This article is part of PharmTech's supplement "Solid Dosage and Excipients 2010."
One of the major challenges in the process industries is to monitor and measure the spillage in manufacturing operations. This challenge arises particularly during operations that involve high-shear mixing. An operation is difficult to maintain if it handles micrometer-sized particles (< 100 µm). Monitoring the spillage and leaks in such dust-forming operations is crucial for ensuring safety and prevents process losses. Particles emitted from a unit operation also can present a risk of cross contamination in a biopharmaceutical and pharmaceutical processing plant. Detailed study of equipment design during the process startup can increase process efficiency, ensure the environmental neutrality and safety of the operation, and prevent cross contamination. Manufacturers can use ultraviolet (UV) light to monitor the particles that are not observable in visible light, and UV light already has been used in applications such as forensics, safety assurance, astronomy, sterilization, pest control, water and air purification, chemical markers, and photochemotherapy (see Figure 1).
Companies can implement the Six-Sigma philosophy and the define, measure, analyze, improve, and control (DMAIC) model to monitor and measure spillage (see Figure 2). As IBM noted, "A goal without a plan is a wish," but the Six-Sigma philosophy helps operators plan experiments methodically (1).
The most crucial phase of the project is the definition, which should be clear and concise and reflect the contributions of all relevant cross-functional groups. The criteria for measuring success for a high-shear mixer must be clear. The goal of processing biopharmaceutical active ingredients is to achieve 100% recovery or eliminate spillage. To achieve this goal, operators must conduct a detailed examination of all of the mixer's major points of connection. Most leakage occurs from gaskets, fittings, and the upper opening of a hopper. Knowing and taking note of these critical points for examination is especially important. When conducting this kind of study, one should always be ready for surprises that result from variations between individuals' perceptions. The author used an IKA Labor Pilot -2000/4 MHD Module (IKA, Wilmington, NC) to mix a solid-liquid-phase dispersion at Genzyme's (Cambridge, MA) Ridgefield, New Jersey, facility (2). This unit comprises an ultrafine spaced rotor-stator assembly.