Breakthroughs Blog: WHO

GHTC welcomes the recent announcement by the World Health Organization (WHO) that it will apply parallel, rather than sequential, processes in developing guidelines recommending the use of novel health products and certifying their safety and efficacy via prequalification (PQ) and/or Emergency Use Listing (EUL). Many of our members and partners have highlighted how the prior procedure, which required guidelines to be in place as a prerequisite to EUL or PQ, was a major bottleneck for innovative products—adding significantly to approval timelines and delaying access to critical new health technologies in low- and middle-income countries.We believe that this new parallel process, which was first trialed during the pandemic for COVID-19 products, could significantly improve and accelerate access to vital innovative health technologies in countries that rely on WHO recommendations for the use of these products. We urge WHO to provide additional details on the implementation of this new process and encourage the PQ program to provide a platform for continued feedback and input from key stakeholders, including product developers, national regulators, procurers, and civil society.We believe that WHO’s PQ program continues to be an essential link in the regulatory ecosystem, and we hope this is just one of several steps WHO will take to reduce bottlenecks and improve the program’s efficiency and impact.  

Interested in more global health innovation news? Every week GHTC scours media reports worldwide to deliver essential global health R&D news and content to your inbox. Sign up now to receive our weekly R&D News Roundup email. Last Friday, the World Health Organization (WHO) announced the prequalification of a novel typhoid conjugate vaccine, developed through a global public-private partnership between SK bioscience and the International Vaccine Institute. Clinical trials in the Philippines and Nepal showed that the vaccine was safe to administer in infants and children as young at 6  months to two years and offered long-term protection with a single dose. As the rising global threats of climate change and antimicrobial resistance amplify the risk of typhoid, which causes between 120,000 and 160,000 deaths globally every year, this vaccine could help grow the global supply of typhoid conjugate vaccines and improve access in low- and middle-income countries through public procurement markets.Researchers have discovered a potent antibody, 95Mat5, that can neutralize a key type of neurotoxin produced by four deadly snake species in South Asia, Southeast Asia, and Africa. Currently, the standard treatment for snake bites, which kill an estimated 81,000 to 138,000 people globally every year and primarily occur in low- and middle-income countries, is antivenoms that consist of a variety of animal-harvested antibodies. These antivenoms can vary in efficacy and can also cause adverse immune reactions because the antibodies they use come from animals. Continued development of 95Mat5, which was synthetically created, could lead to a new antivenom that could be used to treat bites from the world's most dangerous venomous snakes and would be less likely to cause side effects because the antibody is human-derived.FHI 360 is leading a Phase 1 clinical trial of the biodegradable contraceptive implant Casea S, the first trial for a biodegradable contraceptive implant in more than 20 years. Casea S is implanted in the arm and works by releasing a synthetic hormone to prevent pregnancy for 18 to 24 months before dissolving. If proven successful in future trials, Casea S could serve as an alternative contraceptive option in the growing toolkit of products necessary to address the diverse needs and lifestyles of contraceptive users. Currently available implants are highly effective and safe and increasingly popular. Casea S could be an even better option, especially in low- and middle-income countries where users can face barriers to receiving care, because it dissolves by itself, eliminating the need for a removal procedure by a trained medical provider.  

Over the course of the COVID-19 pandemic, more than 1 billion vaccine doses were delivered to the world’s poorest countries via the World Health Organization (WHO)-backed COVAX vaccine sharing scheme. While much attention has gone to evaluating the successes and shortcomings of this effort in the wake of the pandemic, far less has been directed towards the WHO program that helped facilitate the introduction of these vaccines and other technologies by certifying their safety and efficacy—a program that deserves equally nuanced examination.  For decades, the WHO prequalification (PQ) program has played an essential role in accelerating access to health products in low- and middle-income countries (LMICs) by reviewing their safety, efficacy, and quality. It is a stamp of approval that clears the way for multilateral agencies to procure drugs, vaccines, diagnostics, and vector control products, and it guides emerging regulatory agencies that might otherwise lack the capacity to conduct independent reviews. But despite the program’s critical role in the global health ecosystem, it has been plagued by both operational and procedural challenges that create unnecessary delays. External stakeholders highlight pain points in the PQ programThat paradox is on full display in an independent evaluation released last fall of the WHO Department of Regulation and Prequalification, which oversees the PQ program. The assessment lauds the PQ program’s successes in expanding global access to products, especially during the COVID-19 pandemic; however, it also highlights the need for increased communication and collaboration between the PQ department and key stakeholders in the public health