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Press Clipping / Nov 12, 2018

Hovione bulks up, with a twist

C&EN, November 12, 2018

Guy Villax R&D Center in Portugal, Pharmaceutical Services Continuous Tableting | Hovione

A pharmaceutical services pioneer cues up continuous tableting as it doubles manufacturing.

Guy Villax, CEO of Hovione, stands in the central hall of the company’s new R&D center in Lisbon. On the wall beside him is a mural with photographs commemorating the family-owned pharmaceutical chemistry firm’s milestones since it was founded by his parents, Ivan and Diane Villax, 59 years ago. There is also a nearly floor-to-ceiling portrait of Steve Jobs, the cofounder of Apple.

Guy Villax is fond of extolling innovation and inspirational figures such as Jobs and Charles Darwin, who on another mural is quoted regarding species’ responsiveness to change. That mural also nods to an evolution in how Hovione regards the scientists who work in R&D.

His father, he explains, was a man of his times. “He didn’t give much space to empowerment and all that,” he says. Villax, on the other hand, has been giving employee empowerment a lot of space recently.

 

The 7,000-m2 R&D center was designed with low-walled cubicles and picture windows looking into labs and conference rooms. A large tote board on the second floor lists the company’s patents, with a good number of entries—failed applications—crossed out with red lines. Banners from the ceiling celebrate the launch of new drugs for which Hovione supplied active pharmaceutical ingredients (APIs) and other services. There were four in 2017, close to 10% of the 46 drugs approved by the U.S. Food & Drug Administration.

Villax says he wants to get chemists to look up from the bench at the big picture. “It feels a little less inhuman, not doing the Charlie Chaplin things,” he says, referring to Chaplin’s skewering of the machine age in the film “Modern Times.” “If you give people a sense of what it’s all about and how they contribute, they fill in their batch records with greater care. But to keep people excited about doing new things, you have to give them the right tools.”

R&D at headquarters is one thing. Manufacturing on three continents is another, for a family-owned firm with plans to double capacity at most of its sites. But Villax sees a continuum from the lab to the plant in which developments in both realms are guided by innovative science and customer demand. It’s a philosophy that has kept Hovione afloat as many other firms in the drug service industry get swallowed up by financial buyers or big corporations.

Indeed, Hovione has been adding tools beyond the lab, including at its plant in nearby Loures, where it is doubling manufacturing capacity and starting up a finished-dosage drug plant it acquired in 2015 and then retooled.

Meanwhile, the company is adding a second pilot plant at its smaller-scale facility in East Windsor, N.J., and commissioning the second of two manufacturing buildings at a large-scale facility in Cork, Ireland, capacity that has been mothballed since Hovione bought the site from Pfizer in 2009.

The company has also added a wholly new tool in New Jersey—a continuous tableting plant­—for which it has a contract to work with Vertex Pharmaceuticals. Hovione will offer the service for other customers there and in Lisbon, where a similar plant is scheduled to be installed.

Hovione invested about $100 million in 2017 and plans to spend as much again this year and next. The plan over the next three years is to continue investing, especially in Portugal, where the firm will add 165 m3 of chemical synthesis capacity, a spray-dryer building, and a 1,200-m2 analytical lab.

Hovione’s capacity expansion is ambitious but somewhat conventional for a firm whose major investments have historically startled industry watchers. In 1985, for example, Hovione built a plant in Macau, the first instance of a European drug service company investing in China. In 2002, it opened the New Jersey plant, starting a trend of European firms establishing small-scale beachheads in the U.S.

Then came the Cork acquisition, which, in addition to bulking up manufacturing capacity with a plant Pfizer no longer needed, brought a huge spray-drying facility. Hovione pioneered and remains a leader among firms offering this now-popular service.

If anything, the move into tableting is a bit of catch-up for Villax, who not long ago spoke skeptically of peers adding final-dosage service to chemistry. The merger of DSM’s pharmaceutical chemical business with Patheon’s finished-drug service was a seeming vindication of this one-stop-shop approach. Several other firms, including Siegfried, Carbogen Amcis, and Aesica, also invested in dosage-form manufacturing, as Hovione held fast with chemistry alone.

