Outsourcing Analytics for Process Monitoring and Optimization

Monitoring and course correction. Keep the process under observation and control. Calibration. | Image credit: ©Andrii Yalanskyi – Stock.Adobe.com

Accurate and timely analytics are essential to successful development and manufacturing of biopharmaceutical products, whether they are small-molecule drugs, recombinant proteins or antibodies, or novel modalities such as cell and gene therapies. The correct choice of analytical technologies for process monitoring and optimization during process development can reduce timelines and risk while increasing the ability to develop robust, readily scalable processes. Outsourcing of analytics to contract research organizations (CROs) with state-of-the-art capabilities, meanwhile, can help drug developers realize these goals in a cost-effective manner.

Business and technical drivers for analytical outsourcing

Outsourcing of analytics and testing often occurs for a combination of business and biological reasons, according to Alex Sargent, director of process development for cell and gene therapy at Charles River Laboratories, particularly in the case of complex, novel modalities. “For instance, it may be more cost-effective and efficient to outsource routine testing rather than investing in the space, equipment, and personnel needed to run a limited number of assays, making it more practical to rely on external providers,” he explains.

In addition to providing more cost-efficient and scalable solutions, CROs can also offer faster turnaround times to adapt to the needs of client projects as they advance from early development to commercialization, notes Jincui Huang, senior vice-president and head of the analytical sciences and clinical quality control department at WuXi Biologics.

Outsourcing analytics to CROs is also driven by the need for specialized expertise and advanced capabilities, Huang observes. “Many biotech companies recognize that developing and maintaining in-house systems for comprehensive analytics for process monitoring and optimization can be resource-intensive. By partnering with CROs, biotech and biopharma gain access to advanced technologies and methodologies that may not be available internally,” she says.

As an example, Sargent highlights bioinformatics and DNA/RNA sequencing for cell and gene therapies as technologies often accessed by developers through strategic partnerships with CROs.

The increase in outsourcing of biologics production for both drug substances and drug products to contract development and manufacturing organizations (CDMOs) is also leading to more analytics outsourcing, according to Elliott Franco, vice-president of lab operations at Alcami. “Many CDMOs have become true experts in process development and gain deep understanding of each process they work on through establishment of comprehensive analytical capabilities. That expertise allows for easy correlation of data trends to process parameters and thus efficient optimization of processes to maximize reliability and robustness,” he comments.

Increasing automation with room for improvement

Driven by the demand for greater efficiency and robustness in biologics development, automation in analytics is becoming increasingly prevalent among leading CROs. Areas of application can include, according to Huang, sampling, real-time monitoring, and data analysis.

Integrated automated sampling systems, Huang says, allow for collection of samples from both continuous and traditional fed-batch processes in real time without interrupting the processes. Inline process analytical technology (PAT) tools such as Raman spectroscopy and bio-capacitance measurement, meanwhile, when applied in upstream processes, offer real-time, high-frequency, and non-invasive analysis of the cell-culture process through corresponding chemometric algorithms, she observes. In downstream processing, online liquid chromatography with robotic systems offers high-throughput and near-real-time analysis for monitoring of product quality attributes during purification steps, according to Huang.

The ability to follow process milestones (protein concentration, cell densities, critical impurities, etc.) with online sampling/testing capabilities provides the type of data needed to truly understand critical process parameters, Franco agrees.

Advanced digital tools, meanwhile, are transforming the way analytical data are analyzed and used. “Digitalized auto-integration/analysis and predictive modeling help us develop methods in a more efficient way and identify potential risks earlier while continuously improving assay accuracy by analyzing historical and real-time data,” Huang explains.

Additional improvements in automated testing are still needed, however, particularly with respect to process development and optimization for newer modalities such as cell and gene therapies, Sargent contends. “The state of automation in analytics within the cell and gene therapy sector has room to grow, especially when compared to manufacturing,” she states.

In the past few years, there has been a surge of new technologies and platforms for the automated manufacturing of cell and gene therapies that have the potential to streamline operations, expand access, and significantly reduce costs, particularly for autologous therapies, Sargent notes. He believes, however, that, although equally important, automating analytics for process monitoring and testing during development and commercial production has been more challenging. “When talking about autologous cell therapies, for instance, there are thousands of independent batches generated every year, all of which require analytics for quality control and release. To effectively reduce the costs of these life-saving therapies, prioritizing the automation of testing will be critical,” he asserts.

Many benefits of automating outsourced analytics

There are, in fact, many ways in which automation of analytics at outsourcing partners can benefit biologic drug developers. “Automated analytics capabilities provide customers with several significant advantages, particularly when offered by service providers with robust experience in PAT and other automatic analytics technologies,” Huang says.

Specific benefits highlighted by Sargent include faster, more cost-efficient, and more accurate analytics compared to manual techniques. “Removing human error and bias can improve robustness and reproducibility, and outsourcing testing to a partner with automated capabilities can really help someone scale up or scale out their clinical or commercial program,” he remarks.

