Biomarkers came into widespread use for a practical reason: researchers and drug developers needed an objective, measurable way to gauge whether a disease was progressing, or whether a therapy was doing anything at all, without waiting years for clinical outcomes to declare themselves. That need was formalized in 2004, when FDA’s Innovation or Stagnation: Challenge and Opportunity on the Critical Path to New Medical Products report identified the lack of modern development tools — biomarkers chief among them — as a central reason promising science was failing to reach patients (FDA, 2004). Biomarkers do not replace clinical outcomes, but they can shorten the feedback loop, flag safety signals earlier, and help select the right patients for a study.
It is worth being precise about one point that is often blurred in popular coverage: a biomarker is not inherently non-invasive. Sample collection sits on a spectrum. Saliva and urine are genuinely non-invasive. A venipuncture for serum or plasma is minimally invasive. Cerebrospinal fluid (CSF) requires a lumbar puncture, and tissue biomarkers require a biopsy — neither of which is non-invasive by any reasonable definition. What has changed over the past two decades is not the nature of biomarkers themselves, but our growing ability to measure the same analytes in less invasive matrices. In this blog we will look at biomarkers in research, how researchers’ thinking around them has evolved, and which sample types are most useful for which questions.
Defining Biomarkers
The FDA–NIH Biomarker Working Group’s BEST (Biomarkers, EndpointS, and other Tools) Resource — the harmonized glossary both agencies use — defines a biomarker as “a defined characteristic that is measured as an indicator of normal biological processes, pathogenic processes, or responses to an exposure or intervention, including therapeutic interventions,” and notes that molecular, histologic, radiographic, and physiologic characteristics are all types of biomarkers (FDA-NIH Biomarker Working Group, 2016). Two things follow from that definition. First, nothing in it speaks to how the sample is obtained. Second, a biomarker is explicitly not an assessment of how a patient feels, functions, or survives — that is a clinical outcome, and the distinction matters a great deal in study design (Bodaghi, Fattahi, and Ramazani, 2023).
BEST also organizes biomarkers by the job they do: diagnostic, monitoring, pharmacodynamic/response, predictive, prognostic, safety, and susceptibility/risk. That functional framing is more useful to a research plan than the older habit of sorting biomarkers only by the technology used to measure them, because it forces the question that regulators ask first — what decision is this measurement going to support?
Biomarkers may have a variety of characteristics that make them useful in different research applications. Different biomarkers come with differing levels of sensitivity, accuracy, and predictive value — and, importantly, those performance characteristics are only meaningful relative to a defined context of use: the specific population, disease stage, and decision the biomarker is meant to inform. Biomarkers that are measured with proteomic or genomic techniques are known as molecular biomarkers. Molecular biomarkers can typically be found and measured in bio samples such as serum, plasma, cerebrospinal fluid (CSF), and other similar samples (Bodaghi et al., 2023).
Molecular biomarkers are often grouped further by analyte class. Protein biomarkers, for example, include peptides, full-length proteins, and post-translationally modified forms such as phosphorylated tau. Genetic biomarkers (e.g. mutations or polymorphisms in nucleic acid biomarkers such as DNA and RNA and lipid biomarkers are measured by different platforms. other molecules. These markers are useful for detecting and monitoring changes in processes such as inflammation, immune activation, and cellular stress. Cellular biomarkers — for example, immunophenotyping of peripheral blood mononuclear cells — are another category that has become important in clinical and translational research (Bodaghi et al., 2023).
Why Biomarkers Matter in Drug Development
The clearest illustration of why biomarkers exist is the machinery that has grown up around them. FDA’s Center for Drug Evaluation and Research runs a Biomarker Qualification Program whose stated mission is to work with external stakeholders to develop biomarkers as drug development tools, so that qualified biomarkers can “advance public health by encouraging efficiencies and innovation in drug development” (FDA, Biomarker Qualification Program). Section 507 of the Federal Food, Drug, and Cosmetic Act, added by the 21st Century Cures Act in 2016, formalized a three-stage pathway — Letter of Intent, Qualification Plan, Full Qualification Package. Once a biomarker is qualified for a specific context of use, it can be used across multiple drug development programs without FDA re-reviewing its suitability each time (FDA, Drug Development Tool Qualification Programs).
