Best Practices in Biologics Process Development

1. Best Practices in Biologics Process Development As the name suggests, a biologic is a product extracted and developed from biological sources. Generally, biologics are also called biopharmaceuticals. In the present day, scientists and researchers are making commendable progress in manufacturing new and effective biologics. Every now and then, we come to know about the development of a new biologic more advanced and economical than its predecessors. Many companies are involved in developing biologics because of a promising market and a good potential to revolutionize industries. A single breakthrough in the form of an economical and effective biologic product can change the perception of a company. However, the process of biologics development must be well planned so that a company and its consumers can get a strong, pure, and therapeutic product. Biopharma companies are extensively putting a lot of time and effort in biologics process development. This is primarily to enhance the cost-effectiveness and quality of manufactured products. Another reason associated with focusing on process development is to complete the

2. manufacturing way before the set deadline and to adopt sustainable regulatory measures. Furthermore, a well-developed process can overcome the challenges associated with new molecules while increasing the yields and titers at the same time. Let’s take a look at the best practices to enhance pharma process development: ➢Cell Line Development with Physiological Substrates Biologics such asmonoclonal antibodiesand recombinant proteins are extensively manufactured with the help of cell line development. This involves calculated transfection of the host with plasmids. This process allows for a higher degree of control over manipulating cellular functions and processes. In conventional cell line development, manufacturers often struggle with impure products with slower growth rates. However, when synthetic polymers are replaced with relevant substrates, enhanced purity, growth and cell attachment is observed. This also results in higher titers and is flexible in terms of post-translational modifications. ➢Customized Upstream Process Development This is one of the most widely implemented biologics process development methods. Upstream process development while performing microbial fermentation and mammalian cell culture often increases the yield. Instead of following generic upstream process development, companies are now tweaking the process according to the desired protein to make the process even more efficient. This allows a plethora of expression-platforms for mammals and microbes. Moreover, the flexibility of ardent models for perfusion and fed-batch models make it one of the best process development practices. ➢Strategic Technology Transfer Every biopharma firm needs proper supervision for technology transfer during the manufacturing process. Several companies face problems during clinical studies due to the lack of a GMP infrastructure. A well-planned technology transfer influences the biopharma process development to a great extent. This allows the company to scale-up small scale manufacturing (during testing stages) to the production level. Although this is not directly related to the biological aspect of the product, it has a great impact on it. Furthermore, inefficient choice of technology also results in degradation of

3. purity and quality of the biologics since they need stringent environments for proper growth. ➢Downstream Process Development with QbD This includes steps essential for the purification of biologics from the initial phase (cell culture broth) to the final stage. There are many steps involved in downstream process development. Downstream processing includes removal of anti-foam, leached ligands, DNA, proteins of host cells, buffers, fragments, clipped species, etc. Initial processes like sedimentation and centrifugation help in the extraction and isolation of broth culture media. It is then followed by removing the substances which contaminate the biologics. Chromatography and ultrafiltration are then used to separate target proteins from the solution. In the case of intracellular biomolecules, cell debris is extracted by clarification after sonication and high-pressure homogenization. Although downstreaming is an effective method of process development, biopharma industries are applying Quality by Design (QbD) and Process Analytical Technology (PAT) for quality assurance and process consistency. These were some of the practices used in pharma process development to enhance the efficiency and effectiveness of the end product. These days, the biopharmaceutical industry is dedicated to developing even better methods to be used in process development. Researchers are also working with heavy attention on analytical chemistry, mathematical modelling and statistical analysis to strengthen the process of biologics manufacturing, which can be witnessed in upcoming innovations.