SECURECELL LAUNCHES NOVEL SOLUTIONS FOR HIGH-THROUGHPUT BIOPROCESSING

Executive Summary

Securecell is introducing a series of innovative high-throughput solutions to transform the way bioprocess development is done. These solutions are designed to address inefficiencies in traditional workflows by providing a high degree of automation and integration.

The centerpiece of Securecell’s innovation is the Integra1 64 2, a fully automated end-to-end bioprocess development platform featuring up to 64 bioreactors at a 200 mL scale. This system integrates process analytical technology (PAT) and downstream processing (DSP) workflows to allow for real-time process monitoring, process control, and process optimization. The Integra1 64 2 platform offers more functionality, reduces process time, and significantly lowers running costs compared to existing high-throughput technologies considered state-of-the-art. 

Introduction

In line with the rapid pace of modern innovation, bioprocessing technologies have made a significant evolution over the past few decades. Early bioprocesses were slow, inefficient, and heavily reliant on manual labor. With advancements in bioprocessing technologies and methods, individual process steps have been greatly improved. Despite these improvements, holistic workflow concepts remain largely underdeveloped. As a result, the bioprocessing industry lags significantly behind other highly automated sectors, such as the automotive industry. While this gap can be partly explained by for example the strict regulatory frameworks, the bioprocessing industry, along with its technology providers and regulatory bodies, must start looking beyond immediate constraints. By focusing on workflow-oriented, disruptive platforms rather than isolated solutions, the industry can move toward greater innovation and overall efficiency. 

The FDA recognized this gap early in the 21st century and published the FAT guidance on PAT in 2004 ^[1], encouraging companies to use real-time monitoring and control in bioprocessing to enhance overall process efficiency and product quality. This can also be seen as a first step towards a workflow-oriented solution away from isolated unit operations. When we critically assess the situation 20 years later, it becomes clear that the industry as a whole remains far from achieving real-time monitoring and control, and even further from implementing fully automated and holistic workflow-oriented platforms.

In this article, we will explore the critical role of high-throughput bioprocessing platforms in the industry, demonstrate how companies can not only meet but surpass the FDA’s guidance on PAT, and highlight Securecell’s plan to revolutionize traditional workflows with groundbreaking novel technologies (Figure 1 ).

Figure 1: Integra1 64 2. The Integra1 family encompasses the Integra1 64 2, a fully automated end-to-end process development platform featuring 64 bioreactors at the 200 mL scale with integrated PAT, and DSP workflows.

The Importance of High-Throughput Bioprocess Development

By definition, a bioprocess involves living cells, their components, or biological systems to produce or modify products such as pharmaceuticals, chemicals, or biofuels. Many industries depend on efficient bioprocessing workflows to create their innovative products.  A prominent one is the biopharma industry. Given the substantial number of promising advanced therapy medicinal products (ATMPs) in development, it is not surprising that the global biopharmaceutical market is expected to grow at an approximate CAGR of 8.5% between 2024 and 2032, from USD 616 billion to USD 1,183 billion ^[2]. The same holds for other markets where bioprocessing plays a crucial role such as, for example, the synthetic biology market ^[3] or the synthetic food market ^[4]. Given these figures, one might assume that these industries are without any concerns. However, they remain highly competitive, and companies continue to face significant pressure to refine bioprocessing workflows, especially process development and scale-up to efficiently produce the heterogeneous class of ATMPs or other products, to make production safer, more predictable, faster, and more cost-effective.

The biopharma industry has already recognized the potential of high-throughput automated methodologies to accelerate process development ^{[5], [6]}. These methodologies are well-established, especially in drug discovery and cell line development. However, a significant bottleneck persists in process development and optimization because current small-scale high-throughput bioreactor systems fall short in key areas such as customizable automation and digitalization, seamless integration of on-line PAT for critical process parameter (CPP), and critical quality attribute (CQA) analysis, and the ability to incorporate downstream processing (DSP) operations. Additionally, the prohibitive costs of many of these systems limit their accessibility to a broader range of users.

Securecell’s new high-throughput bioprocessing system, the Integra1 64 2 is designed to completely automate process development and address the above-mentioned shortcomings of currently existing technologies. In case you are already heavily invested in a high-throughput solution, Securecell’s SampleBus technology will allow you to integrate existing high-throughput installations into an advanced PAT and optional DSP workflow. To summarize, the novel technologies will have the following benefits:

1.    Enhanced functionality to support workflow-oriented bioprocessing
2.    Cost-effectiveness, offering savings of up to 50% compared to existing high-throughput technologies
3.    Reduced process time through increased data generation and data density
4.    Customization options using modular building blocks

Background of Securecell

Since its foundation in 1995, Securecell has been delivering customized bioprocess automation technologies to the industry. In addition to this project-based automation capability, Securecell offers a product portfolio that enables automated sampling workflows with Numera® and a comprehensive digital framework with Lucullus® for entire bioprocess environments.

