EudraLex Volume 4: EU Annex 21 GMP guidelines

EudraLex Volume 4 Annexes - Annex 21

EudraLex Volume 4: EU Annex 21 GMP guidelines

EudraLex, Volume 4 – Good Manufacturing Guidelines

European Union: EU GMP Guide Updates – EU Annex 21 (News)

Manufacturers/Importers and Sponsors who import medicinal products into the EU/EEA must now comply with EU Annex 21 GMP requirements.

Background to EU Annex 21 GMP guidelines for importation of medicinal products 

  • EU Annex 21 was first published in the EudraLex (Volume 4) on 16 February 2022.
  • Annex 21 GMP guidelines apply to the importation of finished pharmaceutical products as well as to the importation of bulk products and intermediates.

When did compliance with EU Annex 21 requirements become mandatory?

As of 22 August 2022, compliance with EU Annex 21 is mandatory for organisations/MIA holders involved with the importation of medicinal products into the European Union (EU) and/or European Economic Area.


FAQs: Applicability of EU Annex 21 – Importation of Medicinal Products

FAQ #1: Which medicinal products do EU Annex 21 guidelines apply to?

EU Annex 21 is applicable to:

  • Medicinal products physically imported into the EU/EEA from non-EU/non-EEA Member states
  • Including medicinal products intended for:
    • Human Use
    • Veterinary Use
    • Clinical Trials, e.g. Investigational Medicinal Products (IMPs)

EudraLexVolume4Annexes

Imported medicinal products between EEA members

EU Annex 21 requirements do not apply to the importation of medicinal products from one EU/EEA Member State to another EU/EEA Member State.


FAQ #2: Who must comply with GMP requirements in EU Annex 21?

  • Manufacturers and/or Sponsors importing raw materials, APIs, finished medicines and intermediates from non-EU/EEA member states
  • This includes MIA holders (Manufacturers/Sponsors/Importers authorised by the EMA to import:

importation-to-eu-eea-regulations


As of 22 August 2022, Importers, Marketing Authorisation Holders (MAHs), and Clinical Trial Sponsors must comply with EU Annex 21 requirements unless they are importing products from another EU Member State or Member Country of the EEA.


Learn more about EU Annex 21 GMP Requirements for importation of medicines


FAQ #3: Do manufacturers in the UK need to comply with EU Annex 21?

  • The United Kingdom (UK) left the European Union in 2020 (the infamous ‘Brexit’)
  • This means YES – organisations importing medicines from the UK into the EU/EEA must comply with the requirements of EU Annex 21

EU EudraLex volume4 download link EUDRALEX download


FAQ #4: What authorisations are required to import medicinal products into the EU?

  • A Marketing Authorisation Holder (MAH)/Importer or Sponsor must have authorisation from the EMA (Europeans Medicines Agency) in order to:
    • import, process/manufacture, and/or
    • distribute medicinal products in the European Union
  • Authorisation by the EMA is granted via a Manufacturing Import Authorisation (MIA)
  • Written agreements must also be in place between manufacturers/importers, third-country manufacturers, etc.
  • Other EU GMP Guide requirements apply, as detailed in the EudraLex (Volume 4) – Good Manufacturing Practice (GMP regulations) 

EU-EudraLex-PDF-download-link

  • All conditions in the Marketing Authorisation (MA) or Clinical Trial Authorisation (CTA) must also be met

Examples of other requirements per the EU GMP Guide

All entities/sites involved in the importation of medicinal products into the EU/EEA must:

  • Have a documented Pharmaceutical Quality System (PQS) in place
  • Ensure their PQS and related processes, procedures and documents are appropriate for the product type & activities being conducted
  • Ensure their PQS is effective, including but not limited to Owners/Senior Management ensuring:
    • An Ongoing Stability Program is in place
    • All relevant documentation is available to the Qualified Person (QP) for batch certification or confirmation

Learn more about GMP requirements for Batch Certification/Release for Supply.


FAQ #5: Does Annex 21 apply to intermediates imported into the EU/EEA for further processing?

  • Yes – as noted above – Annex 21 applies to:
    • Importation of finished products (imported for distribution in the EU/EEA)
    • Importation of any bulk and intermediate products imported for further processing, prior to QP certification and distribution
  • A Marketing Authorisation (MA) and a Manufacturing Import Authorisation (MIA) are required
  • Conditions of the approved MA or CTA (Clinical Trial Authorisation) must be adhered to by the MA or CTA holder
  • Compliance with other GMP requirements must be ensured via the implementation of appropriate measures/controls including data integrity measures

Fiscal only transactions and EU Annex 21

Fiscal transactions, where no importation takes place and/or products are not being manufactured or distributed in the EU/EEA:

  • Note: EU Annex 21 does not apply to ‘fiscal transactions’ where the product is not actually physically imported into the EU/EEA
  • EU Annex 21 also does not apply to finished medicinal products imported for export purposes only (products that will not be distributed nor further processed in the EU/EEA)
  • Reminder: EU Annex 21 also does not apply to products imported into the EU/EEA from other EU/EEA Member States

Educational presentation: EU Annex 21 – Importation of Medicinal Products

EudraLEX-Volume-4-Eudralexvolume4-ANNEXES-EC-EU-EEA-

Online GMP Compliance Training is available for EU Annex 21.


Want more support with GMP regulations including EU cGMP requirements?

To get started on your understanding of GMP requirements in various regions of the globe, why not sign up for one of PharmOut’s e-learning modules?

Additionally, PharmOut regularly conducts on-site and remote supplier audits on behalf of our clients.


Click the IMAGE BELOW for online GMP training & EU Annex 21 (EudraLex GMP guidance):

EUDRALEX download link EU GMP


Resources and further reading:

Download link for EU Annex 21 – The Rules Governing Medicinal Products in the European Union (Volume 4) EU Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use

Link to the EudraLex Volume 4 GMP guidance

Marketing Authorisation Holder (MAH) according to the EMA

Certificate GMP Training for EU GMP Guide – Annex 21 

Certificate GMP Training for Medical Device Regulations (MDR) – available soon! Bookmark this page.

Contact PharmOut for training large numbers of employees with convenient 1-day intensive GMP compliance training courses delivered via ZOOM (onsite training may be available for large groups of employees, subject to availability. Conditions apply).

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