Cell and gene therapies continue to be an avenue for product development across the Life Sciences and illuminate new possibilities for patient outcomes. These products have led to a wholesale shift in how manufacturers approach and implement cGMP operations and to a reimagining of the production facility. AST’s Principal CQV Engineer, Jason Rossi, weighs in on common errors and solutions when undertaking the design-and-build process.
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1. Saving in Initial Cap Ex, Losing in Long-Term Production
A critical aspect of cell and gene therapy facility design is strategic resource allocation and how early capital investment assessments affect long-term design outcomes. There’s a clear need for a fiscally responsible and advantageous plan at the foundation of a facility design. Too often, short-term cost containment results in the deferral or elimination of infrastructure that ultimately becomes essential. Front-end savings rarely translate to better total cost of ownership. Taking the long view of the operation—understanding the ins and outs of production processes, planning for the realities of day-to-day operations and logistics, and anticipating the scale-up of production—should all serve as fog lines for your initial resource planning.
2. Not Going with the Flow – Bottlenecks and Material Transfer Issues
Optimal cell and gene facility design is, at its core, all about the flow. Flow in and out of the facility is crucial to regulatory compliance and contamination control. And one of the more underappreciated and practical strategies of building a facility is designing around your personnel, material, and process ingress and egress. Cross-traffic between clean and dirty pathways or commingling of waste and product streams introduces significant risk to contamination control and GMP operations. A strategic suite design with distinct paths and areas for product and waste not only reduces risk but also allows for other economical utility-based solutions to be implemented.
3. Insufficient Warehouse Space
One of the first areas either underestimated or sacrificed during facility planning is warehouse capacity. A common rejoinder is that warehouse space does not generate revenue; production space does. However, no aspect of cell and gene therapy production occurs in a vacuum. While there are common workarounds (e.g., renting warehouse space), numerous challenges can arise. What are the downtime risks of managing materials through an off-site facility? Can your batch afford a delay if a component is dropped or lost? Part of the holistic emphasis inherent in Quality by Design principles is to account for any and all factors that could affect your process.
4. Purpose-Built but with No Flexibility
Many facilities are necessarily built around product specifications, and rightfully so. However, a common misstep is not anticipating the flexibility necessary to navigate a sometimes unpredictable development process. Process optimization, changing product pipelines, and scaled-up production can all lead to new demands on the facility. Having contingencies and projections in place is essential. The better you understand your process and associated outcomes, the more prepared your facility will be. A phrase we use often on my team is, “Flexibility is the antidote for uncertainty.”
5. Not Getting Input from Multiple Stakeholders in the Design Phase
It seems intuitive, but it’s common for stakeholder groups not to have open communication or be included during the initial stages of planning and design. Designing around the process and the GMP demands of an ATMP facility is essential, and engineering teams often don’t have those inputs from SMEs on the ground level of a project. Getting a clear CQV perspective, along with feedback from your facility operations team and ultimately the operators who will be running the equipment, will save critical time and prevent costly scope adjustments down the line. If the goal is a robust, efficient cGMP cell and gene manufacturing facility, comprehensive expertise, resources, and best practices will set pharmaceutical manufacturers up for long-term success.
