Requirements of pharmaceutical service providers in aseptic filling
Contract manufacturers in the worldwide pharmaceutical industry must answer to regulatory agencies. However, each market has its own specific demands. In addition, drug manufacturers are increasingly seeking solutions designed to meet their specific needs. The challenge is that pharmaceutical contract manufacturers must be able to offer reliable processes for aseptic filling while also supporting pharmaceutical companies with manufacturing technologies that are both economical and effective.
Until recently, two different technologies were primarily used to perform high-quality aseptic filling of drugs—isolators and RABS. Simply put, isolators are considered the best solution in achieving the highest levels of sterility, unlike RABS, which allows companies to switch products on a line rapidly. RABS is considered the more flexible solution, achieving comparative levels of sterility.
The function of V-CRT
Forecasts suggest that in the future, international regulatory agencies will be demanding limit values when approving drugs. Most likely, microbiological contaminations will be entirely proscribed. Companies that work with isolators will generally be able to meet the new requirements. However, to ensure safe processes, isolators must be thoroughly decontaminated and reset at each product. These format change result in fairly long downtimes. Because manufacturing plants will have to produce quickly and flexibly, decontamination and set-up processes will require greater attention in years to come.
RABS: High quality and flexibility
The technical structure of the V-CRT is based on the passive, open RABS idea, one that has proven its worth. While there is no dedicated ventilation technology, RABS are driven by cleanroom ventilation. Because RABS plants have to be integrated into a higher cleanroom class, the protective housing around the production section is not as clearly separated from the environment as isolators.
Due to automatic decontamination, the level of sterility in isolators is greater than in conventional RABS plants with manual disinfection. However, they are not as flexible. And, it is that high level of flexibility of RABS that delivers the benefit of short downtimes. The challenge, therefore, is to do a filling that is both flexible and safe. One possible solution is an approach that combines the two technologies.
Flexible and sterile with H2O2 decontamination
The originality of V-CRT is that it performs a full decontamination of the cleanroom, including the RABS, by using H2O2. This can be done after each batch. In contrast to wipe and spray disinfection, this hydrogen peroxide method has a greater effect on contamination. For example, the system is better at preventing bacterial load than the isolator because prep work is done behind closed barriers in an aseptic environment.
V-CRT reduces the time it takes for the decontaminants to take effect and, consequently, shortens the down time of the filling line. The net result is a much shorter decontamination time for the cleanroom area of RABS plants.
V-CRT is a closed, fully automated dispersion system that is integrated into cleanroom technology. The H2O2 is not funneled into the cleanroom via the climate control system. Furthermore, most of it is evacuated by way of a separate ventilation system. A system of stainless steel tubes built into the cleanroom walls vaporizes the H2O2 solution into a class ISO 5 and 7 cleanroom through dual-substance jets embedded in the ceiling and walls. The process takes only three hours, incredibly fast by today's standards, and can immediately be followed by preparations for production and the aseptic setup of the cleanroom.
Quality and OEE
V-CRT achieves safety and quality standards that go beyond current good manufacturing practice (cGMP) and as such, is able to compete with the performance of isolators. The shorter down times not only make processes more efficient, but also improve OEE by as much as 30% in comparison to isolator technology. The special conditions required for implementing RABS lines and the fully automated decontamination process are the reason why OEE is optimized. Overall, this cleanroom technology can reduce the time for preparatory production measures and its follow-up steps by nearly half.
Challenges in the future
The challenges for the future will essentially involve three aspects of the V-CRT: duration of decontamination; measurement of the remaining H2O2 concentration; and the aseptic transfer of sterilized materials.
The primary goal was to reduce the decontamination process to less than four hours. This was achieved by using active charcoal filters that have a catalytic effect on the destruction of H2O2.
A second goal is to measure the remaining concentration of H2O2 online during a batch. Absorption and desorption studies will provide information about materials in the cleanrooms that absorb or dispense H2O2 that could have a negative impact on certain materials. Transferring sterilized materials is done using a conventional docking system based on today’s options for the transfer of all presterilized systems.
Innovative technology for aseptic filling
The new manufacturing technology improves quality and safety in systems performing aseptic filling of injection systems. At the same time, it optimizes production processes by making them more flexible and efficient. Put another way, the technology combines advantages of conventional processes—isolators and RABS—and turns them into a new process in aseptic filling. V-CRT meets tomorrow’s official regulations today, and the economic challenges as well.
Gerald Buerkle is vice president of production at Vetter Pharma-Fertigung GmbH & Co. KG in Ravensburg, Germany. He began his career at Vetter in 2002 as head of production and was initially in charge of five manufacturing lines for customer fillings. In 2005, he was named site manager and manufacturing manager at the site Ravensburg Vetter South. Mr. Buerkle has over 18 years’ experience in the pharmaceutical industry.