ABSTRACT
As indicated in the earlier chapters, there are some fundamental differences between biologics and small-molecule drugs. Small-molecule drugs are prepared by chemical synthesis, which are usually not sensitive to process changes, while biological products are made of living cells or organisms, which are very sensitive to process changes. A small change in manufacturing conditions could result in a drastic change in clinical outcomes. In practice, even minor modifications of the manufacturing process can cause variations in important properties of a biological product. Biologics, which possess sophisticated three-dimensional structures and contain mixtures of protein isoforms, are 100-fold or 1000-fold larger than small-molecule drugs. A biological product is a heterogeneous mixture and the current analytical methods cannot characterize these complex molecules sufficiently to confirm structural equivalence with the reference biologics.
