Expert Guidance on Containment Isolator Design and Facility Integration
Expert Guidance on Containment Isolator Design and Facility Integration
Equipment: Containment Isolator
This article discusses how Containment isolators are essential components in high containment environments, such as biosafety level 3 (BSL-3) laboratories, and for handling hazardous drugs with low occupational exposure limits (OELs). They provide a physical barrier between the operator and hazardous materials, preventing exposure to infectious agents or toxins, and allow for controlled and safe handling of select agents as defined by the Centers for Disease Control and Prevention (CDC).
Figure 1: Containment Isolator in cGMP/BSL3 facility
Containment isolators are indispensable components of high containment environments employed to handle select agents in biosafety level 3 (BSL-3) laboratories and hazardous drugs with low occupational exposure limits (OELs), often in nanogram quantities. These isolators offer a physical barrier between the operator and hazardous materials, mitigating exposure to infectious agents, toxins or hazardous drugs. Furthermore, containment isolators enable controlled and safe handling of select agents, defined by the Centers for Disease Control and Prevention (CDC) as biological agents with the potential to pose a severe threat to public health and safety.
Compliance with biosafety and occupational safety regulations governs containment, while current Good Manufacturing Practice (cGMP) imposes requirements on isolator air quality, such as compliance with specific particle counts. This dual compliance with both cGMP and BSL-3 presents a particular challenge for containment isolators. According to Biosafety in Microbiological and Biomedical Laboratories (BMBL) version 6, containment isolators employed in BSL-3 laboratories must satisfy certain requirements, including preventing escape of infectious agents or toxins, providing an easily decontaminable barrier, and having appropriate filters to remove airborne contaminants. This article will examine the critical design elements, ergonomic considerations, and work surface requirements for containment isolators.
When working with selective agents in Biosafety Level 3 (BSL-3) laboratories or handling hazardous drugs with low occupational exposure limits (OELs), containment isolators are essential to ensure a safe and controlled environment for personnel. Intensive reviews of process requirements, work flows and process interventions are key inputs into the development of user requirement specifications (URS).
Critical Design Elements for Containment Isolators
Compliance with regulatory requirements necessitates that containment isolators meet specific critical design elements, which include:
1. Physical Barriers: To avoid hazardous direct contact with materials, a physical barrier separating the operator from the material is imperative. Decontamination-resistant materials like stainless steel should be utilized.
2. Glove Ports: As part of the physical barrier, glove ports should resist the select agent or hazardous drug being handled and allow for easy change or replacement. Additionally, glove designs should incorporate a glove reach test to prevent dangerous leaks in case of glove breakage.
3. Airflow and Filtration: Negative pressure ventilation systems isolate fumes, directing airflow away from operators and towards filters, which remove airborne contaminants. For example, Germfree constructed a hazardous drug manufacturing isolator with a single HEPA supply and double HEPA exhaust, ensuring no hazardous air exited the isolator.
4. Decontamination Systems: Sterilization of interior surfaces and materials can be achieved through systems based on UV-C lamps or hydrogen peroxide vapor (HPV). For instance, a built-in decontamination generator using HPV can be designed for both manual and automatic decontamination cycles.
5. Waste Disposal Systems: The isolator should incorporate a system for disposing of waste materials, such as a vacuum system to collect and contain hazardous waste.
6. Alarm Systems: In case of containment system breaches or faults in airflow or pressure levels, alarm systems must alert the operator.
7. Testing and Qualification: Prior to use, the isolator should undergo testing and qualification to ensure negative pressure maintenance and the prevention of hazardous leakage. Failure mode testing is integral to the overall testing strategy, with failure scenarios identified through risk assessment and built into execution protocols.
Work Surfaces and Cleanability
Clean and sterilized surfaces are vital when handling hazardous materials in a containment isolator. Key requirements for these surfaces include:
1. Work Deck Surfaces: The work deck area where operators manipulate hazardous materials should utilize a smooth, non-porous, decontamination-resistant material like stainless steel.
2. Cleanability: Work deck and isolator surfaces should be easy to clean and disinfect, having a minimal number of seams, corners, and other dirt and contaminant accumulation areas. Surfaces should also resist damage from decontamination agents like vaporized hydrogen peroxide (VHP).
Ergonomic Design Considerations
Ergonomic design considerations ensure containment isolators used for handling select agents or hazardous drugs in high containment environments are comfortable and safe for operators. Key ergonomic design factors include:
1. Comfortable Working Height: Providing an appropriate height for operators prevents hunching over or straining to reach hazardous materials.
2. Adequate Space: The isolator should offer sufficient space for operators to work comfortably and efficiently, including enough room for tools, equipment, and movement adjustments.
3. Adjustable Glove Ports: Glove ports should be adjustable to accommodate different hand sizes and enable operators to work without arm or shoulder strain.
4. Lighting: Proper lighting should be installed inside the isolator, allowing operators to see clearly and work safely. Lighting should be bright enough to illuminate the work surface and materials without causing glare or eye strain.
5. Noise Level: Design should minimize noise, which can cause stress and fatigue for operators, by using noise-reducing materials for the ventilation system and other equipment.
6. Footrests: Adjustable footrests can be provided to enable operators to adjust their posture and relieve stress on their legs and back, accommodating different leg lengths and allowing operators to shift their weight as needed.
7. Accessibility: The isolator should be designed to be accessible to operators with disabilities or limited mobility through features like adjustable height, easy-to-reach controls, and wider doorways.