Tailored Automation Solutions

Securecell has been supporting customers in biopharma with automation solutions, especially for bioreactor control. We have realized numerous projects involving the customized and tailormade deployment of process automation from small lab fermenters to GMP production systems. Thereby, we rely on established technologies such as Siemens PLC control systems and extend the functionality of these installations with the Lucullus® software.

Lucullus®

The Lucullus® Process Information Management System is one of the most comprehensive bioprocess software solutions available on the market. Our customers call it “the brain” or “the conductor of an orchestra”. It enables vendor-agnostic monitoring and control of many devices in your laboratory while automating and digitizing workflows, including process planning, media preparation, process execution, sample management, and process evaluation.

With advanced, state-of-the-art but also customized interfaces, Lucullus® integrates seamlessly into any bioprocess environment, facilitating smooth data capturing and exchange between devices, software, and databases. This integration capability eliminates data silos, prevents data loss, and reduces the need for extensive manual data curation.

Numera®

The Numera® sampling system is a versatile system that not only bridges the gap between bioreactors and analyzers by transferring the sample but also offers sample processing with precise dilution and superior patented filtration technology.

Together with the Lucullus® software, Numera® perfectly integrates into existing bioprocess environments, eliminating the tedious and error-prone manual sampling of bioreactors with automated time or event-based sampling schedules. No manual intervention during upstream processing (USP) is required after the planning phase allowing for automated feedback-loop-based bioprocess control (Figure 2).

Figure 2: Automated feedback-loop-based bioprocess control. The Numera® automated sampling and sample processing system aseptically draws cell-containing samples from the bioreactor. These samples can be optionally processed and then either transferred to a sample collector or sent directly to a fluidically connected analyzer. The Lucullus® software triggers the measurement, imports the analytical data, and assigns it directly to the corresponding process.

In 2018, Securecell’s board of directors decided to develop a platform built on our previous technologies and expertise, including Lucullus®, Numera®, various custom automation projects, experience in high-density blood filtration, and workflow automation. These modular components, or “building blocks,” were integrated into a comprehensive platform, which can be reconfigured like LEGO® bricks to meet specific customer requirements. The culmination of this effort is the Integra1 family, which includes the Integra1 64 2. This model features 32 to 64 fully automated and integrated bioreactors with a 200 mL working volume each. The system has now officially hit the market and is set to transform both the current and future bioprocessing practices.

The name Integra1 might sound familiar. In 2021, Securecell introduced the Integra1 8 30 platform ^[7], which garnered attention from other technology companies. Securecell’s concept and expertise led to the closure of an exclusive contract with a major international corporation to co-develop a bioprocess platform to automate cell and gene therapy workflows. This platform will be launched soon.

Product Announcements

In line with our strategy to pioneering the world’s next bioprocessing solutions that support life scientists to tackle real-world challenges, we are proud to introduce a new portfolio of fully automated high-throughput solutions. 

Integra1 64

The Integra1 64 platform opens new dimensions in the automation and digitalization of high-throughput bioprocesses. Securecell has developed all the essential building blocks over the past three decades to create a unique, unrivaled end-to-end customizable system that sets new standards in throughput, efficiency, footprint, and cost-effectiveness.

Figure 3: The RAM module. Each reactor array module hosts eight fully featured bioreactors and five supply vessels. 

USP - Upstream Process

At the heart of the system is the "reusable" single-use Reactor Array Module (RAM), which features eight bioreactors with a working volume of 200 mL. It also includes five vessels for media, antifoam, and acid/base supply, along with disposable membrane pumps, flow calibrators, gas microfluidic channels, and all other essential components needed to efficiently execute batch, fed-batch, perfusion, or cascaded bioprocesses (Figure 3). The innovative sensor port technology enables in-line monitoring using standard reusable probes, which can access the bioreactors through a patented sensor port. Thanks to this innovation and efficient in-situ sterilization, the RAM can be reused twice for cell culture and up to four times for microbial processes, making it one of the first reusable single-use bioreactor technologies on the market. This unique feature significantly reduces the cost per bioreactor compared to competitive high-throughput single-use technologies.

Figure 4: Integra1 64 2 front view with four cabinets hosting the RAM modules and the SampleBus conveyor belt in the background.

PAT - Process Analytical Technology

The bioreactor contents can be accessed automatically and under sterile conditions through the sampling port. With a cleanable needle mounted to a robotic arm, the sample can be transferred to a vial on a "SampleBus" conveyor belt (Figure 4). The belt transports the sample to a high-density filtration (HDF)-sample preparation station (SPS) and then to a PAT island for analysis. This conveyor system overcomes the distance limitations that often restrict automated sampling applications in modern laboratories.

