The issue of sampling sieves/screens (also called metal meshes) for cleaning validation protocols is a challenging one. For example, those sieves/screens may be used to sift dry powder for particle size control. Small particles may get trapped in the interstices of the crossing wires, and maybe difficult to clean. Those locations may also be difficult to sample. Clearly during the cleaning process, it is possible to utilize (in a manual cleaning process) some kind of plastic bristle brush (with a detergent solution) to help remove product in those “difficult to clean” locations. In such cases, the brushing should be performed on both sides of the sieve/screen. The question then arises as to how the sieve/screen is sampled in a cleaning validation protocol. Clearly a typical swab across the sieve/screen surface may not be adequate. Are there other options?
Well, one option is to dedicate the sieve/screen to just one drug product (or to just one drug active). In that case, the issue of cross-contamination with a different active is avoided. However, a good cleaning process is still needed to maintain the functionality and performance of the sieve/screen. In other words, if the screen is not adequately cleaned, then the sifting performance may be affected, which could result in inadequate separation or perhaps just a slow processing time. If this option were selected, then the only criterion for cleaning effectiveness for the drug product might be just a thorough visual examination. On the other hand, some analytical testing for any detergent used might still be appropriate to prevent adulteration of the next batch by cleaning agent. Now, provided good rinsing is used in the cleaning process, it is not likely this a water soluble detergent will be trapped in the interstices of the sieve/screen in the same way as the drug product. But, as covered later in option two, a simple water sampling rinse though the sieve/screen would most likely adequately recover any detergent left on those surfaces.
So we will now cover a second option. If you use this option visual examination should be done first. This option involves passing a fixed volume of sampling liquid though a defined area of the sieve/screen, and collecting the liquid in a clean collection vessel. The liquid which passes through is then analyzed for the active (or for the detergent). There may be multiple passes of solvent though the same defined surface area. Those multiple passes may involve fresh solvent each time, or the solvent from the first pass may be “recycled” by passing through the screen additional times (thus increasing the percent recovery and the measured residue value in the analytical sample). Another variation is to pass solvent through in one direction, and then flip the sieve/screen over and pass solvent through in the opposite direction. It is preferable that the area of the screen that is sampled be a circular shape (as opposed to a square shape). One technique for limiting the portion of the screen sampled is to use a circular template with a specified circular area, trying to pour the solvent evenly over the portions of the “exposed” sieve/screen. Some may object that a screen “area” of 25 cm2 is not the same as an actual equipment surface area due to the fact that the 25 cm2 is composed of wire meshes (which many add to the actual equipment surface area). However, this may be balanced by the fact that there are “open” areas on the defined 25 cm2 sampled area. These may offset each other, so take this as a reasonable recommendation, but not based on a sound lab study.
A variation on this second option would be to first swab the defined area with a swab before doing the sampling rinse. The swab should be a suitable pointed swab (not a typical “paddle” type swab) so that it can be inserted in the sieve/screen openings so as to loosen any residues (without damaging the mesh wires). It is possible that this could be done with a dry swab (for physical removal) or a wet swab (which may have both a physical removal effect as well as the possibility of a dissolution effect). In either case the swab should be inserted in all “openings” of the sieve/screen. Furthermore, such insertions should be performed while the sieve/screen is in place over a clean collection vessel (the same one that will be used for the liquid rinse sampling process). The reason for this is that if the swab insertion displaces any particles, they would fall into the collection vessel and would be analyzed. Furthermore, once the swabbing is completed, the swab should be placed in the collection vessel so that any residue transferred onto the swab head itself can be analyzed together with any residue from the rinse sampling process.
If the rinse sampling process or the combination of swabbing with rinse sampling sounds too complicated or burdensome, that is a good reason to consider keeping life simple by dedicating sieves/screens.
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