This presentation will provide an overview of some of the analytical tools that are used to assess the quality control strategies of advanced therapies. Specifically, we will discuss global efforts for standardization of methodologies that will support product consistency.

Cell count, a routinely performed fundamental measurement in the biosciences, underpins key decisions in the manufacturing, commercialization, and release of cell-based therapies. The industry seeks tools to gain greater confidence in cell counting measurements. NIST, in collaboration with industry and other government agencies, is developing strategies to provide fit-for-purpose measurement assurance for cell counting in the forms of written standards, experimental designs, and control materials.

Flow cytometry is considered highly complex and difficult, while CLIA’s personnel requirements for clinical flow cytometry are categorized as “high and moderate complexity”. Established manufacturers of flow cytometers have not adequately adjusted their design to accommodate users in the industrial bioprocessing sector. In addition, results from large-scale cell selection and cell characterization assays can vary significantly due to challenges in assay development and technology transfer.

This presentation will discuss considerations when selecting excipients, formulation studies, and novel excipients; what does this mean and what is needed?

Making changes to the manufacturing process is an inevitable part of making a better product. There is a risk if manufacturing changes are made late in the clinical trials that they could potentially change the product’s critical characteristics. In this context, I plan to describe the obstacles and challenges to establishing products’ comparability and discuss the minimal essential elements of a good comparability study and provide a theoretical case study to illustrate how these best practices should be applied.

Determination of comparability for cell and gene therapy products is a continual challenge as these products grow in complexity and accelerate through clinical development. Setting out a strategy for comparing products needs to follow
a set of questions that answer when, why, and how this can be accomplished. This talk will examine setting up a successful approach for comparing cell and gene therapy products through analytical assessment and product function.

Characterization of cell and gene therapies with robust, reproducible, and innovative ligand-binding assays during bioprocessing is an important tool in product characterization to show comparability. We highlight how a microfluidic, automated immunoassay platform streamlines workflows for lentiviral and AAV vector titer and characterization of host cell protein impurities during bioprocessing.

A key hurdle to ensuring patient access to cell and gene therapies (CGTs) and continued growth of the industry is the management of raw materials. The combination of rapid growth, individual product and process complexity and limited industry-specific guidance or awareness presents non-obvious risk mitigation challengesfor transitioning from development to clinical application. Understanding, assessing and mitigating the varied raw material risks for CGT products during product and clinical development are critical for ensuring smooth transitions into commercialization and for preventing interruption of product supply to patients.This article presents a risk-based approach driven by concerns for patient safety that can help focus and coordinate efforts to address the most critical risk factors. Highlighted are some of the highest risk materials common to the manufacture of many CGTs, including the primary starting material, culture media, reagents and single-use components. Using a hypothetical gene-edited cell therapy as an example, we describe the general manufacturing process and subsequently incorporate the described methodology to perform a sample risk assessment. The practical approach described herein is intended to assist CGT manufacturers and suppliers in actively assessing materials early in development to provide a basic starting point for mitigating risks experienced when translating CGT products for clinical and long-term commercial application.

Discussing the cost of goods and common challenges associated with successful process development and GMP manufacturing of cell therapies, from an academic Phase I/II perspective.