1、 See websites for contact details European Medicines Agency www.ema.europa.eu Heads of Medicines Agencies www.hma.eu The European Medicines Agency is an agency of the European Union European Medicines Agency and Heads of Medicines Agencies, 2012. Reproduction is authorised provided the source is ack
2、nowledged. 22 June 2012 EMA/541760/2011 Guideline on good pharmacovigilance practices (GVP) Module I Pharmacovigilance systems and their quality systems Draft finalised by the Agency in collaboration with Member States and submitted to ERMS FG 19 January 2012 Draft agreed by ERMS FG 24 January 2012
3、Draft adopted by Executive Director 20 February 2012 Released for consultation 21 February 2012 End of consultation (deadline for comments) 18 April 2012 Revised draft finalised by the Agency in collaboration with Member States 20 June 2012 Revised draft agreed by ERMS FG 21 June 2012 Revised draft
4、adopted by Executive Director as final 22 June 2012 Date for coming into effect 2 July 2012 Guideline on good pharmacovigilance practices (GVP) Module I EMA/541760/2011 Page 2/25 Table of contents I.A. Introduction . 4 I.B. Structures and processes 4 I.B.1. Pharmacovigilance system 4 I.B.2. Quality,
5、 quality objectives, quality requirements and quality system 5 I.B.3. Quality cycle 5 I.B.4. Overall quality objectives for pharmacovigilance 5 I.B.5. Principles for good pharmacovigilance practices . 5 I.B.6. Responsibilities for the quality system within an organisation 6 I.B.7. Training of person
6、nel for pharmacovigilance 7 I.B.8. Facilities and equipment for pharmacovigilance 7 I.B.9. Specific quality system procedures and processes 8 I.B.9.1. Compliance management by marketing authorisation holders . 8 I.B.9.2. Compliance management by competent authorities . 8 I.B.10. Record management .
7、9 I.B.11. Documentation of the quality system 10 I.B.11.1. Additional quality system documentation by marketing authorisation holders 11 I.B.11.2. Additional quality system documentation by competent authorities 11 I.B.11.3. Critical pharmacovigilance processes and business continuity 11 I.B.12. Mon
8、itoring of the performance and effectiveness of the pharmacovigilance system and its quality system . 12 I.B.13. Preparedness planning for pharmacovigilance in public health emergencies . 13 I.C. Operation of the EU network . 13 I.C.1. Overall pharmacovigilance responsibilities of the applicant and
9、marketing authorisation holder in the EU 13 I.C.1.1. Responsibilities of the marketing authorisation holder in relation to the qualified person responsible for pharmacovigilance in the EU 14 I.C.1.2. Qualifications of the qualified person responsible for pharmacovigilance in the EU . 16 I.C.1.3. Rol
10、e of the qualified person responsible for pharmacovigilance in the EU 16 I.C.1.4. Specific quality system processes of the marketing authorisation holder in the EU . 17 I.C.1.5. Quality system requirements for pharmacovigilance tasks subcontracted by the marketing authorisation holder . 18 I.C.2. Ov
11、erall pharmacovigilance responsibilities within the EU regulatory network 19 I.C.2.1. Role of the competent authorities in Member States 20 I.C.2.2. Role of the European Commission . 21 I.C.2.3. Role of the European Medicines Agency 21 I.C.2.3.1. General role of the Agency and the role of the Agency
12、s secretariat 21 I.C.2.3.2. Role of the Pharmacovigilance Risk Assessment Committee (PRAC) 22 I.C.2.3.3. Role of the Committee for Medicinal Products for Human Use (CHMP) . 22 I.C.2.3.4. Role of the Coordination Group for Mutual Recognition and Decentralised Procedures - Human (CMDh) 22 I.C.2.4. Spe
13、cific quality system processes of the quality systems of competent authorities in Member States and the Agency 23 I.C.2.5. Quality system requirements for pharmacovigilance tasks delegated or transferred by competent authorities in Member States 24 Guideline on good pharmacovigilance practices (GVP)
14、 Module I EMA/541760/2011 Page 3/25 I.C.2.6. Transparency of the quality system of the EU regulatory network 24 I.C.3. Data protection in the EU 24 I.C.4. Preparedness planning in the EU for pharmacovigilance in public health emergencies25 Guideline on good pharmacovigilance practices (GVP) Module I
15、 EMA/541760/2011 Page 4/25 I.A. Introduction This Module contains guidance for the establishment and maintenance of quality assured pharmacovigilance systems for marketing authorisation holders, competent authorities of Member States and the Agency. How the systems of these organisations interact wh
16、ile undertaking specific pharmacovigilance processes is described in each respective Module of GVP. The definition of a pharmacovigilance system is provided in Article 1 of Directive 2001/83/EC as a system used by the marketing authorisation holder and by Member States to fulfil the tasks and respon
17、sibilities listed in Title IX and designed to monitor the safety of authorised medicinal products and detect any change to their risk-benefit balance. The Agency likewise maintains a pharmacovigilance system to fulfil its pharmacovigilance activities. For performing their pharmacovigilance activitie
