DOCUMENT NO: EAC/TF-MED/QMS/FD/COM/N1R0 COMPENDIUM OF QUALITY MANAGEMENT SYSTEM (QMS) TECHNICAL DOCUMENTS FOR HARMONIZATION OF MEDICINE REGULATION IN THE EAST AFRICAN COMMUNITY VERSION SEPTEMBER 2014
DOCUMENTS DEVELOPMENT HISTORY STEPS Development of draft harmonized technical documents for Good Manufacturing Practices (GMP) for the East African Community Medicines Regulatory Harmonization Initiative Draft harmonized technical documents approved by the Steering Committee Release of draft harmonized technical documents for Public Consultation End of National Consultation (deadline for comments) Incorporation of national stakeholders inputs by EAC Secretariat in collaboration with EAC Partner States Release of revised technical documents for regional and international consultation End of regional and international consultation (deadline for comments) Draft technical documents reviewed and adopted by EAC Technical Working Group on Medicines and Food Safety Draft technical documents adopted by the 18th EAC Sectoral Committee on Health Draft technical documents finalized by EAC Secretariat in collaboration with EAC Partner States Final technical documents approved by the 9th EAC Sectoral Council on Health Date for coming into effect DATE 1st August 2012 to 19th July 2013 2nd to 3rd September 2013 16th September 2013 to 29th October 2013 28th February 2014 13th to 17th January 2014 20th January 2014 28th February 2014 12th March 2014 14th March 2014 1st to 4th April 2014 17th April 2014 17th April 2014 i
FOREWORD This Compendium has been developed to provide guidance to EAC Partners States National Medicines Regulatory Authorities to implement Quality Management System (QMS). The Compendium was compiled by the East African Community (EAC) Technical Working Group (EWG) on QMS. The EWG relied on available International Standards (ISO 9000 series, ISO/IEC 17020 and ISO/IEC 17025), WHO guidelines, and other experiences from other medicine regulatory authorities. EAC Secretariat is highly indebted to African Medicines Regulatory Harmonization (AMRH) program partners, Bill and Melinda Gates Foundation (BMGF), the World Bank and the United Kingdom Department for International Development (DFID) for their financial assistance; and African Union New Partnership for Africa s Development (AU- NEPAD) for high level advocacy. The EAC Secretariat also recognizes the important contribution of the Clinton Health Access Initiative (CHAI) in the conceptualization of the African Medicines Regulatory Harmonization (AMRH) Initiative. I would like to thank members of the Technical Working Group (EWG) on Quality Management System (QMS) and the WHO expert who contributed to the successful development of the first edition of these Quality Management System documents. I also wish to thank the staff of EAC Secretariat for their dedicated work and coordination of the implementation of the EAC Medicines Regulatory Harmonization (MRH) Project. I also acknowledge the oversight role of the EAC Partner States Ministries responsible for Health, Ministries responsible for EAC affairs and the EAC MRH Project Steering Committee. Finally, I would like to acknowledge regional stakeholders in Sectors of health, trade and industry in EAC for their valuable contribution into the development of this Compendium. Ambassador Dr. Richard Sezibera Secretary General EAC Secretariat ii
PREFACE The Compendium of Quality Management System Technical Documents for Harmonization of Medicines Regulation in The East African Community, 2014 is an EAC publication which sets out the implementation of Quality Management System (QMS) within EAC NMRAs. This Compendium contains five parts namely: 1. The East African Community Quality Management System Requirement, 2014 2. The EAC Guidelines for the implementation of Quality Management System Requirements for the Regulation of Medicines, Cosmetics, Medical Devices and Diagnostics, 2014 3. The Model Manual on the Implementation of East African Community Quality Management System Requirements for the Regulation of Medicines, Cosmetics, Medical Devices and Diagnostics, 2014 4. The Mandatory Documented Procedures; and 5. Code of Conduct for Partner States National Medicines Regulatory Authorities, 2014. The overall objective of these QMS documents is to facilitate mutual recognition and consistent regulatory services delivery by Partner States NRMAs in the regulation of Medicines, Cosmetics, Medical Devices and Diagnostics in accordance with Chapter 21, Article 118 (c, d and e) of the EAC Treaty in order to safeguard public health and improve economic gains within the Community. The East African Community Quality Management System Requirement have been developed to enable uniform implementation of the Quality Management System (QMS) that applies to the regulation of the quality and safety of various pharmaceutical products and services by the National Medicines Regulatory Authorities of the East African Community Partner States. This document is mainly based on ISO 9001:2008 - Quality Management systems requirements. The EAC Guidelines for the implementation of Quality Management System Requirements has been developed to enable uniform implementation of the EAC Quality Management System (QMS) requirements by the EAC Partner States NMRAs. The Model Manual on the Implementation of EAC Quality Management System Requirements has been developed to define and describe the quality management system, authorities and responsibilities of the management personnel involved in the operation of the system, and provide references to general procedures for all activities of the entire NMRA, based on the EAC QMS Requirements. The mandatory documented procedures describe the quality management system framework and enable EAC partner states NMRAs to provide services that meet applicable statutory and regulatory requirements. The EAC Code of Conduct for Partner States National Medicines Regulatory Authorities aims at promoting public confidence in activities of NMRA by ensuring highest level of integrity of the members of the governing boards, advisory committees and iii
