51st Annual Meeting & ToxExpo - Society of Toxicology

51 st Annual Meeting and ToxExpo
Continuing Education
Regulatory Science: Bridging the
Gap between Discovery and Product
Availability
Regulatory Sciences: Preclinical Drug
Development from Small Molecules to Biologics
PM11
CE Basic
Chairperson(s): Tao Wang, Novartis Pharmaceuticals, Emeryville,
CA, and W. David McGuinn, US FDA, Silver Spring, MD.
Sponsor:
Biotechnology Specialty Section
Endorsed by:
Immunotoxicology Specialty Section
Regulatory and Safety Evaluation Specialty Section
Women in Toxicology Special Interest Group
Drug development is a highly regulated but science-driven process
from early discovery to marketing. Once the drug candidate has been
discovered, preclinical safety evaluations are required to ensure the
safety of the drug during clinical trials, ultimately bridging the gap
between drug discovery and marketing. The preclinical development
of four types of drugs, small molecular-weight drugs, biologics, oligonucleotide-based
therapeutic drugs, and antibody drug conjugates
(ADCs), will be illustrated to emphasize the cross-functional nature
of regulatory sciences. In exploration of this important topic, we will
begin with a focus on small molecular-weight drug candidates, which
require a sliding scale for the degree of development from relatively
minimal regulatory requirements for oncology drug development to
the much more stringent requirements for the development of drugs
for nonlife, threatening conditions and chronic treatment. Next the
focus will shift to large molecule biologics and will provide illustrations
of the unique challenges the regulatory safety assessment and
clinical development that biologic drug candidates present. Our panel
of experts will then focus on oligonucleotide-based therapeutics since
many of the overarching oligonucleotide class-based properties have
been well established, but there unique considerations remain for
each subclass of oligonucleotide. This talk will discuss the preclinical
development of oligonucleotide-based therapeutic drugs, including
antisense, siRNA, and immunostimulatory and aptamer applications.
This course will also cover ADCs, which are composed of monoclonal
antibodies (biologics) conjugated with drugs or cytotoxins (small
molecules). Standard approaches for preclinical safety evaluation of
each of the individual components of these conjugates may not always
be necessary. The regulatory expectations for this class of therapeutics
are continuing to be defined. We will illustrate the safety assessment
challenges and development strategies associated with certain ADCs.
• Regulatory Sciences: Preclinical Drug Development from Small
Molecules to Biologics. Tao Wang, Novartis Pharmaceuticals,
Emeryville, CA.
• The Preclinical Development of Low Molecular Weight Drugs—
Comparison of Oncology and Nononcology Indications.
W. David McGuinn, US FDA, Silver Spring, MD.
• Safety Assessment and Clinical Development of
Biopharmaceuticals. James D. Green, Boehringer Ingelheim
Pharmaceuticals, Inc., Sudbury, MA.
• Development of Oligonucleotide Therapeutics and Its
Toxicological Considerations. Page Bouchard, Novartis Institutes
for BioMedical Research, Cambridge, MA.
• Development Strategies and Safety Assessment of Antibody Drug
Conjugates. Kimberly A. Stickland, Biogen Idec., Inc., San Diego,
CA.
Specialized Techniques for Dose-Response
Assessment and Risk Assessment of
Chemical Mixtures
PM12
CE Advanced
Chairperson(s): Jane Ellen Simmons, US EPA, Research Triangle
Park, NC, and Michael J. DeVito, NIEHS, Research Triangle Park, NC.
Sponsor:
Mixtures Specialty Section
Endorsed by:
Food Safety Specialty Section
Regulatory and Safety Evaluation Specialty Section
Risk Assessment Specialty Section
A variety of methods are available for chemical mixtures risk assessment.
A key step is careful consideration of data quantity and quality
to guide the type of assessment done. Whole mixture methods will be
summarized that, after considering data quality and quantity, do not
differ from single chemical methods. The principal uncertainty for
“sufficiently similarity” is ascertaining that two mixtures are sufficiently
similar so that one may be used as a surrogate of another. Two
approaches for a group of similar mixtures will be reviewed, comparative
potency and geographic site-specific assessment. The course
will focus on component-based methods (toxic equivalency factors,
relative potency factors, binary weight of evidence, hazard index,
target-organ toxicity hazard index, interaction-based hazard index)
as they are the most frequently performed mixtures assessments.
They use single-chemical toxicity and exposure data, with possibly
some toxicity information on defined mixtures of the chemicals of
interest. For each method (whole mixture and component-based), the
presenter will describe data requirements, assumptions, and limitations
and illustrate the application by example. Upon conclusion,
students will be able to navigate the risk assessment flow chart, have
an understanding of the assumptions, limitations, and uncertainties
underlying the presented approaches, and be able to either apply the
presented methods to their own data, or consult more knowledgeably
with risk assessors. The methods and approaches are applicable to the
CE
up-to-date information at www.toxicology.org 59
CE Target Area