Particles on Surfaces: Part 7 – How Clean is Clean For Pharmaceutical Companies?

Let’s focus on one of the most challenging cleaning requirements for the pharmaceutical industry – cleaning equipment used to manufacture injectable materials – so called “parenteral drugs”. These materials must be made in environments that are absolutely clean and sterile, because there is no opportunity for the drugs to be sterilized after packaging – i.e. no possibility of “terminal sterilization”. Not only that, but after a manufactured lot is completed, the equipment and the room housing it must be cleaned so that no traces of either the manufactured drug or the cleaning agents are left on the surfaces… and you thought keeping a clean kitchen was difficult!

How clean is clean for a manufacturer of parenteral drugs? Obviously, the surfaces must pass the visual criteria described in Particles on Surfaces – Part 6:

• wipe to the absence of visible soil, either on the surface, or on the last wiper used,
• examine the surface with bright light or UV light (with eye protection)

Such activities are necessary but not sufficient for these manufacturers. They must be certain, as described above, that there are no lingering traces of the active drug, or the cleaning agents on production equipment. Actually, “no lingering traces” must be qualified. One cannot prove the complete absence of chemical substances (either the active drug or the cleaning agent), only that they are below acceptably low levels, often the limit of detection of a particular measurement.

Since invisible residues may be left on surfaces after cleaning, the industry has resorted to using swabs to sample the cleaned surfaces and subsequently analyzing the swabs.

Obviously, the swabs must be extraordinarily clean for this application and must be efficient at picking up any surface residues of the active drug or the cleaning agents. The sampling swabs are tested using sensitive analytical instruments such as UV-visible spectrophotometers (for active drugs), or Total Organic Carbon (TOC) analyzers (for cleaning agents). If the swab contaminant levels detected by these instruments are below established criteria, then there is no risk of cross contamination for future manufactured lots. That’s clean by pharmaceutical industry standards.