Villax finally blinked in 2015, purchasing a plant literally over the fence from Hovione’s main site in Loures. Villax insists he would never have added dosage services if the plant weren’t adjacent to API manufacturing. He says the company now has two customers for which it does particle engineering, API synthesis, and final product manufacturing at the one site.

 

He emphasizes that Hovione had signed up Vertex for continuous tableting before committing to the cutting-edge technology in New Jersey. Dosage-form service “is not a leap or change in direction,” he insists. “Who do you think showed us the way? The clients.”

In New Jersey, site general manager Filipe Tomás is focused on increasing capacity for clients in the early stages of drug development. “This site cannot be at maximum capacity,” he says. “We expect to be at 60% to 70% occupancy and always be a door to customers when they have a lead.”

And that door is about to open on continuous tableting, which is beginning registration runs and is set to go into commercial production next year. Hovione’s hope that the service will be of interest is borne out several miles away at the Rutgers University Engineering Research Center for Structured Organic Particulate Systems. There, engineers have worked with Vertex and Janssen Pharmaceuticals, firms that Douglas Hausner, associate director of industrial liaison at the center, describes as early adopters. Hovione hired several students and engineers from the center as it secured the contract with Vertex.

Tomás sees the addition of tableting as a natural progression in pharmaceutical services rather than a break from Hovione’s chemistry tradition. The new apparatus, a three-story rig with a belt of tablet troughs running from top to bottom, is utterly unlike the pilot reactors elsewhere in the facility. “This is a technology that we think adds value,” specifically that of speed to market, Tomás says.

He points to a newly constructed space near the tableting machinery in which the company may add blister packaging, a service Vertex is not currently signed on for. The site has also doubled its research space with the creation of an open environment that mirrors the new Lisbon center. Along with a significant increase in staff, the New Jersey labs have increased technical firepower in areas such as particle design and engineering.

Back in Lisbon, Cláudia Ferreira, general manager of R&D services, says research and technology have seen many changes in recent years but have still followed one basic course. “Hovione always takes advantage of its core way of working, which is science driven and innovation driven. That hasn’t changed.”

Rafael Antunes, senior director of R&D, adds that remaining a family-owned company allows Hovione to take risks and make long-term investments, including in its research endeavors. “We like to be challenged,” he says. “We feel we have to differentiate ourselves from the competition, to set the bar high on the technologies we adopt, and to have the right people.”

 

Hovione employs about 90 Ph.D. scientists. Under a program launched five years ago, 11 Ph.D. students are doing research at the firm. The four who have completed their program have been hired by the company.

“What you have in our industry, as in so many others, is an expansion of knowledge and technology,” Villax says. “You have to keep up, and you have to solve problems faster.”

James Bruno, president of the consulting firm Chemical & Pharmaceutical Solutions, says that Villax makes some risky moves but that they tend to pay off, with the latest venture in continuous tableting appearing to be another good one.

“Sometimes I’ve scratched my head and said, ‘What is he thinking?’ ” Bruno says. “But five years later, you got to go back and say, ‘Well, you know, that was a pretty good idea.’ I think Guy always has a tendency to be a step ahead of everybody else in general. He’s doing things that people are thinking about doing.”

Villax says he’s often challenged on the question of whether, despite a good run, a major disruption in pharmaceutical technology might “get Hovione bankrupt.” This, he admits, is a good question.

But he also points to an uninterrupted line in pharmacology development that has yet to be disrupted by genomics, digital technologies, and other game-changing leaps in science.

“I think the pharmacy is something relatively unchanged for 30,000 or 40,000 years. Even when you had hunters and gatherers, I’m sure there were some people who knew what certain plants did for you. So I can’t see what is really going to disrupt us,” he says, smiling. “Famous last words!”

