By Paul Thomas, Senior Editor
As a regular feature on PharmaQbD, we like to call attention to some of the new tools that are enabling drug manufacturers’ QbD efforts–particularly those tools that have been developed specifically with PAT and/or QbD in mind.
For the past several years, Waters Corp. has been working with industry to develop several products which could be considered QbD enablers. A recent contribution is the Acquity UPLC H-Class chromatography method development system. The H-Class was announced earlier this year, but is now at a point where, says Senior Manager for Pharmaceutical Business Operations Dominic Moore, all the “pieces of the puzzle” are in place and available on the market.
What follows is my email conversation with Moore:
PharmaQbD: First, a general question: Waters has been promoting QbD-driven chromatography—what elements of QbD are particularly suited to advancing chromatographic methods?
D.M.: QbD offers a framework through which scientists can learn about the critical parameters that affect their process or product. As such, building the knowledge of these critical effects and the knowledge of where the process parameters allow flexibility without affecting the quality or integrity of the finished product is key. If we look at chromatography as a process, it is possible to define the critical parameters that affect the quality and robustness of the method and therefore define the operating space for the method to allow for regulatory flexibility.
PharmaQbD: How receptive has the industry been in aligning chromatography with QbD? Have technological limitations held them back?
D.M.: Industry was initially a little slow at seeing the benefits of QbD within a chromatographic environment. That is now changing though as we see more and more pharmaceutical companies of all sizes investigating and investing in this approach. This change has come about because they see the benefits that this approach brings to them and also because of the tools that are now available.
PharmaQbD: You have said that Waters now has “all pieces of the puzzle” together (and on the market) for this QbD-oriented LC method development. What are those pieces, and what’s brought them together now?
D.M.: Waters now offers the ACQUITY UPLC H-Class Method Development System including Fusion Method Development Software from S-Matrix. The method development system offers the capabilities of the ACQUITY UPLC H-Class with a configuration suited to method development–namely, expandable column management with up to 6 individually temperature-controlled columns, as well as expanded solvent selection capabilities that allows up to 9 different mobile phases solvents (3 organic and 6 aqueous) to be used in a fully automated manner with no operator intervention.
Combining Fusion Method Development, which applies a QbD approach to method development, and a seamless integration with the Waters Empower Chromatography Data System, we’ve created the most fully-featured and easily implemented method development system on the market today.
PharmaQbD: With this integration of Fusion software with your own data software and UPLC, what can method developers do now that they couldn’t a year ago?
D.M.: The combination of Fusion, Empower and ACQUITY UPLC H-Class in a single-platform method development system provides laboratories with greater ease of use and power to automate method development. Once the experimental design has been defined, Fusion automatically exports to Empower with all the necessary data sets and methods written automatically. Once the experiments have been run, Fusion imports the data and processes it using statistically-valid processes to define the best operating parameters for the method. We think this has been revolutionary in our customers’ hands, as well as in the hands of our own pharmaceutical scientific experts.
PharmaQbD: How sophisticated is the modeling that can be done—i.e., how “multivariate” can it be?—and does it take an expert in statistical process control to generate and assess such models?
D.M.: The modeling itself is extremely sophisticated in that it models the interactivity of all the variables that are studies. Whilst this can sound complex, the graphical interface that Fusion employs means that even with minimal training, a scientist can assess the data meaningfully and therefore develop the most robust, reliable methods possible with ease.
PharmaQbD: Does the full, automated solution change the dynamic of traditional two-phase method development in any way?
D.M.: Yes. With the full automation of the system and speed of UPLC, it allows methods to be developed faster than before. Within a very short period of time a scientist can develop a method for early use or with a little more work they can develop a fully-optimized, QbD-ready, rugged, robust, and reliable method. This efficiency allows the scientist to perform more value-added activities to aid in the productivity of the laboratory.
PharmaQbD: What does it take for legacy ACQUITY UPLC users to migrate to or upgrade to these new capabilities?
D.M.: It is very simple to upgrade. For existing ACQUITY UPLC H-Class users, the addition of the Column Manager (CM-A) and auxiliaries (CM-Aux) will allow them to use up to 6 columns, and the addition of the optional internal solvent selection valve will increase the solvent choices. For ACQUITY UPLC users, it’s as easy as adding a column manager (up to 4 columns) and an external solvent selection valve. In both cases, these additions, plus Fusion software, will give users all of the benefits of a fully automated method development system.
PharmaQbD: Published reports note that manufacturers testing this new approach (versus a one-factor-at-a-time, or OFAT approach) were able to reduce method development time for a complex product from 45-60 days to just two days. Do you expect this to be a “typical” experience?
D.M.: We have seen several instances of customers who have demonstrated significant time benefits in developing methods with this approach. Whilst the example you mention was one of substantial time savings, the savings will vary from method to method and company to company. The other important consideration though is not just the time saved developing methods, but the fact that you are developing QbD-ready methods that are robust, reliable and rugged. This alone will save you time, knowing that the method will pass validation and transfer, as well as be more reliable when used routinely in the laboratory.
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