Companion diagnostic testing is an important part of modern healthcare because it helps clinicians identify which patients are more likely to benefit from specific medical treatments. These tests detect particular biomarkers, genetic variations, or other biological characteristics that can guide treatment decisions. As precision medicine develops, companion diagnostics are becoming increasingly important in oncology, targeted therapies, pharmaceutical research, and clinical laboratory testing.
Unlike general diagnostic tests that help identify or monitor a disease, a companion diagnostic is specifically associated with a particular therapeutic product or treatment decision. Its results can help healthcare professionals determine whether a patient is suitable for a particular medicine or whether additional testing is necessary. Understanding companion diagnostic technologies, test development, validation procedures, and manufacturers provides useful insight into this growing area of medical diagnostics.
What Is Companion Diagnostic Testing?
Companion diagnostic testing is a laboratory-based method used to identify biological markers that help determine whether a specific treatment is appropriate for a patient. These markers, known as biomarkers, may include gene mutations, changes in protein expression, or other measurable characteristics associated with a disease or a response to a medicine.
According to the U.S. Food and Drug Administration, a companion diagnostic provides information essential to the safe and effective use of a corresponding therapeutic product. Depending on the test, it may identify patients who are more likely to benefit from a medicine, those who may face an increased risk of serious adverse reactions, or patients whose treatment response requires monitoring.
Companion diagnostics are particularly relevant in precision oncology, where the molecular characteristics of a tumor can influence treatment selection. They are also important in pharmaceutical development because researchers can use biomarker information to understand how a medicine performs in a defined patient population.
How Companion Diagnostic Tests Work
Companion diagnostic testing generally begins with the collection of a biological specimen, followed by laboratory analysis and interpretation of the results. The exact procedure depends on the biomarker being investigated, the approved diagnostic method, and the associated therapeutic product.
Sample Collection and Preparation
The first stage involves collecting an appropriate specimen, such as tumor tissue, blood, plasma, or bone marrow. Tissue biopsies are frequently used to examine tumor-specific genetic changes or protein expression. Blood-based testing may detect circulating tumor DNA or other biomarkers when a suitable test is available.
After collection, laboratory personnel prepare the sample according to the diagnostic assay's instructions. Proper specimen handling, storage, transport, and preparation are important because unsuitable samples can affect analytical performance and the reliability of the final result.
Biomarker Detection and Laboratory Analysis
The prepared sample is analyzed using a validated diagnostic method. Depending on the test, the laboratory may examine DNA sequences, RNA expression, protein levels, or specific cellular characteristics. Specialized instruments, reagents, assay kits, and laboratory information systems support this process.
The resulting data are compared with established analytical criteria or interpretation thresholds. A report may identify a particular biomarker, indicate whether the result meets the test's defined criteria, or state that the specimen does not provide a conclusive result.
Clinical Interpretation
The final stage connects the laboratory result with the intended clinical use of the companion diagnostic. Healthcare professionals interpret the findings alongside the therapeutic product's approved labeling, the patient's clinical circumstances, and other relevant medical information.
A biomarker result does not independently guarantee that a medicine will work. Treatment decisions require appropriate clinical judgment, and the meaning of a positive or negative result depends on the specific test and its validated intended use.
Major Types of Companion Diagnostic Tests
Companion diagnostics include several technologies designed to detect different biological characteristics. The appropriate method depends on the biomarker, specimen type, required analytical performance, and intended therapeutic application.
Polymerase Chain Reaction (PCR) Testing
Polymerase chain reaction testing amplifies selected DNA or RNA sequences so that specific genetic targets can be detected. Real-time PCR and related molecular methods are used to identify particular mutations or other nucleic acid markers associated with a treatment decision.
PCR-based companion diagnostic assays can be designed for defined genetic targets and may support relatively focused testing workflows. Their performance depends on assay design, specimen quality, target characteristics, and validated operating conditions.
Next-Generation Sequencing (NGS)
Next-generation sequencing allows laboratories to analyze multiple genetic regions simultaneously. Depending on the assay design, an NGS panel may identify mutations, insertions, deletions, gene fusions, and other genomic alterations relevant to a therapeutic product.
