Unknown Peaks in Cleaning Validation Samples

[JDRAT]

Does anyone know of a guideline on how to handle unknown peaks in cleaning validation samples?

[rc_12321]

JDRAT, you better verify wether unknown peaks are due to cleaning agents like detergents ,swab interference ,solvents used in the analysis, placebos used in the manufacture of products , etc .

[JDRAT]

Thank You RC 12321. We have looked at most possibilities of anything that might be associated with that equipment/formula and have come up empty. The peak is 13% of the active peak that we use as the cleaning marker. The sample easily passed the CV criterion. My questions is can this be ignored and how do you decide what you can ignore and what you should follow up on, not just in this case, but as a general practice.

[rc_12321]

JDRAT, In analytical method for cleaning validation other peaks (i.e., unknown peaks) at significant levels may be noted in the chromatogram. These peaks indicate the presence of other residue in the sample. The possibility that the unknown peak is the degradant of active substance after the cleaning process cannot be ruled out.Try to identify the peak wether it is observed in drug product or in other samples .For example, take your HPLC method within a known amount of active and spike it with the cleaning agent (perhaps at the cleaning agent residue limit), and perform the HPLC analysis.
The following letter by FDA includes some remarks on cleaning validation .Hope this helps you.

http://www.fda.gov/ora/frequent/483s/30 ... le_fl.html

[JDRAT]

rc_12321,

Thank you for the reply and the link. I guess this give us direction. Once again, the letter from the FDA shows that if you put it in an SOP you better follow that SOP. We were going in the direction of something similar for unknown peaks in cleaning swab samples. A percentage of the marker drug, total chromatographic area, an attempt to identify the substance and the toxcicity of our actives will all have to factor into our streategy.