Mechanistic models condense complex information into quantitative and interpretable frameworks, which can guide experimental designs for model refinement and process optimization. This presentation discusses how mechanistic models built from historical data can be used to speed up analytical development. A case study on recombinant adeno-associated virus manufacturing showcases how robust mechanistic models can be developed even from sparse experimental datasets that comprise data from a diverse array of analytical tools.

Efficient data integration is crucial for the advancement of automation centers in life sciences. Efforts at the DTU Arena for Life Science Automation (DALSA) and DTU Bioengineering focus on automating data capture, managing the data lifecycle, and ensuring data integration in compliance with FAIR principles. Key processes include automated data capture, handling of retrospective data, and the standardization and migration of legacy data. These practices have the potential to accelerate scientific discovery and enhance the functionality of automated labs. Insights into the future of data integration in biotech labs highlight its transformative impact on research and development.

Pompe disease, a lysosomal storage disorder, is characterized by glycogen accumulation in tissues, leading to elevated levels of glucose tetrasaccharide (Glc4) in biological fluids. In this study, we developed and validated a high-throughput assay for the quantification of Glc4 in human plasma. This method offers a robust, efficient, and non-invasive tool for clinical monitoring Pompe disease, facilitating the assessment of enzyme replacement therapy efficacy.

The unique characteristics of biologics, including high protein concentrations and viscosity, present significant analytical challenges in research and development, often undermining the accuracy of manual liquid handling methods. Implementing modular automation systems, such as the Hamilton Microlab Prep and Andrew Alliance Robot, addresses these challenges by improving turnaround times, resource efficiency, and flexibility. These platforms facilitate medium-to-high-throughput testing for essential assays, including Ligand binding ELISA and plate-based enzymatic activity assays, thereby streamlining development processes and enhancing productivity in both analytical research and quality control laboratories.

A robust UPLC-CAD platform method was developed for quantifying at least 20 lipids, including helper lipids, ionizable lipids, PEGylated lipids, and cholesterol in mRNA-LNP drug products. Optimized mobile phase, gradient, and autosampler conditions enable full separation within 21 minutes, minimizing matrix interference while achieving >90% recovery and acceptable precision across dilution schemes. The method supports GMP qualification for lipid content analysis in current and future mRNA-LNP formulations.

A variety of automated liquid handling systems exist, many differing in price, size, ease of use, and quality. This talk focuses on the development of the Echo 525 Liquid Handler for qPCR after experiencing difficulties with an alternative liquid handling instrument. The challenges experienced with both the alternative liquid handler and the Echo 525 will be addressed, along with the methods used to develop the final automated qPCR method.

Polysorbate degradation in biotherapeutic protein formulations poses significant challenges toward long-term stability. Various assays have been developed for assessing degradation risk. While multiple data sets enhance understanding, they can complicate interpretation. Three case studies are presented to demonstrate how different assays align in evaluating enzymatically-driven polysorbate degradation, categorized into risk informing, characterization, and extended characterization. This framework offers guidance for future work in addressing polysorbate degradation.

Novartis has a broad and diversified portfolio of biologics, where analytics play a vital role in technical development. This presentation highlights strategic approaches to enhance efficiency and speed in analytics, including process standardization, platform implementation, and smart risk adoption (e.g., predictive stability). These elements aim to streamline analytical development, expedite overall progress, and ensure robust support for our biotherapeutic pipeline.

This presentation will explore strategies for optimizing method transfer processes and provide insights on transferring methods as intended. Key focus areas will include the challenges associated with transfer, thorough risk assessment to identify potential pitfalls and mitigate risks early, practical considerations for sample size rationale calculation, and best practices to ensure seamless execution. It will highlight the importance of effective communication and collaboration between labs. Case studies will be shared to illustrate successful method transfers, including lessons learned.

• Data bottlenecks and model generalizability
• Hybrid models: merging structure-based simulations with ML
• Collaboration between formulation scientists and data scientists
• Validation strategies and industrial deployment​​

• Approaches to real-time data processing and decision-making in automated analytical platforms
• Role of machine learning and AI in interpreting multiplexed datasets
• Challenges in standardizing data formats and ensuring interoperability between instruments and software​

This presentation will address the challenges of maintaining product stability and recovery under in-use conditions for novel modalities administered at low doses. It will discuss the impact of formulation parameters and factors influencing low-dose compatibility on product safety and efficacy, using a case study to illustrate the crucial role of surface area to volume ratio and total surface area in the recovery at low concentrations.

Analytical control strategies for biologics and small molecules have traditional control strategies that require further improvements. Our integrated processes and analytical control strategy aim to simplify IPC, release, and stability quality control testing. I will present a step-by-step workflow for initiating and developing the end-to-end control strategy, identifying opportunities, prioritization based on ROI and business values, and the execution plan. For the execution proof-of-concept, we will share several case studies related to complex changes.

At Regeneron, we ensure high-quality reagents through comprehensive biophysical and biochemical characterization. This work highlights the characterization and optimization of two critical reagents using SDS-PAGE, Mass spectroscopy, Analytical Ultracentrifugation, Biacore and SEC-MS, linking their purity and structural integrity to bioassay performance. These case studies underscore the importance of high-quality reagents for consistent and robust potency assay development.

Host Cell Protein (HCP) assays play a key role during process development, characterization, and to support the analytical control strategy. The transition from a generic or platform ELISA to a process specific method can be challenge for in licensed or accelerated programs. A case study will be presented describing the strategy used for establishing a suitable project specific host cell protein assay to support late-stage program.

USP has a set of general chapters to guide bioassay work, from development to validation and even assay maintenance throughout the method’s life cycle. For bioassay development, a stepwise approach should be taken. An endpoint of assay development is to have assay procedure locked, a protocol for the performance of the bioassay is written. After that, method qualification and validation will be implemented to support tox study, clinical trial, and late-stage activities. Bioassays may evolve over time, life cycle management is required to ensure the quality of assay performance.

The concentration of crude oligonucleotide products is an in-process control that needs to be determined after synthesis before proceeding with the purification process. We evaluated SoloVPE as an alternative to LC-UV. Because SoloVPE is a test that can be performed on the manufacturing floor, it enabled generation of the data in a fraction of the time, thus allowing for faster and continuous processing of the material from synthesis into purification.