CMC plays a critical role in the development of a biological product. While it may not be possible for early stage and mid-size biotech companies to have all the necessary CMC resources to steer through the maze and tangle of drug development challenges, there are steps you can take to insure success.
So far, we have covered two essential steps to take:
Today we will consider Step 3 – Employ Simple, Practical, Scalable, Rugged, and Reproducible Technology.
Employ Simple, Practical, Scalable, Rugged, and Reproducible Technology
Drug development and manufacturing is complex and demands the use of many different technologies for upstream and downstream processing of bulk drug substance (BDS) and formulation followed by fill-finish (or alternatives such a lyophilization, etc.) of the drug product (DP) as well as for analytical testing methods used for in-process, release, and stability assessment. As for technologies employed in drug development and manufacturing, resorting to time-tested technologies that are simple, practical, rugged, and reproducible have many benefits. For example, platform technologies are considered valuable to improve efficiency and quality in drug development. The basic premise is that a platform, in combination with a risk-based approach, is the most systematic method to leverage prior knowledge for a given new product. Furthermore, such a platform enables continuous improvement by adding data for every new product developed by this approach, increasing the robustness of the platform.
If the newer technologies do not provide a great advantage over time-tested workhorse technologies, then it doesn’t pay to take additional risk in the march towards clinical manufacturing and advancement to licensure. Producing high-quality and regulatory compliant products quickly and economically is the most important objective. Esoteric technologies that work well in the lab and look promising may not be scalable always and end up being impractical or prohibitively expensive at large scale (e.g., sonication for dispersion and dissolution). Also, there are several emerging technologies (e.g., continuous manufacturing, on-line and real-time analysis of process samples, etc.) that show great potential; they are good candidates for integration in the future. Some of these technologies can be considered later in development or post-approval if they prove their worth and show continued merit from quality, cost, and time viewpoints.
Again, biotech companies must think from the end through to the beginning for biologics manufacturing and perform this analysis as early as possible in the development. This would encompass everything including the selection of technologies for unit processes and sample analyses. It’s necessary that the CDMO partner is engaged in this exercise and analysis.