Enhancing Bioanalytical Workflows with Latest Technology

Scientific conferences offer a venue for stakeholders in the bioanalytical community to converge and discuss current and emerging trends affecting the discipline. In recent years, panel discussions with key opinion leaders, have become a complementary medium to reflect on the direction of travel faced by the business of bioanalysis.

FREMONT, CA: To support traditional small compounds and monoclonal antibody treatments, bioanalytical systems are well-established within the pharmaceutical industry and CROs. These techniques, which mostly use MS/MS in conjunction with HPLC and ligand binding tests, have proved generally useful for determining the pharmacokinetics (PK) or immunogenicity of putative therapies as well as supplementary indicators of pharmacodynamics, safety, or efficacy (LBA). However, the ongoing endeavour to treat or better manage diseases has focused increasing attention on cutting-edge therapeutic approaches. This calls for a wider range of analytical tools, such as improved versions of existing platforms (such as high-resolution mass spectrometry and mass cytometry), as well as hybrid techniques (i.e., a combination of MS-based detection with immunoprecipitation). The ongoing effort to streamline laboratory workflows and enhance processes goes hand in hand with these new technologies. For CROs and pharmaceutical companies, this may be as easy as using automation, which can range from a modest automated liquid handler that does one task very well to more all-encompassing systems like the Gyrolab LBA platform.

In terms of what these novel medication and therapy types signify for bioanalysis, particularly where measurements cross the barrier from drug discovery to drug development, there is an increasing requirement for planning from a pharmaceutical perspective.It may be necessary to analyse the PK by utilising novel methods, pharmacodynamic endpoints, or more functional test readouts to support requests for new therapeutic modalities such as gene treatments and chimeric antigen receptor (CAR) T cells. The following new modalities were also mentioned as examples: 

• The use of oligonucleotides and the requirement for hybridization methods (such as qPCR or branching DNA) or the highest level of sensitivity (small amounts of oligonucleotides in tiny amounts of tissue biopsies).

• Gene therapy as it relates to evaluations of viral vectors, synthesis of missing protein vectors (LBA), and potential immunogenicity of those vectors (LBA, cell-based assays);

• Screening several human cell lines would be necessary for CAR macrophages and CAR T cells in a very iterative procedure under sterile circumstances. Measurements may incorporate concentration-time measurements of cells using flow cytometry (or molecular methods) or examining how the immune system is being enhanced and the related safety instead of typical PK endpoints on a discrete analyte. Flow cytometry and elispot platforms are mostly used to detect immune cell augmentation;

• When the danger of immunogenicity is substantial, stem cell therapies are used for enzyme replacement. Patients who respond to the medication are more likely to develop antibodies against the de novo enzyme or protein because they will perceive it as a foreign antigen. The validation of an anti-enzyme replacement antibody assay is still necessary even if the therapy for enzyme replacements is often intracellular and not circulating. Cellular blebs, apoptotic cells, necrotic cells, and cell waste/debris can all expose patients.

CROs are at the forefront of client requests to adapt instrumentation initially designed for exploratory research and employ it in drug development because the present outsourcing model continues to favour the majority of regulatory studies being externalised (to aid dose selection, asset progression and translational pharmacology measurements). Even though new technologies are often associated with buzzwords (such as multiplexing), sensitivity is still a major factor in how they are implemented (such as measurements of biomarkers expressed at low basal levels).