What is a “Well Characterized Biotechnology Pharmaceutical” (WCBP)?

Founded on the robust drug development database provided by sectors of the biotech industry, the US FDA Center for Biologics Evaluation and Research (CBER) coined the term “Well Characterized Biotechnology Pharmaceutical” for their 1996 symposium “Characterization of Biotechnology Pharmaceutical Products.” Both the advances in analytical biotechnology and the limitations of the available methodologies were discussed, serving as a basis for improving the regulation of biotechnology products.

Prior to 1996, CBER required for product approval both a Product License Agreement (PLA) and an Establishment License Agreement (ELA). The ELA was specific to the facility and process used for that product and prohibited unapproved process fluctuations. For the often very complex and frequently poorly characterized biological products (e.g. vaccines and blood products) the controlled process and facility constraints of the PLA/ELA combination helped ensure the reproducible manufacture of safe and efficacious biologic products.

Both the advent of recombinant gene technology to enable large scale, purified protein manufacture and the development of modern analytical technology to characterize molecular diversity, has facilitated the regulatory evolution of the WCBP concept. When a protein pharmaceutical was “well characterized”, the natural molecular heterogeneity, impurity profile, and potency could be defined with a high degree of confidence. From those discussions in 1996, CBER developed a new approval mode, the Biological License Application (BLA), which places primary emphasis on the detailed analytical characterization of the molecular entity (well characterized) as a means of establishing a reproducible manufacture of the biological pharmaceutical. Nevertheless, the manufacturing process and its inherent critical controls are still addressed, remaining paramount in importance and intrinsically tied to the product. For licensed biotech pharmaceuticals, changes to an existing process may be approved without additional clinical efficacy trials via “comparability protocols”. Although the term “well characterized biological” has been abandoned, having evolved into “specified biological”, the symposium organizing committee has kept the WCBP acronym as a reference to how state of the art bioanalytical methodology drives the evolution of new regulatory policy.