The Central Fractionation Unit of the Belgian Red Cross (C.A.F.D.C.F.) head-quartered in Brussels supplies the domestic market with plasma proteins and acts as a contract manufacturer. The company produces highly purified water (HPW) for cleaning and production purposes. This pharmaceutical quality product is suitable for use as water for injection (WFI). Manufacturing and installing a highly purified water plant that would fulfil the various customer requirements for water processing was a process engineering challenge. Pharmatec GmbH, a subsidiary of Bosch Packaging Technology, is a provider of complete solutions. It supplied a distributor system designed according to the customer's specifications, a system the Belgian company uses to meet a wide variety of requirements.
Fulfilling several specific customer wishes and integrating them into a single plant is the true test of a plant manufacturer's skill. The challenge lies in balancing and harmonizing all the components so as to achieve a homogeneous aggregate that smoothly fulfils the customer's every wish. To achieve this goal the manufacturer may have to integrate two diametrically opposed processes.
Pharmatec was faced with such a requirement when C.A.F.-D.C.F. cvba placed an order for a highly purified water plant in August 2010. C.A.F-D.C.F. is an independent unit of the Belgian Red Cross headquartered in Brussels. In addition to supplying Belgium with plasma products derived from the blood of volunteer donors, C.A.F.-D.C.F. acts as a contract supplier for a range of plasma derivatives. Two hundred employees produce coagulation factors, immunoglobulins, and albumin solutions at the facility at Needer-Over-Heembeek. Highly purified water (HPW), which is more economical to produce, is used in place of water for injection (WFI) in several steps in the production process, especially in cleaning procedures. In Europe WFI is obtained solely by distillation and is used to produce infusion solutions whereas HPW is obtained by means of a membrane separation process. Both water qualities fulfil the same purity requirements. However, substituting WFI with HPW is only allowed in a few situations, for example in the final rinsing process in ampoule filling. To increase its HPW production capacity, C.A.F.-D.C.F. required a highly purified water plant to supply washing machines and Cleaning in Place (CiP) plants.
C.A.F.-D.C.F. was well aware of Pharmatec's expertise in process engineering as it already had a Pharmatec distillation plant and purified steam generator in service. Therefore the company was also awarded the contract for installation of a highly purified water plant. Another factor in this decision was that Pharmatec was able to offer a complete solution. This was a turn-key project in which Pharmatec delivered everything from plant engineering and construction to installation of the pipes and the complete distributor system. C.A.F.-D.C.F.'s activity as a contract supplier posed the greatest challenges in this project. As the Belgian company must be able to respond flexibly to customer requests, the plant requires specific characteristics. These include combining three different sanitization methods which to a certain extent are mutually exclusive.
The way to pure water
The core of the system is the classic highly purified water plant. Generating highly purified water from drinking water requires three treatment steps: pretreatment, processing, and final cleaning. Pretreatment begins with coarse filtration of the water, after which it flows through a water softening plant. Here a resin bed withdraws the hardening components from the water. The water softening plant consists of two filters that are connected in series for safety reasons and can be sanitized with hot water. The treatment step that follows involves initial reverse osmosis and final electrode ionization.
Reverse osmosis is a physical filtration process that withdraws the salt from the water. The medium now has only a residual salt content of one to five percent. This content is then further reduced by electrode ionization. Electrodeionization employs an electrical field in combination with an ion exchange resin to reduce the content of carbon dioxide, silicon dioxide, and total organic carbon (TOC) in the water by up to 90 per cent.
The purified water (PW) generated in this manner, which C.A.F.-D.C.F. uses only for cleaning purposes, is now transformed into highly purified water by means of ultrafiltration. Ultrafiltration is a membrane separating process for the separation of particular impurities and solute substances. The separation is effected based upon molecular weight or size. The separation limit of 6,000 Daltons allows the reliable removal of bacteria, viruses, and pyrogens.
