signals in Primates—Reversible and Irreversible Injury, Kim
Boekelheide, Brown University, Providence, RI.
• Further Characterization of Male Reproductive Injury—Case Studies,
Patrick J. Wier, GlaxoSmithKline, King of Prussia, PA.
• Safety Assessment for Male Reproductive Injury, Robert E. Chapin,
Pfizer, Groton, CT.
CE
42
SOT’s 44 th Annual Meeting