(May 2016) 3 DRAFT FOR COMMENTS - World Health …

1 Working document May 2016 DRAFT document for comment 1 GUIDELINES ON VALIDATION 2 (May 2016 ) 3 draft for comments 4 5 World Health Organization 2016 6 All rights reserved. 7 This DRAFT is intended for a restricted audience only, the individuals and organizations having 8 received this DRAFT . The DRAFT may not be reviewed, abstracted, quoted, reproduced, transmitted, 9 distributed, translated or adapted, in part or in whole, in any form or by any means outside these 10 individuals and organizations (including the organizations' concerned staff and member 11 organizations) without the permission of the World Health Organization.

2 The DRAFT should not be 12 displayed on any website. 13 Please send any request for permission to: 14 Dr Sabine Kopp, Group Lead, Medicines Quality Assurance, Technologies, Standards and Norms, 15 Regulation of Medicines and other Health Technologies, Department of Essential Medicines and 16 Health Products, World Health Organization, CH-1211 Geneva 27, Switzerland. 17 Fax: (41-22) 791 4730; email: 18 The designations employed and the presentation of the material in this DRAFT do not imply the 19 expression of any opinion whatsoever on the part of the World Health Organization concerning the 20 legal status of any country, territory, city or area or of its authorities, or concerning the delimitation 21 of its frontiers or boundaries.

3 Dotted lines on maps represent approximate border lines for which 22 there may not yet be full agreement. 23 The mention of specific companies or of certain manufacturers products does not imply that they 24 are endorsed or recommended by the World Health Organization in preference to others of a similar 25 nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are 26 distinguished by initial capital letters. 27 All reasonable precautions have been taken by the World Health Organization to verify the 28 information contained in this DRAFT . However, the printed material is being distributed without 29 warranty of any kind, either expressed or implied.

4 The responsibility for the interpretation and use 30 of the material lies with the reader. In no event shall the World Health Organization be liable for 31 damages arising from its use. 32 This DRAFT does not necessarily represent the decisions or the stated policy of the World Health 33 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 12 July 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.

5 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.. 2 Working document page 2 Organization. 34 SCHEDULE FOR THE PROPOSED ADOPTION PROCESS OF DOCUMENT 35 : 36 Guidelines on validation 37 38 39 40 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.)

6 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 revision by Dr van Zyl, a participant at the above-mentioned consultation, based on his initial proposal and 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 May 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.

7 3 Working document page 3 Background information 41 42 43 The need for revision of the published Supplementary guidelines on good 44 manufacturing practices: validation (WHO Technical Report Series, No. 45 937, 2006, Annex 4) (1) had been identified by the Prequalification of 46 Medicines Programme and a DRAFT document was circulated for comment in 47 early 2013. The focus of the revision was the Appendix on non-sterile 48 process validation (Appendix 7), which had been revised and was adopted 49 by the Committee at its forty-ninth meeting in October 2014. 50 51 The main text included in this working document constitutes the 52 general principles of the new guidance on validation.

8 53 54 The DRAFT on the specific topics, the appendices to this main text, will 55 follow. 56 57 The following is an overview on the appendices that are intended to 58 complement the text in this working document: 59 60 Appendix 1 61 Validation of heating, ventilation and air-conditioning systems 62 will be replaced by cross-reference to WHO Guidelines 63 on GMP for HVAC systems for considerations in 64 qualification of HVAC systems 65 (update - working document ) (2) 66 67 Appendix 2 68 Validation of water systems for pharmaceutical use 69 will be replaced by cross-reference to WHO Guidelines on 70 water for pharmaceutical use for consideration in qualification of 71 water purification systems (3)

9 72 73 Appendix 3 74 Cleaning validation consensus to retain 75 76 Appendix 4 77 Analytical method validation update in process 78 79 4 Working document page 4 Appendix 5 80 Validation of computerized systems update in process 81 82 Appendix 6 83 Qualification of systems and equipment update in process 84 85 Appendix 7 86 Non-sterile process validation update already published as Annex 87 3, WHO Technical Report Series, No. 992, 2015 88 5 Working document page 5 Guidelines on validation 89 90 91 1. Introduction 92 2. Scope 93 3. Glossary 94 4. Relationship between validation and qualification 95 5. Validation 96 6.

10 Documentation 97 7. Validation master plan 98 8. Qualification and validation protocols 99 9. Qualification and validation reports 100 10. Qualification 101 User requirement specifications 102 Factory acceptance test (FAT) and site acceptance test 103 (SAT) 104 Design qualification 105 Installation qualification 106 Operational qualification 107 Performance qualification 108 Requalification 109 Revalidation 110 Process validation 111 11. Change management 112 12. Deviation management 113 13. Calibration and verification 114 References 115 116 117 118 1. INTRODUCTION 119 120 Validation is an essential part of good practices including good 121 manufacturing practices (GMP) (4) and good clinical practices (GCP).