Protein A alternatives

The Protein A Debate: should we still be looking for alternatives?

Protein A alternativesInterest in researching a cost effective alternative to Protein A has waned in current years. Should we still be on the lookout for other methods of antibody extraction?

Protein A is an essential but costly tool in the manufacture of most monoclonal antibodies (MAb). Protein A makes up approximately 30% of the total cost of production and in the past this has prompted researchers to look into cost effective alternatives. However, this interest seems to have died down in recent years despite the sales of Protein A increasing. In fact, Repligen expect sales of various forms of Protein A to increase by 8-10% per year and further developments in PCSK9 and anti-PD1 driving up sales of Protein A could potentially double Repligen’s earning power. So why has industry productivity slowed down when there is clearly a gap in the market?

Many alternatives to Protein A have been suggested over the past few years, those involving single use membrane chromatography, HCIC (hydrophobic charge interaction chromatography), two step processes, mixed-mode resins and affinity by mimetic Ligans have all been investigated.

Efficiency and yield of alternatives is still not matching up to protein A. Here are some of the key reasons why:

–          Lower binding capacity.

–          They are multistage processes taking up more space and time than the column extraction used with protein A.

–          Lack of Regulatory acceptance compared to Protein A.

–          Easier methods of lowering the cost of production i.e single use technologies, major biotech companies are looking at different stages of processing in which to lower costs rather than the chromatography stage.


Despite promising advances in alternative methods, Protein A looks set to maintain its status as the leading reagent in the extraction of MAb in the future.  If you can think of any other methods or reagents which could potentially rival protein A in extraction of MAb in the future please don’t hesitate to comment below. Or perhaps you are a firm believer in the benefits of Protein A for mAb extraction compared with other methods? Then let us know about it!

If you would like to discuss advances in Protein A or any other recent developments in bioprocessing in person feel free to come down to our Biopharma networking event on Tuesday 5th August in London or come to our meeting Downstream Processing World 2015 on 24-26 February 2015 in Munich.