Rapid Depressurization Based Controlled Ice Nucleation in Pharmaceutical Freeze-drying: The Roles of the Ballast Gas and the Vial.

Controlled ice nucleation offers several key benefits to the pharmaceutical lyophilization process, including reducing lyophilization cycle time, control of ice crystal morphology, and increased consistency of lyophilized product quality attributes. The rapid depressurization based controlled ice nucleation technique is one of the several demonstrated controlled ice nucleation technologies and relies on the rapid discharge of an inert pressurized gas to induce ice nucleation. In this work, a series of custom wireless gas pressure and temperature sensors were developed and applied to this process to better understand the mechanism of controlled ice nucleation by depressurization.

Strategies to Reduce Reconstitution Time of Lyophilized Biotherapeutics.

Lyophilized biotherapeutics with high protein concentration may have long reconstitution times, which pose an inconvenience to the end user. This report describes 2 approaches that lead to reduction of reconstitution time: (1) incorporation of tert-butyl alcohol (TBA) in the prelyophilization formulation and (2) decreased headspace pressure in the final lyophilized vial. Cakes made from prelyophilization formulations containing a range of TBA concentrations were physically characterized.

High shear rheology and anisotropy in concentrated solutions of monoclonal antibodies.

The high shear rheology of three concentrated solutions of immunoglobulin G1 monoclonal antibodies (mAb1, mAb2, and mAb3), differing only in their complementarity determining regions, was characterized using rotary and capillary rheometry. The more viscous solutions (mAb1 and mAb3) showed non-Newtonian behavior at high shear rates exhibiting both shear thinning and appreciable normal stress differences (NSDs) in the shear rate range γ = 10 to 10(4) s(-1) . The rheograms were retraced after γ is increased and decreased, suggesting reversible self-associations under shear.

A new roadmap for biopharmaceutical drug product development: Integrating development, validation, and quality by design.

Quality by design (QbD) is a science- and risk-based approach to drug product development. Although pharmaceutical companies have historically used many of the same principles during development, this knowledge was not always formally captured or proactively submitted to regulators. In recent years, the US Food and Drug Administration has also recognized the need for more controls in the drug manufacturing processes, especially for biological therapeutics, and it has recently launched an initiative for Pharmaceutical Quality for the 21st Century to modernize pharmaceutical manufacturing and improve product quality.