For cell and gene therapies, all stages of the drug development life cycle are complex. The patient, product and supply chain requires specialized sets of capabilities, as standards and protocols differ from more traditional therapy areas.
Specifically, cell and gene therapy development present unique chemistry, manufacturing and controls (CMC) challenges because of inherent properties such as shorter shelf life, variability in starting and ancillary materials, manufacturing and logistical complexities, and cost.
Below is a case study in which strategic regulatory and CMC expertise from Cardinal Health Regulatory Sciences helped guide a biopharmaceutical company’s regulatory and development strategy for a cell and gene therapy product.
Avoiding a clinical hold
A biopharmaceutical company focused on developing novel autologous T-cell therapies had promising findings targeting a rare-disease tumor type. The product had reached the stage in the development pipeline where the company was ready to assemble its Investigational New Drug application (IND). The company referenced a drug master file (DMF) filed by their contract manufacturer in order to provide the required information for the IND, but upon submission, the FDA indicated that there was insufficient data within the master file. The company had only a matter of days to provide the required additional data to ensure that their IND review would continue and not lead to a clinical hold. Experts from Cardinal Health Regulatory Sciences were selected to quickly advise on the next steps.
Additional submissions to advance IND review
The Cardinal Health Regulatory Sciences team began auditing the information that was originally submitted. They quickly recognized that insufficient process-specific DMF information for this type of manufacturing process had been provided in the submission. Experience and fluency with these types of submissions allowed the team to quickly identify the issue. They realized that specific product quality information was needed on ancillary materials used in the manufacturing process, as well as additional information about the manufacturing equipment to ensure that the product would not be contaminated during manufacturing. Within days, the team formulated a strategy and assembled all outstanding information required, ultimately receiving notification that the IND could proceed.
Recovering at-risk clinical batches
The biopharmaceutical company continued to partner with the Regulatory Sciences team to help address significant incidents or amendments that required a timely, strategic response. Some early clinical batches failed release specifications, so the team worked with the company to craft a package for review, to ensure that the batches could be used. The information package included a summary of the investigation into the manufacturing process and analytical testing, the failed test result, the justification and corrective actions as needed and a patient risk/benefit statement. As patients awaiting these therapies are often in dire need and the shelf life of autologous T-cell therapies is extremely short, the submission was extremely time sensitive. The prompt and thorough submissions from the Regulatory Sciences team convinced the FDA to grant an exception for product release and ensured that the custom products were delivered.
Support during clinical development
CMC requirements are very complex for cell and gene therapies, with no room for error or contamination. The Cardinal Health Regulatory Sciences team continued to work with the company throughout the clinical trial and provided multiple follow-up IND amendments with improvements in analytical methods, including rapid microbiology methods and manufacturing processes. The Regulatory Sciences team advised on comparability protocols and data required to support changes in manufacturing sites, while still ensuring proper maintenance of product quality attributes. Their CMC expertise ensured that the company continuously provided improvements and amendments to their IND as advances were made throughout the development process. The orphan drug is currently in phase one clinical trials and multiple lots have been successfully administered.