Preparing for the Clinic

Abstract

Transitioning from preclinical to clinical development can be both an exhilarating and a sobering experience. Presumably, our drug has passed through a rigorous battery of preclinical testing and appears to have the desired safety profile and pharmacologic characteristics for advancement to human study. But embarking upon human experimentation is a serious undertaking. We must ensure that our clinical trial is designed and conducted in as safe a manner as possible. We have an ethical responsibility to ensure that our clinical trial has been designed to optimize the probability of obtaining meaningful results since we are exposing human subjects to a potentially toxic new molecular entity. Furthermore, the drug must be manufactured and quality-tested using exacting standards, typically by a reputable contract manufacturing organization (CMO). Both the Food and Drug Administration (FDA) and Institutional Review Boards (or Ethics Committees outside of the USA) seek to ensure that patients are protected and that the risk-to-benefit ratio is acceptable for any clinical study. Early in the planning process, the development team should engage experts in drug manufacturing and quality control, clinical trial design, and regulatory science. Before the clinical trial can commence, the sponsor (company or physician) must file an Investigational New Drug application (IND) with the FDA. The IND provides detailed information on the nonclinical pharmacology and safety studies, the drug manufacturing and quality assurance (QA) process, and the clinical trial protocol. This chapter provides an overview of clinical trial design, acquisition of clinical grade drug product, and regulatory considerations during the transition into the clinic. Because clinical trials are so expensive, failure to appropriately design the clinical trial can obscure efficacy and force a program to close. Even seasoned clinicians would be wise to talk with other experts before embarking on a clinical trial.