The Third Way for ICH Q7A: A Proposal for Updating Guidance for API Inspections

By Emil W. Ciurczak, Contributing Editor The schematic of a CE instrument is seen in Figure 3. The tube connects two buffer reservoirs charged as + and -. The samples are introduced via the sample vial which takes the place of the anode, causing sample molecules to migrate to the cathode. While similar to gel electrophoresis, this technique allows multiple samples and the use of UV, IR, and other detection methods in lieu of simple stains, etc. The concept is simple, but cleanliness and attention to detail is critical, since such small amounts of material are being assayed . . . not to mention electricity is in play. Figure 4 shows a graphic representation of a column cross-section. In this case, silica lines the column. The electroosmotic flow is seen from anode to cathode. Figure 3. Schematic of capillary electrophoresis set-up. While not overly complex, it is not designed as “simple” quality control tool. The operator needs fair amount of training on the equipment. Figure 4. Graphic representation of column for capillary electrophoresis: mode of operation. It should be apparent that both 2-D NMR and CE would be quite a bit more difficult to operate and cost significantly more than standard “wet” methods seen in the USP, etc. For a simple comparison, the common techniques of HPLC and NIR are compared. The main difference here is that HPLC, like both previously mentioned techniques, requires major sample preparation. NIR uses “neat” samples while all the others require solvent extraction and dilutions, not to mention prepared standards run side-by-side. The operating costs of HPLC versus NIR can be seen in Figure 5. The labor cost is based on $125 (USD) per hour for a trained technician (probably more, in reality). The cost of purchasing and disposing organic solvents, columns, glassware (purchase and cleaning),