Current Therapeutic Antibody Production and Process Optimization

I n today’s biopharmaceutical pipeline, monoclonal antibodies are a predominant modality for a broad range of clinical indications, including inflammatory disorders, oncology, and infectious diseases.1 More than two dozen antibody-based products are commercially available. In 2004, six of the 12 new biopharmaceutics that gained approval in the United States and Europe were antibody-based products.2 Most antibody therapies require high doses over a long period of time, which requires large amounts of purified product per patient. Therefore, manufacturing capacity to meet the demands of antibody production is a real challenge. It is desirable to have highly productive and consistent manufacturing processes. In addition, speed to market is critical to deliver health benefits to patients quickly and to achieve business success. For early-stage clinical studies (Phase I and II), an initial standardized platform process is usually applied to satisfy the material demand and quality requirements within a short period of time, despite the relatively low productivity and robustness.3,4 Once the product candidate is proven safe for patients in an early-phase clinical study, the process is further optimized in order to maximize product yield and process robustness, and reduce the cost of goods for commercial manufacturing. Two major areas of commercial antibody process development are described in this review article: upstream cell culture and downstream purification processes. Upstream process development includes cell line development, media optimization, and cell culture process optimization. Downstream process development comprises cell harvest, antibody capture, viral inactivation, and polishing steps. This article provides an updated review and discussion of the technologies used in recent therapeutic antibody production processes. Cell Culture