MEDICINES FOR EVERYONE

Access to medicines is uneven around the world. Innovative chemical synthesis and engineering technologies could have a profound leveling effect.

Alla Katsnelson
Jan 7 · 22 min read

By Alla Katsnelson

(Photo source: Matt Briney/Unsplash)

THE MOONSHOT: Everyone deserves basic healthcare, but the cost of medicines puts them out of reach for a quarter of the world’s population. A globally centralized pharmaceutical supply chain keeps prices high and puts patients at risk of drug shortages and counterfeit medicines. By developing and deploying novel technologies for pharmaceutical synthesis, we could democratize pharmaceutical production and slash the cost of many medicines, increasing their availability to those who need them.

THE PHILANTHROPY OPPORTUNITY: Chemical synthesis technologies for manufacturing medicines more cheaply already exist, but an initial investment is needed for governments or local companies to adopt them. Philanthropic support could establish the potential of these technologies at the local and regional level. Specific initiatives could include regional demonstration projects that build modern facilities for producing key components of medicines; training programs that build the knowledge base and capacity for low-resource regions to manufacture the drugs they need; and infrastructure to support the launch of small-scale local drug manufacturing.


mble into any of this country’s more than 67,000 retail pharmacies with a sufficient combination of insurance coverage and cash and you probably can waltz out with pretty much any over-the-counter or prescription medicine you might need. This assumption of availability, even by those in wealthy nations, resides on increasingly shaky ground, however. And for billions living in less affluent countries, the availability of drugs — let alone affordable ones — has never been a given.

The American Society of Health System Pharmacists currently includes 204 entries in its list of current drug shortages, with chemotherapy agents, anesthetics, and infectious disease treatments among the top types of medicine affected. One compound on the list is vincristine, a mainstay in treating childhood leukemia with no current alternative in the pharmacopoeia. “This shouldn’t be happening in the United States,” a pediatric oncologist at Stanford University told The New York Times. Yet it is, and U.S. legislators and the U.S. Food and Drug Administration (FDA) are scrambling for solutions. Meanwhile, counterfeit drugs, a growing threat to the U.S. drug supply, complicate the situation further. The FDA has repeatedly issued warnings about sub-par pharmaceutical ingredients and products from India and China. Indeed, drug shortages are at an all-time high across the industrialized world. French regulators, for example, noted this summer that shortages shot up 20-fold between 2008 and 2018.

Officials with the U.S. Food and Drug Administration at one of the postal system’s nine International Mail Facilities (IMFs) inspect drug shipments with an eye on preventing illegal, illicit, unapproved, counterfeit, and potentially dangerous drugs from entering the United States. (Photo source: FDA)

And while in industrialized countries, shortages and counterfeit medicines are akin to disease outbreaks that come and go, in the developing world they are more like perpetual plagues. Globally, 2 billion people — a quarter of the population — have no access to essential medicines, according to the World Health Organization (WHO). What’s more, a recent WHO report found that at least 10.5% of medicines in low- and middle-income countries are either counterfeit or substandard because they contain less than the stated amount of active ingredients. The outcome? Millions of preventable deaths from public health scourges such as tuberculosis, malaria, AIDS, diabetes, heart disease, and a host of other treatable diseases and chronic conditions.

A cadre of chemists, chemical engineers, and healthcare entrepreneurs say they have a solution. These experts are working to harness innovative chemical engineering technologies to make the synthesis of pharmaceutical ingredients significantly faster, cheaper, greener, and more flexible. With these technological advancements, which leverage robotics and artificial intelligence, the production of any given drug could become almost as easy as pressing the “Print” button on a photocopy machine. That capability would turn the problem of drug access on its head — both in the developing and the industrialized worlds.

