By Dr. Hayes, VP and general manager, MPI Research
The complexity of new chemical entities presents significant challenges in terms of developing and validating bioanalytical methods. When evaluating your analytical testing operation or even selecting a CRO to do your analytical testing, pay attention to the following considerations:
Invest in equipment that will improve how your analytical testing is performed. With ever-increasing drug potency, the level of analyte in systemic circulation continues to challenge the limits of instrument sensitivity. You should be investing in state-of-the-art instrument platforms, such as ultrahigh performance liquid chromatography (UHPLC) interfaced to modern LC-MS/MS instruments, for example, Sciex API 5000, Waters Xevo, or Thermo Vantage systems. If using a CRO, evaluate the equipment it utilizes.
Consider the latest innovations that can save you cost and improve performance. For example, many labs and CROs still use conventional ELISA (enzyme linked immunosorbent assay) methods for immunoassay analysis. Consider then the Gyrolab workstation and the Gyrolab CD format, which can enable immunoassays to be performed using only nanoliters of sample. The automation and unique flow-through design reduces “hands-on” time and significantly speeds up throughput. Moreover, the system offers an unprecedented four-log dynamic range, thus reducing the need for repeat sample analysis with additional sample dilution. Compared to conventional ELISA, the Gyros platform has shown equal or better overall performance, while exhibiting a wider analytical range and a reduction in matrix-interference effects. Look for these types of gained efficiencies in all areas of your operation as well as your service providers.
Don’t ignore the impact of rising dose trials on patient safety. The nature of clinical bioanalysis requires high-throughput analysis to ensure patient safety for rising dose trials or first-to-file opportunities for generic drugs. Automated liquid handlers allow chemists to sustain a high level of productivity (e.g. 1500–2000 samples/day). For first-to-file opportunities, this may allow significantly reduced timelines for Clinical Summary Reports (even as few as 20 days from drug availability). You should pay careful attention to workflow and process, along with highthroughput analysis using state-of-the-art automation.
Are you using the most appropriate platform? LC-MS/MS is the standard platform for conventional small molecules, but it may not be the best platform for certain classes of molecules. Investments in GC-MS/MS and perhaps ICP-MS ensure that multiple detection platforms are available to meet all of your needs. For example, ICP-MS is the platform of choice for analysis of metals such as iron, potassium, calcium, and imaging agents in conventional biomatrices like urine, tissues, serum, or plasma.
Most modern immunochemistry groups will utilize MSD Imager 6000 readers as their core platform for performing regulated quantitative immunoassays, qualitative immunogenicity assessments, and cell-based assays for neutralizing antibodies. These systems are quite complementary to Gyrolab™ workstations that may then be utilized for nonregulated biomarker studies of novel biologics.
Are you currently meeting bioanalytical regulatory challenges worldwide? The reliable reporting of data from the quantitative analysis of drugs and their metabolites is at the core of any bioanalytical laboratory. Both sponsors and CROs performing regulated analysis are routinely inspected by worldwide regulatory authorities. The regulatory agencies of different countries each have their respective guidance documents describing the requirements for bioanalytical method validation and the application of these methods to routine drug analysis. Involvement in organizations like the Global Bioanalysis Consortium (GBC) and the Global CRO Council (GCC) afford the sponsor and your CRO forums for addressing scientific and regulatory issues in their operations.
It is easy to continue to approach your analytical testing the same way it has always been done or use the same service providers you have always used. With the pressures of reducing costs and improving timelines, the impact to the overall bottom line of your drug development efforts makes looking for improved ways of operating worth the effort.