Development and evaluation of innovative devices for detecting falsified and substandard vaccines in supply chains

We are increasingly reliant on safe and effective vaccines to prevent infectious diseases. Over 16 billion vaccines were used in 2021 to tackle the COVID-19 pandemic and >~5 million deaths are prevented annually through immunization with vaccines for >20 other diseases. WHO estimates that 10.5% of medical products in low- and middle-income countries are substandard or falsified (SF). Some estimate>1 million deaths/year globally. There are increasing reports of SF vaccines in supply chains, risking impaired vaccine effectiveness. Substandard (often degraded by heat) and falsified (due to fraud, aka counterfeit) vaccines are a neglected global public health problem, with minimal research to inform interventions to reduce the risk. There have been multiple examples, involving thousands of patients, both before, during and after the COVID-19 pandemic, e.g. 60,000 injected with fake vaccines in Niger in 1995 and 250,000 substandard vaccines for children distributed in China in 2018. SF vaccines risk not just ineffective disease prevention but economic and societal harms, including impaired trust in vaccines. A major challenge to mitigate SF vaccine risk is a paucity of devices/methods for SF vaccine screening. Multiple devices will be needed to test at different supply chain levels. This represents a major gap in preparing for vaccine-preventable pandemics, epidemics and multiple endemic diseases. Over the last 5 years we have pioneered research into the development and evaluation of screening devices with high sensitivity and specificity to detect SF vaccines. These include matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF), handheld spatially offset Raman spectroscopy (SORS), and rapid diagnostic tests (RDTs). Importantly, these devices are widely available globally (e.g. SORS for airport security). We work with multiple medicines regulatory authorities, vaccine manufactures, WHO and other national and international organizations to ensure that these methods benefit public health as soon as possible. Our pilot data demonstrate that these repurposed devices can detect falsified vaccines (in the case of SORS, without opening vials/syringes) and we can detect vaccine degradation resulting from excess heat, simply and inexpensively. Our research will provide a step-change in ability to detect SF vaccines in supply chains to mitigate risk to public health globally. In the first 2 years we will expand pilot studies with the most used vaccines in Nigeria plus key vaccines used globally, and MALDI-TOF, SORS, RDTs, and direct heat exposure assays. We will be joined by key collaborators from the Medicines and Healthcare products Regulatory Agency (MHRA) and an RDT developer. We will develop specific RDTs for detecting falsified mRNA vaccines, a key intervention for preventing multiple diseases, but at significant risk of falsification. We will extend the development of innovative methods across multiple devices, and then test them in Nigerian supply chains, to empower supply chain monitoring by medicine regulatory authority inspectors, in alignment with the WHO's global SF 'Prevent, Detect and Respond' strategy.   In Year 3, the Nigerian medicines regulatory authority (NAFDAC) and Obafemi Awolowo University, Nigeria, will evaluate these methods in a near-to-real life evaluation vaccine hub to assess device training requirements and cost-effectiveness, with Mahidol-Oxford-Research Unit, Bangkok, informing implementation strategies. We plan to assess each device in this relevant environment evaluated at the Go/No Go Milestones. The teams have pioneered this new field of research and have expertise, from virology, pharmacy, public health, physics, chemistry, machine-learning (ML) and health economics, to help transform a neglected global public health problem.