Even if one understood little about the development of biologics, last month's congressional testimonies regarding data exclusivity
periods brought home a fundamental point: the complexity of biologics processing presents unique challenges not found in small-molecule
manufacture. As further evidence, at the AAPS National Biotech Conference, the emphasis was on innovation, with the critical
first step being the true understanding of the molecule, as plenary speaker Jim Thomas, Amgen's vice-president of process
and product development stated.
This understading would help define critical quality attributes as the biotech industry begins its discussion toward incorporating
the principles of quality by design (QbD), taking cues from the lessons learned in small-molecule production. As the meeting
progressed, however, the talk in the halls and in meeting rooms focused on a major obstacle: How does industry link molecular
structure and other attributes with biology and therapeutic effect?
The behavior of a biologic can be difficult to explain, let alone predict. One hot-topic problem discussed was the presence
of agglomerates, particulates, and subvisible particles in a formulation. These particles may (and may not) cause opalescense
and phase separation, but so too could mechanical stress, temperature, and pH, as Mary Cromwell (Genentech) explained. Whether,
then, immunogenicity is altered is a huge question. For now, until science bridges the gaps, we must settle for Wim Jiscoot's
(Leiden University) reply: "We simply don't know."
Maribel Rios is a senior editor of Pharmaceutical Technology.