Early Phase Clinical Trials of Biopharmaceuticals

New pharmacological treatments are currently evaluated in humans through clinical pharmacology trials in gradually rising numbers of healthy and patient volunteers. Sufficient information about safety, pharmacokinetic parameters and ideally efficacy, has to be gained before confirmatory therapeutic studies can be justified and accepted by the regulatory agencies, ethics committees, patients and clinicians. Clinical trials of new putative therapeutic agents performed in healthy volunteers (human pharmacology studies) are not considered mandatory, but in practice are frequently requested and conducted. With the exception of cytotoxic compounds, these studies are useful in bridging the knowledge gap between animal and patients during these challenging exploratory phases. The information obtained by pharmacokinetic parameters and safety/tolerability profile of different dose levels will be made available to investigators and clinicians for a rational management of clinical situations in patients. Biopharmaceuticals differ in various ways from the typical chemical entity and some alternative approaches to both the preclinical and clinical evaluation must be considered during the development of this varied class of products. It is acknowledged that a flexible, case-by-case approach is particularly appropriate for biotechnology-derived pharmaceuticals. The main aim of this article is to give a brief introductory overview of the key points to be considered before and during the initial evaluation of biopharmaceuticals in humans. Emphasis will be placed on the general principles applied by investigators to minimise mistakes occurring during the clinical development phase.