I am new to this board, new to HPLC, and new to my current industry. I apologize if my question sounds obviously uninformed and/or naive.

I need to be able to monitor surfaces within pharma facilities for residual mid-sized organics following cleaning to at least qualitatively validating cleanliness. Such chemicals would include active pharmaceutical ingredients (API's) such as antibiotics and steroids, and/or precursors or break-down products. Surfaces would include floors, manufacturing equipment, test equipment.

I assume that I can swab a surface and prepare samples for HPLC. My questions -
1. Could a single configuration of HPLC be general enough to qive useful residual info when I don't know in advance all possible residuals?
2. Is this already a common practice?
3. If it is common, would someone direct me to reference(s) that deal with this type of problem?

Thanks

With HPLC with UV detection, you need standards for everything. With LC/MS you might be able to identify unknowns. Do you have LC/MS?

Henry,

Cleaning validation is common practice in the Pharm industry - I do not think there has been a regulatory inspection at our facilities where we have not had this subject investigated.

It is unlikely that you would be able to come up with one HPLC method that would permit you to analyse anything your company produces - if you could ALL our lives would be much easier! You can look to other analytical methods, such as Total Organic Carbon (TOC), provided you are only concerned with how much residue is there, not what is there.

Our approach has been along the lines of:

1. Work out solubilities of your actives (and excipients).
2. Critically evaluate the cleaning processes for all you products to determine the worst case areas and products to clean (floors are easy; corners of square hoppers, transfer tubes, welds, rubber, plastic are difficult).
3. Look at how you change between products - are manufacturing areas dedicated to products or do you change between products. Work out what the permissable level of contamination would be in the second product from the first (using toxicity, target areas, etc.) and use this as the acceptance limit.
4. Using all of the above, determine what you worst case products are going to be and deal with them first.

Come up with suitable analytical methods for your worst case products (we base our cleaning methods on scaled down assay/degradate methods). If you think there may be more than one product, you could potentially look at developing your own methods, using existing methods as a starting point, but remember that involves much more development and validation work.

CE is now being looked at as an alternative to HPLC for the analytical side, though the steps before you get that far shown above still need to be looked at.

For references, search for "Cleaning Validation" on the Internet - Google came back with a lot of hits, including www.cleaningvalidation.com. I can not vouch for any of these sources though.

Hope this helps.

Thanks to Anon and Tim.
To clarify, I am not directly in a Pharma. I work for a company that is brought into Pharma's for certification, validation and decontamination. There are two major concerns - monitoring the before and after cleanliness of a lab or manufacturing site and ensuring that our own equipment is not carrying contamination between sites. Given the variety of assignments, I am looking for a technique that is fairly general/universal and not require too much capital investment. I acknowledge that I might be unrealistic.
I do not have HPLC or LC/MS at this time.
I will follow up on the "cleaning validation" sites.

This would seem to indicate that a non-specific technique such as TOC may be better for you. Most TOC analysers can also detect inorganic carbon.

Providided you can demonstrate that there is below a certain level of contamination, what is actually is will not usually be critical, unless the company is working with very potent compounds, in which case they should be the ones doing the residual testing for your safety.

Tim,

Thank you. I had not considered TOC previously. However, your points seem on the mark. I am pursuing that direction.