The results indicate that for the representative antibodies shown for the different process permutations, the current purification scheme as outlined is sufficient to produce an acceptable product. A few of the antibodies required minor changes to the platform process to produce the desired product purity, as explained in Table 1. Figure 3 shows the overall virus reduction achieved for the early-phase representative antibodies in the different platform processes. Again, the results indicate that all processes achieved satisfactory viral clearance. However, the current process is advantageous as we increase column capacities to accommodate increasing titers, as insurance for acceptable virus clearance results.
Platform Status
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.