Status Signs for Cleaning Processes

This Cleaning Memo focuses on the signage (labels) that should be used during routine cleaning of equipment in pharmaceutical manufacturing facilities. It will cover possibilities for verbiage to be used in those temporary signs at various times during the cleaning process.

The purpose of such signage is to make sure the various steps in a cleaning process are done in the proper order and they are done in a way that doesn’t compromise manufactured product (which would include the product just made that will be cleaned as well as the next product made in the cleaned equipment). Here is a possible sequence of signs that could be considered for use.

1. Once the manufactured product is removed from the equipment, any processing signage (that might include product name and batch number) should be removed and replaced with a sign such as ”To be cleaned” or “Ready for cleaning”. Some companies may choose to include a time for the end of manufacture (to help calculate the dirty hold time so it is not exceeded); while that could be done, a better option is to capture that time on a permanent document like a cleaning batch record.
   
2. The next possible signage might be something that indicates that cleaning is underway. The prior sign should be removed and replaced with a sign such as “Cleaning in process”, “Being cleaned”, or “Cleaning underway”. Like the “To be cleaned” sign, some companies may choose to include on the sign the time cleaning was started (for correct calculation to make sure the dirty hold time is not exceeded); but a better option is to record that starting time information on a more permanent document. If product are made in a campaign mode and if there is a distinction between “minor” cleaning (done between batches of the same product) and major clearing (done on a product changeover or at the end of a campaign), some companies choose to indicate on the sign whether the cleaning is major or minor. This helps insure that the correct procedure (major or minor) is done. Needless to say, the time of completion of cleaning should be recorded both to help confirm the cleaning procedure was done correctly as well as to provide the “time zero” for the clean hold time; this is preferably captured on a permanent document.
   
3. Once cleaning is completed, there are several options for the next step and therefore the next sign. The key issue is whether visual inspection is done and whether there is a second person check. In some cases the cleaning operator may do a visual inspection as part of the cleaning SOP so that operator inspection might be done before a change of signs. Note also that the expected “visual inspection” result for minor cleaning may be different from that expected result for major cleaning. After the cleaning operator is finished, the sign could be changed to indicate that visual inspection should be done. Examples of such signage include “Ready for supervisory visual inspection” or “Ready for QA visual inspection”. If any swabs are to be taken for routine monitoring, they could also be included here.
   
4. Once visual inspection is done (and possible swab samples are taken), the equipment is ready for the next step, which is QA release. Suitable signage includes “Ready for QA approval” or “Awaiting QA approval”. Note that approval may depend on obtaining swab sample results or it may be an approval “at risk”.

5. Once QA has released the equipment for subsequent manufacture, the previous sign should be removed and replaced with a sign indicating that the equipment has been released. Suitable wording might include “Released by QA” or “Released for manufacture”. Some may choose to add the “expiry period” (based on the maximum clean hold time) to this temporary sign (to help prevent the clean hold time from being exceeded).

It should be noted that some companies may want to include signs at even more intervals, whiles other may want to collapse the number of intervals. These will be determined by the benefits and risks of doing so. Such signage wording and usage should be captured in a SOP covering the entire facility (so that training and compliance are easier).

It should also be noted that the FDA has a “Q&A on CGMP – Production & Process Controls”) dealing with the issue of such signage. It basically states that such labels are “temporary” and need not be retained with the batch records. It further states that the signs do not have to be labels, but could be “dry erase” boards. Here is the text from the FDA website.

“The CGMP regulations for finished pharmaceuticals require the retention of cleaning and use logs for non-dedicated equipment, but no similar requirement exists for retaining what are intended to be quick reference or temporary status labels. Examples of these kinds of status labels include mixing lot ###; clean, ready for use as of d/m/y; and not clean. We see no value in the retention of such labels in addition to the required equipment log or batch record documentation. The labels serve a valuable, temporary purpose of positively identifying the current status of equipment and the material under process. Any status label should be correct, legible, readily visible, and associated with the correct piece of equipment. The information on the temporary status label should correspond with the information recorded in the equipment cleaning and use log, or the previous batch record
for nondedicated equipment.

Labels are merely one way to display temporary status information about a piece of equipment. It is considered acceptable practice to display temporary equipment status information on dry-erase boards or chalkboards. And it would be appropriate for an FDA investigator to verify that the information on a temporary status label is consistent with the log.”

Finally, this Cleaning Memo does not deal with additional signage that may be used during cleaning validation protocol execution to make sure that specified validation protocol parameters (such as making sure that the dirty hold time is at the maximum and making sure that validation sampling is done) are achieved.

I can’t emphasize enough that correct and useful signage (as well as training on its use) is important to assist in making sure the cleaning process is done correctly and efficiently. Such signage may also be helpful during a regulatory inspection, so that a visual inspection of equipment by auditors appropriately considers whether there is an expectation that the equipment be visually clean.