Seminario SSFA. New Guideline on Good Pharmacovigilance Practice (GVP) Fare clic per modificare lo stile del sottotitolo dello schema

Transcription

1 Seminario SSFA New Guideline on Good Pharmacovigilance Practice (GVP) Pharmacovigilance Systems and their Quality Systems Milano, 20th April 2012 GIULIA M. VALSECCHI The proposed GVP - Module 1 Guidance on establishment and maintenance of a Quality Assured Pharmacovigilance System Released for consultation: 21 February 2012 End of consultation: 18 April 2012 Final version effective from July

2 The proposed GVP - Module 1 Legal basis REG 1235/ Article 87 (b) the minimum requirements for the quality system for the performance of pharmacovigilance activities by the Agency DIR 2010/84 - Art. 108 (b) the minimum requirements for the quality system for the performance of pharmacovigilance activities by the national competent authorities and 3 The proposed GVP - Module 1 Table of Contents: I.A. Introduction I.B. Structure and Processes I.C. Operation of EU network Principles of the GVP Module 1 consistent with general principles of ISO 9000 Reference to REG., DIR., IM (Implementation Measures) Fare clic per modificare lo stile del sottotitolo Shall vs Should dello schema 4

3 What is QUALITY? The totality of features and characteristics of a product or service that bear on its ability to satisfy stated or implied needs. [Source: ISO 8402:1994 Quality management and quality assurance Vocabulary, withdrawn and revised by ISO 9000:2000 Quality management systems -- Fundamentals and vocabulary, March ] 5 Quality NOT a qualitative BUT a quantitative concept MEASURED: AGAINST PREDEFINED QUALITY REQUIREMENTS DOCUMENTED : NOT WRITTEN NOT EXISTING 6

4 Quality Dimensions EXPECTED By the client or from the supplier, in order to satisfy its requirements DESIGNED Set of quality attributes of SERVICE/product together with processes and resource organization prepared in order to achieve quality PROVIDED Set of quality attributes of SERVICE/product obtained at the end of a process PERCEIVED What is evaluated by the client in terms of requirement/need satisfaction 7 The Quality Route From QUALITY CONTROL (oriented to products) through QUALITY ASSURANCE (oriented to processes) to QUALITY MANAGEMENT (oriented to systems) 8

5 Quality System Requirements Used Known Documented 9 Continuous Improvement The Quality System is never complete! Objective oriented and systematic development Satisfied Customer/End User as ultimate goal Continuous improvement Reviews for follow-up 10

6 Reference for Pharmacovigilance Quality System Predicate Rules Systems to ensure pharmaceutical quality, defined as established identity, strength, purity, and other quality characteristics designed to ensure the required levels of safety and effectiveness Quality System (i.e. ISO 9000 series) Requirements needed to ensure organizations meet the needs of its customers while striving to meet their expectations, more generic, fits all companies 11 New PhV standards: Changing Perspective Written Procedures Training Audit Document management (record retention) Quality objectives and requirements Structure and process Measurement Improvement FROM QUALITY ASSURANCE TO QUALITY SYSTEM 12

7 Pharmacovigilance: the complex environment Technical Operation Clinical Operation Regulatory Medical Informatio n Legal Investigators CRO Drug Safety Unit Affiliates Ethical Committe e Regulatory Authorities Licensing Partner Quality Assurance Informatio n Technolog y 13 Quality System for Pharmacovigilance The Quality System should be seen as an integral part of the Pharmacovigilance System The following areas are considered in defining the minimum requirements: Resource Management (I.B.5; I.B.6, I.B.7, I.B.8) Compliance Management (I.B.9, I.B.11.3, I.B.12) Record Management (I.B.10, I.B.11) 14

8 Quality System for Pharmacovigilance Systematic Approach Definition of quality objectives General Structure and process specific Definition of method for monitoring Identification of indicators 15 I.B.1 Pharmacovigilance 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(28d)]. A Pharmacovigilance System, like any system, is characterised by its structures, processes and outcomes. 16

9 I.B.2 Quality of Pharmacoviglance system Quality of Pharmacovigilance System can be define as all the characteristics of the system which are considered to produce outcomes relevant to the objectives of PhV. 17 I.B.2 Quality Requirements and Quality Objectives Quality Requirements are those characteristics that are likely to produce the desired outcome (Quality Objective) Overall quality objectives of PhV [I.B.4]: Complying with legal requirements Preventing harm from AE in humans Promoting safe and effective use Contributing to the protection of patients Specific quality objectives in each Module of GVP 18

10 I.B.3 Quality Cycle Establishing structures and planning integrated and consistent processes (quality planning) Carrying out the tasks and responsibilities (quality control) Monitoring and Evaluating how effectively the structures and processes have been established and how effectively the processes are being carried out (quality assurance); and Correcting and improving the structures and processes and the carrying out of those processes Fare clic per as necessary modificare (quality lo stile del improvements) sottotitolo dello schema 19 Model of a process-based quality management system 20

