Downloaded from journal.pda.org on May 4, 2015
Proceedings of the 2013 Viral Clearance Symposium (Princeton, NJ) David Roush, Kurt Brorson and Rich Levy
PDA J Pharm Sci and Tech 2015, 69 140-141 Access the most recent version at doi:10.5731/pdajpst.2015.01053
Downloaded from journal.pda.org on May 4, 2015
CONFERENCE PROCEEDING
Proceedings of the 2013 Viral Clearance Symposium (Princeton, NJ) Viral clearance and inactivation by the bulk protein purification process are a critical component of the overall strategy to ensure the safety of therapeutic proteins derived from mammalian cell culture. A mechanistic understanding of the factors that influence viral clearance and inactivation are essential for ensuring that adventitious agent control is conserved as downstream unit operations are refined and implemented within a design space via a quality by design (QbD) approach or under “modular” operating conditions. The ability to leverage large databases (1) of information on viral clearance has also fostered specific hypothesis-driven experiments that can be performed to address known gaps in mechanistic knowledge. A shared recognition of the (1) critical nature of viral clearance, (2) acknowledged limitations in mechanistic understanding, and (3) opportunities for improvement led to the initiation of the Viral Clearance Symposia Series in 2009. The focus of that first meeting, held in Indianapolis, IN, was to review the current state of viral clearance for specific unit operations, to discuss lessons learned, and to chart a course to experimentally address the gaps. Proceedings were subsequently published in Developments in Biologicals in 2010 (2). The 2 nd Viral Clearance Symposium was held in 2011 in South San Francisco, CA to extend progress made in the 2009 meeting by focusing on research progress to close the gaps identified during the 2009 Symposium, discussing an integrated adventitious agent control strategy and associated risk assessment. It also addressed topics such as QbD approaches to viral clearance, a critical assessment of emerging technologies (e.g., Mixed-Mode Chromatography, Anion Exchange [AEX] Membrane adsorbers) as well as applications of High-Throughput Screening (HTS) to evaluate mechanisms of virus partitioning and clearance. Proceedings from the 2 nd Viral Clearance Symposium were published in a
doi: 10.5731/pdajpst.2015.01053
140
total of 11 articles in the PDA Journal (Vol. 68) in early 2014. The 3rd Viral Clearance Symposium was held in 2013 in Princeton, NJ. The meeting included a review of the follow-up items from the 2nd Viral Clearance Symposium, discussions on addressing gaps in traditional unit operations (e.g., viral filtration, AEX chromatography, protein A chromatography). We also covered new approaches to viral inactivation and clearance (e.g., High-Temperature/Short Time (HTST) treatment as a viral barrier, impact of impurities on membrane adsorbers). Finally, there were several case studies on implementation of an integrated adventitious agent control strategy linking upstream and downstream processes as well as the impact of host cells on viral clearance strategy. Some key highlights of the 3rd Viral Clearance Symposium were significant progress on further understanding “outliers” and mechanistic gaps in traditional unit operations. One topic was an extensive review of approaches and tools to characterize the impact of depressurization on viral filtration performance and potential linkage to virus breakthrough. Another key item was the observation that breakthrough of impurities in AEX chromatography appears to correlate with virus breakthrough. Although further research is required to demonstrate the general applicability of this approach, there is a potential to utilize impurity breakthrough as a surrogate marker for virus breakthrough. This is a big advance because impurity breakthrough is easier to measure in a robust and effective manner. An insightful experimental approach was presented that helped to further explain the mystery behind variable viral clearance observed in protein A chromatography. Results of this approach provide clues explaining this observation; a portion of virus can associate with monoclonal antibodies bound to the protein A ligand - an association that can be disrupted or enhanced via modification of the chromatography buffer conditions. In this issue of the PDA Journal the summarized findings and next steps from the 2013 3rd Viral Clearance Symposium are presented. PDA Journal of Pharmaceutical Science and Technology
Downloaded from journal.pda.org on May 4, 2015
