Implementing a multidisciplinary approach in cell and gene therapy product development is critical to the product’s eventual success or failure. In our experience, the consequence of not effectively developing a product in early-stage development is that often lifesaving treatments are scrapped or delayed by several years.
During a presentation in January 2021, Dr. Tal H. Salz, a gene therapy reviewer at FDA, concluded that Sponsors who do not use a multidisciplinary approach in early-stage development tend to have lower rates of success for the following reasons:
So, the question becomes: how do we solve this? The answer is to implement a multidisciplinary approach in early-stage development utilizing current guidance from the applicable regulatory agency(ies).
In January 2020, FDA published a guidance document entitled “Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs),” which includes a number of recommendations for how to establish cell and gene controls. Most of the guidance’s controls require a multidisciplinary framework to implement.
Establishing effective controls for cell and gene therapy products is a large undertaking. Our recommendation is to start with the end in mind. In this case, understanding patient needs as well as requirements for the final product (aimed at labelling of the drug product) and ensuring you create a realistic roadmap from your starting point through each of the milestones to your destination.
One of the most critical components in implementing a multidisciplinary approach is building a team that matches the deliverables and assigning responsibility for the key CMC sections as well as quality and regulatory oversight. Traditionally the development team provides biophysical characteristics with the related list of potential critical quality attributes (CQAs), critical material attributes (CMAs), and critical process parameters (CPPs) for the treatment. The biophysical characteristics are then vetted through quality to confirm that the CQAs can be tested and then through a qualified regulatory team who can confirm the effectiveness of the CQA to characterize effective product.
Next, the team needs to characterize the process used to manufacture the product. This requires the knowledge of formulation and process optimization subject matter experts to effectively identify critical process parameters and critical material attributes and the applicable controls that can be implemented to consistently maintain acceptable limits for identity, strength (potency), quality, and purity.
From there, you need to develop your supply chain with raw materials that can consistently provide the starting materials to effectively run your process. Robustness trials in the form of design of experiments on relevant parameters (e.g. potency, expression, quality, and purity) are key points that regulatory authorities will look at.
At this point we have individuals from quality control (QC), development, regulatory, and supply chain on our team, but we also need quality assurance to make sure that what is being developed meets expected criteria. Quality assurance builds the framework to ensure abnormalities, mitigations, changes, plans, and controls are effectively administered and documented.
Additional team members should include operations, environmental toxicologist, and engineering. Operations experts review the developed process to determine what is needed to transform a bench scale process to a commercial process, including movement from manual processing to automated, associated controls, and process checks. The engineering team reviews the process and identifies facility, process equipment, and utilities. The environmental toxicologist is needed to review the process, raw materials, and final product to assess the impact on the environment and to ensure a controlled environment is established. It is important to have a team with this knowledge to make sure what is developed can make it to the next phase in the product lifecycle and that each deliverable adds value to the next phase.
Oftentimes development teams do not have access to all these skillsets. ProPharma Group’s Cell and Gene Therapy Center of Excellence has the best people in the industry who can round out your team and craft the development profile including clinical application, monitoring, analytical tests, filing profile, policies, procedures, protocols, or prepare for INTERACT or other regulatory meetings.
The benefit of an agile management approach is that the team can quickly adapt to modifications and understand the impact on achieving goals. The agility starts with the goal and breaks out the deliverables, the flow, and the tasks with the execution teams. Using an agile methodology allows a majority of your team’s time to be spent working on delivering the product, rather than meeting to discuss other topics. The agile approach also activates team members to help out when tasks don’t go as planned or when additional resources are available to expedite delivery before concerns become issues.
Are you in the process of developing a cell and gene therapy product? Although it is ideal to complete in early-stage development, implementing a multidisciplinary approach to product development is critical regardless of where you are in the development lifecycle. Our team of experts can help with all of your cell and gene therapy-related needs at any point in development. Contact us today to learn more about our breadth and depth of expertise and how we can help you reach the next milestone.
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