Why your predecessor device strategy keeps failing review

Written by HATEM RABEH, MD, MSc Ing

Your Clinical Evaluation Expert And Partner

in
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The assumption sounds logical. You have developed three generations of the same product. Each generation built on the previous one. Small improvements. Similar intended purpose. Same clinical application.

So naturally, the clinical evidence from Generation 1 should support Generation 2, which should support Generation 3.

But here is what reviewers actually see: a chain of assumptions that was never properly documented, equivalence claims that rely on outdated technical files, and clinical evaluation reports that treat design changes as negligible without demonstrating it.

The gap between what manufacturers believe they can carry over and what regulatory frameworks actually allow has become one of the most common sources of clinical evaluation deficiencies under MDR.

The Regulatory Foundation for Evidence Carryover

MDR Article 61(5) allows manufacturers to rely on clinical data from an equivalent device. This is the legal basis for leveraging clinical evidence across product generations.

But equivalence is not a declaration. It is a demonstration.

The regulation requires you to prove that devices are equivalent in terms of clinical, technical, and biological characteristics. MDCG 2020-5 provides the framework for demonstrating equivalence, and it is stricter than most manufacturers expect.

When you are dealing with your own product line, the temptation is to assume equivalence is automatic. After all, you designed all the versions. You know the similarities.

But knowing is not the same as demonstrating.

What Actually Breaks Down in Multi-Generational Strategies

The first breakdown happens in the technical comparison.

Generation 1 had a certain material composition, design feature, or software algorithm. Generation 2 changed one element. Generation 3 changed another.

Each change seemed minor at the time. But when you stack them across three generations, you realize the cumulative difference is significant.

I reviewed a case where a manufacturer claimed equivalence between a 2010 version and a 2023 version of a surgical instrument. Individually, each design modification was small. Cumulatively, the contact surface material, the ergonomic geometry, and the sterilization method had all changed.

The clinical data from 2010 no longer reflected the device being submitted.

The second breakdown happens in the clinical characteristics.

The intended purpose may be the same in broad terms, but the indications, contraindications, target population, or duration of use may have shifted.

A device originally intended for short-term use in adults may now be marketed for longer-term use. A device originally designed for a specific anatomical site may now be indicated for multiple sites.

These are not trivial changes. They affect the clinical risk-benefit profile.

The Documentation Gap Reviewers See

When I audit clinical evaluation reports for multi-generational product lines, the most frequent issue is not the absence of evidence. It is the absence of traceability.

The CER references clinical data from a previous generation but does not clearly link that data to the current device. There is no explicit demonstration of equivalence. No technical comparison table. No gap analysis showing what has changed and why it does not affect the clinical validity of the older data.

The manufacturer knows the connection. The regulatory team assumes it is obvious.

But the Notified Body reviewer does not have access to internal development history. They only have the documents you submit.

If the equivalence is not explicitly demonstrated in the clinical evaluation, it does not exist from a regulatory perspective.

This is where the concept of a predecessor device comes in.

Under MDCG 2020-5, you can use your own earlier device version as a predecessor if you can demonstrate equivalence. But you must treat it like any other equivalence claim: structured comparison, documented justification, clear linkage.

You cannot simply reference an old CER and assume continuity.

How Cumulative Changes Affect the Equivalence Claim

Let me walk through how cumulative design changes actually impact equivalence in practice.

Imagine you have three device generations:

Generation 1: Original design, clinical data from 2012.
Generation 2: Changed the coating material in 2016.
Generation 3: Modified the fixation mechanism in 2022.

Now you want to submit Generation 3 under MDR.

Can you use the clinical data from Generation 1?

The answer depends on whether the changes in Generation 2 and Generation 3 maintained equivalence.

If the coating change in Generation 2 altered the biocompatibility profile, then Generation 2 is no longer equivalent to Generation 1. If the fixation mechanism in Generation 3 changed the mechanical performance, then Generation 3 may not be equivalent to Generation 2.

What you need is a chain of equivalence.

You must show that Generation 2 was equivalent to Generation 1, and that Generation 3 is equivalent to Generation 2. Only then can you justify using data from Generation 1 to support Generation 3.

If any link in that chain is missing or inadequately justified, the entire carryover strategy collapses.

When You Actually Need New Clinical Data

Not every design change requires new clinical investigations. But some do.

The decision depends on whether the change affects safety or performance in a way that cannot be addressed through bench testing, biocompatibility evaluation, or literature review.

