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Printable Handouts
Navigable Slide Index
- Introduction
- Agenda
- Goals of preclinical safety evaluation
- Differences defined by product attributes
- Product attributes differences "in general"
- "A blurring of product attributes"
- Composite of product attributes
- Predicting human risk
- Toxicological concerns in biopharmaceuticals
- ICH guidance for safety evaluation
- What is "case-by-case" approach
- Principles vs. practices
- "Case-by-case" approach (across product classes)
- "Case-by-case" approach (within a product class)
- Species / animal model selection
- Key considerations in model selection
- Dose response for biopharmaceuticals
- Immunogenicity in biopharmaceuticals
- Effects of "clearing" antibodies
- Effects of "sustaining" antibodies
- Drug induced neutralizing antibodies
- General toxicity
- General toxicity considerations
- Reproductive and developmental toxicity studies
- Reproductive toxicity: species selection
- Reproductive toxicity: fertility
- Reproductive toxicity: EF/PPND
- Infliximab
- Daclizumab
- Reproductive toxicity: communicating risk
- Carcinogenicity assessment: purpose
- Carcinogenicity: a variety of approaches
- Carcinogenicity assessment: how and when
- Carcinogenicity: alternative approaches
- Carcinogenic risk: cause for concern
- Assessment of carcinogenic risk
- Communication of carcinogenic risk
- Specific considerations: ERTs
- Specific considerations: mAbs
- Specific considerations: ODNs
- FDA guidance for estimating MRSD
- First in human dose selection (1)
- Estimating safe starting dose
- First in human dose selection (2)
- FIH/FIP dose selection: consideration of exposure
- NOAEL vs. MABEL approach
- Acceptable dose multiples
- Addendum to ICH S6
- Intended outcomes of the addendum
- Safer medicine - changing current culture
- Safer medicine - increasing dialogue
- Conclusions
- Acknowledgements
- References (1)
- References (2)
Topics Covered
- Optimization of the clinical development of biopharmaceuticals over the past two decades has relied upon the careful design and judicious use of animals in preclinical studies
- This is not only to allow for the early initiation of clinical studies but to support an uninterrupted clinical development program
- The approach has been referred to as "case-by-case", an approach which is science-based, question-based, experience-based and targeted based upon product attributes
Links
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Talk Citation
Cavagnaro, J. (2009, July 30). Preclinical safety evaluation of biopharmaceuticals: science-based approach of facilitating clinical trials [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved October 13, 2024, from https://doi.org/10.69645/JMBU4818.Export Citation (RIS)
Publication History
Financial Disclosures
- Dr. Joy Cavagnaro has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Preclinical safety evaluation of biopharmaceuticals: science-based approach of facilitating clinical trials
Published on July 30, 2009
46 min
A selection of talks on Clinical Practice
Transcript
Please wait while the transcript is being prepared...
0:00
Preclinical Safety Evaluation
of Biopharmaceuticals.
A Science-Based Approach to
Facilitating Clinical Trials.
Joy Cavagnaro,
President, Access BIO,
Boyce, Virginia.
0:14
This presentation will
outline the goals
of preclinical
safety evaluation,
highlight the differences
between pharmaceuticals
and biopharmaceuticals
based upon a consideration
of product attributes,
discuss what was
considered, at the time,
a new approach to preclinical
safety evaluation,
distinguishing principles
versus practices,
and establishing the
why for case by case.
I'll also outline the key
considerations of study design,
including species and
animal model selection
and the use of
surrogate molecules,
as well as establishing
dose response.
I will discuss the impact
of the immune response
and provide an overview of
the relevance of icities,
including general
toxicity, immunogenicity,
genetic toxicity,
reproductive and
developmental toxicity,
as well as carcinogenicity,
and highlight specific
considerations
based upon selected
product classes.
I'll also provide some insights
as to how best to select
the first-in-human dose,
as well as discussing
an opportunity
for realizing safer medicines.
1:20
The goals of preclinical
safety evaluation
include optimization of
lead candidate selection,
allowing for an early
introduction of new compounds
into clinical trials by
recommending initial starting dose
and dose escalation
scheme in humans,
identifying potential target
organ or organs of toxicity,
and identifying appropriate
parameters to monitor
in the clinic for
any delayed effects.
And to look for reversibility,
if there are effects,
and to identify
at-risk populations.
The goals also include ensuring
an uninterrupted
clinical development,
as well as providing data
in time for decision making
throughout the various
phases of clinical trials,
including Phase 1, 2,
and 3 clinical trials,
and ultimately, for
product labeling.
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