Module 3 Presentations

14/05/2024

Starting materials (SM): Key issues

One of the most frequent Major Objections:  Short synthetic routes  Custom-synthesised starting materials  Few synthetic steps (esterification, salt formation, protection / deprotection)  Insufficient information to assess:  the suitability of SM specification/analytical controls  the impact of material quality to the upstream synthesis and the quality of final drug substance  the introduction and carryover of impurities

 Information on key synthetic steps omitted or SM defined late stage beyond significant chemical transformations

The Organisation for Professionals in Regulatory Affairs

19

Starting materials: What’s the problem?

Major Objection: request to redefine regulatory SM to an earlier stage in the synthesis  Regulator: Limited number of steps under GMP leads to concerns over insufficient control/regulatory oversight. Applicant: Manufacturing decisions already taken – so problematic for applicant with respect to supply chain definition. 

SM redefinition may translate to lengthy delays.

The Organisation for Professionals in Regulatory Affairs

20

10