#10 - Rapid transfer ports in life science applications

Manufacturers of high-value products in the nuclear and life science industries share two common challenges as these products are moved into and out of cleanrooms, isolation chambers, and gloveboxes: ensure purity or sterility so products aren’t compromised, and make certain any hazardous materials used or waste products created are handled safely and securely.

Serving as an indispensable aid in meeting and overcoming these challenges are Rapid Transfer Ports (RTPs), which were developed to provide safe, contained transfer of sterile or hazardous materials and waste as they are moved into and out of containment or isolation. A leading developer and provider of RTP technology is Red Wing, Minnesota-based Central Research Laboratories Inc. (CRL).

CRL has created a full range of RTP technologies designed around the capabilities of the Double-Door Transfer System, allowing materials to be rapidly transferred into and out of a cleanroom, isolation chamber, or glovebox without breaking containment. This helps ensure product purity, quality, and integrity while maintaining an expected level of safety for operators.

Nuclear

CRL’s roots go back to the dawn of the Atomic Age in 1945 when three recent graduates of the Massachusetts Institute of Technology – Frank G. Chesley, Demetrius Jelatis, and Gordon M. Lee – pooled their resources and founded CRL. Thanks to their undergraduate experience as researchers for the U.S. War Department, CRL found immediate success as a company that designed radar-testing equipment for various branches of the U.S. armed forces, as well as the U.S. Atomic Energy Commission. The company’s first breakthrough in this realm came in 1953 with the development of the Model 8 Telemanipulator, which was a safer method of handling radioactive materials.

Fast forward to 1997, when CRL introduced its first RTP model, which consisted of two main components: a stationary Alpha flange mounted to the wall of a contained environment, and the Beta assembly, a mobile container, bag, or other process component attached to the Alpha flange. Both the Alpha flange and Beta assembly consist of a door, seal, and interlock.

The design of the RTP dictates when the Alpha flange and Beta assembly are mated, the interlock helps protect against either of their doors accidentally opening. Also, the doors won’t be allowed to open if the two assemblies are incorrectly docked. Interlocks are incorporated into the flange on the Alpha assembly at the interface with the door handle, preventing the port door from being opened when a Beta assembly isn’t present; keeping the Beta assembly from being removed from the Alpha flange when the port door is open; and preventing the port-door handle from being rotated when the door is open.

Life science

Building and maintaining a safe and secure work environment is a top-of-mind concern for all operators within the life science industry. It requires the creation and maintenance of highly reliable isolated environments that can protect against product contamination and exposure to potentially hazardous materials.

Three operational areas within the life science realm are ideal for the use of RTPs:

• Aseptic manufacturing: From sterile active pharmaceutical ingredient (API) production and product formulation to the transfer of sterile liquids/components and aseptic-filling processes, sterility must be maintained at every stage with no chance that outside contaminants can infiltrate the production process.
• Potent manufacturing: RTPs can play a significant role in keeping contaminants at bay during such high-value applications as high potency active pharmaceutical ingredient (HPAPI) production, the development of potent oral solid dose (POSD) pharmaceuticals, and the packaging and transport of finished APIs and POSDs.
• Aseptic/potent manufacturing: This category combines the requirements of aseptic and potent manufacturing, with special emphasis placed on the production of sterile high potency active pharmaceutical ingredients (SHPAPI), biologics, radiopharmaceuticals, and highly concentrated formulations. RTPs play a leading role in transferring these substances into and out of isolation safely through the prevention of exposure to toxic, hazardous, or dangerous materials.

A closer look

Throughout the years, CRL’s RTPs have evolved through the diligent work of a design and engineering team that’s constantly looking for ways to improve product performance, revealing itself with CRL’s recent introduction of the E Rapid Transfer Port, or ERTP (see sidebar), which promises to make RTP operation easier while maintaining the same product purity and containment capabilities.