staff of EAC Partner States NMRAs through disclosure of any circumstances that could give rise to a potential conflict of interest related to their work. The EAC QMS documents will be periodically reviewed to ensure their continued consistency with any changes in the applicable standards. I would like to thank members of the Technical Working Group (EWG) on Quality Management System (QMS) for Regulations of Medicines, Cosmetics, Medical Devices and Diagnostics under the East African Community Medicines Regulatory Harmonization (EAC-MRH) Project who contributed to the successful development of the first edition of these Quality Management System (QMS) documents that include the EAC Quality Management Requirements, the EAC Guidelines for implementation of the QMS requirements, the EAC Model Quality Manual and the mandatory QMS procedures. I would also like to thank the World Health Organization (WHO) for providing technical assistance towards the development of the QMS documents. Special thanks go to the Bill and Melinda Gates Foundation (BMGF), the World Bank, the New Partnership for Africa s Development (NEPAD) for providing financial support. I am grateful to the staff of EAC Secretariat, the EAC MRH project Steering Committee and EAC Partner States for their effective coordination and implementation of this EAC MRH project. I also acknowledge the valuable contribution of the national and regional EAC stakeholders who reviewed these EAC QMS documents and provided useful inputs. Hon. Jesca Eriyo Deputy Secretary General for Productive and Social Sector EAC Secretariat iv
RESPONSIBILITY FOR IMPLEMENTATION AND LEGAL FRAMEWORK The EAC Sectoral Council Of Ministers of Health recognizes the work done by the EAC secretariat in conjunction with EAC partner states NRMAs and supported by development partners in the development of these QMS documents. These QMS documents will facilitate the implementation of QMS in the EAC Partner States NMRAs. The EAC Sectoral Council of Ministers of Health approves the use of these QMS documents in the East African Community Partner States National Medicines Regulatory Authorities (NMRAs) in accordance with Chapter 21, Article 118 (c, d,e and f) of the EAC Treaty. Implementation of these documents will facilitate mutual recognition of regulatory decisions and attestation of the quality and safety medicines, cosmetics, medical devices and diagnostics manufactured, produced, imported, exported or traded in East African Community. The EAC partner states Ministries responsible for Health shall be responsible for the implementation of these QMS documents by their respective NMRAs. SIGNED by the Hon. Ministers and Leaders of Delegation this 20th day of September, 2014................ Amb. Amina C. Mohamed, CBS, CAV Dr. Abdallah O. Kigoda Hon. Léontine Nzeyimana Hon. Valentine Rugwabiza Hon. Shem Bageine, MP Cabinet Secretary Ministry of Foreign Affairs & International Trade Minister Ministry of Industry and Trade Minister Ministry to the Office of the President Responsible for EAC Affairs Minister for East African Community Minister of State Ministry of East African Community Affairs REPUBLIC OF KENYA UNITED REPUBLIC OF TANZANIA REPUBLIC OF BURUNDI REPUBLIC OF RWANDA REPUBLIC OF UGANDA v
AUTHORS/CONTRIBUTORS Angole Apollo National Medicine Regulation Officer National Drug Authority Kampala, Uganda Chamngei Sichei Cheworei Head, Policy and Planning Unit Pharmacy and PoisonsBoard Nairobi, Kenya Daniel Murenzi ehealth and Informatics Officer EAC Secretariat Arusha, Tanzania Didas Kamazima Mutabingwa Manager, Quality Management Tanzania Food and Drugs Authority Dar es Salaam, Tanzania Eunice Nakimuli Drug Assessment and Registration Officer National Drug Authority Kampala, Uganda Felista Chepwogen National Medicine Regulation Officer Pharmacy and Poisons Board Nairobi, Kenya Gideon Murimi Head of ICT Pharmacy and Poison Board Nairobi, Kenya Gisagara Alex National Medicine Regulation Officer Pharmacy Task Force Kigali, Rwanda Hidaya Juma Hamad National Medicine Regulation Officer Zanzibar Food and Drugs Authority Zanzibar, Tanzania Inyangala Mwende Ronald; Director, Business Support Services Pharmacy & Poisons BoardNairobi, Kenya Kabatende Joseph Coordinator of Pharmaceutical Services Ministry of Health Kigali, Rwanda Khadija Ali Khamis Quality Manager Zanzibar Food and Drug Board Zanzibar, Tanzania Mashingia Jane Senior Health Officer (Medicines and Food Safety) EAC Secretariat, Arusha, Tanzania Mtalo A. Marcelina Laboratory Quality Officer Tanzania Food and DrugsAuthority, Dar es Salaam, Tanzania Mussa Abrahman Hamad Assistant Quality Manager Zanzibar Food and Drug Board Zanzibar, Tanzania Mwesigye John Patrick Senior Health Officer (Medicines Regulation) EAC Secretariat, Arusha, Tanzania Ndayirorereye Marie Louise Head of Sales Department Central d Achat des Medicament Essential, Bujumbura, Burundi Niyungeko Vanis Procurement & Registration Officer Ministry of Health/DPML Bujumbura, Burundi Nyabenda Bonaventure National Medicine Regulation Officer Ministry of Health/DPML Bujumbura, Burundi vi
Nyawakira Anicet Medicine Information Officer Ministry of Health Kigali, Rwanda Prat Alain Technical Officer World Health OrganizationGeneva, Switzerland Ssali Peter Head, Quality Management National Drug Authority, Kampala, Uganda EDITORIAL TEAM Inyangala Mwende Ronald Director, Business Support Services Pharmacy & Poisons Board Nairobi,Kenya Nyawakira Anicet Medicine Information Officer Ministry of Health Kigali, Rwanda Ssali Peter Head Quality Management National Drug Authority Kampala, Uganda EAC-MRH PROJECT STEERING COMMITTEE AND OTHER MEMBERS Kipkerich C. Koskei Registrar / Chief Pharmacist Pharmacy and Poisons Board Nairobi, Kenya Fred Moin Siyoi Deputy Registrar Pharmacy and Poisons Board Nairobi, Kenya Hiiti B. Sillo Director General Tanzania Food and Drugs Authority (TFDA) Dar es Salaam, Tanzania Burhani Othman Simai Registrar Zanzibar Food and Drugs Board Zanzibar, Tanzania Joseph Kabatende Head of Inspectorate/Pharmacy Ministry of Health Kigali, Rwanda Akimana Gladys Pharmacovigilance Officer Ministry of Health Kigali, Rwanda Habib Ali Shariff Chief Pharmacist Ministry of Health Zanzibar, Tanzania William Reuben Ag. Chief Pharmacist Ministry of Health and social welfare Dar es Salaam, Tanzania Gordon Katende Sematiko Executive Secretary/Registrar, National Drug Authority Kampala, Uganda Oteba Olowo Martin Assistant Commissioner, Pharmacy Ministry of Health Kampala, Uganda Bamenyekanye Emmanuel Director DPML/MOH Ministry of Health Bujumbura, Burundi Dr. Ramana NV Gandham Lead Health Specialist The World Bank Upper Hill Nairobi vii
