Total Organic Carbon
The membrane cassette and the UF-DF system should be flushed with water after cleaning to displace cleaning and storage solutions
and to remove residual process material. TOC measurements of the permeate and the retentate flush streams provide a reliable
and highly sensitive means of detecting organic contamination in the system that may arise from product carryover resulting
from poor cleaning procedures. In addition, a mock UF-DF run, containing no protein in the load, was performed after the normal
cleaning procedure had been implemented following the tenth UF-DF cycle. A mock pool was recovered and analyzed for TOC. The
results, shown in Figure 4, indicate that the TOC was less than 1,000 ppb (1.0 ppm) for all the runs except for runs two and
four. The higher TOC content in runs two and four was likely because of the holding of the flush at room temperature for two
weeks until the test could be performed.
The TOC content of the mock run flushes of the retentate–permeate flush was 255 ppb, less than the 500 ppb USP limit for water
for injection (WFI). This result indicates that the cleaning protocol was very effective in removing any residual monoclonal
Residual Total Chlorine Content
Table 3 summarizes the residual total chlorine content measured in the pre-use water flush of the cassettes for the 10 cycles.
These results demonstrate that total chlorine is reduced adequately by the pre-use flush procedures that were implemented
in the studies.
Table 3. Chlorine content after cleaning the ultrafiltration-diafiltration system
This study evaluated a cleaning procedure for polyethersulfone membranes using a Millipore Biomax 30kD membrane. The results
showed that the cleaning solution of 0.5N NaOH with 250 ppm NaOCl at room temperature was effective in cleaning the membrane,
following execution of an ultrafiltration–diafiltration step in a monoclonal antibody process. One 30-min cycle of cleaning
the membrane with 3.0 L of cleaning solution per square-meter membrane area was sufficient to recover the normalized water
permeability to 90% of its initial value. This cleaning methodology also ensures reproducibility of process flux and results
in low total organic carbon (< the USP limit for WFI), and low residual chlorine content in the subsequent UF-DF process step.
These studies demonstrate the adequacy of the cleaning procedure for a PES membrane in a specific device. Although the authors
anticipate that the procedure is broadly applicable, additional testing on other devices is needed to ensure compatibility
with the non-membrane components of the specific device.