I need information about equipment cleaning validation protocols using HPLC. Thank you.

Claudia,

What type of information are you looking for?

If its related to method validation there was a paper published last year in pharmaceutical technology (Validation of Analytical Methods Used in Pharmaceutical Cleaning Assessment and Validation-Robert b. Kirsch(who has contributed to this group in the past)).

If your query refers to setting acceptable residue limits or sampling methods please let me know. You may have already guessed that there are no specific protocols for performing cleaning validation programmes due to the wide variation in manufacturing processes, however the common element in all is the FDA 'guide to inspections validation of cleaning processes' which can be downloaded from their website.

Hope this helps
Adrian

Adrian, thank you for your answer.

I have the FDA document, but it has not helped me very much with the practical issues. Maybe you could help me with specific information about sampling methods and acceptance limits.

I'd like to read the article you mentioned but I don't have an easy acces to this publication. Can I find it in the web?

Again, thank you veeeery much.

Claudia,

I agree that the FDA guideline is not much of a starting block but you will find yourself refering back to it in the future.
With regard to sampling methods again it will depend on your own experience with the products and equipment etc.
Most of the people I've spoken to have used a 100% double knit polyester swab for sampling. From an LC perspective the polyester is heat bonded to the shaft so no adhesives can interfere with your method. Polyester also shows good recoveries from equipment surfaces. Rinse sampling should also be used where applicable, a) because its easy to perform and b) it tends to back up your swab results.

For limits determination the key reference paper tends to be Fourman and Mullen, Determining Cleaning Validation Acceptance Limits for Pharmaceutical Manufacturing Operations (pharmaceutical technology april 93). Most people tend to apply the principles developed by Mullen and co. to their own manufacturing scenario.

The Parmaceutical Technology journal is a free subscription to europe www.pte-mag.com.
If you have any trouble you can contact me offline and I will do my best to forward them to you.

Hope this helps
Adrian.

Some experience with sampling - rinse samples are fine if the FDA goes along with it. Usually tho' the equipment has to be brokendown at least one time and swabs taken from the nooks and crannies.


An approach to swabing reactors and their gaskets is to obtain "coupons" and swab known areas of these. Calculations are then made for the total area.

With regard to types of swab, the polyester type are very practical to use, but they do not have a very large surface area which can cause poor recovery from them. We find that using glass fibre filters (e.g. Whatman GF/F) gives much improved recovery. Their only downfall is that you need something to put them in, for which we use 15ml polypropylene centrifuge tubes.

On rinse samples - their only problem is that the substance you are looking for would generally be the one which isn't water soluble and so may not be washed off the surface. As B. Buglio says, swabing may be required too.

There is a large polyester swab available from Texwipe which has a ~2cm2 head, and is double sided. Most sampling areas tend to be between 5cm2 up to 100cm2. I have evaluated these swabs using LC as a detection method from 100cm2 coupons and have had no problems with lack of recovery (at low and high ranges).
Again each manufacturer will have there own products and equipment to assess so maybe a glass fibre swab or wipe will be more applicable to your scenario.
If recovery is a problem there is always the 2 swab approach. One wet followed by one dry should increase the recovery.
With regard to rinse sampling I agree with Tim; the target analyte may not be water soluble. An accurate rinse sample should be composed of the actual rinsing agent e.g. detergent, solvent etc.
If the target analyte is not soluble in this then the question 'why is it used?' needs to be answered.