Accelerating Companion Diagnostic Development From Strategy to Approval

Contemporaneous approval requires deliberate alignment of diagnostic and therapeutic development plans and regulatory milestones. We develop integrated co-development timelines that synchronize CDx activities with therapeutic program decision points, including pre-submission planning, SRD or IDE determinations, analytical and clinical validation activities, and companion diagnostic and therapeutic regulatory submissions. Differences in therapeutic and companion diagnostic development and regulatory review timelines that may affect contemporaneous approval are considered, along with evolving regulatory pathways for companion diagnostics, including FDA’s publicly announced intent to reclassify many companion diagnostics from Class III to Class II, which may influence development planning and contemporaneous approval strategies. When companion diagnostic and therapeutic timelines diverge, we work with sponsors to implement regulatory and development strategies that mitigate risk and help maintain patient access.

We have conducted gap assessments across multiple organizations, including diagnostic companies at different stages of IVD development maturity. Assessments have included review of diagnostic platform options, regulatory strategy, quality system maturity, technical capabilities, commercial deployment models, and readiness for analytical validation, clinical validation, and market authorization. Our assessments have identified potential gaps before they affected development timelines, allowing us to work with sponsors to develop and implement prioritized remediation plans that reduce program risk and align with development timelines, regulatory objectives, and submission requirements.

Requirements vary depending on the jurisdiction, intended use, study design, patient risk, regulatory status of the diagnostic, where testing is performed, and how results are used in patient management. In the U.S., studies may require an IDE or a Significant Risk/Non-Significant Risk determination. In Europe, IVDR performance studies may require Ethics Committee review, Competent Authority authorization, and preparation of Article 58 and Annex XIV documentation. Additional country-specific requirements may apply when samples, investigational devices, or testing activities cross international borders. We assess applicable requirements and work with sponsors to prepare regulatory and ethics submissions, support authority interactions, and address study modifications throughout the authorization process.

Yes. We help sponsors determine whether an investigational companion diagnostic requires an IDE through Significant Risk and Non-Significant Risk determinations, FDA Pre-Submission interactions, and investigational study planning. For NSR and exempt studies, we help sponsors comply with applicable abbreviated requirements, including investigational labeling. For SR studies, we have extensive experience preparing IDE submissions, supplements, amendments, and annual reports. We also develop Pre-Submission packages to obtain FDA feedback on intended use, analytical and clinical validation strategies, transfer of efficacy and bridging approaches, and other key companion diagnostic co-development decisions.

We develop integrated global regulatory strategies that address U.S. and EU requirements in parallel, identifying where analytical and clinical data can be leveraged across jurisdictions and where jurisdiction-specific requirements require additional evidence, documentation, or studies. Our team has supported companion diagnostic programs through the IVDD-to-IVDR transition and across multiple stages of development, including clinical performance studies, Article 58 and Annex XIV documentation, Competent Authority and Ethics Committee interactions, significant modifications, ongoing compliance activities, and preparation for market authorization. This approach helps sponsors align global development programs while addressing region-specific regulatory expectations.

Our experience extends beyond PMA submission preparation to the regulatory and development activities that support successful approval. Through FDA Pre-Submission interactions, we have helped sponsors develop analytical and clinical validation strategies, including transfer of efficacy and bridging approaches for CTA, and regulatory strategies that align with FDA expectations. We have supported modular and traditional PMA submissions, prepared responses to FDA requests for additional information, and supported companion diagnostic programs through PMA approval and commercialization. Our experience also includes companion diagnostic programs that successfully utilized De Novo Classification Requests and Breakthrough Device Designation, which can simplify regulatory requirements, enhance FDA engagement, and support more efficient development and review pathways.

Yes. We develop clinical performance study plans and protocols that support FDA, IVDR, and international regulatory requirements, including sample selection strategies, reference method justification, endpoint selection and intended use considerations, statistical analysis plans, biomarker-positive and biomarker-negative enrollment targets, transfer of efficacy and bridging approaches, and strategies for incorporation of data generated outside the United States. For IVDR companion diagnostic studies, we also address scientific validity, biomarker rationale, analytical performance, clinical performance, risk management, and performance study reporting requirements. Our protocols are designed to generate valid scientific evidence that supports analytical and clinical performance claims and the intended use of the companion diagnostic.

Analytical validation strategies are developed based on the biomarker characteristics, technology platform, intended use, and clinical application of the companion diagnostic. Validation considerations differ for quantitative, semi-quantitative, and qualitative assays. Our approach considers assay-specific performance characteristics, sample type and availability, biomarker prevalence, biomarker-positive and biomarker-negative representation, sample size requirements, and the appropriateness of surrogate or contrived specimens. Early validation planning helps ensure that analytical evidence is available when needed to support IDE applications, IVDR Article 58 and Annex XIV performance study submissions, trial enrollment, and biomarker-based patient selection. Validation plans, study protocols, and acceptance criteria are developed using applicable regulatory guidance, recognized consensus standards, and jurisdiction-specific requirements to support analytical and clinical performance validation.

Sample adequacy is one of the most common risks in companion diagnostic clinical performance studies. Biomarker prevalence, assay performance characteristics, and intended clinical application are critical considerations in ensuring adequate representation of biomarker-positive and biomarker-negative populations within analytical and clinical validation programs. We evaluate enrollment targets, expected rates of subject misclassification, specimen availability, enrichment strategies, and statistical requirements to support adequate representation of clinically relevant populations. Particular attention is given to transfer of efficacy and bridging programs, where differences between the clinical trial assay and the candidate companion diagnostic may affect patient classification, concordance, estimates of treatment effect, and ultimately the clinical claims supported by the study.

Companion diagnostics are used to support treatment decisions and therefore require ongoing confirmation of clinical evidence throughout the product lifecycle, specifically the scientific validity, analytical performance, and clinical performance that comprise the IVDR performance evaluation framework. Under the IVDR, manufacturers are required to establish and maintain PMS systems that proactively collect and evaluate post-market information throughout the device lifecycle. We assist sponsors with the development of PMS systems, including PMPF plans that maintain alignment with the risk management process and inform updates to the Performance Evaluation Report. For Class C companion diagnostics, PSURs are required on an annual basis, and we support sponsors throughout that reporting cycle. Our PMPF services include post-market clinical performance studies, PMPF planning, Performance Evaluation Report updates, PSUR preparation, significant modification assessments, and integration of post-market evidence within the performance evaluation and risk management processes.

Cutoff values are a critical component of companion diagnostic development because they define how patients are classified and how the test will be used to support treatment selection and other clinical decisions. Key considerations include biomarker biology, analytical performance, intended use, available clinical evidence, and the relationship between biomarker status and treatment effect. We help sponsors evaluate candidate cutoff strategies, assess the impact of alternative classification approaches, and determine the evidence needed to support cutoff selection within analytical and clinical validation programs. Additional considerations may include qualitative, semi-quantitative, and quantitative test results, ordinal scoring systems, equivocal or indeterminate result categories, and the potential impact of cutoff selection on patient classification, transfer of efficacy, bridging strategies, and the clinical claims supported by the companion diagnostic.