The World Health Organization Prequalification Programme—playing an essential role in assuring quality medical products

The global health community is belatedly recognizing the problem of substandard and falsified (SF) medicines.1 Two recent landmark events took place in September 2018: while the first-ever Medicines Quality and Public Health Conference was under way in Oxford, UK, a concurrent meeting was taking place during the 73rd Session of the United Nations General Assembly in New York. This second meeting, cohosted by five African heads of state along with the director general of the World Health Organization (WHO) and the director of the WHO Africa Region, was entitled ‘The Fight for Quality Medicines in Africa—stopping Falsified, Substandard Medicines’. SF medicines are a global scourge, as has been illustrated in recent studies.1–3 Currently the WHO estimates that 1 in 10 medical products globally are substandard or falsified, with considerably higher prevalence in countries with poorly developed regulatory infrastructures. In order to gain a better understanding of the scope of this problem, the WHO initiated a system of surveillance, called the Global Surveillance and Monitoring System (GSMS), in 2012. As this system has been deployed, the global health community is awakening to the disturbing fact that when it comes to SF medical products, the more one looks, the more one finds.4 One of the key components of the WHO strategy to address the global problem of SF medicines has been the Prequalification Programme. This editorial addresses the questions of what is ‘prequalification’ and how does this procedure help to enhance access to quality medical products in the developing world? The WHO prequalification procedure is a mechanism that seeks to ensure a supply of quality-assured products—medicines, vaccines, in vitro diagnostics, other medical devices and, most recently, vector control products—particularly for use in low-income countries. The mandate for the WHO’s work in this area derives from Article 2 of the WHO Constitution, which calls for the WHO ‘to develop, establish and promote international standards with respect to food, biological, pharmaceutical and similar products’, and from Article 21, which states that the World Health Assembly ‘shall have authority to adopt regulations concerning…(d) standards with respect to the safety, purity and potency of biological, pharmaceutical and similar products moving in international commerce’. The term ‘prequalification’ was first used in the context of vaccine procurement. When the WHO’s Expanded Programme on Immunization (EPI) began in 1974, member countries sought to procure vaccines via the Supply Division of the United Nations Children’s Fund (UNICEF). A major challenge faced by UNICEF was to ensure that the vaccines purchased met appropriate standards of quality, safety and efficacy. The need for a unified, standardized process became evident, leading to the creation of the Prequalification Programme in 1987. Subsequently, as the need for quality-assured antiretroviral drugs grew to address the human immunodeficiency virus epidemic, a similar approach was taken for medicines. The medicines Prequalification Programme at the WHO was initiated in 2001. Its vision is simple: good-quality health products for everyone. Its mission is to ensure the timely availability of quality-assured health products for the prevention, diagnosis and treatment of priority diseases, through assessment of the quality, safety and efficacy/performance of these products, with a focus on their suitability for use in resource-limited settings.5 How does it work? Prequalification is based on assessment of a product dossier submitted by the organization/manufacturer seeking prequalification, utilizing accepted international regulatory standards of quality, safety and efficacy/performance, and inspection of the corresponding manufacturing sites, as well as other product-specific elements of evaluation, such as a laboratory evaluation (for diagnostics) or inspection of the clinical trial sites (for medicines). The process is initiated by the WHO issuing an ‘Invitation to Manufacturers to Submit an Expression of Interest for Product Evaluation’ (usually referred to as the ‘Expression of Interest’ [EOI]) for a specific medical product. EOIs are issued by the WHO, by therapeutic area, following consultation with WHO disease programmes. The medicines (referred to as finished pharmaceutical products [FPPs]) or vaccines invited for evaluation have been identified by WHO clinical experts as vital to effective treatment and expansion of treatment programmes or to ensuring improved reproductive health. Usually every product contained in an EOI is already included in the WHO Model List of Essential Medicines or the WHO Model List of Essential Medicines for Children and/or in WHO treatment or other relevant guidelines for specific conditions.6 To date, more than 680 medicines (either FPPs or active pharmaceutical ingredients), 148 vaccines, 331 immunization devices, 71 vector control products and 80 diagnostic tests have been prequalified (unpublished data, WHO). This is an important contribution to the global health community and low- and middle-income countries. The introduction of quality-assured medicines using the WHO prequalification listing can help to displace the SF products that might otherwise be procured. Another key part of the global response to the scourge of SF medicines involves regulatory capacity building. It is clear from GSMS data that countries with weak regulatory capacity are at increased risk for the introduction of SF products. Since 2014, the WHO has been engaged in a process called Regulatory Systems Strengthening (RSS), the first step of which is an objective assessment of member states’ regulatory capacity, utilizing the Global Benchmarking Tool.7 This tool has categorized National Regulatory Authorities (NRAs) into four ‘maturity levels’ ranging from level 1 (no formal approach, but with some elements of a regulatory system) up to level 4 (system operating at an advanced level of performance, with an emphasis on continuous improvement). More than half (99 of 194) of the member states’ NRAs are categorized as level 1. The Prequalification Programme contributes to RSS in two important ways. First is via inspection and prequalification of member states’ quality control laboratories. This programme has prequalified 44 drug quality testing facilities, ensuring the quality and reliability of analyses vital to a well-functioning NRA. This is an important yet often overlooked aspect of regulatory capacity strengthening. Second, each meeting of a Prequalification Team convenes a group of regulators from agencies with a variety of ‘maturity levels’. Regulatory staff from level 1 NRAs work alongside experienced regulatory scientists from a variety of fully mature NRAs (now referred to as ‘WHO Listed Authorities’, previously referred to as ‘Stringent Regulatory Authorities’ [SRAs]). These regular team meetings thus provide a critical opportunity for capacity strengthening, as the experience gained during prequalification team assessments is brought back to the level 1 NRAs. SF medicines are estimated by the Global Economic Forum to be the single most profitable category of trade in illicit goods, with an estimated US $200 billion in revenues annually.8 A concerted, coordinated and well-resourced response by the global health community is long overdue. Hopefully the events of September 2018 indicate that the global health community is ready to fully engage in the fight against SF health products. WHO prequalification is a vital and concrete contribution to this effort. Author’s contributions: Philip Coyne was the sole author of this editorial. Acknowledgments: None. Funding: None. Competing interests: I should declare that I am a part-time consultant to the WHO pre-qualification of medicines programme, although they did not fund any aspect of this work. Ethical approval: Not required.