FDA-regulated research: cellular therapy considerations

Abstract

Background & Aim Regulatory approval from federal health agencies is a requirement to begin most phase 1 clinical trials with investigational agents. Enabling this approval requires evidence of previous human experience or, in the case of novel, fist-in-human treatments, significant preclinical data to support initial approval for use. Proof of concept, method of action and the penultimate safety studies are highly scrutinized and regulatory agencies often seek specific types of studies to provide this data. While a typical battery of pharmacological, pharmacodynamic, and toxicological tests are often used by the pharmaceutical industry, investigator-initiated trials by academic institutions need not always follow that route. In addition, the intricacies that surround cellular and gene therapy treatments make this data difficult to obtain or lacking in clinical relevance, thus dictating changes to the traditional IND-enabling roadmap. In addition to navigating the complex regulatory framework that is the US Food and Drug Administration, trial operation, product manufacturing, oversight and IND maintenance represent considerable hurdles which must be overcome. Despite these challenges, cellular and gene therapy INDs present unique opportunities to foremost provide lifesaving treatments but also do so without many conventional IND requirements. Careful consideration of these factors can lead the development of a successful and efficient implementation of a clinical research plan, so we have established a cell therapy IND algorithm and implemented a planning team to support investigators with a uniform and centralized process to ensure application success. Methods, Results & Conclusion Here we present our initial experience with this process in a new cell therapy program, discussing the pathway towards IND activation focusing on the intricacies that cellular and gene therapy trials present. We also provide our experience with over 20 active, under review and in preparation cellular therapy, gene therapy and combination product submissions. We further discuss type, quality (GLP, non-GLP), depth and breadth of studies required to enable investigator-initiated clinical studies, and challenges and opportunities in operationalizing cellular therapy clinical trials, both from a single- and multi-institution approach.