Dr Thomas Kosian, Senior Expert in Barrier Systems at Syntegon, and Dr-Ing. Christian Dorfner, Head of R&D at InfraSolution, discuss how the two companies have launched the first system for automated HEPA filter scans in barrier systems
When it comes to sterility, there are no compromises in pharmaceutical production. This also applies to HEPA filters, which must be checked regularly. Automated testing solutions for sterilisation tunnels have already been available for quite some time.
So, why not transfer the advantages of this solution to other areas? That's what InfraSolution and Syntegon had in mind when developing a robotic-based filter scan system for RABS and isolators. The advantages are obvious: significantly faster and reproducible results in real-time combined with higher levels of process safety.
HEPA filters are important safeguards for sterile production conditions. In the pharmaceutical industry, they are used for the preparation or filtration of ambient air in production rooms.
As part of their quality management, pharmaceutical manufacturers are obliged to check the performance of their filters at regular intervals using filter integrity tests. The goal is to identify any leaks and avoid serious consequences such as reduced-quality drug products.
The standard procedure for filter integrity tests in sterilisation tunnels and barrier systems has not changed significantly during the last few decades. Most pharmaceutical manufacturers use manual processes. During the examination, an operator manually checks the entire interior and scans the HEPA filters with the help of a measuring probe.
The quality of the filter element is determined by the ratio of the upstream test aerosol concentration and the number of particles detected downstream. A low downstream particle count indicates a correctly fitted seal and an absence of leaks.
An operator must check one module after another when manually scanning the entire length of a sterilisation tunnel. Both the speed of movement and the distance of the probe to the filter surface should remain constant.
DIN EN ISO standard 14644-3 specifies that, depending on the probe geometry, the measuring probe must not be moved faster than 10–12 cm (approx. 4–5 inches) per second, while the measuring tracks should overlap by at least 10% of the probe width. The distance to the filter surface should be a constant 3 cm or less.
Apart from the fact that these tight tolerances increase the probability of unintended damage to the filters, manual tests lead to minimal-but-unavoidable deviations in the path guidance of the measuring probe. Considering that tunnel lengths of several metres are state-of-the-art, it quickly becomes clear how time-consuming and sensitive to errors manual filter integrity tests can be.
Moreover, the test results are documented manually. A connected particle counter captures the incoming particles for each tunnel section and prints the cumulated measuring results on thermal paper every minute. These paper strips, in turn, must be labelled, annotated and multiplied individually. The incoming particles are not assigned to the position of the measuring probe; the measurement engineer must know and verify and leakages in the filter medium.
This paperwork seems outdated compared with other highly efficient production procedures in which robots are already automating important process steps. The International Organization for Standardization (ISO) has also recognised this discrepancy and mentions automated filter integrity tests in the recently revised DIN EN ISO standard 14644-3 — which could provide new impetus to the topic in the coming years.
InfraSolution anticipated this development and launched RobotScanFlex (RSF) for automated filter integrity testing of ceiling filters in cleanrooms as early as 2017. Specific requests led to the expansion of the product family, culminating in the market launch of LinearTwinScan (LTS) for automated filter integrity tests in sterilisation tunnels in 2019.
Installation takes a maximum of 10 minutes and a few simple manual actions. The operator connects the system to the connection ports of the current tunnel section to regulate the aerosol flow during the test and places a linear rail of appropriate length on the conveyor belt.
Two particle counters and two measuring probes automatically measure the number of particles per tunnel section. The integrated evaluation software visualises the results in real-time in a heat map on the connected tablet, including the measured leakages. This way, the entire length of the sterilisation tunnel can be scanned automatically, section by section.
Whoever chooses automated alternatives increases their process safety and achieves more reliable measurements in significantly less time. Regarding sterilisation tunnels, the evaluation time for integrity tests has been halved, all while achieving 100% measurement of the entire filter area.
The LTS system further delivers reproducible results with high data integrity: following the filter tests, the evaluation software generates a digital measurement PDF report including an electronic signature. It combines the data of all the tested filters in a single document that complies with US FDA and GMP standards. This not only reduces the documentation effort for the operator, it also simplifies data storage and quality assurance.
HEPA filters are not only used in sterilisation tunnels. Filter integrity testing in barrier systems such as RABS, cRABS or isolators is highly complex and requires operators to penetrate safety critical areas. InfraSolution and Syntegon are now putting an end to this risk by further enhancing the LTS system.
Two particle counters and two measuring probes of the LinearTwinScan (LTS) automatically measure the number of particles per tunnel section (see image below)
Its centrepiece is a robot arm — the integrated RobotScanFlex (iRSF) — which automatically performs the integrity check of the filters. Companies that are already using the LTS system for their sterilisation tunnels have a special advantage: the robot arm is available separately; the basic equipment consisting of a tablet and two control boxes remains unchanged.
Reducing operator intervention is especially important in barrier systems, which are designed to reduce or even eliminate contact between humans and products. It only takes one operator to mount the robot arm into the pane of the isolator or RABS. The filter scan then proceeds fully automatically.
A kinematic simulation tool uses the dimensions of the barrier system to determine the ideal mounting positions for the robot arm and simulates its complete motion sequence in advance.
Blind spots are a thing of the past: the automated filter integrity tests make sure that previously untested areas are now also covered. The distance to the filters and the robot arm’s movement speed remains constant. If the system detects a leak, the affected filter position is scanned again; the required remeasurement is performed with a resting measuring probe and saved.
This increases process safety and ensures safe and reproducible results in real-time. As with the sterilisation tunnels, documentation is also considerably simplified for barrier systems, which, in turn, leads to significant time savings.
Syntegon’s Versynta Flexible Filling Platform (FFP) was selected as the first global pilot project. The new modular small-batch solution is an individually configurable machine that includes an integrated isolator for filling aseptic and highly potent liquid pharmaceuticals.
It processes different containers such as vials, syringes and cartridges with an output of up to 3600 containers per hour with 100% in-process control. Its simple geometry, future-oriented concept and the constantly increasing demands on production and process quality made Versynta FFP the ideal candidate for the RSF pilot project.
The filter scan system was adapted to the requirements of the Versynta FFP’s closed isolator. This collaboration of two experts with many years of expertise in barrier systems and process technology (Syntegon), as well as technical machine equipment, software applications and robotics (InfraSolution), has resulted in a solution that sets new standards in HEPA filter integrity testing.
The system is under continuous development and will soon be available for use in all isolators, RABS and cRABS.