Dr. Andreas Seiter World Bank 1818H Street NW, G7-701 Washington DC 20043 Apollo. Edson Muhairwe Senior Operations Officer World Bank P.O. Box 4463, Kampala, Uganda Dr.Vincent Ahonkhai Bill and Melinda Gates Foundation, USA Dr. Stanley Sonoiya Principal Health Officer (PHO) EAC Secretariat P.O. Box 1096, Arusha-Tanzania Dr. Kamamia Wa Murichu Chairman Kenya Pharmaceutical Distributors Association P.O. Box 1088-10200, Nairobi, Kenya Mendy Caroline Manager Regulatory, IFPMA Chemin Lovis Dunant 15 1202 Geneva Switzerland Dr. Samuel Azatyan Programme Manager, Medicines Regulatory Support World Health Organization Switzerland Avenue Appia 20, 1211, Switzerland Hetzke Juorg WHO Technical Advisor World Health Organization Switzerland Avenue Appia20, 1211 Geneva, Switzerland Prof. Aggrey Ambali Advisor and Head NEPAD Agency, South Africa Margareth Ndomondo Sigonda Pharmaceutical Coordinator AU NEPAD Agency Midrand, South Africa South Africa Mrs. Chimwemwe Chamdimba Senior Program Officer NEPAD Agency. Mr. Paul K. Tanui Senior Program Officer NEPAD Agency. P. O BOX 1627 South Africa. Janet Okero Senior Programme Officer AU NEPAD Agency Private Bag 218, Halfway Hse Midrand, 1685, South Africa viii
TABLE OF CONTENTS DOCUMENTS DEVELOPMENT HISTORY FOREWARD PREFACE RESPONSIBILITY FOR IMPLEMENTATION AND LEGAL FRAMEWORK AUTHORS EDITORIAL TEAM Table of Content PART ONE: EAC QUALITY MANAMEGENT REQUIREMENTS 0. INTRODUCTION 0.1. Background 0.2. Objectives 0.3. Scope of EAC QMS requirements document QUALITY MANAGEMENT SYSTEMS - REQUIREMENTS 1. Scope 1.1. General 1.2. Application 2. Normative references 3. Terms and definitions 4. Quality management system 4.1. General requirements 4.2. Documentation requirements 4.2.1. General 4.2.2. Quality manual 4.2.3. Control of documents 4.2.4. Control of records 5. Management responsibilities 5.1. Management commitment 5.2. Customer focus 5.3. Quality policy 5.4. Planning 5.4.1. Quality objectives 5.4.2. Quality management system planning 5.5 Responsibility, authority and communication 5.5.1 Responsibility and authority 5.5.2 Management representative 5.5.3 Internal communication i ii iii v vi vii ix 1 2 2 2 2 3 3 3 3 3 4 4 5 5 5 5 5 6 6 6 6 7 7 7 7 7 7 7 8 ix
5.6. Management review 5.6.1. General 5.6.2. Review input 5.6.3. Review output 6. Resource management 6.1. Provision of resources 6.2. Human resources 6.2.1 General 6.2.2. Competence, training and awareness 6.2.3. Impartiality and independence 6.2.4. Confidentiality 6.3. Infrastructure 6.4. Work environment 7. Service realizations 7.1 Planning of service realization 7.2 Customer-related processes 7.2.1. Determination of requirements related to the service 7.2.3. Review of requirements related to the service 7.2.3. Customer communication 7.2.4. Complaints and appeals 7.2.5. Complaints and appeals process 7.3. Design and development 7.3.1. Design and development planning 7.3.2. Design and development inputs 7.3.3. Design and development outputs 7.3.4. Design and development review 7.3.5. Design and development verification 7.3.6. Design and development validation 7.3.7.Control of design and development changes 7.4 Purchasing 7.4.1 Purchasing process 7.4.2 Purchasing information 7.4.3 Verification of purchased product 7.5. Service provision 7.5.1 Control of service provision 7.5.2 Validation of processes for service provision 7.5.3 Identification and traceability 7.5.4 Customer property 7.5.5 Preservation of product 7.6 Control of monitoring and measuring equipment 8. Measurement, analysis and improvement 8.1. General 8 8 8 8 9 9 9 9 9 9 10 10 10 11 11 11 11 11 12 12 12 13 13 13 13 14 14 14 14 14 14 14 15 15 15 15 16 16 16 16 17 17 x
8.2. Monitoring and measurement 8.2.1. Customer satisfaction 8.2.2. Internal audit 8.2.3. Monitoring and measurement of processes 8.2.4. Monitoring and measurement of service 8.3. Control of nonconforming product 8.4. Analysis of data 8.5. Improvement 8.5.1. Continual improvement 8.5.2. Corrective action 8.5.3. Preventive action REFERENCES REVISION HISTORY PART TWO: EAC GUIDELINES FOR IMPLEMTATION OF QMS REQUIRMENTS 0. INTRODUCTION 0.1. Background 0.2. Objectives 0.3. Scope of EAC Guidelines for implementing QMS requirements QUALITY MANAGEMENT SYSTEM 1. General 1.1. Scope 2. Normative references 3. Terms and definitions 4. Quality Management System 4.1. General requirements 4.2. Documentation requirements 4.2.1 General 4.2.2 Quality Management 4.2.3 Control of documents 4.2.4 Control of records 5. Management responsibility 5.1 Management commitment 5.2 Customer focus 5.3 Quality policy 5.4 Planning 5.4.1 Quality objectives 17 17 17 18 18 18 19 19 19 19 20 20 22 22 22 22 22 23 23 23 23 23 24 24 24 24 26 27 28 29 30 30 31 31 31 xi
5.4.2 Quality management system planning 5.5 Responsibility, authority and communication 5.5.1 Responsibility and authority 5.5.2 Management Representative 5.5.3 Internal communication 5.6 Management review 5.6.1 General 5.6.2 Review input 5.6.3 Review output 6.0 Resource management 6.1 Provision of resources 6.2 Human Resources 6.2.1 General 6.2.2 Competence, awareness and training 6.2.3 Impartiality and independence 6.2.4 Confidentiality 6.3 Infrastructure 6.4 Work environment 7.0 Product realization 7.1 Planning of services realization 7.2 Customer related process 7.2.1 Determination of requirements related to the service 7.2.2 Review of requirements related to the services 7.2.3 Customer communication 7.2.4 Complaints and appeals 7.2.5 Complaints and appeals process 7.3 Design and Development 7.3.1 Design and development planning 7.3.2 Design and development inputs 7.3.3 Design and development outputs 7.3.4 Design and development review 7.3.5 Design and development verification 7.3.6 Design and development validation 7.3.7 Control of design and development changes 7.4 Purchasing 7.4.1 Purchasing process 7.4.2 Purchase Information 7.4.3 Verification of purchased product 7.5 Production and service provision 7.5.1 Control of production and service provision 7.5.2 Validation of processes for production and service provision 7.5.3 Identification and traceability 7.5.4 Customer property 32 32 32 33 33 34 34 34 35 35 35 36 36 36 37 37 38 38 38 39 39 39 39 40 40 41 42 42 42 43 44 44 44 44 44 44 46 46 47 47 47 48 48 xii