NGS-based companion diagnostics can be useful when treatment selection depends on one or more molecular biomarkers. However, a result is clinically applicable as a companion diagnostic only when the test's intended use and relevant biomarker-treatment relationship are appropriately established. Not every finding reported by a broad genomic profiling test qualifies as a validated companion diagnostic result.
Immunohistochemistry (IHC)
Immunohistochemistry uses antibodies to detect specific proteins in tissue samples. The technique helps laboratories evaluate whether a target protein is present and, where applicable, determine its expression level or distribution.
In oncology, IHC-based diagnostic assays may assess biomarkers used in selecting certain targeted treatments or immunotherapies. Reliable interpretation requires appropriate staining procedures, laboratory controls, scoring criteria, and adherence to the specific assay's instructions.
Fluorescence In Situ Hybridization (FISH)
Fluorescence in situ hybridization uses labeled probes to identify selected DNA sequences or chromosomal changes within cells. It can help detect gene amplification, rearrangements, or other genomic abnormalities.
FISH may be relevant when a treatment decision depends on a particular genetic alteration that can be assessed through this technique. Its suitability depends on the target biomarker, specimen quality, assay performance, and clinical context.
Liquid Biopsy and Circulating Tumor DNA Testing
Liquid biopsy approaches examine biomarkers in blood or other body fluids. In cancer diagnostics, some tests analyze circulating tumor DNA, which consists of small DNA fragments released by tumor cells into the bloodstream.
Blood-based companion diagnostic testing can provide an alternative when tissue is difficult to obtain or when the associated test is specifically validated for plasma. However, a negative liquid biopsy result does not always exclude a biomarker, because the amount of detectable tumor DNA can vary. Depending on the clinical situation and the test's instructions, additional tissue testing may be appropriate.
Applications of Companion Diagnostics in Precision Medicine
Precision medicine aims to use relevant biological and clinical information to guide healthcare decisions. Companion diagnostics support this approach by connecting biomarker measurements with the intended use of particular therapeutic products.
Oncology and Targeted Cancer Therapy
Cancer treatment is one of the major applications of companion diagnostic testing. Some tumors contain genetic alterations or protein-expression patterns that are relevant to specific targeted therapies. Testing can help identify whether the biomarker criteria associated with a particular treatment are present.
Examples include testing for selected EGFR mutations in lung cancer, BRAF mutations in certain cancers, and HER2 or PD-L1 biomarkers in appropriate clinical settings. The relevance of each biomarker depends on the cancer type, the particular therapeutic product, the assay, and the applicable treatment indication.
Immunotherapy Selection
Certain immunotherapies are associated with biomarker testing that helps determine treatment eligibility or expected clinical relevance. Depending on the indication, diagnostic testing may assess protein expression, genomic features, or other biomarkers.
For example, specific PD-L1 immunohistochemistry assays are used in defined treatment settings. Results must be interpreted according to the assay-specific scoring system and the therapeutic product's approved indication rather than treating all PD-L1 tests as interchangeable.
Pharmaceutical Research and Drug Development
Companion diagnostics can be developed alongside a therapeutic product during pharmaceutical research. During clinical development, researchers investigate whether a biomarker is associated with treatment response, safety, or another clinically meaningful outcome.
This coordinated development process can help establish which diagnostic method is appropriate for evaluating the biomarker and how the test should be used with the corresponding medicine. Early collaboration among pharmaceutical companies, diagnostic developers, laboratories, and clinical researchers can help align the test's intended use with the therapeutic product's evidence requirements.
Treatment Safety and Response Monitoring
Some companion diagnostics help identify patients who may be at increased risk of serious adverse reactions to a particular therapeutic product. Others provide information used to monitor treatment response or support decisions about treatment adjustments when specified by the relevant clinical and regulatory framework.
The role of the test must be established for its particular intended use. A diagnostic that identifies treatment eligibility should not automatically be assumed to provide reliable information about ongoing response or future disease progression.
Companion Diagnostic Test Development and Validation
Developing a companion diagnostic requires scientific evidence that the test measures its intended biomarker reliably and supports its defined clinical purpose. The development process may involve analytical studies, clinical evidence generation, manufacturing controls, and regulatory review.
