What Time Is Best To Bring My CDMO On Board?

By Alex Santos, CMC regulatory scientist

Traditionally, biopharmaceutical companies employed an in-house approach, keeping product development and analytics firmly within their own facilities. An outsider might expect this model to foster close collaboration between departments like analytical development (AD), manufacturing, science, and technology (MSAT), and quality control (QC). Yet, despite physical proximity, collaborating at all often proved challenging.

Over the last five years, we’ve seen a dramatic shift toward outsourcing, with contract development and manufacturing organizations (CDMOs) adding a new layer of complexity but also new opportunities to strengthen interdepartmental collaboration.

This column explores the rise of CDMOs and their potential to enhance, not replace, internal bioprocessing capabilities. By integrating rather than transferring technology, partnerships with CDMOs have the potential to streamline product development, focus on product characterization, and strengthen dossiers for regulatory submissions. 

The premise of integration raises an important question: when is it the right time to bring my CDMO into process development? As we’ll discuss here, the answer might be earlier than you thought and entail more transparency than you’re used to. 

Integrate, Don't Transfer, Your Knowledge

The traditional "technology transfer" model often viewed CDMOs as passive recipients of a finished process. However, this unidirectional approach can lead to knowledge gaps and inefficiencies. Technology integration, on the other hand, brings both parties together to collaboratively establish the manufacturing process and its analytics at the CDMO facility. This fosters a deeper understanding of the product and its intricacies, leading to:

• Reduced Risk: Through early engagement, the CDMO can identify potential challenges and propose solutions before issues arise during full-scale manufacturing.
• Improved Process Knowledge: Collaborative process development ensures a shared understanding of critical process parameters and their impact on product quality.
• Enhanced Regulatory Confidence: Working together strengthens the regulatory package by ensuring data consistency and a clear understanding of the manufacturing process throughout development and commercialization.

Integration requires a shift in mindset that begins as early in process development as possible. Biopharmaceutical companies must view CDMOs as partners, not simply vendors. This collaborative approach necessitates the free flow of information, open communication channels, and joint problem-solving.

With a joint foundational understanding of a product’s process, two key departments — analytics and regulatory — can further benefit from a borderless integration between customer and contractor.

Empower Your Analysts And Operators

A product is only as good as its analytics, and the quality of the data will largely depend on the skills and capabilities of your analysts and operators. In bioanalytics, automation is still in its infancy, meaning human hands are generating most of the critical data being included in regulatory submissions. I work with advanced biologics and cell and gene therapies. One of the biggest issues in my sector has and will likely continue to be limited in-process sample retains. So, it's essential to have well-trained analysts and operators handling and analyzing these materials to prevent waste.

Technology integration elevates the role of operators and analysts beyond mere data generation. These laboratory-based scientists, whether at the CDMO or the partnering organization, should be leveraged as the conduits and liaisons between the partnering organization and the CDMO. This ensures that those most familiar with process, analytics, and sample handling have the most frequent and direct interactions with their partnering organization.

This also necessitates that these professionals be trained in both the partnering organization's standard operating procedures (SOPs) and methodologies, as well as their own; the goal is that these professionals are proficient at conducting the same laboratory techniques and applying sample handling procedures in either laboratory space, be it at the CDMO or the partnering organizations.

This approach offers a multitude of benefits:

• Increased Confidence in Results: With a deeper understanding of the processes and methodologies used by both organizations, analysts can generate data with higher confidence.
• Identification of Gaps: Acting as liaisons, analysts are in a unique position to identify discrepancies or gaps related to sample processing or analytics. This allows for continuous improvement and ensures consistency throughout the entire process.
• Improved Communication: This model fosters better communication between partnering organizations. Operators and analysts from both sides become familiar with each other's workflows, leading to better alignment and synergy in their efforts.
• Enhanced Quality: Ultimately, this collaborative approach leads to an overall improvement in the quality of the product and its regulatory dossier for submissions.

Building A Cohesive Regulatory Narrative

When navigating the complexities of regulatory interactions and submissions for biopharmaceutical products, building a cohesive and unified narrative is paramount. This narrative, which will at one point incorporate nearly every functional group, must demonstrably showcase a consistent understanding and control of the product throughout its entire life cycle.

Building this narrative demands collective planning, mutual accountability, and a dedication to openness and dialogue. Crafting this narrative commences well before functional groups convene, ideally during the phase of partnership negotiations. While details of intellectual property might not be disclosed at this juncture, a regulatory blueprint can be drafted. This blueprint delineates explicit roles and responsibilities for each participant, ensuring all regulatory facets are considered.

For example, when collaborating with a CDMO for a cell therapy's lentiviral vector, discussions shouldn't solely focus on process and analytical readiness. Thorough dialogues about regulatory readiness are vital. This encompasses consideration of target markets, their unique regulatory stipulations, and the necessary measures to adhere to the requirements of competent authorities.

 The benefits of having multiple stakeholders, collaboratively contributing, are manifold:

• Robust Regulatory Package: Through collaboration, both companies contribute to a comprehensive understanding of the product and its manufacturing process, leading to a robust regulatory package with minimal discrepancies.
• Improved Risk Management: Early identification of potential regulatory gaps during the integration phase allows for proactive resolution, reducing risk and ensuring a seamless regulatory pathway.
• Enhanced Patient Safety: A robust, collaborative narrative instills confidence in the product's quality and consistency, ultimately ensuring the safety and efficacy of the therapy for patients.

The rise of CDMOs presents a significant opportunity in bioprocessing. By embracing a new paradigm of collaborative integration, biopharmaceutical companies can leverage external expertise while maintaining control of their technology and processes. By investing in internal scientific capabilities and building a narrative of continuity through early and open communication, this collaborative approach can unlock the full potential of CDMO partnerships, ultimately leading to the development and delivery of high-quality biotherapeutics that improve the lives of patients.

About The Author:

Alex Santos has brought multiple autologous CAR T cell and gene therapies to first-in-human trials as an individual contributor and expert in CMC and analytical development strategy. As a regulatory scientist and consultant, Santos has collaborated to bring several cell and gene therapies, vaccines, advanced biologics, and combination products to market through competent authorities such as the FDA, EMA, MHRA, NMPA, and PMDA.  He has served in progressively responsible scientific and leadership roles within the biotechnology and biopharmaceutical community, leveraging his experience working for companies such as Shire Human Genetic Therapies, Bluebird Bio, Be Biopharma, and Voisin Consulting Life Sciences. Alex holds an M.Sc. in medicinal chemistry from the University of Coimbra in Portugal, and a Master of Public Administration (MPA) and a B.A. in psychology from Clark University in Massachusetts.