In the high-stakes world of aseptic manufacturing, the distance between a successful batch and a multi-million-euro “atypical finding” is often measured in millimeters—the diameter of a tubing line, the viscosity of a bulk solution, or the precise pressure of a nitrogen blanket.
As a CDMO, our mission is simple but absolute: Patient Safety through Process Integrity. But achieving that integrity is not a matter of luck. It’s the result of what we call the “Technical Narrative” the deep, often grueling work of feasibility testing that happens long before the first GMP seal is broken.
I have spent 13 years on the floor at our Jura site. In that time, I have seen that the most expensive mistake a client can make isn’t investing in feasibility; it’s assuming that a process which works on paper will survive the transition to a Restricted Access Barrier System (RABS).
Feasibility is our “detective work.” It is where we bridge the gap between a client’s preclinical success and the operational reality of our cleanrooms. We aren’t just looking for “success”; we are looking for the boundaries of failure.
Bridging Theory and the Floor: The “How” of De-Risking
Feasibility is our “detective work.” It is where we bridge the gap between a client’s preclinical success and the operational reality of our cleanrooms. We aren’t just looking for “success”; we are looking for the boundaries of failure.
1. The Physics of the Fill
When a client presents a molecule, we must decide how to move it. We often debate the merits of peristaltic versus rotary piston pumps. While a rotary pump offers high precision, it can be “hard” on sensitive proteins. A peristaltic pump is gentler on the product but introduces variables like tubing shore hardness (ductility) and diameter.
We use semi-automatic pilot pumps to test these interactions. If a tubing line is too soft, the pump’s occlusion might degrade the material over a long run; if it’s too hard, we lose dosage accuracy. We solve these “micro-challenges” during feasibility, so they don’t become OOS (Out-of-Specification) investigations during a live run.
2. The Filtration Hurdle
One of the most critical “hidden” risks is API adsorption. I have seen cases where the sterile filter membrane—the very thing meant to ensure safety—ends up “trapping” the active ingredient, effectively stripping the product of its potency. Through feasibility, we test different membrane materials and saturations to ensure that what goes into the filter is exactly what comes out.
3. Lyophilization: The Art of the “Cake”
Transferring a lyo cycle from a client’s lab to our industrial scale is never a 1:1 move. We utilize a dedicated development lyophilizer to recreate the cycle. We monitor the “cake” formation: Does it collapse during primary drying? Does it “crawl” up the vial? By recreating these thermal and pressure conditions in a non-GMP environment, we optimize the cycle for stability before it ever touches the commercial line.
The Human Element: Precision and Adaptability
Feasibility requires a specific mindset: a blend of rigid compliance and creative problem-solving. A perfect example occurred during after our RABS revamping. A client needed to transfer an API using a peristaltic pump, but the footprint of the pump was too large for the new RABS configuration. The “Pragmatic Expert” doesn’t just say “no.” We look for an alternative.
We proposed—and rigorously tested—a nitrogen pressure transfer system. The client was initially concerned about vial integrity under pressure. We didn’t just give them an opinion; we ran the tests, proved the safety margins, and delivered a controlled, aseptic solution that met the new environmental constraints without delaying the project.
Problems in aseptic manufacturing are inevitable. The goal of feasibility isn’t to pretend problems won’t happen, but to ensure that when they do, we have already mapped up the solution.
Strategic Stewardship of Rare APIs: Engineering with “Liquid Gold”
In the preclinical and early clinical phases, API is more than just a component; it is “liquid gold.” Its scarcity and cost should never be a barrier to securing your process. At Adragos Jura, handling precious molecules is part of our daily reality. We have developed an agile testing methodology to generate robust data without wasting a single drop of active product.
Our strategy for “de-risking” while protecting your inventory relies on three pragmatic levers:
- Representative Placebos and Surrogates: For the majority of filling and transfer tests, we lead with water or substances like BlanoseTM CMC. This allows us to mimic high density and high viscosity to ensure the equipment handles the physical load without mobilizing the actual API.
- ·The Utility of Expired API: This is a highly effective, real-world approach. It can happen that clients send us expired API specifically for feasibility. It allows us to perform authentic filtration and transfer tests, adapting the manufacturing process and verifying membrane compatibility under real conditions—with zero financial impact on your clinical stock.
- Micro-Batch Modeling: When using the final API is non-negotiable, we reduce batch sizes to the absolute technical minimum. By designing tests with very small volumes, we can identify and fix Critical Process Parameters (CPPs) while preserving as much material as possible for your actual GMP runs.
Engineering the Future
At Adragos Jura, we are moving toward a Standardized Excellence model. By offering clients a suite of validated “standard” configurations for pumps, tubing, and filters, we can accelerate timelines while maintaining the highest safety margins. For the “exotic” projects—the highly viscous, the highly sensitive, or the large-bulk transfers—we apply the full weight of our MSAT and operational expertise.
Feasibility isn’t a delay; it is the “Right First Time” insurance policy that protects your molecule, your investment, and ultimately, the patient.
