With hundreds of gene therapies currently in clinical trials, the demand for manufacturing has exploded in just a few years. Biotech sponsors looking for contract manufacturing organization (CMO) partners face a difficult challenge, as bigger players compete for resources and consolidation reduces the number of prospects. So how do you find the right CMO for you and build a successful relationship? Truth be told, after spending time both on the CMO and biotech side, I think it’s a bit like appearing on the old classic game show ‘The Dating Game’ — the key to success is about asking the right questions and having good answers, as well as being fully committed to making the relationship work.
Know Yourself and What You Need
The first questions you should ask are not for your potential partners, however, but yourself. Clarity around your own needs is invaluable to select the right kind of CMO partner. Does the CMO provide process development, end-to-end production, or just one distinct step of the overall manufacturing process? Do you need a specific manufacturing or analytic capability? Having a clear manufacturing strategy and a well-defined role for a CMO to fill goes a long way toward finding a partner who can help advance your plan for success.
At AVROBIO, for example, our drug product manufacturing uses automated, closed production units, or ‘pods,’ that are about the size of a dishwasher and highly optimized for autologous CD34+ HSC manufacturing. The automation is intended to significantly reduce operator interventions and overall staffing requirements, while the closed system is designed to reduce contamination risks and lessen the need for stringent clean room requirements. This broadens our ‘dating pool,’ which is tremendously useful for a team that runs clinical studies around the world and ultimately intends to treat patients in major markets, if approved. On the other hand, we tend to be choosy in requiring a partner that can fully leverage our proprietary plato® platform to facilitate rapid expansion within and across locations.
Be Sure You Are Ready
Next, consider whether your program is mature enough for transfer into the rigorous environment of a CMO. Many gene therapy programs got their start in an academic setting focused on groundbreaking innovation, with less emphasis on the good manufacturing processes (GMPs) expected by most CMOs. There is nothing wrong with that – academic settings deliver the exciting, proof-of-concept data that is required to get a program off the ground. But once that happens, there is usually more CMC work to be done to ensure that you and most potential manufacturing mates can work together smoothly. So, consider the maturity of your programs and what needs to be done to bring the CMC aspects in-line with GMP expectations. And when you do begin exploring potential partnerships, be clear about where you are as a company and where you want a partnership to lead.
Keep Your Eyes Open
Once you make a connection that feels right, you’ll proceed to prepare the RFP (request for proposal). During this phase, everyone’s on their best behavior, but the hardest work lies ahead.The RFP is the opportunity to match the sponsor’s technical requirements to the capabilities of the CMO, aligning on timelines and costs. This is one of the most important first steps to establishing the relationship. If both sides remain happy after the first few encounters, you’ll proceed to the master services agreement, which lays out the terms of the relationship, the steps for resolving differences and the grounds for separation.
Be sensitive right from the start to signals from the CMO, like their level of responsiveness and ability to keep up with detail. And because red flags can become obvious on either side at this stage, look for potential problems within your own organization, as well. The earlier issues are identified and addressed, the better the relationship will be in the long run.
If all is going well, you’ll initiate technology transfer. This can last a year or longer, and really lets you see the strengths and weaknesses of your new partner, and hopefully yourself. Be humble about your part in the relationship and continue to be wary of assuming that any issues arise from the CMO rather than your own organization’s shortcomings. Companies may blithely paint CMOs as bottlenecks in the development process, but both parties share the responsibility to nurture the relationship along.
Build for the Long-Term
It takes hard, unglamorous work to build a strong bond. In the partnership between biotech and CMO, much of this toil comes down to project management. Cross-functional teams on both sides need to iron out the details in every key area (e.g., quality, manufacturing, controls). Executive buy-in and representation have to be part of the mix. It takes a village to optimize and scale these incredibly important processes, so don’t neglect good governance and process.
Be Willing to Change
And once you’ve done all this hard work, you can’t be afraid to make adjustments. People change, and so do industries. For example, one CMO business trend is a sort of ‘co-working space’ model with a variety of rentable clean rooms sharing a support staff. This setup has potential to be a great fit for AVROBIO’s automated, closed approach, and we are following its emergence with interest as our CMO relationships grow and evolve.
Gene therapy manufacturing is a complex and fast-moving sector, and sometimes it’s hard to keep pace. But it’s important to remember that the essential rules for maintaining a relationship have not changed throughout history — best practices for creating a successful manufacturing partnership boil down to a few enduring principles. If you know your needs, come ready to collaborate, stay alert for signs of trouble, work hard on the relationship and maintain flexibility, there is every chance that you and your CMO will live happily ever after.
Chief Manufacturing and Technology Officer, AVROBIO
Kim has deep global experience in the cell and gene therapy industry, biologics and medical device spaces, with a distinguished track record of innovation and implementation of Good Manufacturing Practices (GMP). Prior to joining AVROBIO, he served as the vice president of operations for Nikon CeLL innovation Co., Ltd, a Japanese contract development and manufacturing organization. During his tenure, he established the company as the preferred provider of custom process development and manufacturing services for cell and gene therapy products in the Japanese market. Previously, Kim held management positions at Lonza, serving as the business director for cell therapy contract manufacturing operations in Singapore for five years, and prior to that as director of operations at Lonza’s Maryland facilities. Kim was also previously the senior manager of the Tissue Processing Lab at CryoLife Inc. He holds a BS from the University of Miami and an MBA from Kennesaw State University.