1 Working document June 2016 Draft document for comment 1 GUIDELINES ON VALIDATION APPENDIX 6 2 VALIDATION ON QUALIFICATION OF SYSTEMS, UTILITIES 3 AND EQUIPMENT 4 (June 2016) 5 DRAFT FOR COMMENTS 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 World Health Organization 2016 26 All rights reserved. 27 This draft is intended for a restricted audience only, the individuals and organizations having received this draft. The draft 28 may not be reviewed, abstracted, quoted, reproduced, transmitted, distributed, translated or adapted, in part or in whole, in any 29 form or by any means outside these individuals and organizations (including the organizations' concerned staff and member 30 organizations) without the permission of the World Health Organization.
2 The draft should not be displayed on any website. 31 Please send any request for permission to: 32 Dr Sabine Kopp, Group Lead, Medicines Quality Assurance, Technologies, Standards and Norms, Regulation of Medicines and 33 other Health Technologies, Department of Essential Medicines and Health Products, World Health Organization, CH-1211 34 Geneva 27, Switzerland. Fax: (41-22) 791 4730; email: 35 The designations employed and the presentation of the material in this draft do not imply the expression of any opinion 36 whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its 37 authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines 38 for which there may not yet be full agreement.
3 39 The mention of specific companies or of certain manufacturers products does not imply that they are endorsed or recommended 40 by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions 41 excepted, the names of proprietary products are distinguished by initial capital letters. 42 All reasonable precautions have been taken by the World Health Organization to verify the information contained in this draft. 43 However, the printed material is being distributed without warranty of any kind, either expressed or implied. The responsibility 44 for the interpretation and use of the material lies with the reader. In no event shall the World Health Organization be liable for 45 damages arising from its use. 46 This draft does not necessarily represent the decisions or the stated policy of the World Health Organization.
4 47 48 Should you have any comments on the attached text, please send these to Dr S. Kopp, Group Lead, Medicines Quality Assurance, Technologies, Standards and Norms with a copy to Ms Marie Gaspard by 15 August 2016. Medicines Quality Assurance working documents will be sent out electronically only and will also be placed on the Medicines website for comment under Current projects . If you do not already receive our draft working documents please let us have your email address (to and we will add it to our electronic mailing list.. Working document page 2 49 50 51 SCHEDULE FOR THE PROPOSED ADOPTION PROCESS OF DOCUMENT : 52 GUIDELINES ON VALIDATION APPENDIX 6 53 VALIDATION ON QUALIFICATION OF SYSTEMS, UTILITIES AND EQUIPMENT 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 Discussion of proposed need for revision in view of the current trends in VALIDATION during informal consultation on data management, bioequivalence, GMP and medicines inspection 29 June 1 July 2015 Preparation of draft proposal for revision of the main text and several appendices by specialists in collaboration with the Medicines Quality Assurance Group and Prequalification Team (PQT))
5 -Inspections, based on the feedback received during the meeting and from PQT-Inspections, draft proposals developed on the various topics by specialists, as identified in the individual working documents. July 2015 April 2016 Presentation of the progress made to the fiftieth meeting of the WHO Expert Committee on Specifications for Pharmaceutical Preparations 12 16 October 2015 Discussion at the informal consultation on good practices for health products manufacture and inspection, Geneva 4 6 April 2016 Preparation of revised text by Dr van Zyl, participant at the above-mentioned consultation, based on the feedback received during and after the informal consultation by the meeting participants and members of PQT-Inspections May 2016 Circulation of revised working document for public consultation June 2016 Consolidation of comments received and review of feedback August September 2016 Presentation to the fifty-first meeting of the WHO Expert Committee on Specifications for Pharmaceutical Preparations 17 21 October 2016 Any other follow-up action as required.
