Modular Processing: Enabling the Future of Biomanufacturing
September 13, 2019
Biomanufacturers continue to search for ways to accelerate and intensify production. Together with facility and process automation, and innovative process technologies such as continuous processing; modular and mobile solutions are key enabling technologies as we look to the process of the future and Industry 4.0.
In this blog, we interview Morgan Norris, VP of Pall Marketing, to uncover key trends and insights regarding this developing technology.
- What does the industry define as modular biomanufacturing?
The scale of the modularity can vary between different users, however, it is generally perceived that modular manufacturing relates to an assembly of preconfigured processing elements, each with a finite, but not necessarily inflexible, functionality. These modular elements can be as small as single unit operations, or can themselves be combined to form more complex, but no less standardized, integrated processing elements. The same definition can also extend to cover entire processing solutions contained within preconfigured facilities. All these perspectives share the core values of the modular approach, using preconfigured solutions, designed to work together to achieve the desired goal without the need to repeat development design choices or select customized solutions.
- In the steps of modular biomanufacturing – such as media preparation, cell culture, purification, compounding/formulation and fill/finish – what varies, and what products do you find the most popular?
The historic focus is on the core processing technologies such as cell culture and purification, however, we see an increasing acknowledgement that the supportive processes, such as buffer preparation, are as critical, if not more so, to the real-world efficiency of a process. Here, increased product titers result in larger volumes of process buffers which can exceed 10,000 L for titers of >3g/L. Ensuring buffer is prepared, QC checked and available for each of the unit operations, poses logistical challenges. Delivering a solution that can integrate with multiple unit operations is needed to support a modular processing philosophy.
The scope of modularity is the largest variable. We deliver a wide range of modular solutions and the scope can vary from complete end-to-end processes to simple combinations of individual steps to work with existing process equipment. Some modular solutions need to integrate with existing facilities and existing distributed control systems. Others simply require local controls. It is easy to think that a modular approach is only advantageous when targeting an entire process and new facility. We believe that having a broad range of flexible technologies allows all end-users to access these benefits.
- What do you see as the most common reason companies use modular biomanufacturing?
Quite simply, it saves time and accelerates the delivery of a process that assures product quality and patient safety. For many years, producers have simplified and accelerated process development by establishing technical processing platforms and then applying these historical decisions to new, but related, processes. These platforms are precursors to the modular approach where many of the low value-adding decisions are taken out of the development cycle to accelerate progress towards the desired goal.
Reducing this development and build time can be used to achieve several objectives. Reducing time to market is the most visible gain, however, reducing the scheduled time to create a functional process from the point of initiation means that investment decisions can be made at a later stage than for traditional approaches. Given that more than 80% of candidates may fail at Phase II and 40% fail at Phase III, this intrinsic uncertainty means that being able to delay the capital investment, without extending the time to market, better controls the investment risk.
Speed alone is a powerful driver but quality is non-negotiable. Here, the prior knowledge obtained through the use of proven solutions means that process risks can be well characterized, mitigated and controlled. Critical performance attributes and control points can be standardized and regulatory and validation precedents can be leveraged to streamline submission.
It is sometimes difficult to separate the benefits of pure modularity from those achieved by adding a degree of process mobility. But where modules can be applied to multiple operations or multiple processes, these can be quickly re-tasked to reduce capital investment and reconfigured to adapt to changing demands or uncertainties.
- What recent products have you developed that can be used in modular biomanufacturing?
Single-use technologies are fundamental to accessing the full set of benefits of a modular manufacturing approach. For example, multi-product facilities manufacturing chemically synthesized compounds routinely reconfigure their processes to quickly manufacture new molecules. These use a standardized set of equipment, typically stainless-steel, to create many different unit operations that then combine to produce the product or intermediate. This version of modular processing delivers the flexibility and agility necessary to be productive in this market. But clearly there are significant differences between small molecule manufacture and bioprocessing that mean that it would be far harder to achieve the same with fixed equipment.
Here, single-use technologies bridge the gap and support the most basic form of modularity while also supporting system mobility. For a product to support a modular manufacturing approach it needs to be versatile enough to accommodate a natural range of process variables while also robust in its operation to deliver the same action across this range.
We have extended the application of single-use to a number of the core unit operations that form the basis of processing modules. The Allegro™ STR bioreactor range, Stax™ mAx clarification platform, Allegro single-use chromatography systems and Cadence™ virus inactivation systems are just four among a wide range of products that are easily integrated into, or support, modular processes. There are more that support greater flexibility within a modular process by working across multiple scales to cover both early phase GMP production and full-scale production. The Cadence BioSMB 80 and 350 systems apply continuous chromatography to scale-out within the same system to cover a range of possible process demands within a single module. All these are complemented by both single-use and continuous ultrafiltration solutions as well as mixing and fluid handling solutions that are essential for the support of a number of these operations.
- What are the key benefits of these products?
From a modular perspective the key benefit across all these, and similar products, is that they perform across a wide range of process scales and process conditions. Without this, any inclusion in a modular platform is inherently limited to a narrow range of process conditions and scales. Next is that they work together. If they cannot work together then they are of no use as part of a modular development. In many instances, products can be natively connected, both physically and digitally to work in harmony. An example here would be using the Cadence BioSMB chromatography systems in conjunction with the Cadence virus inactivation system that communicates to collect elution peaks ready for inactivation and subsequent purification steps.
This communication and connectivity highlights a key future trend where the automation of multiple modules through a centralized system adds a further layer of control and reliability and takes us another step closer to the next generation of bioprocessing.
Learn more about how continuous processing aligns to Industry 4.0, in the blog by Dr Peter Levison.
Morgan Norris - VP Marketing, Pall
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