There are numerous gene therapy product candidates in late-stage clinical development for a variety of applications including rare diseases. Some of these applications offer an opportunity for accelerated approval. While clinical data may provide a rapid path to approval, there remains a huge challenge in providing a robust CMC package that supports accelerated approval. Spanning the gap between these new treatments and more established biological modalities is a major technical and process knowledge challenge. This process knowledge gap is often due to the lack of attribute focused methods and analytical monitoring of non-essential attributes and lack of in-process and characterization data required to fully understand the manufacturing process and allow appropriate process control. Strategies will be presented on the appropriate monitoring of gene therapy product impurities with adeno-associated virus (AAV) data as a case study. Process characterization assays will be presented along with recommendations on supporting orthogonal methodology.  

A successful transfer of analytical methods into QC labs is key for GMP release and stability testing of therapeutic proteins. Product-related impurities are monitored typically by SEC, CE and cIEF, and transfer of these methods involves challenges and requires dedicated efforts and turnaround times. This presentation shows a few cases of how we handle such difficulties and meet timelines.
 

To prevent costly changes to a manufacturing process, it is important to assess which unit operations offer the best removal or inactivation of adventitious agents during downstream process development. This talk addresses the viral clearance capabilities of an affinity resin engineered for adeno-associated virus (AAV) gene therapy applications and utilized a non-infectious viral surrogate to define the operational space in which MVM is removed.

The goal of this presentation is to share recent developments in the analytical approaches to detect, quantify, and differentiate impurities in biologics that are the result of protein-container interaction and aggregation.

Polysorbates are prone to chemical degradation, which can be exacerbated by other excipient and processing impurities, and ultimately compromise the integrity of the final drug product. Additionally, polysorbate micelles create processing challenges because of their similar size to antibodies. Here we present data for alternative excipients that can prevent particle formation in antibody processing and formulation, including chemical stability compared with polysorbate and utility in downstream processing applications.

Particle sizing and analysis are essential steps in formulation development and the monitoring of manufacturing process controls. Scaling to production may introduce previously unobserved extrinsic particles. This presentation will discuss how the identification capabilities of the Hound platform complement particle size and morphology information when unknown particles are observed.

Virus-like particles and other extra cellular particles are a next generation of biopharmaceuticals. They can be produced by a wide variety of host cells. The challenge is the production of high titers and downstream processing. The particle of interest is contaminated with other particles with similar biophysical properties and therefore difficult to separate. Examples will be given for 3 different cell types.

The purification of adeno-associated virus has become an increasingly important topic in the field of biomanufacturing as the prevalence of AAV gene therapies increases. One of the major hurdles facing AAV purification is the separation of empty capsids from full capsids. This presentation will address Precision BioSciences’ advances in downstream chromatography for both capture and empty full separation steps.