An announcement referring to an “EMA inspection” does not necessarily mean that EMA inspectors will visit your manufacturing site. The European Medicines Agency (EMA) coordinates certain inspection activities, while national competent authorities (NCAs) carry them out. The inspectors arriving at your site will therefore normally represent a national authority. The practical questions are which authority is responsible, why an inspection is being requested, and what EMA coordinates behind the scenes.
Scope
This article examines the European Union’s inspection framework for finished medicinal products for human use and active pharmaceutical ingredients (APIs), referred to in EU legislation as active substances. Investigational medicinal products, veterinary medicines and good distribution practice (GDP) are outside its detailed scope.
The inspection network extends across the European Economic Area (EEA), where the competent authorities participate in common coordination and harmonisation activities. However, the territorial scope of international agreements must be assessed separately for each agreement.
One framework, different responsibilities
Three levels of requirements underpin the EU inspection system.
Legislation. Directive 2001/83/EC establishes the principal legal framework for inspections of medicinal products for human use. Under Article 111, competent authorities of Member States must ensure compliance with applicable requirements, including through inspections, which may be unannounced. Manufacturers, including those located in third countries, and wholesale distributors are subject to inspections. Authorities also operate risk-based supervision systems for active-substance manufacturers, importers and distributors within their territories.
GMP guidelines. EudraLex Volume 4 contains the EU guidelines on good manufacturing practice. Part I covers finished medicinal products, Part II covers active substances and is based on ICH Q7, while the annexes address specific manufacturing activities and requirements. Part III contains GMP-related documents and reference material rather than constituting another manufacturing standard.
Inspection procedures. The Compilation of Union Procedures on Inspections and Exchange of Information (CoUP) harmonises inspection practices, procedures and information exchange across the European network. It is maintained through the work of the GMP/GDP Inspectors Working Group.
Who does what?
National competent authorities:
- conduct inspections through their national inspectorates
- issue GMP certificates and statements of non-compliance
- supervise manufacturing and import activities within their respective jurisdictions
The internal organisation of these authorities differs between countries. Functions that appear similar at EU level may be assigned to different national bodies.
EMA:
- coordinates inspections associated with centrally authorised products and referral procedures when requested by the relevant scientific committees
- supports the preparation and harmonisation of GMP guidance
- promotes consistent interpretation of EU requirements
- facilitates cooperation between Member States when third-country manufacturers are inspected
For centrally authorised products, EMA’s coordination is formalised. Inspection requests are managed through the IRIS platform, while inspection reports are prepared by inspectors appointed from national competent authorities.
The applicable coordination procedure was revised in 2026. Its current Version 3 entered into force on 10 September 2026.
The GMP/GDP Inspectors Working Group (GMDP IWG) brings together senior inspectors representing the competent authorities of the EEA. EMA chairs the group and provides its secretariat, while the European Commission is represented. The group develops guidance and procedures, supports harmonisation of inspection approaches and addresses matters relating to mutual recognition agreements.
The essential distinction is that EMA coordinates and harmonises the system, whereas national inspectorates perform the inspections.
Who oversees non-EU manufacturing sites?
The general rule is that a manufacturing site outside the EU is inspected by the competent authority of the Member State where the EU importer is located, unless an applicable mutual recognition agreement (MRA) provides for reliance on inspections conducted by the partner authority.
For centrally authorised products, EMA coordinates the verification of GMP status for manufacturers identified in marketing authorisation applications. The supervisory authority is generally associated with the Member State responsible for the manufacturing authorisation holder importing the product. It may request another EEA authority to conduct the inspection.
The arrangements for active substances require separate consideration.
For API manufacturing sites within the EEA, the supervisory authority is the competent authority of the country where the site is located.
For sites outside the EEA, supervision of associated API manufacturers falls within the responsibility of the competent authority of the Member State responsible for supervising the medicinal product. Inspections of third-country API manufacturers may be conducted where there are grounds to suspect non-compliance.
A third-country manufacturing site can therefore have several relevant authorities at the same time, depending on the products, marketing authorisation applications and importers involved.
There is no single permanent “home inspectorate” for every product manufactured at a particular site. A change of importer may also change the supervisory authority.
What triggers an inspection?
An inspection may be initiated for several reasons.
Marketing authorisation applications and new manufacturing sites. GMP status must be verified for manufacturers identified in an application, including manufacturers located in third countries. An inspection is one possible verification method, but it is not necessarily required in every case.
Routine risk-based supervision. Article 111 provides for repeated inspections of medicinal-product manufacturers and risk-based supervision of active-substance manufacturers, importers and distributors.
