Performance Results

Table 1. Impurity profiles and classifications for various therapeutic monoclonal antibodies using the platform processes outlined in this article

Figure 3. Graph of the log viral clearance values obtained for the therapeutic antibodies shown in Table 1. The changes in color correspond to the processes outlined in Figure 1. From left to right: original process, process 2, process 3, and current process.

The current process, as shown in Figure 1, provides Pfizer with a combination of purification and virus clearance robustness, allowing us to quickly move products into the pilot plant for clinical manufacturing, thus accelerating progress toward the clinic. Even though the other processes shown in Figure 1 also met these criteria, they did not meet our new standard for robustness established by increasing product titers. A process was needed that was more adept at handling changes in the composition of the cell culture broth as well as unexpected increases in titer following scale-up, requiring additional column capacities. Although the current process bucks the trend of reducing the number of unit operations, it increases the chance of meeting the purification needs of a greater number of projects in a shorter time frame. These early-phase purification processes can be optimized further once proof of concept has been achieved.

Next Steps

As cell culture titers continue to increase, the biopharmaceuticals industry will be faced with new challenges, including greater product heterogeneity and increasing impurity levels. As scale increases for early-phase manufacturing, resin capacity must increase to minimize operating costs, and therefore, it will be necessary to carry out studies to determine the impact of these changes on virus clearance and the removal of impurities. If increased capacity cannot meet these needs, alternative separation methods such as simulated moving bed chromatography will become paramount.

It also will become necessary to increase the throughput of nanofiltration devices, so that they do not become the next process bottleneck. In addition, we must develop new technologies for ultrafiltration to meet the need for high-concentration drugs used for subcutaneous injection. These are just some of the challenges facing the industry today.