What price pure water?

Scientists are always ready to specify tighter limits when it comes to water purity, but this comes at a price, says Alan Mortimer, technical director, ELGA LabWater

Drug discovery and increased quality requirements of analytical operations in the pharmaceutical industry require water of the highest possible purity. But high purity goes hand-in-hand with increased cost, so it makes sound economic sense not to specify an unnecessarily high level of purity. General laboratory requirements such as autoclaves, glass washing machines and equipment rinsing systems need pure water. Higher purity water is needed for the preparation of reagents, buffers, media and electro-phoresis gels, and even higher levels of purity for protein extractions in life science applications, and for analytical procedures such as HPLC, atomic absorption spectrometry and ion chromatography.

specific requirements

But while analytical procedures require only relatively small amounts of water, glass washers and autoclaves consume high volumes. Ensuring that the laboratory has the right quantity of the right quality of pure water at the right price is the job of the system design engineer.

Defining the specific requirements of an individual laboratory is the first step in designing the laboratory water system. There are three principal options:

• Mains water feed with total purification at point of use;

• Mains water supplied to a central purified water loop with point of use polishing to high quality;

• Mains water supplied to a local purified water loop with point of use polishing to high quality;

In the first option, mains water is fed directly to each of the laboratories' points of use. As standard plumbing is frequently already in place for sinks and washers, minimal additional pipework is necessary, merely short take-offs at the relevant points. The water is then purified to the required standard at each point of use. However, it means that more purification equipment is needed at each point of use.

In a new laboratory there is often a distribution loop for purified water of a quality suitable for feeding autoclaves, glass washing and so on. In the second option, this loop is supplied with mains water that has been purified by reverse osmosis and/or deionisation in a central plant room. The water is then distributed around the building, where it is polished to the required specification at point of use.

Because the water is already partially purified, both capital and operating costs of the point of use polishers are lower than those required in the first option. But the loop has to be engineered to meet good practice standards, with appropriate recirculation flow rates, materials selection and planned maintenance being taken into consideration.

This option does have a number of disadvantages. It provides no flexibility, so if the system fails, the entire laboratory water supply is shut down.

If a routine sanitisation is being carried out, then every point-of-use system has to be physically isolated to prevent the sanitisation chemicals damaging or contaminating the polishers or lab equipment.

The materials and fittings for the plumbing to the labs are expensive, and the pipework has to be designed very carefully to prevent static areas forming. And there is a lack of local 'ownership', which can lead to conflicts between users about priorities for water use.

hybrid system

The third option, the packaged central laboratory water system or local loop, is becoming increasingly popular. It is a hybrid between the first two approaches, with mains water being fed into a pre-purification system, which then feeds a single laboratory, a suite of laboratories or a complete floor in a facility.

Any necessary polishing can then be carried out at the point of use, but it means high volume flow rates can also be provided directly to the lab's support equipment, such as glass washers, sterilisers and autoclaves.

In comparison with the second option, the cost of additional plumbing is low, with minimal expensive inert pipework in a local loop. Maintenance and ownership conflicts are not an issue, and reliance on others to maintain the supply is minimised, as each local system is independent. Equipment costs tend to be slightly lower with this option and the saving is usually further enhanced due to the lower cost of installing and commissioning a prepackaged and validated system. To minimise the impact on valuable bench space, the point-of-use polishing units can be wall-mounted or included in under-bench cupboards.

System engineering is critical for each specific installation to ensure that appropriate performance specifications are obtained throughout the entire system. One essential component is dynamic distribution, which keeps the water at peak quality by recirculating it through the active purification steps. However, too high a flow rate in a continuous recirculation system can cause a temperature build-up and encourage microbial growth.

The compromise solution is to operate the laboratory purifiers in an intermittent or reduced flow rate mode, which will maintain water quality while minimising heat generation, thus eliminating the need for expensive, complex heat exchangers to cool the water.

smooth surfaces

Also essential is the selection of materials, as these can introduce impurities, particularly organics, that contribute to the overall TOC. The pipes in primary loops should, ideally, be some sort of multilayer coextruded tube, with excellent chemical resistance and low leaching on the internal surface. The structural layers improve strength, while barrier layers minimise gas diffusion. The surfaces must also be smooth, and techniques such as rotational moulding should be used to ensure there are no welded seams in the reservoirs to harbour micro-organisms.

