Clinical Equivalence Assessment Under EU MDR: Technical, Biological, and Clinical Equivalence

Why Equivalence Claims Are Harder Under EU MDR

Under the EU Medical Device Regulation (MDR 2017/745), demonstrating clinical equivalence is one of the most demanding aspects of clinical evaluation. Article 61 and Annex XIV Part A establish that a clinical evaluation may rely on clinical data from an equivalent device — but only if the manufacturer can demonstrate equivalence across three characteristics: technical, biological, and clinical. All three must be met. There is no partial equivalence.

The MDCG 2020-5 guidance document, published in April 2020, clarifies the specific criteria for each characteristic and highlights the differences between the MDR requirements and the older MEDDEV 2.7/1 Rev. 4 guidance. As Greenlight Guru explains, "demonstrating equivalence in the EU is not a simple process" because "EU MDR and MEDDEV 2.7/1 Rev. 4 use different language when discussing equivalence."

This guide provides a practical framework for conducting a clinical equivalence assessment, building the equivalence documentation, and navigating the regulatory expectations that notified bodies apply during conformity assessment.

The Regulatory Framework

Where Equivalence Appears in EU MDR

Clinical equivalence is addressed in several places:

• Article 61(5): Allows clinical evaluation to be based on clinical data from an equivalent device, provided specific conditions are met
• Article 61(6): Requires a contract between manufacturers for full access to the technical documentation of the equivalent device in specific circumstances
• Annex XIV Part A(3): Defines the three characteristics (technical, biological, clinical) that must be assessed for demonstrating equivalence
• Annex XIV Part A(1-2): Requires the clinical evaluation to follow a defined and methodologically sound procedure

The Role of MDCG 2020-5

MDCG 2020-5 is the primary guidance document for equivalence under the MDR. It:

• Compares MDR and MEDDEV 2.7/1 Rev. 4 criteria side by side
• Clarifies that some characteristics must be "the same" (not just "similar")
• Explains what constitutes "sufficient levels of access" to data
• Provides guidance on identifying and using clinical data from equivalent devices
• Covers products without an intended medical purpose listed in Annex XVI (per MDCG 2023-6)

The Three Characteristics of Equivalence

1. Technical Characteristics

Technical equivalence requires that the device and the reference device share similar design, specifications, and operating principles.

MDR Annex XIV Part A(3) criteria:

• The device is of similar design
• Is used under similar conditions of use
• Has similar specifications and properties (including physicochemical properties such as type and intensity of energy, tensile strength, viscosity, surface characteristics, wavelength, surface texture, porosity, particle size, nanotechnology, specific mass, atomic inclusions)
• Uses similar deployment methods, where relevant
• Has similar principles of operation and critical performance requirements

Key difference from MEDDEV 2.7/1 Rev. 4: MEDDEV required devices to be "used under the same conditions of use." MDCG 2020-5 clarifies that "the conditions of use shall be similar to the extent that there would be no clinically significant difference in the safety and clinical performance between the device in question and the device presumed to be equivalent."

Software algorithms: MDCG 2020-5 specifically calls out that "software algorithms which drive or influence the use of a device" must be similar. This includes software algorithms in both embedded software and standalone SaMD. However, equivalence applies to the algorithm and its intended purpose — not to the source code.

2. Biological Characteristics

Biological equivalence focuses on materials and their interaction with the body.

MDR Annex XIV Part A(3) criteria:

• The device uses the same materials or substances in contact with the same human tissues or body fluids
• For a similar kind and duration of contact
• With similar release characteristics of substances, including degradation products and leachables

Key difference from MEDDEV 2.7/1 Rev. 4: Under MEDDEV, exceptions were allowed — manufacturers could use "similar" materials instead of the same materials for devices in contact with intact skin and for minor components. MDCG 2020-5 explicitly states that these exceptions are not acceptable under the MDR.

The distinction between "same materials" and "similar release characteristics" is deliberate. As BSI explains in its equivalence webinar, "processing, design and the use environment may introduce small changes even when the raw materials are the same." This means the raw materials must be identical, but the processed material's release profile can be similar (not identical), as long as any differences do not create clinically significant effects.

3. Clinical Characteristics

Clinical equivalence requires that the device achieves similar clinical outcomes in similar patient populations.

MDR Annex XIV Part A(3) criteria:

• The device is used for the same clinical condition or purpose
• At the same site in the body
• In a similar population (including age, anatomy, physiology)
• Has the same kind of user
• Has similar relevant critical performance according to the expected clinical effect for a specific intended purpose
• Is not foreseen to deliver significantly different performances

Key requirements:

• "Same" applies to clinical condition, site in body, kind of user, and intended purpose
• "Similar" applies to population characteristics and critical performance
• The comparison must address severity and stage of disease

The Equivalence Assessment Process

Step 1: Identify the Reference Device

Select a device that is:

• Already CE marked under the MDR (or validly placed on the market under the MDD/Active Implantable Device Directive during the transition period)
• Within the scope of your intended use
• For which you can obtain sufficient data access

Note: You can reference multiple equivalent devices, but each device must independently satisfy all three characteristics. As MDCG 2020-5 and MEDDEV 2.7/1 Rev. 4 both state, "a combination of features of different devices is not permitted."

