The European Directorate for the Quality of Medicines & HealthCare (EDQM) is updating its policy concerning the acceptability of CEP applications for sterile active substances.
Until now, acceptability requirements have applied to the manufacturing processes only when the manufacturer of the non-sterile active substance carried out the sterilisation operations – required to obtain the sterile grade – in house.
They now also apply in cases when the sterilisation process of the active substance is outsourced to an external manufacturer and/or where a crude or non-sterile substance is purchased from an external supplier and subjected to purification and/or salt formation before sterilisation.
Applicants are asked to bear the following points in mind.
- Companies involved in the sterilisation steps and aseptic handling of APIs should work according to EU GMP rules Part I and Annex 1. The manufacturing site(s) involved will be inspected by the EDQM (and the relevant inspection fees will apply) unless (i) evidence is provided that these manufacturing site(s) undergo routine inspections by an EU regulatory authority and (ii) a valid GMP certificate in compliance with the EU GMP rules Part I and Annex 1 has been issued covering the substance for which an application has been submitted.
- Sterilisation of the API is generally regarded by licensing authorities as part of the manufacturing process for finished medicinal products. Therefore, data on the active substance sterilisation process (including validation data) should be shared with the marketing authorisation applicant/holder for inclusion in the marketing authorisation application, even if the data package has been evaluated by the EDQM.
- This change applies to new CEP applications and to approved CEPs (through a request for revision).