Geographically distributed manufacturing capacity is needed for improved global health security

COVID-19 has tested the world’s ability to respond quickly and equitably to a profound global health crisis. Unfortunately, in many ways, we have collectively failed this test. Yes, safe and effective COVID-19 vaccines were developed only 10 months into the pandemic—the fastest vaccine development cycle in history. But of the nearly four billion vaccine doses administered to date, eight in 10 went to people in wealthy nations, while less than one percent have gone to those in low-income countries. As a result, the surging Delta variant is now having especially devastating consequences in Africa, Latin America, Asia, and other places where much of the population remains unprotected.

Sadly, this vaccine inequity also occurs in other areas of global public health. Because life-saving vaccines and treatments are not available or affordable everywhere, preventable diseases like malaria, pneumonia, diarrhea, and typhoid—largely absent from higher-income countries—continue to kill millions of children a year across the developing world. In my previous position as chair of the Department of Pediatrics and Child Health at Aga Khan University in Pakistan, I saw the suffering these preventable diseases caused many times over. I joined the foundation in 2014 because I wanted to help close these gaps in vaccine access and immunize every child against these illnesses.

Over the years of doing this work, we have learned that expanding the geographic distribution of vaccine manufacturing capacity is critical to achieving vaccine equity. It’s not a coincidence that countries with domestic capacity have received most of the COVID-19 vaccines, while those without have been forced to wait. Vaccine manufacturers located in developing countries (or “DCVMs” for short) are also often more receptive than large multinational corporations to focusing on neglected diseases, especially when those diseases remain endemic in their country or region. For example, Bio Farma in Indonesia is now the sole developer or source of several oral polio vaccines used around the world, even as large multinational vaccine companies have stopped making them.

In short, DCVMs are critical to developing or manufacturing low-cost, high-quality vaccines that can reach everyone. That’s why, over the past two decades, our foundation has given US$1 billion in support to DCVMs and related grantees and has worked with 19 DCVMS across 11 countries to bring 17 vaccines to market. These collaborations have made a tremendous difference all over the world.

Take MenAfriVac, an affordable meningitis A vaccine that came out of a multi-year partnership with PATH and the Serum Institute of India (SII). While bacterial meningitis has become rare in much of the world thanks to vaccines, until very recently it still killed tens of thousands of people a year in sub-Saharan Africa. But since its introduction in 2010, MenAfriVac—the first internationally qualified vaccine developed outside the major multinational pharmaceutical companies and the first vaccine developed specifically for Africa—has effectively ended meningitis as a public health problem there.

Similarly, Euvichol, a low-cost and easy-to-administer cholera vaccine developed by EuBiologics in South Korea, helped rein in several cholera outbreaks in Africa and has prevented further such epidemics all over the world. Typbar TCV, a typhoid conjugate vaccine from India’s Bharat Biotech, has helped reduce typhoid in many countries, including my native Pakistan when it experienced a terrible and extremely drug-resistant typhoid outbreak.

In fact, Indian DCVMs have been particularly fruitful over the years. Bharat Biotech also developed Rotavac, an affordable rotavirus vaccine that costs only US$1 per dose (compared to US$2.50 for others). Along with MenAfriVac, SII has also brought several other low-cost life-saving vaccines to market, such as Pneumosil for childhood pneumonia. And Biological E. Limited, another longtime foundation partner and India’s oldest vaccine company, helped develop a low-cost measles-rubella vaccine that is used around the world, among its other offerings.

We’re also supporting many other DCVM vaccines in the pipeline, from Korean company LG Chem’s work to create a low-cost 6-in-1 combination vaccine, to the effort to expand yellow fever vaccines at Institut Pasteur in Senegal, to cervical cancer–preventing HPV vaccines from China. In these cases and many more, DCVMs are developing safe, effective, and affordable vaccines for diseases that have too often been neglected. In fact, DCVMs now produce almost two-thirds of the vaccine volume for use around the world by Gavi, the Vaccine Alliance.

While we often support direct vaccine development at DCVMs, R&D is only part of the equation. Developing and distributing safe and effective vaccines is an enormously complicated and costly proposition—much more so than developing drugs. (That’s why there’s no “generics” vaccine market as there is for drugs.) There are intensive capital requirements for building large-scale, state-of-the-art, and sufficiently sterile factories and warehouses. A highly trained workforce of chemical engineers, immunologists, clinical researchers, and other experts is needed. New vaccines must go through rigorous clinical studies and regulatory oversight at both the national and international levels to become qualified for use, and sometimes countries do not have robust enough regulatory systems in place to be accredited by the World Health Organization. Local companies must come up with long-term business plans that ensure they can keep the lights on when there isn’t a pandemic driving urgency and demand. And even when a vaccine is at last deemed safe and effective, it must then be mass produced at scale at a consistently high standard and without any variations that might undermine production quality.

Only when all the pieces of the ecosystem are aligned can real progress start to happen. So, along with funding R&D, our DCVM support also includes helping companies and governments build out the necessary infrastructure, catalyzing long-term and stable investments from others and supporting developing nations as they continue to improve their workforce training and regulatory systems.

Because of all these complexities, success in developing high-quality vaccine capacity must be measured in decades rather than months or years. The long time it takes to build this infrastructure seems unacceptable when the need for more vaccines—both for COVID-19 and other infectious diseases—is so acute. That’s why COVID-19 dose donations are so vital in this current crisis and why, as my colleague Cheikh Oumar Seydi writes, it’s also critical to support the institutions leading pandemic response efforts. But over the long term, we can help save millions of lives and advance global health security by expanding and coordinating vaccine manufacturing capacity around the world.

While there are no real shortcuts to building this capacity, a few encouraging developments are on the horizon. For example, recent advances in manufacturing, like “single-use technologies” and process intensification (using smaller apparatuses at higher concentration), can lower the costs of production and improve efficiencies. And by focusing first on “fill-finish” manufacturing capacity—meaning the less (but still quite) intricate process of putting vaccine ingredients in individual or multi-dose vials in a sterile and controlled manner—emerging DCVMs can begin building the systems and getting the regulatory approvals that can lead to building more extensive capacity over time as skills are developed.

Perhaps the most promising trend for rapidly expanding DCVM capacity has emerged during this pandemic, with the arrival of the first safe, effective mRNA vaccines. mRNA technology shows promise for fighting many other diseases, including malaria, tuberculosis, and HIV, and it could also potentially involve much less intricate manufacturing processes when the sector reaches maturity. Nonetheless, and especially given how long it takes, now is the time to build the infrastructure, skills, and regulatory ecosystems that will allow more countries to develop safe, effective, and affordable vaccines, so we can finally close the global gap in public health and protect every child on Earth from preventable diseases.