Overcoming impurity assessment challenges for biotherapeutics

Biotherapeutics have grown to become one of the more promising classes of drug compounds. During the period 2004–2012, the market share of biotherapeutics versus conventional small molecules grew from 12% to 20%, with worldwide sales estimated at US$153bn in 2012.¹ By 2018, sales will increase to $215bn, with an estimated CAGR of 6.4% over the next decade.²

Some of this growth is driven by the advantages offered by biotherapeutics, which include greater specificity, potentially higher efficacy and lower toxicity. However, their development is not without its challenges. For example, as biotherapeutics are produced inside living cells, they must be carefully purified before they can be used in research or the clinic. Undetected contamination with host cell proteins (HCPs) can have very serious implications, triggering undesirable immune reactions in patients.

In one recent high profile example, Inspiration Biopharmaceuticals had to put a hold on the clinical testing of IB1001, an intravenous recombinant factor IX (rFIX) for preventing bleeding in hemophiliacs. During a Phase III clinical trial, a group of patients started to exhibit an immune reaction against proteins from the host cell type used to produce the therapeutic. As would be expected, such hold-ups are costly and time-consuming, often requiring further pre-clinical R&D and an adjustment to the production pipeline.