37th Annual Meeting of the American College of Toxicology
The mission of the American College of Toxicology (ACT) is to educate, lead, and serve professionals in industry, government and related areas of toxicology by actively promoting the exchange of information and perspectives on the current status of safety assessment and the application of new developments in toxicology.
- Background Incidence of Spontaneous Arrhythmia’s in Large Animals K. Norton
- Challenges Associated with the Development and Validation of Flow Cytometry Assays C. Dumont
- Characterization of Cox-1 Inhibitors Effect on Platelets by In Vitro Platelet Aggregation Assays F. Poitout-Belissent
- Characterization of the Göttingen Minipig for Cerebrospinal Administration and CSF Collection Julie Douville
- How Low Can You Go? Generation of Stable Dry Powder Aerosols at Less Than 10 Micrograms per Liter M. Freke
- Morphometric Assessment of GATA4 Expression in the Rat Testis During Postnatal Development K. Takayama
- Procedural Refinement of Peripheral Infusion via a Tail Vein in Large Animals J. Laliberté
- Triple Cannulation Approach for Biodisttribution Studies of Neurologically Active Compounds in Large Animals Julie Douville
- Can You Measure Calcitonin in Rat, Mouse, or Large Animal Serum? Validation of an ECL Method for Calcitonin Quantitation P. Pitsikas
Symposium 9: "What to Do When Things Go Wrong"
Session Chairs: Francis Wolenski, Takeda Pharmaceuticals, Cambridge, MA; and Rob Stachlewitz, Charles River, Reno, NV
This session provided case examples of issues that may arise for early career toxicologists. Six early career professionals from across a variety of fields (industry, contract lab, regulatory, and academia) stated the issue they experienced, how they responded, and how the situation was resolved (either positively or not). After each speaker, a small panel of preeminent toxicologists (Ilona Bebenek, Denis Roy, and Rob Stachlewitz) provided their perspectives about alternative approaches. Two question and answer sessions gave the audience an opportunity to comment and share their experiences. This format was designed to promote an interactive discussion between speakers, panelists, and the audience.
Symposium 13: Juvenile Animal Studies (JAS): Review and Update
Session Chairs: Mike Moore, AZ-Pharma Consulting LLC, Phoenix, AZ; and Alan Hoberman, Charles River, Horsham, PA
Development of pharmaceuticals for pediatric indications presents unique challenges. Documented safe doses for adults can not be simply extrapolated to children based solely on body weight. Data from nonclinical studies in mature animals and clinical data in adults can provide an initial safety assessment for pediatrics including conduct of a pediatric clinical trial. However, often safety effects can not be adequately or ethically assessed in pediatric clinical trials, necessitating the conduct of toxicity studies using juvenile animals. Factors unique to design of a juvenile animal study (JAS) include species and age-related organ and metabolic development, PK/ADME, pharmacology, and practical considerations such as dosing formulation, limitations for administration route and biological sample collection, as well as litter effects, unique husbandry requirements, etc. Additionally, regulatory agencies differ as to the timing of JAS to support a pediatric study. Session presentations included industry and regulatory agency assessments of JAS data bases as to lessons learned and optimal study designs, global harmonization efforts regarding the timing and conduct of JAS studies for pediactric drug development, and unique study design aspects and considerations for each of the three most common laboratory animal species used in juvenile animals studies.
CE 8 – "Genetic Toxicology: Basics for Drug Development"
Session Chairs: Mark W. Powley, US Food and Drug Administration, CDER, Silver Spring, MD; and Leon F. Stankowski Jr., Charles River, Skokie, IL
Genetic toxicology is a critical component of the drug safety assessment process. The overall goal of genetic toxicology testing is to identify test articles capable of damaging DNA as these compounds may also possess carcinogenic properties. Per ICH S2(R1), regulatory testing utilizes a battery approach focusing on gene mutations, structural chromosomal damage (clastogenicity), and numerical chromosomal damage (aneugenicity). Positive results from any of the initial studies may result in additional testing to further define genotoxic risk. Ultimately, genetic toxicology data is integrated into the risk:benefit analysis and may significantly impact regulatory decisions.
This course provided attendees with a working knowledge of regulatory genetic toxicology. Topics included reviews of regulatory studies, ICH guidelines (e.g., M3, M7, and S2), approaches to follow-up on positive results, data integration, the impact of genetic toxicology results on clinical development, and innovations in the field. Considerations unique to both API and impurities will be addressed.
Specific issues related to drug development will be of interest to scientists from the pharmaceutical industry, regulatory agencies, contract research organizations, and consultants. The general topic of genetic toxicology will be relevant to scientists from all employment sectors.