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Experts reveal how to identify the “right” biochemical, the process of sourcing biochemicals, sourcing challenges, and what industry professionals should know about the space.
Sourcing biochemicals adds a layer of complexity on top of an already complex process of sourcing raw materials. Development lifecycles must be considered in addition to good material specification and supply chain risks. BioPharm International interviewed Ryan Crisman, chief technical officer; Sarah Gould, associate director of MSAT (manufacturing science and technology); Jessica Freeman, MSAT process engineer III; David Mandeix, associate director of supply chain; and Christopher Lewis, senior director of quality, all of Umoja Biopharma, on biochemicals and raw materials in upstream processing.
According to Crisman, Umoja Biopharma specializes in immunotherapy, specifically in reprogramming T cells in vivo, which allows a patient’s immune system to target cancer cells.
BioPharm: Where do biochemicals come into the pharma development and manufacturing process? What does this look like for upstream processing, specifically?
Gould: Biochemicals define the final drug product; their quality and composition can impact the critical quality attributes (CQAs) significantly. Biochemicals do not so much come into the process as they are the process, having a prominent role in the identity, purity, and strength of the final drug product. The quality of the biochemicals is one of the most important factors in creating safe and effective drug products. For upstream processing, the cell line dictates the mode in which we run the upstream process. Thus, having the right producer cell for our lentiviral process can really make or break process performance—and, by extension, our ability to intensify the process to commercially-relevant scale.
BioPharm: How do you determine what biochemical type is best?
Gould: We want a high quality and reliable vendor who can partner with us to develop new solutions for lentiviral manufacturing and ensure consistent supply. Most of what is commercially available was designed for other virus types. We have the opportunity to apply some strategies or materials from AAV (adeno-associated viruses) to LVV (lentiviral vectors), but it does not always transfer successfully. Therefore, there is a significant opportunity for biochemical developers to partner with lentiviral development companies.
BioPharm: How does selecting biochemicals compare to raw materials sourcing in biopharma?
Freeman: For many biochemicals, you not only have to evaluate the performance in your process but also how it will be characterized. In some cases, this requires a release method to demonstrate clearance of the biochemical. Sometimes, analytical support is available from the same vendor—an ELISA (enzyme-linked immunosorbent assay), for example—to show clearance in your process. Thus, you are often evaluating both the utility of the biochemical in your process and your analytical ability to demonstrate removal in the process. These requirements necessitate locking arms with vendors to ensure appropriate execution of specialized work. Furthermore, much of that custom work has less clear guidance and practices. Critical industry standards (like a multi-compendial grade) do not currently exist for biochemicals. Biochemicals often make up such intrinsic components of the process (plasmids, cell line, etc.); as such, it is more difficult to ensure a universal standard, such as multi-compendial grades for raw materials. In addition, biochemicals are actively being developed and improved upon, which also makes their standardization more difficult compared to raw materials.
BioPharm: How do you define current good manufacturing practices (CGMP), specifically as it relates to biochemicals? What does that entail?
Lewis: When we refer to CGMP for biochemicals, we would expect suppliers to adhere to GMP requirements in the manufacturing, documentation, testing, release, and distribution of those materials. This would include quality systems that adhere to regulatory requirements and industry standards to provide the appropriate level of control and oversight for their (our) intended use. These systems and processes should be appropriately robust and auditable. When someone claims CGMP, they should have their act together to meet all requirements and standards defined by the agencies.
BioPharm: What are best practices for sourcing biochemicals? For raw materials?
Mandeix: The cost of poor-quality materials—raw or otherwise—cannot be understated. This issue often rears its head when trying to source things fast or cheap. Best practices for sourcing raw materials start with having a good material specification, a robust supplier qualification system, and an understanding of how your needs compare to that of the market at large. Sourcing biochemicals adds complexity to this process, as companies must also account for a development cycle (or sometimes several) and can then be called upon to help your CDMO [contract development and manufacturing organization] de-risk their own supply chains in order to facilitate the production of your biochemical. In either case, strong relationships with your suppliers and an in-depth knowledge of your material are table stakes for any company’s sourcing process.
BioPharm: What does the process of sourcing raw materials look like for your company?
Mandeix: As a relative newcomer to the biotech space that had to deal with the challenges of the pandemic shortly after its founding in 2019, Umoja has had to develop some extremely flexible sourcing strategies. Raw material is sourced with phase-appropriate control and supplier scrutiny (i.e., the specifications for both raw material and supplier tighten as we move from Phase I to Phase III). These systems are still being built out, with an eye towards an end state of commercial compliance for the quality systems. The best practice is to identify several suppliers that can provide what we need within a reasonable timeline and then work with them as we tighten our specifications or change what we need out of the material.
BioPharm: What is one thing you wish the pharma industry knew about biochemicals and raw materials?
Freeman: Companies in the pharma industry should be less fearful of implementing new biochemicals and raw materials into their processes. Companies often fall back on tried-and-true technology ‘because the FDA has seen it,’ and it will make their regulatory submissions more easily digestible. But that doesn’t foster process innovation and is not always the best material for the given use. Larger companies have the advantage of resources to take on that risk instead of falling back on what has worked historically without investigation of new novel solutions.
BioPharm: What trends do you see on the horizon for biochemicals and raw materials? Are there any up-and-coming technologies we should be aware of?
Gould: Expect to see process intensification for lentiviral processes that are starting to mirror what continuous mAb [monoclonal antibodies] processes look like. This means there is a lot of interest in other biochemicals and raw materials to enable intensification, such as continuous filter setups and producer cell lines instead of transient transfection. Producer cell lines and continuous processes enable the higher process throughputs required to meet the expected growth in demand in the gene therapy space.
Meg Rivers is a former senior editor for Pharmaceutical Technology, Pharmaceutical Technology Europe, and BioPharm International.
Vol. 35, No. 11
When referring to this article, please cite it as M. Rivers, "Upstream Processing: Biochemicals and Raw Materials," BioPharm International 35 (11) 20–21 (2022).