One of the most interesting talks I heard at this year’s World ADC summit in San Diego, was Damon Meyer’s presentation about the use of PAT (Process Analytical Technology) on ADC processes at the development stage. Although PAT is well established in the pharmaceutical industry, its use in ADC processes to date, has been scarcely documented.
Damon presented data obtained by Seattle Genetics for one of their site specific thiomAb conjugation processes. In addition to more standard pH, conductivity, and temperature sensors, UV cells and redox probes were also fitted to their vessel-TFF system allowing measurement of the redox potential. The signals from these sensors were all collected throughout the entire process enabling a mapping of the process from different physicochemical perspectives:
- The redox profile generated was a very useful tool for recording the (redox) chemistry carried out, with large variations observed both at the reactive stages – large drop of potential during TCEP reduction, increase during re-oxidation, decrease during NAC quench, and also during the 2 TFF steps – post reduction and post quench. The use of the in-situ redox probe can also further increase process understanding and help process decision making with an example given: re-oxidation at different pH resulted in variable redox slopes upon DHAA additions, with a larger slope indicative of faster reaction.
- Conductivity profile variations follow the buffer switches and were also found to be indicative of solvent / reagent additions (for example, a decrease during DHAA, DMA additions) or clearance (increase during TFF clearance).
- V cells. Multi-wavelength detection on both the retentate and permeate flow paths allowed a better understanding during the TFF steps of selective clearance of process reagents with, for example, the drug clearance (detected at its maximum specific absorbance) shown to be clearing slowest.
- pH and temperature were useful to confirm the process was operated within the expected range.
The work demonstrated the potential for the use of in-situ sensors in process monitoring and understanding. Additionally, a multivariate map yields a blueprint of the process which could be used in the future as another tool to show process consistency, rather than relying solely on final product testing plus a number of discrete in-process analytics and parameters.
Piramal is always keen to improve learning and will evaluate in the near future suitability of the new sensors for adoption on their ADC processes.
Dr Xavier Despinoy
Head of Development Sciences
Piramal Pharma Solutions