Preclinical Evidence (EU MDR & FDA): Decision Tree and Roadmap

Before a medical device can move toward market access, one practical question needs to be answered early: which preclinical evidence is needed first, and which studies can wait?

Preclinical development determines not only study costs but also a device’s regulatory viability and, ultimately, the product’s development and market-access pathway. Nevertheless, many MedTech teams plan their preclinical studies reactively rather than strategically.

The result: evidence requests from Notified Bodies or the FDA (U.S. Food and Drug Administration), wasted time, and avoidable costs. This article provides a structured decision tree for the preclinical development of medical devices and a practical roadmap for both the EU MDR (Medical Device Regulation) and the FDA. It demonstrates how a phase-based approach (feasibility → pilot → GLP) reduces the risk of additional requirements and puts preclinical research on the right regulatory track early on.

EU MDR vs. FDA: Preclinical Development with Two Logics and One Set of Expectations

EU MDR: What the reviewing expert is looking for

The requirements for preclinical development are set out in Annex I of Regulation (EU) 2017/745 (General Safety and Performance Requirements, GSPR). GSPR 10 is a central component here, as biological safety and material compatibility (e.g., in accordance with ISO 10993) must be systematically demonstrated. The verification of mechanical and physical properties is addressed in particular in GSPR 14, while high-level design and risk-related requirements are primarily derived from the general safety requirements (GSPR 1–9).

Where applicable, substance-related requirements under MDR Annex I 10.4—particularly for CMR/endocrine-disrupting (carcinogenic, mutagenic, reprotoxic) substances above the relevant threshold—must be separately evaluated and justified within the technical documentation. Annex II, Section 6.1(b) makes the results of preclinical studies a mandatory component of the technical documentation and requires evidence of GLP compliance, where applicable. This applies in particular to toxicological tests, but is also regularly required by Notified Bodies for submission-relevant biocompatibility studies in animal models.

FDA: Submission pathway, nonclinical evidence, and early consultation

The FDA structures the requirements for preclinical development according to the submission pathways. In the 510(k) pathway, depending on the product type and comparability to the predicate device, bench test data, performance data, and, where applicable, biocompatibility data are often required; the specific scope must be justified on a device-by-device basis. For products requiring PMA (Premarket Approval), 21 CFR Part 814 requires comprehensive nonclinical laboratory studies with GLP compliance in accordance with 21 CFR Part 58. The IDE pathway requires a Report of Prior Investigations covering all previous preclinical studies and clinical trials.

The FDA guidance document “General Considerations for Animal Studies” recommends: proof-of-concept prior to regulatory studies, logically justified sample sizes, and early Q-Submission discussions. For medical devices, the nonclinical evidence requirements are determined by the submission type, risk profile, product-specific regulatory guidelines, and, where applicable, early FDA feedback.

The common denominator of both systems: justifiable study selection, data quality, and complete traceability. Whether it’s an MDR preclinical strategy or an FDA preclinical development pathway, reviewers expect a compelling rationale for why exactly these studies were conducted at exactly this scale.

Decision tree: Which preclinical study at what stage?

Phase 0: Feasibility and laboratory testing → When is this sufficient?

Early exploratory studies may fall outside the formal GLP regime. Nevertheless, the scope, documentation, and usability of the data should be clearly defined in advance. Phase 0 is the early reality check: are existing bench tests and ISO 10993 data enough to explain the risks, or is further testing needed? For low-risk devices (e.g., Class I devices, surface contact ≤ 24 h), a robust feasibility assessment may already be sufficient. This phase identifies concepts that are not viable before costly studies begin.

Phase 1: Pilot study in an animal model → Criteria and outputs

Phase 1 becomes relevant when the device is intended to interact with tissue or when the literature base is insufficient. The pilot study helps confirm the suitability of test methods, refine protocols, and generate initial in vivo data. A GLP-like quality framework means that the study is planned, documented, and quality-checked in a disciplined way, but without claiming formal GLP compliance. Sample size and study duration depend on the research question, model, endpoints, and desired statistical power; pilot studies are typically designed to be smaller in scope than regulatory studies. The results inform the protocol design of subsequent regulatory studies and support Q-Submission discussions.

Phase 2: GLP/regulatory study → Triggers and effort

GLP is typically relevant when nonclinical safety data from formal laboratory studies form a key element of the submission. Whether and to what extent GLP is required or expected depends on the type of submission, study design, and intended use of the data. Requirements include: a study director, independent quality assurance, approved study protocols, comprehensive pathology, and statistically justified sample sizes. Strategic investment in Phases 0 and 1 pays off here: pilot studies prevent costly redesigns under GLP conditions.

