The activities of the EU4H11 Joint Action concern the EU/EEA National competent authorities supervising pharmaceutical manufacturers to verify their compliance with Good Manufacturing Practice (GMP) and pharmaceutical wholesalers to verify their compliance with Good Distribution Practice (GDP).

In the European Economic Area (EEA), the respective national inspectorates are responsible for monitoring manufacturing and trading companies within their own territory. Pharmaceutical manufacturing companies outside the EEA are inspected by the EEA authority where the importer is located – except in cases where the EU has concluded a Mutual Recognition Agreement (MRA) with the respective country, such as with the United States of America and Canada. MRAs are trade agreements aiming at facilitating market access and international harmonisation of compliance standards. In these cases, inspections are mutually recognised.

Harmonisation at the EEA level has a long tradition with the Good Manufacturing and Distribution Practice Inspectors' Working Group of the European Medicines Agency (EMA’s GMDP IWG), consisting of experienced inspectors from national authorities. This group is led and coordinated by EMA. The common basis of inspection-related processes and forms is recorded in the "Compilation of Union Procedures and Exchange of Information (CoUP)", which is continuously updated. Several subgroups were founded to work on dedicated topics on behalf of EMA’s GMDP IWG. In 2024, a subgroup, the Drafting Group on GDP, was established to promote harmonisation in the field of Good Distribution Practice. The quarterly meetings of the GMDP IWG also include the European Commission, observers from EU accession countries, MRA partner authorities, the EDQM, and the WHO.

The JAP (Joint Audit Programme) is an audit programme that has existed since 2002 to evaluate the GMP pharmaceutical inspectorates in the EEA to ensure uniform GMP standards and harmonized procedures of the inspection authorities. The JAP was established by decision of the Heads of Medicines Agencies (HMAs) of the EEA and is implemented by the Compliance Group of the EMA GMDP IWG with support from the EMA Inspections' Office.

In a Joint Audit, the equivalence of the quality system and processes of the inspection authority is evaluated based on 78 indicators. These indicators are harmonized with third countries that have signed Mutual Recognition Agreements (MRA) with the EU. Additionally, the JAP - Joint Audit Program of the EEA is largely unified with the international JRP - Joint (Re-) Assessment Program of the PIC/S (International Pharmaceutical Inspection Co-operation Scheme). The audit results are therefore mutually recognized, and the respective audit requirements are considered covered.

The JAP thus not only contributes to strengthening mutual trust within the EEA but also to strengthening trust between the pharmaceutical authorities of the EEA and those from MRA third countries as well as member authorities of the PIC/S. Efforts for mutual recognition of inspection results significantly contribute to optimizing inspection resources, but also to optimizing the resources of the regulated entities / pharmaceutical manufacturers, as the number of inspections at a site is reduced and the requirement for re-analysis upon import into the EEA is eliminated.

The Mutual Recognition Agreements are each focused on specific products and can be expanded if necessary. For example, in 2023, the MRA with the US FDA was extended to veterinary medicinal products, first for 16 national pharmaceutical authorities in the EEA, with gradual recognition and inclusion of additional inspectorates in 2024.

The Joint Action EU4H11 is ongoing since November 1st 2022. The Kick-off meeting for EU4H 11 was successfully organised as a hybrid meeting at AGES/BASG (AT), Vienna from December 5th to 6th 2022.  During the first few months, the project plans were refined, and processes were defined. Those are continuously implemented in the four mandatory work packages. Co-financing of JAP activities and GMP inspectors’ training activities is ongoing. The activities in work packages 5 and 6 have been launched at the beginning of 2023. Work package 7 activities will start in 2024 as planned. ANSM (FR) is leading work package 5. It aims at strengthening the Joint Audit Programme (JAP) for EU/EEA GMP Inspectorates by optimising training and qualification processes for auditors as well as existing JAP processes. NCPHP (HU) is leading work package 6. It works towards harmonization of GDP inspection standards. A proposal to include GDP to the existing Joint Audit Programme will be developed.

Addition of Project Partners
The addition of seven EU/EEA Medicines Inspectorates for veterinary medicines has been completed. A total number of 39 participating partner agencies has been reached.

