Please share your valuable commnets on the tests which should be conducted on Lidding (ALU) foil for pharmaceutical packaging (i.e Tableting). Is that necessary to do microbial testing? If your answer is affirmative as it’s in contact to the product, what specification(s) and method(s) would be recommended?
Depends on what you are packaging! Thus, the answer is yes and no.
Yes. Many nutritional supplement soft-gels have a specification limit of 3500 CFU/dosage form. Thus, in ‘cleaning validation’ microbes are routinely analyzed using the surface area ratio in the calculations.
No. In a drug product that is going to be sterilized it is not required since the drug product manufacturing must be ‘process validated’.
For references see; Health Canada’s Guide 28 and 29, Eudralex’s (EU) chapters 3 and 5, FDA…
I also assume you take steps to mitigate the formation of endotoxins (LAL) in injectables like compounding with acidic substances (like citric or acetic acids) or processing tanks immediately (and don’t allow them to grow microbes).
Thanks for taking part in the panel. I think cleaning validation is another issue. My question is focus on defining microbial limits on lidding foil (Aluminum foil) which being used in the blistering process of a tablet manufacturing. Is microbial testing should be considered as physico-chemical testing or not?
It’s not a question of physico-chemical testing. If the drug product has a microbial specification then you must consider it.
Obviously any drug product has microbial specification but the question is how to set a microbial limits for Aluminium foil and how to make a sampling plan for it? Do you have any idea?
Yes! It is;
DP Micro. Specification x SA/TSA
SA = Surface Area of a piece of equipment in the manufacturing process train
TSA = Total Surface Area of the entire manufacturing process train
The packaging lid or blister should be sterile or close to it.
The packaging lid or blister is not a critical piece of processing equipment and should not be subject to microbial cleaning validation acceptance criteria (table in production). You can set your own specifications (assuming it would influence the DP specification but this is unlikely).
If you must set a specification, you can justify this limit based on micro. stability results of the DP. However, microbes like to grow in hot and moist environments (which is opposite to what you face, I assume).
Thanks for taking time to answer me. I appreciate that. I’ve never seen the equilibrium you mentioned in your post. I wonder if you could address me any reference for it? Thank you in advance.
No references that I think apply in your case (there are only 4 international guidances/guides). However, review APIC (2014) equations and Dr. Andrew Walsh’s microbial article in ‘Pharmaceutical Technology’.