Biocontamination control techniques for purified water system Water treatment, storage and distribution system for preparation

and distribution of purified water should have the properties to control microbiological contamination. Techniques should be employed during the qualification of water system. The water systems that are operated at 70-80 C are less susceptible to the microbial contamination then the systems operated at ambient temperature because microbes has optimum growth on ambient temperature. A spray ball should be used to prevent the source of contamination in head space of storage tank. Vent filter should be used to avoid the contamination of the storage tank from the outer air entering into the tank. Filter should of 0.2 m pore size and should be validated. Vent filters should be sanitize time to time by appropriate sanitizing agents. Velocity of the water flow should be considered during the validation of water system and same should be maintained during the normal operation of the water system. Deadlegs should not be more than 1.5 times of the pipework diameter. It will help to avoid the stagnant water in deadlegs. If water system is maintained at ambient temperature, it should be sanitized at least once in a week with hot water i.e. >70 C or other suitable sanitizing agent. If chemical sanitizing agent is used then it should be validated for its cleaning procedure to remove from the system. Ultraviolet (UV-Light) light should be used before the return loop to minimize the contamination entering through the water returning into the storage tank.

Passivation of Purified Water System/WFI System in Pharmaceuticals Purified water system and WFI system in pharmaceuticals are needed to be passivated time to time. Following is the procedure or the same. Take the required quantity of Nitric Acid (AR Grade/Commercial Grade) after released by QC. In case of commercial grade, calculate the required quantity of Nitric Acid as per 10% AR Grade with the help of QC (attach COA of Nitric Acid). Prepare the 10% v/v Nitric Acid solution with water kept in a tank and allow to recirculate the same to the required pipeline for 24 hrs. After successful recirculation of above solution, drain it completely. Again fill the tank with fresh water and recirculate it for at least 60 minutes, take sample of fresh water to be filled and after recirculation for analysis of pH then drain it. Again fill the tank with fresh water completely and recirculate it for at least 60 minutes and then take samples from the predefined sampling points for the analysis of pH and then drain it. Repeat the same procedure until the pH value of feed water and samples water after recirculation will be the same. The limit of pH for recirculated water is equal to 1% of feed water.

Quantity required as per 10% AR Grade Nitric Acid Required commercial grade HNO3 (%) = X 100 Assay of HNO3 Total required HNO3 (v/v) ) = Total volume of water (Ltr.) X Required HNO3 (%).

Chemical Sanitization of RO System and Biofilm Removal To control microbial growth, RO systems must be chemically sanitized on a regular basis. Prior to sanitization, it is important to chemically clean the first-pass RO system. This will help to disrupt any biofilm that protects bacteria from contact with the sanitant. It also removes foulants that will react with and chemically deplete the sanitizing agent. Typically this is done in a two-step process. The first step commonly involves the use of an acid cleaner such as Citric Acid to remove the inorganic foulants. Next, a high-pH cleaner such as NaOH is used in order to remove organic foulants. Then the system is sanitized with one of the following agents: Formaldehyde, Hydrogen Peroxide, or Peracetic Acid. It is important to consult the manufacturer of the RO system to determine the correct concentrations of the chemicals that are compatible with the membranes in the system, and always rinse with purified water before changing chemicals. Both cleaning and sanitization processes consist of four steps are; 1. The cleaning chemical is mixed with permeate water in a clean-in-place (CIP) tank. 2. The chemical solution is recirculated through the RO system for 15-30 minutes. 3. The system is left to soak for 20-30 minutes. The system should be started once every 5-10 minutes for a short time to allow fresh solution to contact the membrane. 4. The system be rinsed with permeate water until the residual cleaning and/or sanitization chemicals have been removed. Although the second pass of the RO does not typically require cleaning as frequently as the first pass, a regular cleaning and sanitization schedule should be maintained. This schedule should be based on the microbial concentrations and samples collected from the permeate water from the second pass RO. When microbial concentrations in the permeate begin to rise steadily, sanitization should be conducted. If peracetic acid or hydrogen peroxide is used to sanitize PA membranes, the membrane must be cleaned with an acid cleaner in order to remove free iron and any other transitional metals; otherwise the membrane may be chemically damaged by the sanitization procedure. It is also important to make certain that the sanitant is mixed with water that is free of chlorine. The membranes exposure to the sanitant should not exceed one hour per week at the recommended concentration level, or reduced membrane life may occur. Biofilm Removal Biofilm is a common term used to describe the accumulation microorganisms and their by-product excretions onto the surfaces of a water treatment system (membranes). Because most microorganisms prefer to become attached to a surface, more and more microorganisms will adhere to the surfaces of a water system (membranes). As microorganisms die, they become nutrient sources for other microorganisms. Over time, a film consisting of living and dead organisms will form. A slimy cover called a glycocalyx surrounds the organisms and serves to trap nutrients from the water source and protect the organisms from chemical destruction. To remove a biofilm, it is necessary to conduct a series of sanitization and cleaning steps are; 1. Inorganics should be removed using a low-pH cleaner. 2. Any organic compound or dead microorganisms should be removed using a high-pH cleaner such as NaOH. 3. A sanitizaition should be conducted using a common sanitizing agent such as formaldehyde, chlorine, or peracetic acid/hydrogen peroxide. Then conduct a series of organic cleaning cycles followed by sanitization cycles. Prior to changing chemicals, always flush with purified water. For severe, established biofilms, it may be necessary to

