Having worked soley for so long perfroming cleaning validation with limit resource to expand our program, I wondered what the minium criteria is for selecting the “worst case” API, when specifically trying to detect residual API on product contact surfaces in any given mnufacturing area:
Is it absolutely necessary to consider BOTH the “worst case” API in terms of water solubility AND toxcitiy (LD50 or daily dose calculation) to cover a manufacturing area?
Or to cut workload, could I just consider the “worst case” API via the daily dose calculation (based on theraputic data), and completelty ignore the most water insolbule API, within the matrix of theraputic data created for the manufacturing area?
Alternatively, I would guess that detecting the least water soluble active at the limit of the “worst case” API based on daily dose, would cover both water insoluble and toxicity scenarios, with respect to API?
I could not find any clear guidance on the minimum criteria for “worst case” API cleaning validation, to cover the manufacture of a multitude of products.
Dear Croc,
Identify your worst case molecule based on the toxicity and solubility. The molecule which is having least LD50 value and least solubility in your cleaning solvent (generally water) among all the APIs in your matrix can be considered as WC molecule. If two molecule having same and least LD50 value, then I give preference to solubility as this factor can impact your CV.
Update your CV matrix with all molecules and identify the least MACO. Apply the same value for your worst case molecule (even the least MACO corresponds to different molecule)
I hope I answered your query rightly…
Veerraju N nvr.veeru@gmail.com
Hi,
I think you should perform risk assessment activity for the justification of wost case product among equipment train.
The selection of worst case product will be based on evaluation of product API with other ingredients, operator cleaning experience (comparative cleaning difficulty), solubility in water, Low Potency (most potent), High Toxicity(Low LD50), and may be determined by coupon studies using materials of similar construction.
Regard
M. Luqman
[quote=Luqmanikram]Hi,
I think you should perform risk assessment activity for the justification of wost case product among equipment train.
The selection of worst case product will be based on evaluation of product API with other ingredients, operator cleaning experience (comparative cleaning difficulty), solubility in water, Low Potency (most potent), High Toxicity(Low LD50), and may be determined by coupon studies using materials of similar construction.
Regard
M. Luqman[/quote]
Hello Luqman, thanks for your reply.
Have you any experience of this type of approach standing up to scrutiny from the MHRA/FDA? I have already performed the matrix scoring approach based on the parameters you’ve already described, but was concerned that 600+ different API’s could not be covered scoring on a matrix of data, as the authorities may see things differently. And for example, they may place more emphasis on “cleanability” rather than toxicity or solubility in such a large array of products?
I have opted for detecting the worst case soluble active at the acceptance limit of the worst case carry-over scenario (worst case NOEL calculation, which happens to involve two other API’s). As we have very limited resource to perform cleaning validation.
One way to try to answer your question is to ask yourself why you want to define a worst case in the first place. This could help you to decide on what to do.
I would recommend to prioritize the solubility, or, even better, the cleanability of your substances over their toxicity.
The toxicity is a factor you typically address when you set your limits. A very toxic compound can be very easy to clean and an innoccuous one very difficult to clean.
But you want to clean your equipment and you want to show that your cleaning process is efficient. Efficiency of cleaning has nothing to do with the toxicity of residues, but “hard to clean”, i.e. cleanability (or solubility to make it simple) of residues has a lot to do with it.
Good luck!