11 I.B.5. Principles for good Pharmacovigilance practices The needs of the stakeholders in relation to the safety of medicine are met Leadership is provided by High Management All people are involved according to task and responsibilities and engaged in continuous improvement Resources and activities are defined as structure and processes Risk-benefit balance is continuously assessed Good cooperation between MAH, CA, Patients, HCP, licensing partner is fostered (-> communications) 21 I.B.6. Responsibilities 1/2 What is High Management responsible for? Motivating all staff members, Assigning roles, responsibilities and authorities to staff members according to their competencies and communicating and implementing these throughout the organisation. 22

12 I.B.6. Responsibilities 2/2 What is Management responsible for? Quality system is documented Change are controlled Adequate resources are available and training is provided Suitable and sufficient premises, facilities and equipment are available Effective communication flows are set and applied Any concern is properly investigated Fare clic per modificare Audit lo stile are del performed sottotitolo dello schema Quality system is reviewed at regular intervals to verify its effectiveness and CAPA measures are defined and introduced 23 I.B.7 Training Essential for achieving the required quality Plan, Execute, Check Training record management Initial and Maintenance training Different level according to different responsibilities 24

13 I.B.8 Facilities and equipment Essential for achieving the required quality Properly located, designed, manufactured, and maintained Subject to appropriate checks, qualification and/or validation activities Risk assessment 25 I.B.9.1 Specific Quality System Processes Pharmacovigilance data are continuously monitored, option for risk minimization and prevention are considered and appropriate measure taken All information on the risk of medicinal products is evaluated scientifically Data on serious and non-serious adverse reactions are submitted to the EV database Data are verified and duplicate are detected Communication with CAs is effective Product information is kept up-to-date with the current scientific knowledge Appropriate safety communications with HCP and patients 26

14 I.B.10 Record Management Ensures data/documents maintenance, retrieval and traceability Covers: Completeness, accuracy and integrity of PhV data Internal and external communication Document retention Measure Fare clic shall per be modificare taken at lo each stile del stage sottotitolo in the dello storage schema and processing of PhV data to ensure data security and confidentiality (limited access to authorised personnel) Personal data protection has to be fully and effectively guaranteed in conformity with legal provisions Protection from destruction, expecially during the retention period 27 I.B.11 Documentation of the Quality System All elements, requirements and provisions adopted for the quality system shall be documented in a systematic and orderly manner in the form of written policy and procedures, such as quality plans, quality manuals and quality records. Quality Plan sets the quality objectives and the processes to achieve them Procedures are the way to carry out a process, may take the format of a SOP, Work Instruction or manuals Quality Manual defines the scope of the quality system and the processes Quality Records provides evidence of activities performed 28

15 Quality Manual Table of Contents 29 Traceability between ISO requirements and PhV processes ISO Requirements PhV Processes 4 - QUALITY MANAGEMEN SYSTEM Documentation Management Record Management 5 - MANAGEMENT RESPONSIBILITIES Management Review 6 - RESOURCES MANAGEMENT 7 SERVICE REALIZATION 8 MEASUREMENT Training Facilities, Equipment Safety monitoring Risk Management Case Management Periodic Report Complaint Literature Search Product Information management Internal Audit Deviation Management CAPA 30

16 I.B.11 Documentation of the Quality System Includes Organizational structure documents (organisation diagram, job descriptions) Training plan and records (to be available for audit and ispection) Instructions for compliance management process and critical processes (SOPs, WI) Performance indicators Audit reports Methods for monitoring the system effectiveness Records created as a results of Pharmacovigilance activities Records and report relating to facilities and equipment Records to demonstrate deviation management/capa/effectiveness checks Record management 31 Structure of the PhV QMS documentation Quality Management Manual (QMM) Process 1 Process 2 Process 3 Process X SOP 1 SOP 2 WI 1 Record Record 32

17 Structure of the PhV QMS documentation QMM Process Procedures Work Instructions Forms & Records 33 I.B.11.3 Critical Pharmacovigilance processes Continuous safety profile monitoring Risk management system ICSR processing Signal detection and evaluation Periodic reports management (scheduling, preparation including QC-, assessment and submission) Managing request and communication with CAs Interaction between Pharmacovigilance and quality defects system Appropriate instructions should be available for critical PhV processes Communication about safety Keeping product information up-to-date Implementation of variations 34