Most of the drugs that end up in short supply are generics, rather than their name- brand cohorts. (Photo source: Laurynas Mereckas/Unsplash)

Whether we’re talking about a vincristine injection administered at a hospital in Ohio or antiretroviral drugs distributed at a clinic in South Africa, the majority of drugs in short supply are older generics. Such medicines become unavailable for a myriad of reasons. Cost, public health infrastructure, and geopolitical instability often play a part, though it’s often unclear exactly why shortages of any given drug occur. But one point is beyond dispute: The globally centralized pharmaceutical manufacturing and supply chain frequently is a major underlying cause. A particular drug — aspirin, for example — consists of a biologically active compound (acetylsalicylic acid) as well as inactive ones that help body absorb the medicine. The former is known as an active pharmaceutical ingredient, or API. Too often, the supply of an API relies on a handful of companies, or even just one. Supply problems along the chain — contamination at a plant, say, that causes regulators to shutter it, temporarily or permanently — ripple out to large-scale buyers, such as pharmacies and government or nonprofit distribution programs, and from there directly to patients.

Re-envisioning how these compounds are synthesized and manufactured commercially would pave the way to decentralizing that supply chain and making it more resilient. This wouldn’t just open up access to generics, but even to the growing pipeline of boutique specialty drugs. The current framework for making medicines, based as it is on the idea of mass-producing blockbuster drugs, is ill-suited to many of the more nuanced medicines of tomorrow. New drugs will increasingly target specific gene mutations present in just a sliver of the population, or require preparations of patient-specific cells. Drugs of these sorts will be best made in smaller runs closer to the point of care. Currently, the price tag of these specialty medicines is threatening to upend the healthcare economy, but disruptive chemical synthesis technologies that innovators now are developing could help reframe the costs of these drugs. Small facilities, perhaps even portable devices built to deploy these emerging technologies, could even give end users full control, enabling them to manufacture as much of whatever API or drug they might need.

“At the end of the day, I believe the only way we are going to control prices so that your grandma and my grandma get the medicines they need at an affordable price is to democratize the system,” says Geoffrey Ling, CEO of a Boston-based startup called On Demand Pharmaceuticals.

Already, academic researchers, foundations, companies and governments around the world are beginning to implement this democratizing drug-making technology for the greater good. In South Africa, for example, which repeatedly has tried to jumpstart a drug manufacturing industry in the past few decades, such technology offers the possibility of leapfrogging an outdated manufacturing system, much the way cellular networks made it possible to bypass landlines across the developing world. “This is an absolutely amazing opportunity for us,” says Jenny-Lee Panayides, a senior researcher at the South African Council for Scientific and Industrial Research in Pretoria.

NEW MEDICAL PIPELINES

One chemist who has long believed in a new future for pharmaceutical synthesis is Tyler McQuade, chief technical officer of the Medicines for All (M4ALL) Institute at Virginia Commonwealth University (VCU) in Richmond. About a decade ago when he was a chemistry professor at Florida State University, McQuade found himself noodling on how he could transform the way medicines are made with the goal of creating the economic incentives for making them more widely available and affordable around the world. “Personally, I am a capitalist — I believe in free markets,” says McQuade. “But on the other hand, I feel like [availability of] medicines is a human right. And so to reconcile those two things you have to create economic ecosystems that both support producers but also allow for [drugs] to be provided at a price [people] can afford.”

In an anteroom of the National Academy of Sciences in Washington, D.C., where he had been invited to participate on a panel about how a chemical engineering technology called flow chemistry could be used in the pharmaceutical industry, McQuade struck up a conversation with Frank Gupton, who was on the same panel. Although their work had a lot in common, the two had never met before. McQuade was just a decade into his academic career, while Gupton was a pharmaceutical industry veteran, who had recently been recruited out of retirement to lead the chemistry and chemical engineering departments at VCU. Before he retired in 2007, Gupton had led process development for the North American operations of the Germany-based Boehringer Ingelheim Chemicals for 13 years. But he and McQuade hit it off immediately, and in the months after their 15-minute, pre-panel mind-meld, they started chatting on the phone several times a week.

When Tyler McQuade (left) met Frank Gupton at a conference, the two discovered a common interest in transforming how drugs are manufactured. Now the two work together toward dramatically less expensive ways of producing drugs at their Medicines for All Institute Institute at Virginia Commonwealth University in Richmond. (Photo courtesy of VCU)

Gupton shared McQuade’s interest in re-envisioning pharmaceutical synthesis, and he saw real opportunities to improve the overall manufacturing process in the generics industry. “If you can create processes that are so efficient that essentially making the medicine is free, it gives a lot more latitude for people to explore possible business cases that can meet needs in, say, Africa,” McQuade says. If companies could adopt such processes to produce medicines more cheaply, then buyers — governments of low-income countries, U.S. government agencies such as the President’s Emergency Plan for AIDS Relief (PEPFAR) or nongovernmental organizations such the Bill & Melinda Gates Foundation or Doctors Without Borders — could make them more widely available to patients who desperately need them.