Significant manufacturing changes. Changes to the manufacturing chain or manufacturing arrangements may require regulatory assessment and can lead to an inspection.
Quality defects or suspected non-compliance. Information indicating potential GMP violations may trigger an inspection. EU legislation also explicitly allows unannounced inspections. For third-country API manufacturers, inspections may be conducted where there are grounds to suspect non-compliance.
Verification of corrective actions. Follow-up inspections may be conducted to assess whether corrective and preventive actions (CAPA) and other commitments have been implemented effectively.
The EU system should not be interpreted automatically using FDA terminology. There is no universal mandatory “pre-approval inspection” for every marketing authorisation application. GMP status is verified within the relevant regulatory procedure, and an inspection is requested where necessary.
What does an inspection produce?
Following an inspection, the competent authority prepares a report assessing whether the manufacturer complies with the principles and guidelines of GMP. Under Article 111(3) of Directive 2001/83/EC, the report’s contents are communicated to the inspected manufacturer.
GMP certificate. Where an inspection demonstrates compliance, a GMP certificate is issued where applicable. Under Article 111(5), the certificate should be issued within 90 days of the inspection and entered into the EudraGMDP database.
Statement of non-compliance with GMP (SoNC). Where inspectors conclude that GMP requirements have not been met, the competent authority may issue a statement of non-compliance. The statement is entered into EudraGMDP and made publicly available. It describes the nature of the non-compliance and the measures taken or proposed to protect public health.
Inspection observations and a formal conclusion of non-compliance are not the same thing. Deficiencies requiring corrective action do not automatically result in a statement of non-compliance.
This distinction is important when interpreting inspection outcomes and assessing the regulatory status of a manufacturing site.
MIA, GMP certificates and QP certification
Three concepts are frequently confused: Manufacturing and Importation Authorisation (MIA), GMP certificates and Qualified Person (QP) certification. They serve different regulatory purposes.
Manufacturing and Importation Authorisation (MIA) is the authorisation to manufacture medicinal products in the EU/EEA or import them from third countries. It is issued by the competent authority of the country where the manufacturer or importer operates and recorded in EudraGMDP.
A GMP certificate documents the outcome of an inspection at a particular manufacturing site. It is issued by the competent authority where the inspection demonstrates compliance and a certificate is applicable. The site may be located inside or outside the EU.
QP certification is the Qualified Person’s confirmation that an individual batch meets the applicable requirements. It forms part of the quality system of the MIA holder. For medicinal products imported from third countries, QP certification takes place after physical importation and customs clearance, in accordance with Annex 21.
These concepts should not be treated as interchangeable. A site’s GMP certificate does not replace the importer’s MIA and does not remove the requirement for QP certification of individual batches.
Similarly, a supplier audit or QP certification is not a regulatory inspection. An inspection is an activity performed by a competent authority.
Article 51 of Directive 2001/83/EC also establishes requirements for batch testing following importation from third countries. In general, each batch must undergo the following in a Member State: a full qualitative analysis, a quantitative analysis of at least all active substances, and the other tests or checks necessary to ensure compliance with the marketing authorisation.
Applicable international arrangements may provide relief from these requirements. However, recognition of an inspection does not automatically remove all remaining import obligations.
What can EudraGMDP tell you?
EudraGMDP is the publicly accessible EU database maintained and operated by EMA. Its content is provided by the national competent authorities.
- Manufacturing and Importation Authorisations (MIAs)
- GMP and GDP certificates
- statements of non-compliance
- registration information for active-substance manufacturers
It is an important source for checking the regulatory status of manufacturing sites and other relevant entities.
However, two limitations should be understood. First, a public certificate or statement of non-compliance is not a complete inspection report. Detailed inspection observations and CAPA correspondence are not generally available through the public database.
Second, the absence of a GMP certificate for an API manufacturer does not automatically indicate non-compliance. EU legislation does not require routine inspections of every active-substance manufacturer.
The database should therefore be used as a regulatory verification tool, not as a substitute for a full assessment of a supplier’s compliance status.
API imports and written confirmation
Active substances imported into the EU are subject to specific requirements under Article 46b of Directive 2001/83/EC.
As a general rule, imported active substances must be accompanied by written confirmation from the competent authority of the exporting third country. The confirmation must relate to the manufacturing site and establish that:
- the applicable GMP standards are at least equivalent to those of the EU
- the manufacturing site is subject to appropriate controls, including repeated and unannounced inspections
- information on identified non-compliance is provided without delay
The requirement does not apply to countries included in the list established under Article 111b.
