Quality and Release Criteria: A[n ex-]Regulators Perspective

Christopher A Bravery
cbravery@advbiols.com

Introduction
Importance of characterisation Physicochemical Biological Specifications Basic expectations Dealing with limitations Final thoughts

Common Technical Document (CTD)

Characterisation

Physicochemical Characterization
Select tests Product Specification

Biological Characterisation
Identify possible relevant physicochemical characteristics

Identify possible biological characteristics

[Assumed] Mechanism of Action

Working Theory

Non-clinical models

Clinical data

Literature

ITERATIVE PROCESS

Specifications: Product

Generally based on same approach

Process Characterisation

Methods

See ICH Q2
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Dont Forget Reference Materials

Using the results: Specifications

Literature

Product Knowledge
Clinical data Characterisation data

Stability data Product Starting/raw materials Process

Non-clinical data

Manufacturing experience

Stability

Product knowledge

Specification

Whats been achieved

limitations

Safety considerations

Justification

Potency: A Key Specification

Comparability
Product Specification Extended Characterisation Additional useful tests Comparability Protocol

Physicochemical Characterization
In vitro test/s and assay/s Key physicochemical characteristics Identity, purity, impurities, other.

Stability Studies
Final Product shelf-life, shipping validation, in-use stability.

Select tests

Biological Characterisation
In-process controls In vitro bioassay/s Relevant biological function/s In vivo bioassay/s Select tests

Product Stability Specification

Product Stability Specification

stability indicating Potency assay/s Product Specification

Select test/s

Identify possible biological characteristics

Product compatibility

[Assumed] Mechanism of Action

Working Theory

Final Product container, delivery system, other device

Non-clinical models

Clinical data

Literature

Compatibility Studies

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The Importance of Characterisation

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http://www.advbiols.com/documents/ ImportanceofCharacterisation.swf

Comparability Overview

Extended Characterisation

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ICH guidelines (core principles)

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http://www.advbiols.com/documents/ICH.swf

EMA guidelines

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http://www.advbiols.com/documents/EUguidelines.swf

European Pharmacopoeia
http://www.advbiols.com/documents/PhEur.swf

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Final Thoughts
Specifications are set to control and confirm the quality of the product for a specific qualified/validated process. Specifications are set based on manufacturing experience and all other relevant information. Change the process and the specification may no longer be adequate to confirm or control quality. Comparability may need enhanced testing to confirm the product didnt change (specifications only valid for the qualified/validated process) and to confirm the specifications are still valid, or how they need to change.

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