Continuous Cruising The Pharma Highway
By Louis Garguilo, Chief Editor, Outsourced Pharma
Jim Bonner, Ph.D., Director Drug Product, Shire, says continuous manufacturing (CM) is the pharmaceutical industry’s future.
Eric Jayjock, Ph.D., Director of Continuous Manufacturing, Patheon, who has written a widely read article on the subject, compares batch and continuous manufacturing this way: driving yourself through congested New York City as opposed to programing an autonomous car to cruise a constant speed on a highway.
Douglas B. Hausner, Ph.D., Associate Director for Industrial Relations and Business Development, and member of the Department of Chemical and Biochemical Engineering, Rutgers University, agrees with both the ultimate destination and the vehicle to get there.
All three presented their thoughts in a session at the recent DCAT Week ’17.
State of the Art
In what’s become a go-to introduction piece on CM (What Is Continuous Manufacturing, Anyway? Agreeing On A (Proper) Definition), which Jayjock co-authored with Keirnan LaMarche, Ph.D., Bristol-Myers Squibb, he sets out to better define (and thus explain) the technology. At DCAT, Jayjock boiled this down to two essentials on a sparse slide.
Continuous manufacturing is a process in which:
- The definition of the amount of material expected to have consistent quality (i.e. batch) is not set by the scale of the equipment.
- The ability exists, if necessary, to devise feed-forward and/or feedback control loops which span across separate unit operations utilizing data taken from the process in real time.
According to Jaylock – from the perspective of a CMO, and focusing on the branded-pharma industry – there are five main points to make on the state of the industry and market that affect continuous manufacturing:
- Fewer new blockbuster drugs
- Rising costs to develop products
- New products tend to have smaller volumes, but higher value
- Many new products originate from small/medium pharma firms
- Excess manufacturing capacity exists in today’s factories
To date, the industry has seen two products produced by CM approved by the FDA:
Vertex’s Orkambi (July, 2015) (NDA) and Janssen’s Prezista (April, 2016). Our three experts at DCAT are optimistic that while potentially slower than any of us would have hoped, the business case for CM is being made more persuasively on the manufacturing floors and in the executive suites at all-sized pharma (and contract manufacturing organizations) around the world.
Why We Move Forward
Bonner of Shire outlines the business case to make internally at a pharma company, in a slide titled, “Continuous is Pharma’s Future.”
- Quality
- Design in quality and maintain on factory floor
- Nimble process
- Fast control system response lead to:
- Improved Process understanding
- Enhanced Quality Assurance
- Net Present Value
- CMO product cost savings and Volume growth drive NPV
- Cost
- Literature predicts up to 60% savings
- Conservative ‘should cost’ exercise predicts 20 to 30% savings
- Run rate and FTE’s are key inputs to product cost savings
While we can’t go into these in detail here, we should point out, as Outsourced Pharma readers have seen in these pages, what initially was thought to be a liability of the new technology, enhanced quality is the first point on Bonner’s list in favor of adoption. Tellingly, the next two points for Bonner are financial. CM will require upfront investments, and those initial outlays have to then be expressed by consistent future returns. Again, we’ve covered this subject in Outsourced Pharma.
But what we also hear so often is – as with most all new “disruptive technologies” – the initial technological and financial inertia is hard to surmount.
Why Aren’t We There Yet?
Here’s where we turn things over to Hausner of Rutgers. He outlines what he believes are the four main factors for a slower adoption of this technology that so many see as our eventual manufacturing future.
First is the “regulatory uncertainty around the world.” (Gee, I wonder if we’ve heard that before.) However, in this case, the FDA is leading the way forward and is a positive force. “The FDA can’t be clearer about this [technology],” says Hausner. “They’ve been sounding the horn for the last couple of years.”
For example, Hausner says the most asked question from potential continuous manufacturers to the FDA is: How do we define batch? “The FDA has pretty much said define it in any way you want, as long as you’re consistent with the definition and you define it up front. You can define it by the amount of API you have within your incoming lot, you can do it by runtime, or by volume.”
The bigger regulatory concern for pharma, according to Hausner, is the rest of the world. “We’re hearing biotech and pharma executives say, ‘Great, but that regulatory support from the FDA is only for the US market. What am I going to do in Europe, or in China? We haven’t seen enough of what happens in those markets yet.’”
Hausner’s second factor for slow adoption of CM reminds us of the phrase, “personnel is policy.” He says currently there aren’t a lot of people familiar with this new technology; it's a challenge getting the right people in place.
“It also requires a higher degree of technical skill than perhaps you would have had before,” Hausner adds. “There’s more process engineering that goes into CM. There’s more spectroscopy, and other analytical considerations that are now happening right on the manufacturing floor. Due to those changes, we need to make sure we have knowledgeable and correctly trained people involved.”
The third point for Hausner is equipment remains a challenge. Options aren’t available yet, although this will improve as more need arises. “This is certainly getting better,” says Hausner. “In the last six months, there have been multiple new facilities that are built by other equipment manufacturers, and efforts to provide more options to the market in terms of equipment.”
Finally on Hausner’s list of challenges is an echo of what Bonner of Shire addressed in his business case for switching to CM.
“Capital improvement can be an issue,” says Hausner, “but often this is directly related to the question of how are companies approaching implementation. We’ve seen too many instances of companies that actually have the capabilities to do CM – companies that absolutely will be doing this in the future – but that are passing up on a project, waiting for the next one, passing up on that one, too, and taking these case-by-case, isolated decisions.”
Rather, says Hausner – and our other two experts fully agree – moving to CM should be more of an “all-in” decision. And that may mean even with pockets of existing internal idle capacity.
Destination In Sight
“People who so far have successfully made the transition to CM have approached the decision from a higher level, and making an organizational commitment to it,” Hausner continues our final point above. A good example of this is Eli Lilly, who is doing all their new product manufacturing continuously for solid dose.”
To wrap up here, I’ll leave readers with a summary of Hausner’s four points to get the industry to the finish line at that highway cruising speed we mentioned to start us off.
- Adoption will increase first in areas with an easier pathway to regulatory approval: High volume OTC products are excellent candidates for dedicated lines.
- Biotechs and others with less solid-dose capital investment will activate small-molecule pipelines using CM technology over batch
- Adopters will look to CDMOs who have the high-level personnel, knowledge, and increasingly equipment availability
- Asian players seem eager and have available capital, helping to spread the technology around the world.
--------
DCAT Week ’17 is the annual event of the Drug, Chemical & Associated Technologies Association (DCAT)