Recover and Polish: Improving the Downstream Processing of Biologics with Advanced Software
In preparing to bring a biologic to market, your firm may have gone through the difficult process of selecting a cell line, type of bioreactor, nutrients and feeding scheme for your cells. You may be thinking: the rest of the process should be fairly straightforward now that I have a cell that produces my desired biologic. Unfortunately, downstream processing, which describes the processes that occur between the production of the protein therapeutic from cells to the point at which it is ready for production, presents its own unique challenges. Much can change between the presence of the biologic within a cell and its ultimate purification. Upstream processing steps are complex and the steps for downstream processing of biologics are no different. Specifically, this includes primary recovery, purification, polishing and additional formulation1, each essential to the final chemistry of the biologic.
Effectively Monitoring the Downstream Processing of Biologics
Though these steps must be carefully monitored, appropriate software can assist researchers in tackling these challenges and increasing the likelihood that a biologic works as planned on the market. But from harvesting a culture expressing your biologic of interest, exactly how can software expedite the process from cell separation to the final polishing steps needed to ready a biologic for the market?
Comparison of “starting chemistries” with “end chemistries”: Software that assists in comparing “starting chemistries” with “end chemistries” is an essential component of downstream processing, which often includes a number of major operations including centrifugation, filtration, cell disruption, precipitation and flocculation.2 In characterizing starting chemistries, software can enable firms to automatically record various physicochemical characterization values, such as the readings from UV/visible or mass spectrometry, amino acid analysis, sequencing results, carbohydrate analysis and peptide mapping, among other tests.3
By storing these values and testing samples periodically, researchers can better track the development of their products by comparing the experimental batch to a “biologic standard,” increasing the likelihood that the biologic isolated at the end of this process is the same as the identified standard. Additionally, a better understanding of how various downstream processing events change the chemistry can be achieved by carefully recording the values of physicochemical results following separations, chromatography steps and other aspects of biologic development. Interestingly, if these values or factors are entered into machine learning algorithms, they might also serve as predictive models for understanding how certain downstream processing events affect the final chemistry of a biologic.
Raw materials used in downstream processing and flow charts: Though a list of all materials used in downstream processing might seem trivial, software that encourages the careful documentation of these materials enables researchers to better monitor their products and ensure the reproducibility of their procedures. In terms of raw materials, specialized registration systems enable researchers to carefully monitor the products they purchase. Customizable workflows in which information about raw materials is integrated into the software’s output workflow might also enable researchers to consider where and when they might increase efficiency.
For example, at an initial stage when a specific type of raw material is used, could a cheaper alternative be considered if few modifications are being made of the biologic? Specialized software assists in the discovery of such alternative materials, which might increase both the efficiency and cost-effectiveness of specific schemes. Software can go even further by enabling researchers to create a complete visual representation of the biologic manufacturing flow, which includes information about the equipment and materials used, room or area where specific aspects of the downstream processing occurs, etc. This step can be especially important for ensuring that downstream processes are reproducible and also in detecting where errors may occur.
Software platforms like the BIOVIA Biologics Solution revolutionize how researchers understand and record various manufacturing processes, which in turn ensures the standardization of biologic production. Furthermore, appropriate software provides researchers with clues from which certain processes can be optimized, products more clearly analyzed and biologic yields increased. To consider how else BIOVIA Biologics Solution can assist your firm’s efforts, please contact us today.
- “Overview of Upstream and Downstream Processing of Biopharmaceuticals,” http://www.engineersirelandcork.ie/downloads/Biopharmaceuticals%2020Jan09%20-%202%20-%20Ian%20Marison%20DCU.pdf ↩
- “Downstream Processing: From Cell to Column: Integrated Solutions for Rapid Bioprocessing of Biologics, November 2015, https://www.ucl.ac.uk/biochemeng/industry/mbi/courses/dppr ↩
- “Guidance for Industry: Content and Format of Chemistry, Manufacturing and Controls Information and Establishment Description Information for a Vaccine or Related Product,” January 1999, http://1.usa.gov/1UxmNA8 ↩