Roche AG had commissioned the company EnviroChemie to develop a new procedure for a new production facility in Mexico, which prevents the undesired release of ecotoxicologically contaminating drugs into the environment and eliminates pharmaceuticals in the wastewater directly at the point of origin, even before they enter the general sewage treatment plant. In the first step, the three different methods UV/H2O2 oxidation, ozone oxidation and adsorption on activated carbon were tested on a laboratory scale, and evaluated with regard to ecological and economical aspects. When comparing the validated procedures, ozonisation in this special case proved to be the most effective method, in order to efficiently destroy the active ingredients in the wastewater safely and completely. Based on these results, EnviroChemie designed a large-scale technical plant in the second step and implemented it.
The following article describes the project development and design of the Envochem plant for eliminating active ingredients from the wastewater of the production facility directly at the point of origin.
Pharmaceuticals and their metabolites are detected on an increasing scale in the aquatic environment. The drugs mostly get into the surface and drinking water through the excretions of humans and animals. However, the wastewater of pharmaceutical production facilities can also be contaminated with active ingredients. If the drugs produced are rated as ecotoxicologically contaminating, the wastewater should be treated directly at the point of origin, to ensure that only biodegradable substances end up in the environment
This was the challenge faced by Roche when building a new production facility in Mexico. Two highly effective medicaments for the treatment of cancer are formulated in this facility. In-depth analyses have shown that the two agents Capecitabin (Xeloda) and Mycophenolat Mofetil (Cellcept) could be ecologically critical and should therefore not get into the wastewater. During galenic production, approx. 10,000 litres of wastewater are generated daily, which need to be processed. Only one agent is treated per day. Roche commissioned EnviroChemie to test different procedures for decomposing Mycophenolat Mofetil on a laboratory scale and to implement the results in a large-scale technical plant. The aim was to find a cost-effective and at the same time affordable method with which the drugs can be fully eliminated. Tests with the Capecitabin were carried out in the Institute for Energy Management and Environmental Engineering in Duisburg (IUTA), Germany. Tests for adsorption on activated carbon were performed at Roche Basel in Switzerland.
The specifications for the technology are:
• Reliably deliver results
• Ensure a very high operational safety
• High degree of automation
• Compact construction for the processing plant
• Little handling of chemicals
• Generation of as little waste as possible
For removal of the active ingredients contained in the wastewater, three different procedures were tested on a laboratory scale and evaluated economically.
Apart from the UV/H2O2 oxidation and adsorption on activated carbon, the third method of choice was ozone oxidation. Depending on the product, acid/base/sodium hypochlorite treatments would also come into consideration, which are used at other locations of the said company. However, these procedures were not suitable here for several reasons.
The results showed that the two agents can basically be removed from the wastewater with all three methods. In the present case, ozone treatment of the wastewater best met the requirements within the scope of the patented Envochem technology by EnviroChemie and proved to be the optimum method.
The results of Capecitabin oxidation are shown in figure 1. For this purpose, a sample with an active agent concentration of 200 mg/l was produced. The oxidation process was completed after 20 minutes and required a total of 18.33 g ozone. Based on the lab results, the production plant would have a maximum daily requirement (24h) of 917 g (18.33 g O3 x 10,000 L/200 L) ozone, 38 g would be required per hour.
For the laboratory tests with regard to breaking down Mycophenolat Mofetil and its hydrolysis products, a sample with an active agent concentration of 25 mg/l was produced. In a first step, the hydrolysis behaviour of Mycophenolat Mofetil was examined. It was shown that after approx. 24 hours, 80 percent of the original substance are still present (see fig. 2). The ozonisation attempts demonstrated that Mycophenolat Mofetil is completely destroyed by ozone within a few minutes. A daily requirement of approx. 460 g/d was calculated. Comparing the Capecitabin results shows that dimensioning of the plant is determined by the usage of ozone for its oxidation.
The obtained data were used as a basis to develop an individually adapted wastewater processing plant which meets all requirements. The resulting Envochem system is housed completely in a six metre long container and is designed to run fully automatically 24 hours a day, so that the wastewater can be treated in a continuous process.
The wastewater is supposed to run from the production facility to a storage tank initially, which is equipped with a water gauge and has a volume of 15 cubic
metres. The Envochem plant is directly connected to the tank. The flow rate to the processing system is controlled by a pump with frequency converter and inductive flow sensor. Depending on the liquid level in the storage tank, the flow rate can be varied from 0.4 m3/h to 0.8 m3/h. Solids are retained by a filter system.
The ozone is produced by an ozone generator, which does not draw the oxygen directly from the ambient air, but from an upstream PSA system. An injection system mixes the ozone with the wastewater, which is located in two reactors (see figure 3). There is a slight excess pressure, which ensures an effective reaction of the ozone with the available agents. Excess foam is separated in a second reactor. As the ozone requirement depends on the chemical properties and the concentration of the respective drugs in the wastewater, the patented system is equipped with sensors for measuring the dissolved remaining ozone concentrations after treatment. The system controls the performance of the ozone generator fully automatically, so that there is always a defined ozone concentration of e.g. 2 mg/l. If the ozone requirement increases, the generator automatically produces more, if it decreases, ozone production is also reduced. In order to remove the remaining ozone from the wastewater, the treated water runs through an activated carbon filter. In order to ensure sufficient safety, an additionally available ozone detector in the container issues an alarm if ozone occurs in the ambient air.
The system is equipped with software, which enables simple operation of all installed elements and allows visualisation of the complete process. The user can access the measurement values and the process runs at any time. The generated data are displayed in a table and can be archived easily. Status signals are fully logged and can be viewed at a later time. An optional modem enables remote maintenance and control measures by EnviroChemie, so that in case of an emergency, quick action is possible.
The system was commissioned in Mexico under guidance of EnviroChemie. All measuring instruments and process control systems of the system pre-installed in the container including a breakdown were tested in Germany. In order to verify the functionality of the system, a Factory Acceptance Test (FAT) was performed together with Roche.
The tests for eliminating the pharmaceuticals on a laboratory scale have shown that a reliable system is available with the patented Envochem technology, which can completely decompose residual drugs in the wastewater. Automatic control of the ozone concentration in the wastewater ensures the needbased application of the ozone.
Elmar Billenkamp EnviroChemie GmbH Germany, Jürg Straub, Martin Studer Hoffmann-La Roche AG Switzerland, Jochen Türk, IUTA, Institute for Energy Management and Environmental Engineering, Germany