Determining Maximum Recommended Starting Dose of Systemically Administered Biologics in First in Human Clinical Trials

Abstract

Determining Maximum Recommended Starting Dose (MRSD) in first in human (FIH) studies is a crucial milestone in the development path of a new pharmaceutical drug. It is imperative to determine what is the safe starting dose in these trials, as the drug would be introduced for testing in humans for the first time. There are guidelines from United States Food and Drug Administration (US-FDA) and European Medicines Agency (EMEA) that help in determining this dose. Several determination methods for calculating MRSD are in practice, including Minimal Anticipated Biological Effect Level (MABEL), No Observed Adverse Effects Level (NOAEL), and Minimum Effective Dose (MED) approach. This paper elucidates NOAEL and MABEL methods for calculating the starting dose. This paper also discusses the factors that help in determining which method to choose for a particular study.