XVIII CONGRESSO NAZIONALE GIQAR

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1 SOCIETA DI SCIENZE FARMACOLOGICHE APPLICATE SOCIETY SCIENCES FOR APLLIED PHARMACOLOGICAL XVIII CONGRESSO NAZIONALE GIQAR L Audit al Sistema di Farmacovigilanza: Sottogruppo QA PV Roberta Chiecca Bracco Imaging SpA roberta.chiecca@bracco.com 1 Sottogruppo GIQAR: QA Pharmacovigilance Il Consiglio della SSFA ha approvato, nel corso della riunione del 16 Ottobre 2006, la formazione del nuovo sottogruppo GCP: QA Pharmacovigilance (QA PV) L obiettivo del gruppo è quello di individuare un metodo di audit alla farmacovigilanza. 2 1

2 Sottogruppo GIQAR: QA Pharmacovigilance Quality Assurance: Chiecca (Bracco Imaging SpA - MI) Coordinatore Allavena (Rottapharm Monza - MI) Bruzzese (Istituto di Ricerca Servier Roma) Bussoli (ViroStatics - PV) Diotti (Worldwide ClinicalTrials MI) Marcozzi (Sigma Tau Roma) Piccolboni (Zambon Group Bresso -MI) PV Officer: Longoni (Zambon Group Bresso -MI) 3 Audit al Sistema di Farmacovigilanza Perché? La legislazione europea richiede che il MAH abbia un appropriato sistema di farmacovigilanza. Una delle condizioni che rende appropriato il sistema, è la conduzione di audit interni al sistema di farmacovigilanza. 4 2

3 EMEA position paper 2001 ref. CPMP/PhVWP/1618/01 5 EMEA position paper 2001 ref CPMP/PhVWP/1618/ System requirements All MAHs must have an appropriate system of pharmacovigilance in place. This system should be capable of the following: Expedited reporting Periodic Safety Update Reporting Responding to requests for information from Competent Authorities Continuous monitoring of the safety profile of the authorised medicinal products and notifyng competent authorities and health professionals of changes to the benefit/risk of products Meeting CPMP commitments (where MAHs hold a centralised marketing authorisation) Internal audit of the pharmacovigilance system 6 3

4 Obiettivo dell Audit al Sistema di Farmacovigilanza L audit è una valutazione indipendente condotta dal QA dell Azienda o delegata ad un Contractor esterno. L obiettivo è quello di verificare che gli obblighi regolatori di farmacovigilanza vengano adeguatamente assolti dal MAH e in particolare che i processi e le operazioni per la raccolta, gestione, valutazione e distribuzione degli Eventi Avversi siano condotti in ottemperanza alle normative vigenti, alle lineeguida internazionali e alle procedure operative standard. 7 Introduction Glossary Guide on PV Audit Index Checklists Findings Classification 8 4

5 Modalità Operative Definizione degli obiettivi Definizione della struttura del documento Metodologia di lavoro Suddivisione dei compiti Revisione congiunta di ogni checklist Validazione dei contenuti di ciascuna checklist (PV Officer) Standardizzazione dei formati 9 Introduction Glossary Guide on PV Audit Index Checklists Findings Classification 10 5

6 Guide N Version N Effective from: Issuing Department: PHARMACOVIGILA CE AUDIT GUIDE Prepared by: ame Surname Role Department Date Reviewed by: ame Surname Role Department Date Approved by: ame Surname Role Department Date Supersedes:. Guide N :. Version N :. 11 Guide on PV Audit TABLE OF CONTENTS 1. Purpose 2. Scope 3. Responsibilities 4. Procedure 4.1 Methodology Preparation Phase Execution Phase Opening Meeting Review and Interview Close-out Meeting Reporting Phase 5. References Appendix 1: Classification of the audit findings 12 6

7 Scope: It applies to PV system audits at different levels. PV Central Function Affiliates PV AUDIT Partners Distributors Contractors Vendors 13 Methodology: 1. Preparation Phase 3. Reporting Phase 2. Execution Phase 14 7

