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02/03/2022

Inspections

European and French regulations have set high standards of quality, safety and efficacy of veterinary medicinal products in order to address a common concern for the protection of public and animal health and the environment.

Continuous verification of compliance with these legal requirements shall be carried out by means of checks. To this end, Anses ANMV carries out inspections at all stages of the life cycle of the veterinary medicinal product, i.e. from their development, as well as at all stages of their production and distribution. 

Through the inspection program, Anses-ANMV is constantly monitoring veterinary medicinal products. Its purpose is to guarantee the efficacy and safety data transmitted for the assessment of the benefit/risk balance of medicinal products when applying for marketing authorisation (inspections Good laboratory practice and good clinical practice), then, once the medicinal product has been authorised and marketed, to continuously verify that this balance remains positive after marketing (inspections Good Manufacturing Practices, Good Distribution Practices and Good Pharmacovigilance Practices) and, if necessary, to strengthen the safety of medicinal products through various measures (targeted or thematic inspections and investigations).

The periodicity of inspections shall be determined by a decision of the Director-General of Anses. In order to ensure the effectiveness of inspections, the frequency of such checks shall be modulated in relation to the risk and the level of compliance expected in the various areas. This approach allows Anses-ANMV to allocate resources where the risk is highest. However, in some circumstances, these controls are carried out regardless of the level of risk or non-compliance expected and, in other circumstances, without notice.

The Inspection Unit

As the competent authority for the veterinary medicinal product, the task of Anses-ANMV is to ensure, through its control and inspection activities, the quality of the practices of the stakeholders (MA holders, manufacturers, importers, distributors, testing facilities, test promoters, investigators...) and the quality, efficacy, safety and availability of veterinary medicinal products. It has a team of qualified, qualified and sworn inspectors grouped in an inspection unit.

The inspectors are under the authority of the Director of Anses-ANMV. They carry out inspections on national territory or abroad. They shall ensure that the existing regulatory provisions are properly implemented by the relevant stakeholders.

Consult the list of authorised and sworn inspectors (PDF)  

The operation and organisation of the inspection unit is based on the model proposed by the ISO/IEC 17020, Conformity Assessment — Requirements for the operation of different types of inspection bodies. The unit is regularly audited by its European peers in JAP and BEMA and international audits as part of the OECD’s JRP audits of the ICP/S and osev. It is also subject to periodic evaluation by its international partners under mutual recognition agreements between the European Union and the US FDA, Canada, Australia, New Zealand, Switzerland and Israel. The result of these evaluations is an acknowledgement of the quality of the Anses-ANMV inspection activities and their compliance with ethics and international standards of impartiality, independence and competence.

Carrying out an inspection

Inspection means an assessment of the conformity with a given repository of the subject matter inspected by a qualified person. This includes all the steps from the risk analysis leading to the scheduling of the inspection to the decision based on the judgment of conformity concerning the subject matter inspected. Applied to the scope of the Anses-ANMV, the object inspected corresponds to the establishments and structures under its supervision, the products handled and their activities.

The inspection makes it possible to establish a degree of confidence in the quality of the practices of stakeholders (manufacturers, MA holders, importers, distributors...) who remain primarily responsible for their practices, the quality, efficacy, availability and safety of the veterinary medicinal products handled. These inspections carried out by the Anses-ANMV inspectors aim to:

  • assess compliance of veterinary pharmaceutical structure and establishment practices with Good Practice (BPx) or benchmarks in force for a system, activity or category of veterinary products or medicinal product;
  • conduct technical investigations (sometimes referred to as “investigation”) following the reporting of a particularly significant quality deficiency, incident or event;
  • gather facts necessary for the conduct of the following administrative actions:
    • preparation of a technical opinion in the context of the examination of applications for authorisation to initiate;
    • establishment, renewal or withdrawal of a certificate (good manufacturing, distribution practices, etc.);
    • financial penalties;
    • animal health decision on veterinary medicinal products and activities;
    • suspension of the activity causing the risk (suspension, withdrawal of authorisation, etc.).

The initiation of an inspection in France or abroad may have several origins: The majority of inspections are carried out as part of an annual programme based on a risk mapping, including the nature of the activities carried out by stakeholders, the history of past inspections, specific events... Inspections may also be carried out following an internal referral, in particular following an alert received by Anses-ANMV. Finally, inspections may be carried out at the request of external organisations such as the European Medicines Agency or any other European or international competent authority.

