Sterile Connectors and Disconnectors

1. Single-use fluid transfer lines: Sterile connectors in single-use fluid transfer lines improve flexibility and reliability, reducing operational costs compared to stainless steel piping and valves. Applications extend to seed trains and suite-to-suite transfer where they help avoid cross-contamination. Unlike stainless steel assemblies, single-use fluid transfer lines and sterile connectors do not consume time in maintenance, cleaning, and validation in unit operations. They also eliminate the chances of contamination and reduce mobile vessel weight, enabling manufacturers to manage operational cycles more efficiently by quickly changing process steps or converting to a new product.
2. Sterility assurance:  By incorporating flexible, single-use products, manufacturers are experiencing significant advantages and improvements in sterility. As the variety and volume of biopharmaceutical products increase, the demands for change require the operational flexibility, rapid implementation, and reduced costs that sterile connectors offer. With focus on purity and quality in cGMP production, sterile connectors provide a safe, single-use solution, which reduces storage space and cleaning and maintenance costs.
3. Flexible connections:  Sterile connectors can connect small sterile equipment to large equipment (e.g., bioreactors).
4. Non-sterile environments: Sterile connectors can handle bulk material transfer even in non-sterile environments.
   
5. Bioreactor/mixing/in-line sampling: Many flexible sampling lines with biocontainers, bottles, and/or syringes can be linked to each other via sterile connectors, and the entire assembly can be sterilized by autoclaving or gamma irradiation. This sterile connection to the sample point minimizes the risk of false positives.
   

 

For instance, bioreactor sampling at multiple sites requires a large capital investment in equipment, is labor-intensive, and introduces contamination risk. By utilizing a sterile connector for bioreactor sampling at multiple sites, the process is now secured and capital equipment costs and overhead labor can be significantly reduced.

1. What must be considered while choosing sterile connectors or disconnectors?

Manufacturers should carefully assess their application and sterile connection and disconnection requirements before purchase.

• Check if the sterile connector or disconnector can be pre-assembled before sterilizing and using systems
• Confirm if the process system application is clean, aseptic, or sterile
• Confirm the dimensions of the intended tubing and fitting type required (hose barb or sanitary)
• Check all the process parameter requirements for the sterile connection and sterile disconnection 
• Check the chemical compatibility of the process fluid with the sterile connector
• Identify the user interface and confirm the expected level of manual handling and associated training and maintenance required

 

2. What important parameters should be considered while purchasing sterile connectors?

Some factors to be considered are temperature range (especially in autoclaving), pressure range (crucial for single-use systems), flow rate, fluid compatibility, exposure to high temperature, shelf life, and manufacturing environment (check for particulate contamination, and extractables or animal-derived raw material requirements).

 

3. What are the connector types used in biopharmaceutical manufacturing processes?

Connectors cover a wide range of liquid and air applications in biopharmaceutical manufacturing.  Broadly speaking, fluid transfer applications can be split into two types: (1) sterile fluid transfer or (2) non-sterile fluid transfer, each requiring a different type of connection. For sterile fluid transfer between two separate fluid paths, sterile connectors can be used without the need for laminar flow hoods or isolators. 

 

Sterile connections can also be made if a laminar flow hood or isolator is used to ensure sterility is maintained. For non-sterile fluid transfer between two separate fluid paths, connectors such as quick-connects can be used. These fluid transfer connectors are available with different fitting types such as a sanitary fitting or hose barb fitting and a variety of sizes to suit different tubing diameters, making them suited to a wide range of bioprocessing applications.

 

4. Why are single-use systems beneficial in biopharmaceutical processing?

• Eliminate the need for cleaning and validation
• Reduce capital expenditure, fast setup and turnaround times
• Eliminate the risk of cross-contamination
• Enable Quality by Design (QbD), process analytical technology, and continuous processing 
• Provide flexibility for system reconfiguration
• Ideal for multi-product facilities that can be replicated in multiple locations

 

5. What are the various tests performed to validate sterile connectors?

On a broad scale, connectors undergo the following tests:

• Functional (soiling) Testing: Provides information on the ability of the sterilized sterile connector to maintain a sterile fluid pathway after being intentionally contaminated with bacterial spores
• Extractables Testing: Quantification and characterization of extractables from devices in various solvents based on recommendations of the BioPhorum Operations Group (BPOG)
• Compatibility Testing:  Demonstrates the suitability of the connectors with a wide variety of solvents and solutions that are used in biopharmaceutical applications
• Leak Testing: Demonstrates that the integrity of the sealed connectors is not impacted by sterilization or freezing/thawing post-sterilization
• Burst Testing: Subjected to autoclave sterilization, withstanding maximum pressure
• Shelf Life Testing: Subjected to gamma irradiation and accelerated storage conditions to simulate 3 years of storage, proving intact functionality