Method to overcome Very Low Residue limit

What shall we do when the Residule limit becomes very low which is practically not achieveable?

Can we separate the matrix into two or more parts based on some parameter like minimum therapeutic dose or minimum batch size which lowers the limit ?

Dear Tapan Kumar Panda,

which is exactly the problem: is the cleaning method not capable of achieving the accepted contamination levels, or is the analytical method not capable of detecting them?

I don´t think splitting the matrix makes any difference, but sometimes a detailed manual calculation does, because it may be possible to decide (and justify) on a case by case basis, instead of making a worst of worst of worst case approach, typical to a matrix.

Best regards

Alfred

The problem is that the cleaning method is not capable of cleaning to that limit which is as low as 0.01ppm.

Analytical methods are ok.
In this case what to do?

[quote=Tapan Kumar Panda]The problem is that the cleaning method is not capable of cleaning to that limit which is as low as 0.01ppm.

Analytical methods are ok.
In this case what to do?[/quote]

Dear Tapan Kumar Panda,

0,01 ppm is clearly a low level, but not unusually low (we have limits between 0,4 ppm and down to 0,001 ppm). First aproach is obviously improving the cleaning method (in critical cases we are using an additive to the detergents from Ecolab, COSA PUR 85, which is a strong oxidant; an alternative is using sodium percarbonate, which is the active ingedient of some stain removing pre-wash, or Carbamide Peroxide, the active in some whitening toothpastes). Last resource is sticking to the word “achievable” in the FDA’s GUIDE TO INSPECTIONS VALIDATION OF CLEANING PROCESSES, but in that case it has to be shown at least that the contamination levels reached by the cleaning methods are very reproducible, which is not easy. The critical issue is that extremely low levels of accepted contamination are due to highly potent actives, which could arise a questioning whether they should be allowed to share equipment with actives of much lower potency.

Best regards

Alfred