7.5.5 Preservation of product 7.6 Control of monitoring and measuring equipment 8.0 Measurement, analysis and improvement 8.1 General 8.2 Monitoring and measurement 8.2.1 Customer Satisfaction 8.2.2 Internal audit 8.2.3 Monitoring and measurement of processes 8.2.4 Monitoring and measurement of product 8.3 Control of nonconforming product 8.4 Analysis of data 8.5 Improvement 8.5.1 Continual improvement 8.5.2 Corrective action 8.5.3 Preventive action BIBLIOGRAPHY REVISION HISTORY PART THREE: Model Manual on the Implementation of the EAC QMS Requirements for NMRA 0. INTRODUCTION 0.1 Background 0.2. Objectives 0.3. Scope of EAC QMS model manual QUALITY MANAGEMENT SYSTEM 1. SCOPE 1.1. General 1.2. Application of the Quality Management System 1.3. Exclusions from the EAC QMS requirements 2. NORMATIVE REFERENCES 3. TERMS AND DEFINITIONS 4. QUALITY MANAGEMENT SYSTEM 4.1. General requirements 4.2. Document requirement 4.2.1 General 4.2.2 Quality Manual 4.2.3 Control of documents 4.2.4 Control of records 49 49 51 51 51 51 51 52 53 53 54 55 55 55 57 57 57 58 59 59 59 60 60 60 60 60 60 60 61 61 62 62 62 62 62 xiii
5. Management responsibilities 5.1 Management commitment 5.2 Customer focus 5.3 Quality policy 5.4 Planning 5.4.1 Quality objectives 5.4.2 Quality management system planning 5.5 Responsibility, authority and communication 5.5.1 Responsibility and authority 5.5.2 Management representative 5.5.3 Internal communication 5.6 Management review 5.6.1 General 5.6.2 Review input 5.6.3 Review output 6. Resource management 6.1 Provision of resources 6.2 Human resources 6.2.1 General 6.2.2 Competence, training and awareness 6.2.3 Impartiality and independence 6.2.4 Confidentiality 6.3 Infrastructure 6.4 Work environment 7.0 Product realization 7.1 Planning of product realization 7.2 Customer related processes 7.2.1 Determination of requirements related to the product 7.2.2 Review of requirements related to the product 7.2.3 Customer communication 7.2.4 Complaints and appeals 7.2.5 Complaints and appeal process 7.3 Design and Development 7.3.1 Design and Development Planning 7.3.2 Design and Development Inputs 7.3.3 Design and Development Outputs 7.3.4 Design and Development Review 7.3.5 Design and Development Verification 7.3.6 Design and Development Validation 7.3.7 Control of Design and Development Changes 62 62 62 63 63 63 63 63 63 63 64 64 64 64 65 65 65 65 65 65 65 66 66 66 66 66 66 66 67 67 67 67 67 67 67 67 67 68 68 68 xiv
7.4 Purchasing 7.4.1 Purchasing process 7.4.2 Purchasing information 7.4.3 Verification of purchased product 7.5 Production and service provision 7.5.1 Control of production and service provision 7.5.2 Validation of processes for production and service provision 7.5.3 Identification and traceability 7.5.4 Customer property 7.5.5 Preservation of the product 7.6. Control of monitoring and measuring equipment 8.0 Measurement, analysis and improvement 8.1 General 8.2 Monitoring and measurement 8.2.1 Customer satisfaction 8.2.2 Internal audit 8.2.3 Monitoring and measurement of processes 8.2.4 Monitoring and measurement of services 8.3 Control of non-conforming product 8.4 Analysis of data 8.5 Improvement 8.5.1 Continual improvement 8.5.2 Corrective action 8.5.3 Preventive action REVISION HISTORY Annex 1- Model Process interaction diagram: Annex 2: Model Quality Policy. Annex 3 Medicine Regulations mapping processes PART FOUR: EAC QMS Model Standard Procedures 0. INTRODUCTION EAC Model Procedure for Control of Documents EAC Model Procedure for Control of Records EAC Model procedure for Conducting Internal Quality Audit, EAC Model procedure for Control of Non-Conforming Product Doc. # EAC/TF-MED/QMS/FD/SOP EAC Model procedure for Handling Customer Complaints and Appeals EAC Model procedure for handling Corrective and Preventive Action Model standard operating procedure: 68 68 68 68 69 69 69 69 69 69 70 70 70 70 70 70 71 72 72 72 73 73 73 74 74 75 77 78 86 87 87 102 107 118 118 123 128 134 xv
PART FIVE: Code of Conduct for EAC Partner States NMRA 0. INTRODUCTION 0.1 Background 0.2. Objectives 0.4. Legal basis 1. CODE OF CONDUCT 2. GUIDANCE ON CONFLICTS OF INTERESTS 2. 1. Meaning of conflict of interest 2. 2. Types of Interests 2.2.1. Direct Interest 2.2.2. Interests of Others 2.3. When is the NMRA personnel required to complete a declaration of interests form? 2.4. Examples of interests that must be disclosed 152 2.5. How to analyse the information disclosed? 2.6. Safety of the filled DOI forms 3. GUIDANCE ON CONFIDENTIALITY 3.1. Introduction 3.2 Confidential Information 3.3 Duty of confidentiality 3.4. Continuing duty of confidentiality 3.5. When is the NMRA personnel required to complete a confidentiality undertaking form? ANNEX 1: DECLARATION OF INTERESTS 137 138 138 138 138 138 140 140 140 140 140 141 141 142 142 143 143 143 143 144 145 146 XVI
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PART ONE EAC QUALITY MANAMEGENT S REQUIREMENTS 01
0. INTRODUCTION 0.1. Background One of the goals of East African Community (EAC) Medicines Regulatory Harmonization Project is to have harmonized and functioning Quality Management System (QMS) within the EAC National Medicines Regulatory Authorities (NMRAs) in accordance with national and internationally recognized standards. This document provides requirements for implementing quality management systems in NMRAs of the EAC. All NMRAs in the EAC have management systems for creating and delivering their services to customers. However, some of the NMRAs lack quality management systems which would lead to wasteful processes, poor services delivery and dissatisfied customers. This document outlines the quality system requirements for our NMRA QMS. It is intended that each NMRA uses the document as the basis for developing and implementing its own QMS and for preparing its own quality manual. In addition to providing a basis for self-assessment and a reference document for use by external assessors, establishing and maintaining an effective QMS will generate confidence within and between EAC NMRAs in the assessment of QMS compliance. 0.2. Objectives The overall objective of this document is to ensure that adequate quality standards are maintained in each of the EAC Partner State NMRAs so as to achieve consistency in regulatory service delivery and facilitate mutual confidence and recognition. The specific objectives of this document are to: a) enable the establishment, and maintenance of the EAC QMS all EAC partner states NMRAs; b) enable EAC partner states to adopt a common standard quality system requirements in order achieve consistency in services in the EAC NMRAs; and c) facilitate mutual recognition and confidence amongst EAC NMRAs. 0.3. Scope of EAC QMS requirements document This document specifies QMS requirements for EAC NMRAs in the regulation of medicines, cosmetics, medical devices and diagnostics. EAC NMRAs should co-operate with one another in exchanging experiences in the maintenance and operation of quality systems and in the further development of this document. 02
