The strong demand for cutting-edge biologics, cell and gene therapies puts biopharmaceutical companies under increasing pressure to develop new therapies in a fast, efficient and safe way. Scientists require the latest critical core technologies to create, isolate and characterize the highest value model (e.g. cellular in the case of cell line development processes) for use in Upstream and Downstream Workflows. At the same time, a key need is to reduce the variability in product development, in order to allow the scale-up and generation of a reproducible cell expansion process as well as a robust final formulation.
To meet these customers’ needs, Advanced Instruments acquired Solentim, a global leader for cell line development technologies, and now offers a focused portfolio of scientific and analytical instruments and services for bioprocessing as well as innovative tools tailored to the isolation and characterization of high-value single cell clones. These technologies facilitate the optimization of the bioprocess workflow for advanced biological therapies including monoclonal antibodies, gene and cell therapies and allogeneic iPSC-derived cell therapies.
The Solentim technologies are utilized in the early stages of process development in order to maximize the efficiency of the clonal selection process, triage for the highest producing clones and characterize early critical quality attributes. The Advanced Instruments OsmoTECH® portfolio of osmometers supplies scientists with valuable information for optimizing cell line culture conditions during this clonal expansion phase. Moreover, osmolality is a crucial parameter throughout the bioprocessing workflow, including upstream and downstream processing, as well as formulation development and final drug product release. Therefore, the combination of Advanced Instruments’ and Solentim’s technologies has brought great benefits for their customers by driving efficiency in the cell line development process.
Here, Sarah Mackey, Vice President, Biopharma Business & Corporate Strategy, and Mark Rothenberg, Associate Director Application Sciences at Advanced Instruments, discuss the synergistic effects of the expanded portfolio.
Cell line development: creating the best possible environment for cellular growth
Mackey: The Solentim and Advanced Instruments’ technologies are both employed in the development and manufacturing of advanced therapies such as antibodies, proteins, cell and gene therapies. The products in the Solentim portfolio are used for establishing the Master Cell Banks (MCB) for the cell lines that produce these life-saving treatments.
In the very early phases of process development, when scientists start to characterize cell lines for productivity, osmolality becomes an important parameter. Therefore, the OsmoTECH osmometers are valuable analytical instruments, supporting customers during the establishment of a healthy cell environment and to develop these cell lines. Our customers are leveraging osmometry to create favorable conditions for expanding the selected clones within the cell line development workflow.
Rothenberg: In today’s world, scientists and engineers are looking to develop drugs faster and in an easier way, even when drug production is more complex. The Solentim portfolio provides an extremely comprehensive range of technologies that accelerate the cell line development workflow from start to finish. As well, Solentim cell culture supplements perfectly fit in this stage of the workflow. The Insti reagents, for example, create a favorable environment to enhance cell growth and maintain cell line clonality. Moreover, the MatriClone cloning matrix has been designed to stimulate the clonal growth of induced pluripotent stem cells (iPSCs) in a format that does not require any type of coating process. It is designed for in-solution seeding of iPSC lines and is optically suited for automated imaging.
To further increase process efficiency, osmolality is used to provide valuable data since it is an important metric during each stage of the bioprocess workflow. There’s a lot of growing evidence pointing out the critical role osmolality plays in supporting cell line development. Osmolality is used as a quality metric, for example, in the QC of cell culture media throughout the industry. Measuring osmolality can help detect possible media contamination or formulation errors before cells go into the bioreactor. Each cell line has unique characteristics that require unique media formulations. Therefore, we are putting major effort in understanding the impact of osmolality on overall cell health during cell line development.
Bioprocessing workflow: driving efficiency during manufacturing of advanced therapies
Rothenberg: Cell lines are indeed the tool used to produce new, life-saving therapies. They are the most important capital for any company that is involved in the development of biological drugs. Advanced Instruments’ OsmoTECH and Solentim’s technologies perfectly integrate during the pre-upstream phase of the bioprocess workflow when these cell lines are taken out of prior storage, selected and scaled up for GMP manufacturing in bioreactors. In fact, the combined use of these technologies enables scientists to quickly get information on the overall health and quality of a particular cell line, in order to directly support the expansion of the clones of interest, enhancing process efficiency.
