We will present our recent advances for Bayer's Cell Therapy Platform. Especially, I will focus on how our progress in PAT and automation supports switching from highly manual adherent iPSC cultivation processes to fully automated and closed robotic-controlled cultivation systems with a portfolio of in-line and at-line PAT methods supporting close process monitoring.

This topic explores the integration of microfluidics and miniaturized sensors in bioprocess technology, emphasising lab-on-a-chip (LOC) systems designed for real-time monitoring and control. Advanced 3D printing techniques enable the creation of intricate, customisable microstructures that enhance the precision of biological sample handling and process control. Integrated miniaturised sensors facilitate continuous, real-time detection of critical-process parameters, significantly improving bioprocess efficiency.

Key examples include 3D-printed micromixers for rapid and uniform mixing, spiral separators for continuous cell separation, and microfluidic sensor systems for monitoring process parameters and essential analytes in cell culture, all contributing to enhanced process optimisation.

Accelerated development timelines present unique challenges for analytical workflows. This presentation highlights strategies for adapting internal processes to maintain high standards of quality and compliance while meeting rapid development goals. Explore practical solutions for streamlining analytical methods, integrating automation, and improving cross-functional collaboration to ensure efficiency without compromising the robustness of biotherapeutic development.

The multi-attribute method (MAM) shows promise in biopharmaceutical analysis, potentially replacing traditional methods and closing control-system gaps. This presentation will address challenges such as IT system and instrumentation preparation, method development, suitability assessment, and validation. As Roche/Genentech implements MAM for quality control, practical insights and experiences in overcoming these barriers will be shared.

The pharmaceutical industry is focusing on patient convenience and decentralised care, driving the need for high-concentration liquid formulations with stable protein behavior. However, predicting protein behavior at high concentrations-including risks like viscosity or aggregation-remains challenging, especially with complex molecular designs. We present an early screening process using high-throughput assays to assess critical solution parameters and predict developability risks across various molecule formats early in drug discovery.

Molecular properties that impact developability attributes and outcomes comprises of conformational, chemical, colloidal, and other interactions. These attributes are measured using relevant analytical methods to assess the developability/ manufacturability of the molecule in different formulation. Developability assessment of mAbs has been studied and applying this assessment using the right tools to new modalities such AAV will help streamline capsid selection and candidate selection from discovery to development for new modalities

Ensuring the success of novel biotherapeutics requires rigorous developability assessments and formulation strategies. This presentation delves into methods for evaluating the physicochemical properties and stability of new biologic candidates. Learn how early-stage assessments can inform formulation development to improve manufacturability, enhance stability, and address potential challenges before clinical stages, ultimately accelerating the path to market for innovative therapeutics.

The development and formulation of therapeutic antibodies is a highly complex optimisation task requiring significant time and resources. This can be particularly problematic for emerging engineered antibody formats, such as fragments and bispecifics, which can suffer from developability issues. Here we show a Bayesian optimisation method to improve multiple developability properties simultaneously through formulation design.

We will provide an overview of how various PAT and Data-Driven approaches are used in different process units in our Drug Substance Process Development. we will showcase several PAT applications and how we use them to improve productivity and reduce development timelines. Finally, we will address challenges and pitfalls encountered during implementation of these approaches and share our future vision of using these approaches to transform pharmaceutical manufacturing.

Though AI, ML, and other modern algorithmic data analysis techniques are poised to provide a range of benefits across the biopharmaceutical industry, these advances will be particularly impactful to analytical development. This talk will highlight key considerations from a CMC perspective when implementing AI/ML in analytical development. Additional focus will be placed on recent regulatory guidance pertaining to the development and validation of analytical methodologies utilising algorithmic data processing techniques.

Data obtained and processed near real-time can provide information to confer consistent product quality, less product and resource wastage, and increased productivity, irrespective of variations in process, materials, and operating environment. The practical implementation of Process Analytical Technologies (PAT) requires, however, analytical methods offering sufficient speed, selectivity, and sensitivity. An online Liquid Chromatography (LC) setup enabling real-time monitoring of product quality will be presented.

Clinical therapies based on cells have the potential to cure many diseases. However, populations of cells cannot be purified or analyzed as stringently as drugs. By analyzing changes in macromolecular cell composition, Raman microscopy offers a label-free approach to validate both biomanufacturing processes and final cell products. Using Raman microscopy, we have detected early apoptosis, distinguished stem cells from their differentiated progeny, as well as T-cell subtypes and activation states.

In the rapidly growing field of mRNA medicines, monitoring the efficiency and integrity of the in vitro transcription (IVT) is crucial. Precise monitoring of nucleoside triphosphate (NTP) bases and RNA molecules during IVT is essential for optimising reaction conditions and ensuring high-fidelity RNA synthesis. This presentation discusses the innovative use of Raman spectroscopy as a non-destructive analytical tool that overcomes the limitations of conventional techniques. A data-driven case study will be highlighted which shows that Raman spectroscopy can be used to monitor the consumption of NTPs and formation of mRNA product during the IVT reaction.