Decision tree for preclinical evidence

Minimum data package by device type: general guidance

Implants and active medical devices

The scope of preclinical development and the associated preclinical data depend on the product type, contact type and contact duration. For implants, depending on the material, contact profile, and risk assessment, chemical characterization, selected biocompatibility evidence, and, if necessary, further toxicological or animal testing data must typically be evaluated. For active medical devices, depending on their design, additional evidence on electrical safety, EMC and—where software is present—software development and verification may be required.

Typical testing modules by device type

Note: These requirements are for general guidance. The specific scope of testing is determined by the product-specific risk assessment.

The 10 most common reasons for evidence requests

Experience shows that requests for additional information or evidence from Notified Bodies or the FDA can take several months to address and jeopardize market launch timelines. The most common causes identified in project practice are:

1. Lack of justification for the study design, model selection, or preclinical (animal) model
2. Lack of traceability: study protocol → raw data → report
3. Unclear definition of endpoints or lack of negative controls
4. GLP-like studies without QA sign-off
5. Deviations without CAPA documentation
6. No statistical analysis plan prior to study initiation
7. Test samples not representative of the final product
8. Chemical characterization omitted
9. Insufficient justification for sampling
10. No GLP-compliant archiving

The MiG Process Model: Project Scope Definition → Study Planning → Execution → Reporting

The process model for preclinical development begins with Phase 0 project scoping: product classification, regulatory pathway, and outstanding evidence gaps are evaluated collectively. This results in a prioritized study plan with go/no-go criteria for each phase.

Depending on agreed-upon project responsibilities, the contract research organization (CRO) for preclinical studies, for example, takes on the implementation phase, including study management, monitoring, and quality assurance. Reporting includes final reports structured for direct inclusion in the technical documentation or FDA premarket submission; where applicable, these may include GLP-compliant final reports.

The Phase 0 approach deliberately differs from the reactive preclinical study planning of many manufacturers. Instead of commissioning individual studies on an ad hoc basis, early preclinical study planning results in a coherent evidence pathway.

Roadmap to the Preclinical Study

Graphic: “Roadmap to the Preclinical Study”

Checklist: What study sponsors and CROs must clarify before the study begins

Structured preclinical development requires clear coordination between the study sponsor and the CRO. The following checklist summarizes the most important points to clarify:

• Target regulatory market and submission pathway (510(k), PMA, IDE, CE marking)
• Product classification and risk class
• Existing data set and identified gaps in evidence
• Study design: animal model, endpoints, sample size
• GLP vs. GLP-like requirements
• Timeline, milestones, and governance checkpoints
• Responsibilities for sample provision and logistics
• Report format and archiving requirements

FAQ – Frequently Asked Questions

What is an evidence gap?

An evidence gap refers to a gap between the available preclinical data and the evidence that a regulatory authority or Notified Body expects in a conformity assessment, FDA clearance/approval process, or submission review. The Evidence Gap Check systematically identifies these gaps and prioritizes the next steps.

When is a GLP study mandatory?

GLP is typically relevant when nonclinical safety data from formal laboratory studies form a central pillar of the submission. Whether and to what extent GLP is required depends on the submission type, study design, and intended use of the data—typically for PMA, IDE, or MDR conformity assessments for Class III devices. Less stringent requirements apply to exploratory studies.

How long does Phase 0 take?

The duration of a Phase 0 assessment depends on the project but generally takes several weeks. During this time, existing data is analyzed, a risk assessment is conducted, and the required scope of the study is precisely determined.

What distinguishes GLP from GLP-like?

GLP refers to formal compliance with 21 CFR Part 58 or the OECD principles, including a study director, independent quality assurance, and complete archiving. GLP-like follows the same quality principles (SOPs, traceability) without the full regulatory framework. GLP-like is suitable for pilot studies whose results are incorporated into the protocol design of regulatory studies.

Sources & further links

External References

• FDA – “General Considerations for Animal Studies Intended to Evaluate Medical Devices” (Final Guidance, March 2023)
• ISO – ISO 10993-1:2025 “Biological Evaluation of Medical Devices – Part 1: Evaluation and Testing Within a Risk Management Process”
• EU MDR 2017/745

Internal Links

• Preclinical Data: What makes a robust data package
• Animal Studies & FDA: When animal studies may be required in the FDA pathway
• Medical Device Regulation: Overview of MDR requirements
• Medical Device Classification: Device class as the starting point for the evidence strategy
• Choosing a Preclinical CRO: The operational next step after evidence planning
• Class III Medical Devices: Evidence requirements for high-risk products
• Simulation Techniques: In-silico methods as part of the evidence strategy

As of: May 2026 | Last reviewed: May 2026