Conductivity sensors used in hygienic applications have to withstand regular cleaning in place (CIP) and sterilisation in place (SIP) processes as well as related strong temperature differences. This is why Ever Pharma Jena uses extremely robust conductivity sensors from a well-known expert in the sector for its extensive operations.
Ever Pharma Jena, which was founded in 1950 as VEB Jenapharm and had operated under the name Jenahexal until its acquisition by the Austrian pharmaceutical manufacturer Ever Pharma in 2011, has specialised in the production of aseptic and sterilised preparations in pharmaceutical phials, vials and pre-filled syringes. Today, the annual production capacities of the company amount to 130 million units. The product range includes neurological products, analgesics and hormones mainly for clinic supplies. Ever Pharma Jena specialises in crystal suspensions as well as on hormone preparations, which are produced in strictly separate plants due to the risk of contamination.
Efficient CIP/SIP plant
Because of the wide range of products including different active substances, the firm decided on a process design where the preparation tanks in the production aren’t connected with the filling via a static pipe system. Instead, the plant sections are decoupled through the use of mobile sterile filtrate tanks. “This allows us to have a significantly more flexible production at a higher product variant,” explains Martin Reuther, project manager at Ever Pharma Jena. To establish this process, the company put a new CIP/SIP plant into operation in 2013. This cleaning plant is capable of separately cleaning two sterile filtrate tanks at the same time. If needed, a third cleaning station can be activated. The design results in large time savings with 54 tanks temporarily in alternating use and requiring regular cleaning and sterilisation.
In the preparation plant, the company operates three preparation tanks with a capacity of up to 1,000l. Prior to further processing, the solution prepared in the preparation tanks must be freed from of any existing microorganism through filtration. For this, the tanks are pressurised resulting in the content accumulating the mobile sterile filtrate tanks through corresponding inlet lines and sterile filters. They are located in a plant section of zone A for which, according to the Typical Air Quality Classification (WHO TRS No. 823 Annex 1), the strictest antiseptic conditions are required, including a room temperature that is almost 100 % particle-free. Then, the mobile sterile filtrate tanks with the filtered solutions are transferred to the filling systems where they are filled in primary tanks. To avoid any external contamination during this process, the sterile filtrate tanks are pressurised
Hourly CIP and SIP processes, 24 times a day
The cleaning plant is in operation up to seven days a week, around the clock. As the company produces different substances even in small batches, the process-wetted plant sections are cleaned and sterilised every hour. First, the sterile filtrate tanks are connected to the cleaning plant and the entire process circuit including the emptied tanks is rinsed with demineralised water and cleaning agents.
Two installed spray balls in the tanks provide for a constant and reliable cleaning of the inside.
A toroidal conductivity sensor integrated in the rinsing cycle is used to control the CIP procedure.
Use of conductive and inductive conductivity sensors
For this application, the Ever Pharma Jena engineers decided on the hygienic, toroidal conductivity sensor SE 680 with Memosens protocol from Knick.
Due to its design without any seals, joints and gaps as well as a dirt-repellent surface made of FDA-approved Virgin PEEK, the compact SE 680 is highly durable. The inductive technology isn’t influenced by the polarisation and doesn’t require sensor surfaces that may be subject to corrosion. The SE 680 sensor with an extremely wide measuring range of 0 to 2,000mS/cm at a resolution of 2 μS/cm monitors the entire cleaning process and must ensure that, regardless of the derivative, the primary product and residuals of the cleaning agent have completely been removed from the tank. Afterwards, the final rinse with water for injection (WFI) is executed. Based on the requirements of Ever Pharma Jena, the ultrapure water in WFI quality must show a non-temperature compensated conductivity value of < 2.7 μS/cm. Higher values indicate that there are still undesirable substances or cleaning agents in the water that require additional rinsing.
No more contaminants
To monitor the final rinse with WFI, the SE 605 H Memosens 2-electrode conductivity sensor is used. This sensor was developed by Knick for measuring ultrapure water in the range of 0.001 to 600 μS/cm. The SE 605 H has a hygienic design with two coaxially arranged electrodes of electro-polished stainless steel 1.4435 that shows a surface roughness of < 0.4 μm or < 0.8 μm. The insulator consists of PEEK, all used materials are FDA compliant. The wet and hot environmental conditions in the plant are no problem for sensors with Memosens technology. A particular feature of this digital sensor technology is that the processing of the measured values based on inductive, contactless data transmission and energy supply takes place in the sensor head. This way, sensor-relevant data can also be directly saved and analysed in the sensor enabling the pre-calibration of the sensors in the laboratory. Thanks to a bayonet coupling, the sensor can be easily connected and disconnected without any cable twisting. Furthermore, it allows inductive transmission of the digitised measured values between sensor and process device. The contactless coupling of the plug connection can neither be affected by moisture, corrosion nor by deposits and it ensures a perfect galvanic separation as well as a trouble-free data transmission.
As soon as the SE 605 H measures the required value of < 2.7 µS/cm using the WFI in the last rinsing process, the cleaning process is completed and the SIP process can be started. Here, ultrapure steam, which is heated to 126°C, is led through the system for 15 minutes to reliably sterilise all process-wetted parts of the plant.
Signal transmission in a compact design
The measured values from the sensors are transmitted to the control system via slim MemoRail A1401N analysers in just 12.5mm wide DIN rail housings. These analysers transform the sensor and temperature values into 4 to 20 mA signals and directly transmit them to the control system via two standard-signal current outputs. DIP switches on the front of the housing enable quick and easy configuration of the analysers, which are suitable for all Memosens sensors (pH glass, ISFET, oxygen, conductivity with two/four electrodes or toroidal sensors).
The key criteria for Ever Pharma Jena for selecting the suitable sensors was their robustness against frequent, extreme temperature changes since the hourly cleaning and pure steam sterilisation of a plant isn’t a day-to-day challenge in the pharmaceutical industry. “Of course, the sensors are also heated by the SIP processes 24 times a day from ambient temperatures to approximately 127°C and cooled down again,” Reuther says. “Conventional conductivity sensors won’t withstand this for long. Therefore, our plant manufacturer recommended us to Knick.”
Carsten Koska is with Knick