February 2011-More on ISPE’s RiskMaPP.docx

PAGE \* MERGEFORMAT3 February 2011 More on ISPE’s RiskMaPP As stated in my November 2010 Cleaning Memo, I have serious problems with the ISPE document “Risk-Based Manufacture of Pharmaceutical Products” (Risk-MaPP). My primary objection is not related to using a health-based limit for highly hazardous actives; that is something I also teach. My primary objection is to “collateral” statements made in the document related to how cleaning validation limits have been set in the past (and in the present). Those statements to the effect that current methods of setting limits for actives are “nonscientific” and arbitrary lack support, and are misleading and wrong. Furthermore, the effort of the Risk-MaPP team should not have been to critique current methods of setting limits for actives in general, but they should have focused their critique on current methods of setting limits for “highly hazardous” actives. Current methods for highly hazardous actives are best summarized by the PIC/S PI 06-003 recommendations, in which case those actives should be made in dedicated equipment/facilities or cleaning validation should be performed with limits set as non-detectable by the best available analytical technique. In addition to this major concern, there are other concerns that I have about the document. Some are simple issues and some more complex. Below is a discussion of some of those issues Use of TOC as an analytical techniqueIn section 7.2 is the statement “Recovery studies utilizing Total Organic Carbon (TOC) analysis can be performed with the final determination of the suitability of the existing cleaning procedures augmented by TOC analysis after the initial cleaning”. I seriously doubt whether TOC is an appropriate analytical technique for measuring residues of highly hazardous actives. The reason is that limits for such highly hazardous actives, based on “health-based calculations”, will generally be extremely low. After all, isn’t one of the main points in the Ri