QUALITY MANAGEMENT SYSTEMS - REQUIREMENTS 1. Scope 1.1. General This document specifies requirements for a quality management system where an EAC Partner State NMRA: a) needs to demonstrate its ability to consistently provide product that meets customer and applicable and regulatory requirements. b) aims to enhance customer satisfaction through the effective application of the system, including processes or continual improvement of the system and the assurance of conformity to customer and applicable laws, statutory and regulatory requirements. NOTE: Statutory and legal requirements include national (e.g. national health policy, NMRA Acts, etc); regional (EAC policies on medicine regulation) and international (WHO guidelines, etc) obligations 1.2. Application 1.2.1 The requirements of this document apply to all directorates, departments, units and sections of the EAC Partner States NMRAs. NMRAs may also be required to comply with the following ISO standards and PIC/S guidelines: a) ISO/IEC 17025: 2005 General requirements for the competence of testing and calibration laboratories b) ISO/IEC 17020: 2012 Conformity assessment - Requirements for the operation of various types of bodies performing inspection c) PI 002_3: 2007 PIC/S - Recommendations on Quality system requirements for pharmaceutical inspectorates Where any requirement(s) of these EAC QMS requirements cannot be applied due to the nature of an NMRA and its product, this can be considered for exclusion. Where exclusions are made, claims of conformity to this International Standard are not acceptable unless these exclusions are limited to requirements within Clause 7, and such exclusions do not affect the NMRA s ability, or responsibility, to provide product that meets customer and applicable statutory and regulatory requirements. 2. Normative references This document has been developed according to ISO 9001:2008 - Quality Management Systems requirements. In addition, the following referenced documents are indispensable for the application of the QMS: a) ISO 9000:2005, Quality Systems - Fundamentals and Vocabulary. b) ISO/IEC 17025: 2005 - General requirements for the competence of testing and calibration laboratories 03
c) ISO/IEC 17020: 2012 Conformity assessment - Requirements for the operation of various types of bodies performing inspection d) PI 002_3: 2007 PIC/S - Recommendations on Quality system requirements for pharmaceutical inspectorates EAC Partner states application statutory and legal requirements e) EAC Standards, Quality, Metrology and Testing (SQMT) Act (2006) - revised 2013 f) Any other recognised standard or laws that may be published in the EAC Gazette 3. Terms and definitions For the purposes of this document, the terms and definitions given in ISO 9000: 2005 apply. For the NMRAs, the following terms and definitions for product, customer and Top Management shall apply: a) Customer: organization or person that receives a product. EXAMPLE Consumer, client, enduser, retailer, beneficiary and purchaser. NOTE 1 A customer can be internal or external to the organization. NOTE 2 Regulated Customer : Organisation or person who by the nature of their business are subject to regulation by the NMRAs NOTE 3 Unregulated Customer : Organisation or person who is not subject to regulation by NMRAs. b) Product : Applies to regulatory services intended for, or required by, the customer (regulated and/or unregulated customer) and to any intended output resulting from the product realization processes of the NMRA (e.g. market authorization or medicine registration certificates, licences, permits, good manufacturing practice certificates, good distribution practice certificates, medicine/drug register) c) Top management person or group of people who directs and controls an NMRA at the highest level. 4. Quality management system 4.1. General requirements The NMRA shall establish, document, implement and maintain a quality management system and continually improve its effectiveness in accordance with the EAC QMS requirements in this document. To design and implement the QMS the NMRA shall: a) determine the processes needed for the quality management system and their application throughout the NMRA (see 1.2), b) determine the sequence and interaction of these processes, 04
c) determine criteria and methods needed to ensure that both the operation and control of these processes are effective, d) ensure the availability of resources and information necessary to support the operation and monitoring of these processes, e) monitor, measure where applicable, and analyse these processes, and f) implement actions necessary to achieve planned results and continual improvement of these processes. These processes shall be managed by the NMRA in accordance with the requirements of this EAC QMS Requirements. Where an NMRA chooses to outsource any process that affects product conformity to requirements, the NMRA shall ensure control over such processes. The type and extent of control to be applied to these outsourced processes shall be defined within the quality management system. 4.2. Documentation requirements 4.2.1. General The quality management system documentation shall include: a) documented statements of a quality policy and quality objectives, b) a quality manual, c) documented procedures and records required by EAC QMS requirement d) documents, including records, determined by the NMRA to be necessary to ensure the effective planning, operation and control of its processes. NOTE: Where the term documented procedure appears within this EAC QMS Requirement, this means that the procedure is established, documented, implemented and maintained. A single document may address the requirement for one or more procedures. A requirement for a documented procedure may be covered by more than one document. 4.2.2 Quality manual The NMRA shall establish and maintain a quality manual that includes: a) the scope of the quality management system the documented procedures established for the quality management system, or reference to them, b) a description of the interaction between the processes of the quality management system 4.2.3. Control of documents Documents required by the quality management system shall be controlled. Records are a special type of document and shall be controlled according to the requirements given in 4.2.4. A documented procedure shall be established to define the controls needed a) to approve documents for adequacy prior to issue, 05