8 1. Preparation Phase A PV audit plan is periodically prepared by QA and agreed with the QPPV A preliminary notification of the upcoming audit should be sent well in advance requiring key documents related to the audit scope An audit agenda is prepared by QA and provided in advance to the audited PV function, QPPV and, to any concerned department/function 15 Key Documents: Organisational Charts CVs/Job Descriptions/Training Records for relevant personnel Detailed Description of the Pharmacovigilance System (Summary of PV System) Local PV regulations Table of contents of Company Policies, SOPs, Guideline, WI Specific PV SOPs List of products Contracts/Agreements List of clinical studies and pharmaco-epidemiological studies AEs Listings PSURs, ASRs, IBs Labelling docs (SmPC, US PI, etc.) Other 16 8

9 2. Execution phase: Opening meeting Purpose and scope of the audit Audit programme Personnel to be interviewed Audit logistics and sites involved Criteria/classification for audit findings Time and date of closing meeting Execution phase Review and Interview The number of the audited topics and the personnel interviewed depends on: reasons subject of the audit 18 9

10 Reasons for PV audit Routine For cause Pre-inspection Follow-up Qualification (contractor/vendor) 19 Subject of PV audit PV Central Unit Affiliates Partners/Distributors Contractors/Vendors 20 10

11 2. Execution phase L audit viene condotto attraverso: la revisione della documentazione la revisione dei dati l intervista al personale la visita alle strutture 21 Interview of personnel RECEPTION/CALL CENTRE PATIENT HEALTH CARE PROF. INVESTIGATOR REGULATORY AUT. SALES REPRESENTATIVE CLINICAL RESEARCH MEDICAL INFORMATION PRODUCT MANAGERS REGULATORY AFFAIRS QA MANUFACTURING PV UNIT case management 22 11

12 2. Execution phase Le checklist sono degli strumenti operativi che rappresentano un valido supporto per l auditor durante lo svolgimento dell audit. servono da filo conduttore nella revisione documentale e nelle interviste del personale, aiutano a non dimenticare o trascurare aspetti rilevanti, consentono la standardizzazione delle informazioni raccolte che possono essere utilizzate a scopo analitico 23 Checklists N Title Organization and Personnel Global and Local Policies, Procedures, Working Instructions Out of Working Hours Contact Procedures Spontaneous Adverse Drug Reaction / Adverse Events Reporting Clinical Trial ADR/AE Reporting Annual Safety Reports Case Processing and Quality Control Pharmacovigilance Computerized Systems and Safety Database 24 12

13 Checklists N Title Electronic submission of PV data (Eudravigilance management) Periodic Safety Update Reports Scientific Literature Review Signal Detection and Surveillance Labeling (Update of SmPC and IB) Complaints and Recall Risk Management Plan 25 CHECKLIST N. 1 Organisation and Personnel INDEX Page n. 1.1 Organisation Pharmacovigilance personnel Qualified Person Responsible for Pharmacovigilance (QPPV) Local Responsible for Pharmacovigilance Pharmacovigilance training

14 CHECKLIST N. 1 Organisation and Personnel 1.2 Pharmacovigilance Personnel Notes Findings Y/N Regulatory Reference Internal Ref How many people the PV staff is composed of? Full time/part time Consultants Which are the role and responsibilities of each PV staff member? Is an organisation chart available? Has a QPPV been appointed? Has a deputy of the QPPV been appointed? Vol. 9A Part I b) Vol. 9A Part I 1.2, a) Vol. 9A Part I If applicable, are there PV local responsible(s) appointed in some Member States/third countries? If YES: Is a procedure for the exchange of pharmacovigilance data between the local PV and the headquarter PV available? Vol. 9A Part I, 1.2 For Italy D.L. 219/ CHECKLIST N. 5 Clinical Trial AE/ADR Reporting INDEX Page n. 5.1 Availability and adequacy of the relevant documentation Availability and adequacy of Guidelines/SOPs/Working Instructions Interview with Clinical Personnel Random Check of the cases

15 CHECKLIST N Interview with Clinical Personnel Notes Clinical Trial AE/ADR Reporting Findings Y/N Regulatory Reference Internal Ref Introduce yourself and describe your previous experience Provide your CV Describe your present tasks and responsibilities Are you involved in all phases of clinical development (phase I-IV)? Are you involved in different therapeutic areas? What type of PV training did you receive? Is the PV training adequately documented? Please provide copy of your Training Records 29 CHECKLIST N. 5 Clinical Trial AE/ADR Reporting 5.3 Interview with Clinical Personnel Notes Findings Y/N Regulatory Reference Internal Ref What type of training is provided to the investigators concerning AEs reporting? Is the Investigators training documented? Provide copy of SAE form provided to the investigators In case of SAE, who provides the instructions to the investigator? Describe the instructions provided to the investigator Who is involved from drug safety department? 30 15