References 1. Miesegaes, G., Lute, S., and Brorson, K. Analysis of Viral Clearance Unit Operations for Monoclonal Antibodies. Biotechnology and Bioengineering 2010, 106 (2) 238 –246. 2. Miesegaes, G., Bailey, M., Willkommen, H., Chen, Q., Roush, D., Blu¨mel, J., Brorson, K. Proceedings of the 2009 Viral Clearance Symposium. Dev. Biol. (Basel) 2010, 133, 3–101. David Roush Senior Principal Scientist Merck, Sharp and Dohme Biologics Process Development Kenilworth, NJ Kurt Brorson Research Biologist Division of Monoclonal Antibodies Center for Drug Evaluation and Research U.S. Food and Drug Administration Silver Spring, MD Rich Levy Senior Vice President, Scientific and Regulatory Affairs Parental Drug Association Bethesda, MD
Vol. 69, No. 1, January–February 2015
141
Downloaded from journal.pda.org on May 4, 2015
An Authorized User of the electronic PDA Journal of Pharmaceutical Science and Technology (the PDA Journal) is a PDA Member in good standing. Authorized Users are permitted to do the following: ·Search and view the content of the PDA Journal ·Download a single article for the individual use of an Authorized User ·Assemble and distribute links that point to the PDA Journal ·Print individual articles from the PDA Journal for the individual use of an Authorized User ·Make a reasonable number of photocopies of a printed article for the individual use of an Authorized User or for the use by or distribution to other Authorized Users Authorized Users are not permitted to do the following: ·Except as mentioned above, allow anyone other than an Authorized User to use or access the PDA Journal · Display or otherwise make any information from the PDA Journal available to anyone other than an Authorized User ·Post articles from the PDA Journal on Web sites, either available on the Internet or an Intranet, or in any form of online publications ·Transmit electronically, via e-mail or any other file transfer protocols, any portion of the PDA Journal ·Create a searchable archive of any portion of the PDA Journal ·Use robots or intelligent agents to access, search and/or systematically download any portion of the PDA Journal ·Sell, re-sell, rent, lease, license, sublicense, assign or otherwise transfer the use of the PDA Journal or its content ·Use or copy the PDA Journal for document delivery, fee-for-service use, or bulk reproduction or distribution of materials in any form, or any substantially similar commercial purpose ·Alter, modify, repackage or adapt any portion of the PDA Journal ·Make any edits or derivative works with respect to any portion of the PDA Journal including any text or graphics ·Delete or remove in any form or format, including on a printed article or photocopy, any copyright information or notice contained in the PDA Journal
Proceedings of the 2013 Viral Clearance Symposium (Princeton, NJ) David Roush, Kurt Brorson and Rich Levy
PDA J Pharm Sci and Tech 2015, 69 140-141 Access the most recent version at doi:10.5731/pdajpst.2015.01053
Downloaded from journal.pda.org on May 4, 2015
CONFERENCE PROCEEDING
Proceedings of the 2013 Viral Clearance Symposium (Princeton, NJ) Viral clearance and inactivation by the bulk protein purification process are a critical component of the overall strategy to ensure the safety of therapeutic proteins derived from mammalian cell culture. A mechanistic understanding of the factors that influence viral clearance and inactivation are essential for ensuring that adventitious agent control is conserved as downstream unit operations are refined and implemented within a design space via a quality by design (QbD) approach or under “modular” operating conditions. The ability to leverage large databases (1) of information on viral clearance has also fostered specific hypothesis-driven experiments that can be performed to address known gaps in mechanistic knowledge. A shared recognition of the (1) critical nature of viral clearance, (2) acknowledged limitations in mechanistic understanding, and (3) opportunities for improvement led to the initiation of the Viral Clearance Symposia Series in 2009. The focus of that first meeting, held in Indianapolis, IN, was to review the current state of viral clearance for specific unit operations, to discuss lessons learned, and to chart a course to experimentally address the gaps. Proceedings were subsequently published in Developments in Biologicals in 2010 (2). The 2 nd Viral Clearance Symposium was held in 2011 in South San Francisco, CA to extend progress made in the 2009 meeting by focusing on research progress to close the gaps identified during the 2009 Symposium, discussing an integrated adventitious agent control strategy and associated risk assessment. It also addressed topics such as QbD approaches to viral clearance, a critical assessment of emerging technologies (e.g., Mixed-Mode Chromatography, Anion Exchange [AEX] Membrane adsorbers) as well as applications of High-Throughput Screening (HTS) to evaluate mechanisms of virus partitioning and clearance. Proceedings from the 2 nd Viral Clearance Symposium were published in a
doi: 10.5731/pdajpst.2015.01053
140
