In line with the Marketing Authorisation Holder's (MAH) obligation to keep the dossier up to date, a new or updated Certificate of Suitability (CEP) for an active substance (AS), excipient or starting material/reagent/intermediate used in the manufacturing process of the AS should be submitted as a variation. It is however understood that only the versions of the CEP (i.e. updated certificates) which were used in the manufacturing process of a batch of finished product (FP)/ AS need to be included in the dossier.
CEP updates should be submitted under the appropriate variation classification scope within subsection B.III.1. Each CEP update should be submitted as a variation scope, i.e. an update covering more than one CEP version should be submitted as a grouped variation.
When applying for an update of an approved CEP, the MAH should refer to the previously agreed version of the CEP within the 'Present/Proposed' section of the application form.
If with the submission one or more revisions of the CEP are omitted, the MAH should confirm in the variation application form (section 'Precise scope and background for change') that substance/material from the omitted CEP version(s) was not used in the manufacture of the FP and/or AS during the validity of this certificate(s). Additionally it should be confirmed that any changes introduced by the omitted CEP update(s), do not affect the quality of the AS and/or FP. In case such confirmation is missing, a negative Type IA notification may be issued.
The MAH should also clearly indicate in the 'Present/Proposed' section all changes introduced in the CEP between the latest approved version and the new revision, including all revisions that were not notified. Any changes e.g. to manufacturing sites, additional residual solvents introduced in the CEP by subsequent updates should be declared.
Example:
Submission of an updated CEP version for an already approved manufacturer: R0-CEP-xxxx-xx-rev.02 when the current certificate in the dossier is: R0-CEP-xxxx-xx-rev.00.
If, during the validity of R0-CEP-xxxx-xx-rev.01, material of the CEP was used in the manufacture of the FP and/or the AS, then the MAH should submit a grouping of two IA variations to include both certificates (rev. 01 and rev. 02) in the Module 3 or Part 2 (NTA). The foreseen conditions for each of the respective variations should be met.
If, during the validity of R0-CEP-xxxx-xx-rev.01, material of the CEP was not used in the manufacture of the FP and/or AS, the MAH should only submit a single Type IA variation to include the updated certificate R0-CEP-xxxx-xx-rev.02 in Module 3 or Part 2 (NTA). The foreseen conditions for the variation should be met.
The MAH should also confirm in the variation application form that material/substance from R0-CEP-xxxx-xx-rev.01 was not used in the manufacture of the FP and/or AS during the validity of this certificate and that changes introduced by the revision R0-CEP-xxxx-xx-rev.01 do not affect the quality of the AS and/or the FP. MAH should also clearly list within the 'Present/Proposed' section of the application form all changes introduced to the CEP with revisions 01 and 02.