Module 3 Presentations

14/05/2024

3.2.S.2.4 Control of Critical Steps and Intermediates - 2  Risk based approach to identifying CQAs and hence critical steps, for example: o Reaction conditions on impurity formation o Crystallisation conditions on solid state form  Criticality Score = Impact x Uncertainty o Impact (safety/efficacy effects): Very High (20), High (16), Moderate (12), Low (4), Very Low (2) o Uncertainty (occurrence likelihood): Very High (7), High (5), Moderate (3), Low (2), Very Low (1) o Range 2 – 140; define threshold for CQA eg ≥100

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Identify CQAs by Risk Assessment

Criticality Score

Impact

Uncertainty

Quantitative measure for an attribute‘s impact on safety and efficacy. Using best possible surrogates for clinical safety and efficacy

Known or potential consequences on safety and efficacy, considering: •Biological activity •PK/PD

Relevance of information e.g. •literature •prior knowledge •in vitro •preclinical •clinical •or combination of information

•Immunogenicity •Safety (Toxicity)

Manufacturer‘s accumulated experience, relevant information, data e.g. literature, prior & platform knowledge, preclinical and clinical batches, in vitro studies, structure-function relationships

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