Technology TransferI began the interview by asking Avril if she could tell us about her experience and success with technology transfer. Avril explained that technology transfer can be defined as a body of work shared between specialized personnel to achieve an end product. For bioprocess the goal is running a process at the manufacturing site with either no changes or minimal changes from the original process developed. She then described her experiences of transferring process knowledge from a drug development company to a partner or a contract manufacturing organization, from a process development to manufacturing within the same company, and from one manufacturing location to another geographically separate location. Next we talked about the challenging aspects of moving from a non-GMP lab or pilot plant environment to GMP manufacturing and I asked Avril what makes a process fit for GMP. She explained that the GMP framework is there to guide us but we are ultimately responsible for understanding our product identity, strength, efficacy, & safety, as well as our procedures, equipment, & facilities. All this translates into the expectation from regulatory bodies for product & process knowledge. Within a simple regulatory framework, we are also responsible for determining what our appropriate actions and practices will be. Then we discussed how process development teams can stay one step ahead and prepare for future GMP work. I asked if she could tell us the top three things to consider. Avril said that since the goal is to develop processes that account for variation to secure robust product output, defining Critical Quality Attributes (CQAs) early ensures that you obtain an end product with the quality that you want. In addition, you will also need to consider the Critical process parameters (CPPS) which are the parameters in the manufacturing process that are important to control in order to meet these CQAs. CPPs are typically established with a target set point for control, along with an acceptable range of variability around that target. She said the top three things to consider are:
- Consider if the operating space at small-scale or in the non-GMP setting will be the same after scale-up and in a GMP environment. Identify scale-independent operating parameters in process development – the easy example is maintaining residence time across scales in chromatography. An often overlooked consideration is the bioburden and product degradation risks associated with large scale.
- Use technology platforms to mitigate risks associated with equipment during transfer. Consider technologies that can grow & be flexible across your process development & manufacturing designs. Building process science on similar equipment and with similar operations as manufacturing provides reproducibility. But it can also be simple things, like having the a software platform with similar naming conventions and the ability to compare results files.
- Think about regulatory compliance early. Are the raw materials of GMP grade quality? Consider the costs when scale goes up and ensure there is a security of supply program for critical consumables. Do your analytical methods support your final vision for GMP in terms of sensitivity and implementation? Consider multi-attribute methods and how you can simplify the method if it is performed on the manufacturing floor, in an emerging market, or at an outsourced lab. And remember, both the FDA & ICH point to taking a risk-based approach to your CQA & CPP definitions and revisiting your assessment throughout the development life cycle as you gain more understanding of your product and process.