Purification therapeutic biologies

The extraction and purification of proteins from organisms or biological tissue can be a laborious and expensive process, and often represents the principal reason why vaccines and other therapeutic agents reach costs that become unattainable for many. Downstream processing also can be a major obstacle with respect to cost for large-scale protein manufacturing in plants. However, purification from plant tissues, while still costly, is in general less expensive than purification from their mammalian and bacterial counterparts. Indeed, some plant-derived biopharmaceuticals, such as topically applied monoclonal antibodies, may require only partial purification and thus be even less intensive in terms of labor and cost. 

Metabolites, vitamins, organic and amino acids, and specialty chemicals are commonly referred to as small molecules, particularly in the therapeutic world to differentiate these compounds from proteins or peptides, commonly named biopharmaceuticals or biologi-cals. Many of the same unit operations are applied for the recovery and purification of small molecules as described above. Purification of bulk products has cost constraints, whereas pharmaceuticals are subject to strict purity requirements. 

The development of proteins as therapeutics prior to the 1980s suffered from some major limitations. In some instances, concentration of the desired protein in the sonrce material was low, rendering its isolation and purification laborious and expensive. In other cases, the ability to produce sufficient quantities of some proteins was limited by the availability of starting material, resulting in insufficient production to meet the needs of the patient population. Aside from the quantitative limitations, the presence of infectious agents, mainly viruses, in the tissues and biological fluids of humans and animals posed the risk of infection to the patients. All protein drugs suffered from one or all of these drawbacks (Snape, 1991). 

In the discovery and development of hylan A and hylan B, of course, the most important criteria were their purity and biocompatibility. We could never have used these two molecules as therapeutics without the availability of the test that I developed in the late 1960s to monitor the purification process for the native hyaluronan, and producing NIF-NaHA. This test method was accepted by many regulatory agencies as a standard way of proving the biological compatibility of elastoviscous fluids used in ophthalmic... 

---