 

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The podcast "The Next Discovery" is a six-episode series created by Observador, a leading Portuguese digital newspaper and radio station, in partnership with Hovione. From particle engineering to global leadership in spray drying, discover the technology that enables oral medicines to be effectively absorbed by the body and help treat millions of people. What if some of the scientific breakthroughs that could improve the lives of millions of people were happening right now in Portugal? Welcome to "The Next Discovery. Listen to the third episode of the podcast here, featuring Filipe Gaspar, VP Technology Intensification, and José Luís Santos, Strategic Business Management Senior Director, at Hovione. [English transcription] Nelson Ferreira (NF): Welcome to The Next Discovery. This is a partnership between Rádio Observador and Hovione, a six-episode series in which we show how science developed in Portugal has a real impact around the world. I’m Nelson Ferreira, and in the last episode we explored how APIs—the active pharmaceutical ingredients in medicines—are produced. Today, we move to the next stage: how do we transform that chemical powder into a medicine that our bodies can actually absorb? To help explain this science, I’m joined by Filipe Gaspar and José Luís Santos, who were involved in the creation and development of Hovione’s particle engineering division. Welcome to you both. Filipe, let me start with you. NF: When we hear about a new medicine, we usually think about the molecule that was discovered. But why isn’t that discovery alone enough? What exactly is particle engineering, and what role does it play in turning a promising molecule into a medicine that is truly effective? Filipe Gaspar (FG): Nelson, the active ingredients in many modern medicines are not effective in the form in which they are produced through chemical or biological processes. To work properly in the body, they need to undergo additional transformations. For example, some medicines must be protected from the acidity of the stomach so they can later be released in the intestine, where the environment is less acidic and absorption into the bloodstream can occur. Others require very specific particle sizes. This is the case with inhalation powders, often used to treat asthma or chronic bronchitis. If the particles are too large, they become trapped in the upper airways and never reach the alveoli, where they need to be absorbed. On the other hand, if they are too small, they may simply be exhaled before absorption occurs. Finding the right particle size is therefore essential to ensuring an effective treatment. Another remarkable example is modern oral medicines, which often need to be converted into a different form—the amorphous form—so that the body can absorb them properly. Particle engineering makes all of this possible, overcoming many of these limitations by improving drug absorption, distribution, and therapeutic effectiveness. NF: I believe that in 2003 Hovione made a bold decision and invested in spray drying technology. José, for our listeners, could you explain in simple terms what this technology is, what problem it solves, and why it was so revolutionary at the time? José Luís Santos (JLS): First, it’s worth noting that spray drying has been used for decades in other industries. Think, for example, about powdered milk, instant coffee, or the powdered detergent we use in our washing machines. In all these cases, we start with a liquid—milk, coffee, or a soap-based paste—and transform it into a very fine powder that dissolves almost instantly when mixed with water. This transformation is achieved through spray drying. To explain it simply, imagine a very large chamber, something like a giant hair dryer. Inside, the liquid we want to dry is converted into a spray—a kind of mist—creating extremely small droplets. These microscopic droplets are then dried very rapidly using hot gas inside that giant dryer. In just milliseconds, the liquid evaporates, leaving behind a powder made of tiny particles with properties that, as Filipe mentioned, make them highly soluble. The powders we produce in the pharmaceutical industry are physically similar to powdered milk, instant coffee, or powdered detergent. Now, why was this technology revolutionary for pharmaceuticals? Just as spray drying made it possible to preserve milk for months without refrigeration or gave us coffee that can be prepared in seconds, pharmaceutical spray drying made it possible to create medicines with improved therapeutic effectiveness because they became more soluble. Without access to spray drying technology, many of these medicines would simply not have had a viable path to reach the market and ultimately patients. NF: Filipe, we now have a better understanding of what happens in the factory, but I’m curious about what happens inside a patient’s body. Can you give us some concrete examples? What happens when a molecule looks promising in the laboratory, but the body cannot absorb it effectively? FG: Of course. As surprising as it may sound, most medicines taken orally—tablets and capsules—are actually less soluble in water than glass or marble. Since our gastric and intestinal fluids consist primarily of water, these medicines, in