USE of TOC in Cleaning validation

GOOD VALIDATION PRACTICE (cGVP) CLEANING VALIDATION
1

Please let me know whether determination of TOC in the Rinsk can be used in Cleaning Validation.
Regards,
Dr.Barve

2

Yes, we are currently using TOC determination in Post final Rinse sample waters. However, you must validate TOC method on your detergents, validate cleaning procedures on manufacturing equipment, both with swab and rinse sampling, and then you can apply rinse control at the end of production.

We have spent about one year to do almost all of this; some cleaning procedure validations are still on going. Beside this we have also started an intensive monitoring of rinse sample with control charts in order to facilitate the determination of the efficiency of the current cleaning procedure in use not yet validated.

I hope can help you.
Sheila

3

TOC determination in the rinsewater can be used for cleaning validation, but has two main disadvantages, which both stem from the same issue: The first is that if you use a “worst case” approach, probably one of the selection criteria for this worst case is the solubility in water, and thus spoiling the suitability of TOC which requires the target substance to be at least slightly soluble in water. The other disadvantage is that inspectors are not too happy with rinsewater sampling, because of the dirty pot analogy: When you measure the contamination in the rinsewater, you are measuring the contamination the water has washed away, and not the one that remains in the equipment, which is what ultimately matters. TOC for cleaning validation is very useful for detergents (containing oxidisable organic carbon, not for inorganic phosphates, hydroxides, etc.) and if your target substances are readily soluble in water.

Best regards

Alfred

4

I would be interested to know if anyone out there has experience in using TOC for cleaning validation in a finished pharmaceutical site. We currently use specific methods for our cleaning validation but my eyes were opened to using TOC at a recent seminar i attended. My concerns are two fold

  1. the ‘dirty pot’ issue as discussed above (i would continue swabbing as ‘hard to clean’ areas could still be dirty)

  2. possible false fails due to other materials in the formulation. As TOC is non specific how do i know my active has been cleaned when i have active plus many other materials in my vessel.

I would like to use TOC (a lot cheaper and faster) but from a distance i can think of pitfalls in such an approach which could be picked which would make the process difficult to validate.