Pharmaceutical Separations Technology Forum

Experts from the pharmaceutical industry discuss current and emerging trends in detection techniques, the growing presence of UHPLC technologies and the impact of company consolidation. Participants in this Pharmaceutical Technology Forum include Simon Lomas, brand manager, HPLC and UHPLC products, Phenomenex; Frank Steiner, manager, Small Molecule Solutions, Thermo Fisher Scientific; and Dominic Moore, senior business manager Pharmaceutical Business Operations, Waters Corporation.

What percentage of your analyses use UV detection and what trends do you see with other detection techniques, such as evaporative light scattering detection, mass spectrometry (MS), or charged aerosol detection (CAD)?

Lomas: The use of different detection techniques is strongly driven by the work function of each particular department. We find that liquid chromatography (LC)–MS-MS plays a very important role in medicinal chemistry and DMPK environments, where structural elucidation and metabolite identification are important. In downstream work, groups that may be more focused on product formulation, stability testing or quality control methods depend more on LC–UV methods.

Steiner: UV detection is still sold with more than 70% of our systems in total, with more than half being single variable wavelength detectors and the remainder diode array. Some of the systems with (or for) MS or with CAD have additional UV detectors that are included in the 70%. And 12% have fluorescence detectors.

Moore: That’s an interesting question that has a different answer depending upon which stage of the pharmaceutical development process and which function within that department you are talking about. For our customers who are earlier on in discovery stages, there is an abundance of time-of-flight (TOF) MS detection that is often used to aid the structural elucidation of related substance. Moving into bioanalytical studies, high-sensitivity tandem-quadrupole MS detection is required. In later stages of the pharmaceutical development lifecycle, including QC, a high proportion of detection used is UV-based. However, we are also seeing an interesting trend as our customers are increasingly using single-quadrupole MS detection due to technology improvements that make these detectors more robust, versatile and easy to use. With single-quadrupole MS detection, analysts can generate high-quality, information-rich data with minimal training.

The ultrahigh-pressure liquid chromatography (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 laboratory as fast?

Lomas: Column technology such as Kinetex core–shell products provide UHPLC performance on conventional high performance liquid chromatography (HPLC) systems and are already seen in QC environments. These columns allow R&D groups with UHPLC systems to easily scale their methods to the conventional HPLC systems that are present in QC environments. Instrumentation, however, is a long-term capital investment. As users upgrade and replace their aging conventional HPLC systems, they will probably be more apt to purchase new systems with greater pressure capabilities.

Steiner: UHPLC is still very cautiously adapted by QC and QA labs. Traditionally, still plenty of isocratic methods are used, which demonstrates the very conservative approach, especially for established products. With more and more new drug entities brought to the market, the UHPLC type applications will increase to a similar extent for those labs.

Moore: Traditionally, we have always seen new technology in the pharmaceutical industry be embraced first within the R&D groups where they learn how it supports their scientific innovations. Then as the organization better understands its value, the technology migrates from drug development into commercialization processes. While this has been true with UPLC [Waters] (or UHPLC), pharmaceutical organizations rapidly learned that UHPLC’s high-speed separations and data quality offered a step-change opportunity in analytical productivity, and this is always meaningful to pharma QC where running lean and smart is an important business driver. On average, our customers have experienced that one UHPLC system can do the work of three HPLC instruments. When you supplement the productivity value of UHPLC with the significant solvent savings as well as energy and waste management savings, UHPLC can make a meaningful difference to pharma QC. So yes, we are also seeing a push from users within QC groups to adopt and implement UHPLC, and from QC management to push this technology into their laboratories faster than we have seen with other new technologies.

What factors are influencing the decision to revalidate existing HPLC methods to using UHPLC column technologies (both sub-2-µm and core–shell)?

Lomas: The primary drivers for the conversion of HPLC to UHPLC methods are performance and productivity. By taking advantage of high-efficiency UHPLC and core–shell media, and coupling that with the high linear velocities afforded by ultrahigh-pressure-compatible UHPLC systems, it is often possible to dramatically reduce analysis times, greatly increasing the sample throughput and productivity of laboratories. In addition, because the ultrahigh efficiency of UHPLC media, especially sub-2-µm core–shell media, is directly translated into improved resolution, many of these shorter methods are also able to provide improved chromatography over the original conventional HPLC methods.

Steiner: To revalidate is still extremely unpopular, especially for smaller and mid-sized pharmaceutical labs and generic manufacturers. The effort and risks are perceived to outweigh the benefits. Very often this is not an economically driven decision but rather a “total risk avoiding” policy (never touch a working and validated method).

Moore: In addition to UHPLC’s benefits in separation quality and productivity, we regularly hear from pharma QC management that they realize they can streamline their operations, reduce capital expenditure and their instrument footprint through the introduction of UHPLC technology. The benefits have proven to outweigh the costs associated with revalidation. In fact, this summer we’re starting to see new monographs published where methods have been converted from HPLC to UHPLC, so the last barriers to migrating analytical methods to UHPLC are being broken by pharmaceutical organizations themselves. In addition, some instruments have the ability to seamlessly operate under both HPLC and UHPLC conditions, allowing the laboratory management to standardize on a single platform that has the capacity to run established methods as well as future-proofing themselves with the opportunities made available with UHPLC technology.

How is company consolidation affecting your current work and the methods that you both develop and use?

Lomas: From a practical point of view, as companies consolidate they may find that certain previously used instrument platforms and consumable choices are no longer compatible with the new corporate environment or have been greatly expanded by a merger. This means it is even more important for new methods to be not only robust and reproducible, but also transferable across different system platforms.

Steiner: Not untypically, consolidation in customer market places forces suppliers to follow a similar strategy. Consolidation happens also in the scientific instrumentation and services marketplace and will continue in the foreseeable future.

Moore: Consolidation, down-sizing and right-sizing are certainly things that are impacting our customers in pharma QC. Where these organizations are essentially challenged to do more with less, they are turning to partners for innovations that enable them to maintain their high standards of productivity and quality. This environment is ripe for adopting technologies that are designed to optimize the development and execution of analytical methods, including tracking method performance and asset utilization in a way that ensures that QC laboratory environments can maintain maximum uptime and peak efficiency.