their original crystalline form, dissolve very poorly and can pass through the digestive system without being absorbed into the bloodstream. That would make them completely ineffective. Spray drying solves this problem by transforming them into an amorphous form that dissolves much more easily and can be absorbed by the body. A simple analogy would be to compare an ice cube with snow. Both are solid water, but snow melts much faster because of its structure. Spray drying applies a similar principle to medicines, significantly enhancing their ability to dissolve and be absorbed. NF: José Luís, some of this may sound very technical to our listeners, but the outcome is ultimately that people live longer and healthier lives because of these technologies. Are there concrete examples of medicines that only reached the market and patients because of this technology? JLS: Absolutely. One of the most significant examples involving Hovione was the COVID-19 treatment effort. Hovione participated in the production of Captisol, a compound that was essential in the manufacture of Remdesivir, Gilead’s antiviral medicine, which became one of the few treatments authorized for COVID-19. Another important example is the treatment of hepatitis C. Around 10 to 12 years ago, the disease was virtually eradicated in many parts of the world thanks to new medicines whose manufacturing processes relied on spray drying technology. This enabled those therapies to achieve the solubility and therapeutic effect required. These are just two examples. At Hovione—and across the industry—we are working with a growing number of medicines, including treatments for oncology, cystic fibrosis, and many other diseases that benefit from spray drying technology and the advantages it offers. NF: From what I understand, this technology will continue to play an important role in future discoveries as well. Filipe, when Hovione invested in spray drying, it was a technology that was almost inaccessible and rarely used in the pharmaceutical industry. What did Hovione see that others didn’t? And how did what seemed like a risky bet eventually position the company as a global leader in this field? FG: When we invested in the technology in 2003, we had already identified one or two opportunities. As you said, it was a technology that was practically nonexistent among companies like Hovione that provide services to the pharmaceutical industry. We decided to invest before there was established market demand, which meant taking a significant risk. We were talking about many millions of euros—the cost of an industrial-scale spray dryer. Afterward, we actively developed the market. The demand we saw, particularly the need to improve the bioavailability of oral medicines, confirmed our highest expectations. We have made—and continue to make—ongoing investments in science, technology, and industrial capacity. Over the years, these investments have consolidated Hovione’s position as a global reference in spray drying. Now, we must continue innovating to maintain that position. NF: Based on the examples we’ve been hearing, that doesn’t seem likely to be a problem for Hovione. We also know that innovation doesn’t happen in isolation. Spray drying appears to be another example of that. Hovione seems to have strong ties with academia and universities through master’s and doctoral programs conducted in industrial settings. Is this collaboration the secret to staying at the forefront? JLS: Yes. Our connection with academia has always been very important and continues to be so. Today, we have more than 300 people working in research and development roles, and we maintain strong ties with the academic community. Hovione is one of the largest private employers of PhDs in Portugal, with approximately 120 PhDs on staff, and we actively promote projects in partnership with universities and research centers. FG: I would also like to mention the Hovione Research Program. NF: What is that? FG: It is Hovione’s research program. It is a collaborative initiative with Portuguese academic institutions and has been active for more than 15 years. To give you an idea, at any given time we typically have around 10 PhD candidates and between 20 and 30 master’s students conducting their work in an industrial environment simultaneously. Most of these researchers end up joining Hovione after completing their studies, integrating into the same areas in which they carried out their research. They are a reflection of this collaboration with academia, which has been a key driver not only of our ability to innovate but also of our capacity to attract and retain highly qualified talent. NF: Filipe Gaspar and José Luís Santos, thank you both for showing us that behind every medicine there is an enormous amount of science, innovation, and talent. And often it is invisible technologies—such as the spray drying technology we discussed in greater detail today—that make a difference in the lives of millions of people. This concludes the third episode of The Next Discovery. Next week, we take the next step and discover how Hovione challenged industry tradition by introducing continuous tablet manufacturing. You can listen to the next episodes on observador.pt and on your usual podcast platform. See you at the next discovery.    

