GUIDELINES ON VALIDATION APPENDIX 4 …

1 Working document June 2016 Draft document for comment 1 GUIDELINES ON VALIDATION APPENDIX 4 2 analytical METHOD VALIDATION 3 (June 2016) 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 2016 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.

2 The draft should not be displayed on any website. 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.

3 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. 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.

4 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 Marie Gaspard by 30 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 . 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 GUIDELINES ON VALIDATION APPENDIX 4 52 analytical METHOD VALIDATION 53 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 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 Ms S. Croft, member of the PQT-Inspections Team, and review by Dr van Zyl, participant at the above-mentioned consultation, based on the feedback received during 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 90 91 The need for revision of the published Supplementary GUIDELINES on good manufacturing 92 practices: VALIDATION (1) was identified by the Prequalification of Medicines Programme and a 93 draft document was circulated for comment in early 2013. The focus of the revision was the 94 APPENDIX on non-sterile process VALIDATION ( APPENDIX 7), which had been revised and was 95 adopted by the Committee at its forty-ninth meeting in October 2014. 96 97 The main text was sent out for consultation as Working document entitled 98 GUIDELINES on VALIDATION which constitute the general principles of the new guidance on 99 VALIDATION . 100 101 The draft on the specific topics, the appendices to this main text, will follow.

7 One of them, e 102 analytical method VALIDATION , constitutes this working document. 103 104 The following is an overview on the appendices that are intended to complement the general text 105 on VALIDATION : 106 107 APPENDIX 1 108 VALIDATION of heating, ventilation and air-conditioning systems 109 will be replaced by cross-reference to WHO GUIDELINES on GMP for HVAC systems 110 for considerations in qualification of HVAC systems 111 (update - working document ) 112 113 APPENDIX 2 114 VALIDATION of water systems for pharmaceutical use 115 will be replaced by cross-reference to WHO GUIDELINES on water for pharmaceutical 116 use for consideration in qualification of water purification systems 117 118 APPENDIX 3 119 Cleaning VALIDATION consensus to retain 120 121 APPENDIX 4 122 analytical method VALIDATION updated text proposed in this working document 123 124 APPENDIX 5 125 VALIDATION of computerized systems (update see working document )

8 126 127 APPENDIX 6 128 Qualification of systems and equipment update in process 129 130 APPENDIX 7 131 Non-sterile process VALIDATION update already published as Annex 3, WHO Technical Report 132 Series, No. 992, 2015 133 Working document page 4 APPENDIX 4 134 analytical METHOD VALIDATION 135 136 1. Principle 137 2. General 138 3. Pharmacopoeial methods 139 4. Non-pharmacopoeial methods 140 5. Method VALIDATION 141 6. Method verification 142 7. Method transfer 143 8. Revalidation 144 9. Characteristics of analytical procedures 145 146 1. PRINCIPLE 147 148 This APPENDIX presents some information on the characteristics that should be considered 149 during VALIDATION of analytical methods . Approaches other than those specified in this APPENDIX 150 may be followed and may be acceptable.

9 Manufacturers should choose the VALIDATION protocol 151 and procedures most suitable for testing of their product. 152 153 The manufacturer should demonstrate (through VALIDATION ) that the analytical procedure is 154 suitable for its intended purpose. 155 156 analytical methods , whether or not they indicate stability, should be validated. 157 158 The analytical method should be validated by research and development before being 159 transferred to the quality control unit when appropriate. 160 161 The recommendations as provided for in good laboratory practices and GUIDELINES for 162 transfer of technology should be considered, where applicable, when analytical method 163 VALIDATION is organized and planned. 164 165 2. GENERAL 166 167 There should be specifications for both materials and products.

10 The tests to be performed 168 should be described in the documentation on standard test methods . 169 170 Specifications and standard test methods in pharmacopoeias ( pharmacopoeial 171 methods ), or suitably developed specifications or test methods ( non-pharmacopoeial methods ) 172 as approved by the national regulatory authority (NRA) may be used. 173 174 Well-characterized reference materials, with documented purity, should be used in 175 analysis. 176 177 The most common analytical procedures include identification tests, assay of drug 178 substances and pharmaceutical products, quantitative tests for content of impurities and limit 179 Working document page 5 tests for impurities. Other analytical procedures include dissolution testing and determination of 180 particle size.