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Article / Sep 27, 2021

How the drug services industry found itself prepared for a pandemic

C&EN, 26 September 2021

CDMO drug substance analytical chemistry RD scientists | Hovione

Supply chain discipline has paid off for contract development and manufacturing organizations amid an ongoing crisis

by Rick Mullin

 

The time to repair the roof is when the sun is shining,” said President John F. Kennedy in his 1962 State of the Union address. The metaphor rang true during the Cold War as an admonition to guard against complacency in times of prosperity. More broadly, it registered as the kind of sensible advice that people during all times frequently ignore.

At its outset, COVID-19 proved a case in point, as a containable outbreak spread relentlessly despite years of warning from public health authorities of an imminent pandemic. Yet the crisis also went on to showcase instances of preparedness, foremost of which was the rapid development and deployment of effective vaccines. The pharmaceutical industry emerged as a hero of the pandemic.

Less obvious but just as important was the rapid response of the pharmaceutical services industry, which does much of the heavy lifting for drug companies, working behind the scenes to coordinate the shipment of raw materials, produce active pharmaceutical ingredients (APIs), and formulate finished products within a complex international supply chain.

The sector had been on a 10-year profitability streak before 2020 and has done even better during the pandemic. It navigated challenges posed by COVID-19 on the strength of previous improvements to supply chain management and a yearslong campaign of diversifying services and expanding manufacturing capacity. Those proactive measures put the industry in a strong position when the storm hit early last year.

Indeed, industry watchers say the drug services sector displayed enviable resilience over the past 18 months. “There were issues—I don’t think there were any questions about that. But I think we knew how to deal with it,” says James Bruno, president of the consulting firm Chemical and Pharmaceutical Solutions.

Unforeseen transportation holdups caused problems early on, as did rattled production schedules when companies found they suddenly needed to produce large volumes of APIs such as remdesivir and dexamethasone on a very short timeline. But companies were able to work out the supply chain snags, Bruno says.

 

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Roger Laforce, an industry consultant based in Switzerland, notes that as vaccines advanced toward emergency approval last year, several service companies, often called contract development and manufacturing organizations (CDMOs), were in a position to make vaccines happen. The big Swiss firm Lonza, for example, relied on a 2018 investment in prebuilt manufacturing shells at its facility in Visp, Switzerland, to meet a tight deadline for bringing production of the active messenger RNA ingredient in Moderna’s vaccine on line.

“People who’ve invested in operational excellence—having good supply chain operations and good management practices around their inventory—have actually been able to do pretty well,” says Wayne Weiner, who heads the consulting firm PharmaTech Solutions. “The other thing CDMOs have done a good job at is managing protection for their workers—keeping them safe so they could actually come in and run the plants.”

The pandemic also served to illustrate a dilemma that CDMOs have been bringing to the attention of governments in the US and Europe to little avail—heavy dependence on China for antibiotics and other generic drugs. The global drug supply chain emerged as front-page news when the Donald J. Trump administration considered a “buy American” executive order for pharmaceuticals, and the US government allocated funds to support domestic production of critical drugs. The European Commission also turned its attention to domesticating drug supply. And even as the Joe Biden administration attempts to undo much of the legacy of the Trump administration, the focus on the drug supply chain remains.

 

ABSORBING THE SHOCK

“The CDMO is the shock absorber for the pharmaceutical industry,” says Guy Villax, CEO of Hovione, a Portuguese CDMO with facilities also in China, the US, and Ireland. “Whenever there is a problem, they ask us to fix it.” When an unforeseen requirement for large-scale vaccine manufacturing emerged last year, for example, “the CDMOs got their act together,” Villax says.

And they did so under duress. Villax says that 150 workers at Hovione facilities have tested positive for COVID-19 since the pandemic began. “Every single person has recovered,” he says. There were transportation snags, especially in China, when the pandemic hit, but those were sorted out before long.

And business is “very good,” Villax says. “I remember in April and May of last year, I had a torrent of calls from journalists really keen that I could give them evidence so they could write stories to show that the supply chain was a catastrophe and all the pharmacies would be empty in a short time,” he says. “In fact, none of that happened. I think the supply chain is somehow really resilient.”

One reason for the industry’s preparedness was its ongoing investment in new production capacity well before the pandemic hit. Hovione came into 2020 with a new research center in Lisbon, Portugal, and plans to open a manufacturing building in Loures, Portugal, with new reactor capacity, Villax says. And the firm plans further capacity increases.

The Swiss CDMO Siegfried is among the firms that landed contracts serving vaccine makers. Marianne Späne, chief business officer, says Siegfried had to build a new production line from scratch at its site in Hameln, Germany, to fill and finish vials of Pfizer and BioNTech’s vaccine.

While the company had fill-and-finish capacity, “we had never done vaccines, and in record time we were able to build it up, to validate the process,” she says. Bringing production on line was a matter of close collaboration with Pfizer and BioNTech, Späne says, adding that Siegfried also has a contract to provide Novavax with fill-and-finish services for the vaccine it is developing.

And as it did before the pandemic, Späne says, Siegfried is continually expanding capacity for small-molecule drug manufacturing at all its sites—in Switzerland, Germany, France, Spain, the US, and China—often by debottlenecking or streamlining processes to increase output.

The CDMO is the shock absorber for the pharmaceutical industry. Whenever there is a problem, they ask us to fix it. - Guy Villax, CEO, Hovione

 

Read full article at C&EN.org

 

 

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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. 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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. 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