Abstract

The purpose of this entry is to describe some statistical approaches that might be considered when designing and analyzing comparability studies for biological products or processes. In its most basic form, a comparability study seeks to compare a “test product” to a “reference product.” This is accomplished through evaluation of the extensive data obtained on both the test and reference products from analytical and biological assays as well as from nonclinical and clinical testing. To conclude two products or processes are comparable it is first necessary to define a standard for demonstrating comparability. Without a precise, quantitative definition that is accepted by regulatory authorizes and the scientific community, it is impossible to prove conclusively that two products (or processes) are indeed comparable. But defining such a standard is not straightforward and often relies on expert opinion that, ideally, is driven by quality considerations, regulatory guidance and clinical safety or efficacy concerns. The usual bioequivalence approach that is appropriate for generics is not acceptable for biological products or processes due to their complexity. Regulatory guidance recommends following a step-wise approach utilizing a totality-of-evidence strategy, which requires collaboration among the pertinent experts, including statisticians. The demonstration of comparability does not necessarily imply that the test and reference products are identical but does ensure that any difference or change between them is not considered scientifically or clinically relevant.