Hybrid Facilities for Flexible Biologics Scalability

Hybrid facilities provide necessary flexibility to biologics manufacturing

We’ve compared advantages for single‑use plastic and multi‑use stainless steel bioreactors over a series of blogs. Here, we’ll look at use cases for both single‑use and multi‑use skids in biologics manufacturing and discuss how they can be used cooperatively in hybrid facilities.

What is a hybrid facility?

A hybrid facility uses a combination of single- and multi‑use skids to produce drugs, whether large‑molecule biologics or small‑molecule APIs. While nearly every facility uses at least some disposable components, not even state‑of‑the‑art manufacturing technology can use 100% disposables (especially when operating at scale). In reality, almost every manufacturing site is a hybrid facility, whether scale‑up, clinical, or commercial.

Advantages of single- and multi-use skids for biologics manufacturing

Single‑use advantages

  • Single‑use skids have much lower startup costs and much higher availability than stainless steel skids.
  • They are generally considered to be more environmentally friendly.
  • While still highly customizable, they are more standardized than stainless steel, and can be qualified and validated very quickly. Standardization comes with a broader array of use cases and shorter lead times on new equipment.

Multi‑use advantages

  • Stainless steel skids bring higher capacities and the opportunity for full customization.
  • They are generally cheaper over the full cost of the lifecycle.
  • Multi‑use reactors are difficult to mishandle, offering superior product integrity and higher confidence in the safety of operators.

Complementary, not competing

Single‑use skids achieve higher yields than multi‑use skids in equivalent volumes, but they are primarily available for small bioreactor volumes and have capacity limitations. Stainless steel bioreactors can often be used in cases where single‑use skids are limited, such as for large batch sizes.

The optimal mix of stainless steel and single‑use skids and components will depend on whether the facility is used for scaling, clinical, or commercial production. Both the batch size and the lifecycle costs will vary based on the setting.

Contract manufacturers have a different set of priorities

The considerations of an engineer at a contract manufacturer are entirely different than those of an in‑house manufacturer at a pharma company — regardless of the scale of operation.

The key reason is that contract manufacturers require a higher level of flexibility at their facilities than traditional pharmaceutical setups. Whereas pharma companies tend to be dedicated to a single drug, a contract manufacturer must be ready for rapid changeovers between campaigns. (As a side note, it will be interesting to watch if this changes over the next several years for pharma companies moving from solely focusing on blockbuster drugs to developing orphan drugs, genetic therapies, and other treatments requiring only small batch sizes).

This is likely why CMOs were early adopters of single‑use bioprocessing technologies: they were able to increase batch success and minimize contamination risk, while also achieving savings to the bottom line from reduced cleaning requirements. Further, this meant fewer processes to be validated.

Designing a hybrid facility

Optimal facility layout and automation strategies are specific to the types of equipment used. A roundtable published in American Pharmaceutical Review strongly recommends first choosing the production volumes necessary for each manufacturing step, and then moving on to determine the optimal solution for each skid or piece of equipment. Footprint constraints, connectivity, and specific skid preferences all play a role in determining the best solution.

Example considerations for a hybrid approach

  • Upstream stainless‑steel skids are totally customizable. Reusable bioreactors and fermenters can be much bigger than single‑use reactors, which are limited by oxygen transfer.
  • Single‑use reactors can achieve higher cell densities than multi‑use reactors in the same volume.
  • Stainless steel requires a fair amount of fixed infrastructure for the delivery of cleaned steam, while single‑use equipment is more mobile, often on wheels, for easy reconfiguration of manufacturing areas.
  • Centrifuges are available with fully disposable contact surfaces, and can handle up to about 700 L/hr.
  • Alternating and tangential flow filtration equipment is available fully disposable, to handle up to 1000 L/day.
  • Single‑use chromatography and filtration equipment is widespread — only 1% of large‑scale chromatography columns were single‑use in 2010, a number which jumped to 37% by 2015.
  • Raw materials and buffers mixed in single‑use bags are often added into stainless steel production vessels.
  • Samples may be transferred from stainless steel vessels into single‑use testing equipment.
  • Some stainless steel skids require only chemical cleaning, not steam sterilization. As sterile steam generation presents a challenge and large cost, the lifecycle cost of stainless steel drops dramatically when it is not required.
  • Single‑use facilities can generally get validated for clinical trials in a faster and more cost‑effective manner.
  • Single‑use facilities require more confidence in your suppliers — who need to confirm that they are supplying clean, sterile equipment and will be able to deliver inventory as necessary.
  • Single‑use consumables necessitate holding inventory, which requires physical space (or prompt vendors) and impacts the P&L.