b) to review and update as necessary and re-approve documents, c) to ensure that changes and the current revision status of documents are identified, d) to ensure that relevant versions of applicable documents are available at points of use, e) to ensure that documents remain legible and readily identifiable, f) to ensure that documents of external origin determined by the organization to be necessary for t he planning and operation of the quality management system are identified and their distribution controlled, and g) to prevent the unintended use of obsolete documents, and to apply suitable identification to them if they are retained for any purpose. 4.2.4. Control of records The NMRA shall determine and control the records established to provide evidence of conformity to requirements and of the effective operation of the quality management system. The NMRA shall establish a documented procedure to define the controls needed for the identification, storage, protection, retrieval, retention and disposition of records. A list of the controlled records and their required retention periods shall be established and maintained. 5. Management responsibilities Top management shall develop the strategic plan, business plan, mission, vision, core values for the whole NMRA. QMS requirements shall be clearly identified in the strategic plan and business plan of the NMRA 5.1. Management commitment Top management shall provide evidence of its commitment to the development and implementation of the quality management system and continually improving its effectiveness by: a) communicating to the NMRA the importance of meeting customer as well as statutory and regulatory requirements, b) establishing the quality policy, c) ensuring that quality objectives are established, d) conducting management reviews, and e) ensuring the availability of resources. 5.2. Customer focus Top management shall ensure that customer requirements are determined and are met with the aim of enhancing customer satisfaction (see 7.2.1 and 8.2.1). Records shall remain legible, readily identifiable and retrievable. 06
5.3. Quality policy Top management shall ensure that the quality policy a) is appropriate to the purpose of the NMRA, b) includes a commitment to comply with requirements and continually improve the effectiveness of the quality management system, c) provides a framework for establishing and reviewing quality objectives, d) is communicated and understood within the NMRA, and e) is reviewed for continuing suitability. 5.4. Planning 5.4.1. Quality objectives Top management shall ensure that quality objectives, including those needed to meet requirements for product [see 7.1 a)], are established at relevant functions and levels within the NMRA. The quality objectives shall be measurable and consistent with the quality policy. 5.4.2. Quality management system planning Top management shall ensure that: a) the planning of the quality management system is carried out in order to meet the requirements given in 4.1 as well as the quality objectives, and b) the integrity of the quality management system is maintained when changes to the quality management system are planned and implemented. c) in planning for the QMS, top management shall ensure that a strategic plan is developed. 5.5 Responsibility, authority and communication 5.5.1 Responsibility and authority Top management shall ensure that responsibilities and authorities are defined and communicated within the NMRA. a) The NMRA shall establish an organizational chart that clearly shows the inter-relationship and reporting mechanism of the personnel in the NMRA. b) The NMRA shall establish job descriptions defining the responsibilities and authorities of each of the employee positions on the organizational structure. Management representative Top management shall appoint a member of the NMRA s management who, irrespective of other responsibilities, shall have responsibility and authority that includes: a) ensuring that processes needed for the quality management system are established, implemented and maintained, 07
b) reporting to top management on the performance of the quality management system and any need for improvement, and c) ensuring the promotion of awareness of customer requirements throughout the organization. NOTE: The responsibility of a management representative can include liaison with external parties on matters relating to the quality management system. 5.5.3 Internal communication Top management shall ensure that appropriate communication processes are established within the NMRA and that communication takes place regarding the effectiveness of the quality management system. 5.6. Management review 5.6.1. General Top management shall review the NMRA s quality management system, at planned intervals, at least once a year, to ensure its continuing suitability, adequacy and effectiveness. This review shall include assessing opportunities for improvement and the need for changes to the quality management system, including the quality policy and quality objectives. 5.6.2. Review input The input to management review shall include information on: a) results of audits, b) customer feedback, c) process performance and product conformity, d) status of preventive and corrective actions, e) follow-up actions from previous management reviews, f) changes that could affect the quality management system, and g) recommendations for improvement. 5.6.3. Review output The output from the management review shall include any decisions and actions related to: a) improvement of the effectiveness of the quality management system and its processes, b) improvement of product related to customer requirements, and c) resource needs. Records from management reviews shall be maintained (see 4.2.4). 08
