This study is needed to prove that there is no carryover of residue onto the next product. Carryover includes but is not limited to: previously manufactured product, byproducts, products from degradation, lubricants, cleaning agents and solvents.
The study is completed in both the facility, as well as our laboratory. All studies begin in our laboratory to ensure that the method of detection is appropriate. Some of these studies consist of obtaining evidence regarding linearity, accuracy, precision, stability, intermediate precision, percent recovery, limit of detection and limit of quantization.
Once a suitable detection method has been determined, the cleaning validation plan is executed at the facility.
If the study shows that removal techniques were not effective to reduce all compounds of interest to an acceptable level, the user must modify the procedure and repeat the study. Modification may include contact time, changing the scrub time, changing the rinse water temperature or changing the agents, etc.
After the method has been validated, the user will develop a schedule to sample the equipment on a routine basis to verify that the agents and methods are still acceptable.
There are two methods of accomplishing a residue study: Specific and non-specific.
This study is set up to recover only the compound of interest, and will not identify any compounds other than the compound of interest. This study should be used if you have a potent compound, the compound cannot be detected by a non-specific method, or you are having difficulty in removing a specific compound.
Non-Specific StudyNon-specific studies will indicate if the surface is within limits of all compounds of interest without the need to run individual samples. However, if the sample tested is above the acceptable level, the user cannot determine which compound or compounds were present.
Have questions about cleaning validation? See our answers to the most frequently asked questions.
Pharmacopeia in the United States requires that the disinfectants used in facilities are proven to be effective. This requires the user to provide documentation that the cleaning agent(s) is effective on the hard surfaces present in the facility, as well as resident microrganisms.
Microbial Validation & Verification
USP provides guidance on the types and strains of organisms used for this study and they can be obtained through specific culture collection agencies. Resident organisms are usually obtained through environmental monitoring or product contaminants. The organisms are identified and a culture is prepared accordingly.
The test consists of inoculating the panels with a high population titer of each organism, applying the disinfectant for the required time and swabbing to evaluate the reduction of organisms in a logarithmic value. Studies also need to be completed to show that the compounds of interest have been sufficiently neutralized and that growth is not inhibited.
Items to consider when conducting a study:
- Expiry dating of the cleaning agents – A study may be done at, close to, or after the expiration date of the agent to verify the cleaning agents are still effective.
- Reduced contact time – This will verify if the agent is still effective if the established contact time was not met.
- Improper dilution of the cleaning agent– This study will determine whether the agent is capable of reducing the bioburden if it is not prepared correctly.
If the study shows that the agent was not effective in reducing all microrganisms to an acceptable level, the user must modify the procedure and repeat the study. This can be accomplished in several ways, for instance, increasing the contact time or changing the agents.
After the method has been validated, the user will develop a schedule to sample the equipment on a routine basis to verify that the agents and methods are still acceptable in reducing the bioburden.
Read more about considerations when performing microbial cleaning validation.