Module 9 2024

03/09/2024

Regulatory Review - ISI

Immunogenicity related data: presented in multiple parts of the eCTD (e.g., manufacturing, non-clinical, clinical). Multi-disciplinary approach (PK, PD, ...) From a reviewer’s perspective: often difficult to understand the rationale of the immunogenicity studies and to find the relevant data → unnecessary questions by the assessors (delay and impact on the outcome of the review) → Introduction of an Integrated Summary of Immunogenicity (ISI). Used as a ‘living’ document, populated with relevant information over time.

• 1.8.2 Risk management plan • 2.7.2.4 Special studies

• 2.7.3 Summary of clinical efficacy • 2.7.4 Summary of clinical safety • 5.3.1.4 Reports of bioanalytical and analytical methods for human studies • 5.3.3 & 5.3.5 Clinical study reports (incl. raw ADA data from ADA testing) • 5.3.5.3 Integrated summary of immunogenicity

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Guidelines - European Medicines Agency (EMA)

• Guideline on Immunogenicity Assessment of Therapeutic Proteins EMEA/CHMP/BMWP/14327/2006 Rev.1 Final document released 2017

• Guideline on immunogenicity assessment of monoclonal antibodies intended for in vivo clinical use.

EMA/CHMP/BMWP/86289/2010 Final document released 2012

• Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: non-clinical and clinical issues. EMEA/CHMP/BMWP/42832/2005 Rev1 Final document released 2015

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