Inspections and compliance

In the European medicines regulatory network, the responsibility for carrying out inspections rests with EU NCAs, but EMA plays an important role. The Agency coordinates the verification of compliance with the principles of good manufacturing practice (GMP), good clinical practice (GCP), good laboratory practice (GLP), good pharmacovigilance practices (GVP) and certain aspects of the supervision of authorised medicinal products in the EU. The main verification tool is inspections. Some are carried out routinely, while others are triggered by request from the CHMP or the CVMP in the context of assessing marketing authorisation applications and/or matters referred to these committees in accordance with EU legislation.

EMA coordinates an inspection programme at the EU level to verify compliance with the principles of GMP, GCP and pharmacovigilance. It includes:

• a programme of risk-based GMP inspections based on the results of inspections of pharmaceutical manufacturing sites by trusted authorities;
• a programme of risk-based routine GCP inspections at sites of clinical research organisations (CROs) most often used in the conduct of bioequivalence trials included in a marketing authorisation application in the mutual-recognition and decentralised procedures (in collaboration with NCAs / the Coordination Group for Mutual Recognition and Decentralised Procedures - Human (CMDh));
• a programme of risk-based routine inspections of the pharmacovigilance systems in place for CAPs (in collaboration with NCAs); and
• a two-year programme of routine GCP inspections based on risk factors and a random element to ensure that a diverse range of applications, trials, and sites and geographical locations are covered.

EMA promotes mutual reliance and work sharing with other international authorities to ensure the best use of resources. There are several mutual recognition agreements in place for GMP inspections.

Through its inspectors' working groups, the Agency coordinates the development and setting of standards for GMP, GCP, GLP and GVP. This helps to harmonise standards within the EU and internationally to strengthen global supply chains and improve access to authorised medicines. The delivery of training and capacity building on inspection-related activities for inspectors and assessors, including non-EU regulators, is one focus area for EMA. The Agency is the primary contact point for the notification of suspected quality defects for CAPs and coordinates their investigation, evaluation and follow-up. It also operates a sampling-and-testing programme to supervise the quality of CAPs placed on the market and to check compliance of these products with their authorised specifications.

Inspections

The CHMP and the CVMP can request GMP, GCP, GLP and pharmacovigilance inspections for medicines that are subject to centralised authorisation procedures. These inspections take place worldwide. Overall, non-EU inspections only represent a small part of the total number of inspections performed by the EU/EEA inspectors, who also carry out inspections as part of their national programmes.

GMP inspections

A total of 210 GMP inspections requested by the CHMP or the CVMP within the context of the centralised authorisation procedure were performed in 2024.

In 2024, ten GMP inspections conducted by EEA authorities led to the issuing of a non-compliance statement. This means that medicines manufactured at a site with such a non-compliance statement cannot be sold in the EU.

The EEA authorities issued one statement of GMP non-compliance relating to CAPs, either in connection with the active substance or the finished product; however, no recalls were necessary. When inspections lead to findings, companies must implement corrective action plans agreed with the inspecting authorities.

GCP inspections

The number of GCP inspections increased by 24 % compared to 2023.

Pharmacovigilance inspections

EMA, in cooperation with competent authorities in Member States, maintains a risk-based programme for routine pharmacovigilance inspections of marketing authorisation holders of CAPs and ensures its implementation. It also plays a key role in the coordination of pharmacovigilance inspections specifically triggered by the CHMP or the CVMP and in inspection follow-up.

In 2024, 18 pharmacovigilance inspections were requested by the CHMP or the CVMP. Most EU/EEA pharmacovigilance inspections (over 90 %) are conducted under the national pharmacovigilance inspection programmes, which relate to marketing authorisation holders with product authorisations of all types (including CAPs).

Market surveillance and quality defects

Manufacturers are required to inform the authorities of quality defects in a manufactured product. This can lead to a recall of batches from the market or a prevention of their release by the manufacturer. Where a defect is considered to be a risk to public or animal health, the marketing authorisation holder is requested to withdraw the affected batches of the CAP from the EU market and the supervisory authority issues a rapid alert. The alert is classified from 1 to 3, depending on the expected risk to public or animal health posed by the defective product:

• Class 1 recall: the defect presents a life-threatening or serious risk to health;
• Class 2 recall: the defect may cause mistreatment or harm to the patient or animal, but is not life-threatening or serious; and
• Class 3 recall: the defect is unlikely to cause harm to the patient, and the recall is carried out for other reasons, such as non-compliance with the marketing authorisation or specification.

In 2024, the Agency received 395 suspected quality defect notifications, the highest number recorded in recent years. Of these, 221 cases were confirmed quality defects and led to batch recalls of nine CAPs. None of the defects required a Class 1 recall.

The main reasons for the recall of CAPs in 2024 included:

Manufacturing laboratory control issues: These include out-of-specification results obtained during quality control testing;

Product contamination and sterility issues: These include chemical, microbiological or physical contamination of the medicinal product;

Product label issues: These include issues related to labelling of the medicinal products (e.g. a missing or incorrect batch number);

Product packaging issues: These relate to physical issues (e.g. a mix-up or a damaged container);

Product physical issues: These relate to incorrect product physical properties (e.g. friability, size/shape, leakage).

Parallel distribution

EMA checks that the parallel distribution of CAPs from one Member State to another by a company independent of the marketing authorisation holder is compliant with the rules.

Certificates

EMA also issues electronic-only certificates to confirm the marketing authorisation status of medicines that have either been authorised or for which an application for marketing authorisation has been submitted to the Agency.