Biomarker Identification and Assay Development
The process often begins with identifying a biomarker that may be relevant to a therapeutic product. Researchers examine biological mechanisms, clinical data, and evidence connecting the biomarker with treatment response or safety.
Diagnostic developers then select an appropriate technology, such as PCR, NGS, or immunohistochemistry. They establish the assay design, specimen requirements, laboratory procedures, and result interpretation criteria. The test must be developed for a clearly defined intended use.
Analytical Validation
Analytical validation evaluates how reliably a test detects or measures its intended target. Important characteristics may include accuracy, precision, analytical sensitivity, analytical specificity, reproducibility, and the ability to detect a biomarker near the assay's established detection limit.
Developers may also evaluate interference, specimen stability, reagent performance, instrument variation, and consistency between laboratories. These studies help establish whether the test produces dependable results under its specified operating conditions.
Clinical Validation and Clinical Utility
Clinical validation examines whether the test identifies or measures the intended clinical or biological characteristic. For a companion diagnostic, the evidence must support the relationship between the diagnostic result and the intended use of the associated therapeutic product.
Clinical utility addresses whether using the test provides meaningful information for patient management or treatment decisions. Evidence requirements depend on the particular diagnostic, the therapeutic product, the claimed use, and the relevant regulatory framework.
Quality Control and Laboratory Verification
Quality control is essential for maintaining consistent diagnostic performance. Laboratories use appropriate controls, documented procedures, equipment maintenance, staff training, and quality management systems to monitor testing processes.
When a diagnostic assay is introduced into a laboratory, verification and ongoing performance monitoring help ensure that the method operates as expected within the laboratory's intended workflow. Laboratories must follow applicable requirements and the manufacturer's instructions.
Companion Diagnostic Manufacturers and Suppliers
The companion diagnostics industry includes companies that develop molecular diagnostic platforms, pathology assays, genomic profiling technologies, reagents, instruments, and clinical testing systems. Pharmaceutical companies may also collaborate with diagnostic developers to establish tests associated with particular therapies.
The following organizations are examples of companies active in relevant diagnostic technology markets. Their inclusion does not mean that every product they manufacture is an authorized companion diagnostic.
Roche Diagnostics
Roche Diagnostics operates in clinical diagnostics, including molecular testing, immunoassays, and tissue-based diagnostic technologies. These capabilities are relevant to biomarker detection, laboratory automation, and precision medicine workflows.
Agilent Technologies
Agilent Technologies develops laboratory instruments, analytical technologies, and pathology-related diagnostic products. Its diagnostic portfolio includes immunohistochemistry assays used in specified clinical settings.
Thermo Fisher Scientific
Thermo Fisher Scientific provides laboratory equipment, reagents, molecular biology technologies, and genomic analysis platforms. These technologies support molecular testing and research workflows used in diagnostic development.
Illumina
Illumina develops DNA sequencing technologies and genomic analysis systems. Its portfolio includes sequencing-based diagnostic products, including a comprehensive oncology test with specific authorized companion diagnostic indications.
QIAGEN
QIAGEN develops sample preparation technologies, molecular testing systems, and PCR-based assays. Its technologies support biomarker analysis and other molecular diagnostic applications.
Foundation Medicine and Guardant Health
Foundation Medicine focuses on genomic profiling for cancer care, while Guardant Health develops blood-based and tissue-related oncology testing technologies. Their diagnostic portfolios include tests with specific authorized companion diagnostic uses.
When evaluating companion diagnostic manufacturers and suppliers, healthcare organizations and pharmaceutical developers should examine the specific assay, intended use, regulatory status, specimen compatibility, analytical performance, laboratory requirements, and evidence supporting the relevant biomarker-treatment relationship. A company's general expertise in molecular diagnostics does not establish that every product in its portfolio is suitable for a particular treatment decision.
Regulatory Requirements for Companion Diagnostic Testing
Companion diagnostic tests are subject to regulatory requirements that vary by jurisdiction and product type. Regulatory review generally considers the test's intended use, performance evidence, labeling, manufacturing controls, and relationship with the corresponding therapeutic product.
