Contract development and manufacturing organizations (CDMOs) are increasingly playing a vital role in the cell therapy landscape, helping to minimize risk, lower costs, and broaden accessibility of advanced medicines to more patients. The decision to outsource production services to a CDMO, while important, is merely one of many on the road to clinic.
The “contract” aspect of CDMO nomenclature would suggest a straightforward transactional agreement but viewing the CDMO as a mere service provider is a missed opportunity. In fact, there is much to gain by seeking a true partner organization with an experienced team that understands your science, shares your values, and is committed to your success. Choosing a long-term CDMO partner requires thoughtful diligence, and possibly more time than anticipated, but the advantages and rewards make this process well worth the extra upfront work. In this context, the contract, and the many facets of the partnership sit at the core of a mutually beneficial relationship. Built on trust, this contract will carry the lifecycle of the entire clinical trial process.
Better CDMO Relationships Begin with a Well-Crafted Contract
As one who has established many longstanding relationships and fostered collaborations throughout her career, Rona Singer Weinberg knows firsthand how to lay the foundation for success. Now retired and serving as a program consultant, the founding scientist and cell therapy pioneer of Comprehensive Cell Solutions (CCS) reiterates advice from her plenary presentation at this fall’s CGT Manufacturing and Commercialization Summit: The success of your program begins with a carefully constructed contract.
The success of your program begins with a carefully constructed contract. More than an agreement between you and your chosen CDMO, the contract codifies shared plans and expectations. When done well, it serves as a safeguard, ensuring that the interests of both parties are protected throughout the product development journey. The clarity and comprehensiveness of these agreements are paramount. What follows is a summary of her recommendations.
Define Your Goals.
The typical developer-CDMO relationship is focused on clinical or commercial manufacturing; however, in a climate dampened by dwindling investment, many biotech companies are finding value in earlier engagement with a CDMO. Leaning into a CDMO’s development expertise and understanding of regulatory requirements can help you to refine processes, optimize analytical testing, and make informed decisions with the end in mind. This in turn helps to avoid costly mistakes early on. The goals of the relationship may differ depending on when you approach your CDMO, but it is important for you to articulate realistic, phase-appropriate goals:
- Product and Process Development: The contract should emphasize the evaluation of new technologies and equipment for the development of the product and manufacturing process while enhancing quality and safety. Maximizing throughput and reducing overall processing time should also be part of the contract.
- Processing and Cryopreservation: Ensuring sufficient manufacturing capacity and drug product storage along with adequate resourcing and access to technological capabilities are instrumental and important factors that are specified in the agreement.
- IND Submission: For clinical trials, Investigational New Drug (IND) submissions are a pivotal milestone. Defining manufacturing operations along with drug substance and drug product specifications must be followed and the contract should outline responsibilities and timelines for this critical regulatory step.
- Clinical Trials: From Phase I to Phase III, the contract should provide a roadmap for conducting these trials, including potential need for process and analytical testing optimization and validation.
- Commercial Manufacturing: Will the commercial product be manufactured by the CDMO or transferred to another manufacturer in the future? Does the CDMO offer post-market regulatory support?
Include These Critical Components.
A robust contract should delve into key considerations and delineate responsibilities for all parties involved. Avoid assumptions; details may not always be evident. Be sure to address:
- Tech Transfer and Training: Allocate adequate time for the process that sets the stage for your product’s development.
- Procedure Validations: Define the scope and extent of validation procedures, which are essential for quality assurance.
- Equipment and Supplies: Avoid bottlenecks and protect your program with plans for procuring necessary equipment and supplies.
- Production Schedule and Capacity: Avoid delays with clear expectations for production schedules and capacity.
- Analytical Development (AD): Proper conduct of safety, identity/phenotype and potency testing takes time; make sure to factor in the scope and depth of AD.
- Regulatory Submission and Approval: Don’t leave room for surprises. Define and articulate the path to regulatory approval. Consult early with regulatory agencies whenever possible to ensure your planning aligns with their expectations.
Determine the Details for Technology Transfer, Training, and Documentation.
The contract must address the critical questions of who, what, where, and when it comes to technology transfer, training, and documentation to ensure a fully documented transfer. This allows for both companies to be in alignment regarding the transfer of knowledge, the training of personnel, and the precise protocols to be followed.
Establish Timelines.
Forget “pie in the sky.” A cell therapy program demands meticulous planning and the definition of realistic expectations that account for the following:
- Tech Transfer and Training: Allocate adequate time for the process that sets the stage for your product’s development.
- Procedure Validations: Define the scope and extent of validation procedures, which are essential for quality assurance.
- Equipment and Supplies: Avoid bottlenecks and protect your program with plans for procuring necessary equipment and supplies.
- Production Schedule and Capacity: Avoid delays with clear expectations for production schedules and capacity.
- Analytical Development (AD): Proper conduct of safety, identity/phenotype and potency testing takes time; make sure to factor in the scope and depth of AD.
- Regulatory Submission and Approval: Don’t leave room for surprises. Define and articulate the path to regulatory approval. Consult early with regulatory agencies whenever possible to ensure your planning aligns with their expectations.
The Value of Partnership
In summary, there’s much at stake. The right CDMO can deliver the expertise and infrastructure necessary to navigate the complexities of your advanced therapeutic’s development, ultimately helping you make the most of precious resources on the path to patients. Rather than selecting a transactional vendor, a better approach is to develop a relationship with a true partner who can help you achieve the maximum value from your investment. As a partner that shares the same goals, you can expect your CDMO to be fully transparent, ready for in-depth conversations, and eager to explore options together. The details, then, are captured in a robust contract that lays the foundation for a successful alliance, guiding all stakeholders throughout the execution of your program.
With its Draw-to-Thaw™ portfolio of cell therapy services, Comprehensive Cell Solutions is not your typical CDMO. Few organizations, if any, can provide support from matched donor management and apheresis collections through cryopreservation and recommended thaw protocols, and everything in between. These guidelines are derived from our many years of collaborative relationships with treatment centers and developers of commercial therapeutics who trust CCS’s unique experience with the spectrum of advanced therapy manufacturing. Recent expansion to facilities in Houston, TX and Louisville, KY extend CCS capabilities beyond early phase development to commercial scale manufacturing.
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