Validation of ozone process in Pharma water treatment – V.Baratharaj (CMD of Ozone Technologies and Systems India Pvt Limited)

Chennai, March 07, 2015 –
Water is used in Pharma for production, process, for formulations, for CIP and in Quality control process. There are different grades of water specified for each of these different uses . This article addresses the validation process that could be adopted whenever ozone is used in Pharma water treatment .

Water is required on demand in Pharma processes . That means when ever water is used, it has to be of required quality . There is no time for testing and than deciding to use . That is why Quality Assurance assumes such importance in Pharma Water production .Quality Assurance is involved in approval of water qualiy before use. A validated treatment process becomes a routine

Ozone is used in Pharma Water treatment mainly as insurance of quality. Since Quality of the water has to be consistent, it is only ozone that can gurantees this . Ozone provides this because of its high oxidative actions and for reason that it is eco friendly and does not leave behind any residues, toxic compounds and many of the bacteria such as Gram Negative strains ( Pseudomonas, BTGN), coliforms are all highly susceptible to ozone .

The design of the ozone system should ensure that all pathogens are removed 10 out of 10 times .Water should not re contaminate during storage , distribution and before use, The residual ozone required is very small that covers a wide range of most pathogens found in waters . It also prevents proliferation of pathogens The residual ozone is then destroyed just before use .

There should be an online and off line monitoring process that will ensure that will ensure compliance of water quality as specified.

The following documents are normally created for validation process

a) Design qualification , commonly know as DQ

b) Installtion qualification , commonly known as IQ

c) Operational procedures , commonly known as OP

d) Risk assessment documents

Design & Installation Qualifications:

The following should be considered during design validation process

1) Determination of correct ozone dose ( water specific)

2) Ozone contacting & selection of contact tanks

3) Ozone injection methods – selction of ventury and injection pump & Prevention of back flow to ozone genearator

4) Location of the ozone injection

5) Measurement of ozone residual & Monitoring ozone residual after distruction process

6) Ozone distruction methods including transfer of ozonated water

7) Vent ozone ditruction process and ambient ozone levels

8) Storage of de ozonated water

9) MOC of pipes for ozone integration

10) MOC of Venturi

11) MOC of gaskets of pumps , non return valves , pipe nipples etc

1) Determination of correct ozone dose & concentration

Achieving consistent bacteriological quality is totally dependant on the ozone dose. The ozone dose is determined by the qualiTy of the water, the flow rate and above all the goal of ozonation .Before deciding on the dose a through study on the present treatment system, quality of the water to be ozonated and issues faced by the client ( retero fitting) . Some times it is easier to solve an issue (bactaeriological contamination) if reasons are found, rather than simply adopting ozonation as a means of solution. .

The goal of ozonation is very important. Are you incorporating ozone for primary disinfection? Are you using for Bio fouling removal,? Do you have persistent pseudomonas contamination? Are you looking for residual ozone during storage? Is heavy metals removal your goal? Or are you looking to incorporate ozone to upgrade your present facilities? These are some of the answers that have to be answered by the client.

Ozone concentration : Never accept air fed ozone systems for Pharma disinfection. Using oxygen as feed gas is a better way to go . Not only will the concentration of ozone will be higher (8% and above), it will also facilitate better ozone mass transfer .small oxygen systems that are reliable, are available. Easy to operate & maintain. All oxygen plants come with flow meters and hence valdation becomes very easy. With the present Technology available around the world ( India –no exception) , you can produce not more than 35-36 grams of ozone every 5 liters of oxygen (5LPM) .Use this as a thumb rule when you calculate requirement of oxygen as feed gas . This will produce ozone at 8-9 % concentration. Imported units can produce ozone at higher concentrations but these are for larger units requiring ozone in Kgs. Manufacturers in India claiming to produce 50 grams with 5 LPM oxygen have to be viewed with suspicion.

How to measure ozone production: This is always measured in terms of concentration of the ozone gas , in grams/Nm3. The ozone production is calculated by multiplying this concentration with the flow of oxygen (feed gas) that you introduce into the ozone generator. There are instruments that measure the concentration of ozone of an ozone generator. These instruments are very expensive and not many ozone manufactuers have them. A test certificate needs to be produced certifying the ozone production. If it is going to cost a little extra, manufactuers may be requested to do the test at site or call for a FAT.

2) Ozone Contact time and Contact Tanks

Ozone contact time is crucial for achieving results. As each bacteria has a CT value (contact time x ozone dose) , we need to determine the contact time vis a viz the goal of ozonation . Iron or manganese removal need very small contact time, whereas if the goal is organic reduction, the contact times are higher. Removal of coliforms for example is dose related. Dependant on the contamination level, ozone can achieve up to 3 log reduction of coliform with small doses. Similarly for gram negative organisms, the contact times are larger, doses need to be larger ( for consistent results) .

Based on the contact time, the contact tanks are sized and MOC determined based on whether it is pre treatment (HDPE sufficient), SS if it is post treatment..FRP tanks can also be used. Essentially, the Material of construction of the tanks has to be resistant to ozone at the concentration being applied.

3) Ozone injection methods – selection of ventury and injection pump

Ozone injection is crucial for transferring the ozone into the water. Injectors are normally preferred to diffusers system for small applications like in Pharma, since it gurantees more or less 99% mass transfer efficiency .

