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Virus removal filtration is a critical step in the manufacture of monoclonal antibody products, providing a robust size‐based removal of both enveloped and non‐enveloped viruses. Many monoclonal antibodies show very large reductions in filtrate flux during virus filtration, with the mechanisms governing this behavior and its dependence on the properties of the virus filter and antibody remaining largely unknown. Experiments were performed using the highly asymmetric Viresolve® Pro and the relatively homogeneous Pegasus™ SV4 virus filters using a highly purified monoclonal antibody. The filtrate flux for a 4 g/L antibody solution through the Viresolve® Pro decreased by about 10‐fold when the filter was oriented with the skin side down but by more than 1000‐fold when the asymmetric filter orientation was reversed and used with the skin side up. The very large flux decline observed with the skin side up could be eliminated by placing a large pore size prefilter directly on top of the virus filter; this improvement in filtrate flux was not seen when the prefilter was used inline or as a batch prefiltration step. The increase in flux due to the prefilter was not related to the removal of large protein aggregates or to an alteration in the extent of concentration polarization. Instead, the prefilter appears to transiently disrupt reversible associations of the antibodies caused by strong intermolecular attractions. These results provide important insights into the role of membrane morphology and antibody properties on the filtrate flux during virus filtration. [ABSTRACT FROM AUTHOR]

Purpose: With the applications of more advanced manufacturing technologies being applied to the pharmaceutical industry, continuous processes are at the forefront of innovation. One area that is highly desired to be systematically investigated is material traceability in continuous manufacturing systems. By following federal guidelines already in place, the goal was to address the issue of material traceability in a continuous direct compression tablet manufacturing process. Methods: The residence time distribution (RTD) method has been used for material traceability in continuous pharmaceutical tablet manufacturing process. Utilizing the minimum and maximum residence times for the continuous line pre-production, raw material batch changes that occur during feeder refill can be traced at the outlet of the process. MATLAB programing was used to develop software prototype to trace material components. Results: Developed framework for implementation of material traceability into continuous manufacturing pilot-plant. To demonstrate the application of this framework, a software prototype was developed, which allows the operator to input residence time attributes for each component in the formulation. Using the minimum and maximum residence time values for that component, the lot number is incremented when the change in material batch is predicted to be present in the tablets at the outlet. The tablet lot number is recorded by the control system in real-time. Conclusions: Developed framework and corresponding software allows the material traceability to be fully accounted for during a continuous drug product manufacturing process. A proof of concept was created to demonstrate feasibility of such a system, which has a wide range of applications. [ABSTRACT FROM AUTHOR]