By designing more efficient synthesis routes, McQuade and Gupton believe they can make it significantly more attractive for drug manufactures to make APIs for generic drugs that are widely used in the developing world but are now too expensive for many patients to afford. The strategy they are embracing for devising these new and improved synthesis routes is flow chemistry.

In the lab, chemists have for centuries made molecules using a series of one-pot reactions. Steven Ley, a chemist at the University of Cambridge in England, calls it the “traditional, smelly round-bottomed flask and glassware” approach. The intermediary molecules produced at each step of the process must be isolated (often painstakingly and with a lot of loss of the intermediary) and transferred to the next step, until the full series of reactions yields the final target molecules in the last flask. What this means is that a given chemical must be made in batches. Batch chemistry is how almost all pharmaceutical chemicals are manufactured, though in big pharma factories those little smelly flasks Ley referred to are replaced with industrial-sized vats and tanks. Batch production facilities are relatively cheap to build, but the process creates enormous quantities of waste. Harvest a pound of product from a batch process and you typically will need to manage several hundred pounds of waste.

“If you can create processes that are so efficient that essentially making the medicine is free, it gives a lot more latitude for people to explore possible business cases that can meet needs in, say, Africa.” — Tyler McQuade, Medicines for All Institute

Flow chemistry — also called continuous chemistry — takes a different tack. In a flow or continuous system, engineers feed starting ingredients at one end and the system pumps them through a tube. Along the way, the ingredients undergo a series of reactions in an assembly-line approach. Scaling up production involves simply running the system longer. Not that flow chemistry is a panacea for all that ails batch chemistry, experts note. Some reaction steps — for example, those where compounds tend to crystalize out of solution — don’t work well in a flow reactor. These can clog the production system’s arteries, as it were. And optimizing for a flow approach generally requires telescoping a reaction — that is, reconfiguring it to occur in fewer steps. Nonetheless, the process can be significantly greener — requiring less energy and generating less waste — and safer, because only a small mass of reactants are undergoing a particular chemical process at any given time. What’s more, it generally offers better quality control and yields a purer product. And, of course, it allows manufacturers much greater control over how much of a product they make. A flow chemistry system is more expensive set up, but because it’s more efficient and generates less waste, it is ultimately cheaper.

“You don’t make a motor car or even an airplane one at a time,” says Ley, who has been a pioneer in the use of sophisticated flow technologies for all kinds of chemical syntheses since the 1980s. “You make [cars] by a process — a production line — that allows you to continuously produce a product. And it makes sense that you would do the same chemically.”

Flow chemistry has been used for decades to manufacture commodity chemicals in, for example, the petrochemical and agrochemical industries. But in the pharmaceutical industry, where production volumes are smaller, the approach is just beginning to gain ground. Big Pharma has long resisted adopting flow, and it’s not hard to imagine why. Drug development is a highly conservative industry, and companies have invested billions of dollars into batch-mode equipment and infrastructure. Flow chemistry is not only a disruptive technology, but also “a massive change in philosophy” from the block-buster drug idea that drives so much of the Big Pharma mindset, says Ley. Just as Henry Ford’s auto assembly line transformed the ethos of building cars, making medicinal molecules with flow rather than batch chemistry requires completely reframing the process.

Most pharmaceutical manufacturers are developing flow or continuous manufacturing methods in which chemical inredients flow through multiple chemical reactors that perform sequential reactions and somtimes go all of the way from raw ingredients to finished tablets. (Photo source: Tanja Devald/Novartis).

