Continuous manufacturing (CM) is gaining ground in pharma, much like it is in other industries. According to Bikash Chatterjee, CEO of Pharmatech Associates, the cost and complexity of adopting new technologies are set to decrease, making the processes even more appealing.
Chatterjee will be offering insights and predictions during “Continuous Manufacturing. What’s Driving Adoption?” a panel session taking place May 17 at 2:30 pm EST at CPhI North America 2022. The conference is a ‘smart’ event, held online May 9-27 and in Philadelphia May 18-19. Outsourcing-Pharma connected with him to learn more about the session and CM developments.
OSP: Is CM continuing to evolve? it’s been on the agenda for some time.
BC: There are certainly some serious conversations taking place about continuous manufacturing at this point in the US, and the growing momentum behind it. All major pharma and biotechs now have some manner of continuous program underway.
In some ways, I’m going to say that biologics are actually ahead of small molecules in certain places, particularly in areas like peptide manufacturing. For example, going back to the golden days in the mid-1980s, biotech started with perfusion – and perfusion is fundamentally a continuous manufacturing process. So, it doesn’t surprise me that there’s a foundation of knowledge t being harnessed there.
What’s more, behind the recent geo trends we are also seeing continuous manufacturing going into commercial in several places around the world right now. It is also much more accepted and beginning to mature.
There is a great deal of government focus on reshoring initiatives in the US. Biden’s American Jobs Plan is part of the infrastructure bill. It was just recently approved, with something like $50 billion in it for strengthening manufacturing supply chains of critical goods, including pharmaceuticals such as those on the Strategic National Stockpile list, the drug shortages list, and the FDA Essential Medicines list. Continuous manufacturing is going to be a key component of this going forward. So yes, in the US this is the culmination of a few trends to reach the critical point right now.
OSP: Who is leading on continuous: branded or generic?
BC: No doubt, the companies that are playing in this space right now are typically in the branded drug sector. They’re the innovators, partly because of the sophistication needed from a regulatory compliance perspective—and this paradigm shift takes some energy, a concerted effort.
However, the benefits for anyone playing in the generic space are going to be really significant, as the impact on the cost of goods sold (COGS) can make a huge difference to profitability going forward.
OSP: What are the implications of the US Food and Drug Administration (FDA) Q13 Guidance Document?
BC: Q13 is causing lots of conversation. It’s a very provocative document in many ways, particularly as it recasts the definition of continuous manufacturing to allow it all the way down to almost the unit operation level.
If any component of the overall manufacturing process chain has some continuous component in it, Q13 says that it falls within the purview of the definition of a continuous manufacturing process. It also provides further granularity when it comes to what the expectations would be around process modeling and how companies are, potentially, going to handle non-discrepant material and waste associated with it.
While, at a 100,000-foot level, the advantages of doing a continuous process are clear. The practical hurdles in terms of implementing something like that are not something that a typical generic manufacturer may have in-house. Perhaps only the larger ones will have the internal technical infrastructure to do the more sophisticated process and in-silico modeling to be able to answer the questions you need from a regulatory perspective.
That’s why it’s great that innovators are moving forward, as out of this will come a road map on how to do it. So, I’m very bullish that you’re going to see the implementation of continuous manufacturing—certainly amongst innovator companies. However, you’re also going to see pieces of this become adopted by generic drug manufacturers because the road map will be digestible.
Another positive aspect of Q13 is that the cost of entry has been dramatically reduced. Going forward it’s no longer the entire drug product or the entire drug substance or the integrated supply chain. Instead, it can be a portion of any one of those pieces that provide an advantage to a manufacturer.
If you couple that with some of the government incentive programs going on right now, such as the tax break program, there are good reasons to investigate the benefits and move forward from a theoretical conversation. That’s why I think we’re poised to see a serious push in pharma for continuous and from both small and large molecules.
OSP: Why does Q13 make it simpler?
BC: It has made entry altogether more accessible. Historically, what made it complicated for drug manufacturers was being able to do the necessary studies and generate the data through process modeling that supports a regulatory argument.
But Q13 provides some insight as to what companies need to focus on when it comes to these process models to establish their control strategies. It also talks about what they should focus on if they have got a legacy product that they now want to transition to a continuous process.
The new draft guidance is internationally recognized and coalesces what the industry considers to be best practices for different scenarios. It’s going to be easier for companies to migrate toward continuous processes.
OSP: What do you see as the next steps in the US over the coming two years?
BC: Every major pharma company has some sort of a continuous initiative underway right now. I see us debugging the regulatory framework for doing this and, as we do that on the innovator side, we’re going to gain clarity on the generic side. Downward pricing pressure is on every major political agenda and that’s not likely to diminish anytime soon.
Additionally, with the government funding some of these innovation exercises, the industry has even greater incentives to step into this space and it almost de-risks their first attempts at continuous manufacturing.
OSM: What about the CDMO market—are they ready to implement this?
BC: The bigger CDMOs have the wherewithal to put energy behind it, to build a focused team around it. Most processes deliver ROI on improved control, improved yield, reduced cost of poor quality, and reduced descript material, so for manufacturers, it can pay for itself in less than a year. It’s a no-brainer, and the next stage that will really accelerate everything is real-time release.
CPhI North America is scheduled online May 9-27 and in-person in Philadelphia May 17-19.
