April 1, 2006 (Vol. 26, No. 7)
Ensuring the Quick, Safe, and Sterile Transfer of Fluids for Disposable Process Equipment
Disposable process equipment demands reliable and fast sterile connecting devices. Two of the important issues in disposable manufacturing are ensuring the quick, safe, and sterile transfer of fluids and not forgeting that every transfer needs to be disconnected after use.
Thermal tube fusing is one of the safest and most flexible ways to meet those requirements, and it uses well-known heat sterilization technology. As the existing thermoplastic tubing can be used for the connection of presterilized assemblies, it also avoids costly additional sterile connectors and clamping-off procedures.
When a sterile tube welder is used in pharmaceutical processes, there are important factors that can help to evaluate the right equipment.
Making a thermal hose connection requires that the tubing quality is manufactured out of a thermo polymer that can be fused together under heat influence and has good bonding characteristics.
Hose materials like C-Flex and Tygon meet these requirements, have been successfully used for such applications, and have a long proven history of biocompatibility. New materials like SaniPure can be used for sterile hose welding as well. Other hoses are more difficult to fuse due to their composition and require that a thermo welder be specifically set up for them-.
The important parameters are always temperature, compression, and temperature contact time. Products that are made from silicone cannot be used for a thermal tube connection, as silicone has no thermal bonding characteristics.
One of the major issues in contamination prevention is ensuring that the tubing is completely compressed at the section where the hot blade cuts through before fusing. The importance of this is to assure that the hot sterile blade melts through the compressed section and seals it immediately on both sides.
This also avoids remaining media in the inner hose bore contacting the hot blade and causing burned media or gases (particles) inside the sterile fused hose. During the aligning and fusing process, the compressed sections must be kept sealed to avoid contamination.
It is well known that dry heat is effective for sterilization. It is therefore essential for the hose welding equipment to provide reproducible temperature control as well as a programmable temperature profile.
In this profile the equipment must ensure that the surface temperature of the cutting blade is high enough to provide sufficient inactivation for the time the blade is disconnecting and fusing the hoses together. The D-value of this process can be calculated as follows.
The D-value (time to reach 10log reduction in bioburden) of this process can be calculated according to:
D(T) = Dref x 10(Tref-T)/Z
F(T) = Fref x 10(Tref-T)/Z
In this equation the D-value at a certain temperature can be calculated with the difference between a reference temperature (Tref) and the sterilizing temperature (T). The z-value is the temperature increase in C needed to obtain an extra 10log bioburden reduction.
Depyrogenization procedures typically require an exposure of 30 sec at 250C or 3 sec at 320C. Using an exposure over 350C for 1 sec exceeds this requirement.
Equipment should provide validation guidelines that describe parameters such as depyrogenation temperature, welding temperature, and welding time. Calibration certificates should also be available with the validation package.
Implementing the right sterile tube fuser in bioprocess applications, such as a connecting disposable bag, biosampling manifolds, and upstream and downstream process equipment, can be done easily and efficiently without the need for additional equipment or sterile connect devices.