Disinfect, Autoclave or Use Multiple-Bagged Disposables? Moving Materials into Controlled Areas Safely and Efficiently

Transferring equipment into and out of cleanrooms and critical zones has proven to be one of the greatest sources of contamination in the manufacture of sterile pharmaceuticals. To minimize the potential for adverse effects on patients, cGMP and EU GMP regulations have been tightened. Transfer procedures are complex, with materials typically having to go through two material locks to get from a non-classified area to a grade A cleanroom, RABS, or isolator, the final step ideally in a one-way process (see earlier interview). The safe transfer of materials gets more complicated the more there is to clean, disinfect, and autoclave. For the manufacture of biopharmaceuticals, single-use systems comprising sealed and pre-sterilized components have gained considerable traction in recent years, mainly because they can eliminate cleaning, sterilization, and validation of sterilization procedures, thereby enhancing efficiency, flexibility, and contamination control. Pharmaceutical QC is seeing a similar shift toward using readily irradiated consumables and accessories, with multi-layered packaging playing a significant role.

Just remove a sleeve.

The available range of such disposables for environmental monitoring is constantly expanding. Aseptically filled, ready-to-use settle plates and contact plates that have been gamma-irradiated in triple packaging are already being widely used in facilities that produce sterile pharmaceuticals. They offer the convenience and safety of allowing consecutive layers to be removed when the plates are transferred from lower to higher-grade areas. This avoids having to wipe the outer sleeve with disinfectant upon transfer, a manual procedure with an avoidable potential for handling errors. Disinfectant residues can lead to false negative environmental monitoring results, so it is also important that the culture media are supplemented with the right neutralizing agents to overcome the effects of any antimicrobial activity.

Triple-packaged plate packs can usually be stored outside a cleanroom and at room temperature for extended durations before expiry. Their sleeves should be transparent to allow visual inspection, must have low water vapor permeability, and be easy to open when wearing gloves. For use in an isolator, the sleeve must be impermeable to the VHP used for decontamination and should allow packs to be hung up to save space.

A reservoir of plates for the isolator

To transfer materials that have been sterilized in their sealed packaging into grade A areas, the recently revised EU GMP Annex 1 suggests considering the use of rapid transfer port technology. This allows irradiated rapid transfer bags containing a large reservoir of contact or settle plates in several single-sleeved packs to be attached to the transfer port of an isolator for immediate use, which saves valuable space inside. There is no need to decontaminate the packs of plates, so the number of decontamination cycles is reduced. This enables longer periods of uninterrupted production, which is particularly useful for manufacturing campaigns lasting several days. Our IsoBag^® transfer bags retain their integrity for several connections to the alpha port. When emptied, they can serve to transport the used plates back out. To ensure that the plates do not accidentally open during transportation to the incubator, these transfer bags include triple-bagged, gamma-irradiated transport bags with a zip lock.

Autoclavable versus disposable accessories

Multi-layered packaging can also facilitate the safe transfer of instrument accessories into higher-grade areas. Many active microbial air samplers, for example, have autoclavable aaluminumlids with perforations through which the ambient air is led. The process of getting a lid ready for reuse takes up to two hours because this involves a series of tasks, including the lid’s transfer from the cleanroom to the autoclaving zone, cleaning the lid, packaging it for protection from subsequent contamination, the actual autoclaving process, periodical revalidation of the autoclaving cycle, and the associated documentation. All these steps are no longer needed when using a disposable plastic lid, irradiated in its multiple packaging, that can be used several times during a shift. Using such a lid also avoids damage due to incorrect handling by untrained staff and prevents personnel comes into contact with traces of toxic drug compounds.

The properties that such lids should possess are that they are easy to exchange and affix tight to the instrument, work with the same impaction speed as the standard lid, and achieve comparable recovery rates of microorganisms, which we proved in a simplified validation study according to EN 17141 for our low-particle emission Safe Lids that go with the MAS-100 NT^® active air sampler. The lid’s production process should ensure that it has the correct number and dimension of holes, something the vendor should be able to demonstrate. This can be done by inspecting the sieve pattern of every lid using camera technology, and batch-specific Certificates of Quality should be made available to support regulatory compliance.

Author Details 

Anne Weeks, Commercial Applications Expert, BioMonitoring, MilliporeSigma; Burlington; MA; USA, An affiliate of Merck, KGaA Darmstadt, Germany; Kristian Siedler, Global Product Manager, Commercial Excellence BioMonitoring, Merck LS RTU GmbH, Darmstadt, Germany; Dr Anne-Grit Klees, Lead Expert, Product & Portfolio Manager, BioMonitoring Environmental Monitoring, Merck Life Science KGaA, Darmstadt, Germany.

Publication Details 

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