Hybrid. Continuous. Peptide. Manufacturing. Lilly's Put It All Together.
By Louis Garguilo, Chief Editor, Outsourced Pharma
Perhaps I’ve been pursuing a somewhat unfair exercise of asking readers to focus intently on the facilities at CDMOs by benchmarking them to the absolute best internal facilities at Big Pharma.
The first part of the message is solid: focus intently on the facility you will be inhabiting when potentially working with a CDMO. Sounds elemental, doesn’t it? And if you revisit your overall CDMO selection evaluation- are you in fact getting as detailed as you should?
But the question arises to my approach: Should your CDMO’s facility be on par with the best at Pharma?
I’ll allow for some critical discretion here. At the least, we have certainly learned a lot about the best facilities in the biopharma world.
More than a few readers wanted to learn more about that facility’s “hybrid continuous manufacturing for peptides” technology.
Continuous and Batch Processing As One
The first point of business is to clarify that the word “hybrid” in the new technology does not imply one peptide-producing line using the standard batch technology, and one using continuous-flow production technology, in the same facility.
Hybrid here means a combination production line, with a merger of continuous manufacturing equipment sets and intermittent batch hold technology on one line .
“So we’re putting the two together,” explains O’Shea, “that's the hybrid element.”
The “traditional way” (all batch) is less efficient and burdened with individual steps, she says, not to mention it requires huge solvent usage
Continuous technology allows you to “optimize your residence time, reduce those solvents, and take up a smaller footprint, and other advantages beyond the traditional manufacturing process.”
“We have learned how to best control and run processing for peptides,” she says. “It is in fact novel – the whole concept, along with our advanced data systems for the platform – and exactly why we won thee ISPE awards.
That 2024 ISPE Facility of the Year Award (FOYA) Category Award for Innovation, and subsequently, the Overall Facility of the Year Award, is based on Lilly’s recently completed synthetic peptide manufacturing platform/facility.
It includes the successful installation of several new "process and execution systems" at their Kinsale site in Ireland.
The Details
As mentioned above, the new facility uses “a hybrid manufacturing platform, with liquid phase peptide synthesis/solid phase peptide synthesis (LPPS/SPPS)."
The platform takes the traditional approaches to synthetic peptide production using SPPS to manufacture high purity pre-assembled peptide fragments and combines that with coupling the fragments via LPPS using continuous processing technology.
Lilly says this new platform delivers a significantly increased annual throughput potential, and reduced risks during the manufacturing process.
When we spoke, O’Shea mentioned the "digital plant advancements" as part of this new facility.
An ISPE press release informs us Lilly has devised “an original digital solution for material tracking and generating an accurate genealogy for the continuous process for the hybrid peptide continuous manufacturing platform.”
O’Shea says that the Lilly Kinsale material tracking model “at this scale and complexity for a continuous process, represents a significant step forward for the pharma industry in the use of models to support GMP manufacturing.”
Other technologies include process analytical technology (PAT) control and nanofiltration technology (using ceramic membranes – also a first in the pharmaceutical sector) that can support high-volume throughput at commercial manufacturing scale.
O’Shea believes the ISPE recognition was heavily influenced by the fact the new Kinsale facility was focused on peptides specifically.
“Our industry keeps evolving, she says, and facilities are rewarded for innovating, no matter the modality.
“We keep progressing with manufacturing technology as science moves forward with innovative clinical solutions. Who's to say today what the next medicine innovation will be?
"There are other scientific revolutions happening as we speak, driven by very clever researchers. This is part of our nature; nothing stays the same.
“To me, that is the identifiable constant in our industry. We’re still building a new and very strong small-molecule pipeline. We still have monoclonal. This is an additional platform to an already very strong set of options.”
We Aren’t Discounting People Power
In my youth, I was often warned not to overdo it. (Because I often overdid it.)
So, to prove I’ve learned something over the years, as I wrap up here, let’s backtrack a bit to the opening of that earlier editorial:
“How do we select a CDMO?
How do we select a facility?
The second of these fundamental questions should have equal weight with the first. Unfortunately, question two appears to carry less weight...”
Although this rings true, we are not attempting any denigration of the “CDMO” as a full compendium of human, organizational, strategic, and other factors that make up your amalgamation of due diligence.
People run facilities. You hire them for their skills and their experience.
Project managers assist or can hinder you. Your CDMO’s managers and executives can help solve difficult challenges.
Culture can also be a key enabler or barrier to delivery. How do you find out what the CDMO’s culture is like? “Have lunch with them in their cafeteria,” I’ve heard more than one biotech executive tell me over the years. Similar strategies also prevail.
In fact, earlier we said there is a pre-existing preliminary positive energy and track record associated with those people working at a facility before more investments and added capabilities/capacities are entertained by management and investors.
It's that will to improve that is then harnessed to successfully operationalize the investment.
Perhaps we end with this: The best facilities house the best professionals, and the best professionals get to work in the most state-of-the-art facilities.