Global access to quality-assured medical products: the Oxford Statement and call to action
Authors: Paul N Newton, Katherine C Bond, Paul Newton, Katherine Bond, Victor Abiola, Khadijah Ade-Abolade, Moji Adeyeye, Aria Ahmad, Tahani Ahmed, Pablo Alcocer Vera, Marie Amsilli, Marie Antignac, Chimezie Anyakora, Ayenew Ashenef, Adam Aspinall, Ghulam Rahim Awab, Zaheer-Ud-Din Babar, Wilbert Bannenberg, Jon Bastow, Carine Baxerres, Fred Behringer, Daniel Bempong, Chris Bird, Phonepasith Boupha, Kem Boutsamay, Jason Bower, Beth Boyer, Hazel Bradley, Joel Breman, Céline Caillet, Kashi Barbara Carasso, Phaik Yeong Cheah, Lester Chinery, Aubrey Clark, Erin Coonahan, Rachel Cooper, Philip Coyne, Andre Daher, Nicholas Day, Olivier De Santi, Fulgence Djorou Kouame, Kim Doyle, Ines du Plessis, Catherine Dujardin, Chioma Ejekam, Latifa El Hadri, Facundo Fernandez, Alessandra Ferrario, Clark Freifeld, Assma Gafur Omargy, Naira Mohamed Ali Ghanem, Marie Gill, Mike Grijseels, Philippe Guerin, Nhomsai Hagen, Heather Hamill, Georgina Joan Harigwo, Amalia Hasnida, Matthew Hassett, Cathrin Hauk, Lutz Heide, Peter Horby, Tsatsral Ichinkhorloo, Mike Isles, Richard Wilhelm Otto Jähnke, Alice Jamieson, Roslyn Jones, Tomoko Kakio, Mohga Kamal-Yanni, Harparkash Kaur, Pierre Claver Kayumba, Irina Kazaryan, Matthew Keller, Kalynn Kennon, Felix Khuluza, Stephen Kigera, Kazuko Kimura, Patricia Kingori, Joseph Kitukulu, Tineke Kleinhout-Vliek, Chaitanya Koduri, Maarten Kok, Mirza Lalani, Marie Lamy, Marya Lieberman, Rui Liu, Paul Lotay, Nantasit Luangasanatip, Murray Lumpkin, Susanne Lundin, Tim Mackey, Keiko Maekawa, Marissa Malchione, Boravann Mam, Roland Marini Djang'eing'a, Aronrag Meeyai, Talieh Mirsalehi, Gamal Mohamed Ali, Andria Mousa, Mirfin Mpundu, Immaculee Mukankubito, Ambwene Mwakalobo, Sheilah Catherine Nabukeera, Kris Natarajan, Bernard Naughton, Theophilus Ndorbor, Ariadna Nebot, Phillip Nguyen, Adina-Loredana Nistor, Bah Ngoh Nyaah Fidelis, Piero Olliaro, Eugenia Olliaro, Alberto Olliaro, Kenneth Onu, Sophie Ouvrard, Sachiko Ozawa, Michael Parker, Koray Parmaksiz, Anushka Patel, Daniel Pawson, Andrew Payne, Koen Peeters Grietens, Elizabeth Pettit, Souly Phanouvong, Elizabeth Pisani, Aline Plançon, Oksana Pyzik, Lembit Rägo, Mohammad Sofiqur Rahman, Eurek Ranjit, Raffaella Ravinetto, Joseph M. Redd, David Richmond, Pierre-Yves Sacré, Simon Schäfermann, Sauman Singh, Tariro Sithole, Andrea Stewart, Anita Svadzian, Patricia Tabernero, Fatima Tauqeer, Fiona Theunissen, Emmanuel Yaovi Tossou, Zahra Anita Trippe, Farouk Umaru, Ali Umoru, Serena Vickers, Vayouly Vidhamaly, Andrea Vogt, Lisa White, Nicholas White, Benjamin Wilson, Veronika J. Wirtz, Jessie Hui Zhen Wong, Owen Wood, Jing Xu, Jingying Xu, Shunmay Yeung, Muhammad Zaman, Monique Zambo Biloa, Zuzaan Zulzaga
Journal: The Lancet Global Health (2019)

Substandard and falsified medical products (including medicines, vaccines, biologics, and diagnostics1World Health OrganizationWHO Global Surveillance and Monitoring System for substandard and falsified medical products. World Health Organization, Geneva2017http://apps.who.int/medicinedocs/en/m/abstract/Js23373en/Date accessed: October 16, 2019Google Scholar) represent a significant and growing threat to human health. Substandard medical products result from errors, corruption, negligence, or poor practice in manufacturing, procurement, regulation, transportation, or storage. By contrast, falsified products result from criminal fraud. Although substandard and falsified medical products have been traded for many centuries, in the last few decades the problem has grown with the increased complexity of the global pharmaceutical economy and internet sales.2World Health OrganizationA study on the public health and socioeconomic impact of substandard and falsified medical products. World Health Organization, Geneva2017http://apps.who.int/medicinedocs/en/m/abstract/Js23372en/Date accessed: October 16, 2019Google Scholar Every person has the right to expect that when they use a medical product, it works as intended. But too often, it does not. Recent research evidence paints a bleak picture of global patient harm and economic damage: a systematic review and meta-analysis3Ozawa S Evans DR Bessias S et al.Prevalence and estimated economic burden of substandard and falsified medicines in low- and middle-income countries: a systematic review and meta-analysis.JAMA Netw Open. 2018; 1e181662Crossref PubMed Scopus (124) Google Scholar estimated that 12·4% of antibiotics and 19·1% of antimalarials in low-income and middle-income countries (LMICs) were substandard or falsified, with an estimated economic impact ranging from US$10 billion to $200 billion; in 2015 WHO found alarming failure rates (64%) for vital oxytocin injections;4World Health OrganizationSurvey of the quality of medicines identified by the United Nations Commission on Life Saving Commodities for women and children.https://extranet.who.int/prequal/sites/default/files/documents/UNCoLSC_2015.pdfDate accessed: October 16, 2019Google Scholar a large epidemic of dystonic reactions occurred in central Africa due to mass substitution of diazepam tablets with haloperidol, probably inserted criminally;5Peyraud N Rafael F Parker LA et al.An epidemic of dystonic reactions in central Africa.Lancet Glob Health. 