If you change the material in contact with tissue, you likely need new biocompatibility data. Depending on the nature of the change, you may also need clinical data to demonstrate that the new material does not alter clinical outcomes.

If you modify the mechanism of action, you need to evaluate whether existing clinical data still covers the clinical risks. If the modification changes how the device interacts with anatomy or physiology, clinical data may be required.

If you expand the indications or target population, you need clinical evidence specific to that new use.

I see manufacturers try to stretch equivalence claims to avoid generating new data. They argue that the change is minor or that performance testing proves comparability.

But performance testing proves technical comparability. It does not prove clinical comparability.

Reviewers will ask: does the existing clinical data cover the risks introduced by this change? If the answer is no, you need new data.

The Role of PMCF in Bridging Generational Gaps

Even when equivalence can be demonstrated, PMCF becomes critical for multi-generational product lines.

If your clinical evidence is based on data from an earlier generation, your PMCF plan must specifically address whether the current generation performs as expected in clinical practice.

This means PMCF is not generic. It must be tailored to the specific design changes and the gaps in your clinical dataset.

For example, if you changed the delivery mechanism between generations but kept the implant design the same, your PMCF should focus on evaluating the clinical impact of the new delivery method.

If you expanded the indications, PMCF should target the new patient population.

PMCF becomes the mechanism for confirming that your equivalence assumptions hold true in real-world use.

I have seen CERs where manufacturers claim equivalence based on older data but then submit a PMCF plan that does not monitor the variables that changed between generations. That inconsistency signals to reviewers that the equivalence claim is not properly thought through.

How to Structure Your Equivalence Demonstration

If you are planning to carry over clinical evidence across product generations, you need a clear equivalence demonstration section in your CER.

This section should include:

Technical Comparison:
A detailed comparison of the technical characteristics between the predecessor device and the current device. Include materials, design features, manufacturing processes, and performance specifications.

Biological Comparison:
Evaluate whether changes affect biocompatibility, tissue interaction, or biological response. Reference relevant ISO 10993 testing and assessments.

Clinical Comparison:
Compare the intended purpose, indications, contraindications, target population, duration of use, and clinical claims. Identify any differences and assess their clinical significance.

Gap Analysis:
For each identified difference, justify why it does not affect the validity of the clinical data from the predecessor device. If a gap cannot be bridged, explain what additional evidence is needed.

This structure mirrors the requirements in MDCG 2020-5 and provides reviewers with the rationale they need to accept your equivalence claim.

The key is transparency. If there are differences, acknowledge them and justify why they do not undermine the clinical evidence carryover.

What Happens When the Strategy Fails

When a multi-generational evidence carryover strategy fails during review, the consequences are significant.

The Notified Body will issue a major non-conformity related to clinical evidence sufficiency. You will need to either generate new clinical data or re-establish equivalence through additional documentation.

Generating new clinical data takes time. Depending on the device and the evidence gap, you may need a clinical investigation, which can delay certification by 12 to 24 months.

Re-establishing equivalence requires going back through your design history, technical files, and risk management documentation to build the case you should have built initially.

Both options are expensive and disruptive.

The earlier you identify weaknesses in your generational equivalence strategy, the more options you have to address them before submission.

The Practical Path Forward

If you are working with a multi-generational product line, start by mapping the evolution of your device.

Document every design change, material substitution, indication expansion, and manufacturing process modification across all generations.

Then assess whether each change maintained equivalence. Use the technical, biological, and clinical comparison framework to structure your assessment.

If you identify gaps where equivalence cannot be clearly demonstrated, determine what evidence is needed to bridge those gaps. This may be additional testing, literature analysis, or clinical data.

Build your equivalence demonstration into the CER as a distinct section with clear traceability to the predecessor device technical file and clinical data sources.

Align your PMCF plan with the areas of uncertainty introduced by generational changes.

This approach does not eliminate the complexity of multi-generational strategies, but it makes them defensible.

Reviewers will still scrutinize your equivalence claims, but they will have the documentation needed to verify them.

What separates a successful multi-generational strategy from one that fails is not the absence of design changes. It is the quality of the justification for why those changes do not break the clinical evidence chain.

That justification must be explicit, documented, and traceable.

Anything else is an assumption waiting to be challenged.

Peace,
Hatem
Clinical Evaluation Expert for Medical Devices
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