Biomanufacturing Through the Ages: Creating Next-generation Biologics with Digital Solutions
The earliest evidence of “biomanufacturing” can be found inside of a 9,000-year-old urn discovered in China. According to MIT Professor Paul Barone, chemical analysis of the inside suggested that the vessel was used to make alcoholic beverages with grape, rice, honey and hawthorn fruit.1 In the 19th century, Louis Pasteur, known as the “father of microbiology,” would demystify the process of transforming bread and fruits into alcoholic beverages by uncovering that yeast is used in fermentation to produce alcohol from sugars. In the 20th century, strains of mold mutated by UV and X-ray radiation enabled the production of large amounts of the antibacterial penicillin, while the concept of proteins as therapeutic agents emerged with the isolation of insulin from pigs and cows.2 Though we have used cells to do our bidding for millennia, only recently have we begun to systematically use them to create novel, protein therapeutics.
Modern Biologics Research and Development
In manufacturing today’s biologics, we still rely on cell lines and recombinant DNA technology. However, in a competitive industry environment and with the emergence of biosimilars, challenges associated with “quality metrics” based on purity and potency remain.3 As Neil Lewis of Malvern Instruments discusses, “Biopharmaceuticals are intrinsically heterogeneous in nature and contaminants can originate from any number of sources, including the therapeutic molecule itself in the form of aggregates or misfolded…structural forms.” The development of new quality metrics and the standardization of physiochemical testing processes could be an essential means for controlling the quality of biologics, determining the extent to which biosimilars mimic these drugs and providing safer therapeutic options for patients.
Improving Quality Metrics with Digital Solutions
As is often mentioned, biologics are complicated and their complexity renders them especially susceptible to even slight changes in manufacturing procedures. Furthermore, the results of these changes can be catastrophic for patients, where unwanted adverse reactions include infections, cytokine release syndrome and anaphylaxis.4 Quality metrics to standardize and optimize processes are essential for creating safe therapeutic agents.
In order to monitor the various processes, conduct a myriad of tests needed during and after manufacturing and adhere to a variety of regulations and guidelines, digital solutions offer a vast improvement over paper-based record-keeping. Following are specific stages in the development of biologics in which digital solutions could offer benefits in quality metrics:
Equipment: Choosing the equipment needed to grow and incubate cell lines (bioreactors) and eventually isolate protein drugs (centrifuges and filtration equipment) is not trivial and indeed, there is a “huge difference” in the equipment needed for small versus large biologics.5 Procedures and information about equipment should be carefully documented. It is also essential to monitor various factors such as the last time equipment was cleaned or calibrated, for example. With digital technology, this information and all of its specifics can be presented as a report. In the case that a machine requires a calibration, system reminders can be provided that ensure materials and time are not wasted on useless experiments, shortening cycle times and streamlining the manufacturing process.
Materials: Different host cell lines can be used to make biologics and whichever is chosen has an important impact on the end product. For example, if the host cell is prokaryotic, complicated proteins that require post-translational modifications cannot be created, whereas mammalian cells grow much slower. Determining the type of vectors to use to express a protein, as well as the media and metabolites with which to grow the cells, are additional issues. Digital solutions are important in these steps because they enable clear and careful documentation and tracking of specific choices made, which helps ensure that these processes can be easily and quickly reproduced later. Alternatively, if a specific change results in a greater amount of protein misfolding, for example, researchers can refer to documents to determine where in the process an error occurred.
Production and Detection: Researchers are still unsure of how biologics interact with other elements such as DNA, other proteins, plasmids, RNA, etc. However, bioinformatic tools incorporated into digital solutions can enable researchers to use predictive analytics to identify possible interactions. Analytic tests that occur after the production of recombinant proteins include SDS gels, conformational analyses, carbohydrate characterization, impurity profile, bioassay/function, etc.6 Consolidating results from these tests and others into a unified system supports the establishment and maintenance of quality metrics for the benefit of the company and its eventual customers.
The BIOVIA Biologics Solution is an integrated digital offering that can support all of the abovementioned functions and more. With the suite of tools, work in the lab becomes easier, more efficient and compliant, resulting in an accelerated timeline for drugs, from bench to market. With bioprocessing management systems, accurate procedural and material documentation, a bioinformatics platform and other tools, your company can potentially surpass the competition, while still maintaining quality. To consider more ways the BIOVIA Biologics Solution can assist your company, please contact us today.
- “Biologics,” https://www.coursera.org/ ↩
- “Engineering of Therapeutic Proteins Production in Escherichia coli,” February 2011, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3179032/ ↩
- “Biologics: What Does the Future Hold?,” January 1, 2013, http://www.biopharminternational.com/biologics-what-does-future-hold?id=&sk=&date=&%0A%09%09%09&pageID=2 ↩
- “Challenges and approaches for the development of safer immunomodulatory biologics,” April 2013, http://www.ncbi.nlm.nih.gov/pubmed/23535934 ↩
- “Differentiate By Being Specific,” http://enterisbiopharma.com/differentiate/ ↩
- “Manufacture and Characterization of Biologics and Biosimilars,” http://www.gphaonline.org/gpha-media/gpha-resources/manufacture-and-characterization-of-biologics-and-biosimilars ↩