18、s, marketing authorisation holders, competent authorities of Member States and the Agency shall establish and use quality systems that are adequate and effective for this performance. The legal requirement for quality systems was introduced by Directive 2010/84/EU amending Directive 2001/83/EC (the
19、latter is referenced as DIR) and Regulation (EU) No 1235/2010 amending Regulation (EC) No 726/2004 (the latter is referenced as REG) to strengthen pharmacovigilance in the EU. The minimum requirements of these quality systems are set out in the Commission Implementing Regulation (EU) No 520/2012 on
20、the Performance of Pharmacovigilance Activities Provided for in Regulation (EC) No 726/2004 and Directive 2001/83/EC (the Implementing Regulation is referenced as IR). While there has to be compliance with these legal requirements, the implementation of a quality system should be adapted to the resp
21、ective organisation. By following the overall quality objectives in I.B.4. and the guiding principle in I.B.5. to meet the needs of patients, healthcare professionals and the public in relation to the safety of medicines, the application of the quality system should be adapted to how crucial each ph
22、armacovigilance task is for fulfilling the quality objectives for each medicinal product covered by a quality system. The guidance on quality systems in this Module is consistent with the general principles of the ISO 9000 Standards on good quality management practices, specifically the ISO 9001-200
23、8 Standards on quality management systems, issued by the International Organization for Standardization (ISO). The general application of quality management to pharmacovigilance systems is described under I.B. and requirements specific to the operation of the EU network in I.C In this Module, all ap
24、plicable legal requirements are referenced in the way explained in the GVP Introductory Cover Note and are usually identifiable by the modal verb “shall”. Guidance for the implementation of legal requirements is provided using the modal verb “should”. I.B. Structures and processes I.B.1. Pharmacovig
25、ilance system A pharmacovigilance system is defined as a system used by an organisation to fulfil its legal tasks and responsibilities in relation to pharmacovigilance and designed to monitor the safety of authorised medicinal products and detect any change to their risk-benefit balance DIR Art 1(28
26、d). A pharmacovigilance system, like any system, is characterised by its structures, processes and outcomes. For each specific pharmacovigilance process, including its necessary structures, a dedicated Module is included in GVP. Guideline on good pharmacovigilance practices (GVP) Module I EMA/541760
27、/2011 Page 5/25 I.B.2. Quality, quality objectives, quality requirements and quality system For the purpose of GVP, which provides guidance on structures and processes of a pharmacovigilance system, the quality of a pharmacovigilance system can be defined as all the characteristics of the system whi
28、ch are considered to produce, according to estimated likelihoods, outcomes relevant to the objectives of pharmacovigilance. In general terms, quality is a matter of degree and can be measured. Measuring if the required degree of quality has been achieved necessitates pre-defined quality requirements
29、. Quality requirements are those characteristics of a system that are likely to produce the desired outcome, or quality objectives. The overall quality objectives for pharmacovigilance systems are provided under I.B.4 Specific quality objectives and quality requirements for the specific structures a
30、nd processes of the pharmacovigilance systems are provided in each Module of GVP as appropriate. The quality system is part of the pharmacovigilance system and consists of its own structures and processes. It shall cover organisational structure, responsibilities, procedures, processes and resources
31、 of the pharmacovigilance system as well as appropriate resource management, compliance management and record management IR Art 8(2). I.B.3. Quality cycle The quality system shall be based on all of the following activities: quality planning: establishing structures and planning integrated and consi
32、stent processes; quality adherence: carrying out tasks and responsibilities in accordance with quality requirements ; quality control and assurance: monitoring and evaluating how effectively the structures and processes have been established and how effectively the processes are being carried out; a
33、nd quality improvements: correcting and improving the structures and processes where necessary IR Art 8(3). I.B.4. Overall quality objectives for pharmacovigilance The overall quality objectives of a pharmacovigilance system are: complying with the legal requirements for pharmacovigilance tasks and
