Antisense Oligonucleotide Purification Process: Successes and Challenges During Scale-up

Recently, our first full scale GMP batch for an antisense oligonucleotide was manufactured in the newly built synthesis suite at Biogen. A four-step purification process was then carried out in the existing flexible volume manufacturing facility that, up until this point, has been used for manufacturing Biogen’s protein-based parenterals.  This was our first test case to demonstrate that Biogen can manufacture ASOs safely, at scale, and achieve high purity and yield.  Results are presented on the scalability of the ASO process from bench to GMP scale, highlighting successes and challenges faced with scale-up of the downstream ASO process.
Presented by Robert Gronke, Ph.D., Senior Principal Scientist, Technical Development, Biogen

Robert Gronke is a Senior Principal Scientist in the Technical Department at Biogen, Inc.  For the past 29 years, he’s been involved in the purification development, CMC team leadership, regulatory liaison and new technology assessment for recombinant biopharmaceuticals including Biogen’s commercial products AVONEX (Interferon Beta-1a), a serum-free version of AVONEX, PLEGRIDY (PEG IFN Beta-1a), BENEPALI (Enbrel biosimilar), SPINRAZA (SMA antisense oligonucleotide), APROLIX (Factor IX-Fc), and AMEVIVE (glycosylated fusion protein), along with clinical products including αVβ6, αVβ5, anti-Tau and anti-BDCA monoclonal antibodies, antisense oligonucleotides (SOD-1) and several others.  Rob currently manages a group of 4 associate scientists.
Prior to joining Biogen, Inc., Dr. Gronke was a post-doctoral fellow in the Pharmacology Department at Merck Sharp & Dohme Research Laboratories in West Point, Pennsylvania (1988 – 1989).  He received his Ph.D. degree in Biochemistry from the University of Kansas, Lawrence Kansas in 1987.  Prior to receiving his Ph.D., he was employed as a Research Associate at the University of Illinois, Chicago (1982 – 1983).  Dr. Gronke received a BS degree in Biochemistry from Northern Illinois University, DeKalb, Illinois in 1982.
Followed by Thomas Müller-Späth, Ph.D, CTO at YMC ChromaCon

Thomas Müller-Späth, Ph.D, holds the position CTO at YMC ChromaCon AG, Switzerland. Thomas is the inventor of 10+ patents and has authored and co-authored 30+ scientific articles and book chapters on continuous chromatography for biopharmaceuticals and downstream processing. Thomas frequently presents at international conferences as a speaker and also co-chairs workshops on continuous chromatography.
Thomas studied chemical engineering at the Technical University of Hamburg, Germany, and at the University of California, Berkeley. Thomas gained further R&D experience at Bayer Healthcare in Berkeley, CA, and Beiersdorf, in Hamburg Germany. He obtained his PhD in 2008 in the area of the multi-column-technology for the purification of proteins at the Swiss Federal Institute of Technology (ETH Zurich) in the group of Prof. Morbidelli, where until recently he is also active as a Scientific Advisor.
About YMC/ ChromaCon

Leaders in multi-column chromatography, YMC/ChromaCon has developed and patented novel process principles, process control and simulation software, equipment designs and operating software for batch, cyclic and continuous chromatography. For oligos and peptides these process solutions result in significant yield and purity improvements which are scalable chromatographic solutions. YMC is a Life Science technology company with offices through Asia, India, North America, and Europe. Founded in 1980, and headquartered in Kyoto, Japan, the over 500 employees are providing best-in-class lab and GMP scale process solutions to the bio/pharmaceutical industry; chromatography columns, packing media. resins, LPLC and HPLC bench and GMP scale systems supplier.