PMPF Under IVDR: Building Evidence That Survives Notified Body Review

PMPF Under IVDR: Building Evidence That Survives Notified Body Review

PMPF Under IVDR: Building Evidence That Survives Notified Body Review

Post-Market Performance Follow-up under IVDR 2017/746

Post-Market Performance Follow-up under IVDR 2017/746

Contents

1. Start with the claim

6. What belongs in the plan

2. Clinical evidence sources

7. Evaluation report structure

3. Avoiding a new study

8. Examples by device type

4. Legacy data

9. Common review problems

5. General vs specific methods

10. FAQ

Under the European In Vitro Diagnostic Regulation (IVDR 2017/746), a post market performance follow up IVDR strategy requires continuous, proactive data collection such as clinical studies or systematic registration audits rather than passive vigilance monitoring. To survive Notified Body review, this data must be compiled into a highly structured evaluation report that maps real world performance metrics directly against pre defined, quantitative acceptance. Which clinical performance sources hold up, how to use legacy data and literature, when you can skip a new study, and how to write the evaluation report so the logic is easy to follow.

For post market performance follow up IVDR, A lot of PMPF writing stops at Article 56(6) and a list of Annex XIII headings. That does not help much once you are already running PMS and preparing PERs. The harder question is simpler:

WHAT REVIEWERS ARE REALLY CHECKING

For the claims in your IFU, and the gaps still open in your PER, what post-market data is enough and what is only paperwork?

Below is a practical way to decide which sources count, how far legacy data and literature can take you, how to reduce PMPF scope without looking like you are dodging the requirement, and how to organise the evaluation report. The report layout draws on patterns seen in mature Class C serology files (ELISA-type assays with long market history), written in general terms only.

Start With The Claim, Not The Template For Post Market Performance Follow Up IVDR

Article 56 treats performance evaluation as ongoing work, not a one-off pre-market exercise. Article 56(6) requires updates from the PMPF plan (Annex XIII Part B) and the PMS plan (Article 79). For Class C and D devices, the PER must be updated at least once a year. This supports post market surveillance medical device traceability.

IN PRACTICE

The plan only works if it answers specific performance questions. Generic wording about “confirming safety and performance” does not get you far in review.

Problems that usually attract findings

  • IFU claims wider than the evidence behind them

  • Open PER or risk-file gaps that never become post-market questions

  • PMPF limited to complaints and a literature search, with no link to sensitivity, specificity, cut-offs, or scientific validity

  • A waiver based only on “well-established technology,” with no device-level proof

  • Literature used as if it studied your kit when it only covers the analyte or another manufacturer’s assay

Build a short gap map first

Put these four inputs next to each other before you draft the plan:

Intended purpose  →  PER conclusions  →  Risk-file gaps  →  SOTA claims  →  PMPF questions

1. Intended purpose: what is measured, function, clinical context, population, specimen types, intended user, and exclusions (for example, not for donor screening).

2. PER conclusions: scientific validity, analytical performance, clinical performance.

3. Risk management file: residual risks and open questions, including known limits such as IgM persistence, reactivation, or grey-zone results where relevant.

4. State of the art: guidelines, common specifications if any, competitor performance, EQA expectations.

Claim / uncertainty

Pre-market evidence

Gap after CE marking

PMPF question

Lowest-burden method

Clinical sensitivity ≥98% in symptomatic adults

Single-site residual-sample study, n=180

No multi-site confirmation; paediatric claim not supported

Does sensitivity hold across EU labs and age bands?

Multi-lab leftover-sample concordance + EQA panels

Detects current circulating variants

In silico inclusivity + limited wet panel

New lineages keep appearing

Do emerging variants stay within claimed inclusivity?

Quarterly literature/variant checks + targeted wet testing when risk appears

No biotin interference at OTC doses

EP07 spike study

High-dose biotin use is more common in practice

Are interference complaints or discordants rising?

Complaint coding + targeted survey of high-risk labs

Qualitative serology still within SOTA

Legacy clinical package + IFU claims

No papers naming the device this cycle

Do guidelines and peer assays still support the intended use and cut-off logic?

Time-bounded literature review + equivalence table + peer-assay vigilance

SIMPLE RULE

No gap means no need to invent a study. A real gap should not be buried under “general PMS.” That table is what the plan should be built around.

Clinical Evidence Sources And How They Usually Land In Review For In Vitro Diagnostic Medical Devices

Under  EU In vitro diagnostic medical devices 2017/746 Article 56(3), clinical evidence is the combination of scientific validity, analytical performance, and clinical performance. Article 56(1) matters more than people use it: you must set and justify the level of clinical evidence for the device and its intended purpose. That is the legal basis for not treating every Class B chemistry assay like a Class D programme if the justification is written properly.

