Douglas Turk, PhD, business unit manager, and Uttam Ghosh, department head of R&D/Validation, Eurofins BPT, Toronto, discuss how the contract research organization (CRO) has applied a new approach to the migration of validated test methods.
Q: Could you give a brief overview of the importance of method migration within the Eurofins BPT lab?
A: Analytical method migration and method transfers are something that we, as a CRO, do very regularly, whether it’s from an internal lab or from a client’s method that they want validated or transferred to our facility. We offer a broad range of methodologies under GMP authorization, ISO 17025 accreditation, and ISO 9000 certification. All analyses are performed according to European and British Pharmacopeia (EP and BP), United States Pharmacopeia (USP) and Japanese Pharmacopeia (JP), as well as specific customer methods.
Q: How did this legacy method migration project come about?
A: We had the opportunity to evaluate a new HPLC from Waters, with whom we have had a long-standing relationship. They were interested in understanding the risk and impact of migrating an assay from a legacy HPLC platform in a GMP lab. Of course, the fact that we had the opportunity to evaluate a new HPLC system was appealing, but ultimately we wanted to see how the instrument would perform with the migration of legacy methods in a regulated environment. The goal of the project for us was to ensure that our lab’s potential switchover from aging systems to modern HPLC instruments would be seamless, while ensuring data equivalency and regulatory compliance.
It was an interesting project for us because newer machines typically don’t have as many issues as some of the older instruments. Our clients want their work done on time, and they expect results. They’re not going to understand why their assay is delayed because the HPLC is down, so we need to migrate a method to a new HPLC system. As a CRO, we need machines that don’t break down because if we repeat an assay three times due to equipment issues, that’s time when we’re not running another method. For us, it comes down to productivity and turnaround, but we are also driven by ensuring customers are satisfied with the quality of our work. The best way to achieve those things is to have a solid method on a good platform.
Q: Why did you choose to take a risk-based approach and what does it entail?
A: Risk assessment is a key element of the quality by design approach that many labs have adopted. We used it to proactively identify the actions needed to ensure the performance of validated analytical procedures on the new LC system, and to ensure a smooth method migration between our analytical platforms without the need for us to revalidate, which is both expensive and time consuming. The process started (before purchase decisions were made) with a thorough risk assessment of how or if differences in instrumentation could have an impact on our validated procedures. We then designed the experiments to understand the severity of the potential impact. The eventual results may support the equivalence of the two instruments without requiring the implementation of control strategies, but following this process means we can be confident in the new instrumentation.
The data that was extracted from this approach was also used to inform decision-making on replacing aging legacy instruments, when comparing cost-in-use with the technical advantages of modern instrumentation in applications like routine quality control analysis.
As a CRO, a number of our assays are based on historical methods that our client has been using for many years. They’re often reluctant to change because these older assays are an important component of their legacy submissions to the regulatory agencies, but advances in analytical technology and method development can help clients in the long run with time and cost efficiencies. That’s the advantage of taking a risk-based approach, because you can measure the potential impact of instrument performance and method migration before making that decision.
Q: Can you describe the process of testing the equivalence of the instruments you were comparing?
A: The whole QbD process was a learning curve for us. For the comparative testing, we set up our existing equipment and the new HPLC system with the same column, the same injections, the same mobile phase, and the same prep for both instruments. We were running the tests on the same day, so there were no issues with mobile phase differences, sample stability or column performance. Everything remained as identical as possible. We set the instrument comparison targets at one percent difference in the RSD and three percent difference in the absolute retention times. We’re worried about an absolute retention time being different if we have a standard that we run it against. But, from a method migration perspective, if the standard operating procedure says two minutes plus or minus point two, and you’re at point five, that’s not equivalent. That’s where the new HPLC system showed some benefits; the response to the detector was more than adequate, signal to noise was good, and the reproducibility of the injections was spot on.
Q: For other busy CROs, could you summarize the value of completing such a robust process for the migration of legacy methods?
A: If you are a practical person, you might just go right to the result to look at how your method performed on one platform vs. the second platform. However, if you do that, you don’t gain the knowledge from comparing the two systems throughout the process. It’s beneficial to go through the whole progression in some detail at least the first time. The lessons learned will be useful when considering the replacement of any piece of equipment.
Our next steps are to gather more data over a longer period with diverse methods to give a more complete picture of the instrument. We want to make sure we can perform any kind of project that comes to our door, just like we do now.
We’re always offering new services and that often gets a new client in the door. That’s why we were interested in this risk-based analysis for method migration. We are always looking for opportunities to improve our business and this QbD approach for method migration to newer HPLC platforms is a very useful tool in our toolbox.