Raw material considerations.

Raw materials (RM) testing and control strategy form a major part of the foundation of a well-characterized protein (WCP) or biopharmaceutical. Raw materials may be present in the final vial as excipients or may have product contact earlier in processing. Manufacturers of WCPs should use a scientific approach to set acceptance criteria and test methods for bulk raw materials which are not present in dosage forms in substantial amounts.

Viral validation strategy for recombinant products derived from established animal cell lines.

For products derived from continuous cell lines, regulatory agencies worldwide require that the purification process be validated for its ability to remove or inactivate potential contaminants such as viruses and virus-like particles. New guidance suggests a requirement for statistical evaluation of these studies but the industry has yet to develop such standards. The task of estimating excess capacity is also complicated by variable assays, accumulation of variability in clearance estimates over unit operations, dependence of clearance capacity on operating parameters, and expense of experiments.

Human macrophage colony-stimulating factor heterogeneity results from alternative mRNA splicing, differential glycosylation, and proteolytic processing.

The single gene for human macrophage colony-stimulating factor (M-CSF, or CSF-1) generates multiple mRNA species that diverge within the coding region. We have characterized translation products of these mRNA species from native and recombinant sources. Immunoblots of reduced native M-CSF indicate that multiple glycosylated species ranging from 25 kd to 200 kd are secreted by human monocytes and cell lines.