“In addition to allowing drug developers to avoid the need to make significant capital investments in expensive and complex technologies, automated solutions at CROs often speed up process development and scale-up while also enhancing the robustness of large-scale production by leveraging the CRO’s technical expertise and comprehensive data analytics capabilities,” Huang agrees. This support helps clients make informed decisions, optimize their processes, and ultimately achieve higher yields and better product quality.

“Overall,” concludes Franco, “use of automated analytics typically ensures that processes are well characterized and less likely to encounter failures to meet specifications with access to better and more comprehensive process data.”

CROs face several challenges

There are some challenges to establishing comprehensive automated analytics capabilities, even for CROs serving large numbers of clients. “In general,” summarizes Franco, “establishing automation is costly and requires significant expertise at the interface of manufacturing, process development, and analytical development.”

Cost is often the first challenge when implementing automation for process monitoring and optimization, as the upfront investment to implement new analytical technologies in a process workflow can be significant, Sargent observes. “When transitioning from manual methods to automated systems, it is essential to demonstrate that the new method delivers equivalent readouts and results. For therapeutics developers, particularly those in advanced clinical or regulatory phases, implementing such changes may be impractical or even infeasible, despite potential improvements in throughput or robustness. It thus falls on the CRO to identify clients well-suited to automation and new technologies, particularly early-stage developers or those looking to transition to new platforms,” he comments.

Another issue highlighted by Huang that CROs must be able to overcome is the need to integrate new automation technologies with client-specific practices, as many clients use specific and diverse systems that require harmonization with automated platforms. Use of many different platforms, meanwhile, creates a need to consolidate data from multiple sources into a cohesive format for analysis, which can be complex, she notes. It is also essential to ensure automated systems meet stringent compliance standards, which requires robust validation. In addition, training staff and adapting workflows to incorporate automation can take time.

One strategy for overcoming these challenges, according to Huang, is through investment in advanced infrastructure, development of proprietary integration frameworks, and having a commitment to operational excellence.

Innovation is having an impact

Several exciting advances in automation and analytical technologies are increasing CRO capabilities in the field. First, Huang points to high-throughput automated platforms leveraging robotic systems capable of executing multiple assays simultaneously, which are improving productivity and reducing turnaround times.Many of these systems are designed to be end-to-end platforms, she adds. “The use [of] multiple robotic arms or automated guided vehicles to connect different modules can provide seamless end-to-end automation, from sample management, to analysis and reporting,” she explains. Bioreactors with embedded sensors and integrated advanced analytical systems, meanwhile, enable continuous monitoring of critical process parameters. “These innovations are critical for improving efficiency, scalability, and precision in biologics development,” Huang states.

In cell and gene therapy, the rapid advance of next-generation sequencing technologies and bioinformatics is, according to Sargent, having a transformative impact. Rather than years, hundreds of genomes can be sequenced in a week. Similar advances in transcriptomics, proteomics, and other comprehensive assays are equally important, he observes.

Across all biologics, Sargent believes that the implementation of machine learning and artificial intelligence (AI) in process monitoring and analytics systems is tremendously important. “We are only at the beginning of what AI can do in analytics and process monitoring, and the potential for how it may transform this space cannot be ignored,” Sargent remarks.

Several ongoing needs

While automation in analytics is providing many benefits, limitations remain for CROs looking to maximize the opportunities that can be realized for their customers. Lack of standardization between different vendor systems remains a major issue in this regard, says Huang. “Industry efforts are required to establish open-source standards from software to hardware perspectives,” she notes. That should include development of next-generation technologies for effectively managing and interpreting the overwhelming amount of data generated by automated systems.

Huang would also like to see the development of modular automation solutions, which she believes could help smaller CROs overcome the challenge of high upfront expenditures currently associated with existing automated analytics systems.

Sargent emphasizes the need for more end-to-end analytics solutions for process monitoring. As an example, he points to flow cytometry, which is an essential tool in the cell and gene therapy space. “New advances in cytometers have improved throughput, removed human subjectivity, and automated crucial analysis workflows, but sample prep and staining remain laborious, manual tasks. Having an end-to-end automated solution for sample collection, storage, preparation, testing, and analysis will be key for future development, both for CROs and their customers,” Sargent says.

Automation of potency assays, including testing and analysis, is also needed. “These assays can be a major challenge using existing technologies. Automation and innovative methods/techniques will therefore likely prove critical to enabling a deeper understanding of biology and cellular responses, which will benefit everyone in the field, from academic researchers to drug developers and their outsourcing partners,” he concludes.

About the author

Cynthia A. Challener, PhD, is a contributing editor to BioPharm International®.

Article details

BioPharm International®
Vol. 38, No. 1
January/February 2025
Pages: 26–28

Citation

When referring to this article, please cite it as Challener, C.A. Outsourcing Analytics for Process Monitoring and Optimization. BioPharm International® 2025 38 (1).