16 CHECKLIST N. 10 Periodic Safety Update Report INDEX Page n General Questions PSUR Submission/Periodicity PSUR Content PSUR Archive Safety Agreements Select some PSUR 15 a) Content and Format b) Submission c) Archive 10.7 Additional Question for Audit to Affiliates Additional Question for Audit to PV Vendors CHECKLIST N. 10 Periodic Safety Update Report 10.1 General Questions Is PSURs preparation fully managed inside the company? If no, o Are other companies/organisations involved? o Is there an agreement/contract in place? o Which activities are subcontracted? o Are responsibilities of all parties involved clearly defined? Notes Findings Y/N Regulatory Reference Internal Ref Is there an updated SOP on PSURs management covering preparation, review, approval, distribution/submission to HA and archiving? Is an appropriate distribution list in place? Is it updated? Who is responsible for its preparation? How is it maintained constantly updated? Please describe the process of PSURs preparation including interactions with functions/departments involved 32 16

17 CHECKLIST N PSUR Content Notes Periodic Safety Update Report Findings Y/N Regulatory Reference Internal Ref Are format and content of the PSUR compliant with the requirements of Vol. 9A? If no, please specify any discrepancies. For old PSURs the reference is the guideline ICH E2C and its addendum or Volume 9. Vol. 9A Part I Is the PSUR organised in 11 sections as per Vol. 9A? 1. Executive Summary 2. Introduction 3. Worldwide Marketing Authorisation Status 4. Update of Regulatory Authority or MAH Actions taken for Safety Reasons 5. Changes to Reference Safety Information 6. Patient Exposure 7. Presentation of Individual Case Histories 8. Studies 9. Other Information 10. Overall Safety Evaluation 11. Conclusions Vol. 9A Part I Is the PSUR cover page compliant with the template for cover page included in Vol. 9A? Is the serial number of the PSUR indicated? Are name and presentations of the medicinal Vol. 9A Annex Execution Phase Close-out meeting The audit should be concluded by a closing meeting with at least the key personnel. It is recommended that the QPPV, his deputy or other responsible person for pharmacovigilance should attend the meeting

18 The purpose of the closing meeting is: Summarise findings and observations to ensure that the results of the audit are clearly understood and that there is no misunderstanding To clarify the procedures for the distribution of the Audit Report, for the production of responses (i.e. post audit corrective action plan) and for the follow-up audit if appropriate Reporting phase The Audit Report should includes: Purpose of the audit Details of the audited organizations, Names and titles of the personnel present/interviewed Topics covered Audit findings and recommendations Executive summary of the main issues All audit observations are documented in a clear, concise manner and are supported by objective evidence All reported observations/findings should be identified in reference with specific requirements of the regulations or other related documents (SOPs) against which the audit has been conducted and should be scored according to a predefined classification

19 CLASSIFICATION OF AUDIT FINDINGS In accordance with: Procedure for co-ordinating Pharmacovigilance inspections requested by the EMEA (EMEA SOP INS/PhV/1) CRITICAL: a deficiency in pharmacovigilance systems, practices or processes that adversely affects the rights, safety or well-being of patients or that poses a potential risk to public health or that represents a serious violation of applicable legislation and guidelines MAJOR: a deficiency in pharmacovigilance systems, practices or processes that could potentially adversely affect the rights, safety or well-being of patients or that could potentially pose a risk to public health or that represents a violation of applicable legislation and guidelines MINOR: a deficiency in pharmacovigilance systems, practices or processes that would not be expected to adversely affect the rights, safety or well-being of patients 37 Post audit corrective action plan A written post audit corrective action plan has to be prepared by the audited PV Department, for any finding arisen from the audit, the plan should identify at least the corrective action the function responsible the completion date The implementation of the corrective actions could be assessed via a follow-up audit

20 Perchè è importante definire una metodologia di audit? 39 l assenza di metodo potrebbe non consentire all auditor il pieno raggiungimento dell obiettivo prefissato

21 oppure ottenere informazioni disomogenee e difficilmente comparabili tra loro 41 Grazie per l attenzione attenzione!! Roberta Chiecca Bracco Imaging SpA roberta.chiecca@bracco.com 42 21