TARGET PRODUCT PROFILES FOR NEEDED ANTIBACTERIAL AGENTS: enteric fever, gonorrhoea, neonatal sepsis, urinary tract infections and meeting report TARGET PRODUCT PROFILES FOR NEEDED ANTIBACTERIAL AGENTS: enteric fever, gonorrhoea, neonatal sepsis, urinary tract infections and meeting report TARGET PRODUCT PROFILES FOR NEEDED ANTIBACTERIAL AGENTS: enteric fever, gonorrhoea, neonatal sepsis, urinary tract infections and meeting report Target product profiles for needed antibacterial agents: enteric fever, gonorrhoea, neonatal sepsis, urinary tract infections and meeting report ISBN 978-92-4-000389-7 (electronic version) ISBN 978-92-4-000390-3 (print version) © World Health Organization 2020 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial- ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/ by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization. Suggested citation. Target product profiles for needed antibacterial agents: enteric fever, gonorrhoea, neonatal sepsis, urinary tract infections and meeting report. Geneva: World Health Organization; 2020. Licence: CC BY-NC-SA 3.0 IGO. Cataloguing-in-Publication (CIP) data. CIP data are available at http://apps.who.int/iris. Sales, rights and licensing. To purchase WHO publications, see http://apps.who.int/bookorders. To submit requests for commercial use and queries on rights and licensing, see http://www.who.int/about/ licensing. Third-party materials. If you wish to reuse material from this work that is attributed to a third party, such as tables, figures or images, it is your responsibility to determine whether permission is needed for that reuse and to obtain permission from the copyright holder. The risk of claims resulting from infringement of any third-party-owned component in the work rests solely with the user. General disclaimers. The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of WHO concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted and dashed lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by WHO in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. All reasonable precautions have been taken by WHO to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind, either expressed or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall WHO be liable for damages arising from its use. Printed in Switzerland. Contents Acknowledgements iv Financial support iv EXPERT MEETING ON TARGET PRODUCT PROFILES FOR NEEDED ANTIBACTERIAL AGENTS 1 1 3–4 OCTOBER 2019, GENEVA, SWITZERLAND, MEETING REPORT Introduction 1 The TPP development process 2 Summary of the meeting proceedings 3 Summary of discussions 3 Conclusion 5 2 TARGET PRODUCT PROFILE FOR THERAPY OF UNCOMPLICATED ENTERIC FEVER 7 Introduction 7 Disease burden 7 Antibiotic resistance 7 Available treatment options 7 Therapies in development 7 Purpose of the TPP 8 Access and affordability 8 TPP for therapy of uncomplicated enteric fever 9 3 TARGET PRODUCT PROFILE FOR THERAPY OF DIAGNOSED UNCOMPLICATED GONORRHOEA 11 Introduction 11 Disease burden 11 Antibiotic resistance 11 Available treatment options 11 Therapies in development 12 Purpose of the TPP 12 Access and affordability 12 TPP for therapy of diagnosed uncomplicated gonorrhoea 13 4 TARGET PRODUCT PROFILE FOR THERAPY OF NEONATAL SEPSIS IN HIGH RESISTANCE SETTINGS 15 Introduction 15 Disease burden 15 Antibiotic resistance 15 Available treatment options 15 Therapies in development 16 Purpose of the TPP 16 Access and affordability 16 TPP for therapy in children including neonates with MDR Gram-negative infections 17 5 TARGET PRODUCT PROFILES FOR ORAL THERAPY OF URINARY TRACT INFECTIONS 19 Introduction 19 Disease burden 19 Antibiotic resistance 19 Available treatment options 19 Therapies in development 20 Purpose of the TPPs 20 Access and affordability 20 TPP for oral therapy of acute uncomplicated UTI (cystitis) 22 TPP for oral therapy of acute pyelonephritis 23 TARGET PRODUCT PROFILES FOR NEEDED ANTIBACTERIAL AGENTS iii Acknowledgements The project was led by Ingrid Smith (WHO/ STI Programmes; and Maternal, Newborn, Child & Department of Global Coordination and Partnership Adolescent Health and Ageing for their input and (GCP)/Antimicrobial Resistance (AMR)), under the active participation throughout the process. WHO supervision of Peter Beyer (WHO/GCP/AMR). Ursula would also like to thank all the experts in the scientific Theuretzbacher (WHO consultant and Center for advisory group as well as all external organizations Anti-Infective Agents, Austria) was the leading and individuals who provided comments on the scientific expert and prepared the scoping and draft scoping documents and feedback on the draft TPP documents. GCP would like to thank experts TPP documents during the public consultation. In from the following WHO Departments – Health compliance with WHO transparency procedures, the Products, Policy and Standards; Immunization, feedback received during the public consultation on Vaccines and Biologicals; Global HIV, Hepatitis and the TPP documents was made publicly available. Financial support Funding for this project was kindly provided by GARDP and by the Governments of Germany and Norway. iv TARGET PRODUCT PROFILES FOR NEEDED ANTIBACTERIAL AGENTS Expert meeting on target product profiles for needed antibacterial agents 3–4 October 2019, Geneva, Switzerland Meeting report Introduction This is the report of the scientific advisory group clinical development in 2017, and the report meeting on the development of target product Antibacterial agents in preclinical development profiles (TPPs) for needed antibacterial agents for in 2019, to provide evidence-based guidance and enteric fever (typhoid fever), gonorrhoea, neonatal a public health perspective in developing new sepsis and urinary tract infections, that took place antibacterial therapies.2,3 in Geneva, Switzerland, on 3–4 October 2019. WHO has subsequently formulated TPPs to meet Antimicrobial resistance (AMR) has increased the need for specific antibacterial agents. TPPs worldwide in recent decades, limiting treatment are used by drug developers to provide strategic options for many bacterial infections. In 2015, AMR guidance for product development programmes, was recognized as a global public health challenge and to specify the intended use, target populations with the adoption of the Global Action Plan and desired attributes of potential new products. (GAP) by the sixty-eighth World Health Assembly, In the regulatory context, TPPs help to frame providing countries with a blueprint for action to development in relation to submission of product combat AMR both nationally and internationally.1 dossiers. In the context of public health, WHO TPPs set R&D targets for funders and developers by In response to GAP objective 5, WHO developed outlining the desired performance and operational the Global priority list of antibiotic-resistant characteristics of potential new products. bacteria and the report Antibacterial agents in 1 Global action plan on antimicrobial resistance. Geneva: World Health Organization; 2015 (https://www.who.int/antimicrobial-resistance/global- action-plan/en/, accessed 23 January 2020). 2 Prioritization of pathogens to guide discovery, research and development of new antibiotics for drug-resistant bacterial infections, including tuberculosis. Geneva: World Health Organization; 2017 (WHO/EMP/IAU/2017.12; https://www.who.int/medicines/areas/rational_use/ prioritization-of-pathogens/en/, accessed 23 January 2020). 3 Antibacterial agents in clinical development: an analysis of the antibacterial clinical development pipeline, including tuberculosis. Geneva: World Health Organization; 2017 (WHO/EMP/IAU/2017.12; https://www.who.int/medicines/areas/rational_use/antibacterial_agents_clinical_ development/en/, accessed 23 January 2020). TARGET PRODUCT PROFILES FOR NEEDED ANTIBACTERIAL AGENTS 1 The TPP development process The TPPs for new antibacterial agents were developed the WHO standard procedure