Highly purified media: From design to installation, and beyond

Helmut Sommer, Director Highly Purified Media Systems, Bosch Packaging Technology talks about how Bosch has positioned itself as one-stop provider of process and packaging solutions for the pharma industry

Bosch Pharmatec has designed, manufactured and installed 14 purified and highly purified water generation plants within 12 months. This success is based on the fact that more and more pharmaceutical companies opt for complete systems instead of purchasing single components from different providers. Bosch has rounded off its portfolio for pharma water treatment and has advanced to a complete system provider for pharma water generation. This development underlines Bosch’s position as one-stop provider of process and packaging solutions for the pharma industry.

The pharma and biotechnical industries have a continuously increasing demand for water. This raw material fulfills different functions within the processing, formulation and manufacture of pharma products and active pharma ingredients (APIs). Water is also used as excipient, during synthesis and for the cleaning of packaging and equipment materials. For these purposes, the pharma industry requires different grades of water quality, which are defined in guidelines and regulations.

The microbiological quality of the water is of utmost importance for pharma production companies. The design and development of systems for high purity media such as purified water (PW), highly purified water (HPW), water for injection and water for pure steam are major fields of action for the industry. These systems act as central supply systems. Quality fluctuations or bottlenecks regarding the supply of these raw materials are inacceptable and can have far-reaching consequences for the production line. Therefore, adequate construction and availability decisively contribute to both quality and safety of the entire production chain. Full-range suppliers for high purity media generate crucial advantages for their clients.

Water generation step by step
The generation of purified and highly purified water requires two or three essential process steps respectively: pre-treatment (water softening), treatment (reverse osmosis and electrodeionisation) and – for highly purified water generation – final cleaning (ultrafiltration). Pre-treatment is the most important step in the production of purified and highly purified water. First of all, the components responsible for water hardness, e.g. magnesium or calcium ions, are removed. During the water softening process through ion exchange, the water flows through a bed made of exchange resin. In order to maintain the salt content and conductivity, the hardness components are extracted and replaced by sodium ions with virtually the same amount.

The water softening plant consists of two softening columns in serial or parallel configuration. This set-up ensures a permanent flow, which substantially reduces the risk of microbial contamination in the resin bed. From a microbiological perspective, the softening plant, with its large inner surface of the resin bed, is the most critical element of the entire treatment chain. For the sanitisation of the softening module, Bosch opts for the hot water sanitisation at up to 85°C. Compared to other procedures that require chemicals, e.g. with hydrogen peroxide or sodium hypochlorite, sanitisation with hot water is increasingly preferred. It can operate automatically and its documentation complies with the good manufacturing practices (GMP).

Reverse osmosis and electrodeionisation
The second step in PW and HPW generation, the treatment step, is divided into two different processes: reverse osmosis (RO) and electrodeionisation (EDI). During reverse osmosis, the pretreated water is desalinated. Compared to desalination with ion exchangers, reverse osmosis is the preferred procedure for the first desalination step in modern water treatment plants and is also the procedure of choice for Bosch. Reverse osmosis, a membrane process, is both a mechanical and chemical filtration process. The feed water is pressed through the semi-permeable membrane with a higher pressure than in the case of osmotic pressure. The water is hereby divided into a concentrate form containing the isolated salts and other impurities, and a permeate stream with a very low salt content. The concentrate stream discharges the isolated salts while the permeate stream consists of pure water with less than 1 to 5 per cent of salt concentration. Suspended particles and macromolecules are also filtered out during reverse osmosis.

The second part of the treatment process consists of electrodeionisation, an electro-chemical process (dialysis). Electrodeionisation produces a diluate which not only easily fulfills the requirements for purified water, it also offers quality reserves. The core of this procedure is a constant electrical field which brings the loaded water substances to move around in the chambers by means of the ion exchange resin. At the same time, the spreading of the electric field also continuously regenerates the ion exchange resin by separating the water into hydrogen and hydroxide ions. The ions are transported to the respective concentrate chambers and conducted away. The diluate (ultrapure water) is conveyed to storage. EDI systems offer several advantages: They are unsusceptible to variations in the composition of the feed water. Apart from the reduction of the salt content, carbon dioxide, silicon oxide and TOC (total organic carbon) are also reduced by over 90 percent.

Step three: Final cleaning
For the production of highly purified water, a further step is required: ultrafiltration (UF). The purified water generated by electrodeionisation, which fulfills the requirements in terms of conductivity and TOC value, undergoes a final cleaning process and is treated to become apyrogenic and sterile water. Ultrafiltration is a membrane separating process for the separation of particular impurities or solute substances. The separation is effected based upon molecular weight or size. In the pharma production industry, hollow fibre polysulphone membranes are used. Their separation limit of 6,000 Daltons is far below the size of the impurities to be removed such as bacteria, viruses and pyrogens, thus ensuring the required pharma safety standards. The integrity of the modules can be tested with a so-called bubble test in the plant. The UF plants are also GMP-compliant for hot water sanitisation. The ultrafiltration process is extremely reliable and, compared to the generation of highly purified water through distillation, it is a lot less cost-intensive.

One-stop solutions on the increase
The different stages involved in the complex process of high purity media generation are often performed on distinct units, each unit accomplishing one process. Responding to the growing demands of the pharma industry for quality and flexibility. More and more pharma companies now opt for one-stop generation solutions. The advantages for the user are obvious: Minimising points of intersection, a full-range supplier reduces time consuming and cost-intensive coordination processes. The need for complex interface coordination is reduced and projects are speeded up. Compared to single units, complete systems allow for a much more efficient coordination of the plant system rating. Required sizes are easily defined according to the respective plant requirements. The connection of control systems is inherently ensured. Spare part storage is significantly reduced and simplified, resulting in high plant availability.

With the expansion of its portfolio for high purity media systems, Bosch now designs, manufactures and installs customised water generation units. From drinking water supply to the point of use, the systems allow for the compliant implementation of all stages of water treatment processes. The necessary pretreatment steps are designed based on up-to-date analyses. With their modal structure and a choice of different sizes, the units can be adapted to produce between 400 and 16,500 litres of purified or high purified water per hour. Users benefit from a modular system allowing the use of standard elements. Larger plants are constructed according to customer specifications. All processes are implemented compliant to the strict rules of the pharma industry.