Recent proposals on EU-level
The Joint Audit Programme (JAP) is part of the recently published draft of the new Pharma Legislation, proposed by the European Commission to become mandatory by the respective Regulation (Article 54). According to the proposal, each Member State shall provide trained auditors. In addition, a new Procedure “EU/EEA Programme for Maintenance of Equivalence in Supervision of Good Manufacturing Practice (GMP) Compliance of Pharmaceutical Companies” has been added to the Compilation of Union Procedures on Inspections and Exchange of Information in June 2023 (Rev. 19). This new procedure details elements to achieve and maintain equivalent supervision standards throughout EU/EEA. Amongst others, the active contribution to the Joint Audit Programme by EU/EEA competent authorities through provision of auditors is expected.

Project highlights

• The qualification process for JAP auditors has been finalised.
• The first Joint Action (online) training session for JAP/JRP auditors was held from 5-6 Oct 2023. The training was organised by ANSM with additional support from the European Commission, EMA and Pharmaceutical Inspection Cooperation Scheme (PIC/S). The participation of senior auditors from European or PIC/S authorities as trainers allowed future auditors to benefit from their valuable experience. The training was attended by 150 participants. GMP inspectors / staff of GMP inspectorates have been trained in detail to contribute as an auditor in the future – and/or to strengthen the understanding of the JAP/JRP programmes / indicators as auditee. The recording of the virtual training course will be available for access to EU/EEA Authorities via EU NTC and for PIC/S Participating Authorities via PIC/S Inspectorate’s Academy (PIA).
   

On 3rd and 4th October 2024 the French Medicines Agency ANSM organised the second training for auditors of the Joint Audit Programme (JAP) in the frame of the Joint Action: This face-to-face advanced training course was held at the ANSM facilities in Paris with the following objectives:

• To deepen the knowledge and skills acquired during the initial theoretical training, and to apply them in practical workshops; and
• To immerse the auditors in a real audit situation by carrying out a mock ANSM audit.

The training was attended by 32 participants from 18 Member States, namely Austria, Belgium, Bulgaria, Croatia, Cyprus, Germany, Estonia, Finland, France, Italy, Latvia, Netherlands, Poland, Portugal, Romania, Slovenia, Spain, and Sweden. Furthermore, an observer from the European Commission was present. 4 experienced auditors acted as trainers: Anne Hayes (IE-HPRA), Ana Rita Martins (PT-INFARMED), Andreas Kraßnigg (AT-AGES) and Jacques Morénas (FR-ANSM).

This training course, directed at (future) auditors of the Joint Audit Programme was exceptional by simulating a joint audit of ANSM, colleagues could not only benefit from practising their (future) role applying their technical and social skills. Moreover, this course concept enabled a variety of discussions by sharing experiences of assessments and audit situations. Not only did all participants gain a deeper insight, but also elements with opportunities for improvement regarding the Joint Audit Programme itself have been revealed. This great success was built on months of intense preparatory work by a considerable team from ANSM to develop the training. In addition to detail the course concept comprising a range of colleagues involved in training delivery, the respective self-assessment and documentation of ANSM was prepared and provided. 

In our role as Joint Action Coordinator and on behalf of the entire EU/EEA Inspectors Network, we herewith express our sincere gratitude to ANSM for organising this outstanding training event, as well as to the trainers for their continuous contribution to the trainings. In addition, we are pleased to welcome our colleagues to the pool of JAP auditors!

This training course, and in total three training sessions being organised by ANSM in the frame of the EU4H11 Joint Action, enable us to reach the aim of our project to maintain a substantial number of well-trained, qualified auditors to maintain the Joint Audit Programme on a long-term basis.

Since November 2023, the EU4H11 Joint Action Team is continuously making progress in implementing the action tasks aiming at strengthening the capacity of the GMDP inspectors’ network to enhance equivalency in inspections and GMDP regulatory compliance programmes. 