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The podcast "The Next Discovery" is a six-episode series created by Observador, a leading Portuguese digital newspaper and radio station, in partnership with Hovione. From hard-to-produce antibiotics to innovative therapies, Hovione uses complex and sustainable chemistry to bring safe medicines to patients around the world. What if some of the scientific discoveries that could improve the lives of millions of people were happening right now in Portugal? “The Next Discovery.” Listen to the second episode of the podcast here, featuring Rui Loureiro, scientist at Hovione. [English transcription] From hard-to-produce antibiotics to innovative therapies, Hovione uses complex and sustainable chemistry to bring safe medicines to patients around the world. What if some of the scientific discoveries that could improve the lives of millions of people were happening right now in Portugal? “The Next Discovery.” Nelson Ferreira (NF): Welcome to the podcast “The Next Discovery.” This is a partnership between Rádio Observador and Hovione—a six-episode series where we open the doors of a Portuguese-founded multinational pharmaceutical company to share real stories of science, innovation, and global impact. I am Nelson Ferreira, and in the first episode we explored the story of the basement where it all began more than 65 years ago. Today, we will understand what happens inside this company. We will talk about complex chemistry, because that is where the journey of many medicines that pass through Hovione begins. We will discover how laboratory science becomes industrial processes, how sustainability is part of this transformation, and how all of this contributes to producing medicines that truly help improve and save lives. To guide us on this journey, I am joined today by Rui Loureiro, a scientist at Hovione’s Research and Development Center. Hello, Rui. Welcome to Rádio Observador. NF: Rui, most people may never have heard of Hovione, but they may be taking a medicine where Hovione played an important role. Where exactly do you fit into this long journey that takes a medicine to the patient? Rui Loureiro (RL): Hello, Nelson, good morning—and thank you for the question. The path for a medicine to reach a patient is long. It starts with producing a very small amount of a drug, which through development eventually needs to be produced in kilograms. Let me give an example. Imagine baking cookies. When you buy cookies at the supermarket, someone first made the initial batch at home—but then they needed a partner to scale those cookies to an industrial level. NF: A factory, exactly. RL: Exactly. That is where Hovione comes in. We are that partner for the pharmaceutical industry—helping turn one cookie into many cookies that eventually reach patients. NF: For those listening who are not familiar with this field, people often talk about APIs in the pharmaceutical industry. I had to look it up myself. What is it, and why has Hovione focused so much on it since early on? RL: API can mean different things depending on the field—for example, in IT it means something entirely different. In the pharmaceutical industry, API stands for Active Pharmaceutical Ingredient. In Portuguese, princípio ativo—the component that treats or cures the disease. Using the cookie analogy again: a chocolate cookie has many ingredients—but the chocolate is what defines it. The API is exactly that in a medicine: a small but essential part that delivers the therapeutic effect. Even though tablets contain multiple substances, producing something like a 10 mg tablet of the active ingredient alone is difficult—so other components are added to create the final form. NF: Over many years, Hovione also specialized in complex generics. How did that experience help you move into working with companies developing entirely new medicines? RL: That was a very important step. Developing complex generics means the chemistry required is challenging—it may involve very low temperatures or tightly controlled conditions to ensure we produce the desired result and not something unwanted. Those early capabilities—developing antibiotics and other materials—led the market to recognize Hovione’s expertise. Ultimately, chemistry involves combining building blocks. If someone proves they can assemble the most complex ones, the industry will take notice. That is how we became recognized as a trusted partner for complex pharmaceuticals. NF: I am curious about this idea of “complex chemistry.” You often compare chemistry to cooking—what distinguishes traditional chemistry from the complex chemistry you do at Hovione? RL: Let me simplify for clarity. Complex chemistry depends on the reagents and solvents used. The starting materials may be difficult to transform and may require very specific conditions. The resulting product may also be unstable and require careful handling. Using cooking as an analogy: simple chemistry is like making jelly—you mix powder with hot water and let it set. Complex chemistry is more like making ice cream—it involves a more intricate process, and many people prefer to leave it to specialists. NF: Another fascinating challenge: in the lab, you work at milligram or gram scale, but factories must produce tons. How do you scale from a teaspoon to a truckload without ruining the recipe? RL: That is indeed our biggest daily challenge. Scaling up requires understanding every variable in the process. Going from a small kitchen setup to industrial production