CRED Getting the CMC Dossier Right 2024

28/08/2024

Lifecycle FPS (1)

• Limited data may be available at time of filing which influences specification setting

• FPS is part of continuous improvement, needing revision as manufacturing experience is gained and changes to API, excipients, container closure system, manufacturing facilities and analytical methods

• ICH Q14 Technical and Regulatory Considerations for Pharmaceutical Product Lifecyle Management

• FPS is defined as an Established Condition that assures product quality • Requires a regulatory communication, if changed • Major change, prior approval - e.g. widening of acceptance limits • Minor change, prior approval - e.g. adding/replacing a test method resulting from a safety/quality issue • Notifications, no prior approval – e.g. Adding new test, tightening acceptance limits, complying with pharmacopoeia, etc.

Decreasing impact on product

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Commercial FPS

US JP

EU

EU

Test

Test methods

Release

Shelf-life

Stability

Appearance

Visual

White, round, flat tablet. 7.5mm dia. x 5mm

White, round, flat tablet. 7.5mm dia. x 5mm

White, round, flat tablet. 7.5mm dia. x 5mm

Identification

IR

Complies with reference

Complies with reference

Not tested

HPLC-UV

Complies with reference RT

Complies with reference RT

Not tested

Assay

HPLC-UV

95.0% to 105.0%

93.0% to 105.0%

93.0% to 105.0%

Related substances

Impurity A

0.2%

0.5%

0.5%

Unspecified

HPLC

0.2%

0.2%

0.2%

Total impurities

1.0%

2.0%

2.0%

Dissolution, 45 min

Ph. Eur. 2.9.3

Q=80%, 30 min

Q=80%, 30 min

Q=80%, 30 min

Uniformity of dosage units

Ph. Eur. 2.9.40

Complies

Complies

Not tested

Water

Ph Eur 2.5.12

0.5%

1.0%

1.0%

TAMC 10 3 CFU/g TYMC 10 2 CFU/g Absence of E. coli

TAMC 10 3 CFU/g TYMC 10 2 CFU/g Absence of E. coli

TAMC 10 3 CFU/g TYMC 10 2 CFU/g Absence of E. coli

Microbial quality (annually or every 10 th batch whichever is sooner)

Ph. Eur. 2.6.12 & 2.6.13

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