Since 2017, changes to the European Pharmacopeia have given pharmaceutical manufacturers the choice of producing Water For Injection via distillation (Hot WFI) or a membrane system (Cold WFI). Cold WFI offers many benefits and more and more companies are planning to invest in WFI systems with membrane technologies to maintain an ongoing high-quality water supply…but when might it be better to rent instead of purchasing?
The pharmaceutical sector is a major water consumer and relies on treatment processes to ensure a safe and secure supply of water for injection in bulk that would be expected to be used for the manufacture of parenteral, some ophthalmic and inhalation products and for finishing steps of parenteral grade active pharmaceutical ingredients (API’s).
Historically distillation has been the preferred method for producing WFI for biopharmaceutical businesses who operate in or supply their products to Europe. The European Pharmacopeia described suitable water for injection as obtained by distillation of drinking water or Purified Water only, even though the US and Japan Pharmacopoeias have allowed alternatives for some years.
Since April 2017 however, the revised European Pharmacopoeia monograph 0169 allows the generation of Water for Injection (WFI) by distillation or by a purification process that is equivalent to distillation, offering the industry more choice. This includes membrane systems such as reverse osmosis (RO) coupled with a suitable secondary membrane system such as ultrafiltration (UF). As with distilled water, continuous electro deionization (CEDI) is then utilised after the RO to achieve the conductivity specification.
The system must also adhere to the following:
- contains no added substance
- must be designed to prevent microbial contamination and formation of microbial endotoxins
- must be validated
- correct maintenance of the WFI production unit is essential
The benefits of membranes based system (cold WFI)
Distillation is a very effective method of purification. It offers the reassurance of a phase change from water to steam that removes impurities and results in product water compliant with microbial and endotoxin limits for WFI. However, the use of steam as a heat source means that the plant has to be engineered in compliance with the EU Pressure Equipment Directive. As a result, the capital cost can be significantly higher than that of a reverse osmosis plant.
Cold systems have many other advantages. RO based systems achieve compliance through the use of CEDI and Ultrafiltration (UF) downstream of the RO. UF reduces endotoxin levels and removes any prevailing microorganisms. Modern purified water systems also now incorporate HWS membrane systems, which can control the formation of biofilms, while adequate monitoring and control may offer a low-risk solution. RO based systems also offer lower OPEX than distillation, a smaller footprint, and does not require a complex system design.
The selection of WFI production methods is ultimately about finding the correct balance between cost and risk. Distillation techniques are viewed as less risky than RO based systems, which may be susceptible to biofilm formation if not maintained correctly. However, in a market where margins are under pressure, the savings offered by RO based systems are highly attractive and a growing number of clients are looking at ways to reduce costs without affecting the integrity of the system.
Plants for hire
In response to an increased demand for plant for hire and to the new European Pharmacopoeia Monograph 0169, Mobile Water Services has entered the rental market with its proven ORION® technology, an asset suitable for the production of cold water for injection, already counting several references with major pharmaceutical manufacturers worldwide, including blue chip companies.
The ORION® system is the result of 20-year experience in the production of purified water with membrane based system RO+EDI, the most advanced system on the market and the most demanded by the Pharmaceutical and Cosmetic Industry for the production of water as an ingredient.
Combining the technologies of reverse osmosis, continuous electrodeionization, ultrafiltration and a system for thermal sanitization at 85º C that ensures the microbiological quality of the treated water, the ORION® provides Water for Injection. In addition, the ORION® is enabled with HubgradeTM for on-line monitoring of the main system parameters and predictive and preventive service offer for quantity and quality assurance.
Why buy when you can rent
During the last decade, an increasing number of pharmaceutical companies have created a demand for long-term equipment rental, particularly in cases when the return on capital investment will not be met during the lifetime of the project, mostly for a period of fewer than 5 years. A multi-year “pay-as-you-go” scheme may be the most suitable option, providing a more cost-effective approach to water purification, and enabling the water system to be covered by the operations budget, leaving the capital available for core investments.
In cases when capital investment is the most sensible route, a mobile system can still meet the additional requirements in the interim period between increased demand and a permanent solution being installed. A complete turnkey project can take up to 10 months from initial installation to completion, followed by validation, including performance qualification steps that can take up to 6 months depending on the size of the system. Mobile water systems are already fully validated and can be introduced into the main water purification supply in a 2–3 week timeframe. A final benefit afforded by the rental market is the opportunity for companies to conduct production trials as they monitor the effect of water quality on their manufacturing processes. Temporary treatment plants provide a cost-effective means of finding out whether making a substantial capital investment is worthwhile.
New way of thinking
The rental model may be relatively new to the water technology market, but there is a solid business case for many pharma companies to opt in, whether to deal with an increase in production, cover planned maintenance, or carry out production trials.
Increased options and flexibility in the water technology market can only help to provide the reassurance pharmaceutical companies need that their supply of pharma-grade water is safe, secure and can reliably support continuous production.