The HDF-SPS cabinet facilitates efficient cell removal through automated centrifugation and clarification, while also managing sample preparation tasks such as dilution and derivatization. This ensures samples are optimally prepared for analysis on the PAT island (Figure 5 ).

Figure 5: Integra1 64 2 complete front view, displaying the vial loading station, four cabinets housing the RAM modules, the High-Density Filtration and Sample Preparation Station (HDF-SPS), and the PAT island. The system is presented in its compact footprint, with the SampleBus conveyor belt hidden behind the cabinets.

The PAT island can be flexibly equipped with a range of analytical devices. Securecell supports cell analyzers from Roche and Beckman Coulter, biochemical analyzers from Roche and Nova Biomedical, HPLC systems from Thermo Fisher and Agilent, and UPLC/LC-MS systems from Waters. Additionally, Raman flow cells can be utilized to generate Raman spectra, with immediate validation via corresponding reference measurements. 

DSP - Downstream Processing

Just like in upstream processing, downstream operations must be tailored and optimized for each specific process to efficiently isolate, purify, and concentrate the synthesized drug substance or other products. 

In the Integra1 system, once the bioprocess run is complete, the bioreactor contents can be automatically emptied and transferred into 150 mL or 250 mL bottles placed on the "performance bus" conveyor belt. These bottles are then transported to the downstream section, where the contents undergo a stepwise purification process. First, cells and debris are filtered out, and then the filtrate is processed through various chromatography techniques. Like the upstream section, the downstream section can be equipped with a range of devices, including but not limited to affinity chromatography, size exclusion chromatography, ion exchange chromatography, and more (Figure 6). 

Figure 6: Layout of an Integra1 64 2 including the PAT island and the DSP part. Similar to the PAT island, the DSP part can be configured with devices of choice by the customer. Securecell will supply #6 «Tape Filtration Unit» Cell Removal, #5 «Tape Filtration Unit» Micro Filtration, and #4 «Tape Filtration Unit» Ultra Filtration. The chromatography workflow (#1-#3) is defined by the customer.

SampleBus

As mentioned earlier in this article,  high-throughput technologies in process development help reduce costs by increasing data density and enabling decision-makers to derive optimal scale-up models. The initial investments into such technologies are often substantial, and once implemented, these systems are typically used for many years. The needs of operators may change over time but unfortunately, standard suppliers do often not have the willingness, competence, or resources to support the expansion or customization of these platforms.  One specific and often mentioned need is the integration of these platforms with analytical devices to establish an automated workflow for CPP and CQA measurements.

Built on the back of Securecell’s own high-throughput Integra1 64 technology, specifically the “SampleBus” conveyor belt system, we extend the analytical capabilities of existing high-throughput platforms such as Sartorius' Ambr® 250. This extension enables the automated transport of samples from up to six Ambr® 250 systems to an integrated PAT island. This highly customizable solution extends the range of analytical devices compatible with the Ambr® 250 HT and uncouples automated sampling from distance limitations. The Lucullus® Process Information Management System runs in the background, orchestrating process planning, process execution, sample management, and process evaluation  (Figure 7).

Figure 7: Layout of a SampleBus for Ambr® 250 including the PAT island. With this setup, each bioreactor of up to six Ambr® 250 systems can be sampled four times every 24 hours, the sample transferred onto the SubBus and SampleBus, and the sample analyzed with a selection of analyzers.

The Ambr® 250 HT sampling robot dispenses the sample into a Sample Transfer Unit (STU) (#2) through a non-invasive process. From the STU, the sample is transferred into a vial located on the SubBus. The vial containing the sample is then moved onto the SampleBus (#1). Before injection into an analyzer, the sample is sent to the HDF-SPS station for processing (#3). In this module, cells can be removed, and the sample can be diluted, derivatized, and then transferred to the PAT island for analysis (Figure 8). 

Figure 8: Overview of HDF-SPS station for automated cell removal, clarification, dilution, and derivatization.

The SampleBus for Ambr® 250 HT or also other high-throughput systems provides the highest level of insight for process development and optimization for your Ambr® 250 systems.

Outlook

In the meantime, Securecell has entered into cooperation agreements with market-leading manufacturers of analyzers to integrate the essential PAT technologies (e.g., LC-MS) directly into the Integra64 2 system and, consequently, into the SampleBus.

Currently, Securecell is in negotiations with reference customers for both the Integra64 2 platform and SampleBus technology and has already concluded the first contracts. Additionally, the company is looking for further interested partners who wish to contribute their specific requirements to the development of these systems and invest in shaping the future of bioprocessing technology.

References

Ambr® is a registered trademark of “The Automation Partnership (Cambridge) Limited”.