6. Resource management 6.1 Provision of resources The NMRA shall determine and provide the resources needed a) to implement and maintain the quality management system and continually improve its effectiveness, and b) to enhance customer satisfaction by ZZ meeting customer requirements. 6.2. Human resources 6.2.1 General Personnel performing work affecting conformity to product requirements shall be competent on the basis of appropriate education, training, skills and experience. NOTE: Conformity to service requirements can be affected directly or indirectly by personnel performing any task within the quality management system. 6.2.2. Competence, training and awareness The NMRA shall: a) determine the necessary competence for personnel performing work affecting conformity to product requirements, b) where applicable, provide training or take other actions to achieve the necessary competence, c) evaluate the effectiveness of the actions taken, d) ensure that its personnel are aware of the relevance and importance of their activities and how they contribute to the achievement of the quality objectives, and e) maintain appropriate records of education, training, skills and experience (see 4.2.4) f) develop a code of conduct in accordance with national public service code of conduct 6.2.3. Impartiality and independence a) The NMRA shall be responsible for the impartiality of its activities and shall not allow commercial, financial or other pressures to compromise impartiality. b) The NMRA shall identify risks to its impartiality on an ongoing basis. This shall include those risks that arise from its activities, or from its relationships, or from the relationships of its personnel. However, such relationships do not necessarily present an NMRA with a risk to impartiality. c) If a risk to impartiality is identified, the NMRA shall be able to demonstrate how it eliminates or minimizes such risk. d) The NMR shall have top management commitment to impartiality. 9
e) The NMRA shall be independent to the extent that is required with regard to the conditions under which it performs its services. f) The NMRA shall establish a documented procedure to manage impartiality and independence 6.2.4. Confidentiality a) The NMRA shall be responsible, through legally enforceable commitments, for the management of all information obtained or created during the performance of its regulatory activities. The NMRA shall inform the client, in advance, of the information it intends to place in the public domain. Except for information that the client makes publicly available, or when agreed between the NMRA and the client (e.g. for the purpose of responding to complaints), all other information is considered proprietary information and shall be regarded as confidential. NOTE: Legally enforceable commitments can be, for example, contractual agreements. b) When the NMRA is required by law or authorized by contractual commitments to release confidential information, the client or individual concerned shall, unless prohibited by law, be notified of the information provided. c) Information about the client obtained from sources other than the client (e.g. complainant, regulators) shall be treated as confidential. d) The NMRA shall establish a documented procedure to manage confidentiality 6.3. Infrastructure The NMRA shall determine, provide and maintain the infrastructure needed to achieve conformity to product requirements. Infrastructure includes, as applicable, a) buildings, workspace and associated utilities, b) process equipment (both hardware and software), and c) supporting services (such as transport, communication or information systems). 6.4. Work environment The NMRA shall determine and manage the work environment needed to achieve conformity to product requirements. NOTE: The term work environment relates to those conditions under which work is performed including physical, environmental and other factors (such as noise, temperature, humidity, lighting or weather). 10
7. Service realizations 7.1 Planning of service realization The NMRA shall plan and develop the processes needed for service realization. Planning of service realization shall be consistent with the requirements of the other processes of the quality management system (see 4.1 as appropriate). In planning servicerealization, the NMRA shall determine the following, as appropriate: a) quality objectives and requirements for the service; b) the need to establish processes and documents, and to provide resources specific to the service c) required verification, validation, monitoring, measurement, inspection and test activities specific to the service and the criteria for serviceacceptance; d) records needed to provide evidence that the realization processes and resulting service meet requirements (see 4.2.4 as appropriate) The output of this planning shall be in a form suitable for the NMRA s method of operations. 7.2 Customer-related processes 7.2.1. Determination of requirements related to the service The NMRA shall determine: a) requirements specified by the customer, including the requirements for delivery and postdelivery activities, b) requirements not stated by the customer but necessary for specified or intended use, where known, c) statutory and regulatory requirements applicable to the service, and d) any additional requirements considered necessary by the NMRA. 7.2.2. Review of requirements related to the service The NMRA shall review the requirements related to the service this review shall be conducted prior to the NMRA s commitment to provide a service to the customer (e.g. Licensing, Product registration and market authorization, certification, GMP inspection and others) and shall ensure that a) service requirements are defined, b) service requirements differing from those previously expressed are resolved, and c) the NMRA has the ability to meet the defined or new requirements. Records of the results of the review and actions arising from the review shall be maintained (see 4.2.4). Where the customer provides no documented statement of requirement, the customer requirements shall be confirmed by the NMRA before acceptance. 11