ecosystem, including product developers, national regulatory authorities, procurers, and other WHO departments. It also notes how manufacturers who apply for PQ are especially keen to have more visibility into PQ decision timelines and roadmaps for the release of related technical standards and guidelines. Stakeholders also unanimously highlighted the limited resourcing at WHO headquarters as a key constraint across the PQ department. According to the evaluation, the department’s resources have remained stable between 2018 and 2022 (from 114 staff members in December 2019 to 115 in December 2022). However, the scope and the workload across all teams have increased substantially over the same period. This assessment echoes recommendations from a 2022 report from GHTC and the Duke Global Health Innovation Center, which also urged PQ to increase visibility into anticipated timelines for decision gates throughout the review process so developers can better anticipate communication and decision-making. The report also recommended that the PQ program be more transparent in publicly disclosing information on how it is performing against these targets, as well as provide access to regularly updated public databases with complete milestone information on all prequalified products. Moving towards greater efficiency and transparency Fortunately, recent moves by WHO suggest the agency is beginning to take this feedback seriously and pursue remedies. Alongside the release of the evaluation, WHO announced the forthcoming launch of a new electronic portal for processing PQ applications. The portal promises a one-stop shop for applicants to file applications and relevant documents, receive status notifications, and track and respond to requests—offering them a real-time picture of their application status. This portal should also drive major efficiency improvements, as applications are currently processed manually, meaning that WHO staff handled the more than 1,000 PQ applications received in 2022 without automated support mechanisms. For national regulatory agencies, particularly those involved in WHO’s Collaborative Registration Processes—which allow for regulators to rely on evaluations carried out by WHO and other participating stringent regulatory authorities to accelerate their regulatory decision-making—, the portal provides a single location where they can also access all relevant information and documents in tandem with WHO. Importantly, the portal will also capture process-related milestones in greater detail and integrate with the WHO website, which we hope will allow PQ to improve reporting and transparency. While, unfortunately, the intended January 2024 launch of the portal has been delayed to the second quarter of the year, the rollout of the portal should be a welcome step toward a more effective, efficient, and transparent PQ program. A new path forward for novel products?Alongside pursuing operational improvements to processing applications, it is also vital that WHO reevaluate the PQ process itself to ameliorate bottlenecks that delay access to critically needed new technologies. Our 2022 report identified the interplay between the PQ process and the release of WHO treatment and use guidelines as one such process area ripe for change. Currently, WHO PQ procedure states that before a product can complete the PQ process and be listed, the product must already be featured in published WHO policy guidelines that recommend its use in clinical practice or public health policy. Stakeholders with whom we spoke identified this sequence as an obstacle and a source of delay for the PQ of novel products since the committees that develop guidelines, which operate outside the PQ process, will not release them until the clinical data upon which the guidelines are based are formally published in peer-reviewed literature, which can often take some time. During the COVID-19 pandemic, WHO proved these functions could occur more flexibly and in parallel. For example, WHO released regularly updated “living guidelines” for COVID-19 therapeutics as new clinical evidence emerged and, in 2022, released interim guidance for novel shorter-course treatments for drug-resistant tuberculosis. WHO PQ also initiated and advanced PQ review of the COVID-19 antiviral known by the brand name Paxlovid before related guidance was released, ultimately announcing the PQ of the product on the same day as the living guidelines for COVID-19 therapeutics were updated to recommend its use. There is an opportunity for WHO to more broadly adopt lessons from this experience by both expanding the use of interim or living guidelines and redefining the process for prequalifying novel products so PQ and guidelines development can occur more in parallel. We hope PQ will pursue this opportunity with haste, as it could be a potential game changer and significantly reduce the timelines for product evaluation, helping products ultimately reach patients faster. We also urge member states to adopt policy changes and provide the PQ program with the resources it needs to meet its growing scope and demands. Despite some of its constraints, the PQ program remains a key cog in the global health ecosystem and an important driver of improved product access. There are indications that WHO and other key stakeholders have realized that changes must be made, as the current structures are weighing down the program's ability to quickly facilitate access to critical technologies, especially novel products. By implementing changes to make the application and review process more user-friendly and efficient and the procedure itself more streamlined, we believe the program can better deliver on its mission to make high-quality essential medical products available to all who urgently need them.