2017; 5: e137-e138Summary Full Text Full Text PDF PubMed Scopus (13) Google Scholar recent data from Europe highlight key neglected issues with the quality of medical devices;6Godlee F Why aren't medical devices regulated like drugs?.BMJ. 2018; 363k5032Crossref Scopus (9) Google Scholar and the SEVEN study in sub-Saharan Africa found that 16·3% of 1530 randomly sampled cardiovascular medications (anticoagulants, antihypertensives, and statins) failed Active PharmaceuticaI Ingredient content analysis.7Antignac M Diop BI Macquart de Terline D et al.Fighting fake medicines: first quality evaluation of cardiac drugs in Africa.Int J Cardiol. 2017; 243: 523-528Summary Full Text Full Text PDF PubMed Scopus (30) Google Scholar In the face of mounting harm, regulatory bodies are alarmingly underequipped. WHO recently stated that "Fewer than 30% of the world's medicines regulatory authorities are considered to have the capacity to perform the functions required to ensure medicines, vaccines and other health products actually work and do not harm patients."8World Health OrganizationTanzania is first African country to reach an important milestone in the regulation of medicines.https://www.afro.who.int/news/tanzania-first-african-country-reach-important-milestone-regulation-medicinesDate accessed: October 16, 2019Google Scholar Few national medicines regulatory authorities (NMRAs) have a policy of publicly releasing data on substandard and falsified medical products and there has been minimal discussion of local policies on how to engage appropriately with the public about such reports. In September, 2018, the first international Medicine Quality and Public Health Conference was held at Oxford University, UK, to discuss opportunities and solutions to ensure that all people have access to affordable and quality-assured medical products. Delegates developed the short Oxford Statement, calling for investment, policy change, and action to eliminate substandard and falsified medical products. The statement was born out of discussion between governments, national and international agencies, non-governmental organisations, professional associations, and academic institutions who together examined the latest evidence on the epidemiology and public health implications of substandard and falsified medical products. Here, we expand this statement with a call to action (panel) and research agenda (appendix 2).PanelThe Oxford Statement on Medicine Quality and Public HealthBuilding on growing evidence of the prevalence and impact of substandard and falsified medical products, it is time to make access to quality medical products an immediate global priority and encourage research informing policy and implementation.We support:(a)The recommendation from all WHO Member States, accepted by the 2017 World Health Assembly, that defines substandard and falsified medicines in public health terms(b)WHA Resolution 67.20, calling on Member States and WHO to strengthen national medicines regulatory authorities (NMRA)And we call for accelerated progress towards global access to quality-assured medical products through:(a)Adoption of WHO's "Prevent, Detect and Respond" strategy under the Member State Mechanism framework1World Health OrganizationWHO Global Surveillance and Monitoring System for substandard and falsified medical products. World Health Organization, Geneva2017http://apps.who.int/medicinedocs/en/m/abstract/Js23373en/Date accessed: October 16, 2019Google Scholar(b)Collaboration and harmonisation for the global strengthening of medicines regulatory systems, guided by the WHO Global Benchmarking Tool for NMRAs(c)Increased investment by nations, regional bodies, and international donor agencies in financial and capacity building mechanisms that facilitate:•All national NMRAs achieving the highest possible WHO Maturity Level•Appropriate expansion of local manufacturing capabilities implemented according to Good Manufacturing Practice•Strengthening medical product supply systems and post-market surveillance(d)Increased investment by research funders for assessing the impact of substandard and falsified medical products, especially on patient outcomes, economic cost, and antimicrobial resistance, and the cost-effectiveness of interventions to eliminate substandard and falsified medical productsKey needs in the prevention domain:•Equitable access to affordable quality-assured medical products, without stockouts•Robust quality assurance systems for registration, production, procurement, distribution, pharmacovigilance, post-marketing surveillance, and enhanced data sharing of medical product quality•Consistent quality requirements for production and procurement across public and private sectors, nationally and internationally, for both domestic use and export•Improved regulatory