[quote=kharkar]Dear Sir,
Dear Sir,
Regarding cleaning validation, we need to have your guidance.
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For multiproducts facility, by considering the product matrix approach, lowest batch size, it is practically very difficult to acheive the MAR value. For e.g. next product batch size is 3 kg, then 30 mg is practically very difficult to achieve.
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If some equiments we are going to use for next product and some equipments are not required. Can we considered only those equipments which are going to use in next product. But the cleaning validation report will not be completed as we do not know which product is going to manufacture in remainig equipments.
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If the analytical claning method validation is done on UV, and LOD is 0.5 ppm. After cleaning if we are getting the value of cleaning samples as 0.4 ppm how it is possible. Even if we have taken it as not detected, then we have to consider 0.5 ppm as LOD value. By considering this vaule if the final value of left over residue is more than that of acceptable limit (MAR value by calculation, taking daily dose of previous and next product). What to do?
Pl. help us to resolve these problems.
Rgds-Uday Kharkar[/quote]
Dear Uday,
although there are some unclear items, i will try to go through:
1- When using a product matrix approach, inherently you are using the worst of the worst cases, so very low acceptance limits are usual. Nevertheless, and depending on product surface, batch size and product potency, 30 mg is a quite high value. As an example, we manufacture 110 different formulations in eight main manufacturing trains, and our accepted contamination levels are around 0,01 µg/cm², or, in a 100000 cm² equipment, 1 mg in the whole piece of equipment.
2- The accepted contamination level is established per piece of equipment, again depending on which is the worst case contaminant (highest potency/lowest solubility) and the worst case contaminated (lowest batch size/highest daily intake) products. Which is actually the next product does not really matter, and it can even be a nonexistent product which takes the lowest batch size manufacturable in the equipment (data from equipment PQ) and the highest daily intake of all the manufactured products. The cleaning validation should, in my opinion, be designed for each cleaning procedure (actually, you are validating the cleaning process stated there), and thus it should not be necessary to wait for validating the cleaning procedure of the last piece of equipment to close the report.
3- When the LOD of your analytical method is higher than the maximum allowed contamination samples, then it is simply not suitable for cleaning validation. Take into account that the contamination levels are roughly 1000 times lower than the levels used for product analysis, and thus the analytical method used for product analysis is normally not usable for cleaning validation. In some cases it is possible to eliminate dilutions, concentrate samples, make multiple injections in an HPLC, and thus develop and validate an analytical method derived from the product analysis method, but for direct UV reading there are very few options. The advice is to complete all the calculations needed for the product/equiment matrix, and only then develop the analytical method, directly aimed at bracketing the calculated limits (50% - 150% of the target concentration, although my advice would be to try to go down to 10% - 150%, to be on the safe side with new products added to the matrix).
Best regards
Alfred