repeat this process 5-10 times. During each step, the sanitization agent should be in contact with the system for 15-30 minutes. Purified Water System in Pharmaceuticals Regeneration of Resins REGENERATION OF CATION EXCHANGER. NOTE: DURING REGENERATION OF CATION BED ENSURE THAT THE DEGASSER PUMP IS OFF. Take approx. 28 L DM water HDPE regeneration tank. Add approx. 14 L of 33% HCl solution to it. Mix. Keep it ready for injection. (Quantity requirement to be calculated as per system design). Open raw water inlet valve. Open valves of AC filter. Check whether all the valves of cation exchanger are closed. Dip the free end of PVC tube attached to valve of cation exchanger into the HCl solution. Open valves and control an injection rate of HCl solution into the cation exchanger required as per the system design. (In order to stuck the acid solution by Venturi principle direction of flow is with gravity during regeneration and against gravity during normal operation). As soon as the injection of HCl solution is over, close valve and rinse for 20 minutes. After 20 minutes close the valves and up rinse the cation exchanger. Check the pH; continue rinsing until the pH reaches between 2 3. If the pH is less than 2, continue up rinsing for some more time. Frequency of regeneration : Twice a week. REGENERATION OF ANION EXCHANGER. NOTE: DURING REGENERATION OF ANION BED ENSURE THAT THE DEAGSSER PUMP IS OFF. Take approx. 36 L of DM water in HDPE regeneration tank. Dissolve approx. 4 kg of NaOH into it. (Quantity requirement to be calculated as per system design). Open raw water inlet valve. Check whether valves of AC filter of the cation exchanger are open and all the valves of anion exchanger are closed. Dip the free end of PVC tube attached to anion exchanger into the caustic solution. Open valves and control the opening of valve in such a way so as to maintain an injection rate 3.5 L/minute of caustic solution into the anion exchanger, required as per system design. (In order to stuck the acid solution by Venturi principle direction of flow is with gravity during regeneration and against gravity during normal operation). As soon as the injection of caustic solution is over immediately close the valve and down rinse anion exchanger at least for 30 minutes. After 30 minutes, close valve. Open valve for up rinsing of exchanger for 15 minutes. During up rinsing, switch ON the main switch as well as the switch of panel board in order to start the degasser pump. Ensure that all other switches are in OFF position and level of water is maintained more than half in the degasser tank. Check conductivity and pH. Conductivity should be less than 30 S/cm and pH between 7.5 9.5. If the conductivity is higher than 30 S/cm or pH is higher than 9.5, up rinsing may be continued for some more time. Frequency of regeneration : Twice a week. REGENERATION OF MIXED BED EXCHANGER. Take approx. 6 L DM water in HDPE regeneration tank and add approx. 3 L of 33% HCl solution to it and mix. (Quantity requirement to be calculated as per system design).

Dip the free end of PVC tube attached to valve of mixed bed ion exchanger into the solution prepared. Take 10 L of DM water in another HDPE regeneration tank. Dissolve 1.25 kg of NaOH into it. (Quantity requirement to be calculated as per system design). Dip the free end of PVC tube attached to mixed bed ion exchanger into the solution prepared. Open raw water inlet valve. Check whether the valves of AC filter, valves of cation exchanger, valve between degasser tank and degasser pump of anion exchanger are open. Switch ON the main switch as well as the switch of panel board in order to start the degasser pump. Ensure that all other switches are in OFF position and level of water is maintained more than half in the degasser tank. Close all valves in use. Open valves for backwashing of mixed bed exchanger for 10 minutes. Then close all the valves of mixed bed ion exchanger for 5 minutes for setting of mixed resins. (This operation helps to segregate the anion and cation exchange resins in the mixed bed depending on their density differences).