Summary of achievements 

Work Package 4 & 5 – Strengthening the Joint Audit Programme by co-funding of JAP activities, optimising training and qualification processes of JAP auditors and optimising existing JAP processes 

• The activities of the Joint Audit Programme (JAP) are continuously co-funded: Co-funding is not only provided for travel, accommodation and subsistence costs of auditors travelling to on-site audits and face-to-face trainings. Moreover, NCAs providing auditors and sponsors to run the JAP and dedicating resources for initial and continuous training of auditors receive financial support for the respective personnel costs.
• The qualification process for new JAP auditors was applied by EMA in 2024 for assignments of 2025 audits in a pilot phase, as agreed by the Compliance Group.
• Rules on reimbursement of JAP auditors’ cost detailing provisions regarding the reimbursement of JAP auditors’ expenses, were finalised and adopted by the Compliance Group, with implementation starting JAP audits in September 2024. The major change is the application of daily allowance rates established on EC level.
• A JAP audit report review checklist was developed to harmonise the JAP audit report review amongst Compliance Group sponsors. The Compliance Group agreed in September 2024 to use the checklist for a 1-year-pilot phase.
•  An advanced training course for JAP auditors was organised by ANSM at its facilities in Paris from 3rd - 4th October 2024 (refer to dedicated section). 

Work Package 4 & 7 –Strengthening the capacity of EU/EEA GMP inspectors by co-funding of GMP training activities and optimising training and qualification processes of GMP inspectors 

• Training activities of GMP inspectors are continuously co-funded. NCAs select trainings depending on their needs, ranging from basic to continuous training, from F2F events or online courses organised by different regulatory entities, associations and training providers to joint inspections for training purposes (Joint Inspections Training, see below). 
• The Joint Action EU4H11 supported the launch of the JIT – Joint Inspection Training of EMA in 2023. The training program aims to coordinate offers and demands for observing GMP inspections for training purposes in another EU/EEA member state. Co-funding is offered both for trainers and trainees.
• In March 2024, EU/EEA GMP inspectors and EU/EEA Heads of GMP inspectorates have been invited to complete questionnaires on training and qualification of GMP inspectors, training needs and sustainability of GMP inspectorates. 35 Heads of EU/EEA GMP Inspectorates (response rate: 83%) and a total of 148 EU/EEA GMP inspectors replied to the questionnaires. The results have been shared amongst the network and are used to define and implement recommendations. Furthermore, they will be considered for further training organisation and sustainability actions.

Work Package 6 – Strengthening the EU/EEA GDP inspectors’ network by harmonising GDP inspections standards

• A questionnaire on guidelines on GDP of medicinal products for human use and wholesaling activities was drawn up to perform a review of the implementation of the EU GDP legislation and notably the GDP guidelines in national GDP legislation. The questionnaire was distributed to EU/EEA NCAs and responses of 29 member states were received. The analysis of the answers is ongoing.  
• The proposal to extend the Joint Audit Programme to GDP, which was worked on since spring 2023, was finalised. It comprises a JAP GDP indicators list/audit checklist, the respective interpretation guide as well as related procedures and templates. The elaborated draft will be the basis for further discussion by the Compliance Group and finally by the entire competent EU/EEA GDP inspectorates. 

Besides the work of the technical work packages, it is highlighted that the tasks of the mandatory work packages in the established frameworks (project management/coordination, dissemination, evaluation and sustainability) are continuously implemented.

• A total of 20 joint audits with on-site date in the period from 01/11/2022 to 31/10/2024 have been co-financed. 
• By end of October 2024, 25 NCAs out of the total 42 EU-EEA NCAs (60 %) provided auditors to maintain the Joint Audit Programme (JAP).
• 32 participants from 18 EU-EEA Member States/NCAs attended the advanced training course for JAP auditors from 3rd to 4th October 2024. 
• During Joint Action runtime (1/11/2024 – 31/10/2025), we welcome additional 33 co-auditors and 14 lead auditors to run the JAP. 13 auditors-in-training join audit teams before acting as an auditor. 
• By end of April 2024, a total of 74 trainings attended by 57 EU-EEA GMP inspectors have been co-financed.
• By end of October 2024, 7 joint inspections for training purposes were performed: 7 NCAs acted as hosting NCA/trainer and 4 NCAs participated as trainee in the EU/EEA cross-border JIT - Joint Inspections Training Programme.