When human polymorphonuclear basophils, a type of white blood cell with antibodies of the immunoglobulin E (IgE) type on its surface, are exposed to anti-IgE antibodies, they release histamine from their intracellular granules and change their staining properties. The latter can be demonstrated at dilutions of anti-IgE that range from 1 x 10(2) to 1 x 10(120); over that range, there are successive peaks of degranulation from 40 to 60% of the basophils, despite the calculated absence of any anti-IgE molecules at the highest dilutions. Since dilutions need to be accompanied by vigorous shaking for the effects to be observed, transmission of the biological information could be related to the molecular organization of water.

Biologic manufacturing processes typically employ clarification technologies like depth filtration to remove insoluble and soluble impurities. Conventional depth filtration media used in these processes contain naturally-derived components like diatomaceous earth and cellulose. These components may introduce performance variability and contribute extractable/leachable components like beta-glucans that could interfere with limulus amebocyte lysate endotoxin assays. Recently a novel, all-synthetic depth filtration media is developed (Millistak+ HC Pro X0SP) that may improve process consistency, efficiency, and drug substance product quality by reducing soluble process impurities. This new media is evaluated against commercially available benchmark filters containing naturally-derived components (Millistak+ HC X0HC and B1HC). Using model proteins, the synthetic media demonstrates increased binding capacity of positively charged proteins (72-126 mg g media) compared to conventional media (0.3-8.6 mg g media); and similar values for negatively charged species (1.3-5.6 mg g media). Several CHO-derived monoclonal antibodies (mAbs) or mAb-like molecules are also evaluated. The X0SP filtration performance behaves similarly to benchmarks, and exhibits improved HCP reduction (at least 50% in 55% of cases tested). X0SP filtrates contained increased silicon extractables relative to benchmarks, but these were readily removed downstream. Finally, the X0SP devices demonstrates suitable lot-to-lot robustness when specific media components are altered intentionally to manufacturing specification limits.

Increasing the adoption of disposable technologies in various process steps, including such critical steps as sterile filtration and final filling, has become a major trend in the biopharmaceutical industry. However, because of the large volumes and variability of feed streams in clarification and prefiltration processes, it has not been easy to incorporate today's disposable technologies into depth filtration applications.