is not just about bigger equipment—it requires entirely different systems and expertise. We work with multidisciplinary teams—chemists, engineers, analytical specialists—to control every variable that affects product quality. In a typical GMP (Good Manufacturing Practice) process, there are 4–5 main steps. And across those steps, we may need to control around 350 variables to ensure the final product meets quality standards for patients. NF: When people think of chemistry, they often think of something negative. But Hovione has been developing more sustainable approaches. What does sustainable chemistry mean in practice? RL: Sustainability is a daily priority. We design processes with sustainability in mind from the very beginning. We follow green chemistry principles—avoiding harmful reagents whenever possible. And when that is not possible, we apply the “four Rs”: reduce, reuse, recycle, and recover. For example, just as the paint industry moved from solvent-based to water-based systems, we are also moving toward chemistry in water. This reduces the carbon footprint of our processes. We are also exploring micellar chemistry, flow chemistry, and even reactions without solvents at all—similar to grinding ingredients together with a mortar and pestle. These approaches help reduce waste and improve efficiency. NF: Looking to the future—will chemistry remain our best tool to save lives, and in a more sustainable way? RL: Absolutely. That is what motivates me every day. Artificial intelligence is already helping identify targets and design molecules—but those molecules still need to be produced. That is where chemistry remains essential. It is the foundation for creating and improving medicines. Innovation and sustainability will go hand in hand—and that is the path we are committed to. 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The podcast "The Next Discovery" is a six-episode series created by Observador, a leading Portuguese digital newspaper and radio station, in partnership with Hovione. And what if some of the scientific discoveries that can improve the lives of millions of people were happening right now in Portugal? The Next Discovery. Listen to the first episode of the podcast here, featuring Diane Villax, co-founder of Hovione. [English transcription] Welcome to The Next Discovery. This is a series of conversations, created in partnership between Observador Lab and Hovione, an international pharmaceutical company of Portuguese origin, that will open the doors to its world and share real stories of science, innovation and global impact. Over six episodes, we will meet the people behind technologies that help develop and manufacture innovative medicines for the world’s largest pharmaceutical companies that improve the lives of more than 80 million patients every year. I am Nelson Ferreira and, in this first episode, we will discover how an unlikely story, which began in a basement in Lisbon, became a story of global leadership. To talk about this legacy, I have the honour of welcoming Diane Villax, co-founder and non-executive board member of Hovione, who at the age of 91 remains a living witness to this journey. Nelson Ferreira (NF): Welcome, Mrs Diane Villax. Let us begin our conversation in 1959. Hovione was born in an unlikely way, in a basement in Lisbon, founded by your husband, Ivan Villax, by you and by two other partners. How did you manage family life and, at the same time, the birth of a pharmaceutical company, all in the same space? I imagine that created some interesting logistical challenges. Diane Villax (DV): From the beginning, we decided that we would manufacture raw materials for the pharmaceutical industry, that is, the active ingredients of medicines. We had no money, so it had to start from our home, which was in a residential neighborhood in Lisbon. Right from the start, we divided the tasks. My husband, a brilliant Hungarian chemical engineer, would be the inventor, the producer and the salesman, while I would take care of all the administrative side: imports, exports, accounting and banks. I kept those responsibilities for at least 30 years. At the same time, we also thought about the values that would guide us over this long period: transparency, innovation, the pursuit of excellence and great consideration for everyone who would come to work with us over the years. NF: Very early on, your husband made it clear that Hovione would not compete on low price, but rather on quality and on solving complex problems. What was it like to apply this principle of rigour when resources were still scarce? Especially because, from day one, it always seems to me that your objective was global. The world would be your market. DV: From the beginning, we felt that Portugal, with a population of 10 million people, would not be a very significant market, and that the world would be ours. Perhaps we were a little naïve, because we were entering a global market that was already quite sophisticated. But the decision was made and we moved forward. We moved forward and were fortunate that Japan discovered us quite quickly. They came knocking on our door, because of course we did not have the means to knock on theirs. At that time, they did not manufacture; they only formulated, so they needed to buy raw materials. My husband had invention patents for independent processes and there were long discussions. They felt that our technology was good, our IP was very robust and our quality was excellent. This led to a cooperation that lasted 10 