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.
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.
The antibody purification platform process used in Pfizer's Global Biologics organization has undergone changes over the years
in response to increases in both production scale and cell culture titers. These changes have resulted in a purification scheme
that takes advantage of previous knowledge to reduce development time, while ensuring that product purity and virus clearance
are sufficient for clinical manufacture. The goal is to manufacture early-phase material without having to perform downstream
development, and the current process as outlined in Figure 1 is capable of meeting that goal. However, further increases in
titer will likely bring more challenges, and thus it will be necessary to implement additional modifications to our process
to keep pace with increasing upstream productivity.
We would like to acknowledge the entire purification group in Global Biologics for their help, as well as the cell culture
groups for their provision of the cell culture broth necessary to complete these studies. In addition, these studies would
not have been possible without the support of the process development analytics group.
JUDY GLYNN is senior principal scientist, TIMOTHY HAGERTY is scientist, TIMOTHY PABST, PhD, is senior scientist, GOPINATH ANNATHUR is senior scientist, KRISTIN THOMAS is senior scientist, PAUL JOHNSON is scientist, and NATARAJAN RAMASUBRAMANYAN, PhD, is an associate research fellow, and PAUL MENSAH, PhD, is an associate research fellow, all at Pfizer Global Research and Development Global Biologics, Bioprocess R&D, Chesterfield,
MO, 636.247.6519, firstname.lastname@example.org
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