Compliance: Overview

All organisations involved in the development, marketing, manufacture and distribution of medicines are responsible for ensuring that they comply with all relevant standards set out in European Union (EU) legislation and guidelines on pharmaceuticals. The European Medicines Agency (EMA) is responsible for harmonising these standards at EU level. It also coordinates inspections to verify compliance.

Compliance in the product lifecycle

Research and development	Marketing authorisation application	Post-authorisation
Good laboratory practice (GLP)
Good clinical practice (GCP)
Good manufacturing practice (GMP)
	Pharmacovigilance inspections
Sampling and testing
	Good distribution practice (GDP)
Quality defects and recalls
Falsified medicines: reporting obligations

EMA's role

EMA coordinates inspections for human and veterinary medicines authorised under the centralised procedure or in the context of a referral, on request from the Committee for Medicinal Products for Human Use (CHMP) or Committee for Medicinal Products for Veterinary Use (CVMP).

EMA does not conduct inspections itself but requests that the inspection be carried out by national authorities in the EU Member States.

EMA is the primary contact point for reporting a suspected quality defect with any centrally authorised product and is responsible for coordinating the investigation, evaluation and follow-up of such cases.

EMA also operates a Sampling and testing programme to verify the quality of centrally authorised medicines placed on the market and to check their compliance with their authorised specifications.

In addition, EMA plays a key role is in coordinating and harmonising EU-wide activities, including:

• developing and harmonising standards at EU level;
• developing EU guidelines on inspections and related procedures;
• preparing guidance through inspectors working groups;
• coordinating advice on the interpretation of regulatory requirements.

Inspections: verifying compliance

Authorities in the EU regularly inspect sites within and outside the EU involved in developing, manufacturing and distributing human or veterinary medicines intended for the EU market, to verify their compliance with the relevant standards.

These inspections ensure that the rights, safety and wellbeing of clinical-trial subjects are protected, and the reliability and integrity of data that support the authorisation of medicines and their quality, safety and effectiveness once on the market.

An inspection may either be 'for cause', when it is triggered by a finding of possible non-compliance with relevant standards, or routine, when inspections are carried out as part of a surveillance programme.

Inspections are conducted both for authorised medicines and for medicines under evaluation in the EU.

An overview of the different types of inspection EMA's CHMP can request as part of the assessment and monitoring of human medicines under the centralised authorisation procedure is available below.

GCP inspections

Why compliance matters	Provides public assurance that the rights, safety and wellbeing of trial subjects are protected and that clinical trial data are credible
Purpose of inspections	Confirms that clinical trials supporting a marketing authorisation application are conducted in line with GCP standards and all relevant legal and regulatory requirements in the EU
Sites in scope	Any site where clinical trials that are part of an application are carried out, no matter where in the world it is located
When they occur	EMA's CHMP can request a GCP inspection at any stage in the evaluation of a medicine. The evaluation of the need for a GCP inspection is a routine part of this process. For more information, see: Points to consider for assessors, inspectors and European Medicines Agency inspection coordinators on the identification of triggers for the selection of applications for routine and for-cause inspections, their investigation and scope of such inspections
Impact of adverse outcomes	If a GCP inspection reports critical or major findings on the conduct of clinical trials supporting a marketing authorisation application: the CHMP evaluates the impact of the findings on the medicine’s benefit-risk balance and on the rights, safety and wellbeing of clinical trial subjects the CHMP may request analyses of clinical trial data excluding the affected patients or sites
Publicly available information	Each medicine's assessment report includes information on the: types and locations of sites inspected; any impact of inspection findings on the benefit-risk assessment of the medicine. For the latest statistics on GCP inspections requested by the CHMP, see Annual reports.
International cooperation	If the clinical trials took place outside the EU, and if EMA has a confidentiality arrangement with the responsible non-EU regulator, the two jurisdictions may: exchange information on inspection findings and their interpretation; conduct collaborative inspections. For more information see International agreements.
More information	Good clinical practice Good clinical practice (GCP) inspection procedures Obtaining an EU marketing authorisation, step-by-step The evaluation of medicines, step-by-step How EMA evaluates medicines for human use Pre-authorisation guidance: Inspections
Related materials	Visual guide: GCP inspections requested by the CHMP between 1997 and 2019 Infographic on the 1,000 GCP inspections requested by the CHMP

