Quality and Release Criteria:

A[n ex-]Regulators Perspective

Christopher A Bravery
cbravery@advbiols.com

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 Introduction

ü  Importance of characterisation

ü  Physicochemical
ü  Biological
ü  Specifications
ü  Basic expectations
ü  Dealing with limitations
ü  Final thoughts

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 Common Technical Document (CTD)

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 Characterisation

Physicochemical Characterization
Select Product
tests Specification

Biological Characterisation

Identify  possible
relevant  physicochemical
Identify possible biological characteristics
characteristics
[Assumed] Mechanism of Action

Working Theory

Non-clinical
Clinical data Literature
models

ITERATIVE PROCESS

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 Specifications: Product

Generally based on
same approach

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 Process Characterisation

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 Methods

See ICH Q2
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 Don’t Forget Reference Materials

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 Using the results: Specifications
Stability
data
Literature Product
Knowledge Product

Non-clinical
Starting/raw
data Characterisation materials
Clinical data
data
Process

Manufacturing Product
Stability Specification
experience knowledge

What’s been Safety

limitations Justification
achieved considerations

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 Potency: A Key Specification

Comparability Physicochemical Characterization Stability Studies

Final Product
Key
Product Extended In vitro test/s and Identity, purity, shelf-life, shipping
physicochemical
Specification Characterisation assay/s impurities, other. validation, in-use
characteristics Select
Additional stability.
tests
useful
tests
Comparability Product Stability
Protocol Specification
Biological Characterisation

Product Stability In-process stability

In vitro bioassay/s
Specification controls indicating
Relevant
Select Product
biological Potency assay/s
Select tests Specification
function/s
test/s
In vivo bioassay/s

Product
compatibility
Identify possible biological characteristics

[Assumed] Mechanism of Action

Final Product
container, delivery
Working Theory system, other
device

Compatibility
Non-clinical Studies
Clinical data Literature
models

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 The Importance of Characterisation

http://www.advbiols.com/documents/
11 ImportanceofCharacterisation.swf
Comparability Overview
 Extended Characterisation

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 ICH guidelines (core principles)

14 http://www.advbiols.com/documents/ICH.swf
 EMA guidelines

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

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 Final Thoughts

ü  Specifications are set to control and confirm the quality

of the product for a specific qualified/validated process.
ü  Specifications are set based on manufacturing
experience and all other relevant information.
ü  Change the process and the specification may no longer
be adequate to confirm or control quality.
ü  Comparability may need enhanced testing to confirm
the product didn’t 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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