2024 will be a pivotal year for global health. With a record number of national elections, including one in the United States, many multiyear global health architecture reform processes are set to come to a close, and with several major replenishment and resource mobilization campaigns taking place, there is a palpable sense of “now or never” permeating global health discussions.  The World Health Organization (WHO) Executive Board (EB) meeting, which serves as the kickoff to the multilateral calendar, served as the first test on whether stakeholders could come together to ensure that progress continues. While the week offered welcome moments of political support for research and development (R&D), there is a sense that leaders have not yet met the moment to get the world back on track toward achieving the Sustainable Development Goals (SDGs).  Here are some key reflections from a busy week in Geneva:  Deadline looms over pandemic accord and International Health Regulations processes  As in previous years, the WHO’s role in global health emergencies was a central topic at the EB. Just weeks before the fourth anniversary of the COVID-19 pandemic, delegates received a new update from WHO on strengthening the global architecture for Health Emergency Prevention, Preparedness, Response and Resilience, which focused on the need for sustained political leadership and financing to drive the reform agenda forward. And while not on the official EB agenda, the work of amending the International Health Regulations (IHR) and finalizing a pandemic accord also loomed large. Little of the debate focused on specific proposals of these deliberations, though advancing access to medical countermeasures, vaccine equity, and regionally distributed manufacturing all got mentioned during these sessions. Instead, member states zeroed in on the process itself, with delegates seeking to inject a new sense of urgency to finalizing deliberations and adhering to the May deadline. Despite this, Poland became the first country to publicly question the feasibility of the current timeline, calling for a possible extension, signaling that there is also trepidation around how much progress can be achieved with limited negotiation days. The sessions on health emergencies also became the platform for geopolitical proxy battles, with the Russia and Ukraine and Israel and Palestine conflicts spilling over into the global health security debates. Several heated exchanges nearly derailed proceedings, and much airtime was spent addressing grievances.Tuberculosis, immunization, and neglected tropical disease reports highlight setbacksMultiple sessions during the week highlighted the continued disruption in healthcare caused by the pandemic. Despite reaching the midpoint in implementation of the SDGs, global progress remains off track in many key areas. This includes the fight against tuberculosis and neglected tropical diseases, which the WHO highlighted as requiring a renewed focus from member states.  The importance of investing in local production, strengthening laboratory capacity, and ensuring new tools are better adapted to the communities they are meant to serve were all key themes that came out of these sessions.Routine immunization levels are also still lagging behind pre-pandemic rates, with uneven progress regionally.  In its report to the EB, the WHO has documented that the current progress is not enough to meet targets set in the WHO’s Immunization Agenda for 2030. Low- and middle-income countries spoke of the cost of vaccinations as a major financial burden and challenge.  Yet there were notes of optimism too: 2024 is also expected to be a major year for immunization, with the rollout of two new malaria vaccines and two new polio vaccines, bringing the world closer to eradicating some of the planet’s deadliest diseases. Antimicrobial resistance shifts into bigger focus With the UN High Level Meeting on Antimicrobic Resistance (AMR) scheduled later this year and the WHO’s global action plan on AMR coming to an end in 2025, AMR was expected to be a prominent topic at this year’s meeting. While it made its way back on to the official agenda, it unfortunately did not receive as much attention as anticipated, with the agenda item being pushed late into the evening on Friday.  Member states ultimately advanced a resolution sponsored by Thailand which calls on member states to support R&D for new tools to combat AMR, to strengthen the capacities and standards of laboratories, and to participate in the WHO’s Global Antimicrobial Resistance and Use Surveillance System (GLASS), though several countries also wished to discuss the decision further ahead of the World Health Assembly (WHA) in May where it will be up for formal adoption. In his remarks on the topic, WHO Director-General Dr. Tedros Adhanom Ghebreyesus echoed the calls for stronger surveillance; the development of new vaccines, diagnostics, and antimicrobials; and measures to make these interventions accessible and affordable. New resource mobilization push for WHO  EB members supported the proposal for an investor round to raise funds for WHO, which would likely be held in November, with uncharacteristic enthusiasm last week. The WHO Working Group on Sustainable Financing’s report to the 2023 WHA highlighted that WHO’s budget is “up to 86% dependent on generous donors” and that only “roughly 14% of WHO’s finances are truly predictable”. The future effectiveness of WHO will depend on changing how the agency is funded. Progress has been made to increase the percentage of assessed contributions received in the form of member state dues, but far more flexibility and predictability in voluntary contributions will be needed to meet this moment. The idea of a WHO investment round, similar to those hosted by the Global Fund and Gavi, the Vaccine Alliance was accepted in principle by last year’s WHA. Dr. Tedros was charged by member states to provide a framework and justification at this year’s EB, and he delivered his investment case.  The investment framework is closely aligned with WHO’s 14th General Program of Work and the new strategic roadmap for the agency, but this WHO resource campaign will also have to compete with a number of replenishments set for this year, including for Gavi, as well as a resource push for the World Bank Pandemic Fund. This year feels like a make-or-break moment for the SDGs and the 2030 agenda. Yet the EB felt too much like business as usual, with ambition getting bogged down in a bloated agenda, geopolitical battles, and the minutia of internal processes. The urgency highlighted by several delegates on EB topics was not matched in the action or the commitments countries made in Geneva last week. While the EB did not jeopardize the potential of many processes moving forward, it did too little to contribute to the necessary forward momentum we will need to achieve the ambitious agenda set out by global leaders.