Translating scientific discoveries into meaningful patient impact will always be a challenging yet rewarding endeavor. As the industry evolves, partnerships between CDMOs and biopharma startups have become fundamental to success as increasingly complex medicines demand an array of specialized skills to empower innovation and deliver safe, efficacious therapies to patients.
We spoke with Jennifer Chadwick, an experienced industry expert and founder of Jennifer Chadwick Consulting, for a Q&A to discuss the current and emerging needs of biopharmaceutical innovators working in this exciting era of therapeutic advancement.
Q: What are some of the unique needs of new biopharma companies when compared to more established pharmaceutical companies?
While many different types of people are inspired to build biopharma companies, a large percentage of new therapeutics companies are created by first-time founders who come from academia or basic science labs and tend to excel at discovery research. These innovators have strong scientific or technical expertise, but little to no business or development experience, so the development and manufacturing components of biopharma may be relatively new to these founders. In contrast, large pharmaceutical companies are quite practiced at drug development, with established structures designed to move new discoveries into efficient development pathways.
CDMOs and other consultants can provide crucial guidance for new companies navigating drug development pathways by providing insights that improve the likelihood of successful tech transfer and commercialization. Many startups underestimate the work involved in transitioning into a GMP-friendly process. For example, techniques that may be common in a research or academic environment (such as centrifugation) are rarely transferred into a GMP manufacturing process unless absolutely necessary, and then adoption of new processes is costly and requires substantial time and effort to accomplish. Extensive analysis is required to replace these processes to ensure that the new process is generating the same product based on equivalent results. This often includes an array of assays, importantly, cell-based assays that are challenging to fine-tune. Bridging the gap between research and development requires significant foresight and knowledge that CDMOs are well-equipped to provide.
Q: How has the role of CDMOs evolved over the past decade? How are today’s biotech founders approaching outsourcing differently than they might have previously?
Outsourcing was much less common ten or twenty years ago. The dominant mentality of biopharma companies was to “build it ourselves,” which was reinforced by investors focusing on companies that had control over their own development and manufacturing. However, as the complexity of biopharma therapeutics grows, so does cost. Outsourcing has become the norm, with over 85% of products being manufactured at CDMOs. The growth in outsourcing makes sense because a small company can tap into the full array of resources, including the knowledge and expertise a large entity has established, leading to increased speed and efficiency. When you have organizations with developed expertise at your disposal, outsourcing becomes much more attractive from an investment perspective.
The business aspects of working with a CDMO are also better understood. Startups and their investors are more familiar with the process and understand that their IP is still protected when working with these organizations. CDMOs also help de-risk the development process for biotech organizations. Risk is reduced not only because key processes are in the hands of experienced teams who are less likely to make costly mistakes, but also because they are more equipped to develop rigorous CMC (chemistry, manufacturing, and controls) documentation. As boards and investors learn from previous failures, CMC has become increasingly recognized as an important component of success and hence appreciation has grown for the services that CDMOs offer.
Q: What are some features, capabilities, or approaches that make a CDMO a good fit for a biopharma startup?
What makes a good CDMO partner is going to vary depending on the product being developed. As I mentioned earlier, the tech transfer step is much more involved than many new businesses appreciate. In addition to transitioning into GMP-friendly processes, businesses must align to regulatory requirements. For instance, during analytical development, a lot of thinking goes into which attributes will rise to the level of a CQA (critical quality attribute) and the analytical assays and methods needed to reliably monitor those attributes. There are important judgement calls that must be made about how analytical tools are applied to generate robust data for regulatory submission. The complexity can be further compounded if the product requires a dispensing device, as is becoming more common for biologics. There are important considerations around formulation, viscosity, and surface interactions that may not have been contemplated fully during the early research phase, that then later need to be addressed.
It’s extremely valuable and reduces risk for startups to talk to multiple CDMOs. It enables a team to understand the CDMO’s technical abilities, existing infrastructure, and modality-specific expertise so they can assess alignment with the needs
of their product. CDMOs can help newer biopharma companies by being clear about those points and providing insights related to risk and cost when approaches are new and a gap needs to be filled. They can also parse through existing analytical data and advise on what’s needed to move into a tech transfer. In addition, it’s important for early biopharma companies to keep their costs contained and prioritize the right use of often limited funds. Before partnering with a CDMO, companies may need to collect further data in-house, refine analytical methods or work with a specialty CRO to develop an analytical technique that will later need to be implemented at the CDMO. CDMOs can help build the relationship by providing this advice on the front end, acknowledging the financial pressure that startups face, and collaborating to find cost-effective methods for transitioning into development.
Finally, it’s important to consider the ability of the CDMO to scale with the company, including an appropriate balance of scaling out versus scaling up for biologics. Biopharma startups may want to minimize the need to transfer between facilities and providers. This is especially important if the product is
sensitive to concentration effects or has stability concerns, as these factors can have a significant impact on the ability to move between facilities. Furthermore, startups should consider which components of the product require specialization or customization and which components can rely on more cost-effective standards. By developing a deeper understanding of the nuances of their product, startups can better evaluate which CDMOs are prepared to grow with them.
Q: Can you talk about the importance of flexibility in a CDMO partnership, particularly as programs evolve or priorities shift?
Flexibility is essential, as there are many unknowns in creating new products and processes that result in deviations from an original plan, and adapting to these unforeseen events creates a foundation for establishing trust in the partnership. Early-stage companies face significant financial constraints and must navigate strict timelines to ensure their product progresses first to IND readiness for Phase 1 dosing, which often unlocks access to the next round of capital to support progression to Phase 2 and the manufacturing scale up required to supply the next phase. CDMOs can establish a strong foundation by investing in the relationship upfront during pilot programs. Providing time-sensitive assistance to prepare the product for the next stage can be the deciding factor that determines whether a new company hits key benchmarks or not. CDMOs who are willing to strategically invest resources in helping their clients succeed are more likely to see a return on that investment. A successful pilot program helps clients secure critical funding, which then allows biopharma startups to begin the cost-intensive manufacturing phase with their trusted CDMO partner.
The partnership between a CDMO and a startup will be strongest when both parties are mutually invested and work as a cohesive team. For biopharma companies, that starts with doing the homework to interview relevant groups. This will involve multiple conversations, and ideally a visit to the facilities, to understand the CDMO’s capabilities, capacity and their technical expertise. CDMOs can contribute to this conversation by providing regulatory guidance and advice on tech transfer best practices. This also includes having honest discussions about capabilities and demonstrating a willingness to help startups overcome early-stage challenges. Today, these partnerships are the cornerstone of successful biopharma innovation, helping bring new medicines to the patients who need them.