GMP certificate: proof of good manufacturing practice compliance

Article 111(5) of Directive 2001/83/EC requires the competent authority to issue a certificate of good manufacturing practice within 90 days of an inspection if the inspection shows that the manufacturer complies with the principles and guidelines of GMP. The principles are set out in Commission Directive (EU) 2017/1572 for medicinal products and in Commission Delegated Regulation (EU) 2017/1569 for investigational medicinal products, and the detailed guidelines are in EudraLex Volume 4: Part I for finished products, Part II for active substances, Part III for GMP-related documents and the annexes, including Annex 16 on certification by a qualified person. Certificates are entered in the EudraGMDP database, as are statements of non-compliance.

A certificate records the site, the scope of the inspection (dosage forms, operations such as sterile manufacture or packaging, and active substances where applicable) and the inspection date. It is not a licence: the manufacturing and importation authorisation is the legal permission to operate, while the certificate is evidence that a particular inspection found the site compliant. Third-country sites are inspected by an EU authority on behalf of the Union, or recognised through a mutual recognition agreement, and their certificates also appear in EudraGMDP.

Applicants rely on certificates in marketing authorisation applications and variations: Module 1 includes a declaration by the qualified person that the active substance manufacturer complies with GMP, and the authority checks EudraGMDP for the finished product site. A current certificate, or an inspection in the last three years, is what assessors expect to see before a new site is accepted; otherwise a pre-approval inspection is requested and the procedure waits for it.

What goes wrong: a certificate on file has expired in practice because the last inspection is more than three years old, and the national authority asks for a new inspection at the point of the variation; a contract manufacturer's certificate covers packaging but not the sterile operation now proposed; a non-compliance statement issued to a site is noticed only when a batch is held at import; and certificates for third-country sites are assumed to be mutually recognised when the MRA covers only certain product types. Watching EudraGMDP and reading the scope line are the two checks that catch most problems.