Inspection steps include:

  • initiation of the inspection: an inspection mission shall be assigned to one or more inspectors accompanied, if any, by an expert. They are part of the inspection team. The site concerned is notified or not of the imminent inspection;
  • preparation of the inspection: the inspection team shall be aware of the site inspected, its history, the products handled there and the activities carried out;
  • the inspection itself: the inspection team assesses on-site or remotely the site’s compliance with one or more given benchmarks;
  • the inspection report: the inspection concludes with the drawing up of an inspection report by the inspection team indicating the deviations from the benchmarks. The inspection report is drawn up through an adversarial process through the sending of a preliminary report to the inspected site. The latter may indicate its responses, preventive or corrective actions to remedy any deviations identified. On the basis of these replies, the final report shall be drawn up and shall enable the conclusion of compliance of the site or to take the appropriate decisions in the event of non-compliance.

Inspection follow-up can be of different kinds: 

  • administrative action includes notices and warnings, suspension of the activity causing the risk (suspension, automatic modification, withdrawal of authorisation, etc.) and financial penalties;
  • criminal proceedings;
  • the ordinal suites.

To request an inspection

The different areas of inspection

Objectives: Inspections of non-clinical and pre-clinical safety studies according to Good Laboratory Practice (GLP) aim to ensure the quality and integrity of the data obtained in non-clinical trials on veterinary medicinal products for marketing authorisation so that they can be recognised internationally (including OECD countries) without the need to replicate the studies. GLP is a quality assurance system for the organisation of non-clinical safety studies relating to human and animal health, the environment and the conditions under which such studies are planned, conducted, monitored, recorded, reported, archived and disseminated.

Relevant stakeholders

  • facilities and test sites carrying out non-clinical and pre-clinical safety studies on veterinary medicinal products.

Consult the list of test facilities for the ANMV inspection program (PDF) (see ETAVET) 

Benchmarks:

Community rules

  • parliament and Council Directive 2004/10/EC of 11 February 2004;
  • directive of the European Parliament and of the Council 2004/9/EC of 11 February 2004.

French regulations on veterinary medicinal products (ANMV)

GLP inspections are carried out in accordance with the Code de la santé publique (CSP), in particular Articles L. 5141-1, L. 5141-2, L.5141-4, L. 5146-1, R. 5141-2, R. 5146-1, R. 5146-2, in accordance with the Order of 28 January 2005 below:

  • order of 28 January 2005 on good laboratory practice for veterinary medicinal products and their inspection and verification procedures and on the issuing of documents attesting their compliance;
  • decision 2010/03/131 of 24/03/2010 on the state of play of the test facilities and Annex “GLP file — State of play”;
  • decree No 2013-118 on the protection of animals used for scientific purposes.

To access the regulatory referential

Objective: The purpose of inspections of clinical studies according to good clinical practice (GCP) is to ensure the quality and integrity of the data obtained in clinical trials on veterinary medicinal products for marketing authorisation. Good clinical practice is an international standard of ethical and scientific quality for the design, conduct, monitoring, registration, audit, analysis and drafting of clinical study reports assessing the efficacy of veterinary medicinal products. Compliance with this standard guarantees the integrity of the clinical study data, respect for animal welfare, the protection of personnel involved in the study, the environment and human and animal food chains.

Stakeholders:

  • experimental or field sites where clinical trials are conducted;
  • clinical Trial Investigators;
  • clinical Trial Sponsors;
  • subcontractors and providers involved in these clinical trials (CROs, Analysis Laboratories...).

Benchmark:

  • VICH GL9: good clinical practice

To access the regulatory referential

Objectives: the purpose of inspections for the manufacture of veterinary medicinal products is to verify the conformity of sites that manufacture veterinary medicinal products, even if they are only intended for export, which take part in one of the steps in the process of manufacturing a veterinary medicinal product or which import veterinary medicinal products, with Good Manufacturing Practices (GMP). Any manufacturer of veterinary medicinal products destined for the EU market, anywhere in the world, must comply with GMP. GMPs require that medicinal products be of consistent high quality, suitable for their intended use, and meet the requirements of the marketing authorisation or clinical trial authorisation.

Stakeholders:

  • veterinary pharmaceutical establishments referred to in Article L. 5142-1 and R. 5142-1: manufacturer of veterinary medicinal products and veterinary medicinal products subject to clinical trials, importer of veterinary medicinal products and veterinary medicinal products subject to clinical trials;
  • sites based in third countries responsible for at least one stage of the manufacture of veterinary medicinal products intended for the EU market;
  • other structures take part in one of the steps of the process of manufacturing a veterinary medicinal product: quality control laboratory, radiosterilisation site...

The competent authority for sites engaged in manufacturing and importing active substances used in the manufacture of veterinary medicinal products is the ANSM. 

