EU GMP Annex 21 (Importation)

Annex 21 applies to MIA holders importing medicinal products into the EU/EEA from third countries — both bulk product and finished product. It covers human medicines, veterinary medicines and investigational medicinal products. It does not apply to active pharmaceutical ingredient (API) importation (Part II Chapter 17 covers API import) or to intra-EU/EEA transfers (those are governed by Chapter 7 and the Mutual Recognition framework).

It applies regardless of where physical importation occurs (port, airport, bonded warehouse) — the controlling concept is the legal importation under the MIA, which is performed at the importation site named on the authorisation.

Annex 21 applies to both, with the responsibilities of each documented in the MIA, the Site Master File and the Quality Agreement chain back to the third-country manufacturer.

1. Maintain a Quality Agreement with the third-country manufacturer covering responsibilities, GMP compliance, change control, deviation reporting, complaints, recall, and access to manufacturing records.
2. Ensure the third-country manufacturer holds the appropriate GMP status — either an equivalent recognition (MRA / SCA partner countries: US, Japan, Israel, Switzerland, Canada, Australia, New Zealand, UK) or a positive EU GMP inspection.
3. Receive, store and handle the imported product under conditions appropriate to the product (cold chain, controlled-temperature storage, etc.).
4. Perform importation testing per the testing strategy (full testing, reduced testing with justification, or reliance on third-country testing under an MRA).
5. Review the third-country batch documentation against the EU dossier and product specifications.
6. QP certifies each batch per Article 51 before the batch is placed on the EU market.
7. Manage deviations, OOS, complaints and recalls with the third-country manufacturer in real time.

The QP certifying the imported batch personally takes responsibility that each batch complies with EU law and the marketing authorisation. The QP must have evidence to support that judgement — the batch record (or a faithful summary), the manufacturer's certificate of analysis, the importation testing results, the deviation history, and confirmation that the manufacturing site's GMP status remains valid. Annex 21 makes the documentation expectations explicit and adds a requirement that the QP has timely access to the underlying manufacturing records.

Annex 21 reiterates the long-standing position that imported batches must be re-tested in the EU (Article 51(1)(b)) — full testing is the default. Reduced testing is permitted where: (a) the third-country manufacturer is under an MRA / SCA that recognises the equivalence of GMP and testing, and (b) the importation strategy is documented and justified in the PQS.

Even under MRA-based reduced testing, the importation site must perform identity testing on every batch and retain reserve samples per Article 80 of Directive 2001/83/EC. Risk-based justification for the reduced strategy must be revisited on changes to the manufacturer, formulation, container-closure or analytical methodology.

• Quality Agreement with the third-country manufacturer (and any third-country contract testers).
• Site Master File for the importation site reflecting the import activities and the supply chain.
• Importation strategy document — covered tested attributes, frequencies, justification, MRA status, reserve sampling.
• Per-batch importation file — manufacturer's batch records or summaries, CoA, importation testing results, deviation history, QP certification record.
• Periodic review of the third-country manufacturer's GMP status, including reliance evidence (inspection certificate, MRA confirmation).
• Change-control flow that captures third-country changes affecting the imported batch.

Since Brexit, the UK is a third country to the EU and the EU is a third country to the UK. Importation between the EU and Great Britain (excluding Northern Ireland, which follows the Windsor Framework specifics) requires importation MIA on both sides for batches moving in each direction. Annex 21 applies on the EU side; the UK Human Medicines Regulations 2012 (as amended) apply on the UK side. The two regimes are aligned in substance but operationally separate.

• QP certification based on CoA alone, without batch-record visibility.
• Reduced testing strategy without documented MRA reliance and identity testing per batch.
• Quality Agreement out of date with the actual third-country activities.
• Reserve sampling missing or below the volume required for hypothetical re-test.
• GMP status of the third-country manufacturer not re-verified after inspection cycle changes.
• No mechanism to capture third-country deviations until they show up in batches months later.