Comparative TOC Rinse-Up Study Of Pharmaceutical Tubing
Introduction
Total organic carbon (TOC) content provides a measure of the cleanliness of single-use materials and components considered for use in pharmaceutical manufacturing processes. A material’s cleanliness is a critical quality attribute to establish fitness for purpose in a variety of applications. For example, the selection of appropriate tubing can be assessed by determining TOC levels as a function of rinse-up volume using water. TOC measures the total amount of organic compounds containing carbon atoms that can be oxidized. TOC measurements do not differentiate among the contributing chemical organic species. TOC measurement is therefore considered a high level marker. In this technical bulletin, the results of a rinse up study to measure the TOC from four different tubing types is presented. BioFlex® TPE, C-Flex® 374, Colorite PVC, and Dow Corning® Pharma 50 silicone tubing were each rinsed with deionized (DI) water, which was then sampled and analyzed off-line to determine the TOC content from each.
Materials and Methods
One 10 ft. length of ¼” ID x ⅜” OD tubing segment for BioFlex® TPE (Meissner Filtration Products part no. 91T49G33), C-Flex® 374 (Saint Gobain, part no. 374-250-2), PVC (Colorite, part no. 7088G-015), and Dow Pharma 50 Silicone (Dow Corning, part no. 4007687) was gamma irradiated at 28.0-35.2 kGy and tested 35-37 days post gamma. Each 10 ft. tubing segment was rinsed with DI water in a single pass at a flow rate of 5.0 ± 0.5 L/min. DI samples were collected in clean HDPE bottles at the end of each tubing segment in increments of 60 mL. “Blank” samples were collected immediately before each tubing segment was connected to the in house DI water line. All rinse-up tubing samples were analyzed using an Anatel® Access 643 TOC analyzer. Three TOC measurements were taken from each sample collected. All TOC measurements from the rinse up samples were averaged and corrected for the average TOC measurement from the Blank samples.
Results and Discussions
The results of comparative TOC rinse-up for tubing are shown in Figure 1. Measurements from BioFlex® TPE tubing were the lowest among the four tubing types, with 43 ppb TOC for the first 60 mL, then decreasing to background levels. C-Flex® 374 followed a similar decreasing pattern, but with a higher measurement of 140 ppb TOC from the initial 60 mL collection. Dow Pharma 50 tubing contained 144 ppb TOC initially, and decreased to 29 ppb TOC at 480 mL volume. The Colorite PVC tubing did not show any consistent decreasing trend and had high and low measurements of 326 ppb and 251 ppb TOC, respectively. These results indicate that the choice of tubing type has a significant impact on TOC of the rinse water. Furthermore, the study shows that TOC levels can decrease significantly with DI water rinsing, and the degree of the reduction is highly dependent upon the material composition of the tubing.
Conclusion
The TOC content of tubing presents a high level marker to assess a material cleanliness and help determine a material’s fitness for use in pharmaceutical processes. This study measured TOC levels from water rinsing of four 10 ft. ¼” ID x ⅜” OD tubing segments, which were selected from four different manufacturers: BioFlex® TPE (Meissner Filtration Products), C-Flex® 374 (Saint Gobain), PVC (Colorite), and Dow Corning® Pharma 50 Silicone (Dow Corning). The results indicate that BioFlex® TPE tubing had the lowest initial TOC level. Tubing TOC levels decreased for BioFlex® TPE, C-Flex® 374 and Dow Pharma 50 with increased rinse up volume. BioFlex® TPE TOC measurements decreased to background levels at a rinse up volume of 0.12 L while C-Flex® 374 required 0.24 L to reach backgrounf TOC measurements. Colorite PVC tubing had the highest TOC measurement without any significant decrease within the first 480 mL flush volume.
Figure 1. Results of comparative TOC rinse up for tubing types.