By Carnley Norman, Vice President of Manufacturing Operations at KBI Biopharma, and Anshuman Bansal, Head of Process Analytics, BioContinuum™ Platform at Merck KGaA, Darmstadt, Germany
The inherent molecular complexity and vulnerability of biologic drugs to their surrounding conditions makes the manufacturing process for them challenging and complex. As opposed to small molecule drugs, which are synthesized through chemicals, large molecule biologic drugs (produced using living cellular organisms) have significant variability in how they function and perform. Therefore, any factors that can affect their robustness and quality during manufacturing must be understood in order to design a manufacturing process that consistently delivers a safe and effective drug. Sources of variation include a drug manufacturing’s cellular environmental conditions, the raw materials used, the behavior of the biologic itself, and even the equipment used for manufacturing. If these sources of variations are not well understood and are not tamed at their roots, they usually result in a butterfly effect. Propagation of these variations through the processing stages can lead to catastrophic and uncontrolled outcomes and process failures.