By Louis Garguilo, Chief Editor, Outsourced Pharma
An exasperated pharma veteran publically voiced a widely shared concern via an open question: “Our industry’s been engaged in tech transfer for some 30 years, so why haven’t we gotten really good at it?”
“It does make me wonder,” replied a second industry executive at the same forum. “I’ve seen tech transfer at Big Pharma continue to pose problems through this decade, including between internal sites. It remains a challenge.”
That ongoing challenge has increasingly led to another question, this one posed in more hushed tones (and some conspiratorial drama): “Do you think the CMOs have developed strategies for tech transfer that may be superior to pharma’s own?”
Here’s what some professionals have to say.
EXPERIENCE TRANSFERS WELL
“One of my first projects years ago was perceived as a straightforward commercial tech transfer from a customer,” recalls Siddharth J. Advant, president — Biologics, Kemwell Biopharma. “We thought, ‘It’s a set commercial product, so what’s the big deal?’ But as many now know, when you have to fit a process into a new facility, not everything performed in the original location is going to work in the next one. I’ve learned it’s not a matter of who has the best tech transfer strategies but, more importantly, who has the most experience.”
Besides his general tenet regarding the primacy of experience, Advant suggests a specific approach to more effectively transfer product into any facility: Scale-down models should be performed to gain a deeper understanding of challenges before proceeding to the desired scale up within the CMO’s manufacturing format. “Of course the client has to agree to the strategy, and be a willing partner in these activities,” says Advant.
That final comment on client acceptance can be the most difficult part of the equation, according to so many I’ve talked to over the years at CMOs and from some personal experience. It’s the sponsor’s project. They are paying, and they often feel they know what’s best in the transfer process. Advant says that to help gain acceptance — or recognition of experience and knowledge of at least one’s own facilities and equipment — his company shares a “guidance policy” with clients. He says that when CMOs clearly detail the aspects and their methodology of tech transfers at the different stages, it helps ensure both sides understand the experiences of the other and also helps in setting realistic goals.
“It’s not that we have to do everything our way or even a certain way,” concludes Advant. “But at the end of the day, the CMO is expected to deliver to the customer. And that starts right off the bat with the project transfer working out.”
SIZING UP YOUR PARTNER
Hank Stern, VP CMC, Alexo Therapeutics, says it’s difficult to determine whether one organization does tech transfer better than another. However, he lets us in on some telling research regarding the potential costs of a commercial-scale project, which may help inform a sponsor on technology-transfer discussions and decisions.
Stern puts that in perspective. “If you ever went to a CEO at a smaller pharma company and said, ‘We need 40 FTEs to do a tech transfer,’ it’s just not going to happen. All sponsors, particularly smaller pharma or virtual companies, need to ask: ‘How do I fully leverage the systems and processes at my CMO?’ You may feel like you lose some control, but you can effectively minimize resources and gain the full experience of your partner manufacturer.” The key here, of course, is to make sure sponsors have selected the CMO with the right experience for their projects.
Ulrich Ernst, SVP Manufacturing & Quality Operations, Amunix Operating, Inc., agrees the methodology and best practices selected for a tech transfer depend on the partners involved. He’s arrived at his views from the perspectives of someone who has worked at large and small pharma, and as a contract manufacturer. Here are his three “points of attention” for both partnering organizations:
“First is the overall scope of the project the client is bringing in. By that I mean it’s important for both sides to ensure there’s proper communication on the intent, scale, specific needs, timing, and quantities to be delivered, and all the expectations around those parameters. Scale is important both on an operating level and in terms of the technical requirements at that level. You’re building a lot of detail into a mutual plan for success.
“Next, you need to explore and understand strengths and weaknesses on both sides. A large partner on either side may bring a lot to the table, but a smaller one can bring certain pieces as well. If any of the pieces, such as process development, project and facilities management, or quality requirements, differ from the partner’s expectations, you’ll run into problems at some point.
"I’ve learned it’s not a matter of who has the best tech transfer strategies but, more importantly, who has the most experience."
Siddharth J. Advant
President of Biologics, Kemwell Biopharma
“Finally, understand the structures that need to be in place around the project, including starting with doing a business development plan. You need agreements that ensure alignment from business, legal, technical, and quality standpoints. Ensure you understand the obligations of both partners. The best tech transfer strategy is the one where both sides are completely on the same page.”
Getting on that same page may require another pair of hands. Assisting with tech transfer is one of the most important roles consultants and other trusted partners play in the client-provider relationship.
Ulrich Ernst, SVP Manufacturing & Quality Operations, Amunix Operating, Inc.
For example, there are times when sponsors have been working with a CRO or CMO because of recognized expertise or relationships earlier in the life of the project. The sponsor, though, may become less certain of the CMO’s prowess for the next phase. Both Stern and Ulrich agree if you don’t feel comfortable — or have the sense that either you or your partner does not have the capability — you should consider finding a third-party source to help you, whether that’s a consultant or another partner company.
Of course bringing in a third party to help you understand or execute on a critical tech transfer can also add an additional layer of complexity. However, according to Ulrich, what nobody wants is to “have to do it twice, because of some failure the first time.” Despite the pressures, he says, there’s usually more time that first time, and it gets more expensive with any failures. “Smaller sponsors also understand well the financial pressures and the cost rationalization that’s going on in the industry today. The expectation is, if you don’t know something, you should know somebody who does, and you should bring them on board to help sooner rather than later.”
"All sponsors, particularly smaller pharma or virtual companies, need to ask: ‘How do I fully leverage the systems and processes at my CMO?’"
VP CMC, Alexo Therapeutic
What sponsors may find after conferring with consultants is that a solid dose of introspection is in order and, perhaps, so is a renewed commitment to the same partner. Stern suggests if you’re a small company contracting a CMO, and it’s not quite working out, perhaps from a new technology-transfer perspective, you probably do want to see if you can work through it. He puts it this way:
“You treat the CMO as one of your employees. If your employee is not working out, you want to make sure you’ve provided clear direction. What part of ownership are you taking for any problem or uncertainty in capability? Have you provided sufficient resources and information? Have you communicated closely and provided feedback? Are you willing to invest in your partner to add capacity or ensure capabilities? You should be saying, ‘Hey, here’s where it’s not working out. Can you change staff or equipment? Can you change the way you’ll process this?’
“However,” he continues, “just like that employee who’s not working out, you’re not going to spend forever figuring things out. At some point and in some cases, you have to say, ‘Look, this is not a good relationship for either of us.’ Often it’s also better for the CMO to move on.”
A final word from Kemwell’s Advant: “If you’ve had the right discussions throughout the relationship, both sides will already know clearly and be prepared for what is coming next. Again, the best transfer techniques and decisions are always a result of mutual understanding.”