Mackey: From companies generating monoclonal antibodies to companies developing gene therapies or leveraging primary or engineered cells for therapies such as iPSCs, our products perfectly fit in their production processes. Further, CDMOs and CMOs working on cell line development will benefit from the wide spectrum of products. As a part of that decision making process, we give our customers the ability to bring all of their data together in one date management system, which makes it a format that is very easily understood. In fact, when companies utilize several different devices, each of them providing pieces of the information, they currently need to invest a lot of time and resources in manually combining and matching data sets together. Our STUDIUS™ software lays out all of these different parts of the workflow. So from VIPS™ to Cell Metric® to ICON™ and then to the future osmolality software, all of these systems pool data together automatically.
This data automation ensures both an automated analysis, maintenance of data integrity and an automated audit control. At any time scientists can track what happened to their cell line at different stages of the process. We’re also bringing data management into the process. The power of the system is to triage top clones from the process at the touch of a button – the ability to select top clones for specific productivity plus confirmed clonal origin. STUDIUS™ will ensure 21 CFR part 11 compliance and fulfill the requirement for completing the CLD components of an IND submission document.
Optimal technology: increasing the speed of the bench to market process
Mackey: Currently, physical and digital automation of the manufacturing process is the biggest trend in bioprocessing. Our products need to physically integrate with ease into automated cell line development processes using automated liquid handling or robots. For example, our newest product, the OsmoTECH® HT, is the first osmometer that’s built in a 96-well plate based format and fits perfectly into the static phase of the cell line development workflow. Also, our systems offer automated data analysis and data management with the support of artificial intelligence. The latter is a really hot trend in our market space; analytical instruments need to have built-in, advanced analysis and machine learning tools. These tools help make the process more predictable and obtain answers quicker without taking physical samples from the process.
Rothenberg: The area of cell line development is developing at a very fast pace. Therefore, customers’ needs and requirements are also changing and maturing very quickly. We get continuous feedback from our customers to ensure that we adapt our technologies to their evolving needs.
Mackey: Customers are already moving very quickly towards artificial intelligence, automation and miniaturization. As a result, we’re already anticipating those changes within our R&D department. In terms of therapeutic focus, we see a trend towards more complex drugs, such as multi-specifics, and delivery mechanisms which require more robust manufacturing technologies. In the viral vectors workflow, which serves the gene therapy market, companies are moving from utilizing transient transfections to more robust stable cell lines.
With regard to cell therapies, the future will mark the use of allogeneic therapies instead of the present autologous therapies, which rely on the use of a patient’s own cells. Allogeneic therapeutic approaches would pave the way for the mass production of large batches of cell therapeutics that can be used for many patients at a fraction of the cost. For these purposes, stable cell clones are a prerequisite.
The acquisition of Solentim by Advanced Instruments means our combined technologies will play a key role in the development of iPSC manufacturing workflows. Here, cells are not used for producing the therapy but become the therapy themselves. For this purpose, we adjusted VIPS™ to fit into a GMP workflow with a traceability perspective, from the calibration to the single-use consumables all the way through to GMP-compatible software that has all the required 21 CFR Part 11 compliance features.
See how the combined technologies of our OsmoTECH and Solentim Portfolio advance workflows throughout the whole process of the development and manufacture of biologics:
The integration process: a customer-centric approach
Rothenberg: In terms of company integration, I’ve been involved in several integration processes during my career. It’s my belief that the acquisition of Solentim into the Advanced Instruments family has been the smoothest and the most collaborative. People are working together to promote a cohesive, focused and cultural-friendly environment. The goal is to develop technologies which improve the efficiency of the bioprocess workflow, which has been rather complicated and expensive. We have a clear understanding of our customer needs and are focused on delivering best-in-class technologies.
We’re very focused on solving customer problems and delivering effective, clever solutions. We provide our customers with a broad expertise and a strong support system. Advanced Instruments has been able to accelerate R&D investments, helping to bring important innovations faster to the market.
Mackey: Innovation is really critical in this market. Our customers are looking to create breakthrough drugs, with a real patient impact, faster. We’re focused on how to best support them in getting the answers they need faster. By prioritizing the rapid expansion of the new R&D team, we can accelerate product development and continue, from an innovation perspective, to stay ahead.