CRED Getting the CMC Dossier Right 2024

28/08/2024

3.2.P.2 Pharmaceutical Development

General biowaiver criteria: Article 4.1.6 BE Guideline

a) the pharmaceutical products are manufactured by the same manufacturing process, b) the qualitative composition of the different strengths is the same, c) the composition of the strengths are quantitatively proportional. If deviations, condition c is still considered fulfilled if condition i) and ii) or i) and iii) are met:

i) the amount of the active substance(s) is less than 5 % of the tablet core weight or capsule content;

ii) the amounts of the different core excipients or capsule content are the same for the concerned strengths and only the amount of active substance is changed;

iii) the amount of a filler is changed to account for the change in amount of active substance. The amount of other excipients is the same between strengths.

Alejandro Montón Silva

The Organisation for Professionals in Regulatory Affairs

15

3.2.P.2 Pharmaceutical Development

Analytical conditions biowaiver of strength: Annex III-Point IV.1.1 BE Guideline

• Apparatus and speed: paddle (50 rpm) or basket (100 rpm)

• Volume of dissolution medium: 900 ml or less

• Temperature of the dissolution medium: 37±1 °C

• Sampling schedule: e.g. 10, 15, 20, 30 and 45 min

• pH: 1.0-1.2, 4.5 and 6.8

• NO SURFACTANTS

• Use of enzymes acceptable for gelatin capsules/gelatin-coated tablets

• Impact of excipients with effect on GI absorption (sorbitol, mannitol, SLS…) should be discussed

Alejandro Montón Silva

The Organisation for Professionals in Regulatory Affairs

16