action, governance, accountability, and transparency across the medical product lifecycle, including appropriate public access to data on registered quality-assured medical products, inspection outcomes, product recalls, and for internet sales•Sustained enhanced funding and support for the WHO Essential Medicines and Health Products Department, including the WHO Pre-qualification Team and the Substandard and Falsified Medical Products Group•Education of health workers, policy-makers, and the public on the importance and impact of quality-assured medical products, safe procurement, and distribution, and incorporation of thes elements into pharmacy, nursing, and medical curricula•Global convergence of standards and medical products regulation regionally and globallyKey needs in the detection domain:•Increase in laboratory capability to perform timely risk-based monitoring and detection of substandard and falsified medical products throughout supply chains and collaboration between inspecting organisations•Increased investment in innovative field screening devices for the rapid detection of substandard and falsified products and their standardised evaluation including cost-effectiveness analysisKey needs in the response domain:•Strengthened administrative and legal frameworks of NMRAs to respond promptly and appropriately•Mandatory timely reporting by all of substandard and falsified medical products to relevant NMRAs and WHO Substandard and Falsified Medical Products Group by all state and non-state actors•Clear plans for governmental and international organisations responses to substandard and falsified medical product "outbreaks", including procedures to engage with the public and health workers, to ensure timely and appropriate public health response•Analysis of substandard and falsified epidemiology data to improve prevention, detection, and response Building on growing evidence of the prevalence and impact of substandard and falsified medical products, it is time to make access to quality medical products an immediate global priority and encourage research informing policy and implementation. We support: (a)The recommendation from all WHO Member States, accepted by the 2017 World Health Assembly, that defines substandard and falsified medicines in public health terms(b)WHA Resolution 67.20, calling on Member States and WHO to strengthen national medicines regulatory authorities (NMRA) And we call for accelerated progress towards global access to quality-assured medical products through: (a)Adoption of WHO's "Prevent, Detect and Respond" strategy under the Member State Mechanism framework1World Health OrganizationWHO Global Surveillance and Monitoring System for substandard and falsified medical products. World Health Organization, Geneva2017http://apps.who.int/medicinedocs/en/m/abstract/Js23373en/Date accessed: October 16, 2019Google Scholar(b)Collaboration and harmonisation for the global strengthening of medicines regulatory systems, guided by the WHO Global Benchmarking Tool for NMRAs(c)Increased investment by nations, regional bodies, and international donor agencies in financial and capacity building mechanisms that facilitate:•All national NMRAs achieving the highest possible WHO Maturity Level•Appropriate expansion of local manufacturing capabilities implemented according to Good Manufacturing Practice•Strengthening medical product supply systems and post-market surveillance(d)Increased investment by research funders for assessing the impact of substandard and falsified medical products, especially on patient outcomes, economic cost, and antimicrobial resistance, and the cost-effectiveness of interventions to eliminate substandard and falsified medical products Key needs in the prevention domain: •Equitable access to affordable quality-assured medical products, without stockouts•Robust quality assurance systems for registration, production, procurement, distribution, pharmacovigilance, post-marketing surveillance, and enhanced data sharing of medical product quality•Consistent quality requirements for production and procurement across public and private sectors, nationally and internationally, for both domestic use and export•Improved regulatory action, governance, accountability, and transparency across the medical product lifecycle, including appropriate public access to data on registered quality-assured medical products, inspection outcomes, product recalls, and for internet sales•Sustained enhanced funding and support for the WHO Essential Medicines and Health Products Department, including the WHO Pre-qualification Team and the Substandard and Falsified Medical Products Group•Education of health workers, policy-makers, and the public on the importance and impact of quality-assured medical products, safe procurement, and distribution, and incorporation of thes elements into pharmacy, nursing, and medical curricula•Global convergence of standards and medical products regulation regionally and globally Key needs in the detection domain: •Increase in laboratory capability to perform timely risk-based