United States Regulatory Framework
In the United States, the FDA oversees applicable in vitro diagnostic devices and maintains a list of authorized companion diagnostic devices. Depending on the product and regulatory pathway, a diagnostic may require premarket approval or another applicable form of authorization.
The authorized indication matters because a test may be approved for particular biomarkers, specimen types, cancer types, or therapeutic products. Laboratories and healthcare professionals should consult the current device labeling and the associated drug labeling when determining the appropriate clinical use.
European Regulatory Framework
In the European Union, companion diagnostics are regulated under the In Vitro Diagnostic Medical Devices Regulation, known as IVDR. The framework includes requirements for conformity assessment and, in applicable cases, consultation with the European Medicines Agency regarding the suitability of the diagnostic for the corresponding medicinal product.
Manufacturers must assess the requirements applicable to their product and intended market before placing it on the market. Regulatory authorization or conformity assessment in one jurisdiction should not automatically be assumed to establish authorization in another.
Challenges in the Companion Diagnostics Industry
Despite advances in precision medicine, companion diagnostic development presents several scientific, operational, and regulatory challenges. One important challenge is ensuring that a biomarker is clinically meaningful and that the test measures it consistently across relevant specimens and laboratory environments.
Another challenge is the coordination of diagnostic development with pharmaceutical research. A therapeutic product and its associated test may require aligned development timelines, evidence generation, labeling, and regulatory submissions. Changes to the therapeutic indication or biomarker interpretation may also require additional assessment.
Access to suitable specimens, specialized laboratory equipment, skilled personnel, and validated testing workflows can affect implementation. In addition, complex genomic testing may generate findings whose clinical significance is uncertain. Appropriate interpretation, patient privacy safeguards, and transparent communication of test limitations remain essential.
The industry must also address differences in regulatory requirements, reimbursement arrangements, laboratory infrastructure, and healthcare access across regions. These factors can influence how quickly an approved diagnostic becomes available in routine clinical practice.
Future Trends in Companion Diagnostic Technologies
The future of companion diagnostic testing is closely connected to advances in molecular biology, sequencing, computational analysis, and personalized medicine. As biomarker research progresses, diagnostic developers are investigating ways to measure increasingly complex biological characteristics and support more specific treatment decisions.
Comprehensive genomic profiling is helping researchers evaluate multiple genetic alterations within a single testing workflow. Advances in liquid biopsy technologies may expand the applications of blood-based biomarker detection where supported by clinical evidence and appropriate authorization.
Artificial intelligence and computational pathology may also assist with analyzing complex diagnostic data, identifying patterns, and supporting standardized interpretation. However, the clinical usefulness of these approaches depends on rigorous evaluation, appropriate validation, and compliance with relevant regulatory requirements.
Another developing area is the coordinated design of therapeutic products and diagnostic assays from the early stages of drug development. Closer collaboration between pharmaceutical companies, diagnostic manufacturers, biotechnology researchers, and clinical laboratories may help align biomarker evidence with the intended treatment application.
Conclusion
Companion diagnostic testing connects laboratory science with treatment decisions by identifying biomarkers associated with the safe and effective use of specific therapeutic products. Technologies such as PCR, next-generation sequencing, immunohistochemistry, and fluorescence in situ hybridization support different approaches to biomarker detection, while analytical validation, clinical evidence, and regulatory oversight help establish appropriate use.
For diagnostic manufacturers, pharmaceutical developers, and clinical laboratories, understanding companion diagnostic assay development, quality control, regulatory requirements, and specimen handling is essential. As precision medicine continues to evolve, companion diagnostics will remain an important part of biomarker-guided treatment, particularly in oncology and targeted therapy development. Their value ultimately depends on reliable testing, scientifically supported clinical interpretation, and use within the intended treatment context.
Disclaimer: The information provided in this article is for informational purposes only. We do not make any claims or guarantees regarding the accuracy, reliability, or completeness of the information presented. The content is not intended as professional advice and should not be relied upon as such. Readers are encouraged to conduct their own research and consult with appropriate professionals before making any decisions based on the information provided in this article.