Annex 1 and fill-and-finish processes: effects on aseptic packaging and stopper feeding

Mit einer Übergabelösung wird das Handling innerhalb des Isolators wesentlich vereinfacht. In Kombination mit Peak-Vorrichtungen lässt sich die Installation der Rotationskolbenpumpe ohne direkten Kontakt dieser produktberührenden Materialien realisieren. / A transfer solution significantly simplifies handling within the isolator. In combination with peak devices, the rotary piston pump can be installed without direct contact with these product-contacting materials.

Ein vollautomatisches System, das falsch ausgerichtete Stopfen erkennt und diese sicher und Annex-1-konform aus der Zuführbahn zur Stopfensetzstation entfernt. Handschuheingriffe an dieser sensiblen aseptischen Position werden damit vermieden. / A fully automatic system that detects misaligned stoppers and removes them safely and in compliance with Annex 1 from the feed track to the stopper insertion station. This prevents the use of gloves at this sensitive aseptic position.

With the implementation of the EU GMP Annex 1 ("Manufacture of Sterile Medicinal Products"), pharmaceutical companies are facing new challenges, particularly in the fill-and-finish processes—the filling and final processing of medicinal products. Annex 1 introduces expanded requirements for the operation of both existing and new production lines. Our expert, Ralf Wagner, Sales Director for the DACH region, Portugal, and Spain at Optima Pharma, explains the effects on aseptic packaging and stopper feeding and presents suitable solutions.

Reducing manual interventions: automation is key

A central requirement of Annex 1 is the minimization of manual intervention in the production process, as described in §8.16. While glove interventions are still permitted, they must be analyzed in a strictly risk-based manner and explained in the Contamination Control Strategy (CCS). Automation solutions are therefore essential to reduce interventions and meet the requirements of Annex 1.

Start-up processes and automated empty slide valves

In the processing of the sterilization tunnel, so-called manual approach and empty travel frames or automated empty slide valves can be used. These systems ensure that containers are evenly distributed within the tunnel during production. In the past, such interventions were often carried out manually (insertion of the start-up/empty gate valve, removal by means of gloves in the aseptic environment), which, according to the new guidelines, can lead to the exclusion of the affected containers due to the interruption of the air flow. By using automated empty drive systems, these manual interventions can be avoided, which not only increases efficiency, but also increases product quality and product safety.

Automated removal of misaligned stoppers

Another example of innovative, AI-based automation is the removal of misaligned stoppers in the feed lanes. A robotic arm equipped with an autoclavable needle is used here. This technology correlates with camera systems, digital twins and artificial intelligence to identify mispositioned stoppers without interrupting production and remove them in a fully automated manner without the need for manual intervention. This solution is also suitable for high-performance equipment, as it significantly reduces the need for glove interventions at critical points in the process, thus minimizing downtime and possible consequential errors.

Optimized removal of tyvek cover paper

Another important process step is the removal of Tyvek cover paper from trays or tubs. Optima has developed an autoclavable solution that minimizes the risk of particle contamination. The use of suction cups at the edges of the cover paper in combination with de-ionisation rods reduces the risk of particle contamination in containers to a minimum. This is an important step towards meeting the requirements of Annex 1 and ensuring product quality.