[quote=hhd_hrdjobs]Hi,

I want to know some information about calculation for cleaning(swab) study.

If I scrub in 4x4 inch area of equipment which is cleaned either by cleaning agent or by solvent and then inject this solution in to HPLC after making equal concentration with standard solution,how I calculate amount of previous product in particular equipment?

Also I want to know that what limit is desirable of previous product in next manufacturing product based on dose unit and batch size?

What is the 10 ppm criteria for cleaning validation?[/quote]

Dear hhd_hrdjobs,

first question is simple: Multiply the amount of product (or better: contaminant, because you dont test for the entire product but only for one or few contaminating target substances) found in your 4x4 inch area, by the area of the equipment surface that is in product contact (in square inches) and divide by the 16 inch² swabbed area. This is the absolute amount of contamination in the whole equipment.

The desirable limit is a little more complicated and there is more than one approach, so I give you ours: Assuming the worst case, that the whole contamination present in the equipment goes into the batch of the next product, you need to calculate the amount of contaminant allowed in one batch of the next product. To make it clearer, lets assume the following as an example:

Contaminant: Substance C, with therapeutic dosages of 2 mg, 4 mg and 10 mg, all taken once a day.

Next product: Product N, with batch size 500 kg, dosage 10 mg and 20 mg, maximum intake of its active is 50 mg/day, dosage unit weight of N is 200 mg.

Shared equipment product contact surface: 10 000 inch²

Starting point is the amount of contaminant (from the previous product) accepted as being taken with the “next” product. Common approach is to regard the active ingredient of the previous product as the contaminant to look for. For solids, an active ingredient intake of 1/1000th of the lowest therapeutic dosage of that active is usually regarded as harmless (for parenterals this factor is 1/10000th).

So, in the example, the maximum amount of contaminant allowed to be taken in per day is 2 mg/1000=0,002 mg/day.

This means that with the daily intake of the next product, the maximum allowed of contamination is 1/1000th of the daily therapeutic dosage of the contaminant. To be on the safe side, the maximum daily intake of the next product is considered. So, in the example:

Maximum daily takings of N is 50 mg/10 mg= 5 takings a day. This means that the 0,002 mg of C are allowed to be contaminating these 5 takings, so per taking of N, 0,002/5= 0,0004 mg C is allowed, or, what is the same, 0,0004 mg of C in 200 mg (one dosage unit) of N. The batch size of N is 500 kg, equivalent to 500.000.000 mg N, so if there are 0,0004 mg C allowed in 200 mg of N, in 5000.000.000 mg N there will be allowed :

(0,0004 mg C * 500.000.000 mg N)/200 mg N= 1000 mg C per batch N.

This is the maximum amount of contaminant C allowed to be present in one batch of the next product N, and thus distributed over the entire equipment surface which is in contact with product. With an equipment product contact surface of 10 000 inch², the limit of contaminant per 16 inch² swabbed area will be: (1000 mg C/10 000 inch²)*16 inch²= 1,6 mg C

Last question: The 10 ppm criteria is essentially the same, only that it does not use the minimum therapeutic daily dosage of the contaminant as the starting point, but takes an (arbitrary) limit of 10 ppm (= 10 mg/kg) of contaminant (10 mg contaminant per 1 kg of next product). This criteria is normally used in cases where the minimum therapeutic dosage of the cntaminant is relatively high, and the calculated limit contamination would allow a visibly dirty equipment. Common practice is to use the lowest calculated limit between both criteria.

Hope this is understandable, and that I have not made any calculation mistakes!

Best regards

Alfred