Manufacturing innovation driven by tackling a rare class-effect




For decades, CSL Behring has earned a reputation as a leader in innovation that is driven by its promise to deliver for the immunoglobulin (Ig) community. PRIVIGEN® is the first and only prolinestabilised 10% intravenous Ig, and HIZENTRA® was the first 20% subcutaneous Ig on the market.

As the use of Ig to treat an increasing number of medical conditions has grown considerably, the numbers of reported cases of infusion-related, clinically significant haemolysis (a rare side effect marked by the rupture of red blood cells and the release of their contents into the plasma) have also risen throughout the entire intravenous Ig (IVIg) class. For PRIVIGEN, this rise has been observed primarily in patients with blood type A, B or AB, and who are receiving the highest doses of Ig.

From the beginning, CSL Behring took an active role in addressing this side effect by studying IVIg–related haemolysis, raising awareness and implementing changes to reduce its incidence. IVIg contains antibodies against blood types A and B, also called isoagglutinins, derived from the donor plasma. It rapidly became clear that the antibodies, which can destroy red blood cells of these blood groups, are an important factor contributing to the risk of haemolysis.

CSL Behring R&D scientists became engaged in proactively making specific changes at critical points along the production pathway for PRIVIGEN and HIZENTRA, immunoglobulin subcutaneous, in order to reduce the risk of haemolysis. That work resulted in an interim step of plasma screening for anti-A antibodies and is now culminating in the final step: the addition of Ig IsoLo®, an immunoaffinity chromatography (IAC) step, which is being embedded into production processes globally. This step is designed to lower anti-A and anti-B isoagglutinin levels specifically in Ig products.

The IAC step has been fully operational in both the Bern, Switzerland, and Broadmeadows, Australia, facilities as of December 2015, and the first lots of PRIVIGEN produced using this new process were shipped to the US. The IAC step has been approved by regulatory agencies in a number of countries, including the US, Europe, Canada, Australia and Switzerland. All PRIVIGEN shipped to these countries will be manufactured with the IAC step and as regulatory approval is obtained in other countries, the IAC step will be integrated into producing their PRIVIGEN.

Again in the forefront of the industry, this innovative production step could one day become standard for all immunoglobulin manufacturing.

Immunoaffinity chromatography is a method of separating biochemical mixtures based on a highly specific interaction between antigen and antibody