How to clean and disinfect new purity water system pipe before star up 3

[zhangbd]

We just have finished install a new purity water system in site, and before the first commission of this system, also to meet requirement of QA or cGMP compliance, we must clean and disinfect the system pipe/valves according to necessary procedure. So I want to know if we have a standard SOP about this operation?

Thanks and Regards

zhangbd

Janssen China

 

[greg87]

Sanitization can be performed with chemicals: hydrogen peroxide or peracetic acid solutions. Makeup a dilute solution in the tank and circulate through the system. Draw off at each use point to ensure exposure to all piping. After a period of time, flush. Sample to ensure no residual.
Concentration and time are the two variables. For hydrogen peroxide, a 10% solution circulated for 12 hours is very conservative. A solution of Minncare by Minntech is a good choice for a peracetic acid solution, and preferable to hydrogen peroxide. A 1% solution circulated for an hour (after you are sure it has reached all parts of the system) will do it. Minntech can provide you info and test strips.

I am assuming that the pipe has been installed clean, and if it is stainless steel, it has been passivated.

 

[MedicineEng]

Zhangbd:

Greg87 is right but this only applies to the PW production plant, not to the PW distribution loop.
For the loop, before you do the sanitization you will have to make some other steps:

I assume that the pipe and tank are SS316L internal polish, food grade (<0.51uRa if I am not mistaken);

1.After the weldings and the pipe all manufactured and put in place you will have to degrease it. As you know, pipes are quite dirty and also welding releases some &quot;greasy&quot; material. You can do this with a normal washing powder. Charge the tank around 10-20% and then add the washing powder. Be very careful with the quantity, due to the foam formation when you put the loop pump working. So, I recomend that you use a low foam detergent;
2.You recirculate this solution for 30minutes, one hour, discahrge and rinse the tank and pipes with fresh water several times.
3.Then, you need to passivate the tank and the distribution loop. As you know, PW has a pH acid, so you need to passivate the SS to increase it's resistance. For that, you use a solution of nitric acid at 5%.
Charge the tank about 8-12%. Then, you need to heat up the system up to 80C and recirculate the solution 30 minutes. After that, cool dowm and make the neutralization with sodium hodroxide. VERY IMPORTANT!!! Be careful with the addition of NaOH to the solution of nitric acid. The reaction is highly exotermic. As such you will have to add the NaOH very slowly if possible with the recirculation pump switch on. After Ph=7 is achieved (you have to control with a Ph papaer indicator), let the neutral solution circulate for about 30 minutes. Discharge the tank and fill up to 10-15%with PW water. Then recirculate for about 2 hours. Repeat this step until you don't have traces of nitric acid or NaOH.
4. Now you can sanitize the tank and the loop. Usually in this sanitization we don't use any chemical it is just a thermic sanitization that is controlled by the PLC program of the PW skid. Usually you have two types of thermic sanitization: one at 80C that is recirculating for 2 hours, and other at 121C (a kind of sterilization) that recirculates for 30 minutes.

For both you have to have the PW level in the tank of about 15%.

All this is for the PW storage and distribution loop.

For the PW production plant you can use Greg's suggestion. Usually, for microbiological contamination, we use also formaldehyde solution.
I suggest to you that you contact the supplier to give you some support, otherwise you might have big headaches with the system.
PW systems are very sensitive and a permanent attention has to be given to it.
Just as an example, in my actual PW system and since the area where my actual company is installed (Southeast China)is very hot and humid we had to install a system that permanently cools down the water below 23C because as you know, above 25-27C the probabilities of having microbiological contamination increase very much.

I hope that this information is useful to you.

PR

 

[greg87]

PauloRibeiro is correct that if the system is stainless steel, then it must be passivated prior to sanitization, as I stated. The actual water spec for your “high purity” system may impact what really needs to be done. Stainless steel high purity water systems would normally use stainless tubing, sanitary fittings, would be welded (either by machine or manual) without filler rod, and would be installed “clean” by trained personnel. With this approach, there would not be grease or welding spatter. Since the installed system is still not perfectly clean, standard passivation procedures include cleaning as a first step, usually with hydroxide, prior to the passivation steps. Passivation is best be contracted to a company who does it regularly. Most companies that perform passivation use chelated chemicals rather than nitric acid.

If you have the equipment set up to heat sanitation, that is best. Systems at pharmaceutical facilities and labs that do not have the heat exchangers etc, use hydrogen peroxide or peracetic acid to sanitize the entire distribution system, as well as the production system. Both of these chemicals are effective and, more importantly, are non-contaminating. These chemicals are also appropriate for plastic systems. I do think formaldehyde should be added to any pure water system.

You will need to sanitize the system (production and distribution) periodically. How often will depend on the quality of the installation. You will need to sample every day to determine when the microbial load on the system is starting to get close to your limit.

 

[MedicineEng]

Zhang:
Greg is right. The use of formaldehyde in a PW system should be avoided, specially because it is dangerous for the health and some special cares have to be taken when you are handling it. If you use it, you have also to have a kit to detect in order to check if you still have formaldehyde after the rinsing of the system (you can use a Merck kit 1.08028.0001-Formaldehyd Test).
Formaldehyde is very hard to remove from the system. Just for you reference, every time that we use it, we need to make a 16/20hours rinsing to assure that no formaldehyde is in the system.
Some systems replaced formaldehyde by peracetic acid, but as far as I was told, there are some old versions of reverse osmosis membranes that cannot withstand with the peracetic acid.

Please give us your feedback on how are the things going with your PW system.

PR

 

[dtreacy]

Hi,
I agree with the above, Formaldehyde should be definitely avoided when it comes to purified water system.
For degreasing a caustic based solution should be used. Detergents should be avoided, as it may be impossible to prove to the regulatory authority or your own QA department that they have been effectively removed by rinsing.
Nitric acid or chelated chemicals can be used for passivation. The function of the passivation is to re-establish the protective layer on the surface of the steel, which was removed by welding. (Its also good if you have a rouging problem).
Sanitisation can be carried out either chemically (Hydrogen Peroxide / Peracetic acid mixes such as Oxonia), thermally 85 degC or through the use of Ozone generators and injectors.
If you are using chemical or ozone sanitisation. Turn off your UV lamps during sanitisation and turn them back on during rinsing (this will degrade the Ozone / hydrogen peroxide.
Also make sure that your UV lamps are off when thermally sanitising as the heat will damage the UV lamps.
Periodically monitor chemical concentrations during sanitisation as the sanitant may be used up doing its job.

Hope this is of further help.

Regards
Daragh