Step 2: Conduct the Gap Analysis

For each of the three characteristics, perform a detailed side-by-side comparison:

• List every MDR criterion for each characteristic
• Document the corresponding data for your device and the reference device
• Identify any differences
• Evaluate whether each difference is clinically significant

Use the equivalence table format provided in Annex I of MDCG 2020-5 as a template for documentation.

Step 3: Evaluate Clinically Significant Differences

Not all differences disqualify an equivalence claim. MDCG 2020-5 states that the assessment "shall conclude whether the listed technical, biological and clinical characteristics in the MDR are similar to the extent that there would be no clinically significant difference in the safety and clinical performance of the device."

Differences must be:

• Fully disclosed — you cannot hide differences
• Scientifically evaluated using preclinical and clinical data
• Justified with evidence showing the difference does not affect safety or performance

If differences have been introduced to address specific safety or performance issues, MDCG 2020-5 notes these must be "duly justified."

Step 4: Document Data Access

MDR Annex XIV Part A(3) requires "sufficient levels of access to the data relating to devices with which they are claiming equivalence." MDCG 2023-7 clarified that this means access to the data needed to establish clinical, technical, and biological characteristics — not necessarily the complete technical documentation.

For the manufacturer's own devices: Full access is typically available through internal documentation.

For another manufacturer's device: A formal agreement or contract is required for the exemption case described in Article 61(5) — specifically when the clinical evaluation is based on sufficient clinical evidence from a device for which equivalence can be demonstrated. Without a contract allowing full access to ongoing data, equivalence claims cannot be sustained for the purpose of conformity assessment.

For Class IIb and higher devices: Notified bodies scrutinize data access more rigorously. Access to the technical documentation of the equivalent device is expected.

Step 5: Integrate Into the Clinical Evaluation Report

The equivalence assessment becomes part of the clinical evaluation report (CER), which must:

• Reference the equivalence assessment as a source of clinical data
• Explain how equivalence data supports the safety and performance conclusions
• Address any gaps between equivalence data and the device's specific intended use
• Be updated as part of the post-market clinical follow-up (PMCF) process

MDR vs MEDDEV 2.7/1 Rev. 4: Key Differences

Practical Examples

Example 1: Orthopedic Implant

A manufacturer develops a new hip stem using the same titanium alloy (Ti-6Al-4V) and the same hydroxyapatite coating as a predicate device already CE marked under MDR.

Example 2: Software-as-a-Medical-Device (SaMD)

A manufacturer develops an AI-based diagnostic aid for detecting diabetic retinopathy. The algorithm uses a different neural network architecture than the reference device.

In this case, the different algorithm architecture would likely prevent a straightforward equivalence claim. The manufacturer would need additional clinical data to supplement the equivalence assessment.

Example 3: IVD Device

A manufacturer develops a PCR-based test for SARS-CoV-2 using the same target gene and primer sequences as a reference device.

Common Pitfalls and How to Avoid Them

1. Claiming Equivalence Without Data Access

This is the most common reason equivalence claims are rejected. If you cannot demonstrate sufficient access to the data supporting the equivalence claim, the claim fails. Plan data access agreements early in development.

2. Ignoring "Same" vs. "Similar" Distinction

MDR is specific: some characteristics must be identical ("same"), while others need only be similar. For biological characteristics, the materials must be the same — "similar" materials are not acceptable. For technical characteristics, design and specifications can be similar, but conditions of use must not create clinically significant differences.

3. Not Disclosing Differences

Every difference between your device and the reference device must be identified and evaluated. Hiding or omitting differences will be discovered during notified body review and will undermine your entire clinical evaluation.

4. Claiming Equivalence to an Annex XVI Product

Products listed in Annex XVI (without an intended medical purpose, such as contact lenses or dermal fillers) cannot serve as equivalent devices for medical devices. MDCG 2023-6 provides specific equivalence guidance for these products.

5. Using Multiple Devices to Build One Equivalence Profile

You cannot combine characteristics from different devices. Each reference device must independently satisfy all three characteristics. If no single device is equivalent across all three, you need to generate new clinical data.

6. Not Updating the Equivalence Assessment

The equivalence assessment must be maintained throughout the device lifecycle. Changes to the reference device, new post-market data, or updated clinical guidelines may require re-evaluation.

Documentation Checklist

A complete equivalence assessment package should include:

• Identification of the reference device(s) with CE marking details
• Side-by-side comparison table covering all MDR Annex XIV criteria
• Gap analysis identifying all differences
• Scientific justification for why differences are not clinically significant
• Evidence of sufficient data access (contracts, internal documentation)
• Reference to preclinical data supporting technical and biological claims
• Integration into the clinical evaluation report
• Plan for maintaining and updating the assessment during PMCF

Key Takeaways

Clinical equivalence under EU MDR requires demonstrating that your device matches a reference device across technical, biological, and clinical characteristics — with some characteristics requiring "the same" (not just "similar") attributes. MDCG 2020-5 is the authoritative guide for navigating the differences between MDR and MEDDEV 2.7/1 Rev. 4. The assessment must be documented, all differences disclosed and justified, and sufficient data access demonstrated. For complex devices, SaMD, and novel materials, equivalence claims face heightened scrutiny — plan early, document thoroughly, and consider whether generating new clinical data may be more efficient than defending a borderline equivalence claim.