34、responsibilities; preventing harm from adverse reactions in humans arising from the use of authorised medicinal products within or outside the terms of marketing authorisation or from occupational exposure; promoting the safe and effective use of medicinal products, in particular through providing t
35、imely information about the safety of medicinal products to patients, healthcare professionals and the public; and contributing to the protection of patients and public health. I.B.5. Principles for good pharmacovigilance practices With the aim of fulfilling the overall quality objectives in I.B.4.,
36、 the following principles should guide the design of all structures and processes as well as the conduct of all tasks and responsibilities: The needs of patients, healthcare professionals and the public in relation to the safety of medicines should be met. Guideline on good pharmacovigilance practic
37、es (GVP) Module I EMA/541760/2011 Page 6/25 Upper management should provide leadership in the implementation of the quality system and motivation for all staff members in relation to the quality objectives. All persons within the organisation should be involved in and support the pharmacovigilance s
38、ystem on the basis of task ownership and responsibility in a degree according to their tasks and assigned responsibilities. All persons involved with the entire organisation should engage in continuous quality improvement following the quality cycle in I.B.3 Resources and tasks should be organised a
39、s structures and processes in a manner that will support the proactive, risk-proportionate, continuous and integrated conduct of pharmacovigilance. All available evidence on the risk-benefit balance of medicinal products should be sought and all relevant aspects, which could impact on the risk-benef
40、it balance and the use of a product, should be considered for decision-making. Good cooperation should be fostered between marketing authorisation holders, competent authorities, public health organisations, patients, healthcare professionals, learned societies and other relevant bodies in accordanc
41、e with the applicable legal provisions. I.B.6. Responsibilities for the quality system within an organisation A sufficient number of competent and appropriately qualified and trained personnel shall be available for the performance of pharmacovigilance activities IR Art 10(1), Art 14(1). Their respo
42、nsibility should include adherence to the principles defined in I.B.5 For the purpose of a systematic approach towards quality in accordance with the quality cycle (see I.B.3.), managerial staff (i.e. staff with management responsibilities) in any organisation should be responsible for: ensuring tha
43、t the organisation documents the quality system as described in I.B.11.; ensuring that the documents describing the quality system are subject to document control in relation to their creation, revision, approval and implementation; ensuring that adequate resources are available and that training is
44、 provided (see I.B.7.); ensuring that suitable and sufficient premises, facilities and equipment are available (see I.B.8.); ensuring adequate compliance management (see I.B.9.); ensuring adequate record management (see I.B.10.); reviewing the pharmacovigilance system including its quality system at
45、 regular intervals in risk- based manner to verify its effectiveness (see I.B.12.) and introducing corrective and preventive measures where necessary; ensuring that mechanisms exist for timely and effective communication, including escalation processes of safety concerns relating to medicinal produc
46、ts within an organisation; identifying and investigating concerns arising within an organisation regarding suspected non- adherence to the requirements of the quality and pharmacovigilance systems and taking corrective, preventive and escalation action as necessary; ensuring that audits are performe
47、d (see I.B.12.). Guideline on good pharmacovigilance practices (GVP) Module I EMA/541760/2011 Page 7/25 In relation to the management responsibilities described above, upper management within an organisation should provide leadership through: motivating all staff members, based on shared values, tru
48、st and freedom to speak and act with responsibility and through recognition of staff members contributions within the organisation; and assigning roles, responsibilities and authorities to staff members according to their competencies and communicating and implementing these throughout the organisat
49、ion. For competent authorities, all persons involved in the procedures and processes of the quality system established for the performance of pharmacovigilance activities shall be responsible for the good functioning of that quality system and shall ensure a systematic approach towards quality and towards the implementation and maintenance of the quality system IR Art 8(5). I.B.7. Training of personnel for pharmacovigilance Achieving the required quality for the conduct of pharmacovigilance processes and their o