Much of this work is done pre-competitively. The Critical Path Institute’s Predictive Safety Testing Consortium, for example, brought industry, academic, and regulatory scientists together to qualify a panel of six urinary biomarkers of drug-induced kidney injury — clusterin, cystatin-C, KIM-1, NAG, NGAL, and osteopontin — which can flag renal injury within roughly 24 hours, well ahead of serum creatinine (C-Path, 2025). More recently, FDA qualified glutamate dehydrogenase (GLDH) as a liver safety biomarker, giving developers a liver-specific alternative to ALT and AST in patients whose muscle disease confounds those traditional tests (C-Path, 2025). Neither of those markers is “non-invasive” in any special sense; both are valuable because they answer a question sooner and more specifically than the standard of care.
A biomarker that has been shown, through extensive evidence, to reliably predict clinical benefit may be accepted as a validated surrogate endpoint. FDA notes that surrogate endpoints are used when the clinical outcome would take a very long time to observe, and that between 2010 and 2012 roughly 45 percent of new drugs were approved on the basis of one (FDA, Surrogate Endpoint Resources). That is the economic and ethical argument for biomarker science in a sentence: fewer patients, less time, and earlier go/no-go decisions — provided the underlying evidence is genuinely there.
Biomarker-Rich Research Samples
With so many types of biomarkers available to researchers, it should come as no surprise that there are a variety of bio samples that are of interest. Some samples of note are saliva, urine, CSF, plasma, and serum. Each offers a different window into a different set of biological processes — and each carries a different collection burden, which is often the deciding factor in study design. It helps to think of these matrices along two axes at once: what the sample can tell you, and what it costs the participant to give it.
Saliva is used to study biomarkers related to metabolism, immunology, DNA/RNA, and hormones. Collection of saliva is safe and non-invasive, making for readily available samples to researchers. The biomarkers can provide insights into oral and general health as well as give indicators on the presence of systemic disease and some cancers (Melguizo-Rodriguez, Costela-Ruiz, Manzano-Moreno, Ruiz, Illescas-Montes, 2020).
Another sample that can be collected non-invasively and is rich in biomarkers is urine. Like saliva, urine samples are inexpensive and readily available to researchers. Urine samples contain metabolites, peptides, and proteins that give insights into normal biological processes, disease states, and responses to therapeutic or drug treatments. Biomarkers in urine can provide information on kidney health or the presence of kidney damage, the presence of cancer and other diseases, and can be used to monitor and track general health trends over time (Sequeira-Antunes and Ferreira, 2023). Urine is also the matrix behind one of the most consequential regulatory biomarker successes to date — the FDA-qualified drug-induced kidney injury panel described above.
CSF sits at the other end of the collection spectrum. CSF surrounds the brain and spinal cord and is uniquely rich in markers of neurologic health, but obtaining it requires a lumbar puncture — a procedure that is invasive, uncomfortable, and impractical to repeat frequently or at population scale (synthetic or artificial CSF is available as a cost-effective matrix for assay development and in vitro work, though it is not a substitute for patient samples in a discovery setting). Biomarkers found in CSF are typically studied in relation to brain function, brain injury, and neurodegenerative diseases such as Alzheimer’s disease and related dementias.
Alzheimer’s disease is the clearest case study of how the field actually moves. Amyloid and tau pathology were first established in brain tissue at autopsy, then measured in living patients in CSF and by PET imaging, and only then shown to be reliably measurable in blood. Plasma phosphorylated tau species — p-tau181, p-tau217, and p-tau231 — now track brain tau pathology closely enough to serve as accessible surrogates (Kim, Shin, and Chang, 2025), with p-tau217 immunoassays performing comparably to CSF biomarkers in identifying abnormal amyloid and tau pathology (Ashton et al., 2024). In August 2026 FDA cleared a single-biomarker plasma p-tau217 test to help rule amyloid pathology in or out in adults 55 and older presenting with cognitive decline (Medical News Today, 2026). Saliva and tear-fluid markers for neurodegeneration are an active area of investigation but remain exploratory. The progression is worth noting because it is the same progression most biomarker programs follow: establish the biology in the most definitive matrix available, then work outward toward something you can actually measure repeatedly in a clinic.
The last sample types we’ll discuss are plasma and serum. Blood products are a staple of in vitro research and are only minimally invasive to collect, which is precisely why so much translational effort goes into moving markers into this matrix. Blood products are rich in biomarkers used to study immune responses and function, pathology, coagulation, and more. Serum biomarkers are especially popular for studying disease processes and therapeutic response. Complement serum — including guinea pig complement — is used to study the complement cascade of the innate immune system, in applications such as complement-dependent cytotoxicity assays and hemolytic complement activity testing, rather than coagulation. Plasma, which retains clotting factors, is the appropriate matrix for coagulation work and for many pharmacodynamic measurements.
