By Jeff Mazzeo, Biopharmaceutical Business Director, Waters Corporation
Large molecules pharmaceuticals, also referred to as biotherapeutics, are the fastest growing segment of the pharmaceutical industry. It is becoming more apparent that these large-molecule biotherapeutics, based on recombinant technology, are increasingly contributing to the drug pipeline. An important implication of this trend is that pharmaceutical analytical laboratories traditionally focused on small-molecule therapies are more often being asked to take on large-molecule projects.
While this transition may seem to be straightforward, it is not that simple. For example, take the case of process-related impurities. Certainly impurities are a challenge for small-molecule therapeutics, however because these therapeutics are made using organic synthesis, the number and type of process related impurities are typically much smaller compared to large-molecule biotherapeutics, which are made by living organisms. The process for making large-molecule therapeutics presents potential for a wide variety of process-related impurities that need to be controlled and analyzed throughout the development process. Furthermore, both due to their large size and the process by which they are made, large-molecule drugs have a high degree of microheterogeneity. This microheterogeneity must be also controlled and analyzed throughout the development process. The combination of the size of the molecules and their heterogeneity necessitates a battery of analytical techniques be applied to their analysis and characterization.