The Purification Insights Blog

Just before the Christmas break, Lars, Haneskog, Bio-Works R&D Director, presented a new and proven strategy for downstream processing at the New Horizons in Biologics and Bioprocessing conference. It was met with great interest and several enquiries and, for those that missed it, we asked Dr. Haneskog to give us a brief summary of what was discussed.

Improving downstream bioprocess economy depends on fine-tuning an enormous range of parameters, from culture and harvesting to purification and final polishing. Success depends on the ability to troubleshoot difficulties and identify novel approaches that will boost process efficiency in a cost-effective manner. This is particularly true when high-value chromatography columns are used in the process. Bioburden and cleaning-in-place procedures can reduce column lifetime and capacity, and threaten product quality and yield. An alternative approach that protects these valuable columns is to reverse the first two steps to remove the potentially damaging components of a feedstock before proceeding with highly selective capture followed by polishing. We call this ECP... 

Peptide therapeutic agents are enjoying increasing success but they are challenging to produce and, not least, to purify. Purity requirements are, in fact, approaching those for small molecules. Synthesis generates a crude mixture containing failed sequences and chemical variants. 

The environmental impact of pharmaceutical R&D and production is considerable. Although the industry is rather conservative and also constrained by regulatory guidelines, there is increasing interest in the implementation of sustainable practices that not only improve corporate social responsibility (CSR) performance but also reduce costs and increase efficiency. This effort is embodied in the concept of Green Chemistry and includes reducing the use of toxic solvents in production and purification, which is a considerable problem. Solutions include recycling and the use of upstream protective columns that remove bioburden to increase the life-cycle of columns used downstream, or even make certain solvent-consuming steps redundant altogether.

When it comes to many serious and challenging diseases, healthcare has reached a point of unsustainability, due to drug costs. For example, sustained therapy for an autoimmune disease or cancer, involving large amounts of monoclonal antibodies (mAbs), might not be a viable option for simple economic reasons. As a consequence, healthcare authorities want to reduce the cost of drugs by encouraging the development of biosimilars. When biological drugs are off-patent they can be copied – which is cheaper than developing the novel drug, but still challenging because of the need to demonstrate the same efficacy and safety. Drug purification, a key to successful manufacture of biologicals, must also adapt by exploiting products and technologies that lower the overall cost of production.

As our understanding of diseases at the molecular level increases, so does the potential for monoclonal antibody (mAb) - related therapies. Platform approaches to mAb production, including purification, are a key to their successful manufacture and, in particular, streamline process development.

The global diabetes pandemic has created a massive demand for insulin, especially in China, which is expected to soon have half the world’s diabetes patients. Meeting this demand means developing extremely efficient production methods that can supply affordable insulin with high purity. A promising approach is to add an orthogonal step upstream the main reverse-phase chromatography (RPC) peptide purification to increase purity and also guard the expensive high-performance RPC columns from bioburden and stringent cleaning-in-place procedures.

In 2015, the monoclonal antibodies (mAbs) market was estimated to be USD 85,4 billion and predicted to reach approximately USD 130 billion in 2023^[1]. However, new research points at a much higher number. According to Zion Market Research, the global mAbs market will reach USD 219 billion by the end of 2023^[2]. The market growth was much higher than expected only a few years ago, and even this number might be surpassed as we approach 2023.

Monoclonal antibodies, mAbs, form a well-established, technologically advanced segment of the pharmaceutical industry offering hope for large groups of patients who have difficult-to-treat cancers, rheumatoid arthritis or other serious diseases. More than 50 percent of the biopharmaceuticals on the market today are mAbs and more mAb therapies are in the pipeline ^[1]. The quality requirements of mAbs are very stringent, leading to high costs of production as well as high treatment costs. In this article we will take a look at mAb purity and give an overview of two strategies that can be used to develop a suitably pure protein – In-process control and Quality by Design.