18 I.B.12. Monitoring performance and effectiveness Reviews of the systems by management (Management Review) Risk based audits at regular interval Quality system documentation reviewed at regular interval Review program Compliance Monitoring Evaluating Fare clic the per modificare effectiveness lo stile of del actions sottotitolo taken dello with schema medicinal product for the purpose of minimising risk and supporting the safe use CAPA system in place The organisation should define in advance the method for monitoring and the indicators to be used to demonstrate the effectiveness in operating the Pharmacovigilance system 35 I.C. Operation in the EU network I.C.1 Overall Pharmacovigilance responsibilities of the applicant and the MAH in the EU I.C.2. Overall Pharmacovigilance responsibilities within the EU regulatory network The MAH shall operate a Pharmacovigilance system and shall establish and follow a quality system In some circumstances, it should be possible to establish more than one Pharmacovigilance system (i.e. in case of specific products such as vaccines or product available without medical prescriptions) 36

19 I.C.1.1. Responsibilities of the MAH in relation to QPPV The MAH shall have permanently and continuously at its disposal an appropriately qualified person responsible for Pharmacovigilance in the EU (QPPV) Job description of QPPV In addition a local contact person acting at national level and reporting to QPPV The QPPV shall have the necessary level of authority 37 I.C.1.1. Responsibilities of the MAH in relation to QPPV The MAH should ensure that the QPPV receives/can access all the relevant information, in particular: Emerging safety concerns and other information related to benefitrisk evaluation of a medicinal products covered by the Pharmacovigilance system On going or completed clinical trials Compliance information Outcome of regular reviews of quality system 38

20 I.C.1.2. Qualification of QPPV in the EU Theoretical and practical knowledge for the performance of Pharmacovigilance activities Expertise or access to expertise in relevant areas Qualification of QPPV shall be assessed prior appointment QPPV should be provided with training on MAH s Pharmacovigilance system(s) before taking up the position 39 I.C.1.3. Role of the QPPV The QPPV is a natural person Shall reside and operate in the EU Accessible through QPPV s contact details A Back up person shall be ensured Responsible to establish and maintain the MAH s Pharmacovigilance system Authority and responsibility over the Pharmacovigilance System Master File The QPPV may delegate specific tasks, under supervision, to appropriately qualified and trained individuals, for example, acting as safety experts for certain products, provided that the QPPV maintains system oversight and overview of the safety profiles of all products. Such delegation should be documented 40

21 I.C.1.3. Role of the QPPV Oversight over the functioning of the system in all relevant aspects, including its quality system: SOPs Contractual Agreements Database operations Compliance data regarding quality, timeliness of expedited and periodic reporting Audit reports Training of personnel in relation to Pharmacovigilance Should be aware about the validation status of the database and informed about significant changes 41 I.C.1.4. Specific Quality System processes of MAH in EU Submission of adverse reaction data to EV within the legal timelines Monitoring the use of terminology, with data entry staff being instructed in the use of terminology Retention of essential documents describing the Pharmacovigilance system as long as the system described in the Pharmacovigilance System Master File exists and for at least further 5 years after it has ceased to exist Retention of Pharmacovigilance data and documents relating to authorised medicinal products as long as the MA exists and for at least further 10 years after the MA has ceased to exist Product information is kept up-to-date with current scientific knowledge, including the assessments and recommendations made public via the European medicines 42

22 I.C.1.4. Specific Quality System processes of MAH in EU RECORD RETENTION The retention periods apply unless longer periods are required by applicable regulatory requirements or national law During the retention period, retrievability of the documents should be ensured Documents can be retained in electronic format, provided that the electronic system has been appropriately validated and appropriate arrangements exist for system security, access and back-up of data. If documents in paper format are transferred into an electronic format, the transfer process should ensure that all of the information present in the original format is retained in a legible manner and that the media used for storage will remain readable over time. 43 I.C.1.5. Quality System Requirements for PhV task delegated by MAH The MAH may transfer any or all of the Pharmacovigilance tasks, including the role of the QPPV, to another organisation or person (where the same requirements apply to a person as for an organisation). The ultimate responsibility for the fulfilment of all Pharmacovigilance tasks and responsibilities and the quality and integrity of the Pharmacovigilance system, however, always remains with the MAH All guidance provided in GVP is also applicable to the other organisation to which the tasks have been delegated Detailed, up-to-date and clearly documented contractual arrangements between the MAHand the other organisation are in place, describing arrangements for delegation and the responsibilities of each party. 44

23 I.C.2. Overall Pharmacovigilance responsibilities within the EU regulatory network Role of Competent Autorities in Member States Role of European Commission Role of EMA Secretariat Pharmacovigilance Risk Assessment Committee (PRAC) Committee for Medicinal Products for Human Use (CHMP) Coordination Group for Mutual recognition and Decentralized Fare Procedure clic per modificare Human (CMDh) lo stile del sottotitolo dello schema Specific quality process for CA in MS and Agency Quality system requirements for PhV task delegated by CA in MS 45 The challenge Complex Organizations Cross-company processes Many interfaces (internal and external, i.e. Competent Authority, Agency) Information flows Communication requirements Regulatory risks Protection of public health High level of performance 46

24 The opportunity Make Good Practice as Practice, Invest Quality Thank you! 47