Pharmaceutical Separations with UHPLC

As ultrahigh-pressure liquid chromatography (UHPLC) gains ground as a technique of choice among scientists in the pharma and R&D community, questions arise as to how this may affect the QC lab and its current methods. Participants in this technology forum are Tony Edge, Technical Chromatography Consumables Division Thermo Fisher Scientific; Diab Elmashni, LC and LC/MS, Senior Marketing Manager, Thermo Fisher Scientific; and Michael Frank, Marketing Manager Analytical HPLC, Agilent Technologies.

The UHPLC approach to high-speed separations has been well accepted by the pharma R&D community. Do you see UHPLC making it into the pharma QC lab as fast?

Frank: UHPLC is not being adopted in pharmaceutical QC as fast as it has in R&D, but its use in QC is constantly growing. The reason is that pharma companies have to invest a lot of time and money in the development of analytical methods. This means the willingness to replace existing legacy methods is rather low, and investments in new UHPLC equipment need to be economically justified. Clearly, UHPLC has improved the development of new methods significantly because of its higher speed and resolution. But QC labs still have to deal with existing methods. So, the utilization of a new UHPLC system in a pharma QC lab depends on whether the UHPLC system is able to run legacy methods and deliver exactly the same results as conventional HPLC systems used previously. Of course, any new UHPLC method can be run on a UHPLC system, but not necessarily a legacy method. A UHPLC system has, by nature, a different, optimized flow path that will create different mixing behavior of the solvents and thus, often different chromatographic results. For sure, no one in pharma QC wants to see different results with a validated method as a result of changing the LC equipment. Another issue is the fact that in global pharma companies, method development is not necessarily carried out at the same site (or even in the same company) as the QC lab that has to perform the analysis — and this could mean that not even the same analytical equipment is used. To make method transfer straightforward, and to achieve a fast uptake of UHPLC systems into pharma QC labs, a universal LC system would be required. Such a system should be able to emulate the system behavior of exiting conventional HPLC systems and to run any LC-method developed on any LC system with just a mouse click, and finally be controlled by any established software. Such a system would really justify the investment in UHPLC systems in pharma QC labs.

Edge: Ultimately, the techniques and assays that are developed in the R&D labs will be transferred into pharma QC labs. The advantages of the UHPLC approach have already been admirably demonstrated in the R&D setting, but there is a learning curve with the introduction of this technology. As a result, it will take some time to transfer QC laboratories to using a fully UHPLC approach, because this requires substantial investment in terms of instrumentation. The methods themselves are already routinely transferred from R&D into QC, so transferring the technology will be expedited a lot more easily than with just a straightforward introduction of technology. There is currently some resistance from QC labs to invest in the new technology; however, with ever-increasing upper limits being made available from the pump manufacturers, the availability of purely low pressure (