To this day, one of the least explored dimensions of drug development and manufacturing outsourcing is the “no-choice partnership.”
This might be an inherited relationship. For example, a biopharma licenses in a molecule whose progress has been closely tied to a certain service provider – where most, if not all the actual development and manufacture has taken place, and where that applied knowledge and experience-through-practice resides.
Or, a second case – on the increase nowadays – where biopharma companies establish such unique platforms, advanced sciences and technologies for new therapies, that only a select few CDMOs can actually assist them.
These, and other restricting circumstances of choice, can exacerbate long-held concerns over “single sourcing,” desires for “redundancy” through various sources, and working with the best fitting partners.
All of this, then, leads to increasing pressures on drug sponsors to deploy best practices to quickly evaluate, effectively work with, and productively manage “acquired” CDMOs.
Mulkerrin participated in a discussion titled: “Where To Outsource And What To Consider.” Let’s start with comments he made in response to a question about accessing “company culture” at prospective external development and manufacturing partners.
In not uncharacteristic understatement, after listening to others reply, Mulkerrin said, “So our experience has been driven a little differently.”
“ADC Therapeutics was established as a spin out of Spirogen, and inherited contractors we needed to continue to work with. They are the experts in the area of products we need manufactured. Also, because we're making high-potent ADCs – the chemicals we're working with are toxins – there are a limited number of organizations who can actually work with our products.”
What to do in such a delimited space?
“Because we have to work with some specific contractors” continued Mulkerrin, “this means we will work with organizations anywhere in the world – India, China, the U.S., and Europe. Geography cannot be a criteria in the choice of partners. The criteria is quality in what they do and produce. And that has its challenges. “
So rule one: Go to where the capable and quality CDMO resides. Don’t further limit your choices by geography.
And rule number two might be this: Despite the relative lack of selection options, still do a thorough evaluation – and try to influence to the extent necessary – the CDMO’s culture. Even with limited choices, says Mulkerrin, a CDMO that continues to operate with an inadequate culture is simply the wrong CDMO.
“We look to access the people in their organization – their personnel must exhibit personalities we can in fact work with,” is how he frames it.
But what about the consequences of not accepting one of the few CDMOs out there?
“It is a problem,” says Mulkerrin calmly. “You can add to our situation that because the molecules have such a high potency, and our batch sizes are quite small, some otherwise capable CDMOs might not be interested, or scheduling can be difficult.
“We of course have to manufacture antibodies as well. The good news is in the antibody space, it's much easier to find organizations to conduct the manufacturing. So a second-source strategy there is not challenging.
“But when it comes to the synthesis and conjugation, you simply have to live with the fact you will be single-sourcing for several components, and some of the manufacturing steps. That's a risk you have to take, but you have to clearly understand how you're going to manufacture sufficient material to get your critical supply.
“There are no easy answers,” he says after a slight pause. “Each biopharma has to put in place it’s own strategy for dealing with the fact that if something happens, you will need to react quickly. You will have to depend upon the expertise of your team, and all the organizations you're working with collectively, to be able to recover and get back on track.”
So lesson three: Little choice cannot mean no choice. Or no strategy to mitigate risk. There must be viable contingency planning to overcome the identified risks. Otherwise, you may decide you have to build your own facilities and internal expertise, if that is indeed an option.
Or, unfortunately, perhaps your other option is to rethink the entire premise of your programs, and business.
Maybe There Are (Some) Choices After All
Before the panel discussion ended in San Diego, another attendee asks about vetting CDMOs, when there are in fact a number of vendors who can support you.
“We’ve developed a process,” Mulkerrin answers. “For example, for two steps in our process there's less than a handful of players in the world who can actually accommodate the business. So we have to be diligent in how we determine which of those CDMOs can actually do the best work for us.
“One thing to point out is that no matter how small our company has been – and we were as few as 5 people – one aspect of our search process necessitates going to and talking with companies before we ever send out an RFP. We make sure these are companies we can potentially work with first.”
Mulkerrin also says part of his selection process includes a “separate quality audit before starting to work with any organization.” He has either an internal or consultant quality professional or a QP (Qualified Person) if the CDMO is in Europe, conduct a full quality audit.
But there’s yet another challenge for Mulkerrin.
“We have to be diligent through development work even outside of GMP. One reason is we have [proprietary] development processes we contract out.”
This is a challenge many more biopaharma do or will face as the industry continues to evolve towards the model of platform-enhanced performance, productivity, IP-protection and production.
“Therefore,” Mulkerrin explains, “transfer from one development organization into a second CDMO, for example, will involve 3-way CDAs.”
“These agreements are the framework of relationships. They must also ensure the people from two different contract organizations can actually talk to each other about the project. Detailed instructions are critical, so it’s important we as the sponsor are involved every step of the way.”
And he means every step. Mulkerrin recognizes at times he’s been criticized for such a high-level of involvement.
But this is our final lesson here: Don’t let criticism knock you off your game.
“I do know the way we handle our contract work is a bit unusual,” he acquiesces, “and we are very involved – perhaps more than some other sponsors. But I think other biopharma companies should do the same.
“We work with our partner organizations on a day-to-day basis. We spend a lot of time at each organization when we need to. We make sure we all understand the process, and we all communicate effectively.”
And finally: “I think there're a variety of ways to establish your own processes, but you must have those processes in place.”
In that, says Mulkerrin, you have no choice.