For drug candidates that have yet to be commercialized, there isn’t necessarily a strong economic incentive for finding the best possible synthesis routes for making an API or a full drug formulation, says McQuade. “The research chemists at GlaxoSmithKline are not paid to make efficient syntheses — they are paid to make as many molecules per unit time as they possibly can, so that the company can screen those molecules for potential hits,” he says, referring to molecules that show initial promise that could lead to a big drug product. “Once they find a potential hit, they need it scaled very quickly.” Companies like GlaxoSmithKline and Merck are counting on selling that new drug for big bucks to recoup the research and development costs, so the initial investment is in the discovery, not in the manufacturing.

Still, this reluctance by companies making novel drugs to embrace flow chemistry is starting to shift. For more than a decade, the FDA has been encouraging drugmakers to adopt continuous processing, touting its promise for preventing drug shortages. In 2015, Vertex Pharmaceuticalsin Boston became the first company to produce a new drug, the cystic fibrosis medicine Orkambi, using that technology. Three years ago, Eli Lilly announced plans to invest $40 million to build a continuous manufacturing facility in Ireland. Today, pretty much every major pharmaceutical company has begun to invest in flow chemistry, at least for experimental use.

But for generics, the math is completely different. Because generic drugs sell for significantly less than newer drugs under patent, at every stage of the supply chain — from raw materials to the APIs these form into to finished drug with APIs, binders, and other ingredients — “everybody’s trying to squeeze the last little bit from the guy below them,” McQuade explains. Whereas the active ingredients cost about 5% to 10% of the selling price for a drug under patent, it’s closer to 50% to 70% for a generic. With margins being much thinner in the generics world, savings at every step of the manufacturing process matter more. “That then becomes an opportunity to drive down the cost and increase access to those generic products,” Gupton says.

“You make [cars] by a process — a production line — that allows you to continuously produce a product. And it makes sense that you would do the same chemically.” — Steven Ley, University of Cambridge

McQuade’s and Gupton’s shared vision quickly turned into a collaboration to use flow chemistry to find more efficient synthesis routes for generics used in the developing world. At first they struggled to secure funding for a pilot project, but in 2012 Gupton tapped into the Clinton Health Access Initiative, which gave him a small grant to look at redesigning the API for the antiretroviral drug nevirapine. That drug molecule is a key component in anti-HIV antiretroviral drug cocktails meant to prevent the development of resistance to any one drug.

Drug molecules are built from smaller fragments, and that’s how the duo decided to rebuild nevirapine. McQuade and Gupton split nevirapine’s API molecule into two parts, and based on their results on the first part they tackled, they secured a bigger bolus of cash: In 2014, the Gates Foundation came through with $5 million to finish the job. That meant re-designing the synthesis for the second half of the compound, then putting the two processes together and demonstrating that the new process was scalable. Eventually, they were able to get a manufacturer to start making API for nevirapine at lower cost. Once the API price goes down, major buyers such as PEPFAR or the Gates Foundation can put pressure on pharmaceutical companies to sell the drugs for less.

Chemically synthesizing the HIV-thwarting drug Nevirapine (bottom left) requires making one intermediate (top right) and reacting it with a small amine ingredient (middle right), and treating the result of that action (bottom right) with the the strong base sodium hydride (NaH) to trigger the final ring-forming reaction. Researchers at Medicines for All have developed a new manufacturing method for producing the drug. (Diagram source: Wikipedia)

With nevirapine, Gupton knew what he was getting into. He had overseen its manufacture when he was with Boehringer Ingelheim. “I thought we actually had a pretty good process, but we were able to drive the cost down about 40% using some innovative approaches to assembling the molecule,” he says. The original synthesis required 60 kilograms of starting ingredients to yield one kilogram of the drug, but the new process cut the starting amount down to 4 kilograms, or by more 93%. “Not only did we reduce the waste, we also increased the overall yield for a five-step synthesis from 58% to 94%,” says Gupton.

It’s not just flow chemistry that makes it happen. As a matter of fact, Gupton says, the processes M4ALL develops are platform-agnostic, so that manufacturers could glean benefits whether they use batch, flow, or a combination of these processes. The VCU team starts by conducting a techno-economic analysis to identify where in the process efficiency gains are most likely to affect the final cost of the product. “While that sounds obvious, it turns out that very few chemists do it,” McQuade says.

