The Top Drug Development Partners Talk A Good Game
By Louis Garguilo, Chief Editor, Outsourced Pharma
“So again, here’s where the development piece comes in with a good CDMO,” says David Grote, Vice President of Strategy, GrayMatter Partners.
“Again” because we are wrapping up an extended conversation in which he keeps doubling back to that point.
Grote was joining me from a temporary location in Florida; approaching hurricane Melissa had he and his wife evacuate Cuba, from where he consults in the pharma industry currently as his wife serves the U.S. as a Navy doctor at the military base there.
We can say, though, Grote's windswept perspective is perfect for discussing with us the state of development and manufacturing outsourcing.
The CDMO Dialogue
That good CDMO – which he habitually differentiates from the many he believes are not – should effectively dialogue with a customer, as such:
“Well in our experience for this type of process, you are looking at XX many grams per liter of titer. And so that's what type of product this is and we should design our plans around.”
On the other hand, he says, should you have a CDMO working on program that is relatively unknown (e.g., “a more novel monoclonal antibody or even fusion protein”), the CDMO can provide you a solid starting place:
“This is the cell line we'd recommend you utilize, and if you use XX cell line for this type of product, you should get somewhere around XX range of yields. “
The CDMO’s formulation scientists can chime in:
“Based on your modeling and some animal studies, you're anticipating a potency of somewhere around XX value which will work out to maybe a dose in XX range.”
A benevolent CDMO – because you have invested the time to provide all the details/background/plans for your potential product – will also consider your target assessable patient population.
The CDMO should know whether they are computing capacity/equipment/materials/human resources/timelines for an initial population of 1,000 patients or 100,000 thousand, which leads to a batch-scale and batch-frequency discussion.
I’m sure readers get the point here. Grote is all about CDMO dialogue. He believes it happens less frequently or fervently at a detailed level than it should.
As concerning, when it does … sponsors don’t seem to listen carefully.
CDMO’s As Dialogue Demons
The question is are CDMOs (ok, even good CDMOs) skilled at acting in the capacity of consultants?
It's still a mix, Grote says, even among the CDMOs with the best reputations. However, on the whole, he does think CDMOs have improved across the board.
In what way? He asks me to recall how it used to be just CMOs (no “D” for development], “so you'd bring them your product mostly developed.”
He recalls early attempts to test the new paradigm when CMOs started to advertise development capabilities.
“At Teva years ago, we worked with both a Europe-based CDMO and Celltrion, a CDMO in South Korea. We simultaneously kicked off development of a AJOVY migraine drug with both companies as a sort of competition.
Pfizer had previously done some development work on the process, and Grote's in-house professionals were doing some work at the same time.
“We came up with a much higher yielding process than the external providers," he says. “No offense to anyone – and we stayed with Celltrion for the manufacturing of the product [more on that below]."
But his point is that advising on and creating a development path leading to the best manufacturing process for your product requires a certain skillset.
"Even today, you need to ensure your CDMO can do all that," Grote warns.
Despite the warning, today sponsors will find that CDMOs, for example, can "simulate different cell lines, conditions, media formulations … a good CDMO today excells at such capabilities and can help you with optimization.”
Alas, another warning about that optimizing; it requires careful consideration. Too much tinkering can delay schedules, lead to cost overruns, and if your product does not make it through the clinic, a large organizational loss.
Back to the AJOVY narrative above, Grote ends with this:
“Right after we did our PPQ [process validation] runs at Celltrion, they received a warning letter from the FDA for a different customer’s product. We had to scramble; we had our pre-approval inspection coming up.
"And we pulled it off nicely! We got our successful PAI in about nine months after that warning letter.
“It comes down to how you communicate and react to a 483 and challenging situations that is most important. Celltrion was a great partner. We had a rapport with them.
Where did that rapport begin? How was that trust pre-established?
Echoing our theme above, "Having talked through the development of the product was a great help," says Grote.
In other words, CDMOs have been correct in strategizing that their earnest addition of development service and the requisite set of capabilities can help to cement long-term customer relationships.
So much hinges on the dialogue. Here's hoping your CDMO talks a good game.