Report to the European Commission on Pharmacovigilance audits carried out in the Medicines Evaluation Board, The Netherlands period of time from

Transcription

1 Report to the European Commission on Pharmacovigilance audits carried out in the Medicines Evaluation Board, The Netherlands period of time from September 2013 to September 2015

2 1. INTRODUCTION Applicable legislation: Article 101 (2) ofthe Directive 2001/83/EC states: "Member States shall,...perform a regular audit of their Pharmacovigilance system and report the results to the Commission on 21 September at the latest and then every 2 years thereafter." This report provides an overview of the audit activities conducted from September to September by the internal audit system of the Medicines Evaluation Board (MEB), the Netherlands. 2. BRIEF DESCRIPTION OF THE PHARMACOVIGILANCE SYSTEM Introduction The MEB has been designated as the national competent authority for the performance of pharmacovigilance [as in DIR Art in the Netherlands. The MEB pharmacovigilance system is used to fulfil the legal tasks and responsibilities in relation to pharmacovigilance: to monitor the safety of authorised medicinal products and detect and confirm any change to their risk-benefit balance. The detailed operational requirements of all MEB pharmacovigilance tasks are set out in the MEB's policies, standard operating procedures (SOPs) and work instructions which are part integrated quality management system. The spontaneous reporting system is maintained by the Netherlands Pharmacovigilance Centre Lareb on behalf of the collects reports from health care professionals and consumers, maintains the national database, carries out signal detection on national data and reports any signals to the MEB. These activities are fully subsidized by the MEB. Lareb has an ISO 9001; 2008 certificate. For Lareb a separate reporting is done (see Annex A). The inspection tasks are performed by the National Health Care Inspectorate is a separate organization which works in close laision with the MEB. The Health Care Inspectorate (IGZ) promotes public health through effective enforcement of the quality of health services, prevention measures and medical products. 2.1 Legislation The EU legislation places an obligation on Member States to operate a pharmacovigilance system for the fulfilment of their pharmacovigilance tasks and their participation in Union pharmacovigilance activities (Article 101(1) Directive 2001/83/EC). Directive 2010/84 has been transposed into Dutch legislation by amendment Medicinal Product Act on 20 December Section 3 of Chapter II Commission Implementing Regulation (EU) No 520/20125 specifies the minimum requirements for the quality systems performance of pharmacovigilance activities by national competent authorities. Pagina

3 2.2 Organisation structure, responsibilities and resources The organisational structure MEB agency is shown below: PT' The staff size of the MEB agency is about 275 fte. The agency supports the decision making of the MEB Board. The Board consists of doctors, pharmacists and scientists. Board members are appointed by the Minister of Health. The agency is mainly funded by fees. About 25 fte is allocated to the Pharmacovigilance (PV) department. The PV department is arranged according to a matrix structure led by the Head of Pharmacovigilance. The PV assessors have one primary pharmacotherapeutic focus and mainly conduct assessment tasks for one of the four human pharmacotherapeutic groups. The experts dedicated to the EU (scientific) committees involved in pharmacovigilance activities (Pharmacovigilance Risk Assessment Committee - PRAC, Committee for Medicinal Products for Human Use - CHMP and Coordination Group for Mutual Recognition and Decentralised Procedures Human- CMDh) are embedded in the 'European Cluster'. The MEB is responsible for assessing (changes in) the benefit risk profile of a medicinal product by performing a variety of pharmacovigilance tasks. The operational and regulatory support for product-related procedures (e.g. RMP, PSUR, etc.) is provided by the pharmacotherapeutic groups. Pharmacovigilance specific expertise to perform these tasks is delivered by the PV division and this is complemented with other expertise (e.g. pre-clinical, quality, communication) from other departments as necessary. The decision making MEB, including pharmacovigilance decisions, is laid down in a policy document which describes in detail which type of decision needs to be taken at a certain level. 2.3 Training In line with relevant EU legislation and the requirements MEB's quality management system, all MEB staff are recruited on the basis of their adequate qualifications and experience. All incoming and existing personnel receive initial and continued training in relation to their roles and responsibilities. At the organisational level the MEB has a strategic staffing plan in place in line with its ambitions. It is supported by an action plan which covers recruitment, permanent education and mobility of MEB staff. The Pharmacovigilance department is included in these plans. Education of PV staff is structured among three lines. Pagina 2 van 8

