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Behind Gilead’s twice-yearly HIV prevention medicine is a unique story of manufacturing innovation; years of design decisions, scientific problem solving and global coordination that began long before any clinical results were available.
For the last three years, Stacey Ma, Executive Vice President, Pharmaceutical Development & Manufacturing, has led that effort. In this conversation, she explains what makes Gilead’s long-acting PrEP uniquely complex, how global access considerations influenced manufacturing decisions (and vice versa), and the bold decisions that preceded approval.
Q. So much about what makes this therapy so transformative is how it’s made. Where does that story begin?
Once medicines are discovered by researchers, they then are traditionally given to different teams to figure out how to develop and manufacture them. This one was different from the beginning. Over the course of the last 17 years — long before I joined the company —Gilead scientists have been thinking about the drug from every angle: Does it work? Is it stable? Can we scale it? Is it cost effective to make? Our process chemists did a tremendous amount of Research & Development to come up with a recipe that could answer these questions, and dozens of others.
I often describe it like building the most complex LEGO set you can imagine – but a LEGO set that has to work biologically. Every piece has to fit precisely and be assembled in a very specific order. Each component, and the final product, has to be of high quality, stable, durable and scalable in real-world conditions. From the very beginning, we also knew we needed to address global climate realities head on. Long before we had a final product, we pursued a formulation and a packaging design that could tolerate heat, long transport routes and extended timelines from manufacturing to patient, all without compromising delivery or access. These early decisions weren’t an afterthought, but instead they fundamentally shaped every development and manufacturing choice that came after.
Q: You’ve described it as the most complex small molecule you’ve ever worked on. What makes it so challenging?
The molecule itself is extraordinarily complex. It’s huge for a small molecule – roughly five times larger than aspirin – and it takes more than 50 chemical steps to produce. Fifty steps – and that’s just the chemistry! Most small-molecule drugs have half that number of steps, at most.
It also requires a specialized injectable formulation, a sterile manufacturing process and a container that won’t interact with the medicine over time. Going from raw materials to a single finished treatment can take 18 months — sometimes closer to two years. Every step has to be exactly right, because a single mistake early on can have a ripple effect through the entire process.
If I can use a different analogy, imagine making an incredibly delicate souffle. In addition to following the recipe precisely and baking it at a very specific temperature for exactly the right amount of time, this particular recipe also calls for ingredients you have to grow, harvest and process yourself (or buy from a highly specialized market that makes it exclusively for you). On top of that, some of the recipe's 50+ steps require chemical reactions that must be done in a specific sequence, which means you’re relying on your partners and suppliers to move with as much precision as you are. One small mistake anywhere in the process will cause the souffle to collapse. And then you have to bake the souffle while wearing specialized equipment in an environment that’s more sterile than an operating room.
That’s just scratching the surface of what makes this product’s production more than just a scientific innovation: it’s a manufacturing marvel.
Q. Were there moments where you thought, “I don’t know how we’re going to do this”?
Of course. One major challenge, which is public, involved an early issue with the vial material. The drug’s formulation interacted with the glass. We had to bring together chemists, formulators, analytical scientists and manufacturing partners to redesign the vial using a completely different material. That process took years, but it ultimately strengthened the product and the process. It was a true cross-functional effort and a reminder that even the container can be a scientific challenge.
Q. What else kept you up at night during your team’s part of the process?
The fear that even one person might be without the medicine they need. That’s what drives me. Many of the regions where long-acting PrEP could have the greatest impact are resource limited, and we have to ensure uninterrupted supply. That responsibility is enormous.
Q: Gilead often says that “manufacturing is access.” What does that mean in practice?
It means that planning for commercialization and access doesn’t start at approval. It starts years earlier with the decisions you make during process development.
For this drug, we knew we wanted to make it available as broadly as possible as quickly as possible, so we made an unprecedented choice: we began transferring manufacturing technology (the “recipe”) to six partners who committed to making generic versions, months before the product was approved anywhere in the world. We knew we were taking a risk, pursuing voluntary licenses and regulatory approvals in parallel. Very few companies attempt something like that.
Plus, because we knew it would take some time for our voluntary license partners to come online, we committed to producing millions of doses at no profit. We did this to allow people in high incidence countries to receive the medicine while generic partners ramped up their own capacity. That’s what we mean by “manufacturing is access.”
Q: What does this 17-year journey mean for the future of drug development?
Everything we’ve learned leads us forward. Long-acting formulation, scalability, stability, global tech transfers — those are capabilities we had to build or refine to make this happen, and they don’t disappear once one product is launched.
The manufacturing lessons we learned apply well beyond HIV medicines. They shape how we think about future potential long-acting medications and how we design them from day one, so that access isn’t an afterthought.
For me, the most meaningful part is when you think about the people who could benefit — that’s what makes the complexity worth it.