Most finished medicines placed on the Greek and EU market rely on active substances manufactured outside the Union. The Falsified Medicines Directive closed that door to unverified supply: an active substance imported into the EU must arrive with documented evidence that the site making it works to standards equivalent to EU GMP. The obligation sits with the importer, but the consequences land on the marketing authorisation holder and, ultimately, on the Qualified Person who certifies the batch.
The written confirmation: what it is and who issues it
Article 46b of Directive 2001/83/EC requires each consignment of imported active substance to be accompanied by a written confirmation issued by the competent authority of the exporting third country. It is not a supplier declaration and it cannot be written by the manufacturer. The confirmation must attest that:
- the GMP standards applied at the manufacturing plant are at least equivalent to those laid down in the Union;
- the plant is subject to regular, strict and transparent controls, including repeated and unannounced inspections;
- findings of non-compliance will be communicated to the Union without delay.
The European Commission publishes a template for the document. In practice, the most common failures are administrative rather than technical: a confirmation that names the wrong site address, omits one of the active substances actually shipped, or has expired against the underlying GMP certificate.
Where the requirement is waived
Article 111b allows a third country to ask the Commission to assess its GMP supervisory system. Where the assessment is positive, the country is added to a list and written confirmations are no longer required for imports from it. The countries and territories currently listed are Switzerland, Australia, Japan, the United States, Brazil, Israel, South Korea, Canada and Taiwan.
Two points are routinely misread. First, listing covers the country, not an individual site – it removes the paperwork, not the GMP obligation. Second, the list is short and stable, and it does not include several of the largest API-exporting jurisdictions. A separate, narrow waiver also exists where an EU Member State has itself inspected the exporting plant and found it GMP-compliant; that waiver runs only for the validity of the resulting GMP certificate.
Registration under Article 52a
Importers, manufacturers and distributors of active substances established in the Union must register their activity with the competent authority of their Member State – in Greece, the National Organisation for Medicines (EOF). The registration form has to be submitted at least 60 days before the activity begins, and if the authority notifies the applicant within that window that an inspection will take place, the activity cannot start until clearance is given. Registrations, GMP certificates and non-compliance statements are published in EudraGMDP, which makes them visible to your customers, your partners and any inspector reviewing your supply chain.
The QP declaration and the audit behind it
Import documentation is necessary but not sufficient. The marketing authorisation dossier requires a declaration from the Qualified Person of the finished-product manufacturer that the active substance has been manufactured in accordance with EU GMP. EMA publishes a template for it, and the expectation is unambiguous: the declaration rests on an audit of the active substance manufacturer, whether conducted by your own auditors or by a third party whose report you have formally assessed and approved. Annex 16 makes the certifying QP responsible for having access to that documentation and for the continued reliability of any outsourced audit.
The practical test is whether you could reconstruct, on request, the full chain from API manufacturing site to certified batch: registration, written confirmation or listing basis, audit report and assessment, and the QP declaration that ties them together.
How PQRA helps
PQRA supports importers, manufacturers and MAHs across the whole API compliance chain – preparing and maintaining EOF registrations under Article 52a, reviewing written confirmations and listing status before shipment, running and assessing supplier audits, drafting QP declarations for regulatory dossiers, and preparing sites for GMP inspection. We work across Regulatory Affairs and Quality Assurance so that what the dossier says and what the quality system does remain the same thing.
Contact PQRA to review your active substance supply chain documentation before an inspector does.
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