Switching to hybrid

There is no standardized method for integrating single‑use and stainless steel into the same facility. That being said, if moving toward a hybrid solution seems advantageous, there are certain skids which may be easier to transition away from stainless steel.

Media mixing and buffer prep equipment is generally simple to transition from stainless steel to plastic, single use. The single‑use equipment mirrors the reusable equipment fairly closely and can therefore drop into existing setups relatively easily. The frequent changeovers required by these skids also mean that switching to single use increases uptime and availability by eliminating cleaning steps.

Bioreactors are also fairly simple to transition between stainless steel and plastic. Most early challenges with single‑use control systems have been overcome, and single‑use systems provide flexibility to move toward perfusion setups and continuous manufacturing that steel cannot achieve. And, as discussed earlier, it is not uncommon for a single‑use seed reactor to feed a stainless steel production reactor.

As the biologics and overall pharmaceutical industry has begun operating by the principles of quality by design and are thinking about validation early on, hybrid facilities are proving to be quite advantageous. Hybrid setups allow for a mix of customization, flexibility, and off‑the‑shelf validation, while balancing lifetime costs, quality, and availability to your biologics manufacturing process.

Enabling Liquid Hydrogen Fuel Systems in Maritime Innovation

Alicat MCRQ Mass Flow Controllers Support TU Delft Hydro Motion Team’s Hydrogen Boat for the Monaco Energy Boat Challenge

Feb 21, 2025 | Bioreactors & Fermenters

Empowering Discovery on Water

The transition to sustainable energy in the maritime sector demands more than ambition, it requires precision. That is why Alicat Scientific is proud to support the TU Delft Hydro Motion Team as a Bronze Partner in their groundbreaking 2025 campaign: to design, build, test and race Mira, a liquid hydrogen-powered boat at the Monaco Energy Boat Challenge.

Equipping this innovative project with our MCRQ mass flow controllers enables the team to manage hydrogen fuel delivery safely and accurately, helping them prove that liquid hydrogen can power the next generation of clean marine propulsion.

Mira at the official reveal, Hydro Motion Team’s 2025 liquid hydrogen-powered boat.

Figure 1: Mira at the official reveal. Hydro Motion Team’s 2025 liquid hydrogen-powered boat.

The Challenge: Making Hydrogen Work for Maritime Transport

The goal of the TU Delft Hydro Motion Team is as ambitious as it is inspiring: to design, build, test, and race a fully functioning boat powered by liquid hydrogen, all within one year, and to compete at the Monaco Energy Boat Challenge 2025. But beyond the competition itself, the team’s mission reaches further. By proving that a boat can operate successfully on liquid hydrogen, they aim to spark broader innovation across the maritime sector and demonstrate hydrogen’s potential as a clean, scalable alternative to fossil fuels.

This project builds on the team’s past successes with compressed hydrogen, already a proven, zero-emission marine fuel. But as the team pushes for longer range and greater onboard efficiency, storage volume and energy density become the next major challenges. To solve this, the team chose to work with liquid hydrogen. With a volumetric energy density three times higher than compressed hydrogen at 350 bar, liquid hydrogen offers a powerful solution for saving space and extending endurance, key requirements in performance vessels.