For each API process they develop, the M4ALL team creates a manual explaining their synthesis process and distributes it to manufacturers, starting with those that already make the relevant API. But what really drives the cost down is when a new player enters the market using this new technology from the get-go, McQuade says. That’s what happened for nevirapine, and this year the Gates Foundation calculated that the $5 million the Foundation invested in funding M4ALL to redesign the synthesis of nevirapine yielded a savings of more than $11 million in money spent on the drug — a pretty good return on investment. “We don’t care who adopts our technology,” says McQuade. “We just want to have a positive effect on accessibility.”

M4ALL is finishing up its process development work on a total of four HIV medicines. Working with the Gates Foundation and other foundations and nonprofits providing medicines in the developing world, M4ALL now plans to tackle several other medicines for malaria, tuberculosis, infant health, and other conditions. (In addition to funding M4ALL’s nevirapine effort, the Gates Foundation gave the group $10 million to redesign two other drug APIs, as well as $25 million in 2017 to turn the M4ALL initiative into a formal institute.) Already, M4ALL is moving beyond generics to tackle new drugs as well. Some of the medicines in its portfolio aren’t yet on the market, McQuade notes.

MAKE-YOUR-OWN MEDICINES

The VCU researchers weren’t the only ones interested in cheaper and better drug synthesis. Right around when McQuade and Gupton met, the Defense Advanced Research Projects Agency (DARPA), which oversees ambitious technology development projects for the U.S Department of Defense, began an initiative called Pharmacy on Demand. It’s objective was to create a portable continuous-manufacturing device that could — as the program title suggests — produce drugs on demand. Its brainchild, Geoffrey Ling, came up with the concept during his time as a battlefield physician and then started the program in 2011, when he was working at DARPA. McQuade did his own tour of duty at DARPA from 2013 and 2017, a period that overlapped with Ling’s tenure there. “This is an idea that was born on a plateau in Afghanistan,” says Ling, a neurologist at Johns Hopkins in Baltimore, Maryland, and head of a consultancy advising on health care technologies.

Ling recalls the incident that seeded the idea in his mind. He had needed to stabilize a severely wounded soldier with a traumatic brain injury but found that bromocriptine — the drug he sought for normalizing the patient’s blood pressure, heart rate and breathing — wasn’t available. Eventually, the Air Force flew it in to him. He was grateful to get it, but he couldn’t help thinking there had to be a better way. A portable chemistry set that could automatically make specific drugs like bromocriptine with the addition of ingredients and the press of a button is not as far-fetched an idea as it might appear, Ling says now, because many widely-used drugs consist of just carbon, hydrogen, and oxygen and their chemistry is not especially complex.

In 2016, researchers at the Massachusetts Institute of Technology unveiled a compact and portable system for manufacturing a variety of pharmaceuticals on demand. (Photo Source: MIT News)

Back in the early 2000s, researchers at the Massachusetts Institute of Technology (MIT) in Cambridge had partnered with Novartis to create the Center for Continuous Manufacturing, one of the earliest publicly-disclosed efforts to explore the place that flow chemistry could have in the pharma industry. So, when DARPA announced in 2011 that it would fund several teams to design such a system, a trio of MIT chemists and chemical engineers who were part of that center landed a research contract. They had already created a shipping-container-sized machine that could make a high blood pressure drug called aliskiren. In 2016 they reported success with a smaller system — about the size of a refrigerator, that could be reconfigured to make several simple drugs, including anesthetic lidocaine and the antihistamine diphenhydramine, says Timothy Jamison, a professor of chemistry at MIT who co-led the project.

Since then, the team has been working on further automating that process. In work published in January 2019, Jamison and his colleagues designed a device that uses flow synthesis to manufacture multiple pharmaceutical chemicals based on synthesis routes identified with the help of a machine learning network. Every chemical reaction is different, and there’s no standard set of recipes for producing specific compounds. Developing a synthesis route with particular specs — one that produces minimum waste, say, or delivers an especially high yield — can be a bit of an art. The machine learning network essentially relies on statistical learning from published studies and databases to propose promising synthesis routes that a human, with their limited knowledge, might not have thought of.