There is also a separate waiver mechanism. Under Article 46b(4), a Member State may exceptionally waive the written confirmation requirement where necessary to ensure the availability of medicinal products, provided the relevant manufacturing site has been inspected by a Member State and found compliant with GMP.
The waiver cannot extend beyond the validity of the relevant GMP certificate, and Member States applying it must inform the European Commission.
A recent inspection by an EU Member State does not, by itself, eliminate the written confirmation requirement.
The written confirmation and an EU GMP certificate are separate legal instruments.
A separate inspection track: EDQM and CEP holders
The European Directorate for the Quality of Medicines & HealthCare (EDQM) operates a separate inspection programme associated with Certificates of Suitability to the European Pharmacopoeia (CEP). EDQM is neither EMA nor a national competent authority.
Under the CEP programme, EDQM organises inspections of CEP holders in cooperation with EU/EEA national authorities.
Where an inspection identifies GMP non-compliance, the relevant statement is issued by the participating national competent authority. EDQM may subsequently take action concerning the affected CEPs, including suspension or withdrawal.
This inspection track can operate alongside the national regulatory supervision of an active-substance manufacturer.
Recognition versus regulatory cooperation
The EU inspection system combines internal recognition arrangements with international regulatory cooperation. These mechanisms have different legal implications.
Recognition within the EU. Under Article 122 of Directive 2001/83/EC, inspection conclusions reached by a Member State under Article 111 are valid throughout the Union.
Member States may request inspection reports from one another and from EMA. Refusal to recognise an inspection conclusion is possible only in exceptional circumstances on public health grounds, with the relevant notification requirements applying.
This is recognition of inspection conclusions and should not be confused with the mutual recognition procedure for marketing authorisations.
Agreements with third countries. The EU has GMP mutual recognition agreements with Australia, Canada, Japan, New Zealand, Switzerland and the United States. A comparable agreement with Israel operates under the Agreement on Conformity Assessment and Acceptance of Industrial Products (ACAA).
Depending on the agreement and its scope, these arrangements may allow reliance on inspections conducted by the partner authority, waiver of certain batch-testing requirements, and exchange of inspection information and information on quality defects.
The scope and operational status of each agreement must be checked separately.
For example, the EU–US pharmaceutical GMP agreement became fully operational for most human medicines on 11 July 2019. EU authorities may accept FDA documentation concerning third-country manufacturing facilities on a case-by-case basis.
The United Kingdom has a separate regulatory relationship with the EU following Brexit. The relevant provisions are contained in the dedicated annex to the EU–UK Trade and Cooperation Agreement.
PIC/S: cooperation, not automatic recognition. EMA participates in international harmonisation through the GMP/GDP Inspectors Working Group, which maintains alignment between EU GMP guidance and the Pharmaceutical Inspection Co-operation Scheme (PIC/S) GMP Guide.
PIC/S participation supports the alignment of standards, inspection procedures and inspector training. However, participation in PIC/S does not, by itself, establish automatic mutual recognition of inspections conducted by another authority.
Checklist before an EU inspection
For manufacturers supplying medicinal products to the European market, the following points provide a practical starting framework.
- Identify the importer and country of import. Establish which company imports the product into the EU and where it is located. This is a key starting point for identifying the supervisory authority.
- Determine the marketing authorisation procedure. Establish whether the product follows the centralised, national, decentralised or mutual recognition procedure. This affects how GMP verification and inspection coordination are organised.
- Identify the applicable product and GMP requirements. Distinguish finished medicinal products under Part I of EudraLex Volume 4 from active substances under Part II and ICH Q7. For APIs, determine whether written confirmation under Article 46b is required, whether an Article 111b exemption applies or whether an individual waiver is available.
- Check EudraGMDP. Review current GMP certificates, relevant statements of non-compliance and the available regulatory history. Understand what the public database does not disclose.
- Review the QP and importation arrangements. Identify who certifies batches, where physical importation and customs clearance take place, whether batch testing in the EU is required and whether an applicable international agreement provides relief.
- Maintain readiness for unannounced inspections. EU legislation explicitly allows unannounced inspections. Ensure that site-access procedures and the responsibilities of relevant personnel remain effective without prior notice.
- Prepare for quality-related signals. Review how quality defects and recalls are communicated to the competent authority and ensure that the communication history is properly documented.
- Establish an adverse-outcome response plan. Define responsibility for CAPA, communication with the authority and responses to potential statements of non-compliance, including the coordination and notification of other relevant authorities.
The next article in the series examines the EAEU inspection system: one set of common inspection rules, national inspectorates and the regulatory nuances arising from this combination.
