Breakthroughs Blog: Diagnostics

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.

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. Two new reports from the AMR Industry Alliance, a coalition of companies and trade unions in industries working to combat antimicrobial resistance (AMR), highlight both progress and setbacks in the field of antimicrobial resistance research and antibiotic development, as the threat of AMR rises globally. A survey of members demonstrated positive findings, including many industry members having implemented measures to support antimicrobial stewardship and efforts to increase antibiotic access in lower-resource countries, as well as having invested in AMR-relevant R&D. On the other hand, there has been a decline in AMR researchers over the last few decades, leading to less published research on AMR and fewer patents on new antibiotics, the decline particularly acute when compared to cancer and HIV/AIDS. The findings highlight the need for government and private sector incentives to provide adequate funding and investment for AMR research and novel antibiotic development, as well as for efforts to introduce young scientists to the field.The Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) recently announced $1.8 million in funding to biotechnology company Visby Medical to develop a portable rapid diagnostic test that detects Neisseria gonorrhoeae, the pathogen that causes gonorrhea, as well as its susceptibility to ciprofloxacin, an oral antibiotic that was formerly a go-to treatment, which can no longer treat resistant forms of the pathogen. The test would allow health care providers to rapidly test and refer patients to the right treatment while hopefully ensuring that ceftriaxone, the only remaining effective antibiotic against resistant N. gonorrhea, is properly managed. The funding will also support the development of a test for N. gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis in men based on urine samples.The Coalition for Epidemic Preparedness Innovations (CEPI) will provide up to $2 million in funding to German biotech company LenioBio GmbH for a preclinical proof-of-concept for using its commercially available, plant-based, and cell-free technology to produce proteins for use in clinical trials testing vaccines against epidemic and pandemic threats in 20 to 40 days. If proven successful, this approach could greatly reduce the time it traditionally takes to manufacture vaccine proteins using other methods, which would be a major boon to CEPI’s 100 Days Mission to develop vaccines against novel pathogens with pandemic potential within 100 days of identification. The easy-to-use technology could also be rolled out for use in remote or low-resource settings, allowing greater availability of and access to future vaccines in those settings. 

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 Wednesday, the World Health Organization and the Medicines Patent Pool announced a new nonexclusive license agreement with SD Biosensor for the firm’s rapid diagnostic testing technology, which, through a phased technology transfer plan, will allow sublicensees to manufacture the technology, with additional benefits for the broader effort of manufacturing capacity-building in low- and middle-income countries. The agreement was negotiated under the COVID-19 Technology Access Pool (C-TAP), which was launched at the beginning of the COVID-19 pandemic, but it includes a broad range of diseases, including HIV, malaria, and syphilis. The rapid testing technology is the basis of SD Biosensor’s COVID-19 antigen test and is ideal for low- and middle-income countries because it has no equipment requirements and is easy to use with high sensitivity. The announcement also coincided with the unveiling of a new business model, the Health Technology Access Pool, which will succeed C-TAP and address other priority health issues beyond COVID-19.A new project—FLAVIVACCINE—from a diverse consortium of partners aims to increase the European Union’s ability to combat epidemic and viral threats in Europe and globally by supporting the development of a pan-flavivirus vaccine candidate that could protect against multiple flaviviruses, such as dengue, yellow fever, Zika, and West Nile. Beyond seeking a vaccine candidate, the project also aims to provide support across the R&D value chain, offering a boost to the broader global pandemic preparedness and response capability. The project is being organized by public and private institutions, including universities, research institutions, and a vaccine developer, spanning seven countries in Europe and the United States.A new grant to the Drugs for Neglected Diseases initiative (DNDi) from the Bill & Melinda Gates Foundation will support the development of innovative new drugs for sleeping sickness and river blindness. Specifically, the $20 million grant spanning until 2027 will support a single-dose cure for sleeping sickness and a short-course new treatment for river blindness, both diseases with a major footprint in sub-Saharan Africa and for which new tools are urgently needed to accelerate progress toward elimination, despite enormous progress in controlling them in recent years. These investments build on earlier-stage research also supported by the Gates Foundation.

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. The Genomic Surveillance Unit at the Wellcome Sanger Institute and the Centre for Epidemic Response and Innovation at Stellenbosch University are partnering to advance the practice of genomic surveillance, which has been around for decades but really came to the forefront during the COVID-19 pandemic and has the potential to improve global efforts against other infectious diseases, including malaria and cholera. During the COVID-19 pandemic, there was huge global investment in genomic surveillance infrastructure, with the Stellenbosch lab being the first to confirm the discovery of the Beta and Omicron variants. In the last year alone, the work of the two labs has contributed to doubling the number of sequences available for dengue, chikungunya, and malaria parasites. Genomic surveillance uses sequencing to get data about the genetic material of a pathogen, which is then used to track how the pathogen is changing or spreading.Researchers from the Health and Medical Research Institute at Japan’s National Institute of Advanced Industrial Science and Technology have developed a bioluminescent assay that could serve as a rapid, low-cost, and convenient test to complement laboratory testing for COVID-19. The test uses a bioluminescent molecule found in some small crustaceans that glows when it reacts with the virus that causes COVID-19 in a saliva sample and can be used with commercially available handheld luminometers at the point-of-care. The research team is planning for initial commercialization in the Japanese and US markets.ProteinLogic and Stellenbosch University will use a $1.35 million grant from the Bill & Melinda Gates Foundation to determine whether an immunoassay technology being developed by ProteinLogic can be used to monitor treatment response to tuberculosis (TB) antimicrobial chemotherapy in patients. ProteinLogic's ImmiPrint testing technology is a protein-based test based on predictive models developed through machine learning that aims to offer rapid, efficient, and cost-effective discovery of diagnostic biomarkers across multiple diseases. Its new partner, Stellenbosch University, has been leading clinical trials on TB diagnostic biomarkers. In the face of the growing threat of drug-resistant strains of Mycobacterium tuberculosis, there is an urgent need for new technologies to monitor the effectiveness of current treatments, in addition to the need for novel treatments and prevention methods for TB.