By Louis Garguilo, Chief Editor, Outsourced Pharma
At the Novartis-MIT Center for Continuous Manufacturing, director and MIT professor, Bernhardt Trout, turns serious and gets to the point. Or perhaps to the counterpoint.
“Yes, there are major benefits to taking batch approaches and putting them together in continuous mode,” says Trout, who in 2007 was instrumental in forming the university’s relationship with Novartis, and the creation of the center. “But the higher benefits are when you incorporate new approaches throughout your drug development and manufacturing effort.”
“I’ve witnessed new chemical processes developed through chemistries that you wouldn't do in batch, but you can now with continuous. We’ve been able to utilize more reactive intermediates that you can generate in situ – so you don't need a large amount of them – in a way you will never be able to in batch. We’ve developed all kinds of continuous crystallization processes that are run differently from batch and provide significant advantages. These are what truly reap the benefits of continuous.”
Just a few miles away, Salvatore Mascia has staked his career on demonstrating to drug companies how to reap those benefits. He’s president of CONTINUUS Pharmaceuticals, Inc., a company dedicated to advancing the continuous paradigm throughout the drug industry. And as we’ll see later on, that includes contract development and manufacturing organizations. Mascia, who oversaw the initial Novartis end-to-end system development, spun CONTINUUS out of the Novartis-MIT center in 2012 – and grabbed some of the researchers and scientists that had worked closely with Novartis on his way out.
Both Trout and Mascia – and a growing number like them – are fast advancing the technologies of continuous manufacturing (also referred to as continuous flow). Most importantly, they are alerting the drug industry that this disruptive innovation is not only about enabling new forms of manufacture, but also the discovery and development of novel molecular entities, and all the processes by which we bring new drugs to patients.
Janet Woodcock, Director of the Center for Drug Evaluation and Research (CDER) at the Food and Drug Administration (FDA), seems to agree. She attended the Novartis-MIT Center for Continuous Manufacturing’s opening ceremony, and according to Trout, has visited almost every year since. There will be no hiding behind regulatory burdens when it comes to bringing this technology forward.
Spreading The Word … And Some IP
Trout and Mascia credit Novartis for taking the lead in pursuing the continuous paradigm, and helping spread the technology and operational solutions throughout the industry.
Part of that formula includes having MIT as the patent holders of intellectual property (IP) that came out of the Novartis-MIT collaboration. So while Novartis is building a line at its facility in Switzerland to make drugs continuously from the start of ingredient production through the end of coating tablets, Mascia founded his company based partly on his ability to license some of the same technologies. “Our goal,” says Trout of the center’s role, “is to spread these technologies further, and work to further build on what has been developed.”
We’ll talk directly to Novartis in our next article. However, says Mascia, “I believe in part the intent of Novartis is to make sure the technology is spread, so companies throughout the industry are all talking to the global regulatory bodies about the technology and related innovations.”
Mascia is doing his share in that particular endeavor. In November, CONTINUUS announced it was awarded a $4.4 million contract by the FDA to develop an end-to-end continuous pilot plant. The grant is titled, “Advancement of Integrated Continuous Manufacturing (ICM) Unit Operations.”
“The goal is to provide the FDA a model system of continuous processing for assistance in informing future guidelines for continuous manufacturing,” explains Mascia. He hopes to build a system specifically dedicated to providing, for instance, understanding of how to determine an API’s quality without isolation, real-time release, and other applicable concepts. “I think this has the potential to help set the foundation for new regulatory guidance on continuous processes,” he adds.
Meanwhile, some companies in Europe are specifically focusing on providing equipment – which of course tends to be much smaller than that for batch processing. Mascia procures equipment for his operations from the Italian company I.M.A (Industria Macchine Automatiche), which also partners with CONTINUUS.
In other parts of the world, the FDA gave Janssen the okay to move from batch to continuous for production of HIV drug Prezista, at its facility in Gurabo, Puerto Rico. Pfizer and others are also pursuing the move from batch to continuous. In the spring of last year, Lilly said it would invest nearly $40 million to build a continuous manufacturing facility at its site in Cork, Ireland. In 2014, Vertex included a 4,000-square-foot continuous manufacturing facility in its new South Boston location.
Sending It Down The Supply Chain
Important to readers of OutsourcedPharma.com is the topic of how innovation and new technologies can be spread throughout the external supply chain. One example is Hovione’s announced plans to host and operate a commercial-scale continuous manufacturing facility in New Jersey as part of an agreement with Vertex.
Mascia is also lending a hand in spreading the technology to contract development and manufacturing organizations.
“This is what I really wanted to talk about,” he tells me. “I believe continuous flow technology is a powerful tool when considering CDMOs and CMOs. Being able to develop processes quickly, and put these in line to produce and deliver product similarly fast, reduces costs to customers, and offers customers a complete solution. This should help service providers significantly increase their market shares.”
He adds: “My understanding is that even today, some sponsors keep projects in house, out of concern for reliability and speed-to-market, and for reasons of capacity, as well as some others. So a technology like this in the hands of a CDMO is basically a tool to enhance their capability significantly, and in my mind, enhance the outsourcing trend even more.”
Mascia says CONTINUUS is currently in talks with a “leading CDMO to potentially find an alliance.” Even more, it sounds to this editor that CONTINUUS itself might become a pure CDMO. “It’s certainly something we could consider,” Mascia replies. “It’s not what we are focused on today; now we are trying to help sponsors and other service providers make this shift, but there are many avenues.”
*Look for our discussion with Novartis in part two.