TOC specification for cleaning validation

GOOD VALIDATION PRACTICE (cGVP) CLEANING VALIDATION
1

Dear all,

We are doing cleaning validation for machine that is used for producing sterile product.We use rinsing method and we analyze WFI that was already used to rinse machine surface using TOC method. We are now using TOC specification for WFI, which is < 500 ppb, as the acceptance criteria but recently we realize that our acceptance criteria is not right because WFI that already already contact with machine surface should have higher TOC value than pure WFI. So we try to determine the new specification which have correlation with product marker MACO for that machine but we are still confuse how to convert the product marker MACO into its TOC equivalent. Please help us to find the solution. Thank you very much.

Best Regards,

Fina A.G.

2

For determining of the MACO of any product, please calculate the Carbon content in the API for the product. While converrting the cleaning validation results consider this corbon percentage to determine the TOC equivalent

3

Suppose you have defined 10 ppm acceptance criteria than you have calculate carbon of API and Total carbon of your product.

For example: Name of Product: XYZ

Total carbon in API : 10

Total carbon in Product: 13

Qty of Carbon in API : 10 x 12 (mol. wt) = 120

Total Qty of carbon : 13 X 12= 156

Now you analyze rinse sample and observed: 156 carbon its mean your equipment having one molecule of API.

Accordingly You may calculate your acceptace criteria as 10 ppm qty of API how much containt carbon

4

Dear Suresh Garg,

I am having some problem to understand your explanation on the TOC calculation. Could you please explain it with an example. I hope that it would be more clear.

Example:

Our TOC results: 303 ppb
Our Blank TOC results: 25ppb

  1. How to calculate/convert the results into a value that we can compare with our acceptance criteria?

  2. How to set an acceptance criteria for TOC based on 10 ppm limit? Previously, we set the limit at <500ppb and it seem to be wrong.

Let say that the API for the product is Simethicone, Aluminium Hydroxide & Magnesium Hydroxide

[quote=suresh garg]Suppose you have defined 10 ppm acceptance criteria than you have calculate carbon of API and Total carbon of your product.

For example: Name of Product: XYZ

Total carbon in API : 10

Total carbon in Product: 13

Qty of Carbon in API : 10 x 12 (mol. wt) = 120

Total Qty of carbon : 13 X 12= 156

Now you analyze rinse sample and observed: 156 carbon its mean your equipment having one molecule of API.

Accordingly You may calculate your acceptace criteria as 10 ppm qty of API how much containt carbon[/quote]