Feasibility discussion on whether cleaning validation is required for culture medium filling
First of all, what we need to confirm is, under what circumstances, clean verification is required. According to the body of GMP: "article 143 cleaning methods shall be verified and verified to be effective in preventing pollution and cross contamination. Cleaning validation should be considered equipment usage, the detergents and disinfectants used, sampling method and location, and the corresponding sampling rate, the nature of the residues and limit, sensitivity factors such as residue method."
Appendix: verification and confirmation article 39 in order to confirm the validity of the cleaning operation rules for equipment directly in contact with the product, cleaning verification shall be carried out. The limits for residues of active substances, detergents and microbial contamination shall be reasonably determined based on the materials involved.
Summarize two regulations, it is for possible contamination and cross-contamination (direct contact with the equipment and products or regions) cleaning method, in order to prove the cleaning method can effectively eliminate possible contamination and cross-contamination, need cleaning method for cleaning validation.
Media fills, the equipment is used and direct contact with the product of the culture medium is may produce pollution to the product, so after media fills the cleaning method is accord with the requirement of the above for cleaning validation, there is no doubt that is the need for validation, if not do, certainly do not conform to the regulations.
So how to do the cleaning verification after the filling of culture media? Because the cleaning verification is aimed at the cleaning process, it can be divided into the following situations:
1. The cleaning method after culture medium filling is consistent with that after product production
In this case, you need to do is in your original cleaning validation scheme, as your products will be medium for analysis, analysis of various kinds of products, such as solubility, toxicity index, and then to determine the target of cleaning validation, choose residue limit and test method. This does not require a separate clean writing scheme for medium filling.
2. The cleaning method after filling media is not consistent with that after production
In this case, you will need to draft the plan separately. The content and requirements of the plan will be the same as those of the clean verification. How to do this is not discussed here, because this is a technical job, and every company has different choices, which will be discussed later.
Some friends will also ask, I only do the culture medium filling twice a year, so how to do the cleaning verification? Can we replace the cleaning verification with the cleaning confirmation? First of all, for those of you who are building a new pharmaceutical factory, you don't have to say that the culture medium is filled three times, and you have enough time and lots to do that.
If you haven't, what about the friends you need to add now? First of all, cleaning verification requires you to do it three times, without specifying how long you need to do it. Three times is a year and a half time, you finish once, write a periodic report not ok? Finish three times and give another report, ok?
Secondly, although article 49 of the appendix states that "for drugs in the development stage or products not frequently produced, the method of confirming the cleaning effect after each batch of production can be used instead of the clean verification." But it was also stated that "each subsequent cleaning confirmation shall be made in accordance with the relevant requirements of this appendix." Is there any difference between the requirement of cleaning confirmation and the requirement of cleaning verification?
You are willing to write a report, every batch of media fills out to do the cleaning validation, or willing to finish three batch of cleaning validation, on the premise of cleaning method does not change, you don't need to do it again after cleaning effect monitoring?