If you’re getting ready to study biomarkers in your next research project, make sure you source the right high-quality samples for the job. Innovative Research is a trusted supplier of blood products, bio samples, and bio fluids that you can utilize in your biomarker research. Browse our full catalog or click the links in this blog to check out our products. Looking for a custom collection? Let us know! You can reach us via email at sales@innov-research.com.
Innovative Research’s portfolio of products are for Research Use Only. Not intended for human or diagnostic purposes.
Citations
Ashton NJ, Brum WS, Di Molfetta G, et al. Diagnostic Accuracy of a Plasma Phosphorylated Tau 217 Immunoassay for Alzheimer Disease Pathology. JAMA Neurol. 2024;81(3):255-263. doi: 10.1001/jamaneurol.2023.5319. https://jamanetwork.com/journals/jamaneurology/fullarticle/2813751
Bodaghi A, Fattahi N, Ramazani A. Biomarkers: Promising and valuable tools towards diagnosis, prognosis and treatment of Covid-19 and other diseases. Heliyon. 2023 Feb;9(2):e13323. doi: 10.1016/j.heliyon.2023.e13323. Epub 2023 Jan 30. PMID: 36744065; PMCID: PMC9884646. https://pmc.ncbi.nlm.nih.gov/articles/PMC9884646/#abs0010
Critical Path Institute. New Biomarkers Could Improve Early Detection, Monitoring of Kidney Injury. Press release, March 6, 2025. https://c-path.org/new-biomarkers-could-improve-early-detection-monitoring-of-kidney-injury/
Critical Path Institute. FDA Qualifies C-Path Biomarker GLDH to Detect Liver Injury in Clinical Trials. Press release, November 19, 2025. https://c-path.org/fda-qualifies-c-path-biomarker-gldh-to-detect-liver-injury-in-clinical-trials/
FDA-NIH Biomarker Working Group. BEST (Biomarkers, EndpointS, and other Tools) Resource. Silver Spring (MD): Food and Drug Administration (US); Bethesda (MD): National Institutes of Health (US); 2016-. https://www.ncbi.nlm.nih.gov/books/NBK326791/
FDA clears first single-biomarker blood test for Alzheimer's: 4 experts weigh in. Medical News Today; August 27, 2026. https://www.medicalnewstoday.com/articles/fda-clears-first-single-biomarker-blood-test-alzheimers-4-experts
U.S. Food and Drug Administration. Innovation or Stagnation: Challenge and Opportunity on the Critical Path to New Medical Products. March 2004; Critical Path Initiative. https://www.fda.gov/science-research/science-and-research-special-topics/critical-path-initiative
U.S. Food and Drug Administration, Center for Drug Evaluation and Research. Biomarker Qualification Program. https://www.fda.gov/drugs/drug-development-tool-ddt-qualification-programs/biomarker-qualification-program
U.S. Food and Drug Administration. Drug Development Tool (DDT) Qualification Programs; Section 507, Federal Food, Drug, and Cosmetic Act (21st Century Cures Act). https://www.fda.gov/drugs/development-approval-process-drugs/drug-development-tool-ddt-qualification-programs
U.S. Food and Drug Administration. Surrogate Endpoint Resources for Drug and Biologic Development. https://www.fda.gov/drugs/development-resources/surrogate-endpoint-resources-drug-and-biologic-development
Kim KY, Shin KY, Chang KA. Blood-Based Tau as a Biomarker for Early Detection and Monitoring of Alzheimer's Disease: A Systematic Review and Meta-Analysis. Int J Mol Sci. 2025;26(21):10330. doi: 10.3390/ijms262110330. https://www.mdpi.com/1422-0067/26/21/10330
Melguizo-Rodríguez L, Costela-Ruiz VJ, Manzano-Moreno FJ, Ruiz C, Illescas-Montes R. Salivary Biomarkers and Their Application in the Diagnosis and Monitoring of the Most Common Oral Pathologies. Int J Mol Sci. 2020 Jul 21;21(14):5173. doi: 10.3390/ijms21145173. PMID: 32708341; PMCID: PMC7403990. https://pmc.ncbi.nlm.nih.gov/articles/PMC7403990/
Sequeira-Antunes B, Ferreira HA. Urinary Biomarkers and Point-of-Care Urinalysis Devices for Early Diagnosis and Management of Disease: A Review. Biomedicines. 2023 Mar 29;11(4):1051. doi: 10.3390/biomedicines11041051. PMID: 37189669; PMCID: PMC10135468. https://pmc.ncbi.nlm.nih.gov/articles/PMC10135468/
