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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!”

 

Read the article at C&EN online

 

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Developing drugs with poor water solubility remains a major challenge for pharmaceutical manufacturers, because solubility impacts bioavailability and effective drug delivery. The vast majority of small molecule drug candidates have low water solubility. For more than two decades, the most successful particle engineering technology to improve drug solubility and bioavailability has been spray drying with an amorphous solid dispersion (ASD) platform. Spray drying improves the solubility of oral drugs, inhalable particles, and excipients, and increases the stability of heat-sensitive drug products. Hovione, recognized globally for its industry-leading spray drying capabilities, has recently completed a $100 million investment cycle to enhance its operations in New Jersey. This initiative has successfully doubled Hovione’s spray-drying capacity in the US, strengthening its position in the industry. Hovione’s Expanded U.S. Site in East Windsor, NJ  The first phase of the expansion in East Windsor, NJ, delivers a new 31,000 square foot facility and houses two size-3 spray dryers (PSD-3). This additional capacity allows Hovione to meet increasing customer demand for ASD development and good manufacturing practice (GMP) commercial production. GMP operations are scheduled to commence in the second quarter of 2026.  Hovione has also acquired 15 acres of neighboring land, strategically positioning itself for future growth and evolving customer needs for U.S. manufacturing. The newly acquired greenfield site will provide future support for PSD-4–scale commercial production as well as continuous and batch tableting production. It will also be a hub for centralized logistics, enhanced quality control laboratories, and next-generation research and development facilities.  A Global CDMO with a Growing U.S. Footprint  Hovione has operated in New Jersey for more than two decades, establishing itself with a strong U.S. presence for the production of drug substances, intermediates, and finished drug products. A continued emphasis on an integrated service offering, including spray drying, supports delivering innovative medicines to patients more quickly.  The expansion of the East Windsor site addresses the rising demand for U.S. manufacturing and is an integral part of the company's ongoing global growth strategy, with facilities in Portugal, Ireland, and Macau. The company continues to bolster a cohesive network for drug development and commercial manufacturing unified by a corporate quality system and governance framework.  The integrated offering enhances development speed and eases technology transfers by unifying the team's technical skills, proprietary technologies, and digital platforms to efficiently produce drug substance to drug products at a single-site, through Hovione’s “one site, one partner” vision. Furthermore, Hovione’s strategic partnership model offers customers exclusive access to advanced technologies and resources while aiding in the optimization of their development programs and ensuring sustained value creation.  End-to-End Spray Drying and Particle Engineering: From Grams to Tons Hovione is a global leader in spray drying and particle engineering. Services include solubility enhancement and controlled-modified release via development and production of ASDs of both small and large molecules, supporting various modalities. ASD-HIPROS, Hovione’s proprietary spray drying screening platform, identifies optimal formulations that offer optimal performance and stability. By increasing production volume in the US, Hovione will meet customer demand for spray drying services:  Development services in the laboratory (1 g – 1 kg batches)  Pilot scale production (0.5 – 25 kg batches)  Small-scale production (5 – 200 kg batches)  Large-scale commercial manufacturing (50 – 400 kg batches) A Commitment to Sustainability  Hovione’s core values include a commitment to sustainability at all facilities. This commitment is reflected in a business strategy that focuses on improving the communities where the company operates. Hovione’s sustainability policy and strategy align with the UN Sustainable Development Goals and include adherence to science-based targets in line with the Paris Agreement to address climate change. Meeting these goals has required a dedication to process intensification and ensuring sustainability of manufacturing processes. This has been possible through strategic planning and commitments from senior management to ensure sustainability is addressed throughout the drug development life cycle.  Partner with a Technology-Leading CDMO for U.S. Manufacturing   As demand for poorly water-soluble drug formulations continues to rise in the U.S., expanding spray drying throughput is essential to meet the need for innovative therapeutics. 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