Module 9 2021

22/03/2021

1ST STEP TO ADDRESS RESIDUAL UNCERTAINTY = IMPACT OF CQA DIFFERENCES

PK

Efficacy

Theoretical General literature Literature on reference product Studies on biosimilar Mass contribution

Immunogenicity

Safety

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CRITICALITY ASSESSMENT OF QUALITY ATTRIBUTES INITITIALLY PROPOSED BY FDA

• 2/3 Indicator non granular attributes that directly impact safety/potency • e.g. bioactivity, receptor binding

These required to fall within +/- 1.5 SD for results from multiple reference product batches. Quality range approach generally ±3SD based on

Very High Tier 1

• Non Tier 1 attributes that have at least some potential impact on safety/ potency

High Tier 2

multiple reference product batches.

• Non quantitative or heavily granular or attributes with low/no impact on potency PK/safety/immunog. e.g. fully active natural variants

Descriptive Graphical display

Low Tier 3

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15