Where service requirements are changed, the NMRA shall ensure the relevant documents are amended and that relevant personnel are made aware of the changed requirements. 7.2.3. Customer communication The NMRA shall determine and implement effective arrangements for communicating with customers in relation to: a) service information, b) enquiries, new service information including amendments, and c) customer feedback, including customer complaints 7.2.4. Complaints and appeals 7.2.4.1 The NMRA shall have a documented procedure to receive, evaluate and make decisions on complaints and appeals. 7.2.4.2 A description of the handling process for complaints and appeals shall be available to any interested party upon request. 7.2.4.3 Upon receipt of a complaint, the NMRA shall confirm whether the complaint relates to its activities for which it is responsible and, if so, shall deal with it. 7.2.4.4 The NMRA shall be responsible for all decisions at all levels of the handling process for complaints and appeals. 7.2.5. Complaints and appeals process 7.2.4.6 The handling process for complaints and appeals shall include at least the following elements and methods: a) a description of the process for receiving, b) validating, c) investigating the complaint or appeal, and deciding what actions are to be taken in response to it; d) tracking and recording complaints and appeals, including actions undertaken to resolve them; e) ensuring that any appropriate action is taken. 7.2.4.7 The NMRA shall be responsible for gathering and verifying all necessary information to validate the complaint or appeal. 7.2.4.8 Whenever possible, the NMRA shall acknowledge receipt of the complaint or appeal, and shall provide the complainant or appellant with progress reports and the outcome. 7.2.4.9 The decision to be communicated to the complainant or appellant shall be made by, or reviewed and approved by, individual(s) not involved in the original activities in question. 7.2.4.5 Investigation and decision on appeals shall not result in any discriminatory actions. 12
7.2.4.10 Whenever possible, the NMRA shall give formal notice of the end of the complaint and appeals handling process to the complainant or appellant. 7.3. Design and development 7.3.1. Design and development planning The NMRA shall plan and control the design and development of service. During the design and development planning, the NMRA shall determine: a) the design and development stages, b) the review, verification and validation that are appropriate to each design and development stage, and c) the responsibilities and authorities for design and development. The NMRA shall manage the interfaces between different groups involved in design and development to ensure effective communication and clear assignment of responsibility. Planning output shall be updated, as appropriate, as the design and development progresses. NOTE: Design and development review, verification and validation have distinct purposes. They can be conducted and recorded separately or in any combination, as suitable for the service and the NMRA. 7.3.2. Design and development inputs Inputs relating to service requirements shall be determined and records maintained (see 4.2.4). These inputs shall include: a) functional and performance requirements, b) applicable statutory and regulatory requirements, c) where applicable, information derived from previous similar designs, and d) other requirements essential for design and development. The inputs shall be reviewed for adequacy. Requirements shall be complete, unambiguous and not in conflict with each other. 7.3.3. Design and development outputs The outputs of design and development shall be in a form suitable for verification against the design and development input and shall be approved prior to release. Design and development outputs shall: a) Meet the input requirements for design and development, b) provide appropriate information for purchasing, production and service provision, c) contain or reference product acceptance criteria, and; 13
d) specify the characteristics of the product that are essential for its safe and proper use. NOTE: Information for production and service provision can include details for the preservation of product. 7.3.4. Design and development review At suitable stages, systematic reviews of design and development shall be performed in accordance with planned arrangements (see 7.3.1) a) to evaluate the ability of the results of design and development to meet requirements, and b) to identify any problems and propose necessary actions. Participants in such reviews shall include representatives of functions concerned with the design and development stage(s) being reviewed. Records of the results of the reviews and any necessary actions shall be maintained (see 4.2.4). 7.3.5. Design and development verification Verification shall be performed in accordance with planned arrangements (see 7.3.1) to ensure that the design and development outputs have met the design and development input requirements. Records of the results of the verification and any necessary actions shall be maintained (see 4.2.4). 7.3.6. Design and development validation Design and development validation shall be performed in accordance with planned arrangements (see 7.3.1) to ensure that the resulting product is capable of meeting the requirements for the specified application or intended use, where known. Wherever practicable, validation shall be completed prior to the delivery or implementation of the product. Records of the results of validation and any necessary actions shall be maintained (see 4.2.4). 7.3.7. Control of design and development changes Design and development changes shall be identified and records maintained. The changes shall be reviewed, verified and validated, as appropriate, and approved before implementation. The review of design and development changes shall include evaluation of the effect of the changes on constituent parts and service already delivered. Records of the results of the review of changes and any necessary actions shall be maintained (see 4.2.4). 7.4 Purchasing 7.4.1 Purchasing process The NMRA shall ensure that purchased product conforms to specified purchase requirements. The type and extent of control applied to the supplier and the purchased product shall be dependent upon the effect of the purchased product on subsequent service realization or the final service. The NMRA shall evaluate and select suppliers based on their ability to supply product in accordance with the organization s 14