CEP for Sterile Drug Substances: EDQM issues Draft Guidance for Content of Dossier

EDQM has published the draft guideline on Content of the dossier for sterile substances for public consultation.

For a sterile drug substance (API), sterilisation process should be described in CEP application along with data for validation of sterilisation method in the dossier. Sterilisation of active substances is regarded as part of finished product manufacture. So much so that the sterilisation process and validation data should also be shared with the Marketing Authorisation (MA) applicant for finished drug product. If both sterile and non sterile substances are produced by an applicant (or manufacturer), separate CEP dossiers shall be submitted and separate CEP will be granted, with subtitle Sterile for the sterile substance.

For a sterile substance the ICH Q7A – Good 12 Manufacturing Practice for Active Pharmaceutical Ingredients is only applicable upto point immediately prior to the material is rendered sterile; for sterilisation and aseptic processing the EU GMP for Medicinal products including Annex 1 is applicable. (Refer: GMP (Good Manufacturing Practices) – Medicinal Products and Active Pharmaceutical Ingredients (APIs) guidance’s)

Applicants for CEP shall provide information on sterile manufacturing process in section 3.2.S.2.5 of the dossier. The information should include the justification for method of sterilisation – sterile filtration, dry heat sterilisation, sterilisation by the use of ionising radiation or by the use of ethylene oxide gas

When aseptic preparation/sterile filtration is used, information of sterilisation process shall include manufacturing areas and compliance with Annex 1 of Eudralex Volume 4, EU GMP for Medicinal products. Schematic description of the sterilisation process steps till packing of the sterile active in final container (from dissolution to filtration and isolation drying, blending and filling in containers) shall be provided. Details of filters used and filtration conditions shall also be included. Validation data for the filters used (both sterile and non sterile), microbial challenge tests shall be provided. Filter compatibility and potential extractables/leachables data to prove no toxicologically relevant amounts of extractables or leachables are released from the filters into the filtered solution shall be provided. Data shall also be provided on reuse of filters and bulk holding time.

Media fill studies data for three recent studies and frequency of media fill studies should be included. Details of the methods used to sterilise the packaging components are to be provided and integrity of packaging should be validated. If a retest period is claimed in the application, stability study should include sterility testing at the end of the retest period

The draft document shall be available for public consultation till 15 August 2024 and after consultation phase final guidance will be made available.

EDQM / CEP:  Content of the dossier for sterile substances, (Draft Guidance – PA/PH/CEP (23) 54, draft 4, May 2024)