Because of its ligand binding capabilities, Protein A has become the most widely used tool for the selective monoclonal antibody (mAb) according to Jonathan Robinson, head of business development at the UK’s National Biologics Manufacturing Centre.
He told Biopharma-Reporter.com this role is likely to continue, explaining that although it accounts for about 30% of the cost of making an mAb, Protein A's efficacy means it is still used more often than alternatives like ion exchange and hydrophobic interaction chromatography.
This view is shared by Repligen - a major manufacturer of Protein A ligands - which told us “Protein A media remains the choice for affinity chromatography due to its exquisite ability to rapidly bind antibodies and only antibodies, while all other proteins and impurities flow through.
“The advantage to Protein A media is that it can achieve in a single step what other methods of purification require multiple steps to achieve,” the firm said, mirroring the opinions of Robinson who added “the regulatory acceptance of Protein A processes means that most people stick with it.”
Repligen continued: “There have been many efforts to develop alternatives to Protein A media over the years, but interest has seemed to decrease. There are more cost-savings to be achieved in other area of the manufacturing process, such as adoption of single-use technologies.”
MAb growth and Protein A sales
Waltham, Massachusetts-headquartered Repligen holds the intellectual property on the latest engineered variants of Protein A, and supplies its ligands to the industry.
The company has long-term supply agreements with GE Healthcare and EMD Millipore (known as Merck Millipore outside North America) who make and sell Protein A media by attaching the ligands to their proprietary beads, and says it expects “annual sales to grow in the range of 8%-10% per year” to reflect the strong growth in the MAb market (over 15% 4-year CAGR 2010-2013).
Furthermore, “potentially groundbreaking anti-PCSK9s (for elevated LDL-C), the anti-PD1s (melanoma, lung and other cancers) and the anti-ILs being studied for severe asthma,” will drive sales of its Protein A.
Whilst the firm is aware of some niche manufacturers of Protein A media who serve a small percentage of the benchtop and pre-clinical use market, any firm looking to compete with Repligen would be subject to a number of barriers of entry, the company continued, including long-term supply agreements, 15 years of technical expertise and security from its dual manufacturing plants.
CORRECTION - The original article stated Repligen was the sole manufacturer of Protein A ligands. This has since been changed to 'major' manufacturer as there are other companies who produce Protein A ligands for use in Protein A resins.