One of the most critical points in a drug’s journey to patients is the successful scaling up from R&D to manufacturing. Having a seamless scale up process is essential for not only ensuring safety but also for maximizing the potential success of new drugs when they get to market. Though not a simple process, scale up purely means increasing production to meet demand for clinical trials or commercialization. This involves crucial steps such as increasing the size of equipment and vessels, implementing new quality control measures, optimizing manufacturing processes to adapt to larger scales, and ensuring compliance with regulatory guidelines.
While there is not necessarily one single inflection point that triggers scale up, there are several points throughout the lifecycle of a drug where it could be needed. Oftentimes when a drug hits toxicology and Phase I studies, scale up is required to transition from R&D to the initial manufacturing scale and then again when moving from Phase I to Phase II if the study expands to other indications. Finally, during Phase III of drug development, after the drug has proven safe and effective in smaller groups of people, there is typically a crucial scale up to meet the larger demand required for clinical trials and eventual commercial supply after approval.
Going through the process of scale up successfully and resourcefully can significantly help maximize the commercial success of your drug product. A process with greater production efficiency and lower operating costs can be the key difference between profitability and market failure. At Cytovance Biologics, we have extensive experience in navigating both the common and unique challenges of scale up at every stage. Below, our experts have shared a few tips that can help ensure this complex process is completed optimally for you.
1. Plan for Regulatory Compliance Early On
Forethought at the R&D level is the foundation for the end product’s quality, making it crucial to factor in quality by design principles and phase-appropriate quality management as early as possible. Risk management is a critical piece here and even though it is often thought that formalities are not needed during the R&D phase, they are necessary to ensure functionality, reproducibility, predictable manufacturability, and traceability throughout the product lifecycle. Establishing robust quality control measures early can also help enable the final product to meet all regulatory requirements without timely and costly hurdles at the finish line. Leverage existing cGMP systems whenever possible, be an advocate for quality culture, and look at the full lifecycle matrix from CMC to CGMP to map out detailed plans, guide step-by-step decisions, and make the right phase-appropriate decisions.
2. Consider All Aspects of Scale Up During Process Development and Optimization
When working through process development and optimization, it is important to always have scale up in mind when making key decisions and choices – if a product that is produced at bench scale can not be produced at commercial scale, is it even a product? This means constantly striving to increase productivity and improve overall product quality while simultaneously simplifying protocols, enhancing supply chain security, and choosing sustainable reagents and process conditions to increase manufacturability. And since the process for making lab-scale batches is guaranteed to be different than for large scale, be prepared to alter your manufacturing process by proactively having a plan in place for how that will be achieved.
3. Understand the Impact of Raw Materials on Your Process and How Variations in Quality and Composition Can Affect It
The quality of your end product starts with the quality of your raw materials. Making an extra investment today by using CGMP grade from the beginning of your project, will go a long way tomorrow when you get to regulatory filings. Utilizing a smart system to validate materials providers and identify common stock options will help with raw material qualification and FDA and EMA compliance. Aside from simplifying the regulatory paperwork, raw materials can have a HUGE impact on the manufacturing process itself. Because of that, it is important to use modern process analytical technologies to help provide comprehensive process characterization. Tools such as online cell counters, DO and pH sensors, and metabolite analyzers monitor product quality attributes to better illustrate what process parameters are linked to those critical quality attributes, providing you with improved process control.
4. Validate Your Manufacturing Process Appropriate to The Clinical Phase
It is important to define process parameters throughout the progression of each clinical phase by establishing trending analyses. This will not only provide better insight into how your process is performing overall but will also help establish critical control points as you progress toward Phase III. To do this successfully, be sure to test for process efficiency and keep robust documentation every step of the way.
5. Make Sure the Facility is Designed for Scalability
When choosing a CDMO, it is a significant advantage to work with one that has end-to-end capabilities or a seamlessly integrated network of partners that can provide equipment and the required technical expertise from process development all the way through to commercial scale. In being able to offer the complete suite of services required from beginning to end, the process of scale up will go much more efficiently. On top of comprehensive capabilities, the facility needs to have the right infrastructure to support full scale up and enable the ability to meet commercial drug product demand once approved.
Partnering with Cytovance Can Simplify Your Journey
Efficient scale up is challenging because no two drugs are the same and therefore no two drug manufacturing processes can be scaled up in the exact same way. Therefore, it is crucial that you choose to work with experienced partners who can provide invaluable assistance in both planning and executing the scale up process. Be sure to partner with an experienced provider that can free flow information and personnel between all areas and groups involved throughout the drug development lifecycle.
At Cytovance, we have strategically integrated our R&D and tech transfer/MSAT teams to ensure that every process is developed with scale up in mind and pride ourselves on cultivating strong organizational philosophies around collaboration and ingenuity. Our responsive nature, reliable processes, and resourceful approach will help ensure a successful scale-up of your process to deliver a quality product through to market.
To learn more about Cytovance’s offerings and how we can help accelerate your drug development journey, contact us today.