Benchmarks

  • directive 91/412 EC sets out the GMP principles and guidelines applicable to veterinary medicinal products in the EU. In addition, Regulation 2019/6 sets out related provisions;
  • the EU GMP Guide provides an interpretation of these principles and directives, complemented by a series of annexes that modify or increase requirements for certain types of products, or provide more specific instructions on a particular topic;
  • decision No 2015-03-076 of 11 March 2015 on good manufacturing practices for veterinary medicinal products signed by the Director-General of Anses was amended on 28 April 2016 by Decision No 2016-04-143, on 5 May 2017 by Decision No 2017-04-123 and on 27 May 2021 by Decision No 2021-118. This is a consolidation of the provisions in force and the transposition of common European guidelines for medicinal products for human use and veterinary medicinal products within the inspection group of the European Medicines Agency (EMA) with the participation of experts from Anses and ANSM.

To access the regulatory referential

Objectives: the purpose of inspections concerning the preparation of veterinary autovaccines is to verify that the sites preparing veterinary autovaccines comply with the French good practice of preparing autovaccines (BPPA). In France, veterinary autovaccines concern only inactivated bacterial immunological veterinary medicinal products which are manufactured from pathogens or antigens from one or more animals belonging to an epidemiological unit and which are used to treat the said animal(s) belonging to the same epidemiological unit or to treat one or more animals belonging to a unit with a confirmed epidemiological link.

Stakeholders:

  • autovaccine preparation establishments authorised under Article L5141-12 of the CPMP;
  • sites based outside France in charge of the preparation of autovaccines for the French market.

Benchmarks

  • order of 14 November 2016 on the preparation of autovaccines for veterinary use for ruminants;
  • order of 14 November 2016 amending the Order of 6 March 2008 on good practices in the preparation of autovaccines for veterinary use.

To access the regulatory referential

Objectives: inspections of the wholesale distribution of veterinary medicinal products are intended to verify that the sites distributing veterinary medicinal products comply with European good distribution practices. These measures on good distribution practices ensure the identity, integrity, traceability and quality of veterinary medicinal products throughout the supply chain. In addition, these measures ensure that veterinary medicinal products are properly stored, transported and handled and remain in the legal supply chain during storage and transport.

Stakeholders:

  • veterinary pharmaceutical establishments referred to in Article L. 5142-1 and R. 5142-1: 
    • wholesale distributor of veterinary medicinal products;
    • manufacturer engaged in the distribution of veterinary medicinal products they manufacture.
  • subcontractors: transport, storage...

The competent authority for sites carrying out activities for the distribution of active substances used in the manufacture of veterinary medicinal products shall be the ANSM.

Benchmarks:

  • commission IMPLEMENTING REGULATION (EU) 2021/1248 of 29 July 2021 on measures on good practices for the distribution of veterinary medicinal products pursuant to Regulation (EU) 2019/6 of the European Parliament and of the Council;
  • commission IMPLEMENTING REGULATION (EU) 2021/1280 of 2 August 2021 on measures on good practices for the distribution of active substances used as raw materials in veterinary medicinal products in accordance with Regulation (EU) 2019/6 of the European Parliament and of the Council.

To access the regulatory referential

Objectives: the purpose of inspections of pharmacovigilance activities of veterinary medicinal products is to verify the compliance of the sites involved in the European pharmacovigilance system for veterinary medicinal products with good European pharmacovigilance practice. Veterinary pharmacovigilance concerns the surveillance, evaluation and improvement of the safety of veterinary medicinal products, with particular reference to adverse events in animals and humans related to the use of these medicinal products. This also involves the collection of information on adverse events due to the non-compliant use of veterinary medicinal products and investigations into the validity of the withdrawal period and potential environmental problems related to the use of veterinary medicinal products.

PPVs apply to marketing authorisation holders, their representatives, the European Medicines Agency (EMA) and medicines regulatory authorities of EU Member States. 

Stakeholders:

  • marketing authorisation holder, QPPV, responsible for placing on the market;
  • subcontractor and pharmacovigilance provider.

Benchmarks:

  • commission IMPLEMENTING REGULATION (EU) 2021/1281 of 2 August 2021 laying down detailed rules for the application of Regulation (EU) 2019/6 of the European Parliament and of the Council as regards good pharmacovigilance practices and the format, content and summary of the pharmacovigilance system master file for veterinary medicinal products; 
  • a good veterinary pharmacovigilance guidelines (VGVP guideline) provides a detailed interpretation of the principles and guidelines contained in good pharmacovigilance practices. This guideline is divided into modules covering the main processes of pharmacovigilance:
    • module: Collection and recording of suspected adverse events for veterinary medicinal products; 
    • module: Signal management;
    • module: Communication of veterinary pharmacovigilance; 
    • module: Pharmacovigilance systems, their quality management systems and pharmacovigilance system master files; 
    • module: Pharmacovigilance controls and inspections; 
    • module: Glossary. 

To access the regulatory referential