Last week, FDA published draft guidance on Manufacturing Changes and Comparability for Human Cellular and Gene Therapy Products. It’s a great start for an industry that’s been hungry for standardization.
The state of CGT guidelines today
The past few years have seen a broad array of cell and gene therapy (CGT) technologies in development, and a similarly wide range of analytical approaches to quality control. Historically, companies in this space have each built bespoke workflows dependent on enough cells to split into multiple distinct assays for transduction efficiency, surface protein expression and editing analysis, and a pipeline to piece the data together. The process is needlessly time-consuming and complex.
As noted in the guidance, “CGT products can be highly sensitive to manufacturing changes,” and precise analytical methods are needed given that small variations in an attribute can have a profound impact on quality. Through a string of clinical holds across the industry, we have seen the need for better analytical assays, especially for clinical batch lots. That was the inspiration behind the CGT assays we’ve developed on our Tapestri Platform, to ensure patient safety and cell product quality. Through just one assay, developers can assess multiple genetic attributes along with immunophenotype in 20,000 cells at a time, at single-cell resolution, producing robust data. In one recent example, comparability release studies by a gene therapy developer showed that Tapestri offered more precise transduction efficiency measurements than their ddPCR-based method and reduced workflow time from several weeks to two days.
The guidance also spells out the types of CMC (chemistry, manufacturing, and controls) changes that would require a new IND (investigational new drug) submission. This serves as a reminder that better characterization of cell therapies before reaching the clinic is critical to prevent avoidable issues that could endanger patients.
The future of CGT standardization
As FDA finalizes its guidance, we encourage the agency to refer to the work ongoing by National Institute of Standards and Technology’s Genome Editing Consortium. Through the consortium, leading genome editing researchers and cell therapy developers are helping develop industry standards for analytics by assessing the capabilities of a range of assay technologies. Consistent with FDA’s goals, we believe the results of these studies will provide invaluable clarity, laying the groundwork for cell therapy’s limitless future.