4 1)The PV professionals can participate in MEB wide teaching methods including more in depth education and clinical lessons; 2 ) four times a year the IVIEB organizes academies with specific pharmacovigilance issues; 3 ) PV professionals follow tailor chosen conferences, symposia, courses or coaching. New employees attend an introduction program based on the PV curriculum. A master apprentice model is being used for training on the job. Staff are allocated cases of increasing complexity according to competence and experience. For the development of professionals, giving presentations and education themselves is at least as instructive as its monitoring, hence the staff are encouraged to give presentations and education inside and outside the MEB. During annual appraisal interview, individual training plans are set On top of this the MEB PV division is heavily involved in various research topics on pharmacovigilance - e.g. risk communication, minimisation, signal detection- together with national academia. Positive side effect of this academic cooperation, is the state of the art knowledge; the MEB's network is also used for training purposes of MEB PV staff. 2.4 Facilities and Equipment One MEB's working principles is the smart building, smart working principle. MEB has one location which serves as a meeting point In case of a crisis (business continuity) the building is not a critical factor. MEB staff can work from any location at any time and actually do. All activities/processes are digitalized. For the primary processes an enterprise content management system is in place. 2.5 Compliance management Compliance management is mainly dealt with through several measures: e.g. business rules, enterprise content management system, time tables, defined procedures, quality control, templates, management reports, and governance measures. For all PV activities an audit trail in the MEB's IT systems is available. The record management is explicitly addressed in PV internal audits. The MEB has drawn up a Code of Conduct in order to help our staff in this respect. This Code of Conduct sets out the standards of conduct to be observed by all MEB staff, including members of the board and external experts, and including the Veterinary Medicinal Products Unit and the Novel Foods Unit. The Code of Conduct consist of: Standards of good administrative conduct; Conflicts of interest; Confidentiality and secrecy; Policy on events and gifts. The integrity policy of the Ministry of Health states that each division has an integrity officer. The MEB has two employees appointed as integrity officers. They have received training and meetings are being organized by the Ministry. A whistle-blowing policy is in place for the public administration at the national level. 2.6 Documentation of the Quality system The detailed operational requirements of all MEB pharmacovigilance tasks that constitute the MEB's pharmacovigilance system are set out in the MEB's policies, standard operating procedures and work instructions, which are part of the MEB's integrated quality management system (ISO 9001 certification). The pharmacovigilance system is embedded in the overall quality system which for example also takes into account the strategy, governance, and business and resource planning of the MEB and all licensing activities. Responsibilities and delegation of tasks for all staff including pharmacovigilance are described in the Quality manual (e.g. organization & formation Board decision making policy document, job descriptions, sign off decision document etc.). Pagina 3 van 8

5 All documents which are part of the Quality management system, including those for pharmacovigilance processes, can be found in the MEB's Learning Guide. This is a web-based software tool which makes the following information available to the MEB staff: Quality manual (quality documents; content related regulatory/assessment instructions); Workflow descriptions for our primary processes; role based in detail descriptions on how to work with our primary process supporting enterprise content management system; E-learning modules. The content management Learning Guide meets the ISO 9001 requirements (procedure in place). 2.7 Business continuity Several important elements of business continuity are in place; e.g. protection of individual health of staff, smart building & smart working principle, back up measures IT, pandemic plan etc. However no overarching business continuity plan is in place at the organisational level. We refer to the outstanding improvement issue on business continuity. The MEB participates in the Incident Review Network. 2.8 Monitoring of performance and effectiveness Performance is monitored in several ways, and at different levels. At the operational level peer review mechanisms are in place for Pharmacovigilance processes within the PV division, but review also takes place through discussion of reports in meetings with the Board in which the assessors have to reflect with the Board members on the assessment reports. After each meeting the Board gives feedback on the quality of the reports and the discussion being held. At the business level several management reports are available at the department level, at the process/procedure level, and at the individual level. Also a balanced score card is monthly available. For the business planning, management also performs a yearly forecast on the resources required by the MEB. PV activities are included in this forecast. Since much of the work of the MEB is within the context of the EU network, the conthbution in all aspects of the work of the network is monitored, for example: For PRAC rapporteurship appointments for initial applications in the centralised procedure, the MEB is one of the leading member states, looking at the number of RMP assessments performed in 2014; Looking at the numbers of safety referrals done in 2014, the MEB is also one of the leading member states. EU IT projects are very important for the performance of PV The MEB allocates considerable resources to the coordination and management of EU IT projects related to pharmacovigilance. The MEB attaches considerable importance to the principles of transparency and openness towards the public. In addition, this basic rule is enshrined in specific legislation and regulations with which the MEB is obliged to comply, such as the Government Freedom of Information Act and the Personal Data Protection Act. Pursuant to these Acts, data which can be traced back to individual persons and which represents commercial interests is confidential. Co-operation within the European network likewise obliges the MEB to exercise restraint with respect to disclosure in current procedures in which dossiers and (preliminary) assessment reports are exchanged within the European Union. The agenda and minutes of MEB meetings are available to the public by law, and the MEB publishes assessment reports which are likewise available to the public. National licenses are published in the Medicines Data Bank, which can be accessed on the MEB website. licenses in question are European, the MEB refers users to the European Medicines Agency website. The MEB's annual reports are also published on its website. Pagina 4 van 8

