Cleaning Polyethersulfone Membranes After Ultrafiltration-Diafiltration in Monoclonal Antibody Production - Polyethersulfone membranes can be cleaned safely, effectively, and economically. - BioPharm
In the pharmaceutical industry, ultrafiltration (UF) membranes are used extensively in the downstream purification of recombinant
proteins or monoclonal antibodies. However, the fouling of membranes after a unit operation—especially when recombinant proteins
or monoclonal antibodies are highly concentrated—is a common problem. Typically, normalized water permeability (NWP) of a
membrane can be reduced to about 20 percent of its original permeability at the end of an ultrafiltration-diafiltration (UF-DF)
operation.
Several reports describe membrane cleaning procedures using acid, alkali, high temperature, enzymes, and hypochlorite.1-6 These methods, which often involve extensive cleaning with a series of chemical reagents, are time-consuming, unsafe, or
expensive. For example, using NaOH combined with high temperature is effective for cleaning the membranes,2,6 but poses safety concerns in the laboratory and in manufacturing operations. Enzymatic cleaning is relatively safe, but
can be expensive.5,6 More recently, an abstract by Davis and Abraham described the use of NaOH and hypochlorite for UF membrane cleaning, but
it contained limited detailed information.7 Consequently, there is a great need to develop an effective, safe, economical, and easily scalable cleaning method for the
UF-DF operation.
Manufacturers often choose polyethersulfone (PES) membranes for applications requiring high-flux, low-to-moderate protein
binding, and high resistance to chemical cleaning and sanitization solutions. This article describes an effective, safe, and
economic approach for cleaning a PES membrane at ambient temperature, using a scale-down simulation of the antibody UF-DF
process with a cleaning solution of 250 ppm sodium hypochlorite in 0.5 M NaOH. The solution is fairly generic and can be used
on most PES membranes. We show the results after 10 cycles of cleaning the membrane post UF-DF, in which the water permeability
of the membrane was maintained. We also present total organic carbon (TOC), residual chlorine content, and process flux test
data to demonstrate the effectiveness of cleaning and the ability to wash out the cleaning reagent.
MATERIALS AND METHODS
Ultrafiltration Modules
Figure 1. Experimental set-up
This study was carried out by using two PES Biomax 30kD cassettes with C-screen (0.01 m2 total area) in a Pellicon XL Labscale system (Millipore Corporation, Billerica, MA) with an external peristaltic pump. The
Pellicon XL devices were chosen to conserve the amount of protein and buffers needed for the trials. The experimental set-up
is shown in Figure 1. The cleaning method and operation conditions for the study are shown in Table 1 and a UF-DF cleaning
process flow diagram, together with controls for cleaning effectiveness, is shown in Figure 2.
RESULTS AND DISCUSSION
Figure 2. Ultrafiltration-diafiltration cleaning process. Cleaning solution: 250 ppm NaOCl in 0.5 M NaOH. Storage solution:
0.1 N NaOH
The parameters used to measure the effectiveness of cleaning were NWP, process flux, TOC, and residual chlorine content.
