BACKGROUND The bottleneck for real time control and real time release is lack of product‐specific in‐line sensors or fast at‐line methods suitable for model‐based prediction of process outcome. The most common sensors for protein purification are UV absorbance values measured at 280 and 260 nm. They have very high selectivity for proteins which contain aromatic amino acids. The 260 nm signal is more selective for nucleic acids. This work addresses the question if osmolality can be used as an additional predictor for protein purification. RESULTS An antibody intermediate purification step in flow‐through mode was evaluated. The flow‐through fractions were collected and then subjected to analysis for antibody concentration and osmolality. UV280, UV260, UV214, pH and conductivity have been measured on‐line by the chromatography workstation. Different combinations of on‐line sensor signals and osmolality have been used to find out if molality is a valuable predictor. The root mean square error was used for assessing the quality of the model‐based prediction of quantity with partial least squares in this chromatography process. Predictors UV280, UV260, UV214, pH and conductivity showed equal root mean square error (0.274) as UV280, UV260, UV214, pH, conductivity and osmolality (0.274). Lowest mean square error (0.244) was found with UV280, UV260 and osmolality as predictors of quantity. CONCLUSION Osmolality as an at‐line method is an excellent predictor together with UV280 and UV260 for protein quantity in model‐based prediction using partial least squares methodology. © 2019 The Authors. Journal of Chemical Technology & Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Background: Antibiotic lock therapy is an interventional modality used for treatment and prevention of central-line associated bloodstream infections. Stability and compatibility data for combinations are lacking, limiting clinical use. Objective: Compatibility and stability of daptomycin lock solutions in combination with azithromycin, gentamicin, and heparin or sodium citrate were evaluated up to 96 hours. Methods: Eight candidate lock solutions were prepared for compatibility and stability testing. All solutions were prepared in glass vials, and included daptomycin 1mg/mL in varying combinations with heparin 100 – 1,000 units/mL, trisodium citrate, azithromycin and/or gentamicin. Lactated Ringer’s solution was added as a diluent in a sufficient quantity to bring the total volume up to 5mL. Drug stability in the admixture was determined by the degradation of the components. The quantification of drugs was performed using Waters Alliance HPLC using Phenomenex Luna C8 (2), 150*2.6mm, 5µ column. A gradient run was executed for 20 minutes with 0.45% ammonium dihydrogen phosphate, pH 3.25 as eluent A and acetonitrile as eluent B at a flow rate of 1.0mL/min. Each solution was visually inspected for particulates and color change. Lock solutions were tested in triplicate. Results: Daptomycin degradation was <10% for all solutions at 48 hours, and for 7 of the 8 solutions at 72 hours. Gentamicin degradation was <5% for solutions in combination with daptomycin and trisodium citrate. No physical incompatibilities were detected. Conclusion: Study data support the stability and compatibility of daptomycin with additives in solution, allowing for fewer exchanges and longer dwell times for a lock solution. The addition of azithromycin or gentamicin may offer synergy and/or extended spectrum of activity. Daptomycin bioactivity with trisodium citrate needs confirmation.