Regulatory Issues and Drug Product Approval for Biopharmaceuticals

Regulatory Issues and Drug Product Approval for Biopharmaceuticals

INTRODUCTION

The term “biopharmaceuticals” is used to describe biotechnologically derived drug products. Biopharma-ceuticals are protein-based macromolecules and include, insulin, human growth hormone, the families of the cytokines and of the monoclonal antibodies, antibody fragments, and nucleotide based systems such as anti-sense oligonucleotides, siRNA and DNA preparations for gene delivery. These are large complex molecules and are often heterogeneous mixtures compared to synthetically manufactured, pure small molecules.

In the first years of the new millennium the regulatory landscape for biopharmaceuticals changed. Before that time only original biopharmaceuticals were approved by FDA and EMEA (Table 1) following the normal pathway of approval including full scale clinical trials to ensure efficacy and safety and this pathway still stands for original biopharmaceuticals. Then, a number of biopharmaceutical drugs ran out of patent and the introduction of generic versions of biopharmaceuticals became the center of lively debates: the new products were called biosimilars (EMEA) or follow-on biologics (FDA) and issues of debate were, for instance, structuring of the clinical trial programs. The regulatory process for biosimi-lars/follow-on biologics is an evolutionary process. Up until recently we have considered biopharmaceu-ticals as one homogeneous class of compounds. But, that is an oversimplification. The requirements for approval of biosimilar products should be based on the structural complexity and clinical knowledge of and experience with the reference biopharmaceutical product. The information provided here reflects the status at December 2006.