Responding to cell & gene fill-finish and automation scale-up challenges

Before delving into some technical details of cell and gene therapy manufacturing, it’s worth pausing to reflect on the human stories that drive this innovation. These therapies are not just scientific marvels - they're changing lives.

The human impact

Take, for example, a mother with young children diagnosed with stage four non-Hodgkin lymphoma with probably weeks or a few short months left to live. After exhausting all standard treatments, she was given an experimental CAR-T cell therapy. Within a month, her cancer had vanished - her own genetically modified T-cells had eradicated the disease.

Then there’s a young boy with spinal muscular atrophy, a genetic condition once deemed a death sentence. After receiving a single gene therapy infusion, his condition stabilised, allowing him to build strength and look forward to a future that once seemed impossible. These are not outliers, they’re emblematic of a revolution in how we can now treat disease.

Why 3P innovation entered the space

At 3P, we’ve always aligned ourselves with complex, high-value pharmaceutical manufacturing challenges, such as inhalers, sustained release formulations and injectable drug delivery devices. So when cell and gene therapies began to gain momentum, we recognised a familiar pattern: transformational therapies facing barriers around scale, cost, and quality, with a real and present need for innovative automation.

This isn't just another biotech trend, it’s a paradigm shift in medicine. And it needs the right manufacturing infrastructure to increase access to patients and to reduce costs.

Manufacturing: From lab to line

Most cell and gene therapies originated in academic settings, where open systems and manual handling were common. These environments were never designed for commercial production or global distribution.

At scale, contamination risks, process inconsistency, and labour constraints demand a shift toward closed or functionally closed systems. More production systems are running within aseptic isolators and highly controlled equipment to maintain aseptic conditions.

Isolators are capital-intensive and slow to commission - but they offer superior long-term efficiency and lower per-patient costs, especially when dealing with high-value therapies.

Economic pressures and the workforce challenge

These cures don’t come cheap. Many costing more than £1million, which still represents good value compared to the costs of a lifetime of chronic care.

However, their production demands highly skilled labour and strict compliance with global regulations. The shortage of qualified aseptic technicians is a real bottleneck. Automation isn’t just about efficiency and costs, it’s about patient access.

Automation: The industry’s next leap

History shows us that transformative shifts often hinge on manufacturing innovation. In the early 20th century, Ford’s assembly line didn’t just reduce costs, it made cars accessible to the masses. Cell and gene therapy needs a similar moment.

Automation can lower cost per treatment, improve consistency and quality, reduce reliance on highly skilled labour and enable faster scale-up.

At 3P, we’re focused on making that leap a reality. Within this sector we decided to play to one of our pre-existing strengths which was aseptic fill-finish. For cell and gene this is inextricably linked to the primary drug container.

Containers and cold chain complexities

There are three main types of primary drug containers to consider: cryovials, vials, and bags. These therapies are stored and shipped at cryogenic temperatures, which limits the materials that can be used to manufacture the containers. Cryovials are used during development and again for QC sampling. Approved therapies are ultimately filled either into bags or vials. While autologous therapies tend to use bags, allogeneic therapies more commonly use vials due to the larger number of primary containers required.

Each container type has trade-offs. Bags, for instance, can be made to pretty much any size and shape but are more likely to fail and rupture during cryogenic storage. This is due to weak points around creases formed during filling – it is no accident that they tend to be constrained within an aluminium tray to try to protect them. Vials come in fixed sizes but are more robust. Vials also tend to be preferred by care providers due to familiarity. Additionally, many of these bag and vial systems are proprietary to the cell production equipment provider. This locks in end users and limits flexibility whilst driving up costs. 3P understand this which is why our equipment is agnostic to the primary drug container.

Regulatory demands and technical design

Manufacturing in this space is governed by stringent global standards like Annex 1 and 21 CFR Part 11. These regulations dictate everything from airflow and cleanroom design to electronic record-keeping and material traceability. It takes a village to raise a child and it takes a complex integrated system to produce a cellular therapy – the automation is a small but important part.

At 3P, we engineer every detail to ensure our designs meet these ever more exacting standards. We design our transmissions with compact, high performance servomotors. These are hidden within technical areas sealed away from the processing area (the processing area is where the product and containers are processed). Everything in the process area is designed from a hygienic perspective, even the bolts we use are custom-engineered, polished and some even have an integrated seal. We have designed our own robots to create cartesian (X-Y) movement from rotary motions through seals because that is more hygienic than more conventional linear systems. We understand the value of a product failure such that we integrate monitoring systems as standard. It's a technical minefield, but one we’re well equipped to navigate.

Tailored solutions for a complex sector

With a proud heritage developing custom manufacturing systems for the pharmaceutical sector, we were able to harness our engineering talent to develop platform technologies tailored specifically for the cell and gene space. We are also able to customise these platform technologies in response to client demand.

When designing any of our platforms, we aim to create systems that are as compact as possible - we understand that cleanroom space is always at a premium. We also integrate feedback sensors so that, from a QA perspective, the machine can confirm it has produced a good product. When you’re handling a therapy worth over a million pounds per dose, the cost of a failed fill is simply too high.

When we focused on vial filling we ensured that our compact benchtop system included weight feedback to ensure every fill, from first to last, was measured. We ensured that the open time before a stopper is added was minimised. We also designed an associated crimper. Like the filler it was compact and came with force feedback to ensure every crimp was measured. We used rotary crimping principles borrowed from larger machines which we knew produced a minimum of particulate. Finally, we ensured that the two units could sit side by side within a biosafety cabinet to save cleanroom space.

When it came to cryovial filling we again designed a system specifically for this use case. We again designed a compact system with integrated weighing. We also ensured that it could process a standard rack of cryovials and fill each one in turn. To protect the cells, we ensured that the time from unscrewing the cap, to filling, to recapping, was kept to a minimum. We also understood that cell viability is a crucial quality measure which is adversely impacted by long and inconsistent fill times after cryopreservant (usually DMSO) is added. Overall processing time was made as short as possible.

These machines are now built to stock due to growing demand, and with good reason. We understand that many of our clients have aggressive timelines to get their multi-million pound therapies to market. If we can save a few valuable months by stocking equipment, we are more likely to win orders.

Thus far, I’ve only mentioned our benchtop range. The same attention to detail is clearly evident in our larger robotic fill-finish equipment, designed to fill tubs of primary drug containers. The automation is housed within a complementary isolator, engineered by the same team who designed the automation itself. This holistic approach - designing both the isolator and automation together - has resulted in what we believe to be the most compact robotic fill-finish platform available. And if, like most of our clients, you’re short on cleanroom space, that compactness really matters.

3P innovation’s vision for the future

At 3P, we believe that the prosperous future for advanced therapies will increasingly depend upon associated automation. Not just because it reduces cost, but because it ensures quality, and repeatability. This in turn will increase patient access for these lifesaving therapies.

We’re proud to be part of the solution - offering not just equipment, but a partnership grounded in technical depth and a deep understanding of regulatory and operational realities. Our goal isn’t to build machines, it’s to enable cures.

If cell and gene therapies are the future of medicine, then automation is how we bring that future to life.

Explore cryoFIL®: 3P innovations cryovial filling platform.