So are you preparing and filing a Marketing Authorisation Application (MAA) in Europe? What needs to be considered and what timelines do you need to work towards?

Active Pharmaceutical Ingredients or APIs must be manufactured in compliance with EU GMP and this compliance is confirmed by the QP declaration, which is submitted with the MAA. Such a declaration is required from each EEA finished product manufacturing site and/or from each site of importation/batch certification to confirm that the active substance has been manufactured in accordance with the EU-GMP Guide, Part II: Basic Requirements for Active Substances used as Starting Materials. The basis for this declaration will be examined during EU GMP inspections at the site of batch release. The EMA has issued a QP declaration template to help enhance the efficiency of the regulatory process and prevent any questions during the assessment phase.

So, what do you need to consider as the QP signing the declaration? Are you confident that all of the API sites meet the requirements of EU GMP? Are there available audits to support this? At what stage do you need to consider planning for the audits at the API manufacturer?

The QP declaration should be based upon an audit of the active substance manufacturer, however, there are no specific requirements around the use of third party audits to support the QP declaration. As the QP, it is important that you consider the suitability of the auditor- ensure you review the auditor CV to satisfy yourself that they have the relevant experience and training for conducting the audit. Ideally, the audit agenda is agreed by the QP in advance or if not, verify that the agenda covers all of the necessary areas within the scope of the audit.

Has the supply chain for the API been completely established? All sites involved in the manufacture of the API must be listed with their address and relevant function  i.e. complete synthesis, intermediate synthesis, micronisation etc. In the case of an intermediate which is itself an active substance and is supported by either an independent Active Substance Master File (ASMF) or Certificate of Suitability (CEP), the manufacturing sites of the intermediate should also be registered in the marketing authorisation and be the subject of a QP declaration. Of critical importance is the identification of the stage in the API supply chain where “Active Substance Starting Materials” are entered into the process- it is from this point that the QP declaration is expected to cover.

Audits of sites involved in API manufacture must have been completed normally within the last 3 years and an on-site audit is expected. Summary details of the audits must be included within the QP declaration. It is also possible that one QP can sign the declaration on behalf of all involved QPs where quality technical agreements are in place underpinning GMP responsibilities. In order to meet the timelines of the MAA, ensure you give yourself sufficient time to ensure quality technical agreements are in place outlining GMP responsibilities of all relevant parties and that audits have been scheduled by experienced auditors. Allow yourself time for a detailed review of the audit report (if conducted by third-party) following the report write-up including a review of the auditor CV. Start the planning process early to allow sufficient time for a QTA to be signed and to allow the scheduling of any required audits. Contact MIAS Pharma today for any advise or help in establishing this timeline.

If you would like to get in touch with MIAS Pharma, please email info@miaspharma.com or call us on +353 (1) 846 3605.