Nanomedicine research has grown quickly during the past few decades with much of the focus placed on drug delivery. Nanoparticles provide benefits such targeted efficacy while reducing toxicity and side effects. Controlling the size of these nanoparticles is critical. While the majority of the particle size measurements of these particles are in the lab, it is now possible to make these measurements at-line in the manufacturing environment. This presentation explains the pioneering work performed at BIND Therapeutics, Inc. in Cambridge, MA to incorporate online dynamic light scattering measurements into the manufacturing process of their Accurins nanoparticle drug candidate.
Dynamic light scattering (DLS) is a preferred technique for measuring the size of submicron particles. PSS now has several systems installed in customer manufacturing operations that track particle size during production runs. The at-line system removes a sample from the process, dilutes the sample to avoid multiple scattering effects, measures the sample, and then repeats the procedure. The PSS at-line DLS system was installed downstream of a high pressure homogenizer and set up such that it can grab an emulsion sample from the process stream every ~2 minutes. The fluidics of the DLS are set up such that the emulsion sample is diluted in water in a similar manner to the downstream Accurin process, and auto-diluted in a flow cell to a concentration that produces ideal light scattering intensity (~300 kCt/sec).
Data will be shown that relates particle size to homogenizer pressure, first for small scale, then larger scale batches of nanoparticles. The at-line DLS system was integrated into the Accurin manufacturing process and was used to determine optimum conditions and assure the particle size was within the desired specification during the complete batch. Taking the measurements at-line reduces the lag time between making process changes and obtaining the particle size data required to assess if the change produced the desired effect. In addition, product quality is better monitored than by taking samples to the lab for off-line batch analysis. At-line DLS appears to now be a valuable process analytical technology.
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