monitoring and detection of substandard and falsified medical products throughout supply chains and collaboration between inspecting organisations•Increased investment in innovative field screening devices for the rapid detection of substandard and falsified products and their standardised evaluation including cost-effectiveness analysis Key needs in the response domain: •Strengthened administrative and legal frameworks of NMRAs to respond promptly and appropriately•Mandatory timely reporting by all of substandard and falsified medical products to relevant NMRAs and WHO Substandard and Falsified Medical Products Group by all state and non-state actors•Clear plans for governmental and international organisations responses to substandard and falsified medical product "outbreaks", including procedures to engage with the public and health workers, to ensure timely and appropriate public health response•Analysis of substandard and falsified epidemiology data to improve prevention, detection, and response These actions will require advocacy and political commitment spanning diverse sectors, to mobilise sustainable investment in people and infrastructure through collaborative capacity building, sustainable financing mechanisms, and good governance. Partnerships between NMRAs, regional bodies, and other key stakeholders need significant strengthening. Although NMRAs are keystones for many actions, they need to work in close collaboration with related actors including Ministries of Health, Finance and Trade, and Science and Technology; pharmaceutical manufacturers and distributors; medicine procurers; funding and implementation agencies; central medical stores; pharmacists; innovators; academics; law enforcement agencies; the judiciary; and civil society, including patients' organisations. Accountability and transparency by all is critical to promote progress towards country and international development goals. Initiatives such as the #MedsWeCanTrust campaign are building awareness, serving as a tool so that patients, health workers, governments, policy makers, the pharmaceutical industries, and others understand the role they can play in calling for and making the commitments and policy changes necessary to ensure that the medical products that reach people work. Substandard and falsified medical products cause maltreatment, harm patients, weaken health systems, undermine universal health coverage and the Sustainable Development Goals, and are counter to the fundamental principles of people's right to health. With significant human health and economic consequences at stake, urgent action is needed now. This online publication has been corrected. The corrected version first appeared at thelancet.com/lancetgh on November 13, 2019 and further corrections were made on April 27, 2020 This online publication has been corrected. The corrected version first appeared at thelancet.com/lancetgh on November 13, 2019 and further corrections were made on April 27, 2020 We declare no competing interests. For the full list of signatories see appendix 3. We are very grateful to the Vice-Chancellor of the University of Oxford, the Nuffield Department of Medicine's Centre for Tropical Medicine & Global Health, the MORU Tropical Health Network, the Infectious Diseases Data Observatory, and Keble College, for their help in hosting the conference and all those who attended and gave such wonderful contributions. We thank Eshe Hill for her marvellous help. Generous support was provided by the Bill & Melinda Gates Foundation, Wellcome Trust, United States Pharmacopeial Convention, the Medicines for Malaria Venture, the Regional Centre of Excellence for Vaccines, Immunization and Health Supply Chain Management, Rwanda, and Concept Foundation to support attendees from LMICs. The opinions expressed are those of the authors and do not necessarily represent the opinion of their employers. Download .pdf (.15 MB) Help with pdf files French translation of the comment Download .pdf (.15 MB) Help with pdf files Supplementary appendix 2 Download .pdf (.23 MB) Help with pdf files Supplementary appendix 3 Correction to Lancet Glob Health 2019; 7: e1609–11Newton PN, Bond KC, on behalf of the Oxford Statement signatories. Global access to quality-assured medical products: the Oxford Statement and call to action. Lancet Glob Health; 2019; 7: e1609–11—In this Comment, the URL for the short Oxford Statement should have been "https://www.iddo.org/news/mqph-short-statement-2018". Additionally, some of the signatories were missing from appendix 3. These corrections have been made, and a new French translation added as Appendix 1, as of Nov 13, 2019. Full-Text PDF Open AccessCorrection to Lancet Glob Health 2019; 7: e1609–11Newton PN, Bond KC, on behalf of the Oxford Statement signatories. Global access to quality-assured medical products: the Oxford Statement and call to action. Lancet Glob Health 2019; 7: 1609–11—In this Comment, the signatories were not correctly listed on PubMed. This has been rectified as of April 27, 2020. Full-Text PDF Open Access