The complexity of gene therapy products and the constant changes in production sites and manufacturing processes pose challenges to developers regarding reproducibility and comparability of results. This presentation will highlight the challenges in analytical measurements for gene therapy and the significance of global available Standards in enabling data comparability cross-manufacturing processes and clinical trials.

• Demonstrating the methods are stability-indicating
• Types of stability study and their purpose
• Excipient stability​

Sensorion is a biotech company dedicated to the development of therapies to treat, prevent and restore in the field of hearing loss. Two novel gene therapy programs include deafness due to Otoferlin deficiency as well as Usher Syndrome type 1. Since the Otoferlin gene exceeds the AAV packaging capacity, the dual AAV vectors have been developed. The product characterization and quality control of these vectors will be discussed.

To make good decisions in the manufacturing of gene therapy vectors, scientists need high-quality analytical information, immediately. Transmission electron microscopy (TEM), enables direct visualization of viral vectors and their assessment by a comprehensive morphological characterization. Using our intuitive TEM systems for the analysis of viral vectors allows monitoring product contamination, purity and morphology in-house by non-experts rapidly, saving time, money, and delivering a safer and better characterized final product.

Molecular complexity is magnified significantly with cell and gene therapies, as is the need to pursue adaptation, targeted innovation, translation, and implementation of high resolution analytical measurement approaches to further the understanding and development of these novel modalities.This talk will describe the translation of how multi-attribute mass spectrometry method (MAM) and ion mobility-mass spectrometry (IMS-MS) analyses enable advances in the identification and control of viral vector quality attributes.

As the gene therapy field continues to expand and companies increase the number of product batches manufactured per year, the burden on quality control for product release increases significantly. The presentation will showcase CGT Catapult’s advanced analytical platform for AAV product characterisation, which includes assay development for improving precision, assay automation and in-line product characterisation for closed processes.

Distinguishing aggregated API from other particle types is important for understanding the root cause of instability. Existing methods are unreliable, too cumbersome and difficult to use in many workflows. With Aura, you can now finally count, size, and characterize aggregates and identify them as proteins, non-proteins, or other molecules.

The quality and performance of complex analytical reagents are arguably as critical to product quality as raw materials.  Even different batches of some materials may require re-evaluation of the analytical method at some level, especially where custom made.  This talk will discuss what is expected along with tips and advice on how to avoid issues.

One of the primary challenges in manufacturing of vaccines is rapid feedback on biophysical properties that represent critical quality attributes (CQAs). Lacking real-time measurements of these quantities, the process must be sampled for at-line or off-line characterization, leading to delayed response.

This talk focuses on real-time multi-angle light scattering (RT-MALS). This novel process analytical technologly measures key quality attributes of macromolecules and nanoparticles: Molecular weight, size and particle concentration.

In this talk we describe the process adaptions and challenges during scale-up from small scale into final GMP scale. We present the elimination of all open process steps e.g. by implementing closed systems for ultracentrifugation to ensure scalability and consistent quality of the drug product. Further, we provide our concepts regarding removal of potential adventitious agents and our considerations in terms of low product volumes towards the end of the downstream process.

Transient transfection of suspension cells is the most commonly used method for AAV manufacturing. However, this method shows some limitations when upscaling the process. To address this concern, we developed a novel transfection reagent showing increased AAV titers and improved transfection protocol for large scale bioreactors.

The use of lentiviral vectors in cell therapies require the manufacture at large scale of high quality material to enable efficient cell transduction. This work discuss the main challenges lentiviral vector cell therapies face and present strategies and novel technologies to be adopted to enable effective manufacture as well as cell transduction. of cells.

Immunoassays are commonly used to analyze titers and impurities during viral vector bioprocess development, but drawbacks in precision, dynamic range, and lengthy protocols are problematic. Advances in immunoassay technologies have improved assay robustness and throughput, reducing delays in cell and gene therapy manufacturing. Examples from Gyrolab® microfluidic, CD-based immunoassay platform will be presented demonstrating AAV vector titer, LV titer, and HEK 293 host cell protein impurity analysis improvements. 

Lentiviral vectors have been increasingly used as a tool for gene and cell therapies. Currently, the low stability of this virus, mostly due to the fragility of the membrane envelope, sensitivity to pH, and conductivity variation is hampering the clinical-to-market transition. To overcome some these hurdles in downstream, we report an improved lentivirus purification process focus on the use of new materials as a replacement for traditional purification techniques.

There is a need for advanced process analytical technologies that can monitor essential bioreactor nutrients and cellular metabolites alongside bioreactors in process development labs. Shown here is a new benchtop analyzer called the REBEL. The REBEL enables wide (32 analytes) and rapid analysis of cell media with just ten microliters of sample to expedite process development decisions. This presentation will highlight the platform's general capabilities and several applications.