As it stands, the robotic synthesis system the MIT team designed is great, says Ling, but there’s a long way to go before the system can be used outside of academia. “It does what it says it’s going to do. But can it be mass produced? Hell no. I mean, this is a damn Swiss watch,” says Ling.

A work in progress, this robotic system automates the synthesis of pharmaceutical chemicals and can inlcude machine-learning algorithms to automatically propose synthesis routes that human chemists might not initially know to consider. (Image from From Coley et al., Science 365, eaax1566 (2019). Reprinted with permission from AAAS).

For one thing, the system has to be optimized for commercial use and rejiggered to comply with Good Manufacturing Practice (GMP). That means it has to follow a specific set of regulations designed to prevent contamination and production errors and to ensure that adequate records are kept of the process. Then it needs approval by the FDA. To accelerate these advances toward a commercial end point, Ling in 2017 founded On Demand Pharmaceuticals in Boston and licensed the technology from MIT. And he asked the VCU team, which has extensive experience in the commercial sector, to help ready the system for commercialization. The idea, he says, is “to turn this beautiful Swiss watch, quite frankly, into a Timex.”

Ciprofloxacin, the primary treatment for exposure to anthrax and some other biological threats, is a current synthesis target in a collaboration to demonstrate new methods for manufacturing drug molecules. (Image Source: Wilipedia)

In a collaborative agreement with VCU, On Demand Pharmaceuticals is refining the MIT machine’s ability to produce the antibiotic ciprofloxacin at commercial scale and to gain FDA approval for it. Ciprofloxacin is the drug of choice for anthrax and several other biological threat agents, and Ling’s company started with it because its primary constituency is the military. But the platform has successfully synthesized 15 other molecules, Ling says, and some of those are very much suited for a developing world market.

A MAKE-IT-LOCAL-EVERYWHERE MODEL

Even without the miniaturized platform, for a developing nation like South Africa these advanced chemical manufacturing technologies offer particular promise: Seeding a regional pharmaceutical manufacturing industry would simultaneously contribute to the country’s economy and free it from dependence on the global pharmaceutical market.

The country’s disease burden is heavy. One in five adults the ages 15 and 49 has HIV. Malaria, antibiotic-resistant tuberculosis and other infectious diseases are rife, too. Drug shortages are constant, and one in five drugs in the country is thought to be counterfeit or of undocumented origin, says Jenny-Lee Panayides, from the country’s Council for Scientific and Industrial Research. The antiretroviral program in South Africa’s coastal province of KwaZulu Natal distributes drugs to hundreds of thousands of HIV-positive people each month. “We are one of the biggest purchasers of these types of drugs [in the world],” says Panayides. “And we run out of them regularly.”

That’s a problem anywhere, but in a country where the majority of patients who need such medicines live in poverty, it’s worse still, Panayides says. Often, people come to the clinic from a village or township, spending a high percentage of their salary — if they even have a salary — to get there. “For the nurse to say to them, ‘Please come back next week’ — after a few times of that, they just stop coming back,” she says.

Synthetic chemist and microbiologist Jenny-Lee Panayides of the Council for Scientific and Industrial Research in South Africa is betting that new streamlined methods of chemical manufacturing will make drugs more widely accessible in her country. (Photo source: CSIR)

Despite South Africa’s high need for medicines, very few of them are manufactured there. Manufacturing overall tends to be somewhat backwards; companies on the whole don’t embrace modern production methods, automation, or forward-looking business models, Panayides says. Yet another major gap is skills: Currently, a work force able to participate in a drug manufacturing industry is virtually nonexistent. And yet, the country does have some good bones on which such an industry could be built. For example, although most APIs are imported, many local companies formulate medicines from APIs and inactive ingredients and sell them. “Our local access to finished medicines is really strong, we have these great distribution and marketing channels, and we have many routes to get products to our patients,” Panayides says.

