Maintaining Integrity: Effects of SIP Sterilization on PTFE Valve Diaphragms

The fully automated and computer-integrated test equipment monitored and controlled steam temperature, pressure, and valve actuation, providing real time data display and collection. The system was also pre-programmed for automatic control and sequencing of SIP cycle heat-up, exposure and cool-down stages.

The SIP sterilization procedure was based on field Case 3 above. The valve was actuated by circulating clean water at 25°C/70 psi. After each 100 actuations, the valve was set to full open position and the PTFE diaphragm was SIP sterilized. SIP cycle parameters were 145°C/45 psi steam for 20 minutes exposure, followed by fast water quench cooling. The valve and PTFE diaphragm underwent a total of 40,000 actuations and 400 SIP cycles. The SIP parameters for heat-up, exposure and cool-down were automatically plotted for steam temperature and pressure, as shown in Figure 5.

Actual average SIP cycle parameters were 145°C (295 °F)/49 psi for 20 minutes. During the SIP cycle, the PTFE diaphragm was also subjected to steam conditions of 152°C (305°F)/60 psi for two minutes, due to a steam pressure spike caused by the pressure regulator. The plot also shows that the PTFE diaphragm was very rapidly cooled to ambient temperature with the cold water quench.

Figure 5. SIP Cycle Steam Temperature and Pressure Plots

The valve was disassembled and the PTFE diaphragm was inspected after each 10,000 valve actuations and 100 SIP cycles. Small blisters were first noted during the initial inspection at 100 SIP cycles. During subsequent inspections at 200 and 300 cycles the blisters progressively increased in size and number. The final condition of the diaphragm after 400 SIP cycles is shown in Figure 6. Blisters formed on both the front and back, indicating permeation through the PTFE diaphragm. The blisters leaked small amounts of clear liquid when cut open for examination. In addition, the diaphragm again sustained external bead deformation, flex stresses and permeation damages. Steam permeation caused the EPDM backing diaphragm to soften, split and adhere to the PTFE diaphragm.

The inset photo in Figure 6 depicts internal morphology of the blisters taken with a high-power digital camera microscope. The photo clearly shows blistered expansions and crevices, which could harbor microbes and compromise sterility if they split open under continual operation.

Figure 6. Modified PTFE Diaphragm with SIP Induced Blisters

Mechanics of Blister Formation
Liquids and gases will permeate PTFE to different extents depending upon pressure and temperature.  Permeation involves molecular-level diffusion into PTFE, and is accelerated by an increase in temperature and pressure. Small molecule liquids and vapors will permeate PTFE more quickly than large molecules. Steam is a small-molecule permeant known to cause blisters in PTFE pipe liners during steam-cold water thermal cycling tests [15]. The PTFE-lined pipes withstand temperatures up to 260°C (500°F) and can be used in continuous steam up to 177°C (350°F) without adverse effects. However they should not be used in steam-cold water cycling due to stress-cracking and blistering [16]. PTFE components such as steal-braided hoses and tubes also can be used successfully in continuous steam applications up to 198°C (388°F), but again they are not recommended for steam-cold water cycling [17].

Blistering of PTFE diaphragms during SIP has largely caught the pharmaceutical and bioprocessing industries by surprise. Referenced literature sources are vague and do not provide clear explanations of this phenomenon. SIP sterilization produces a temperature and pressure gradient in the PTFE diaphragm, causing absorption of small amounts of steam vapor, which condenses within the diaphragm upon rapid cooling. When steam is reintroduced for the next SIP cycle, the entrapped water expands to vapor, forming micropores. In poorly manufactured PTFE diaphragms containing voids, steam vapor will also condense in these voids. Repeated pressure and thermal cycling expands these micropores and voids, ultimately forming water-filled blisters. These blister formations depend on SIP cycle frequency, exposure time, temperature, pressure of the saturated steam and the rate of cooling. During slow cooling, temperature and pressure decrease gradually allowing steam vapor to diffuse out of PTFE diaphragms. During rapid cooling, temperature and pressure decrease more quickly than the steam vapor can diffuse out of the part.

The new trend of high-temperature and high-pressure SIP cycles to achieve faster sterilization of cold spots in aseptic system are subjecting upstream PTFE diaphragms to more aggressive sterilization and cooling conditions. As a result, these diaphragms are more prone to failure from cracking, splitting, deformation and SIP steam-induced blisters.

Conclusions and Recommendations
SIP sterilization is critical to the operation of pharmaceutical and bioprocessing facilities. Demands for increased production, frequent batch changes, higher-temperature sterilization, and rapid cooling are causing diaphragm failures, including SIP-induced blisters that can compromise sterility if not detected and replaced early enough.

To avoid such failures, plant owners and operators can more precisely control SIP parameters, notably steam temperature and pressure. Equipment and piping systems can be thermally insulated to minimize heat losses and improve temperature uniformities during SIP cycles. Thermal insulation can also serve to lower steam temperature and pressure and reduce SIP cycle times by heating cold spots more efficiently.