Therapy with injectables (such as cytostatics, hormone preparations, neurological drugs, other special injectables) promises patients significantly improved chances of recovery. Doctors inject the active ingredient as a sterile liquid solution. Systems from Waldner play an important role in its production.
About half a million people in Germany are diagnosed with cancer every year. Due to improved medical care, however, the chances of being cured have increased significantly in recent years. Chemotherapy plays an essential role in the treatment. This involves the hospital staff intravenously administering an active substance known as a cytostatic. EVER Pharma, with headquarters in Unterach, Austria, has specialised in the production of this active ingredient, along with other classes of active ingredients.
Sterile solutions or suspensions are needed to administer injectables. The basic material is a powder from which EVER Pharma produces a liquid in an absolutely pure and sterile environment at a plant in Jena, in Thuringia. The liquid solution is then filled into vials, ampoules or ready-to-use syringes. The Process Systems Division provides a consistent, perfectly coordinated complete solution for the entire process of liquefaction (formulation). This ranges from the containers to the isolators and from all of the peripherals to the control components. The Process Systems team supplied and installed a total of three plants in Jena: one for the production of neurologically active substances, one for hormone preparations and one for the production of cytostatics.
Isolators protect employees from toxic atmosphere
“The protection of our employees during the entire manufacturing process is our top priority. Our employees must be able to rely 100% on the technology around them. Isolators offer maximum safety here, states Dr Manfred Nussbaumer, Head of Engineering at EVER Pharma. This is because the operators must not come into contact with or inhale the highly toxic active ingredient powder under any circumstances. You can open the containers at the isolator using gloves, remove the powder and weigh out the correct quantity. The weighed active ingredient is then also transferred in an isolator to a container and then stirred together with the water for injection, dissolved and mixed with additives.
“Basically, two different types of containers are used: The mobile version holds up to 250 litres of dissolving liquid and can be pushed up to the isolator and docked. To prevent contamination of the ambient air, the powder is transferred hermetically into the container. There is also a stationary version that can hold up to 1,000 litres and is firmly connected to the isolator,” explains Thomas Knaup, sales employee at Waldner Process Systems. After the dissolution process, the liquid is fed directly to machines that fill the solution into syringes, ampoules or special injection vials. In addition to the isolators and containers, Process Systems also supplies all the process equipment required for the transfer of the active ingredient and the seamless interaction of the individual components. This also includes piping, valves and technical systems for taking samples from the liquid.
CIP system ensures sterile environment
“It is important for us to ensure an absolutely sterile environment throughout the process. Since we produce and fill various products for our customers, the systems must be comprehensively cleaned at regular intervals. This is the only way to reliably avoid cross-contamination,” says Dr Nussbaumer. “For this purpose, we have provided a Cleaning-in-Place (CIP) system with which the entire equipment can be flushed and cleaned without time-consuming disassembly,” adds Thomas Knaup. Next comes the sterilisation of the components, most of whose surfaces are made of stainless steel. Here, they are heated to 130 degrees to kill any remaining germs. “For the entire process chain, from the production of the solution to the cleaning and sterilisation of the equipment, all system components come from a single source. This is enormously important to ensure the highest level of sterility,” says Thomas Knaup.
HAS Technologie GmbH, which has been part of the Waldner Group since 2022, is responsible for the entire control technology, including the process management system. Sophisticated control software including recipe management paves the way for the continuous automation of the systems.
Holistic solution package from a single source
“We benefit from a holistic solution package that allows us to handle all batch formulation processes consistently. Whether containers, isolators, transfer technology or control systems – we receive all the necessary components from a single source. This allows us to reduce technical interfaces to a large extent and thus guarantee the consistency of our production processes,” states Dr Manfred Nussbaumer. “We already knew the Waldner experts and their professional working methods from an earlier project involving a different company constellation. At that time, a very competent team had emerged with whom we quickly built up trust. Our high level of satisfaction was ultimately the deciding factor that led us to place another order with this proven partner,” adds the project manager at EVER Pharma.
