CRED Getting the CMC Dossier Right 2024

28/08/2024

Drug Substance – Quality Attributes

Microbial limits

● DS capable of supporting growth - Water activity determination

● Synthetic route has steps which reduce micro-organisms?

● If need a spec, use pharmacopoeial limits

● Can justify no testing or periodic testing

(ICH Q4B Annex 4 A, B, C)

Sterility

● Ph.Eur. 2.6.1. Sterility, JP 4.06 Sterility Test, USP <71> (ICH Q4B Annex 8)

● Decision Trees in ICH Q6A very useful to define impact and guide development

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Analytical Methodology

No universal list of ‘acceptable’ methods

Techniques can be divided into

● Qualitative (Meets test)

● Semi ‐ quantitative (Limit tests)

● Quantitative (Reports a numerical value or quantity)

All analytical methods should be scientifically sound/fit for purpose

- Supporting development understanding or specification control

- Appropriately validated – increasing rigour as development progresses to full ICH validation at time of NDA

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