But storing and using liquid hydrogen introduces challenges. The fuel must be kept at -253°C, requiring insulated cryogenic tanks. The team addresses this with a custom double-walled, vacuum-insulated carbon-fibber tank system, limiting heat ingress to just 7 watts, equivalent to a small LED bulb. To avoid wasting energy, waste heat from the fuel cell is used to bring hydrogen up to the required ~20°C operating temperature before reaching the fuel cell.

These trade-offs (boil-off rates, tank volume, storage weight, and onboard vaporization) are exactly the kinds of real-world constraints this project is designed to explore. And while Mira is a compact, foiling boat, the broader engineering question remains: could a system like this scale to larger vessels, such as ferries? That is the kind of thinking Alicat is excited to support with partners who are pushing the boundaries of what is possible.

The Role of Alicat: Flow Control After Vaporization

In Mira’s hydrogen system, hydrogen is stored as a cryogenic liquid. Before reaching the fuel cell, it passes through a vaporizer, transitioning into gas at ambient temperature. This phase is critical: delivering gas at the right pressure and flow requires stable regulation, fast feedback, and precise control.

Simplified diagram of the Hydro Motion Team’s hydrogen system.

Figure 2: Simplified diagram of the Hydro Motion Team’s hydrogen system.

To meet this need, the team integrated the Alicat MCRQ mass flow controller immediately downstream of the vaporizer. This device manages the mass flow of hydrogen gas into the fuel cell and enables:

  • Delivers stable and precise feed pressure to the fuel cell.
  • Measures hydrogen consumption through real-time mass flow monitoring
  • Monitors pressure and temperature to help prevent fuel cell issues like dehydration or fuel starvation.
  • Supports test validation and real-world performance optimization.

Compact, ATEX Zone 2 certified, and designed for fast system response, the MCRQ integrates easily into the tight constraints of a race-ready vessel. Its role is vital during system development, helping the team collect data, tune parameters, and prepare for race-day performance. In short, it helps translate bold hydrogen engineering into operational reliability.

Alicat’s MCRQ unit mounted inside the Hydro Motion Team’s hydrogen control system.

Figure 3:  Alicat’s MCRQ unit mounted inside the Hydro Motion Team’s hydrogen control system.

Why the MCRQ Was Selected

The Hydro Motion Team, together with our application engineers, selected the Alicat MCRQ series for its proven capability in low-flow hydrogen gas applications, offering a powerful combination of precision, speed, and safety. Key features that influenced the decision include:

  • Flow range of 0–1.5 g/s, which translates to ±0.01 g/s uncertainty at a nominal 1 g/s flow, small enough to maintain consistent fuel cell output.
  • 4–20 mA analog output, chosen specifically for its high-speed update rates (kHz range)
  • ATEX Zone 2 IIC certification, requiring minimal additional safety infrastructure.
  • Upstream valve position, enabling precise regulation of downstream feed pressure, supporting target values like the ~2.5 bar commonly seen in fuel cell stacks.
  • ±1.0% accuracy of reading (or ±0.2% of full scale)

Together, these features provide the team with a robust, compact, and responsive solution, a key enabler of real-world testing and a step toward scalable, clean hydrogen propulsion.

Competition Progress and What Comes Next

The TU Delft team unveiled the boat, Mira, earlier this year and is now deep into the testing phase, preparing for the Monaco Energy Boat Challenge 2025.

As testing progresses, the team continues optimizing the integration between hydrogen storage, vaporization, and control systems. Alicat’s instrumentation plays a central role in capturing this performance data for analysis and refinement.

This partnership represents more than a technical contribution. It reflects our belief that sustainable innovation thrives where education, engineering, and real-world experimentation meet.

By supporting the Hydro Motion Team and their work on Mira, Alicat contributes to:

  • Advancing liquid hydrogen fuel systems in marine transport
  • Empowering hands-on engineering education
  • Promoting practical low-emission propulsion technologies

We are honoured to be part of this project and proud to know that our instruments are helping to steer the future of clean maritime energy.

Together, we are not just measuring hydrogen. We are helping to Fuel the Future.

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