6 Delegation of tasks The MEB has overall responsibility for pharmacovigilance in the Netherlands. Certain tasks have been delegated by Law to Lareb regarding the ADR reporting and signal detection on the national database according to national legislation. 3. INTERNAL AUDIT ACTIVITY FOR THE PERIOD UNDER REVIEW 3.1 RISK ASSESSMENT risk assessment exercise was conducted in order to determine the pharmacovigilance system audit priorities for the period under review. The final audit strategy was prepared based on this risk assessment and was approved by the executive management of the MEB. By the end of PRAC has classified all PV-processes into three categories: high-medium-low risk. 3.2 SUMMARY OF THE AUDITS FOR THE PERIOD UNDER REVIEW AUDIT ASSIGNMENTS FOR THE PERIOD UNDER REVIEW All audits listed were performed in line with the guidance provided in the GVP Module IV Pharmacovigilance audits. Audit No Audit title Date of audit report Business Continuity PV processes Dec Agenda PRAC and follow-up on PRAC decisions/advice Dec Signal detection and management (ermr) Jan 2014 Communications after C H M P and P R A C meetings Dec Business Continuity PV processes ( ) Objective and scope To review compliance against GVP module I on business continuity requirements Audit body Internal audit team MEB Opinion No business continuity plan for PV-processes is in place that meet the requirements of GVP module I. Perform a risk analysis for designing an agency wide business continuity plan. Involve relevant external parties in the business continuity plan. In case of IT failure the agency is still capable of putting messages on its website. Pagina 5 van 8

7 3.2.3 Agenda PRAC and follow-up on PRAC decisions/recommendations Objective and scope To check adherence to the internal procedures; to check record management, to check communications with the Board, to check communications between PRAC, CHMP and CMDh members, to check communications between PRAC members and case managers from Pharmacotherapeutic groups Audit body Internal audit team MEB Opinion Preparations for PRAC agenda and follow-up on PRAC advice and recommendations are generally well controlled; it appears to be an effective process. Some instructions need and update. Strategic ambitions needs to be reflected in PRAC assessment policy of the agency. Training of staff on recognition of PRAC communication and information advised. Improve communications with EMA (case labeling) Signal detection and management ermr's ( ) Objective and scope Check adherence to the procedures. Fill in the GVP checklist to check compliance with GVP module IX - Signal Management Audit body Internal audit team M E B Opinion The process is well controlled, GVP compliant and very well documented. Audit team suggests to shift a certain task from PV-department to the information processing (RIC) department Communication after meetings ( ) Objective and scope To check the process which leads to regular news messages on the MEB website after CHMP and PRAC meetings. Risk Communication (e.g. DHPCs) excluded Audit body Internal audit team MEB Opinion The process is not well defined, no instruction(s) available, process owner is not clear, also the process seems to be too complex. Pagina 6 van 8

8 Audit outcomes and actions Actions based on [number of] audit outcomes which are reported and rated as 'Critical and as 'Major', in line with the guidance provided in the GVP Module IV Pharmacovigilance audits. Audit Find Audit outcomes Action Action Type of No description description end on status of follow-up actions 03-1 No business Major Develop 1 Jan Plan to be implement 2013 continuity plan for and 2017 approved in Annual PV-processes in implement 2015 ISO remark place that meet the business requirements of continuity GVP module plan 04-1 No formalized Major Internal Oct Process Monitoring 2014 approach for working 2015 progress by publishing feedback group to formal QM from plenary define and approval department CHMP/PRAC on the simplify the October MEB website process 2015 Pagina 7 van 8

9 FOLLOW-UP 4.1 SUMMARY OF ACTION PLANS FROM PRIOR BIENNIAL REPORTS The following table provides an overview of earlier audit outcomes issued by the internal audit teams and their implementation by the MEB at September For action from audit outcome graded as: Total Implemented Number not implemented Not started In progress Critical NA NA NA Major NA NA NA Total NA NA NA 4.2 OUTSTANDING ISSUES FROM PRIOR BIENNIAL REPORTS Direct Healthcare Professional Communications; two out of five issues outstanding. In addition to the internal audit, scientific research has been done on the effectiveness of hsk communication, specific DHPC (Piening S, Communicating risk Thesis Rijksuniversiteit Groningen, These findings has led to significant new insights and revision of a MEB policy document which is out for public consultation. Major changes in the DHPC-processing will be implemented after the public consultation has taken place DECLARATION The MEB confirms that this report contains a complete account of all pharmacovigilance system audit activity performed in the period under review to fulfil the obligations of this organisation under Directive 2001/83/EC /Regulation (EC) of the National Competent Authority Date 1 Delete as necessary - National Competent Authorities are required to perform regular audit of their Pharmacovigilance system and report the results to the Commission on 21 September at the latest and then every 2 years thereafter. (Directive 2001/83/EG The European Agency is required regular independent audits of its phamnacovigiiance and report the results to its IVIanagement Board on a basis. (Regulation (EC) No.726/2004 Art 28f) Pagina 8 van 8