CRED Getting the CMC Dossier Right 2024

28/08/2024

The Clinical FPS

• Clinical FPS should be phase appropriate and reviewed according to current state of development and available data • EU focus is predominantly patient safety for IMPs • In contrast, US increases contribution of CMC/quality development data on the IND in phase 2/3 • FPS starts resembling “to be filed” specification as clinical development progresses to Phase 3 • Following are mandatory tests: • Identity | Assay | Degradation products • Formulation specific tests should be included, as appropriate • e.g. disintegration/dissolution for OSDs; UoD; pH, endotoxins and sterility for parenterals

• Acceptance limits base on available CMC data and pre-clinical data • Wider limits are permissible. e.g. assay 90%-110% vs. 95.0%-105.0% • Disintegration in lieu of dissolution

• Analytical method described and suitability confirmed/demonstrated (full validation not required)

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The Clinical FPS - Phase 1 to Phase 3

Test

Test methods

Release specification

Appearance

Visual

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

Identification

IR

Complies with spectra of reference standard

Test

Test methods Release

specification

HPLC-UV

Complies with RT of reference standard

Appearance

Visual

White, round tablet

Identification

HPLC

Complies with RT of reference

Assay

HPLC-UV

90% to 110% LC

Related substances

Assay

HPLC

90% to 110% LC

Impurity A

0.5%

Related substances

Unspecified

HPLC-UV

0.2%

Individual

2.0%

HPLC

Total

2.0%

Total

5.0%

Dissolution

Ph Eur 2.9.3

Q=80%, 30 min

Disintegration

Ph. Eur. 2.9.1 Complies

Uniformity of dosage units

Ph Eur 2.9.40

Complies

Water

Ph Eur 2.5.12

1.0%

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

Microbiological quality

Ph Eur 2.6.12 & 2.6.13

The Organisation for Professionals in Regulatory Affairs

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