This post is about Parts Washer qualification. This covers any manner of automated system that cleans parts out-of-place (Clean-out-of-place = COP). This includes process parts washers, glassware washers, laboratory parts washers, etc. all of which may be termed COP washers.
The scope of a performance qualification of a washer is the performance of the equipment with defined recipe(s) and load(s). Be sure to capture the recipe and load configuration in the protocol prior to execution or as part of the execution itself. This is how the recipe and load configuration become “validated.” The recipe includes all steps and parameter values, and the load includes what parts or components will be washed and how they will be arranged. You’ll need to include a picture or diagram.
One thing you’ll want to know is if the washer recipe cleans all areas of your load. One of the easiest ways to do this, and an industry standard, is riboflavin testing. Riboflavin testing is as simple as completely covering all surfaces with a riboflavin solution (typically around 0.02% weight/volume of riboflavin to WFI or purified water) and then verifying none remains following the wash recipe. Riboflavin is used because it fluoresces under UV light and is non-toxic, making it optimal for this kind of testing. I recommend riboflavin testing in a development phase, because recipes are often tweaked as a result of this test (e.g. length of rinse steps may be increased). One key point is that you’ll need to interrupt the wash recipe before any drying steps, because unless wet, it will be difficult to see riboflavin on surfaces, even under UV light.
What else do you need to consider? Assuming your washer is cleaning product-contacting or “direct contact” components, you’ll need to be concerned with removing:
- Hard-to-clean or insoluble excipients
The removal of API is critical for non-dedicated equipment, i.e. equipment that is used in the manufacturer of more than one drug product. In this case it is critical that you ensure residual API is below a calculated limit. More on that below.
If you have any hard-to-clean (e.g. insoluble) excipients or components to your product, you may need to pay special attention to those in cleaning. Surface swabbing may be the only way to assure removal of insoluble excipients.
Bioburden is of course the level of microbial activity on a surface. This should be below the limit required by the process. Endotoxin is the left-over bits of bacterial cells that can be harmful. Because endotoxin is non-living, it must be tested for with another method than bioburden.
Additionally, it is important to ensure detergents are rinsed away sufficiently and that a high concentration of residues are not left on surfaces.
Three main methods exist for testing the “cleaniness” of parts in a washer or any surface being cleaned for that matter: visual inspection, rinse water sampling, and surface swabbing. Visual inspection is the process of looking at a surface to see if it is clean. While certainly not as quantitative as water or swab testing, visual inspection can be used to support cleaning validation and qualification of washers (see here).
Rinse water sampling is testing performed on rinse water, the idea being that the rinse water should be clean, demonstrating equipment is clean. The big assumption there is that contaminates are soluble and will be rinsed away. If you don’t have soluble contaminates, or don’t know the solubility, that’s where surface swab sampling comes in.
Surface swab sampling is the collection of contaminates from a surface using a formal swab process. Typically the swabbing process is defined in the protocol or SOP. You’ll also need to consider recovery factors, i.e. the amount of a particular contaminate you expect to recover from a given surface with your swab process. You’ll want formal documented recovery studies to support your recovery factors (more here). You also need to validate the analytical methods used on swab samples, since these will likely not be standard.