total of 11 articles in the PDA Journal (Vol. 68) in early 2014. The 3rd Viral Clearance Symposium was held in 2013 in Princeton, NJ. The meeting included a review of the follow-up items from the 2nd Viral Clearance Symposium, discussions on addressing gaps in traditional unit operations (e.g., viral filtration, AEX chromatography, protein A chromatography). We also covered new approaches to viral inactivation and clearance (e.g., High-Temperature/Short Time (HTST) treatment as a viral barrier, impact of impurities on membrane adsorbers). Finally, there were several case studies on implementation of an integrated adventitious agent control strategy linking upstream and downstream processes as well as the impact of host cells on viral clearance strategy. Some key highlights of the 3rd Viral Clearance Symposium were significant progress on further understanding “outliers” and mechanistic gaps in traditional unit operations. One topic was an extensive review of approaches and tools to characterize the impact of depressurization on viral filtration performance and potential linkage to virus breakthrough. Another key item was the observation that breakthrough of impurities in AEX chromatography appears to correlate with virus breakthrough. Although further research is required to demonstrate the general applicability of this approach, there is a potential to utilize impurity breakthrough as a surrogate marker for virus breakthrough. This is a big advance because impurity breakthrough is easier to measure in a robust and effective manner. An insightful experimental approach was presented that helped to further explain the mystery behind variable viral clearance observed in protein A chromatography. Results of this approach provide clues explaining this observation; a portion of virus can associate with monoclonal antibodies bound to the protein A ligand - an association that can be disrupted or enhanced via modification of the chromatography buffer conditions. In this issue of the PDA Journal the summarized findings and next steps from the 2013 3rd Viral Clearance Symposium are presented. PDA Journal of Pharmaceutical Science and Technology
Downloaded from journal.pda.org on May 4, 2015
References 1. Miesegaes, G., Lute, S., and Brorson, K. Analysis of Viral Clearance Unit Operations for Monoclonal Antibodies. Biotechnology and Bioengineering 2010, 106 (2) 238 –246. 2. Miesegaes, G., Bailey, M., Willkommen, H., Chen, Q., Roush, D., Blu¨mel, J., Brorson, K. Proceedings of the 2009 Viral Clearance Symposium. Dev. Biol. (Basel) 2010, 133, 3–101. David Roush Senior Principal Scientist Merck, Sharp and Dohme Biologics Process Development Kenilworth, NJ Kurt Brorson Research Biologist Division of Monoclonal Antibodies Center for Drug Evaluation and Research U.S. Food and Drug Administration Silver Spring, MD Rich Levy Senior Vice President, Scientific and Regulatory Affairs Parental Drug Association Bethesda, MD
Vol. 69, No. 1, January–February 2015
141
Downloaded from journal.pda.org on May 4, 2015
An Authorized User of the electronic PDA Journal of Pharmaceutical Science and Technology (the PDA Journal) is a PDA Member in good standing. Authorized Users are permitted to do the following: ·Search and view the content of the PDA Journal ·Download a single article for the individual use of an Authorized User ·Assemble and distribute links that point to the PDA Journal ·Print individual articles from the PDA Journal for the individual use of an Authorized User ·Make a reasonable number of photocopies of a printed article for the individual use of an Authorized User or for the use by or distribution to other Authorized Users Authorized Users are not permitted to do the following: ·Except as mentioned above, allow anyone other than an Authorized User to use or access the PDA Journal · Display or otherwise make any information from the PDA Journal available to anyone other than an Authorized User ·Post articles from the PDA Journal on Web sites, either available on the Internet or an Intranet, or in any form of online publications ·Transmit electronically, via e-mail or any other file transfer protocols, any portion of the PDA Journal ·Create a searchable archive of any portion of the PDA Journal ·Use robots or intelligent agents to access, search and/or systematically download any portion of the PDA Journal ·Sell, re-sell, rent, lease, license, sublicense, assign or otherwise transfer the use of the PDA Journal or its content ·Use or copy the PDA Journal for document delivery, fee-for-service use, or bulk reproduction or distribution of materials in any form, or any substantially similar commercial purpose ·Alter, modify, repackage or adapt any portion of the PDA Journal ·Make any edits or derivative works with respect to any portion of the PDA Journal including any text or graphics ·Delete or remove in any form or format, including on a printed article or photocopy, any copyright information or notice contained in the PDA Journal
