(February 2018) DRAFT FOR COMMENTS 6 - who.int

1 Working document February 2018 DRAFT document for comment VALIDATION 1 appendix 6 2 GUIDELINES ON QUALIFICATION 3 (February 2018) 4 DRAFT FOR COMMENTS 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 World Health Organization 2018 25 All rights reserved. 26 This DRAFT is intended for a restricted audience only, the individuals and organizations having received this DRAFT . The DRAFT 27 may not be reviewed, abstracted, quoted, reproduced, transmitted, distributed, translated or adapted, in part or in whole, in any 28 form or by any means outside these individuals and organizations (including the organizations' concerned staff and member 29 organizations) without the permission of the World Health Organization. The DRAFT should not be displayed on any website.

2 30 Please send any request for permission to: 31 Dr Sabine Kopp, Group Lead, Medicines Quality Assurance, Technologies Standards and Norms, Regulation of Medicines and 32 other Health Technologies, Department of Essential Medicines and Health Products, World Health Organization, CH-1211 33 Geneva 27, Switzerland. Fax: (41-22) 791 4730; email: 34 The designations employed and the presentation of the material in this DRAFT do not imply the expression of any opinion 35 whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its 36 authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines 37 for which there may not yet be full agreement. 38 The mention of specific companies or of certain manufacturers products does not imply that they are endorsed or recommended 39 by the World Health Organization in preference to others of a similar nature that are not mentioned.

3 Errors and omissions 40 excepted, the names of proprietary products are distinguished by initial capital letters. 41 All reasonable precautions have been taken by the World Health Organization to verify the information contained in this DRAFT . 42 However, the printed material is being distributed without warranty of any kind, either expressed or implied. The responsibility 43 for the interpretation and use of the material lies with the reader. In no event shall the World Health Organization be liable for 44 damages arising from its use. 45 This DRAFT does not necessarily represent the decisions or the stated policy of the World Health Organization. 46 47 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 Xenia Finnerty by 30 April 2018.

4 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 48 49 50 SCHEDULE FOR THE PROPOSED ADOPTION PROCESS OF DOCUMENT : 51 VALIDATION 52 appendix 6 53 GUIDELINES ON QUALIFICATION 54 55 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)-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.)

5 July 2015 April 2016 Presentation of the progress made to the fiftieth meeting of the WHO Expert Committee on Specifications for Pharmaceutical Preparations (ECSPP) 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 ECSPP 17 21 October 2016 Preparation of revised text by Dr van Zyl based on the feedback received during the public consultation and the ECSPP meeting March 2017 Circulation of revised working document for public consultation February 2018 Consolidation of COMMENTS received and review of feedback May June 2018 Working document page 3 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 at the

6 Informal consultation on GMP and inspection, Geneva July 2018 (tbc) Circulation of revised working document for public consultation August 2018 Consolidation of COMMENTS received and review of feedback October 2018 Presentation to the fifty-third meeting of ECSPP 22 26 October 2018 Any other follow-up action as required .. Working document page 4 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 ECSPP at its forty-ninth meeting in October 2014.

7 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. One of them, 104 the Validation on qualification of systems, utilities and equipment, newly entitled Guidelines 105 on qualification, constitutes this working 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 Guideline on Qualification updated text proposed in this working document 134 (new title) 135 Working document page 5 136 137 appendix 7 138 Non-sterile process validation update already published as Annex 3, WHO Technical 139 Report Series, No.

8 992, 2015 140 141 Brief background on the changes in this document 142 There was some confusion regarding the title. It is therefore suggested to change the title to 143 GUIDELINES ON QUALIFICATION. In this way, the general principles in qualification are 144 addressed which can be applied for systems, equipment, etc. 145 146 Based on the COMMENTS , the general chapters on objective and scope were written to make it 147 clear that the guidelines address principles of qualification that can be applied, as appropriate, to 148 premises, systems, utilities and equipment and to include the application of risk management 149 principles. 150 151 Moreover, duplication was removed, logical flow of concepts addressed and aligned with 152 international texts and the COMMENTS . The V Model has been removed based on the feedback 153 received. In the former published text on qualification, protocol formats were included.

9 These 154 protocol formats were extracted from training materials and were intended to serve as examples. 155 In view of the feedback that seemingly manufacturers took them as absolute examples to be 156 used, these examples have been removed in the current version. 157 158 159 160 Working document page 6 appendix 6 161 GUIDELINES ON QUALIFICATION 162 163 1. Principle 164 2. Scope 165 3. glossary 166 4. General 167 5. User requirement specifications 168 6. Factory acceptance test and site acceptance test 169 7. Design qualification 170 8. Installation qualification 171 9. Operational qualification 172 10. Performance qualification 173 11. Requalification 174 12. Qualification of in use systems and equipment 175 176 1. PRINCIPLE 177 178 In principle, premises, systems, utilities and equipment should be appropriately designed, 179 located, installed, operated, cleaned, maintained and qualified to suit their intended purpose.

10 180 181 Quality management systems should be in place to ensure that these remain in a qualified 182 state throughout their life cycle. 183 184 Products should be manufactured on qualified equipment. 185 186 2. SCOPE 187 188 These guidelines describe the general approach to qualification for, premises, 189 systems, utilities and equipment. 190 191 The principles in these guidelines may also be applied to the qualification of instruments, 192 analytical instruments and testing devices; where appropriate. 193 194 These may include and are not limited to: certain rooms; water purification systems; 195 cleaning systems; heating, ventilation and air conditioning systems; compressed air systems; gas 196 systems; steam systems; as well as production equipment and analytical instruments. 197 198 Separate guidelines in this series address other principles in validation such as process 199 validation and cleaning validation (see references at the end of this document).