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Navigable Slide Index

1. Introduction
2. Agenda
3. Goals of preclinical safety evaluation
4. Differences defined by product attributes
5. Product attributes differences "in general"
6. "A blurring of product attributes"
7. Composite of product attributes
8. Predicting human risk
9. Toxicological concerns in biopharmaceuticals
10. ICH guidance for safety evaluation
11. What is "case-by-case" approach
12. Principles vs. practices
13. "Case-by-case" approach (across product classes)
14. "Case-by-case" approach (within a product class)
15. Species / animal model selection
16. Key considerations in model selection
17. Dose response for biopharmaceuticals
18. Immunogenicity in biopharmaceuticals
19. Effects of "clearing" antibodies
20. Effects of "sustaining" antibodies
21. Drug induced neutralizing antibodies
22. General toxicity
23. General toxicity considerations
24. Reproductive and developmental toxicity studies
25. Reproductive toxicity: species selection
26. Reproductive toxicity: fertility
27. Reproductive toxicity: EF/PPND
28. Infliximab
29. Daclizumab
30. Reproductive toxicity: communicating risk
31. Carcinogenicity assessment: purpose
32. Carcinogenicity: a variety of approaches
33. Carcinogenicity assessment: how and when
34. Carcinogenicity: alternative approaches
35. Carcinogenic risk: cause for concern
36. Assessment of carcinogenic risk
37. Communication of carcinogenic risk
38. Specific considerations: ERTs
39. Specific considerations: mAbs
40. Specific considerations: ODNs
41. FDA guidance for estimating MRSD
42. First in human dose selection (1)
43. Estimating safe starting dose
44. First in human dose selection (2)
45. FIH/FIP dose selection: consideration of exposure
46. NOAEL vs. MABEL approach
47. Acceptable dose multiples
48. Addendum to ICH S6
49. Intended outcomes of the addendum
50. Safer medicine - changing current culture
51. Safer medicine - increasing dialogue
52. Conclusions
53. Acknowledgements
54. References (1)
55. 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

Series:

• Non-Clinical Testing for Toxicity of Pharmaceuticals

Categories:

• Clinical Practice
• Pharmaceutical Sciences

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 June 5, 2023, from https://hstalks.com/bs/1353/.
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Publication History

• Published on July 30, 2009

Financial Disclosures

• Dr. Joy Cavagnaro has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.