For a producer of medical biopolymers, a solution employing Thornton in-line multi-parameter measurements has significantly increased real-time response to system changes. In addition, this customer has benefited from reduced off-line lab testing and sampling errors, plus minimised downtime and maintenance of the pure water system while meeting regulatory compliance.
Background
Pharmaceutical water quality must be measured on a real time basis. All medical and pharmaceutical products during the course of manufacture utilise either Purified Water (PW), Water for Injection (WFI) or Highly Purified Water (HPW), directly as an ingredient, solvent, diluent, the vehicle for transmission, reagent, or for cleaning of the manufacturing process.
All pharmaceuticals must abide by the regulations of the Pharmacopeia of the country in which they will be marketed and sold. For the US, pharmaceutical corporations must follow the United States Pharmacopeia (USP) and the regulations for water detailed in Test Chapters ‹645› Water Conductivity and ‹643› Total Organic Carbon. Other International Pharmacopeias publish regulations for their specific market and, due to active efforts for global harmonisation, the water regulations have become significantly harmonised among the USP, EP, JP, ChP and IP (India).
The owners of the water system (plant production, engineering or quality control departments) must monitor the process analytics and physical measurements throughout the system to measure and control quality from the feed water inlet to final distribution. Typically, these in-process measurements include conductivity, TOC, dissolved ozone, pH, flow, tank level, temperature and pressure. Managing multiple measurements is less complex and more cost-effective for the system operator when a multi-parameter transmitter is utilised to monitor multiple parameters simultaneously.
Ozone for disinfection in pharmaceutical water production
Sanitisation of pharmaceutical water systems has historically relied upon either chemical or heat processes, but today ozone production systems are being installed in more water systems as an alternative method. Ozone (O3), an unstable tri-atomic form of oxygen, is 2,500 times stronger as a disinfectant than chlorine. In addition, ozone reacts with organics to break them down ultimately to CO2, thus removing colour, odour and eliminating a food source that could encourage growth of biofilm.
Ozone, when dosed at the proper concentration and monitored before and after the ozone destruction system, meets the Pharmacopeia regulation for ‘no added substance’. The increased use of ozone as a sanitisation method over the past decade can be attributed to a number of reasons including:
- Effectiveness in microbial and biofilm destruction
- Reduced operating costs
- Avoidance of harmful by-products
Pharmaceutical manufacturers are concerned about the increasing costs of regularly sanitising a large pharmaceutical water system with heat or steam and their impact on the operating budget. As energy costs increase, the use of ozone becomes more attractive contributing to a trend that is expected to continue into the future.
Case Study – Symatese Biomaterials
Symatese, located in Chaponost, France, specialises in the extraction, purification and synthesising of implantable organic polymers (such as collagen types I and IV, calcium alginate and hyaluronic acid gels, etc.) and the manufacture of implantable medical devices. Symatese operates in an optimum quality environment, in compliance with European and International Pharmacopeia regulations, to assure their products have a strong presence and quality reputation in their markets.
Thanks to the company‘s expertise in the area of biopolymer technologies, Symatese supplies products at varying stages of manufacture, from raw materials, to in-process components and finished products. The biopolymers processed by Symatese are accredited by the European Community.
Real-time monitoring of purified water system
The procedure of synthesising Symatese biopolymers requires the highest water quality and quick reaction to any potential non-conformity. It is therefore necessary to monitor critical parameters such as total organic carbon (TOC) and dissolved ozone (O3). In order to reduce the number of off-line laboratory tests, eliminate potential sampling errors and to increase the speed of response, the Methods and Industrialisation Manager at Symatese decided to implement on-line measurements in the Purified Water system.
On-line instrumentation enables simultaneous monitoring of water quality at different points in real time. TOC is measured in the Purified Water return loop and ozone is monitored continuously in multiple locations: before UV destruction to ensure effective sanitisation, following UV treatment to verify ozone has effectively been destroyed, and in a third location downstream in the water loop to verify that complete loop sanitisation has been successful.
Benefits of on-line process analytics for compendial High Purity Waters
Symatese found daily off-line sample testing to monitor and control TOC, with the associated waiting period, difficult to manage. Furthermore, taking multiple samples increased the risk of false positives resulting from possible contamination from airborne impurities and sampling technique. The manager at Symatese wanted stable, reproducible and reliable real-time measurements, with accurate, easy to maintain and reliable equipment that conformed to EP standards, as well as United States Pharmacopeia methods USP <643> TOC. Management also insisted on a simple installation with a configuration that required minimal user training and sensor maintenance.
In order to meet these requirements, the experts at Mettler Toledo Process Analytics proposed a solution employing the Thornton 5000TOC Total Organic Carbon sensor and three dissolved ozone sensors with a multi-channel, multi-parameter transmitter. Measurements are transmitted to a PLC (Programmable Logic Controller) that records and maintains a record of system performance data for regulatory review.
Advantages of the Mettler Toledo Thornton solution
Mettler Toledo Thornton meets customer requirements with these benefits:
Thornton TOC sensor:
- Continuous, real-time measurements
- Easy operation, maintenance and calibration
- Simple on-line installation at critical measurement point
Dissolved ozone sensor:
- Robust stainless steel sanitary sensor and measurement chamber meets rigorous installation requirements
- Simple membrane replacement with combination inner body/membrane tip
- Quick cable disconnect
Multi-channel, multi-parameter transmitter:
- Intelligent sensor inputs with simple plug and measure multi-parameter installation
- Multi-channel inputs allows TOC and ozone measurements in ONE transmitter
- User friendly interface with simple set-up and operation
Enhanced performance and reduced costs for Symatese
The solution provided by Mettler Toledo Thornton has allowed Symatese to obtain immediate, reliable and compliant TOC measurements with reduced costs. Ozone is now monitored at multiple locations to assure the sanitisation cycle is effective and complete. Furthermore, the installed ozone system has resulted in a reduction in the amount of time the loop is immobilised during sanitisation.
For more information on pharmaceutical applications, visit: www.mt.com/pro_pharma. To download the White Paper, click here.