GMP inspections

Why compliance matters	Provides public assurance that medicines on the EU market are of consistently high quality, appropriate for their intended use and meet the requirements of the marketing authorisation or clinical trial authorisation
Purpose of inspections	Confirms that any medicine intended for the EU market is manufactured in compliance with GMP standards and all relevant legal and regulatory requirements in the EU
Sites in scope	Any site manufacturing a medicine intended for the EU market, no matter where in the world it is located Sites in the EU are routinely inspected by the national authority Inspections are typically performed at manufacturing sites located in third countries, for which a mutual recognition agreement (MRA) with the EU does not apply or when the products are not covered by the MRA For more information see:  Mutual recognition agreements (MRA) International collaboration on GMP inspections
When they occur	EMA's CHMP can request a GMP inspection at any time during a medicine's evaluation or after a medicine is authorised in the EU.  For more information, see: Good manufacturing practice Obtaining an EU marketing authorisation, step-by-step The evaluation of medicines, step-by-step How EMA evaluates medicines for human use Pre-authorisation guidance: Inspections
Impact of adverse outcomes	If a GMP inspection leads to adverse findings, the company must implement a corrective action plan agreed with the inspectors
Publicly available information	The EudraGMDP database holds the data collected during GMP inspections by EU authorities, including those requested by the CHMP. Each medicine's assessment report includes information on the: types and locations of sites inspected; any impact of inspection findings on the benefit-risk assessment of the medicine. For the latest statistics on GMP inspections requested by the CHMP see Annual reports.
International cooperation	If a medicine is manufactured outside the EU, and if the EU has a mutual recognition agreement (MRA) with the country in question on the conformity assessment of regulated products, the two jurisdictions can: rely on each other's GMP inspection system; share information on GMP inspections and quality defects; waive batch testing of products on import into their territories; EMA also takes part in international initiatives to: exchange information on inspection planning and outcomes; conduct joint inspections for manufacturing sites of common interest. For more information see:  Mutual recognition agreements (MRA) International collaboration on GMP inspections
More information	Good manufacturing practice Mutual recognition agreements (MRA) EudraGMDP database International collaboration on GMP inspections Obtaining an EU marketing authorisation, step-by-step The evaluation of medicines, step-by-step How EMA evaluates medicines for human use Pre-authorisation guidance: Inspections

GLP inspections

Why compliance matters	Provides public assurance that the validity, integrity and reliability of non-clinical safety, toxicological and pharmacological data submitted for regulatory evaluation and approval are credible
Purpose of  inspections	Confirms that non-clinical studies supporting a marketing authorisation application are conducted in compliance with GLP standards and all relevant legal and regulatory requirements in the EU
Sites in scope	Any site where pivotal non-clinical studies are carried out, no matter where in the world it is located
When they occur	EMA's CHMP can request a GLP inspection at any stage in the evaluation of a marketing authorisation application.  For more information, see: Triggers for audits of good laboratory practice (GLP) studies
Impact of adverse findings	If inspectors report critical or major findings on the conduct of non-clinical studies, the CHMP evaluates the impact on the medicine’s benefit-risk balance.
Publicly available information	Each medicine's assessment report includes information on the: types and locations of sites inspected; any impact of inspection findings on the benefit-risk assessment of the medicine.
International cooperation	If the non-clinical studies took place outside the EU, and if EMA has a confidentiality arrangement with the responsible non-EU regulator, the two jurisdictions may: exchange information on inspection findings and interpretation; conduct collaborative inspections. The EU is a signatory to the OECD mutual acceptance of data (MAD) agreement, which allows participating authorities to rely on each other's monitoring programmes for GLP compliance.
More information	Good laboratory practice compliance Pre-authorisation guidance: Inspections OECD: Principles of Good Laboratory Practice (GLP) and Compliance Monitoring

Pharmacovigilance inspections

Why compliance matters	Provides public assurance that marketing authorisation holders, or third parties acting on their behalf, have adequate systems in place for the safety monitoring of medicines on the EU market
Purpose of inspections	Confirms that the marketing authorisation holder has personnel, systems and facilities to meet their pharmacovigilance obligations
Sites in scope	Any party carrying out pharmacovigilance activities in whole or in part, on behalf of or in conjunction with, the marketing authorisation holder, no matter where in the world it is located
When they occur	EMA's CHMP can request a pharmcovigilance inspection at any stage during the evaluation of a marketing authorisation application or after a medicine is authorised.  For more information, see: Coordination of Pharmacovigilance inspections Pharmacovigilance inspection procedures: human Guideline on good pharmacovigilance practices: Module III – Pharmacovigilance inspections
International cooperation	EMA can exchange information on pharmacovigilance inspection findings with non-EU regulators with which EMA has signed a confidentiality arrangement.  For more information see International agreements.
More information	Coordination of Pharmacovigilance inspections Pharmacovigilance inspection procedures: human Good pharmacovigilance practices Guideline on good pharmacovigilance practices: Module III – Pharmacovigilance inspections

For more information on the authorisation of medicines in the EU, see: 

• Obtaining an EU marketing authorisation, step-by-step
• The evaluation of medicines, step-by-step
• How EMA evaluates medicines for human use