Andreas Müller

Pure water is a raw material of particular importance to the pharmaceutical industry. Drinking water is the basis for the treatment of water for pharmaceutical applications; it is the starting point for the production of the various pharmaceutical water qualities, such as purified water, highly purified water and water for injection. 			

One would think that a pretreatment process is not so important for these applications. However, the times when drinking water was mostly refreshingly cool and clear are long gone and suitable pretreatment systems are becoming increasingly important. This article aims to provide background information on water pretreatment, explain when and where pretreatment systems are necessary, and describe the investments and operating costs involved. 

Pretreatment of raw and surface water is advisable, and is in some cases indispensable, when it results in better operating reliability and a longer operating lifetime for the downstream plant and equipment. Modern treatment systems for the production of water for the pharmaceutical and cosmetic industries include several process stages, namely water softeners, reverse osmosis units and electrodeionization units.  						

The demineralization methods that use membranes (reverse osmosis and electrodeionization) place high demands on raw water quality. The use of pretreatment systems such as ultrafiltration units is intended to prevent insoluble substances in the water, such as iron, manganese, micro-organisms and organic substances, from being deposited on the membranes. The following are the most important quality parameters with respect to 'membrane fouling' in reverse osmosis systems: the silt density index should not exceed 3 SDI

 units and the amount of total suspended solids should be less than 0.5 mg/L.  

For particles suspended in the water, the use of simple filter systems is the easiest pretreatment method. Such systems act as a protective filter upstream for the actual treatment units for pharmaceutical water. 						

Their task is to protect the units that follow against mechanical damage by the coarse particles often carried in the public water supply system. Depending on the pore size of the filters, the retention ability of these systems is limited to particles larger than 50 μm. 

Figure 1 provides an overview of the size of the suspended particles and of the separation limits of the various filtration methods. This clearly shows that sand, rust, clay and protozoa with particle sizes as low as 5–10 μm can be removed with fine filter systems. However, these systems cannot be used to improve the water quality with respect to the particularly critical particle sizes of less then 5 Âµm or to completely remove bacteria and viruses. 

 Figure 1 Comparison of particle sizes and separation limits.

Until now, extended pretreatment of problematical raw water has been done with cartridge filters or precoated filters. As can be seen from the diagram, these can be used to remove most of the particles suspended in the water. 			

The drawback of such systems is that cartridge filters cannot normally be backwashed and must be replaced; particularly if the water contains large amounts of suspended solids. This, in turn, reduces the availability of the water treatment plant and increases its operating costs. For this reason, cartridge filters are mostly used as pure 'polishing filters' upstream of reverse osmosis units.  

Precoated filters can be backwashed, but their use requires additional materials in the water treatment process. Because this does not comply with the idea of a modern treatment process for pharmaceutical water, these systems are generally used only in special cases in the pretreatment stage of such water treatment systems. 			

Moreover, interruptions in plant operation can lead to detachment of the filter cake and to long downtimes. Membrane-based filtration systems such as sterile filtration, microfiltration and ultrafiltration are promising methods for the treatment of raw water. The advantages of these systems are clear: 					

they permit very good removal of particles and germs

they can be cleaned and  disinfected with chemicals.

Until recently, membrane-based methods such as microfiltration and ultrafiltration were used primarily in the sector of drinking-water treatment to remove most of the particles from surface water, groundwater and spring water affected by surface water.  			

The removal of bacteria and viruses is becoming more and more important. Both of these can be removed by either microfiltration or ultrafiltration. Microfiltration permits the almost complete removal of bacteria but, in contrast to ultrafiltration, is unreliable regarding the removal of viruses. 			

For this reason, ultrafiltration systems are now being increasingly used in the sector of membrane-based water treatment.  

Membrane technology is now an interesting opportunity for considerable simplification of the treatment of problematical raw water, resulting in economical benefits. It therefore makes sense to introduce raw water ultrafiltration systems to the sector of water treatment for pharmaceutical applications. Figure 2 shows the heart of such a system. 

Figure 2 Raw water ultrafiltration - a plug and play pretreatment system.

When planning and developing processes, designers can select from a wide range of available membrane materials that are optimized for different applications. Currently, asymmetrical hollow-fibre membranes best meet the requirements of raw water ultrafiltration. 						

				In contrast to the symmetrical membranes, the asymmetrical membranes consist of a thin fine-pored skin (active separation layer) and a coarse-pored supporting layer below it (Figure 3). 

Figure 3 Asymmetrical hollow-fibre, membrane polymer hydrophilic PES.

The active layer determines the separation performance of the membrane, while the supporting layer simply supports the active layer and has no effect on the separation performance. 

Several membrane polymers, such as cellulose triacetate, polypropylene and polyethersulfone (PES) are available. At the moment, PES is the most commonly used membrane polymer. 			

