I’ve been having issues with swab recovery studies lately in regards to failures and would like to get some opinions and suggestions if possible. We currently use a 65 % acceptance criteria for our recovery factors and in several instances the detergents being studied (CIP-100, CIP-200, and ProKlenz Booster) are recovering around 31 % for EPDM and 50% for 316 Stainless Steel surfaces causing a lot of extra investigation leading me nowhere and a lot of deviations written in my protocols. Shouldn’t the swab recovery factor be more like a guideline or For Information Only, where whatever you get it’s what it is, instead of being an acceptance criteria (pass or fail)?
Thank you
I have seen several outfits with a 40% minimum recovery requirement. but more importantly I think there are some things you can do to get a better recovery… Additional swab, vortex, pH adjustment. Have you tried any of these?
Dear Datanys,
Before I answer to your question, we need to understand what the regulatory guidelines say about “recovery studies/recovery factor”.
FDA says: “The firm should challenge the analytical method in combination with the sampling method(s) used to show that contaminants can be recovered from the equipment surface and at what level, i.e. 50% recovery, 90%,etc. This is necessary before any conclusions can be made based on the sample results. A negative test may also be the result of poor sampling technique.”
ICH says: “The analytical methods should be challenged . . . to show that the contaminants can be recovered from the equipment surface and to show the level of recovery as well as the consistency of recovery.”
Points to Consider for Cleaning Validation (Technical Report No. 29) says: “The results obtained must be corrected for the incomplete recoveries due to the sampling and sample preparation processes, and the corrections must be factored into the analytical calculations.”
From the guidelines it is very clear that the sampling method should be robust and reproducible. Hence, the swab recovery factor isn’t like a guideline or for information only. Recovery study is an integral part of qualification of sampling technique. Generally, recovery factors >50% are considered acceptable for cleaning validation studies. Since you are obtaining recovery factors less than that, it is advisable to look into your sampling method carefully. Make your sampling method more robust, for that you may change the swab material, try using different solvent (change pH of the solvent if required), use more than one swab for the surface under study, use different swabbing directions etc. I would suggest you to go through the following published articles:
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Yang, Pei; Burson, Kim; Feder, Debra; Macdonald, Fraser; “Method Development of Swab Sampling for Cleaning Validation of a Residual Active Pharmaceutical Ingredient”; Pharmaceutical Technology, January 1, 2005
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Silvia Lombardo, Prasad Inampudi, Anthony Scotton, Gary Ruezinsky, Randall Rupp, Somesh Nigam; “Development of surface swabbing procedures for a cleaning validation program in a biopharmaceutical manufacturing facility,” Biotechnology and Bioengineering, Volume 48 (5), Pages 513-519, 1995.
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Kathy Miscioscio, “Choosing the Correct Swab for Cleaning Validation”, CleanRooms January, 1997.
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J.A. Smith, “A Modified Swabbing Technique for Validation of Detergent Residues in Clean-in-Place Systems,” Pharm. Technol. 16(1), 60-66 (1992).
Hope I was of some help,
Thanks for all the inputs. We actually tried a couple of different swab techniques, such as hot water and different solvents, and it did help a little but not much. I’ll ask our group to tried different pHs and will check the articles/papers suggested.
Thanks again
[quote=DATANYS]I’ve been having issues with swab recovery studies lately in regards to failures and would like to get some opinions and suggestions if possible. We currently use a 65 % acceptance criteria for our recovery factors and in several instances the detergents being studied (CIP-100, CIP-200, and ProKlenz Booster) are recovering around 31 % for EPDM and 50% for 316 Stainless Steel surfaces causing a lot of extra investigation leading me nowhere and a lot of deviations written in my protocols. Shouldn’t the swab recovery factor be more like a guideline or For Information Only, where whatever you get it’s what it is, instead of being an acceptance criteria (pass or fail)?
Thank you[/quote]
Dear Datanys,
as stated above, the 50% recovery is only a rule of thumb, and what is more critical is the reproducibility. The issue with low recovery factors is that when it comes to correct the obtained results by these factors, you may get strange values (figure out: with 50% recovery you have to double your results, but what if the recovery is 2%? Will you 50-fold your results? Where is the limit?). The problem is that the overall method error (method including spiking, drying, swabbing, swab extraction, dilution, analysis, etc.) is the sum of errors from all kind of sources, some of them are relative errors and some are absolute errors, and the absolute errors begin to gain weight as the recovery decreases. If you dare to identify and quantify all the errors from all these sources, (which is much like the calculation of an instrument uncertainty), you probably will find out that with recoveries below 50% your variability gets too high, forcing to lower the accepted contamination levels.
Again, as stated above, try improving the swabbing method, and start identifying the source of the analyte loss (spiking on the swab, in the flask, in the solvent , etc. and determining how much analyte loss each step adds to the overall loss). Too, i would give a try to rinse sampling, which after all is much more representative for detergent elimination than swabbing is.
Best regards
Alfred