As far as the water purification itself is concerned, optimum results are obtained using a combination of complementary technologies (figure 1). All have their strengths, and there is a good degree of overlap between them. For example, while reverse osmosis is primarily used to remove organic and inorganic impurities, some low molecular weight organic impurities will pass through the RO membrane. They can, however, be removed by adsorption on activated carbon. Ion exchange is principally used to remove ions and carbon dioxide but special versions have also been developed to take out colloidal impurities.

Analytical chemists work on the premise that the water they are using always meets the requisite quality standard. Consequently unexpected - and unnoticed - poor quality water is likely to lead to misinterpreted data, and wasted time and effort.

Continuous monitoring of resistivity and TOC provide an excellent overview of system status, but they cannot, on their own, provide total confidence. This can come only from a system that is designed to minimise the chance of impurities accidentally leaching through into the purified water supply.

In the Purelab Ultra, ELGA LabWater achieves this by series twin pack operation, in which two purification cartridges are used in series.

back-up system

The first cartridge is used to purify the water and its quality is tested, before passing through the second polishing cartridge. This means that any weakly ionised impurities that may elute from the primary cartridge as it approaches exhaustion will be removed by the second cartridge, which has barely been used and hence is fully effective as a polisher.

Meanwhile, the intermediate monitoring means the growing ineffectiveness of the first cartridge is easily detected and it can be changed before problems with the final water can occur.

This may sound expensive, but because the first cartridge has a back-up, there is no need to exchange it immediately, allowing any purging, rinsing and conditioning procedures that are required on cartridge change to be carried out at a convenient time rather than possibly interfering with ongoing laboratory work.

It also maximises cartridge life since it can be fully exhausted rather than exchanged as soon as impurities begin to break through.

Good laboratory practice requires access to certain operations - such as quality alarm set points - to be restricted, and consumables to be traceable. System configuration parameters can be assured with PIN codes or passkeys, so only trained, approved personnel can alter critical operational parameters, or initiate procedures such as sanitisation.

Data tags can be used to keep track of consumables. Everything from date of manufacture, resin type and batch number to the identity of the operator can be stored on a memory chip built into the consumable.

The microprocessor management system can also detect if deionisation cartridges are incorrectly fitted, or even whether they have been used before, and in what position.

Validation is an accepted part of pharmaceutical manufacturing systems and, as laboratory facilities are subjected to closer scrutiny, the need to comply with GLP and GMP requirements is increasing. While some factors like materials in contact with the water, alarm set points and operating regimes can, to a large extent, be prevalidated, the final validation process must take place on the installed system.

validation requirements

A validation support manual is invaluable in making this process as smooth as possible. Just as with production plant, this should include information on applicable products, standards conformity and maintenance contracts, as well as full specifications for the various stages of validation - design qualification, installation qualification, operational qualification and performance qualification.

No matter how well the system is designed, micro-organisms can still grow in ultrapure water, so all systems will need to be sanitised as a routine part of maintenance.

The sanitising agent should come into contact with all wetted surfaces, otherwise rapid re-growth can occur.

Figure 2 shows bacterial data collected over a five-month period for three different types of system:

• the dark blue graph shows the water quality obtained from a static reservoir, which had been filled with highly purified water. Despite this, bacteria counts rose to over 1000 cfu/ml.

• the green graph, where water from a similar reservoir was recirculated, the results were much better.

• by far the best results were obtained from the system shown in orange, where water was taken from a dispense tap that was part of the recirculating loop, just after the purification unit and just before the return water was fed back into the reservoir. Even without a point-of-use filter, counts of less than 0.1cfu/ml were achieved consistently.

Most laboratory water systems use a storage reservoir to allow for high draw-off volumes and the drop in water level as the reservoir is emptied draws in atmospheric air containing carbon dioxide and, possibly, solvent vapour from the laboratory.

Nitrogen blanketing, as is commonly used in production scale systems, is not a practicable option on laboratory scale, but a composite vent filter, which removes particulates, microorganisms, organics and carbon dioxide, is an effective alternative.

The increasingly stringent requirements in laboratories pose a challenge when creating an effective, reliable ultrapure water system.

But even the most demanding legislative specifications and validation requirements can be met provided that the process system is properly specified and engineered.