I have an other question about cleaning validation.
I have one equipment that i use for liquid product and semi-solid product (ointment, cream, gel). After worst case matrix calculation, i found that liquid product is worst case than semi solid product. If i use the same cleaning process for the both kind of product, could i validate the cleaning process for semi-solid product by liquid product? or i have to separate the 2 categories of product, and make two independant validations? one for liquid and another for semi-solid?
It is possible to validate cleaning of cosmetic product by liquid form and vice versa?
Interesting, I’m working with the same problem these days.
I do not have much experience, but I think it is possible and should be based on the worst risk assessment of the whole train, establishing the worst case (WC) for various parts of different equipment and calculate residue limits with the traditional criterion with the total surface area of the train. Then the swab and rinse samples for the WC selected for each part should not exceed the calculated limit, and the sum of all rinses from each WC site selected should not exceed the limit. The same procedure with the swabs for each worst case.
Please correct my opinion if I am wrong.
In my case it is not a single dedicated API but they are several APIs, that should be grouped.
I imagine that each equipment has a different cleaning procedure and what if I ask and I would like to know is what happens in the case you mention, if any of these cleaning procedures for some reason requires different cleaning solutions, and I mention it because in my case this is happening and probably should change the cleaning methodology and may be not.
Example of the train with which I must work.
Synthesis Reactor: Cleaning solution (acid detergent) and water.
Spin-dry equipment: Only pressurized water.
Spray-Drying equipment: Only pressurized water.
These are the data collected from the "production experience."
Best regards.
Fabian.
Dedicated facilities do not have to have cleaning validation performed, that is determining carryover acceptance criteria. You still clean and have cleaning procedures.
In the same vein for dedicated equipment you can calculate your worst case based on the ‘theoretical daily dosage (TDD)’ rather than toxicity. Or just use a ‘visual residual limit (VRL)’.
Because you do not have a dedicated facility be sure you ascribe (somewhere) that you mitigate potential carryovers by using PDA TR (technical report) #29 and 49 (Points to consider…). They talk about changing HEPA filters and air exchanges. You will be challenged, but this will give you some bullets in your gun!
So there is 1 product? Is that was dedicated means, or is there one family of products (mammalian vs yeast). I’m confused why you said it is dedicated, but have different equipment. Are there multiple various processing routes for the same product.
But if you have multiple product, you can determine the worst case product, and use that for cleaning validation. You need to defend which product is worst case (there are a number of ways to do this). Once you have determined that, then you can do cleaning validation on that product, with verification of the other products as well.
Also, even a dedicated facility needs to look at detergent, microbial build-up, and other aspects of cleaning a truly dedicated process, even though lot-to-lot carryover is less of a concern.
For be clear, i use 6 equipments (equipment train) in the manufacturing process of my product (1 filler, 4 tanks of 200 L, 221 L, 500 L and 1060 L, and a Filter holder). All this equiments are only use for this product. The question was:
1-can I make a grouping of tanks and choose only one for valided the three others.
2- what validation i have to make for dedicate equipment (microbiology, cleaning agent, product residu)?
1 - All tanks / vessels should be part of your analysis. You should evaluate the tanks and look for hard to clean areas. There might not be any hard to clean areas in a tank - so you might not need to sample that tank at all (but you should probably still perform visual inspection). But the total volume will be part of your calculations for carryover since the surface area will be part of the calculations if you are doing swab sampling.
2a - Look at clean hold times and sterile hold times as part of a media fill (if aseptic process).
2b - Regardless of dedicated equipment or not, you still need to confirm the removal of cleaning agents.
2c - Regardless of dedicated or not, you should at least confirm cleaning via visual inspection.
For visual inspection please determine visual inspection cleaning limits (using a coupon study typically)
I need your help about a discussion we have at this time in our company and we have no point of agreement. This is about the criteria for determining the worst case product. Some colleagues propose to limit themselves to 3 criteria ie toxicity, solubility and cleanability. Other colleagues believe that in addition to these 3 criteria, we have to add 2 other criteria like “the raw material type criteria” (active, excipient etc …) and “raw material concentration criteria”.
What comments in this specific case can you make? do you find these 2 additional criteria are relevant or are without any real impact for the determination of the worst case products?
I believe there are quite a few criteria which could come into consideration. Paper based risk assessments are a good starting point, but most guidelines suggest confirming worst case considerations using a coupon study, looking at visual detection limits and also looking at residual (determined by cleaning in a laboratory type setting).
I don’t see solubility in determining your worst case since toxic compounds can be both water soluble and insoluble. I only see solubility involved in developing a cleaning solution. Particularly, you can clean a piece of equipment using a water soluble cleaning solution but leave behind a ‘toxic dose’ of a water insoluble API.
While these 2 other criteria should be discuss in your cleaning validation protocol, I don’t see them as part of your risk assessment. It makes no sense to perform cleaning validation of a GRAS (generally regarded as safe by the FDA) excipient. It is the API that is most toxic and has a known physiological effect. While you can discuss the excipients in the formulation I would not target them as compounds of interest.
Potency in the drug product formulation is part of your risk assessment. Again I would discuss whether the facility manufactures the raw material or the drug product.
There are some CMO’s that make a bulk pharmaceuticals (raw material) for clinicals and thus the ADE or PDE has not been determined. Thus, I would use the 10 ppm solution particularly since the final manufacturing process train has not be finalized and the cleaning solution(s) have not been finalized. I would also dedicated some equipment to mitigate the possibility of carryover.
For every cleaning (even the same product) the FDA requires the equipment to be visually clean. So for dedicated equipment (one product only) everything is GRAS since there is no carryover which would contaminate the next lot. So yes, even GRAS items still are required to be cleaned from the equipment to at least a visual level…
For example if you have a protein on the surface of some equipment, and the protein is safe (GRAS) its still needs to be cleaned off since it can cause a biofilm to start.
It really isn’t as simple as looking at ADE, PDE, LD50, toxicity, etc of the API. There are other factors involved in determining your worst case product for cleaning.