With demand for specialized treatments and therapies increasing, the pharma industry is increasingly interested in advanced, effective aseptic filling and packaging solutions. Ute Schleyer (US), Vetter project manager of site and plant development, spoke with Outsourcing-Pharma (OSP) about the factors driving demand for aseptic solutions, including its V-CRT integrated cleanroom technology.
OSP: Have regulatory requirements around aseptic processes and technologies become more stringent in recent years?
US: Many global authorities have been increasing their regulatory requirements for process safety. New and revised guidelines are upcoming.
This includes the Annex 1 of the EU GMP Guide "Manufacture of Sterile Medicinal Products" – considered the most important European regulatory standard for the manufacturing of sterile pharmaceutical products. The current draft of Annex 1 states that the expected result of microbiological findings within isolators and restricted access barrier systems (RABS) is 0 colony forming unit (cfu) recovered, and that all critical surfaces that encounter sterile materials should be sterile.
Visual inspection requirements for particles are also becoming increasingly stringent. Regulatory trends are shifting from today’s best practice of “essentially free” toward the more demanding standard of “practically free.”
OSP: What sorts of market factors are impacting the field?
US: Pharmaceutical product manufacturing will require ever-increased flexibility and face more stringent requirements for microbial and particulate contamination control. Pharmaceutical and biotech companies around the world are already feeling these pressures on their aseptic filling processes.
Many of these organizations are adapting their strategy accordingly. They’re taking advantage of innovative production methods, designed to enhance and advance current manufacturing processes.
OSP: Could you please explain some of the key differences between isolator and RABS technology, and perhaps the challenges and advantages associated with each?
US: Isolators are completely sealed units, entirely “isolated" from the outside environment. They must undergo extensive decontamination, which limits the level of adaptability and efficiency these facilities can achieve.
RABS technology involves barrier and dynamic airflow separation between environment and drug product, while also offering the advantage of faster set-up, efficient product changeover, and variability. Consequently, RABS enables multi-product manufacturing operations with shorter downtimes.
OSP: Could you please explain the V-CRT cleanroom concept?
US: With global demand increasing and regulatory requirements stiffening, drug manufacturers are responding with innovative new approaches that push beyond isolator and RABS technology. Vetter Cleanroom Technology (V-CRT) is such an approach; as one of the leading global CDMOs, Vetter developed this holistic cleanroom concept combining the advantages of both conventional solutions
V-CRT makes it possible to achieve safety and quality standards that keep up with the performance of isolators while still offering the flexibility advantages of RABS. This innovative concept is based on the central idea of fully automated decontamination of the entire cleanroom, including RABS, using hydrogen peroxide (H2O2); it also acknowledges all working steps related to aseptic filling – including set-up and filling, monitoring, and analytics.
OSP: How does this technology improve upon existing solutions, and what current challenges does the technology help users mitigate?
US: Designed to optimize the versatility and efficiency of pharmaceutical production processes, V-CRT minimizes the risk of contamination and offers several advantages over existing concepts. Rapid decontamination enables efficient product changeover. H2O2 decontamination of the entire cleanroom prior to each batch minimizes the risk of microbial contamination; consequently, no germ has been detected within the barrier since the first V-CRT room using a batch-based decontamination was commissioned in 2017.
Furthermore, continuous online monitoring of multiple variables helps ensure the effectiveness of the decontamination process. The containment approach follows the concept of the closed system since the RABS doors are no longer opened following H2O2 decontamination.
In addition to high reliability and reproducibility, this cleanroom concept also offers the significant advantage of speed. Depending on the size of the cleanroom, the entire decontamination cycle can be completed in less than 2.5 hours.
Suitable catalysts and a highly effective ventilation system enhance H2O2 degradation and lead to short decontamination cycles. Preparations for production and the aseptic set-up of the cleanroom can begin immediately. Shorter downtime streamlines processes and improves overall equipment effectiveness (OEE).
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