Ergonomic design plays a crucial role in protecting operator safety and enhancing efficiency, as operators handling select agents in high containment environments are particularly vulnerable to fatigue, stress, accidents, and injuries.
Figure 2: Passthrough from QC Lab Transferring Materials to Containment Isolator in cGMP/BSL3 facility
Passthrough technology plays a crucial role in ensuring the safe transfer of materials in and out of containment isolators while maintaining containment integrity. Incorporating passthrough systems into containment isolator design enables efficient and secure transfer of items, reducing the risk of exposure to hazardous agents or cross-contamination. Key aspects of passthrough technology in containment isolators include:
1. Interlocking Doors: Passthrough systems often feature interlocking doors, ensuring that only one door can be opened at a time. This design prevents the simultaneous opening of both doors, maintaining the containment barrier and minimizing the potential for hazardous materials to escape.
2. Decontamination Procedures: Prior to transferring materials between the isolator and external environment, a decontamination step should be incorporated into the passthrough process. Commonly used methods include chemical disinfection with a suitable agent, such as vaporized hydrogen peroxide (VHP).
3. Sealed and Leak-Proof Design: Passthrough chambers should be designed to maintain airtight seals, preventing the leakage of hazardous agents or contaminants. This design feature ensures containment integrity is maintained, protecting both the operator and the environment.
Integrating Containment Isolators into Facilities
The integration of containment isolators into facilities is of paramount importance for ensuring seamless workflow, maintaining biosecurity, and optimizing the use of available space. Proper integration involves a holistic approach, considering factors such as facility layout, equipment, and workflows. Key elements in integrating containment isolators into facilities include:
1. Facility Layout: Containment isolators should be strategically placed within the facility, ensuring they are easily accessible for operators and do not obstruct other essential processes. The placement should also take into account necessary service connections, such as electrical, plumbing, and ventilation systems. In a recent project, Germfree designed a cGMP/BSL-3 facility from the inside out allowing the containment isolators to drive the facility design.
2. Equipment Compatibility: The containment isolator should be designed to accommodate and integrate with any necessary equipment required for the specific processes carried out within the isolator. This can include process equipment, consumables, sample processing, analytical instrumentation, or waste disposal systems.
3. Workflow Optimization: To enhance the efficiency and safety of operators, the containment isolator should be integrated into the facility’s existing workflow. This can be achieved by conducting a thorough analysis of the facility’s procedures and adjusting the containment isolator’s design accordingly, ensuring it aligns with the facility’s standard operating procedures and minimizes disruptions.
4. Compliance with Regulations: Integration of containment isolators into facilities should take into account relevant regulatory requirements, such as FDA 21CFR part 210 and 211, BMBL guidelines, local building codes, and environmental health and safety standards. Compliance with these regulations ensures the facility operates within legal parameters and maintains a safe working environment.
Figure 3: Operator Working on Containment Isolator in cGMP/BSL3 facility
Containment isolators are essential components in high containment environments, such as biosafety level 3 (BSL-3) laboratories, and for handling hazardous drugs with low occupational exposure limits (OELs). They provide a physical barrier between the operator and hazardous materials, preventing exposure to infectious agents or toxins, and allow for controlled and safe handling of select agents as defined by the Centers for Disease Control and Prevention (CDC).
Critical design elements of containment isolators include physical barriers, glove ports, airflow and filtration, decontamination systems, waste disposal systems, alarm systems, and testing and qualification procedures. Work surfaces and cleanability are also important design considerations, with biodecontamination systems, such as vaporized hydrogen peroxide (VHP), ensuring the sterilization of interior surfaces and materials. Ergonomic design considerations, including comfortable working height, adequate space, adjustable glove ports, lighting, noise levels, footrests, and accessibility, enhance operator safety and efficiency.
Passthrough technology is a vital aspect of containment isolators, providing a secure means to transfer materials in and out of the isolator while maintaining containment integrity. Key features include interlocking doors, decontamination procedures, and sealed, leak-proof designs.
The successful integration of containment isolators into facilities requires considering factors such as facility layout, equipment compatibility, workflow optimization, and compliance with regulations. This integration ensures seamless workflows, maintains biosecurity, and optimizes the use of available space.
By incorporating critical design elements, ergonomic considerations, passthrough technology, and effective facility integration, containment isolators provide a safe and efficient means to handle hazardous materials, protecting operators, the environment, and public health.
Germfree, a leading innovator in the field of containment solutions, is renowned for its expertise in designing and manufacturing state-of-the-art containment isolators. With a focus on stringent quality standards, compliance, and operational efficiency, Germfree consistently delivers advanced, reliable, and user-friendly containment systems. Their extensive experience, combined with a deep understanding of both industry requirements and end-user needs, positions Germfree as a trusted partner in creating tailored solutions for high containment environments, ensuring the utmost protection for operators, the public, and the environment.
1. Centers for Disease Control and Prevention (CDC). (2017). Biosafety in Microbiological and Biomedical Laboratories (BMBL) (6th ed.). U.S. Department of Health and Human Services.
2. National Institutes of Health (NIH). (2019). Biosafety in Microbiological and Biomedical Laboratories (BMBL) (6th ed.). U.S. Department of Health and Human Services.
3. World Health Organization (WHO). (2004). Laboratory biosafety manual (3rd ed.). World Health Organization.
Join our Sales Engineer, Sean Bartholomew, and Mechanical Engineer, Krishna Aravinthan, as they discuss the technologies and advantages of Germfree's compact, rapidly deployable 24' Mobile BSL-2 Laboratory Solution.