Flexible sanitization
The HPW obtained is temporarily stored in a 25,000 liter tank before being conveyed via a distributor system (the loop) to the loads throughout the facility. The distributor system must be regularly sanitized to maintain the high microbiological quality of the water. This step represents the greatest challenge for Pharmatec. As a contract supplier, C.A.F.-D.C.F. responds to its customers' specific needs, and these require different methods of sanitization in the loop. As a rule the company prefers ozonization because of its high efficacy and comparatively low energy costs. At the same time CAF-DCF must remain flexible not only in the production of its plasma products but also with respect to the respective required sanitization methods. This means being able to switch back and forth between ozonization, hot water sanitization, and pressurized water sterilization. Implementing these three variants poses some very contradictory requirements.
In ozonization the gas is dissolved by vortexing in the cold water of the tank and from there it is conveyed throughout the entire loop. The thermal disinfection methods differ in the temperatures used; hot water sanitization involves a temperature of 85°C and pressurized water sterilization of 121°C. In the latter method, the tank is also closed to the atmosphere to pressurize the system. Because for cost reasons the tank contents are drained to a defined level prior to sanitization, the free area within the tank increases. Both gasless methods require the use of spray nozzles in order to ensure proper sanitization of the surface not covered by highly purified water. The stainless spray nozzles are installed in the return line of the loop and regularly spray the tank. Yet if the water in the return line contains ozone, the spray heads will cause the ozone to escape due to a loss of pressure. This means it is no longer dissolved in the water. Therefore the combination of hot water and ozone is highly unusual.
The position of the tank posed another challenge. The situation at the site required the use of a horizontal tank for the C.A.F.-D.C.F. project. The reduced height of the water column contained within it means that there is a risk that too little gas will dissolve in the water during ozonization. This dilemma was solved by extending the pipe that feeds ozonized water into the tank to make it as long as the entire tank. The pipe was designed with a series of holes on the bottom to achieve the best possible distribution within the tank. This design developed by Pharmatec ensures sufficient ozonization.
Double valve solution for cleaning branch lines
Sanitization of the loop also includes the branch lines to the consumers. Here, too, Pharmatec had to find a customer-specific solution to ensure both sanitization and complete emptying of these branch lines. The engineers opted for a double valve solution. A compressed-air valve is placed at the beginning of every branch line and a normal valve at the end. This solution makes it possible to drain residual water from the branch line and dry the line after the load has been disconnected. This avoids microbial contamination of the line. When the loop is sanitized, these valves are opened sequentially for cleaning the branch line. The valves are operated by means of a Programmable Logical Controller. This controller is also used to regulate the removal of HPW by the loads. The pressure in the loop could not accommodate simultaneous removal by every load. This would result in air being drawn into the system instead of water being released. To avoid this, each load first sends a query to the control system (removal management system) which then determines the order of release. This is done according to the urgency of the query.
Even the nozzles in the plant are unique. Their design minimizes dead space and requires less pipe, which reduces the risk of bacterial contamination for the customer. A unique solution was also developed for removal of hot and cold water. The basic circulating temperature of HPW is 20°C. However, certain loads such as washing machines require a higher temperature. An additional subloop was constructed for these cases. The subloop conducts the water through a heat exchanger and heats it to 80°C. Only then is it conveyed to the point of removal.
All five of these specific challenges were effectively addressed with customer-specific solutions. The result is a complete highly purified water plant tailored to C.A.F.-D.C.F.'s specific needs. The team consisting of seven employees implemented the project on schedule and the plant was able to go into operation in just over a year. "We are perfectly satisfied with how the plant runs," says Kris Raspoet, Assistant Manager Engineering at C.A.F.-D.C.F. "Pharmatec's experienced team focused squarely on quality and planning in order to achieve the project objectives," adds Project Manager Eric Hoogenes. This successful cooperative venture paved the way for a subsequent project for Pharmatec.
(Courtesy: Bosch Packaging Technology)