1. Device-specific clinical performance studies: strongest for novel claims, companion diagnostics, Class D, and any claim that cannot be tied to your device through other data.

2. Leftover / residual sample studies: often the most efficient post-market option for IVDs, because you are checking the quality of the result, not intervening on a patient.

3. Routine diagnostic testing data: LIS extracts, discordant-result logs, peer method comparisons. Useful when representativeness and analysis methods are clear.

4. EQA / ring trials / proficiency testing: strong for real-world reproducibility across sites; one of the specific methods Annex XIII Part B points to for IVDs.

5. Published literature and guidelines: usually enough for scientific validity. For clinical performance, only when you can show the data applies to your device: same analyte, similar technology, comparable intended use, and performance metrics you can transfer.

6. User surveys and support inquiries: helpful for usability, off-label use, and rare matrix issues. Weak as the only support for sensitivity or specificity unless the survey is designed like a study.

IF THE IFU STATES A NUMBER

Sensitivity, specificity, LoD, agreement reviewers expect a data path that can still defend that number after market release. Literature alone rarely does that for Class C or D unless it is about your device or a carefully justified equivalent.

When the literature does not name your kit

For older serology assays, a review window often returns no papers on the manufacturer’s own product. That is common. The problem starts when competitor or analyte-level papers are written up as if they were device-specific clinical performance.

When A New Clinical Performance Study May Not Be Needed For PMPF IVDR

Annex XIII Part A, 1.2.3

Clinical performance studies are required unless you give a proper justification for using other sources of clinical performance data. A justification that usually holds includes:

  • scientific validity is not in dispute

  • analytical performance is complete and device-specific

  • clinical performance is supported by literature and/or routine diagnostic experience that applies to this device or a justified equivalent

  • the intended purpose is not novel (no new population, specimen type, or clinical decision claim)

  • residual risks do not depend on unproven clinical performance parameters

USUALLY ACCEPTABLE

Class B serum creatinine on a mature platform, years of EQA, published method comparisons for the same reagent system, no open performance trends. PMPF can rest on EQA, literature, and complaint or discordant analysis.

USUALLY REJECTED

Class C molecular assay claiming saliva when the only clinical literature is for NPS or serum. The specimen-type claim creates a gap that literature on another matrix cannot close.

Article 2(39) and devices where clinical performance is not meaningful

For in vitro diagnostic medical devices, MDCG 2022-2 notes that clinical performance data may not be expected for some products, such as non-sterile specimen receptacles, microscopy slides, or certain general reagents. You still need a performance evaluation and a written justification. Reduced PMPF should focus on functional or analytical performance and safety signals, not invented diagnostic accuracy endpoints.

Annex XIII Part B, Section 8 and the more common outcome

The regulation allows a documented case that PMPF is not appropriate for a specific device. Full waivers are uncommon. What mature Class C files more often conclude is:

TYPICAL WORDING THAT CAN WORK

General PMPF methods remain in place. No additional dedicated PMPF study is needed at this time.

That only works if the report shows the supporting package, not just the sentence:

Evidence element

Role in the argument

Time-bounded literature and guideline review

Scientific validity and SOTA are still current

Equivalence / similar-device table

Claims sit within the peer performance range

Vigilance on peer assays (MAUDE, HPRA, FSCA)

Class risks are watched even if your kit has no events

Complaints and support cases coded by performance impact

Diagnostic failures are separated from packaging issues

Exposure denominator (kits sold or estimated tests)

Complaint counts can be interpreted

CAPA / internal reports with performance impact

Manufacturing issues closed without residual performance risk

Stability through labelled expiry

Analytical performance holds for the claimed lifetime

No FSCA or serious incidents for the device

Benefit–risk is not challenged by vigilance

Intended-use boundaries monitored

Off-label or misuse signals are tracked

RESTART TRIGGERS

New intended purpose, design or cut-off change, rising performance complaints, guideline shift, peer-class FSCA pattern, EQA failure trend. Without triggers, “no additional study” looks like a permanent opt-out.