Injection system consists of an injector, a pump, and back flow prevention methods. Selection of injector will depend on the following factors:

1) Ozone gas flow

2) Ozone gas pressure

3) motive flow through venturi

4) Pressure of water before and after venturi

Each ventury has a performance curve and we need to keep this in mind. Only reputed branded makes should be used. Locally fabricated SS venturies are best avoided as they will not be supported with performances curve .and do not prevent back flow prevention

The injection pump will than be decided based on the motive flow and pressure required by the venturi to suck the ozone gas into the venturi. This should be supported by the performance curve of the pump. A wrongly designed venturi system will leak ozone in the plant room

Reputed venturies come with in built back flow prevention devices. But we still have to design a suitable non return valve and a back flow prevention methods . Back flow if not prevented will damage the ozone dilectrics causing it to fail

MOC of venturi can be either Kynar (PVDF) or SS

Static mixers are not often required when the selection of the venturi and the pump are perfect.. Static mixers are more often used in larger pipe sizes and are often combined with other mass transfer devices

4.) Location of the ozone injection : Few tips for selection of injection location:

a) Injectors are to be installed well below the ozone generator.

b) The ozone delivery tube should be long

c) The injector must not be too far away from the pump

d) Injections musts be installed preferably on the main delivery line of the injection pump and must have a by-pass arrangement.

Pre ozonation: means ozone location before filtration system –

Post ozonation: means after initial treatment of chlorination, Sand filteration and /or UF

5) Measurement of ozone residual & Monitoring ozone residual after distruction process

The most important step is a validation process. This validates the design, validates the injection design and the contact time. Any faulty design will not produce the required ozone residual. It is expected that an ozone residual of between 0.1 to 0.2 ppm is achieved as this range will almost certainly eradicate pathogens if the contact time is achieved.

Ozone residual is measured by means of an Dissolved ozone analyser. The analyser has to be supported by a calibration certificate . The sensors take samples of water before and after ozone distruction to measure the ozone residual. It is displayed prominently on the controller. A NO solenoid valve is connected to one relay output of the analyser. This closes and diverts the water back to the ozone tank incase if ozone is present after UV distruct

It should be noted that the sensors require undergoing polarisation before it can start sensing. This procedure will take between 24-48 hours .The sensors are to be initially immersed in an electrolyte provided by the OEM . Sensors are to be caliberated at least onec a year for validation.

After ozone distruct , there is nother sensor to measure the dissolved ozone levels. This time it should be zero . Any small amounts of ozone will trigger closure of the solenoid valve and open the by pass valve to re direct the water back to the ozone tank. A zero ozone level validates the working of the ozone distruct.

7) Ozone distruction methods including transfer of ozonated water

Normally a UV lamp is used for this purpose. It is essential that the UV lamp is installed along with intensity monitors so that the user is aware of the deteriorating life of UV lamps . A zero ozone measurement after the UV lamp validates the UV lamp . The transfer pumps are designed based on the flow required and mostly does not need to operate at higher pressures

8) Vent ozone distruction process and ambient ozone levels & Monitoring ambient ozone levels

Dissolved ozone is likely to get stripped inside the ozone tank. As a safety requirement is always recommended to install a ozone destructor at the vent. This is a thermocatalytic unit that destroys the small zmounts of ozone that may escape through the vent of the ozone tank. . This will also prevent any ozone leaking in the plant room

An ambient ozone sensor monitors the ambient ozone levels in the plant room. There are different types of ambient ozone sensors , some are graphic and hoots on reaching the safety ozone levels , others acan be linked to shut of ozone syetm in case of leakages . he safety levels are normally fixed at 0.01 ppm in the plant room. Ozone toxicity levels are 0.1 ppm exposed to over 8 hours . So the safety threshold is very high for ozone

9) Storing deozonated water : It is strongly advised not to store deozonated water before use . It is preferable that an left over water is either drained and the water sent for ozonation once again before use in process .

Validation of MOC

1) Pumps : wet parts must be SS , All gaskets and seals ozone resistant

2) Ventury : SS or Kynar

3) Tank nipples : gaskets must be ozone resistant

4) Tanks : SS or HDPE or FRP ( LDPE to be avoided)

5) Ozone hoses : Teflon or silicon only

6) Sensor hoses : Silicon

7) Pipes and fittings: SS or UPVC

Risk assessment :

A risk evaluation document need to be prepared as a QA record. This is a document that identifies the possible risk or failures in the process and porbable control measures . Risks are classified based on its severity as High Medium and Low . This should be carefully prepared after discussions with the technology provider to ensure that the assessment is complete and nothing is missed

Opertional Procedures & Training

This is best obtained from the technology provider and integrated with the existing operational procedures of water treatment. . During installstion training is provided to two or more nominated operators , that will include trouble shooting, and routine maintenance of the equipment

Author –

V.Baratharaj ,is a qualified Pharmacist and has nearly 25 years experience in Ozone and is the Chairman and Managing Director of Ozone Technologies and Systems India Pvt Limited , a leading Chennai based Company specializing in ozone applications .He can be contacted at otsilozone@gmail.com .

K.Altaf, Managing Editor, The Pharma Times, https://thepharmatimes.in/