Cell culture media impact on drug product solution stability.

To enable subcutaneous administration of monoclonal antibodies, drug product solutions are often needed at high concentrations. A significant risk associated with high drug product concentrations is an increase in aggregate level over the shelf-life dating period. While much work has been done to understand the impact of drug product formulation on aggregation, there is limited understanding of the link between cell culture process conditions and soluble aggregate growth in drug product. During cell culture process development, soluble aggregates are often measured at harvest using cell-free material purified by Protein A chromatography. In the work reported here, cell culture media components were evaluated with respect to their impact on aggregate levels in high concentration solution drug product during accelerated stability studies. Two components, cysteine and ferric ammonium citrate, were found to impact aggregate growth rates in our current media (version 1) leading to the development of new chemically defined media and concentrated feed formulations. The new version of media and associated concentrated feeds (version 2) were evaluated across four cell lines producing recombinant IgG4 monoclonal antibodies and a bispecific antibody. In all four cell lines, the version 2 media reduced aggregate growth over the course of a 12 week accelerated stability study compared with the version 1 media, although the degree to which aggregate growth decreased was cell line dependent. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:998-1008, 2016.

Sun exposure as a risk factor for nuclear cataract.

BACKGROUND: Cataracts are the leading cause of blindness and visual impairment throughout the world. An association of sun exposure with cortical cataract has been well established, but the association with nuclear cataract remains unclear. METHODS: This case-control study was nested within the Nambour (Australia) Trial of Skin Cancer Prevention conducted between 1992 and 1996. We compared 195 cases who had a nuclear opacity of grade 2.0 or greater with 159 controls. Structured questionnaires were used to ascertain lifetime sun exposure history, eyeglasses and sunglasses use, and potentially confounding variables such as education and smoking. RESULTS: There was a strong positive association of occupational sun exposure between the ages of 20 and 29 years with nuclear cataract (odds ratio = 5.9; 95% confidence interval = 2.1-17.1). Exposure later in life resulted in weaker associations. Wearing sunglasses, particularly during these early years, afforded some protective effect. CONCLUSIONS: This study provides new evidence to support a link between sun exposure and nuclear cataract. Risk was highest among those with high sun exposure at younger ages.