All RTP models feature the Double Door Transfer System, but additional features have been developed that give the technology more flexibility, including:

• Handle designs that use minimal rotation to break the seal on the Beta container, simplifying operation while maintaining a high safety level
• Streamlined interlock system with interchangeable three- and four-bayonet Beta mount inserts that can be replaced without breaking containment
• Standard 316L stainless-steel body construction with three port-door options:
  • Stainless steel for use in strong chemical/radiation, some aseptic applications
  • Polypropylene for use in pharmaceutical, chemical, nuclear applications
  • Liquid-transfer for use in sterile filling-line, fluid-transfer applications
• Elimination of pinch points on the handle, minimizing glove damage
• Elimination of exposed fasteners, creating a smoother surface for easier cleaning
• Compatibility with various Beta assembly options

Before the introduction of the ERTP, CRL had already created two different iterations of its original RTP model that incorporated some of these advanced features: the Sterile Liquid Transfer Port (SLTP) and the Sterilizable Rapid Transfer Port (SRTP).

Sterile Liquid Transfer Port (SLTP): The patent-pending SLTP, a component within CRL’s Sterile Liquid Transfer System, helps enable efficient, safe, and contamination-free transfer of aseptic liquids from sterile product devices through a barrier wall and into a cleanroom or isolator. This design helps the SLTP satisfy Ring of Concern challenges where the Alpha door and Beta assembly meet – an area that’s constantly at risk of becoming contaminated. The SLTP overcomes this challenge by allowing the sealing surfaces to be heat sterilized. Other advanced features and benefits of the SLTP include:

• A standard steam-in-place cleaning process with dedicated docking plate enabling proper Beta flange placement during sterilization activities
• Polypropylene or stainless-steel protective collar at the Ring of Concern
• Alpha flange equipped with mechanical interlocks that help prevent improper port operation
• Product connection tube with inner surfaces polished to 15µm and sloped to aid in drainage
• Extended polypropylene or stainless-steel Alpha port door accommodating longer product- connection tubes
• Single- or multi-connection Beta flange with a condensate- drain connection
• Alpha and Beta flange body construction of 316L stainless steel
• Silicone gasket seals
• Tri-clover fittings on product tubes for reusable, validated, and rapid aseptic-hose connection and disconnection
• Testing and approval for use at hydrostatic pressures up to 3.4 bar (50psi)
• Sterilizable Rapid Transfer Port (SRTP): The SRTP offers CRL’s traditional Double-Door Transfer System design and enhances it by featuring patented dry-heat sterilization technology. Unlike conventional UV-sterilization techniques, CRL’s dry-heat sterilization process eliminates concerns associated with contaminated seals that may result from inconsistent aseptic wiping or the shadowing and stacking of aseptic components. This makes SRTPs ideal for the transfer of components that require high sterility-assurance levels, such as stoppers, vials, and caps, into a sterile isolator or aseptic barrier system. This high sterility is achieved through the installation of an electric heater in the Alpha flange at the seals’ intersection. This critical high-temperature zone is heated to 375ºF (190ºC) for a predetermined length of time after the Alpha and Beta flanges have been docked. Independent tests have shown that this dry-heat sterilization technique can yield up to a 6-log microbial reduction level at the sealing surfaces of the SRTP.

  Other advanced features of the SRTP include:

  • 316L stainless-steel Alpha flange with polypropylene or stainless-steel door
  • Polypropylene or stainless- steel protective collar at the Ring of Concern
  • Silicone gasket seals
  • Automated port-door functions
  • Automated protective collar
  • Molded medical-grade polymer Beta flange with various bag materials
  • Automated loader system for Alpha/Beta flange decking

CRL offers all its RTPs in 105mm, 190mm, 270mm, and 350mm diameters, corresponding to the Alpha/Beta assembly’s opening. Those sizes are also compatible with the various ancillary components available, with the exception of Single-Use Beta Bags, which are currently only available in 190mm.

Conclusion

The nuclear and life science industries must safely and efficiently produce products that meet all standards for purity and consistency. CRL RTPs have proven for the past quarter-century to be reliable companions for those journeying through the nuclear and life science industries.

About The Author: Rob Weber is the manager of projects & proposals for Central Research Laboratories (CRL), a DESTACO company. He can be reached at rweber@destaco.com.

Central Research Laboratories (CRL)
https://crlsolutions.com