Frequently Asked Questions
Manufacturing & Technology
Manufacturing Process
Q: What are the key challenges in scaling cell therapy manufacturing from clinical to commercial production?
The primary challenge is that the subtle "process noise" that is manageable (or even unnoticed) in a small-scale clinical setting becomes amplified into a catastrophic roar at commercial scale. The core issues are not just about making more of something; they are about battling inconsistency.
Most companies struggle because the manual, high-touch processes that get them through early phases are inherently noisy and hide process flaws. At scale, these flaws emerge as critical bottlenecks, leading to inconsistent cell viability, unpredictable potency, and outright batch failures. We've seen companies lose 18+ months and significant funding because they focused on scaling a process without first making it "bulletproof." The real challenge is achieving a state of control where your process is so robust, it consistently absorbs biological variability while producing a predictable outcome.
Would you like to discuss how a Process Robustness Roadmap could help you eliminate noise before it jeopardizes your timeline and budget?
Q: How do you ensure GMP compliance while implementing automation?
Our philosophy is simple: GMP compliance is a natural byproduct of a well-understood, robust process; it's not a layer you add on at the end. You cannot validate a "noisy," unpredictable process into a state of compliance. The key is to engineer a "quiet" process first.
When we help you implement automation, our focus is on building quality into the design from the start. This means:
Eliminating Noise: A process with minimal variability has fewer deviations, making validation straightforward.
Traceability by Design: Automated systems are implemented to capture every critical parameter digitally, creating an unassailable data trail for your batch record.
Controlling Change: We establish clear SOPs and change control protocols for the automated system itself, ensuring it remains in a validated state.
Many companies underestimate the complexity of validating automated systems, leading to regulatory delays. We help you build a process that is so well-controlled that validation becomes a confirmation of what you already know, not a discovery of new problems.
Equipment & Technology
Q: What automation technologies offer the best ROI for cell therapy manufacturing?
The highest ROI doesn't come from a specific piece of hardware; it comes from applying the right technology to a process that is ready for it. The most common mistake we see is companies buying expensive automation to fix a flawed, manual step—the classic "Automation Trap."
Our approach is to first identify the biggest sources of process noise and then select the technology that most effectively eliminates them. With that said, we typically find the highest returns in:
Closed, Automated Fluidics: This directly attacks operator-induced noise and environmental variability, providing immediate gains in consistency.
Automated Centrifugation/Washing Systems: Counterflow systems, for example, can dramatically improve cell recovery rates and reduce variability compared to manual methods.
Automated Formulation & Filling: This removes the risk of human error in critical final steps, ensuring dose consistency and sterility.
The key is to select configurable, modular platforms that can solve your biggest noise problem today and adapt as your process evolves.
Q: How do you evaluate whether to build custom automation or use off-the-shelf solutions?
This decision should be driven by the elegance and robustness of your process, not the other way around. A complex, "noisy" process often forces a company into expensive, high-risk custom automation because no standard equipment can handle its quirks.
Our evaluation is based on a "manufacturing-first" hierarchy:
Can we simplify the process itself? The primary goal is always to engineer the process to be so robust and simple that it fits a proven, off-the-shelf solution. This is the lowest-risk, most cost-effective path.
Can we use a hybrid approach? We often recommend using proven, modular platforms for standard operations (like cell washing) and focusing custom development only on the truly novel, proprietary steps where no off-the-shelf option exists.
Is custom automation the only option? If a custom solution is absolutely necessary, it must be justified by a rigorous cost-benefit analysis that includes not just the upfront build, but the hidden costs of validation complexity, long-term maintenance, and specialized operator training.
Quality & Business Strategy
Q: What are the critical quality control points in automated cell therapy manufacturing?
In a manufacturing-first mindset, the goal is for QC to become a verification step, not a constant firefighting tool. A "bulletproof" process reduces the burden on QC by being inherently consistent.
In an automated system, the most critical control points are those that monitor the health of the process itself in real-time, not just the final product attributes. This is proactive quality. Key points include:
Incoming Material Verification: Automated barcode scanning and verification to prevent wrong-reagent errors.
In-line Process Monitoring: Integrated sensors that track temperature, pressure, pH, and cell density at each transfer step, ensuring the process stays within its validated "quiet" state.
Automated Viability/Count Checks: In-process checks after critical steps (like centrifugation) to immediately flag deviations.
The goal is to design a system with built-in quality checks that can pause or flag a batch if a parameter drifts, allowing for intervention before the entire batch is compromised.
Q: When is the right time for a cell therapy company to invest in manufacturing automation?
The question isn't just when to invest, but what to invest in at each stage. Waiting until commercial launch is too late, but over-investing in the wrong technology too early is equally disastrous.
We advocate for a staged, pragmatic approach that aligns with your development and funding runway:
Phase I: Invest in Process Understanding. This is the time to hunt process noise, simplify manual steps, and design for robustness. The "automation" here is intellectual—designing a process that will be easy to automate later.
Phase II: Invest in Modular, High-Impact Automation. Once core parts of your process are stable, implement proven, off-the-shelf systems for your biggest noise sources (e.g., closing a critical cell wash step). This generates immediate consistency gains and valuable data.
Before Phase III: Invest in the Full, Integrated System. With a "bulletproof" process now defined and de-risked, you can confidently invest in the full-scale automation platform required for your pivotal trial and commercial launch.
This stage-gate approach ensures you avoid the Automation Trap, deploy capital wisely, and build a process that is ready for commercial success.