“Projects quite often realize too late that their R&D process cannot just be copy-pasted from the lab into the manufacturing facility.”
Dr. Jenny Prange is Head of Project Management at the Regenerative Medicine Technologies Platform (RMTP) at Wyss Zurich, an accelerator embedded within ETH Zurich and the University of Zurich. With a background spanning molecular biotechnology, a PhD in human physiology, and hands-on experience translating an advanced therapy medicinal product (ATMP) from bench to clinical trial at University Hospital Zurich, Jenny brings both scientific depth and manufacturing expertise to early-stage biotech projects.
In this PharmaSource podcast episode, Jenny explains why the leap from academic research to GMP-ready clinical manufacturing is consistently underestimated, what it actually takes to build a robust CMC strategy, and how translational facilities like Wyss Zurich are filling a critical gap in the biotech development landscape.
The Regulatory Knowledge Gap
The most consistent challenge Jenny encounters when a new project arrives at Wyss Zurich is a fundamental lack of regulatory literacy. Most team members come from purely academic environments where concepts like the Investigational Medicinal Product Dossier (IMPD), the Investigator’s Brochure, or clinical study protocols are entirely foreign.
“Since most of the members of those projects are purely of an academic background, they have never heard of the IMPD before they come to us,” says Jenny. “The understanding that those important and comprehensive documents are the basis for setting everything up is just not there.”
This gap has direct consequences for project timelines. For example, one project at Wyss Zurich initially estimated just six months to translate its process from lab to clinical-grade production. In reality, it took two and a half years. Each time the team addressed one gap, another surfaced, and none could be skipped before moving into the clinic. The cause, Jenny explains, was that the researchers had no prior framework for understanding how long it takes to generate the required documentation, or to test that documentation in a regulated environment.
Why Poor Preclinical Documentation Creates Downstream Delays
One of the more preventable sources of delay, Jenny argues, lies upstream of the manufacturing translation process: the quality of preclinical documentation.
“The basis of it all is how well everything was documented in the preclinics,” she explains. “From my academic background, I know that the interest of supervisors in how well you document your experiments ranges from not interested at all to well… slightly interested, as long as you can generate a graph that is presentable for publication.”
This cultural gap between academic research practice and the documentation standards required by health authorities is one that the broader scientific publishing community is beginning to address. Peer-reviewed journals increasingly request robust foundational data at submission — the same data that regulators will eventually require.
Jenny sees greater alignment between publication standards and regulatory expectations as a meaningful opportunity to improve the quality and completeness of data entering the clinical development pipeline.
Materials and Reagents: The Hidden Compliance Challenge
One of the most tangible aspects of the academic-to-clinical transition involves the materials used in the manufacturing process. In R&D settings, reagents and consumables are typically research-grade: functional for generating experimental data, but not certified to the standards required for use in a clinical product.
“The classical situation is that material used in R&D labs is usually also R&D grade,” Jenny explains. “When you ask manufacturers, those materials most likely don’t have any certificates proving they’ve been tested for relevant analysis types, and those certificates are exactly what you need when you do clinical production.”
The Wyss Zurich team systematically reviews every material entering the GMP process, assessing which require replacement with higher-grade equivalents, which need additional testing, and which are missing critical data entirely, for example, stability or shelf-life information for starting materials such as fresh tissue or blood products. The cost differential between research-grade and GMP-grade materials is substantial, often more than double, which is why cost-constrained academic projects default to lower-grade materials during the research phase.
In some cases, a pragmatic middle ground exists. If a buffer component is available only with a sterility certificate but lacks endotoxin or mycoplasma testing, Jenny’s team will design an additional in-process testing step to compensate, ensuring the quality standard is met even when the commercial grade is not available.
What the Process Translation Actually Involves
When a university spin-out or early-stage biotech arrives at the RMTP, the process assessment begins immediately. The team evaluates the proposed therapy, the existing R&D process, and the infrastructure requirements needed to integrate that process into the cleanroom environment.
“What often surprises people is the scale of documentation required,” Jenny notes. “A one-and-a-half to two-page R&D protocol can easily become eight separate manufacturing instructions once translated into a GMP-compliant format.”
Beyond documentation, the translation process involves several parallel workstreams: characterizing and qualifying analytical assays (distinguishing in-process controls from release assays), defining a potency assay strategy, assessing which assays provide results fast enough to support timely product release, running technical batches, and ultimately performing process verification to lock the process ahead of clinical use.
The final step before clinical preparations begin is an aseptic process simulation, commonly called a media fill, which validates both the process itself and the operators carrying it out. For ATMPs, where every product is biologically distinct, Jenny stresses that there is rarely a one-size-fits-all solution. The potency assay strategy in particular requires early dialogue with regulators to align expectations.
Manufacturing as a De-Risking Tool for Investors
Beyond its regulatory function, manufacturing capability plays a strategic role in how early-stage projects present themselves to investors. Jenny explains that projects arriving at the RMTP are typically at a stage where compelling preclinical data exists, but investors remain cautious about the unknowns associated with human application.
“If biotechs approach investors with just ideas, there’s a huge risk associated. You don’t have preliminary data on how that would work in humans,” she says. “Wyss Zurich comes into play because we offer the project the chance of gathering that first clinically relevant data, and with that, they can reduce the associated risk for investors.”
In practice, this often extends to the design of Phase 1 trial protocols. While first-in-human studies are primarily safety-focused, Jenny notes that principal investigators (PIs) frequently seek to incorporate preliminary efficacy endpoints as secondary measures, recognizing that investors will look for any signal of therapeutic effect, even at an early stage.
The Broader CDMO Ecosystem
Jenny positions Wyss Zurich as a predecessor to commercial CDMOs. A translational bridge that prepares projects for the CDMO environment they will eventually need to enter.
“The higher hurdle is the jump from R&D to first-phase clinical trials,” she explains. “The jump from first to second phase is comparatively smaller. What we do is set the groundwork, and when a project leaves us, we can essentially hand over a package of documents to the CDMO so they can say, ‘here is our process, this is how we did it, let’s set it up here’. This can help the process go smoothly.”
Building Relationships With Regulators
One of the mechanisms Wyss Zurich uses to support regulatory preparation is access to Innovation Office meetings with Swiss Medic. Structured sessions where current and prospective projects can present their strategies, ask direct questions about CMC approaches, and receive a reality check from the authorities themselves.
“Projects can ask the regulators how they want to approach their CMC strategy, or what additional studies they would need before being accepted for a clinical study, and they get a reality check directly from the authorities,” Jenny explains. “For ATMPs especially, every product is different, so you have to come up with your own potency strategy. Getting input from regulators early is invaluable.”
The importance of early and ongoing regulatory engagement is the central piece of advice Jenny offers to biotech founders just beginning to think about their CMC strategy.
“Consider CMC as early as possible, and dedicate the right resources to it,” she says. “Hire someone specifically focused on this. These questions are too important to be tackled on a side note. Get external advice, not only from key opinion leaders, but from the authorities themselves — to understand what is expected, and also to understand what is realistic for your specific product. In the end, it comes down to building those relationships with authorities as early as possible.”
