In biopharmaceutical manufacturing, process development is the design and optimization of a method to help you create a viable drug candidate from a biomolecule, be it a monoclonal antibody (mAb), recombinant protein, viral vector, or other biological product. To be successful in this endeavor it is essential that the design of the process inherently selects and promotes molecules that have the greatest potential for scalability and commercial manufacture.
Biologics process development is an active undertaking that seeks continuous improvement along the entire length of the drug development timeline. Many aspects of biologics process development are compatible with automation, but despite being “automated,” there is nothing robotic about this science. Excellent process development requires skill and experience, and when guided by the appropriate expertise, it will accelerate your path to market. A contract development and manufacturing organization (CDMO) can help you understand the nuances and tactics involved in process development.
Biologics process development can be divided into upstream and downstream. In its very simplest form, upstream biologics process development involves optimizing all the parameters required to produce your biologic at large scale, while downstream biologics development involves harvesting, purifying, and concentrating your final product from the total materials generated upstream. Each step has different analytical requirements to measure progress to goal.
The first step of upstream biologics process development is to establish the clonal cell line you will use for manufacture, and to bank it. A cell bank is a store of genetically identical cells divided into multiple vials that that are cryopreserved for future use. The research cell bank (RCB) is usually used for early discovery and development work. However, once you’ve selected, optimized, and tested your final clonal cell line it’s time to create a master cell bank (MCB). These are the cells you will use for all your future GMP operations, so they must be diligently tested for contaminants such as bacteria, fungi, and mycoplasmas. Viral screening is also required. Once tested and characterized, cells from the MCB are expanded to form the working cell bank (WCB). Toxicology studies of your well-maintained and produced cell lines focus your objective. This cell line development (CLD) proves the growth, stability, and efficacy of your production system and informs scale-up strategies.
In the early stages of drug development your focus will be small-scale preclinical evaluation, but it’s important to keep in mind the ultimate goal of a viable drug substance that can be manufactured at scale. To this effect, it’s important to carefully define your product’s critical quality attributes (CQAs) and measure the outputs of your process against them. This is where analytical development and biologics process development go hand in hand. Failure mode and effects analysis (FMEA) will test your molecule’s robustness in regard to eventual product quality and probability of successful manufacture. If you follow quality by design (QbD) principles, which encompass scientific knowledge, process understanding, design, and process control to further develop and optimize your process – and use this to define your critical process parameters (CPPs) – this will set you up for later success with regulatory agencies.
Ultimately, defining and improving key methodologies enhances productivity, process robustness, and product quality in the late-stage upstream biologics process and beyond. Good process is its own reward.
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Downstream biologics process development comprises the harvest, purification and concentration of your drug candidate, as well as its final formulation into a drug substance. The groundwork laid in upstream process development begins to pay off here since you’ve been continuously refining, tightening, and strengthening your processes. Optimizing the conditions of production improves recovery and purification. And because you’ve paid attention to formulation development since early upstream efforts, integrating with process and analytical development activities all along, you’ve saved time and reduced risk. Your candidate is ready for advancement.
Your success, is partly attributed to the virtuous cycle of process development: the continual loop of refining processes, increasing robusticity, making endpoints, avoiding pitfalls. As an experienced, flexible, integrated CDMO, Scorpius BioManufacturing understands the challenges of current biopharmaceutical manufacturing. To find out more about how we can help you, contact us today.