As regulatory standards evolve, the implementation of select technologies becomes vital to meet the requirements of cleanroom environments. In the latest update to the EU GMP Annex 1 in 2022, isolators have emerged as the preferred technology in aseptic fill finish processes to ensure ideal cleanroom conditions and minimize microbial contamination associated with human interventions.
The automated decontamination of isolators is a critical element of the overall Contamination Control Strategy (CCS). According to the EU GMP Annex 1, the decontamination process should ensure thorough microbial decontamination of its interior. Decontamination methods (cleaning and sporicidal disinfection) should render the interior surfaces and critical zone of the isolator free of viable microorganisms.
Vaporized Hydrogen Peroxide (VHP) Decontamination Cycle:
Among various chemical options for decontamination, vaporized hydrogen peroxide (VHP) has become the go-to choice for its compatibility with most materials, safety profile, effectiveness against a broad spectrum of microbiological contaminants, and relatively short cycle times. With a long history in the healthcare industry, VHP has proven its efficacy in ensuring the sterility of isolator interiors.
The VHP decontamination cycle involves four main steps: Conditioning, Gassing, Decontamination, and Aeration. Prior to initiating the VHP decontamination cycle, a thorough cleaning of the isolator interior is essential to prevent any residues that might inhibit the surface decontamination process.
Conditioning: Remove as much relative humidity (rH) as possible with the isolator by injecting dry air. Target rH: 20% or less. rH is reduced to avoid condensation of H2O2 during next phases.
Gassing: VHP is injected into the isolator. rH must be controlled to avoid condensation – target 90-95% rH. If rH exceed 100%, condensation will start to form.
Decontamination: Hold the isolator at target concentration of VHP for a specified time.
- rH: 90-95%.
- H2O2 concentration: 500-800 ppm.Time: 30-60 minutes.
Aeration: VHP is removed from isolator by changing the air volume many times. Complete when VHP concentration reaches less than 1ppm. rH is returned to normal level 40-60%.
The Validation Process:EU GMP Annex 1 mandates the validation and control of decontamination methods within defined cycle parameters. The validation process must demonstrate a Sterility Assurance Level (SAL) of a 6 log reduction of bioburden (1 out of 1,000,000 bacteria will survive).Biologic indicators (BI) are used to determine the effective kill rate of the VHP cycle. These BIs are placed in pre-determined critical and challenging areas inside the isolator. Critical areas, determined by users and specific processes, include high-touch points, format parts used for container manipulation, and equipment touched by gloves. Challenging areas include partially obstructed areas, upper corners of isolators (VHP tends to settle to the lower areas), gloves extended (not folded over), and hanging items. Typically, 3x BIs are placed at all high-risk areas to demonstrate VHP effectiveness.
Chemical indicators (CI) may also be used during gassing cycle development to provide immediate feedback compared to BIs and help to identify challenging areas within the isolator.
The integration of isolators and VHP decontamination represents a robust solution in meeting the regulations outlined in the EU GMP Annex 1 2022. As cleanroom technologies continue to advance, these innovations underline our commitment to maintaining the highest standards of contamination control. By adopting these technologies and following validated procedures, companies can not only comply with regulatory requirements but also ensure a sterile and controlled environment for aseptically filled products, safeguarding both the products and, ultimately, patient safety.
Ready to elevate your contamination control and comply with the latest EU GMP Annex 1 standards?
Discover the transformative power of Vaporized Hydrogen Peroxide for isolator decontamination. Don’t let complexity hinder your compliance. Reach out to us at hello@nodeviation.com to ensure a sterile, safe environment for your aseptic processes today!
Augustus Graham is the Process Technical Lead here at No deviation. With a rich background in the pharmaceutical industry and over ten years of international exposure, Gus has honed his expertise as a Process Engineer across various sectors, including parenteral pharmaceuticals, active pharmaceutical ingredients (API), and vaccine production.
His vast project management experience ranges from overseeing large-scale greenfield projects to leading precision upgrades during planned facility shutdowns. He is motivated by a constant drive to enhance his skills and is committed to maintaining the highest standards of cGMP compliance. His dedication not only ensures the reliability of production equipment but also the refinement of processes essential for the consistent delivery of high-quality pharmaceuticals. Graham thrives on teamwork and finds immense satisfaction in collaborating with a diverse group of engineers, working together to develop comprehensive solutions that ultimately help deliver vital vaccines to those in need.
