Hydrogen peroxide vapour decontamination can be integrated effectively into the overall design of isolators to speed up changeover time.
4-glove Sterility Test Isolator - Helvic Laboratories
To meet the challenge of decontaminating isolators, the process is increasingly being integrated into the overall systems design. Envair reveals some of its recent solutions using hydrogen peroxide vapour decontamination
Companies are increasingly applying the use of isolators in contamination-sensitive operations as a means to cut costs and increase production flexibility. Controlling the immediate environment around the product, rather than the whole room, is in many cases more cost-effective, as long as the operator’s ability to manipulate the process is not unduly restricted by the isolator.
However, the use of isolators can make cleandown and decontamination of the process, either between batches or products, more complex. Envair offers a range of standard isolators and bespoke isolators with fully integrated hydrogen peroxide vapour (HPV) bio-decontamination systems.
Working with both Bioquell and Steris, the two market leaders in HPV bio-decontamination, Envair has developed fully integrated PLC control systems for a variety of applications, including aseptic production, filling processes, sterility testing and terminally sterilised enclosures. Designs include unidirectional and turbulent airflow systems, individually decontaminated transfer chambers, mobile transfer isolators, connection to ancillary aeration units and integration with rapid gassing transfer hatches.
In addition to hydrogen peroxide vapour technology, continuous particle monitoring and viable air monitoring are often an integral part of the design. Equipment for specialised applications such as sterility testing can also be integrated into the isolator to give a complete solution.
One recent example of a project completed by Envair was the supply of a sterility test isolator for Helvic, based in Trentham, Staffordshire, UK. Helvic carries out contract sterility testing for a wide range of pharmaceutical companies, including a large amount of work for a manufacturer of radiopharmaceutical tracers for use in Positron Emission Tomography. The isolator provided for Helvic is one of Envair’s standard Pharm-Assist FLF isolators adapted for sterility testing.
The isolator has four gloves, a transfer chamber at each end and a unidirectional airflow zone in the main chamber that extends over the full length of the chamber.
The isolator is fully integrated with a Bioquell Clarus L2 HPV generator and a Bioquell Aeroflow unit for a quicker overall cycle time. The Aeroflow catalytic aeration unit comprises a fan and catalytic filter that accelerates the removal of HPV following the decontamination process. This enables a higher air volume flow during the aeration part of the gassing cycle.
The sterility tester itself is a Millipore Steritest Equinox Isofit Pump with a streamlined construction designed specifically for integration into isolators. As with the HPV generator, the sterility tester is integrated into the isolator control system so that the sterility test operation can only take place after the HPV decontamination process is complete.
Another feature of the design is that the drain that runs from the sterility testing unit to a carboy underneath the isolator during normal operation can be disconnected from the carboy prior to the gassing cycle and attached to the isolator chamber. This enables the HPV to pass through the tubing and sterilise it.
Environmental monitoring inside the main chamber of the isolator is not only a regulatory requirement but also critical to ensure that there are no false positive results from the sterility testing. This can happen should external contamination somehow enter the samples being tested. This isolator is therefore provided with integrated monitoring of both particulates and viables.
The real-time particulate monitoring is by Pharmagraph and comprises: a 1cfm particle counter with >0.5µm and >5.0µm channels; a stainless steel ball valve (diverter valve) for diverting the HPV gassing through the probe and back to the isolator during gassing (a particularly useful innovation as it allows for the sample tubing to be biodecontaminated); and a Pharmagraph CC9044 controller. This provides the digital input/output interface to link with a) the PLC system of the isolator, b) the vacuum control (pump motor and valve, and c) the diverter valve. The software used in this application is the Pharmagraph enVigil Lite.
Viable monitoring is by the Cherwell SAS microbial air sampler for isolators. This has the stainless steel sampling head permanently inside the isolator chamber, connected by Lemo connection to the control unit on the outside, thus eliminating the need for the sampler to be continually passed in and out of the isolator with all the associated contamination risks.
The isolator is fully automated, including the pressure decay test, and the human machine interface (HMI) on the front of the isolator pulls together all the main controls, interlocks and alarms for the isolator itself, the sterility tester, the particle monitoring system and the microbial air sampler. The integral printer above the right hand transfer chamber provides a printed record of all isolator functions and alarms, making it much easier for the system to comply with GAMP and 21 CFR Part 11.
In another recent case, a sterility test isolator was supplied to Smith and Nephew, China for the manufacture of bandages and dressings at its facility in Suzhou.
2-glove Sterility Test Isolator - Smith & Nephew, Suzhou, China
In this instance the isolator was an Envair two-glove Pharm-Assist, finished in polished stainless steel internally and externally, and the HPV generator was the Steris M100S. This generator is designed to be physically integrated within the isolator footprint and is fixed underneath the main chamber.
This particular isolator does not have an integrated sterility test unit, as this was not a requirement, but it does have integrated particle and viable monitoring. Particle monitoring is provided by a MetOne 6015P particle counter with an associated PC running the Pharmagraph enVigil-Lite software. The MetOne 6015P is located outside of the main chamber of the isolator connected by a short length of particle tubing to the sampler head inside.
The viable monitoring is by a Cherwell SAS in a similar arrangement. Once again, all the controls, interlocks and alarms that integrate the components of the system are pulled together on the HMI at the front of the isolator; and again, all the critical readings and alarms are available as a printed record from the integrated printer to facilitate compliance with regulatory requirements.
A complete solution
Envair’s systems are offered with a full validation package including Design Qualification, client witnessed Factory Acceptance Testing, Installation Qualification and Operational Qualification. The validation packages have also been approved and validated on licensed and unlicensed healthcare, pharma and research sites.
To ensure the optimum technical solutions, the company can provide both traditional 2D CAD concept designs and 3D CAD modelling. Timber mock-ups can also be prepared to help resolve awkward material handling issues at the design stage.