There’s more than one way to
Challenges and potential of the cold membrane process for WFI
New Delhi, January 15, 2020: Drinking water is the basis for producing water for pharmaceutical purposes – in all national pharmacopoeias. What was long prohibited in the EU has been a reality for the past two years: water for injection (WFI) can also be produced using the coldmembrane process. The challenge: although there are official requirements for safe WFI, they do not apply to the manufacturing process. Will the cold membrane process be able to establish itself in the long run?
Drinking water invariably contains certain substances that must be removed for pharmaceutical purposes. The international pharmacopoeias draw a distinction between two levels of pharmaceutical water: Purified Water (PW) and Water for Injection (WFI). While PW is primarily used as a base material prior to treatment in further stages and for producing pure steam, WFI is intended for use in injection and infusion solutions for parenteral application. The manufacturing processes used for PW and WFI are prescribed by the respective pharmacopoeias. Until 2017, the European regulations differed considerably from comparable pharmacopoeias, for instance in the U.S. or Asia: distillation was the only process permitted in the EU for the production of WFI.
Hot is out, cold is in– right?
The revision of WFI monograph 0169 in the European Pharmacopoeia can rightly be considered a small revolution: since its entry into force on April 1, 2017, alternatives to distillation have also been permitted in Europe, including the “cold” membrane processes reverse osmosis and electrodeionization in combination with an additional ultrafiltration step. In comparison to distillation, the membrane processes are economically and ecologically more efficient, since they eliminate the need for additional plants, the energy required to generate hot steam, and the associated costs. However, a final market decision on the optimal manufacturing process has not yet been taken.
Accordingly, pharmaceutical companies are currently testing a variety of cold membrane processes. As a rule, changes in the pharmaceutical industry take time – after all, patient safety is at stake. The regulatory requirements for WFI as a product are correspondingly stringent. Although authorities such as the EMA and WHO, as well as professional organizationslike the ISPE, are intensively focusing on the topic, there are still no detailed regulations or recommendations for a uniform production process. However, there’s one point that all agree on: a risk-based approach for plant planning and operation is essential. If the current pilot projects deliver stable and cost-efficient results, there is nothing standing in the way of wide spread application.
Reaching the goal with a risk-based approach
Which WFI production process is best suited for pharmaceutical manufacturers above all depends on the projected microbiological risk – a contamination could have fatal consequences. Therefore, the key question is: how can optimal operational safety be achieved? To ensure that the pharmaceutical water produced using the cold membrane process meets all quality criteria, the potential risks of bacterial contamination must be assessed and minimized as far as possible.
At the beginning of the treatment chain, pre-treatment is especially important; it removes substances from the water that could adversely affect the subsequent membrane processes or form deposits. The pre-treatment processes used vary depending on the substances initially present in the water, and can be installed in a sequential arrangement or in combinations. In order to remove coarser particles from the water, using multiple filtration stepsis recommended. Oxidative substances, microorganisms and organic carbon (TOC) must also be removed from the water during pre-treatment. Activated carbon adsorbs TOC, while microorganisms can either be killed using oxidative chemicals such as chlorine or ozone, or rendered inert using UV radiation.
Sanitization as a decisive factor
The subsequent softening of the drinking water prevents so-called “hardness formers”like calcium or magnesium from forming insoluble compounds in the water. As an alternative to softening, the solubility limit of hardeners can be increased by means of chemicals referred to as antiscalants. In some cases, operators must prove to the authorities that noantiscalantsremain in the final product. Accordingly, softening the water with cation exchange resins is more advisable and reliable. That being said, softening also involves the greatest risk of contaminating pharmaceutical water. Therefore, hot-water sanitization of the resin during production is recommended.
In the context of pharmaceutical water treatment, sanitizationis vital to minimizing the risk of contamination in all stages of the process. This can be done using hot water or chemicals; though chemical sanitization involve slower investment costs,it is only partially automated and less effective than hot-water sanitization.
From RO to EDI to UF
The subsequent treatment step, reverse osmosis (RO), is exclusively intended toremove ions, particles, microorganisms and other undesirable substances. RO always produces a certain amount of wastewater, which can be reduced to a minimum using process engineering solutions. Consequently, pharmaceutical companies can address aspects such as sustainability and resource-efficient production with the help of suitable facilities. RO does not remove dissolved carbon dioxide, which increases the water’s conductivity. Membrane degassing based on air stripping is a frequentchoice for removing this free CO2. The procedure is comparatively simple and cost-efficient, since it does not normally require the use of additional nitrogen or vacuum.
The continuous electrodeionization (EDI) method involves a combination of membrane processes and electrodialysis andcan reduce the water’s conductivity to below 0.2 µS/cm. The ultrafiltration modules, which areinstalled downstream,are used to remove endotoxins and bacteria, so that the water complies with the acceptable limits. The concentrate byproduct created by ultrafiltration (UF) can then be re-circulated upstream of the RO, so that no wastewater is produced. Regular monitoring of the transmembrane pressure and integrity tests yield insights on the condition of the filter modules and the effectiveness of the filtering.
Combining foresight and process know-how for success
Provided all steps in the WFI manufacturing process are optimally planned and coordinated, pharmaceutical companies can benefit from immense energy savings,not to mention an improved environmental balance – which is also why the amendment to WFI Monograph 0169 in Europe could not have come at a better time. In no other region are energy costs rising so rapidly. At the same time, no other region is as committed to achieving more sustainable production processes. If the cold membrane process proves to be a success here, transcontinental companies are sure to expandit to other regions as well.
But that is still a long way off. The tasks at hand are to draw the right conclusions from ongoing projects, make adjustments as needed, and organize the rollout to local sites. This will require the courage to invest in a new process. It will also requireahealthy measure of foresight – because, as already mentioned, changes in the pharmaceutical industry take time, and a very thorough approach. In addition, manufacturers will need a reliable partner who can not only supply the right equipment, but also has many years of process know-how and can support them with risk assessment, planning, validation and documentation. On this basis, investments in forward-thinking technologies will pay off, paving the way for the widespread and standardized use of the cold membrane process.
Corporate Comm India(CCI Newswire)
