Single-use systems have risen in popularity for numerous reasons, one being disposability that eliminates cleaning requirements and risk of cross contamination. Disposable hose barb and sanitary flange connectors are crucial to both the assembly of individual process systems and to ensuring a controlled fluid path communication between process systems. Many features of disposable connectors, which have been long proven in critical medical equipment design, are now being integrated into a broad spectrum of biopharmaceutical applications.
Process designers in the biopharmaceutical industry are constantly being challenged to come up with user-friendly, cost-effective systems and components that comply with the industry's strict regulations (and potential concerns). A significant amount of time in this design process is put toward the selection of sanitary fittings, clamps, and tubing connectors for the transfer and management of media, buffers, intermediates, APIs, bulk drug products, and final formulations.
Choosing the right disposable components, however, can be a challenge. Plastic connectors offer more options for material selection, user interface, and customized design than metal connectors. Users often rely on system integrators to recommend connector fittings, but a basic understanding of the options available with plastic connectors will help system designers, integrators, and end-users specify the most optimized features to achieve peak performance in the equipment design.
Connectors may be considered in several categories:
- Traditional fittings, including hose barb and sanitary flange (e.g., hygenic, tri-clamp) and associated clamps
- Quick-connectors and disconnectors, which facilitate aseptic fluid path communication, or closure and separation, under strict environmentally controlled conditions
- Steamable fittings, which enable sterile communication between stainless and single-use polymeric systems
- Sterile connectors and disconnectors, which facilitate sterile or aseptic communication, or closure and separation, between single-use systems under reduced environmentally controlled conditions.
Choosing the most ideal connector first requires a careful assessment of the application and its connection and disconnection requirements. The following must be considered:
- Can connection be pre-assembled prior to system sterilization and/or use?
- What are the dimensions of intended tubing and sanitary fittings?
- What is the process system application—clean, aseptic, sterile?
- What are the process connection and disconnection requirements?
- What is the user interface? Consider the level of human handling expected with the system and connectors or disconnectors.
Once the application is defined, the following are prime factors to be considered:
- Temperature range. Staying within the minimum and maximum temperature tolerances that the connectors will need to function. Depending on connector material, temperature tolerances can range from -70 °C to 93 °C and above. For most single-use systems sterilized by gamma radiation, temperature extremes may not be a concern, but where systems are autoclave sterilized, resistance to steam autoclaving will be crucial. For systems to be frozen, shrinkage, burst pressure, and resistance to embrittlement will be crucial.
- Pressure range. Determining the minimum, maximum, and working pressures that the connectors will be expected to tolerate. With single-use systems, pressure range is typically a crucial concern.
- Flow rate. Assessing the required volume per minute and the effect of fluid pulsation and modulations from connect and disconnect forces. Where the lumen size is comparable to the tubing or pipe diameter, connectors provide little additional resistance. Even if somewhat narrower, the short length of a connector will not reduce flow significantly unless one is operating at high flow rates.
- Fluid compatibility. Analyzing the solvent property, viscosity, sensitivity, and corrosiveness of the fluid, powder, or gas to be moved through the connection.
- Exposure. Be aware of the degree of impact from external or internal conditions, such as UV, wind, dust, vibration, radiation, gases, water submersion, chemicals, or cleaning agents and mechanical stress; radiation resistance, cleanliness.
- Manufacturing environment. Molded and extruded plastics are typically low in particulates, bioburden, and free of endotoxins by the nature of their manufacturing process. Visible particles ("flash") may be generated in the mold release step, however, if not well controlled. Review manufacturing conditions with connection supplier or integrator to maintain cleanliness and minimize risk of particulate contamination.
- Extractables, animal-derived raw materials. Due to the small contact surface area of connectors relative to the total contact area of a single-use system, as well as the small surface area to process fluid volume ratio, extractables from connectors will generally not contribute significant amounts of migrants (potential leachables ) to the process. Pre-qualification per United States Pharmacopeia (USP) <87> or <88> Biological Reactivity Tests will generally be sufficient. Extractables can also be reviewed for absence of International Conference on Harmonization (ICH) Q3 Class 1 Solvents and any known genotoxicants, which should be avoided.
The requirements of the application will then determine what materials would be best suited for the connectors.