Evaluating manufacturing process profile comparability with multivariate equivalence testing: Case study of cell-culture small scale model transfer.

This article studies the Generalized Mahalanobis Distance (GMD) approach proposed by Hoffelder which measures the dissimilarity of two multivariate Gaussian distributions with arbitrary covariance matrices and unequal sample sizes. This investigation demonstrated that, with appropriate adjustment, the GMD approach can achieve the targeted nominal Type I error and provide sufficient power for testing equivalence between two profile populations. The adjusted GMD approach was applied to examine the equivalence of harvest profiles between a 12L small scale model and 2000L manufacturing scale in a transfer study performed at Sanofi Specialty Care Framingham Biologics.

Mechanistic complexity of subvisible particle formation: links to protein aggregation are highly specific.

There is little knowledge available on the mechanistic features of the protein aggregation pathway, which lead to subvisible particles (SVPs) (0.1-100 µm in size). Additionally, the relationship between soluble aggregates (SAs) (those that are less than 0.

Endosialin is expressed in high grade and advanced sarcomas: evidence from clinical specimens and preclinical modeling.

We previously surveyed the expression of endosialin/ CD248/TEM-1 by immunohistochemistry in human clinical specimens of sarcomas and documented expression in tumor cells, stromal cells and vasculature. In the present study, we completed a retrospective analysis of the diagnostic reports available for these same samples in order to identify high-grade and metastatic disease. Our results show that endosialin can be detected in advanced disease.