Spring Intro 2023

06/03/2023

Annex I of 2001/83/EC ANALYTICAL, PHARMACOTOXICOLOGICAL AND CLINICAL STANDARDS AND PROTOCOLS IN RESPECT OF THE TESTING OF MEDICINAL PRODUCTS

Non-Clinical: • Rationale for species and animal models • PD ‘Proof of Concept’ (Biodistribution with functional activity monitored) • Target Selectivity • Biodistribution (Persistence, Clearance and Mobilisation) and Germline Transmission • Shedding and Risk of Transmission (Environmental Risk Assessment) • Integration • Immunogenicity / Immunotoxicity

Clinical: • Concomitant Therapy / Surgical Procedures • Training plan for healthcare professionals • Long-term follow-up of safety and efficacy • Shedding • Persistent expression

Quality: Risk-based approach Traceability Starting materials Characterisation Product and process related impurities

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Quality Guidelines – Similarities to Other Biological Products

Since gene therapy products contain genetic and other biological materials, many of the quality, efficacy and safety considerations which apply to other modern biotechnological products will apply to some stages in their manufacture. • Amplification in a host raises concern over homogeneity of the amplified product • All components of the transfer vector should be appropriated characterised. • Replication ability of viral vectors is an issue. • Gene Therapy Product Quality Aspects in the Production of Vectors and Genetically Modified Somatic Cells

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