13/14 December 2023
More than three years ago, the EMA has published two draft documents for a template for the QP's declaration concerning GMP compliance of the API used as starting material and verification of its supply chain called "The QP declaration template":
1. The draft template for the Qualified Person's declaration
2. the respective draft Q&A on the template for the Qualified Person's declaration
The QP Declaration should be provided in support of an application for a new marketing authorisation, variation or renewal of a medicinal product(s) authorised in the Community, using EU or national procedures within the scope of the respective Directives.
The consultation for the template ended on 30 April 2011. In June 2014, the final version was published together with a template guidance. Now, three months after publication of the final document, the comments from 2011 have been published.
The answers to these comments also give some useful and interesting background information on EMA's expectations when it comes to API supplier auditing and qualification.
The 93 page document shows that some comments provided by the various interest groups - like the European QP Association - have been taken into consideration, and a few suggestions for improvement have been implemented. When it comes to audit information, fewer details are requested now. Confirmation of the supply chain traceability has been deleted; the API "supply chain should be established, qualified and documented and addressed through GMP".
The wording of the draft declaration ''I have evaluated each of the named contract acceptors… …. Audit(s) was/were conducted by properly qualified and trained staff….'' has been changed to a more formal phrase, not implying the necessity for a personal check by the QP.
But EMA also declined many industry proposals for the QP Declaration:
Some stakeholders thought that most of information being requested in the template should be part of GMP audit or supplier qualification programme rather than to inclusion in a regulatory dossier submission. But the template is still part of the regulatory submission. And EMA still considers a maximum three year period for API audits as good practice. Exceptions to this standard might only be possible on a case by case basis, which cannot be generalised.
The wish that GMP certificates from a relevant Competent Authority can replace audits by the company will remain a wish. EMA refers to its Q&A document* where it is stated that audits should be performed by or on behalf of the Marketing Authorisation Holder or acceptable third party auditors. However "API manufacturing sites, which have been inspected by an EU Competent Authority and found GMP non-compliant, should not be used as sources of API". Audits by accredited audit bodies who audit on behalf of the contract acceptor are also not accepted. Furthermore the API supplier needs to be assessed and deemed satisfactory before purchase of the material. Only in exceptional cases, e.g. atypical actives, where the QP Declaration is not based on an on-site audit, then other documentation (not the QP template) will need to be submitted according to the guidance document and considered on a case by case basis. It will be possible to share API audits and audit reports, if supported by appropriate contract arrangements.
The fear of the European QP Association and other stakeholders, that disclosing (internal) audit reports during inspections by the Competent Authorities might trigger a process of parallel audit reports (one for the official part to show during inspection and in parallel a second one used internally) was not acknowledged. So GMP inspectors might request these audit reports during regulatory GMP inspections.
The request for a sufficient transition period of 24 months for the implementation of the QP declaration was declined ("not considered necessary").
EMA emphasises that the QP Declaration should cover the designated starting material, as shown in the summary of the route of synthesis given in the DMF. Some stakeholders thought it might be better to refer to an Active Substance Master File (ASMF) and limit the QP Declaration only to the API manufacturing site involved in the last quality relevant manufacturing step.