or 15 years and was very profitable for both sides, I believe. NF: In the 1980s and 1990s, Hovione took a more significant leap forward. What were the decisions, the technological bets or even the moments of greatest courage that allowed this small Portuguese company to become a leading multinational? DV: In 1982, after a successful inspection by the FDA, the regulatory authority in the United States of America, we entered the American market with our generic doxycycline antibiotic. The inventor’s patent had already expired and we had an independent manufacturing process. It was a huge, demanding and competitive market, but one that respects good service and quality. And it was indeed a major leap, because the market was so large that we had no real sense of what it would mean, and demand was much greater than what we were able to produce. I remember, it must have been the summer of 1983, many people probably had to postpone their holidays to the autumn or winter, because missing delivery deadlines was not an option. Later, in the 1990s, we entered a new business area: services. We realized that large American pharmaceutical companies, as well as small biotechs, were increasingly inclined to outsource the development work for new molecules. This is a very long period, which can take four, six or even 10 years — the development process for new molecules before they are approved by regulators and become commercial products. So we began to offer this development service, and it went very well. From there, we developed new technologies, such as spray drying, for poorly soluble molecules, because this could greatly increase their bioavailability. Today, this services area is our largest business segment. NF: Hovione today works with 19 of the world’s 20 largest pharmaceutical companies. How do you maintain the agile, pioneering spirit that was born in that basement, when today the company has 2,600 employees, more than 300 scientists, and has even become the largest private employer of PhDs in Portugal? DV: Agility has to be maintained. For example, during the pandemic, we suddenly received large, unexpected orders to manufacture a component of Remdesivir, which was the product authorized to help Covid patients. So agility has to be maintained, and we always maintain our quality. Today, with more than 60 years of history, clients come to us because they know they can count on our quality and on our responsibility to produce and deliver on time what they order. NF: There is another impressive figure here. Your products reach 80 million people every year and Hovione participates in up to 10% of the new medicines approved annually by the FDA in the United States. When you look at this impact, do you feel that the dream of 1959 has been fully achieved? DV: I think it has been far exceeded. When we founded Hovione, my husband, who was a scientist, simply wanted to have his own laboratory. But he never imagined that we would develop in such a way that, today, we are sought out by major international pharmaceutical companies, which frequently come to us. NF: This is a series about science, but it is also about people. And the rigour, ethics and long-term vision that Diane always brought to management are still present at Hovione. What message would you leave to the scientists who join Hovione today with the mission of finding the next discovery? From what I understand, Diane makes a point of welcoming them whenever they join the company. DV: Yes. Four times a year, twice in English and twice in Portuguese, I speak to the newcomers at Hovione, giving them a very brief account of our journey, our values, our objectives, our dreams, the challenges we faced and how we overcame them to get to where we are today. And I always recommend that anyone who joins this company must work with passion. They must work with passion and always remember that our work is to produce medicines for those who need them. We have the privilege of serving patients. We are a company that works for society. I think “In it for life”, which is our motto, has a lot to do with us, because we have been here for 67 years as a family company, and that is how we intend to continue for many good years to come. Above all, in the healthcare sector, there is a great advantage, because we can look at the long term. We do not have to think about stock market results every quarter, as public companies do. And, on the other hand, we are here precisely to give life to those who need it. “In it for life.” NF: At the age of 91, how does Diane herself maintain this passion and continue to make long-term plans? DV: Because I was a founder of this company. I see it progressing and developing successfully, so it is a joy for me. And I have a large family coming after me. I have six grandchildren and seven great-grandchildren, and I hope to leave the company to them so that they can continue it as I managed it. NF: That is truly inspiring. Mrs Diane Villax, thank you very much for sharing the memories and inspiration of this legacy, which remains very much alive. It was a privilege. This was the first chapter of The Next Discovery. In the coming weeks, we will continue to open the doors of Hovione to discover how Portuguese talent is leading the world, from complex chemistry to particle engineering, from respiratory therapies to next-generation biological medicines.   You can listen to the next episodes on observador.pt and on your usual podcast platform.    

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