Articles 57, 58 and 70

If you do need new post-market data, study design drives the regulatory load (see MDCG 2025-5):

Situation

IVDR frame

What it means day to day

Any performance study

Article 57

Ethics and scientific integrity still apply

Non-CE or off-label use with invasive sampling, interventional use, or added risk

Article 58

Full authorisation pathway

CE-marked within intended purpose, no extra invasive or burdensome procedures

Art. 57; often no Art. 70(1)

Leftover-sample PMPF often sits here

CE-marked within purpose with extra invasive or burdensome procedures

Article 70(1)

Notification required

Companion diagnostics using leftover samples

Art. 58(2) carve-out

Evidence expectations remain high

One practical way to limit burden without skipping evidence is to design PMPF studies on leftover samples within the intended purpose, with pre-set endpoints, instead of defaulting to interventional designs that pull you into Article 58 or 70. This keeps post market performance follow up IVDR evidence focused and allows PMPF IVDR studies to remain proportionate.

Legacy Data Under MDCG 2022-8 For Post Market Surveillance IVDR

Long market history helps the proportionality argument. It does not replace the PMPF evaluation report. Treat IVDD-era material as input to appraise, not as finished IVDR evidence.

Legacy asset

How to use it

Common review pushback

Old clinical performance studies

Map to Annex XIII characteristics; check quality, bias, population, comparator

Not representative of current purpose or EU population

Analytical verification

Re-present against current GSPRs and claimed specimen types

Missing modern interferents or incomplete precision design

Literature files

Re-run with search strategy, inclusion rules, appraisal, and applicability

Unstructured collection of supportive papers

Complaints and vigilance

Turn into performance trends and PMPF triggers; separate packaging from diagnostic issues

No link to performance claims

EQA participation

Use as an ongoing method with acceptance criteria

Certificates filed but never analysed

Stability programmes

Link labelled lifetime to lot data through expiry

Lifetime claimed but not shown post-market

For post market surveillance IVDR, MDCG 2022-2 is clear that IVDD clinical performance studies are “other sources of clinical performance data.” They do not automatically meet Annex XIII 2.3. Quality and completeness still need assessment, usually with literature and/or routine diagnostic experience alongside them.

1

List every performance claim in the current IFU, including grey-zone rules and exclusions.

2

Rate each claim as strong, partial, or weak against the legacy package.

3

Close gaps that cannot wait for post-market work (novel claims, Class D common specifications, CDx bridging, new matrices).

4

Move acceptable residual uncertainties into PMPF questions with timelines.

5

Use the first PMPF evaluation report as the base for the future IVDR PER.

General Methods Vs Specific Methods For Post Market Surveillance Medical Device Evidence

Annex XIII Part B expects methods for proactive collection of safety, performance, and scientific data. In the absence of an IVD-specific template, many teams adopt MDCG 2020-7 and 2020-8 from PMCF. These methods support post market surveillance medical device evidence and keep post market surveillance IVDR planning connected to the PER.

Overlap with PMS and PSUR is normal. What matters is traceability: which outputs update the PER, risk file, IFU, and SSP for Class C and D, plus a clear statement on impact to technical documentation. In post market surveillance medical device documentation, post market surveillance IVDR traceability should remain clear.

  • Mature Class C qualitative serology: often general methods plus EQA and stability, with a justified “no additional study” conclusion if performance complaints are absent and SOTA is stable. Peer-assay problems in public databases should still be discussed as class risk.

  • Infectious disease molecular assays: usually need variant or strain surveillance and wet confirmation when in silico risk appears.

  • Quantitative clinical chemistry: EQA against peer methods often beats a weak survey.

  • Companion diagnostics: concordance with the clinical trial assay logic, label changes, and new indications.

What Belongs In The PMPF Plan For Post Market Performance Follow Up IVDR

For a mature qualitative serology kit, the question can be softer but still measurable: no performance-related complaint trend above a set rate per kits sold; EQA outcomes within IFU interpretation rules; no guideline change that makes IgM-only use without reflex testing unacceptable.

  • Each method linked to a question, owner, analysis approach, and decision rule

  • Direct references to PER and risk management sections

  • Schedule aligned with Article 56(6) and PSUR timing (annual for Class C and D)

  • A real similar-device table under Annex XIII Part B 5.2(f): principle, analyte, cut-off or grey zone, specimen, procedure differences, published Se/Sp, comparability score

  • Clear reasons for methods you are not running

Evaluation Report Structure For IVDR Performance Evaluation

The report should read as a decision record for the cycle, not a reprint of the PER and not a dump of raw tables.

Scope  →  Activities  →  Literature (two streams)  →  GSPR mapping  →  Complaints  →  CAPA / stability / FSCA  →  TD impact  →  Conclusion

Literature: keep two jobs separate

  1. Cycle PMPF literature: short window (for example 6–12 months): safety signals, peer-assay problems, recalls.

  2. Scientific validity refresh: analyte condition association, guidelines, longer look-back if needed (Annex XIII Part A 1.2.1).

