Cell and gene therapies (CGTs) 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 10 common errors and solutions when undertaking the design and build process.
1. Saving in initial capital expenditure, losing in long-term production
A critical aspect of CGT 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. The realities of an operation over the long term (understanding the ins and outs of production processes, planning for 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 CGT 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. Following drug substance principles instead of drug product principles
Much of the risk in misapplying traditional pharmaceutical standards to CGTs arises from adhering to drug substance standards rather than drug product standards. The latter is considered a non-sterile process in design and is subject to additional formulation and filtration. This isn’t the case in cell and gene manufacturing, where, in many instances, the final drug product and drug substance are nearly identical. What does this error practically look like in the cleanroom? Misgraded operations, improper pressure cascade design, and skip-grade setups are aspects that can be easily improved by adopting a more principled aseptic processing approach.
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