Overcoming CMC Challenges for a Start-Up Company
Interview with Educo Life Sciences expert Raz Eliav
We interviewed Educo Life Sciences trainer Raz who teaches on the CMC Essentials course. During our discussion, we delved into the significant challenges that small biotech start-ups encounter when embarking on CMC development. Importantly, Raz also offered valuable insights into potential solutions to overcome these challenges.
You can watch or read the interview below.
Could you tell me the main CMC challenges that small biotech start-ups face? What are they up against?
Indeed, there are numerous challenges in the realm of CMC, which is often referred to as the “funnel of death” due to the high-risk nature that many biotech start-ups confront. The pharmaceutical and biotech industries are heavily regulated, directly impacting patient safety and public health. Consequently, developing new drugs carries immense risk, both for patients and for businesses. Start-ups in this space often grapple with several key challenges.
First and foremost, striking the right balance between regulatory compliance and patient safety, while operating within real-world constraints, is crucial. These start-ups typically operate on tight budgets, relying on fundraising rounds as their primary source of income. Every endeavour they undertake is financially demanding. Moreover, their progress can be slow, which doesn’t sit well with investors who seek quicker returns. Striking the delicate balance between pursuing the right actions at the right time is a perpetual challenge.
Adding to these complexities is the fact that start-ups typically consist of small teams. In some cases, it’s as lean as two scientists and a CEO. These teams heavily depend on external resources like contract manufacturing organizations (CMOs), contract research organizations (CROs), and consultants. Unfortunately, each of these service providers often views the situation from their specific standpoint, potentially causing conflicting interests and risk appetites. For instance, a CMO’s primary concern may be the success of a particular batch, while not fully comprehending the broader financial intricacies faced by the start-up. Navigating these conflicting perspectives becomes even more challenging in virtual organizations.
Moreover, the cost of rectifying issues later in the development process, especially during advanced clinical stages, can be exorbitant and present a significant regulatory risk. Companies often find themselves constrained by past decisions, a situation that doesn’t resonate well with investors.
In essence, from the outset of a project to its culmination in the market, risks are omnipresent. These risks span from finding the right equilibrium between development activities, financial constraints, and real-world limitations. It’s precisely why we aptly term this journey the “funnel of death.” As you observe the number of companies that embark on drug development, you’ll notice a gradual decline in their numbers over time. This decline underscores the multifaceted challenges beyond just developing a safe and effective drug. It’s also about demonstrating safety and efficacy, managing costs, and establishing efficient manufacturing processes.
Another formidable challenge is material supply. In the early stages, when drug development is still largely in the realm of science, most attention understandably centres around the clinical aspects. The supply of materials tends to receive less focus. Even as clinical programs advance, the prevailing mindset often leans towards addressing material supply as an afterthought. While this approach aligns with the ultimate goal of patient well-being, it can pose significant challenges.
CMC development entails more than proving a drug’s safety and efficacy. It requires the consistent production of the drug at high quality and scale. Achieving this consistency can be as challenging as the clinical aspects, especially in the case of advanced therapies like gene therapy.
For start-ups, the situation is further complicated by their focus on rare diseases and orphan designation, which often leads to expedited clinical development. While this is advantageous for getting treatments to patients swiftly, it can make CMC development the bottleneck, delaying progress to the next clinical trial or market entry due to a lack of ready materials.
Lastly, there’s the issue of knowledge management, particularly outsourced knowledge. Many start-up companies operate virtually, relying on external entities for various aspects of drug development. This distributed approach makes retaining critical knowledge within the company a formidable challenge.
Knowledge retention becomes challenging when everything is outsourced. Each service provider may have a unique perspective, potentially leading to conflicts and information silos. Onboarding junior personnel is also problematic, as small start-ups require individuals who can handle multiple roles effectively. This reliance on a limited pool of experts can lead to knowledge loss when key individuals depart, creating knowledge silos.
In summary, small biotech start-ups grapple with challenges related to decision-making, material supply, and knowledge management, all of which are critical to successful CMC development.
Can you share your potential solutions for addressing these hurdles?
In my opinion, the foremost consideration is treating knowledge as a valuable asset. Drug development is essentially a process of accumulating knowledge, starting from zero knowledge about a molecule and progressing towards a marketable product. To address these challenges effectively, we need to recognize the value of knowledge and treat it as an asset. This perspective leads us to systematically map areas where knowledge is generated throughout our endeavours.
We must crystallize this knowledge in an accessible format, ensuring that insights gained from various activities are not lost but contribute to the overall understanding of the project. This is crucial for both ongoing operations and future decision-making.
A key practice is to adopt digital tools for knowledge management. We are currently in an era of digital transformation, and these tools, including AI-based solutions, offer the capability to capture and organize vast amounts of data and text. However, it’s important to start small, focusing on specific pain points, such as capturing stability data in a digital format. This incremental approach can gradually lead to a more comprehensive and accessible knowledge management system.
Moreover, using established tools like the CTD Module 3 framework can provide a solid structure for managing CMC knowledge. It offers a comprehensive overview of CMC activities, helping us maintain a clear perspective and identify gaps in our program. This framework, while not exhaustive, remains a valuable tool for knowledge organization.
In conclusion, effective knowledge management is a multidisciplinary effort that necessitates a commitment from management to allocate resources for digital transformation. While it may not yield immediate returns on investment, it is essential for ensuring clarity, transparency, and success in drug development projects.
Watch the interview below:
Raz teaches the following courses:
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