Spring Intro 2023

06/03/2023

ICH Preclinical Biotechnology Guidelines

• M3(R2) Non-clinical safety studies for the conduct of human clinical trials and marketing authorisation for pharmaceuticals

• S6 Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals (1997 & 2012)

• S9 Nonclinical Evaluation for Anticancer Pharmaceuticals – Potentially relevant to other end stage/high mortality indications

• CHMP guideline on strategies to identify and mitigate risks in first-in human studies and early clinical trials with investigative medicinal products (EMEA/CHMP/SWP/28367/07rev1) .

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ICH S6 - Conventional preclinical approaches may not be appropriate for biopharmaceuticals

Species Selection

Immunogenicity

 Use Relevant species ● Appropriate receptor or epitope needs to be expressed  Consider use of transgenic animals expressing the human receptor or the use of homologous proteins  Sample size problems can occur ● Primate studies

 Use validated and sensitive assay to measure antibodies

 Characterise responses as neutralising or non-neutralising

 Antibody formation should not be the sole criterion for the modification of duration or early termination of a preclinical safety study

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