Bioprocessing

Nov 15

Bioprocessing, also known as biotechnology, is utilized in the production of pharmaceuticals, foods, flavors, fuels, and chemicals with the assistance of a biocatalyst such as enzymes, microorganisms, plant cells, or animal cells in a bioreactor. This blog will provide an overview of the manufacturing processes for pharmaceutical products, focusing specifically on liquid medicines

Upstream Processing

Upstream processing is the initial and crucial step of bioprocessing. It involves various important activities that set the foundation for the entire process. During upstream processing, raw materials and components are carefully selected and prepared to ensure optimal conditions for the subsequent stages. This includes sourcing high-quality raw materials, conducting thorough analysis and testing, and implementing strict quality control measures. Additionally, upstream processing involves the cultivation and maintenance of cell cultures or microorganisms in a controlled environment. This step plays a vital role in the production of biopharmaceuticals, vaccines, and other biotechnological products, as it directly impacts the quality, yield, and efficiency of the final output. Several important activities include media preparation, seed train, and bioreactor operation.

Media preparation involves the careful selection and preparation of raw materials and components that are necessary for optimal conditions during the bioprocess. This step ensures that the culture medium provides the necessary nutrients and environment for the growth and maintenance of cell cultures or microorganisms. Proper media preparation is crucial for achieving high-quality and efficient bioproduction.

Seed train refers to the process of cultivating and maintaining cell cultures or microorganisms in a controlled environment before transferring them to the bioreactor. This step involves the gradual adaptation of the cells to the specific conditions of the bioprocess, allowing them to reach their maximum productivity. The seed train is essential for establishing a healthy and robust cell culture that will yield the desired output.

Bioreactor operation is another critical activity in upstream processing. This involves the management and control of the bioreactor system, including monitoring and adjusting various parameters such as temperature, pH, dissolved oxygen, and agitation speed. Optimal bioreactor operation ensures the proper growth and productivity of the cell culture or microorganism, leading to the desired biopharmaceutical or biotechnological product.

Downstream Processing

The next step in the bioprocessing workflow is downstream processing, which takes place directly after upstream processing. Once the necessary activities and preparations have been completed during upstream processing, the focus shifts to downstream processing. This crucial stage involves a series of steps and techniques to purify and isolate the desired product from the bioreactor output.

During downstream processing, the primary goal is to separate and purify the desired biomolecules or biopharmaceuticals from the complex mixture obtained from the bioreactor. This involves various techniques such as filtration, chromatography, centrifugation, and precipitation. Each technique is carefully selected and optimized to achieve the highest purity and yield of the target product.

Filtration is one of the initial steps in downstream processing, used to remove large particles and debris from the bioreactor output. This helps to clarify the mixture and remove any unwanted impurities that can interfere with subsequent purification steps. Some common filtration process are sedimentation-based clarification, direct flow filtration, and tangential flow filtration.

Chromatography is another key technique employed in downstream processing, which utilizes the differential affinity of biomolecules to separate them based on their properties such as size, charge, or hydrophobicity. This technique enables the isolation and purification of the target product from the complex mixture.

Centrifugation is a widely used technique in downstream processing, which utilizes the differences in density to separate and collect the desired biomolecules. By spinning the mixture at high speeds, the heavier particles or biomolecules are forced to the bottom, allowing for their easy removal and isolation.

Precipitation is another important technique in downstream processing, which involves the addition of specific agents to induce the formation of insoluble complexes or aggregates. These complexes can then be easily separated from the solution, leading to the purification of the target product.

Chromatography is used at different phases of downstream to fulfill different purposes. Different kind of chromatography is used to target specific properties of the desired product. Some common Chromatography include protein A affinity and other affinity ligands, ion exchange, expanded bed adsorption (EBA), and hydrophobic interaction chromatography.

Drug Product (Fill-Finish)

In the final step of the bioprocessing workflow, the drug substance obtained after downstream processing is transferred to the drug product. This step is of utmost importance as it involves the conversion of the purified drug substance into a finished product that is ready for use.

In the fill-finish process, the drug substance is diluted with water for injection (WFI) and filled into vials. The process begins with vial washing to clean the vials. The washed vials then pass through a sterile tunnel for drying and further sterilization. Next, the sterilized vials are transferred to the filler where they are filled. The final step in the fill line is either the capper or lyophilizer. The capper seals the caps on the vials, while the lyophilizer freeze-dries the filled vials to extend their shelf life and facilitate transportation. Once the "fill" stage is complete, the filled vials undergo labeling and packaging for the finishing touches.

Throughout the entire bioprocess, purification steps in downstream processing represent the most significant portion of the expenses, accounting for approximately 80% of the overall production cost. It is crucial to note that each drug substance undergoes a distinct downstream processing procedure as a result of varying contaminants and properties. Substantial efforts are dedicated to formulating and refining the processes for each individual substance, ensuring optimal purity and efficacy levels are achieved. Countless bioformulated medicines are produced, but there are many more that are under development to help treat and prevent diseases. The continuous development of new bioformulated medicines is a testament to the never-ending effort in the field of bioprocessing.