Last week, the U.S. Food and Drug Administration (FDA) released draft guidance concerning the design of early stage clinical trials involving cellular and gene therapy (CGT) products. This guidance aims to assist drug manufacturers in developing what typically will be phase 1 trials, which include the “initial introduction of an investigational new drug into humans.”

Early stage clinical trials using CGT products can involve the consideration of factors that may not be as common to the design of other types of pharmaceuticals, such as clinical safety, preclinical, chemistry, manufacturing, and controls issues, thus the need arises for additional guidance from the FDA. The FDA noted that some CGT products “may pose substantial risks to subjects” because of their “high potential for immunogenicity, or the need for relatively invasive procedures to administer the product.” In addition, these types of products may be altered by the microenvironment in which they are placed and may differentiate into “undesired cell types,” so greater caution is necessitated.

In its draft guidance, the FDA listed various manufacturing, preclinical, and clinical trial design issues for manufacturers to consider before proceeding with the use of CGT products. One such issue is that certain CGT products can take multiple weeks to manufacturer and any delays in this process could impact an individual’s treatment regimen. Also, it is important to consider the dosing model used in humans because calculating based on animal studies “can be less reliable than the customary allometric scaling typically used for small molecule pharmaceuticals.”

With respect to the actual design of the early phase trial, the FDA stressed the importance of conducting a safety evaluation that would assess the “nature and frequency of potential adverse reactions and an estimation of the relationship to dose.” The risks and benefits of the trials may also vary based upon the study population, and subjects with “less advanced or more moderate disease” would most likely be able to tolerate the trial and retain function compared to sicker subjects. Finally, the FDA stressed the importance of adequate monitoring and follow-up to early phase trials to determine both “expected and unexpected safety issues.”

For more information, please see the FDA’s “Considerations for the Design of Early-Phase Clinical Trials of Cellular and Gene Therapy Products,” available here.