The advantages of this polymer are its chemical resistance to chlorine (200000 ppm-h) and its resistance to a wide pH range (pH 1–14). The separation limits of raw water ultrafiltration membranes are currently in the order of 100–200 k-Dalton or pore sizes of 0.020–0.050 μm 

In most cases, the water flows from the inside of the hollow-fibre membranes, or in the reverse direction for backwashing. The hydraulic diameter of most hollow-fibre membranes is in the range of 500–3000 μm, a compromise between a high packing density (1000 m

 and a maximum solid load (200 mg/L) of the membrane modules. 

The structure of hollow-fibre membranes is similar to that of a heat exchanger. They consist of bundles of hollow fibres cast with epoxy resin into so-called collectors at both ends to provide good separation of the filtrate space from the concentrate space.  

For both of the membrane separation methods (microfiltration and ultrafiltration) a distinction is made between dead-end filtration and cross-flow filtration. In dead-end filtration, the raw water flows orthogonally through the membranes, rather like water passing through a coffee filter, and the particles removed from the water accumulate on the surface of the membrane, forming a filter cake, which gradually grows in thickness over time (Figure 4). 			

In contrast to this, cross-flow filtration has a flow of water parallel to the membrane surface (Figure 5). Again, particles removed from the water can accumulate on the surface of the membrane, but the cross-flow across the membrane is intended to control the formation of this covering layer.  

The control of this covering layer is the main problem of all membrane processes. In cross-flow systems with reversible formation of the covering layer, the increased shear forces that result at the surface of the membrane from, for example, increasing the rate of flow cause a permanent increase in the flow of filtrate. 

The drawback of such systems is the resulting additional energy consumption. For this reason, it is always necessary, in cross-flow systems, to find a compromise between increasing the filtrate output by increasing the rate of the cross-flow and using the smallest amount of energy. 		

The above comments apply primarily to cross-flow filtration. However, dead-end filtration is now being used increasingly, especially in applications where the raw water contains only low concentrations of particles that need to be removed. Here, the resulting covering layer on the membrane surface forms a flow resistance that gradually increases and thus, slowly reduces the amount of filtrate that passes through the membrane. In order to prevent complete blockage of the flow of filtrate, the membrane modules must be rinsed periodically. In most cases, the feed pressure (P

 [filtrate pressure]) is increased to compensate for the reduction in the filtrate flow-rate (V

 [volume permeate]), as shown in Figure 6. The feed pressure varies between 0.5 and 2.5 bar. If the feed pressure reaches a preset maximum value rinsing of the modules is started.  

Figure 6 Dead-end filtration with constant Vp.

Many systems prefer a time-controlled rinsing of the membrane modules. Figure 7 shows the dead-end operation of a membrane system with a constant feed pressure and a gradual reduction in the output of filtrate. This configuration is rarely used today because it cannot guarantee a constant output of filtrate. 			

Figure 7 Dead-end filtration with constant PF.

The central element of all membrane systems is the membrane module. The other parts of the plant form the periphery and normally consist of a back-washable coarse filter upstream of the plant; a storage tank for the raw water, which decouples the plant from the water supply; a pressure booster with frequency-controlled pumps; the tank for storage of the filtrate; and the backwashing pumps for cleaning the membrane modules. Figure 8 shows a process flowchart of a pretreatment plant as a reference for the following description of the operational concept. 

Figure 8 Process flowchart of an ultrafiltration system - a modular raw water ultrafiltration system that is delivered ready to go. 			

According to the chosen example, coarse particles in the raw water are removed by a so-called coarse filter (pore size 90 μm) located before the raw water storage tank. The precleaned raw water is pumped by frequency-controlled pumps through the membrane unit. The entire system is controlled on the basis of the rate of filtrate flow, as described above.  

Before the raw water enters the actual membrane stage, it is again filtered in a coarse filter with a pore size of 90 μm to prevent mechanical damage to the membrane elements by any coarse particles that may enter the raw water storage tank. Depending on the preselected filtration performance, and on the temperature and quality of the raw water, there should be a trans-membrane pressure loss (TMP) of 0.2–0.6 bar during the filtration cycles. 			

The water leaving the hollow-fibre membranes is collected in the filtrate storage tank, from where it is distributed to the downstream process. The filtration process is interrupted every 15–60 min to backwash the membrane modules with filtrate. Additional cleaning of the membrane stage with chemicals is also provided. Depending on the water quality, the various cleaning chemicals are added to the backwashing water. The most important operating parameters are shown in Table 1, together with details of the cleaning chemicals, operational restrictions and plant parameters. 

Table 1 Typical operating parameters for dead-end ultrafiltration. 

Under normal operating conditions, it should be possible to achieve a water output of 90-95% with ultrafiltration systems. Further important points are the filtrate quality that can be achieved and the degree to which particles, bacteria and viruses are eliminated.  

Articles

Pure water is a raw material of particular importance to the pharmaceutical industry. Drinking water is the basis for the treatment of water for pharmaceutical applications; it is the starting point for the production of the various pharmaceutical water qualities, such as purified water, highly purified water and water for injection.