This article delves into the world of isolators, exploring their importance in the pharmaceutical and biotech industries, the challenges of innovating aseptic isolator design, best practices, key aspects of design optimization, and how Germfree meets industry needs.

Defined by the Royal Pharmaceutical Society as a “containment device that utilizes barrier technology for the enclosure of a controlled workspace”, isolators physically separate one part of a system from another, typically to prevent interference or contamination between the parts.¹ Isolators are used in various industries, such as pharmaceutical dispensing, animal containment, nuclear medicine, manipulation of toxic waste, among others, to protect sensitive equipment or processes from external influences, ensuring optimal performance, reliability, and safety.² An isolator has four essential elements:²

1. A separative device, that encloses the workspace;
2. A transfer device, that allows materials to move in and out of the enclosed area;
3. An access device, through which the work can be carried out;
4. And a decontamination system, that maintains sanitation or sterility.

They are available in a variety of sizes and configurations, making them extremely versatile and adaptable to the specific application requirements.

The Pharmaceutical industry must adhere to strict aseptic requirements throughout the manufacturing process to ensure the safety and effectiveness of medicines. Sterility assurance, which is critical in drug manufacturing, ensures product safety.³

Isolators are indispensable components of cleanroom environments, offering a physical barrier between a pharmaceutical process or activity, and operators or their surrounding environment. Therefore, aseptic isolators must meet specific critical design elements to comply with regulatory requirements and to reflect the intended application and decontamination method.

Germfree has been developing isolators for over a decade, building on more than 40 years of experience as manufacturers of custom Class III Gloveboxes. We are known for pushing boundaries and setting new standards in cleanroom technology with groundbreaking product design.

Germfree produces advanced current good manufacturing practices (cGMP)-compliant pharmaceutical isolators that function as gas-tight enclosures, effectively creating a barrier that ensures aseptic conditions and containment. These isolators are tailored to meet the specific demands of various applications and operations.

The optimal design for an isolator should strive for safety and efficiency, and overall success of product manufacturing. This demands precision and collaboration throughout the process. Refining the isolator design requires a meticulous approach, to ensure optimal performance and adherence to regulatory standards. At Germfree, our teams are at the forefront of understanding these requirements, working to deliver the best solutions. This experience means we understand that a robust isolator design process requires a few key factors:

• A well defined user requirement specification and an understanding of laboratory architecture
• Knowledge of the required physical structure, internal environment, interaction technology, monitoring system, and the standards or local regulations/requirements⁴
• Careful consideration of the method of decontamination⁵
• Clearly defined roles and responsibilities, with regular design reviews
• Optimized collaboration between partners and materials vendors, such as sheet metal

Product protection is crucial in isolator design, enabling the manipulation of non-hazardous sterile materials, while minimizing the risk of exposure to hazardous substances.

Germfree joined efforts with AST to develop an innovative sterile fill isolator technology that will redefine standards in the pharmaceutical industry. Together, we worked to ensure the highest level of operator and product protection, providing a complete barrier from the materials, while being ergonomic to the user.

Significant measures went into assuring sterility within the chamber. For example, the design of the state-of-the-art inflatable gasket system creates a gas-tight barrier within the chamber during operation, while still allowing for the ingress and egress of materials. The system allows for complete decontamination at a much lower peroxide concentration than the competition, drastically reducing our aeration cycle time.

Additionally, the isolator can be fully assembled off site, before being shipped to the final location for mounting on the product and final assembly.

Great innovation brings unique challenges, for instance – regarding biologics and combination products, where traditional sterilization processes are not as effective or cannot be used.³ Building isolator technology involves overcoming hurdles related to material compatibility, precision engineering and regulatory compliance.

The development of isolator technology requires precision engineering, with tolerances being a major concern. Therefore, it can be a challenge to achieve a sleek, smooth structure of the unit. The structure should also have no overhang between the working modules and the HVAC (heating, ventilation and air conditioning) housing, while allowing serviceability from the cleanroom side, to maintain the regulatory compliance needed for biopharmaceutical companies.

At Germfree, we specialize in designing and manufacturing cutting-edge isolators, establishing ourselves as a leading innovator in the field of aseptic solutions. Our focus on stringent quality standards, compliance, and operational efficiency ensures the production of safe, high-quality compounded medications, which benefit patients and healthcare providers alike. Our 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 cGMP environments.

To find out more about our aseptic solutions, book a discovery call today:

• Sales: 1 (386) 265-4300
• Service & support: cs@germfree.com

References:

1. Royal Pharmaceutical Society, Quality Assurance of Aseptic Preparation Services: Standards. Part A, Fifth edition. Beaney AM. Available at: https://www.rpharms.com/Portals/0/RPS%20document%20library/Open%20access/Professional%20standards/Quality%20Assurance%20of%20Aseptic%20Preparation%20Services%20%28QAAPS%29/rps—qaaps-standards-document.pdf [Accessed March2024].
2. Midcalf B. Isolators: protecting operator and product. Hospital Pharmacy Europe. Available at: https://hospitalpharmacyeurope.com/news/editors-pick/isolators-protecting-operator-and-product/ [Accessed March 2024].
3. Lambert BJ, et al. Sterility Assurance Across-Sectors – New Paradigms and Tools. Front Med. Technol. 2021 Aug 3:622710. Doi: 10.3389/fmedt.2021.622710.
4. Rahe H. Understanding the critical components of a successful cleanroom and barrier isolator project. Am J Health Syst Pharm. 2000 Feb 15;57(4):346-50. doi: 10.1093/ajhp/57.4.346. PMID: 10714972.
5. Midcalf B. Pharmaceutical isolators: design considerations. Hospital Pharmacy Europe. Available at: https://hospitalpharmacyeurope.com/news/editors-pick/pharmaceutical-isolators-design-considerations/ [Accessed March 2024].