6 Working document page 3 Background information 91 92 The need for revision of the published Supplementary GUIDELINES on good manufacturing 93 practices: VALIDATION (World Health Organization (WHO) Technical Report Series, No. 937, 94 2006, Annex 4) was identified by the Prequalification of Medicines Programme and a draft 95 document was circulated for comment in early 2013. The focus of the revision was the APPENDIX 96 on non-sterile process VALIDATION ( APPENDIX 7), which had been revised and was adopted by the 97 Committee at its forty-ninth meeting in October 2014. 98 99 The main text was sent out for consultation as Working document entitled 100 GUIDELINES on VALIDATION which constitute the general principles of the new guidance on 101 VALIDATION . 102 103 The draft on the specific topics, the appendices to this main text, will follow.
7 One of them, 104 the VALIDATION on qualification of systems, utilities and equipment, constitutes this working 105 document. 106 107 The following is an overview on the appendices that are intended to complement the general text 108 on VALIDATION : 109 110 APPENDIX 1 111 VALIDATION of heating, ventilation and air-conditioning systems 112 will be replaced by cross-reference to WHO GUIDELINES on GMP for HVAC systems 113 for considerations in qualification of HVAC systems 114 (update - working document ) 115 116 APPENDIX 2 117 VALIDATION of water systems for pharmaceutical use 118 will be replaced by cross-reference to WHO GUIDELINES on water for pharmaceutical 119 use for consideration in qualification of water purification systems 120 121 APPENDIX 3 122 Cleaning VALIDATION consensus to retain 123 124 APPENDIX 4 125 Analytical method VALIDATION 126 will be replaced by update - working document 127 128 APPENDIX 5 129 VALIDATION of computerized systems 130 will be replaced by update - working document 131 132 APPENDIX 6 133 Qualification of systems, utilities and equipment updated text proposed in this 134 working document 135 Working document page 4 136 APPENDIX 7 137 Non-sterile process VALIDATION update already published as Annex 3.
8 WHO Technical 138 Report Series, No. 992, 2015 139 Working document page 5 GUIDELINES ON VALIDATION APPENDIX 6 140 VALIDATION ON QUALIFICATION OF SYSTEMS, UTILITIES AND 141 EQUIPMENT 142 143 1. Principle 144 2. Scope 145 3. Glossary 146 4. General 147 5. User requirement specifications 148 6. Factory acceptance test and site acceptance test 149 7. Design qualification 150 8. Installation qualification 151 9. Operational qualification 152 10. Performance qualification 153 11. Requalification 154 12. Qualification of in use systems and equipment 155 156 1. PRINCIPLE 157 158 Systems, utilities and equipment should be appropriately designed, located, installed, 159 operated, cleaned and maintained to suit their intended purpose. 160 161 Products should be manufactured on qualified equipment to ensure batch-to-batch 162 consistency 163 164 Procedures should be in place to ensure that systems, utilities and equipment remain in a 165 qualified state throughout the life of the system, utility and equipment.
9 166 167 2. SCOPE 168 169 These GUIDELINES describe the general aspects of qualification for systems, utilities and 170 equipment. 171 172 The principles in this guideline may also be applied to the qualification of instruments 173 and testing devices, where appropriate. 174 175 Systems, utilities and equipment that may have an impact on the quality of products, 176 should be appropriately qualified. These may include, where appropriate: computerized systems; 177 water purification systems; heating, ventilation and air conditioning systems; compressed air 178 systems; steam systems; production and quality control of equipment and instruments. 179 180 Documented impact assessments should support decisions for the exclusion of systems, 181 utilities and equipment from qualification.
10 182 183 184 Working document page 6 3. GLOSSARY 185 186 design qualification. Documented evidence that the premises, supporting systems, 187 utilities, equipment and processes have been designed in accordance with the requirements of 188 good manufacturing practices. 189 190 factory acceptance test. A test conducted at the vendor s premises to verify that the 191 system, equipment or utility, as assembled or partially assembled, meets expected specifications. 192 (new) 193 194 installation qualification. The performance of tests to ensure that the installations (such 195 as machines, measuring devices, utilities and manufacturing areas) used in a manufacturing 196 process are appropriately selected and correctly installed and operate in accordance with 197 established specifications. 198 199 operational qualification.