Dear Colleagues,
please, can you help me as I do not belong to the ‘‘cleaning’’ world, I am actually an technician. But…I need your recommendations and advices.
It is about cleaning validation of mesh from sieve. We have here a solid dosage non aseptic production.
Now, I need to purchase a new one vibrating sieve within 0,5 and 1 mm sieves (two kind original and two pcs in reserve).
I have problem now as my QA Dept wants from me to change request to the supplier and to buy more than 10 pcs of meshes with explanation that is good and easier way for cleaning validation of mesh after sieving???
Ok, but meshes are very expensive, and it will cost almost like half of all machine price!!!
Please, give me some advices from your experiences, is it good and normal solution and idea ( to buy many, many…meshes)
Is it difficult to validate the cleanless of the mesh??
How is correct procedure for the same in my case???
Is it necessity to use HPLC for that reason??? Or just analyse a remain of sample after cleanig-washing and rinsing???
Ehhh…I am really a little bit in doubt and much more confused about all these… If you ask me,…I think that is not good idea to buy many meshes as I think that will couse other problems…for example…to explaine where you hand all those meshes, how you marked them, which one will use and when, it will increase a risk to mix differ mesh, also…what will happen when we need to work a new product?? To buy again new mesh???
At the end…one 0,5 size mesh is 540 EUR and 1mm mesh is 815 EUR:confused:
I think that they are want to avoid to validate mesh. Simply, they can tell to inspector that’s not need to validate cleanless if we use only one mesh for only one material.:eek:
I think that we do not need to buy more meshes, just validate cleaning method and than we can use one mesh for differ supstances. Am I right or not??
You are right cubica.
Just doing cleaningvalidatioon on single mesh you can save using multiple mesh. The cleaning validatiobn is done on the non dedicated equipment. Having multiple mesh wil avaoid that ? But what is problesm in performing the cleaning validation on the mesh ? that is easier than going for the multiple mesh? What do you think ?
Dear Anil, on the first, many thanks for answers and help given to me.
next…I still think, the best solution is to validate cleanless for one working and one spare mesh and sieve differ components trough the same meshes.
We will just approve that is this solution possible trough cleaning validation procedures and that is all. Of Course, any time we check cleanless of the mesh trough validation, we need to get good results. And I hope, it will be like that.
My friends, meantime…my QA Dept advised me that is not necessity to buy more meshes:) so,…I won!!!
thanks for help, now I am only interesting about procedure, how to approve (after sieving, washing, rinsing and drying) that is mesh clean. What is procedure??? I just want to know for my knowlendge base.
in our experience, the best way is to go for dedicated sieves. We have limited the “dedication” to actives, that is, we have bought one mesh per active ingredient that needs sieving, one for the excipients and one additional spare sieve. The cleaning validation is possible, but, depending from your acceptance limits, the cleaning method has to be very drastical (in many cases including ultrasonic cleaning and/or chemical destruction of the contamination) because of the contamination occluded between the mesh wires at the crossings. For the same reason the preferred sampling method is rinsing, because the swab recoveries are extremely low, and obviously a stainless steeel coupon is not a representative surface for a wire mesh. At least in our case the cost of manpower and chemicals for the development of the cleaning method and the method validation (analytical and recovery test) outnumbered the acquisition of dedicated sieves, with the additional safety of minimising mesh confusion (they are color coded) and eliminating cross contamination. If regardless of all this you want to validate the cleanliness of the mesh, contact me for some advice.
in our experience, the best way is to go for dedicated sieves. We have limited the “dedication” to actives, that is, we have bought one mesh per active ingredient that needs sieving, one for the excipients and one additional spare sieve. The cleaning validation is possible, but, depending from your acceptance limits, the cleaning method has to be very drastical (in many cases including ultrasonic cleaning and/or chemical destruction of the contamination) because of the contamination occluded between the mesh wires at the crossings. For the same reason the preferred sampling method is rinsing, because the swab recoveries are extremely low, and obviously a stainless steeel coupon is not a representative surface for a wire mesh. At least in our case the cost of manpower and chemicals for the development of the cleaning method and the method validation (analytical and recovery test) outnumbered the acquisition of dedicated sieves, with the additional safety of minimising mesh confusion (they are color coded) and eliminating cross contamination. If regardless of all this you want to validate the cleanliness of the mesh, contact me for some advice.
Regards
Alfred[/quote]
In this case I would like to know that for validating the cleaning method for a mesh how do you fix a residue limit since the quantity of the next material which might be seived is never fixed
I am interesting also, on the first I’d like to know what is correct procedure to validate mesh’s cleanless…residue quantity or HPLC method?? I am talking about HPLC method as my QA person told me that is correct procedure only HPLC method (to determine remain of supstance)
oohhh…I forgot…Dear Lalit, I think that is viscosity (adhesievness) of material also very important, because…in the case you have an sticky material …it is very possible to find bigger residue into sample after washing and rinsing. Dear Alfred, what is your comment?? How is your procedure??
kindly regards,
cubica:)
sorry for the late reply, i just dropped in from vacations.
To validate the cleanliness of a sieve the approach is exactly the same as for every piece of equipment: Take it as a part of an equipment train, determine the two worst cases [worst contaminant API (most potent, most insoluble, hardest to clean, etc.) and worst contaminated product (worst combination of largest number of daily intakes and smallest batch size)]. Then calculate the surface of each piece of equipment, sum the surfaces of the pieces shared by both worst cases, calculate the accepted contamination limit (which will be unique for each piece of equipment with the same combination of both worst cases), and you will get the acceptance limit in µg or mg per unit surface. One of these pieces of equipment will be your sieve, and by this way you will set the acceptance limit. It is difficult to figure out that the quantity of next material sieved is never fixed, because the batch size should be fixed, and as such the quantity to be sieved, only that for the worst case approach you will have to take the smallest batch to be sieved.
To validate the cleanliness, first step (after validating the analytical method at and around the expected target values) is the recovery test. Usually for a mesh the swab sampling has too low recoveries (unless it is a perforated metal screen and not a wire mesh) and you need to resource to sampling by rinsing with a solvent that is appropiated for the target substance. A stainless steel coupon is not representative for the type of surface to be sampled, so you need a sample of the mesh (ask the manufacturer of the sieve), or to carry out the recovery test on the equipment itself. In that case you need to be careful to spike the mesh with an amount of target substance slightly below your acceptance limit, to be on the safe side not to contaminate the equipment on purpose with contaminant above the limit. Then sample the mesh rinsing it with a fixed quantity of solvent (you can optimise the quantity, but usually 0,5 - 1 ml/cm² of sampled surface is a good starting point) and determine the recovery factor. Last step is the cleaning test, carrying out three (or more) cleanings after manufacturing the product with your target substance and sampling the mesh exactly by the same way as you did in the recovery test. After all this you will regret not having used dedicated sieves!
Regarding the post about the adhesiveness of the material, this is one of the parameters to take into account when you carry out the risk analysis to determine the worst case target substance. When setting up the matrix for the risk analysis take into account the excipients and not only the API’s, regardless of the fact that excipients typically pose a lower risk than API’s. Nevertheless, the visual cleanliness of the sieve is a precondition for the validation, so the sieve needs to be free of sticky residues before sampling.
Dear Cubica: I could not understand the question about residue quantity vs. HPLC method, for i do not know what you mean by residue quantity. Could you clarify?
