In other words, the phase-appropriate quality approach emphasizes the requirements of the current phase of the product (i.e. cell therapy) development cycle. This approach recognizes that the strategies for maintaining the quality of the product may change over time—creating a small measure of flexibility.
Some key concerns in each phase under this product development methodology include (but may not be limited to):
Materials accepted on cost of acquisition (CoA) and critical vendors qualified
Processes validated with PPC identified and controlled
Validation of analytical methods
Materials have been fully qualified and tested upon receipt as appropriate
Defining Development by Design
Development by Design, or DbD, is a process that takes into account considerations of quality, scalability, sustainability, and cost of goods to smooth out the path from phase 1 clinical trials to commercialization.
The 4 Pillars of DbD:
There is heavy reliance on processes to meet CQAs. Automation, closed-system design, and compliance with applicable regulatory standards (like cGMPs) are key for improving the robustness and control of processes.
2. ScalabilityThe ability to scale up from limited clinical trials to large-scale commercial production is a key concern for the viability of a product. Anticipating quality risks and other challenges that come when the scale of production changes from clinical trials to commercialization is necessary for minimizing disruptions.
Even when quality and scale objectives are met, there is a risk that manufacturing cannot be sustained for the full lifecycle of the cell therapy product. To mitigate sustainability risks requires full assessments of the entire supply chain and the overall manufacturing process.
4. Cost of Goods (COGs)
Cell therapy often has a relatively high COG compared to more traditional pharmaceuticals. Minimizing the cost of goods can often impact other DbD pillars, such as the sustainability of the cell therapy.
This approach to cell therapy development leans more on taking the long view—planning ahead early on in the process to save time, money, and energy during later development cycles. The benefit of using this methodology is that it can help cell therapy developers plan out the path to commercialization with greater consistency.
Are These Approaches Mutually Exclusive?
Not necessarily. In most cases, if a manufacturer is engaging in the development by design methodology, they’re going to need to take into account the phase-appropriate quality concerns anyways for each phase of their clinical trials. After all, if the quality requirements of the current cell therapy development phase aren’t being met, then the therapy won’t be able to achieve FDA approval.
Basically, DbD’s planning requires the therapy developer to take into account the needs of different production phases, so phase-appropriate quality could be considered a part of the DbD process. DbD just front-loads many considerations so that the development process can proceed more smoothly from one phase to the next.
Phase-appropriate quality and development by design are closely-related approaches to cell therapy development that can go hand-in-hand. Each can be used to set goals and quality standards for your cell therapy development and help you overcome the challenges of getting from phase 1 clinical trials all the way to commercialization.
Brian Hampson, Vice President, Global Manufacturing Sciences and Technology, Hitachi Chemical Advanced Therapeutics SolutionsBrian Hampson is Vice President, Global Manufacturing Sciences and Technology, tasked with leading Hitachi Chemical Advanced Therapeutics Solutions ("HCATS") Center for Innovation and Engineering (I&E).
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