Bio-decontamination of a pharmaceutical aseptic filling line

A pharmaceutical production facility required bio-decontamination to remove Staphylococcus epidermidis contamination of an aseptic filling suite (c.1000m³). The target area consisted of an aseptic zone (c.300m³) and a clean zone (c.700m³) with areas ranging from European GMP Grade A (equivalent to Class 100) to Grade D (equivalent to Class 100,000).

The key criteria used to select the method employed were: (i) proven efficacy against S. epidermidis; (ii) ability to meet FDA regulatory requirements; (iii) in situ bio-decontamination of intricate filling, capping, washing and freeze-drying machinery; (iv) residue-free technology to ensure that no toxic residues contaminated the product; (v) minimisation of lost production time; and (vi) documented verification of the biological efficacy of the process.

Solution

BIOQUELL’s Room Bio-decontamination Service (“RBDS”), as the only solution to fulfill all the above criteria, was selected to treat the area. The aseptic and clean zones were bio-decontaminated sequentially. Six Clarus™ ‘R’ hydrogen peroxide vapour generators were strategically placed in the zones to ensure even vapour distribution, eight Clarus™ R2 aeration units were also included to remove the H2O2 vapour at the end of the cycle and an instrumentation module was located in each zone to monitor the key parameters in real time.

Each zone was then sealed before bio-decontamination commenced and remained sealed until the H2O2 vapour had been removed at the end of the process via catalytic conversion to water vapour and oxygen. (The buildings air-handling unit (AHU) was used to accelerate the aeration.)
The entire process was monitored and controlled from outside the room via the control computer and the perimeter of each zone was monitored for leakage using hand-held hydrogen peroxide vapour sensors.

Gassing Cycle Verification

Geobacillus stearothermophilus spores dried onto metal discs and sealed in Tyvek pouches were used as biological indicators (BIs) to verify the efficacy of the bio-decontamination project. Two different inocula were used: BIs inoculated at >1.0x10⁶ for standard locations and BIs inoculated at >1.0x10⁴ for challenge locations. Standard BIs were distributed around the building according to BIOQUELL’s protocols. Challenge BI locations were established prior to the bio-decontamination of each zone. In addition, metal discs experimentally inoculated with S. epidermidis were included in the target area.

Results

The G. stearothermophilus BIs were retrieved after aeration and incubated for seven days at 60^oC. Positive control BIs that were not exposed to the bio-decontamination process showed signs of growth. 72/72 BIs from standard locations and 15/15 BIs from challenge locations were fully deactivated, showing no signs of growth. BI challenge sites included: inside the filling, capping, washing and freeze-drying machines, inside AHU ducts and inside a transfer hatch. 37/37 S. epidermidis discs used as additional BIs were fully deactivated.

None of the equipment that was exposed to the hydrogen peroxide vapour was affected, demonstrating the excellent materials compatibility of the RBDS process.

Conclusion

The bio-deactivation target of a 6-log reduction in Tyvek pouched G.stearothermophilus spores in standard locations and a 4-log reduction in challenge location was demonstrated throughout the suite. The entire bio-decontamination project was completed in three working days. The RBDS system provides a very rapid and effective bio-decontamination system, which combined with the rapid aeration method, produces a minimal cycle time.

This system is frequently used in many other applications such as the bio-decontamination of specific problem-causing micro-organisms or for general bio-decontamination of laboratories, including CL3 facilities, cleanrooms, pharmaceutical manufacturing plants and hospitals. The RBDS system is infinitely scalable so that very large areas and entire buildings (as in this case) can be rapidly and effectively bio-decontaminated.