1 2 3 4 WHO/BS/2016.2300 5 ENGLISH ONLY 6 7 8 WHO Guidelines for the Production Control and 9 Regulation of Snake Antivenom Immunoglobulins 10 NOTE: 11 This document has been prepared for the purpose of inviting comments and suggestions on the proposals 12 contained therein, which will then be considered by the Expert Committee on Biological Standardization 13 (ECBS). Publication of this early draft is to provide information about the proposed WHO Guidelines for 14 the Production Control and Regulation of Snake Antivenom Immunoglobulins, to a broad audience and to 15 improve transparency of the consultation process. 16 The text in its present form does not necessarily represent an agreed formulation of the Expert Committee. 17 Written comments proposing modifications to this text MUST be received by 30 September 2016 in 18 the Comment Form available separately and should be addressed to the World Health Organization, 19 1211 Geneva 27, Switzerland, attention: Department of Essential Medicines and Health Products (EMP). 20 Comments may also be submitted electronically to the Responsible Officer: Dr C Micha Nübling at email: 21 [email protected]. 22 The outcome of the deliberations of the Expert Committee on Biological Standardization will be published 23 in the WHO Technical Report Series. 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Dotted lines on maps represent approximate border lines for 34 which there may not yet be full agreement. 35 The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by 36 the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the 37 names of proprietary products are distinguished by initial capital letters. 38 All reasonable precautions have been taken by the World Health Organization to verify the information contained in this publication. 39 However, the published material is being distributed without warranty of any kind, either expressed or implied. The responsibility for 40 the interpretation and use of the material lies with the reader. In no event shall the World Health Organization be liable for damages 41 arising from its use. 42 Second edition, draft (August 28, 2016) WHO/BS/2016.2300 Page 2 1 CONTENTS 2 1 List of abbreviations and definitions used ............................................................................ 9 3 2 General considerations ..................................................................................................... 15 4 2.1 Historical background ................................................................................................... 15 5 2.2 The use of serum versus plasma as source material ........................................................... 15 6 2.3 Antivenom purification methods and product safety ......................................................... 15 7 2.4 Pharmacokinetics and pharmacodynamics of antivenoms .................................................. 16 8 2.5 Need for national and regional reference venom preparations ............................................ 16 9 3 Epidemiological Background ............................................................................................. 17 10 3.1 Global burden of snakebites ........................................................................................... 17 11 3.2 Main recommendations ................................................................................................. 18 12 4 Worldwide distribution of venomous snakes...................................................................... 19 13 4.1 Taxonomy of venomous snakes ..................................................................................... 19 14 4.2 Medically important venomous snakes ............................................................................ 22 15 4.3 Minor venomous snake species ...................................................................................... 24 16 4.4 Sea snake venoms ........................................................................................................ 25 17 4.5 Main recommendations ................................................................................................. 25 18 5 Antivenoms design: selection of snake venoms ................................................................ 26 19 5.1 Selection and preparation of representative venom mixtures .............................................. 26 20 5.2 Manufacture of monospecific or polyspecific antivenoms ................................................. 26 21 5.2.1 Monospecific antivenoms .................................................................................... 26 22 5.2.2 Polyspecific antivenoms ...................................................................................... 27 23 5.3 Main recommendations ................................................................................................. 28 24 6 Preparation and storage of snake venom .......................................................................... 29 25 6.1 Production of snake venoms for immunization ................................................................. 30 26 6.1.1 Quarantine of snakes ........................................................................................... 30 27 6.1.2 Maintenance of captive snakes for venom production ................................................ 30 28 6.1.3 General maintenance of a serpentarium .................................................................... 32 29 6.1.4 Snake venom production ........................................................................................ 33 30 6.2 Staff responsible for handling snakes .............................................................................. 36 31 6.2.1 Safety and health considerations ............................................................................. 36 32 6.2.2 Personal Protective Equipment (PPE) for snake or venom handling ............................. 36 33 6.2.3 Procedures to be followed if a bite occurs ................................................................. 36 34 6.3 Main recommendations ................................................................................................. 38 35 7 Quality control of venoms .................................................................................................. 39 36 7.1 Records and traceability ................................................................................................ 39 37 7.2 National reference materials .......................................................................................... 39 38 7.3 Characterization of venom batches ................................................................................. 40 39 7.4 Main recommendations ................................................................................................. 40 WHO/BS/2016.2300 Page 3 1 8 Overview of the production process of antivenoms ............................................................ 42 2 9 Selection and veterinary health care of animals used for production of antivenoms .......... 44 3 9.1 Selection and Quarantine period ..................................................................................... 44 4 9.2 Veterinary care, monitoring and vaccinations ................................................................... 44 5 9.3 Animal health and welfare after inclusion in the herd ........................................................ 45 6 9.4 Main recommendations ................................................................................................. 46 7 10 Immunization regimens and use of adjuvant .................................................................. 48 8 10.1 Animals used in antivenom production ............................................................................ 48 9 10.2 Venoms used for immunization ...................................................................................... 49 10 10.3 Preparation of venom doses ........................................................................................... 49 11 10.4 Detoxification of venom ................................................................................................ 50 12 10.5 Immunological adjuvants ............................................................................................... 50 13 10.6 Preparation of immunogen in adjuvants ........................................................................... 50 14 10.7