For each stream, record databases, dates, keywords, inclusion and exclusion rules, numbers retrieved and included, appraisal, and whether any hit is device-specific.

Map findings to GSPRs

  • GSPR 1 intended performance and safety under normal use

  • GSPR 5 use-error risks (trained user, IFU clarity, grey-zone and retest rules)

  • GSPR 8 benefit–risk still acceptable; known limits managed (for example IgM not used alone)

Complaint coding

Bucket

Examples

What it means for PMPF

Diagnostic performance

False reactive or non-reactive results, invalid rates, cut-off disputes

Direct challenge to claims

Reagent / kit physical quality

Leakage, particulates in controls, shipping damage

Manufacturing or CAPA issue; check whether performance was affected

Use / instrument setup

Invalid runs linked to washer or reader setup

May point to IFU or training actions under GSPR 5

Documentation only

No product defect

Record for completeness

ALWAYS INCLUDE

An exposure denominator (kits sold or estimated tests) for the same period, and a cross-reference to the PSUR for Class C and D so the two documents do not diverge.

Close with an explicit technical documentation impact line: no change to IFU, PER, risk file, or design or named updates with owners. A conclusion that the device “remains safe and effective” without that line leaves the Article 56(6) loop incomplete.

Examples By Device Type

Common Review Problems

What gets rejected

Why

What to do instead

PMPF limited to complaints

Does not confirm performance proactively

Add EQA, concordance, SOTA or equivalence work, or targeted studies

One generic plan for the portfolio

No device-specific questions

Build the gap map from PER, risk file, and IFU

Literature without applicability

Cannot support your numbers

Separate scientific validity, SOTA, and device-specific data

Complaint counts without exposure

Rate cannot be interpreted

Report kits sold or tests in the same window

Packaging issues counted as clinical performance

Confuses the performance story

Code by diagnostic impact

“No additional study” with no supporting package

Looks like avoidance

Show the bundle, triggers, and next review date

No technical documentation impact line

Breaks the Article 56(6) loop

State change or no change, with owners if needed

PMPF and PSUR tell different stories

Traceability failure

Share source tables and cross-references

10. Working Approach

1

Claims drive evidence obligations. Narrow claims and clear exclusions reduce work more than a clever waiver.

2

Gaps create questions; questions create methods. Methods without questions are filler.

3

Legacy data is usable after appraisal. Market age supports proportionality; it does not skip the report.

4

Interventional studies can often be avoided. The performance question cannot.

5

Mature Class C serology can support “no additional study” only with a full general-methods package and restart triggers.

6

Article 56(1), Annex XIII 1.2.3, and Part B.8 work when written as evidence arguments.

7

The evaluation report should show: activities, evidence, GSPR and benefit–risk impact, technical documentation impact, and next actions.

IF YOU ONLY DO ONE THING

Open the PER, list every claim that is only partly supported, and assign each claim a post-market method, an owner, and a decision rule. That list is the PMPF plan.

FAQ

What is PMPF under IVDR?

Can PMPF be waived?

When can I avoid a new clinical performance study?

Does PMPF apply to legacy IVDs?

What evidence sources do Notified Bodies usually prefer?

Which articles apply to leftover-sample PMPF studies?

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Don't let European red tape stall your vision. We simplify complex EU building regulations so you can focus on creation. Explore our blog for the clarity you need during your project and the insights required for post-completion compliance. Read on for smoother approvals and smarter builds across Europe.

Don't let European red tape stall your vision. We simplify complex EU building regulations so you can focus on creation. Explore our blog for the clarity you need during your project and the insights required for post-completion compliance. Read on for smoother approvals and smarter builds across Europe.


Global Regulatory Support, Built Around Your Device

Morulaa supports medical device and IVD manufacturers with global registration, technical documentation, quality management and post market compliance. Through our regulatory specialists and local partners, we provide coordinated support across key international markets.

© Morulaa HealthTech Pvt Ltd. All Rights Reserved.

Global Regulatory Support, Built Around Your Device

Morulaa supports medical device and IVD manufacturers with global registration, technical documentation, quality management and post market compliance. Through our regulatory specialists and local partners, we provide coordinated support across key international markets.

© Morulaa HealthTech Pvt Ltd. All Rights Reserved.

Global Regulatory Support, Built Around Your Device

Morulaa supports medical device and IVD manufacturers with global registration, technical documentation, quality management and post market compliance. Through our regulatory specialists and local partners, we provide coordinated support across key international markets.

© Morulaa HealthTech Pvt Ltd. All Rights Reserved.

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