One of the first believers in the prospect of using flow chemistry and other high-tech chemical manufacturing tools to make medicines in South Africa was Darren Riley, senior lecturer in chemistry at the University of Pretoria. Before taking up the post in 2013, he had worked for three years at iThemba, a local pharmaceutical R&D company, half owned by the South African government and half owned by several international scientists, Ley among them. During that time, Riley had spent time in Ley’s lab, and when iThemba folded, he brought what he learned to his own lab. Not long after that, Panayides and her colleagues were finishing up a strategic analysis of South Africa’s economy — a process that underscored the potential for a drug manufacturing sector.

Recently, Panayides and Riley first began collaborating with King Kuok “Mimi” Hii, a chemist at Imperial College London, where she was setting up the Center for Rapid Online Analysis of Reactions (ROAR). ROAR, which opened in January 2019, is a chemical synthesis resource facility that includes both flow and batch technology as well as extensive automated analysis tools, to help researchers develop the most efficient synthesis routes for their compounds of interest. “People come to us to use a wide variety of equipment to get really good quality data about particular aspects of their chemistry,” says Ben Deadman, a chemist at Imperial College who works with Hii at ROAR. “They take that knowledge back home and use it to advance their own science.”

Over the past couple years, Riley and his colleagues worked with Deadman, Hii, and others at the center, traveling to London and hosting the Londoners in Pretoria, to troubleshoot the chemical synthesis processes. With a recent grant from the South African government, Riley’s team is now putting the finishing touches on the largest flow chemistry facility in Africa and among the largest academic flow chemistry labs in the world. He collaborates closley with Panayides and her government colleagues, who recently opened a smaller, government-run translational facility: : the academic lab devises flow and batch-flow hybrid synthesis routes for APIs of several key drugs, and the government lab then pilots their production to GMP standards at a kilogram scale. The plan, Panayides says, is to have these compounds ready to enter the country’s drug approval process in 3–5 years. Once they’re approved, local companies with the know-how and the technology will be able to churn them out. Other drugs — antiretrovirals, tuberculosis medicines, oncology drugs, and anti-inflammatories — would follow, sustaining a fledgling drug manufacturing industry serving South Africa and the surrounding region and allowing them to make the drugs they need, rather than relying on the vagaries of global pharmaceutical manufacturing.

“At the end of the day, I believe the only way we are going to control prices so that your grandma and my grandma get the medicines they need at an affordable price is to democratize the system.” — Geoffrey Ling, On Demand Pharmaceuticals

It’s too early to say whether South Africa’s API manufacturing bid will succeed. The skills gap is one big issue: Panayides estimates that fewer than 10 people in the country currently have the know-how to run a pharmaceutical manufacturing facility that incorporates advanced flow technology. However, the government lab, Riley’s lab, and that of another flow chemistry collaborator, Paul Watts at Nelson Mandela University in PortElizabeth, are working to train the needed labor force. A more immediate problem is funding, which is dwindling. Without outside investment — for example, from multinational pharmaceutical companies or philanthropies — the effort will hit shaky ground in about 2 years.

Yet establishing this capacity in a country like South Africa is really where the rubber hits the road. Refrigerator-size boxes that produce drugs on the battle field at the press of a button might need a few more years of development before they’re ready for deployment, but new technologies for chemical synthesis that can sharply reduce the cost of drugs and democratize their production are here and ready to go. It won’t be cheap and it won’t be easy, but if South Africa can garner the support it needs to nurture a home-grown generic drug industry using these technologies, the country can serve as a beacon of possibility for other low-resource regions. M4ALL’s Gupton, for one, envisions enabling centers of excellence in pharmaceutical production across Africa and elsewhere that could produce what’s locally needed. “From my perspective, that would be a real breakthrough,” he says.

But in the long run, these technologies can also solve a bigger global problem. Enterprising ventures in industrialized countries can adopt them too. Both a hospital network in Cincinnati and an HIV clinic in Pretoria would be able to make the medicines needed in their respective regions at locally affordable prices, sidestepping the issues with the international supply chain for pharmaceuticals and returning production to regional or local control. Says Gupton, “That’s where I think the opportunity is for the future.”


Alla Katsnelson is a freelance science writer and editor specializing in biology, health and medicine, technology, and science policy.

The Moonshot Catalog

A to-do list of big doable projects for a forward-looking future

Alla Katsnelson

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The Moonshot Catalog

A to-do list of big doable projects for a forward-looking future

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