Background of Annex X section 1.1d of MDD 93/42/EEC

Roland chung

Trusted Information Resource
#1
Hi forum,

Does any one know the background of Annex X section 1.1d of MDD 93/42/EEC? How will it happen?


Where demonstration of conformity with essential requirements based on clinical data is not deemed appropriate, adequate justification for any such exclusion has to be given based on risk management output and under consideration of the specifics of the device/body interaction, the clinical performances intended and the claims of the manufacturer.
Adequacy of demonstration of conformity with the essential requirements by performance evaluation, bench testing and pre-clinical evaluation alone has to be duly substantiated.
 
Elsmar Forum Sponsor

Remus

Involved In Discussions
#2
EU Commission wants all manufacturer to perfrom clinical evaluation. If you have a medical device, where its not complies with clauses 1, 3, and 6 of Annex I of 93/42 then you don't have to write a clinical evaluation. (All devices must complies 1, 3 and 6....)

In my opinion EU regulations are broken...
 

kreid

Involved In Discussions
#3
As said above there is a strong desire to have specific clinical data about a device.

Recently the MEDDEV describing Clinical evaluation (MEDDEV_2_7_1 rev 4 clinical evaluation) has been updated and strengthened.

Previously clinical evaluation was often carried out by doing generic literature reviews and this is something the the EC are trying to discourage.

I recommend having a look at the MEDDEV to (maybe) help answer your question.
 

Marcelo

Inactive Registered Visitor
#8
I cannot say what the background is, but I can show my opinion on what it means in practice as I've used this approach with several clients.

Take care because this is a long read with several different concepts being woven together.

First, there's the essential requirement that a clinical evaluation is required for all devices. This makes sense.

Annex X mentions:
As a general rule, confirmation of conformity with the requirements concerning the characteristics and performances referred to in Sections 1 and 3 of Annex I, under the normal conditions of use of the device, and the evaluation of the side-effects and of the acceptability of the benefit/risk ratio referred to in Section 6 of Annex I, must be based on clinical data. The evaluation of this data, hereinafter referred to as "clinical evaluation", where appropriate taking account of any relevant harmonized standards, must follow a defined and methodologically sound procedure based on...
Also, clinical data means:
clinical data" means the safety and/or performance information that is generated from the use of a device. Clinical data are sourced from:
– clinical investigation(s) of the device concerned; or
– clinical investigation(s) or other studies reported in the scientific literature, of a similar device for which equivalence to the device in question can be demonstrated; or
– published and/or unpublished reports on other clinical experience of either the device in question or a similar device for which equivalence to the device in question can be demonstrated;
The mentioned requirement:
Where demonstration of conformity with essential requirements based on clinical data is not deemed appropriate, adequate justification for any such exclusion has to be given based on risk management output and under consideration of the specifics of the device/body interaction, the clinical performances intended and the claims of the manufacturer. Adequacy of demonstration of conformity with the essential requirements by performance evaluation, bench testing and pre-clinical evaluation alone has to be duly substantiated.
is related to the exceptions to the "as the general rule".

What does this mean in practice?

Section 1 of Annex I is usually seen as the ER related to safety and to the acceptability of the benefit/risk profile

Sections 3 of Annex I is usually seen as the ER related to performance

Sections 6 of Annex I is usually seen as ER the related to acceptability of undesirable side-effects

(you can clearly see this in MEDDEV 2.7.1 Rev 4).

Although the MDD itself does mention benefit a few times, including the general requirement on benefits outweighing risks, it does not have a definition of benefit nor a definition of clinical performance. This is one of the problems that lead to, historically, CE marking being focused in device performance and not on patient benefit.

MEDDEV 2.7.1 Rev 4 does have a definition of "clinical performance" that also includes a "definition" of benefit.

Clinical performance: behaviour of a medical device or response of the subject(s) to that medical device in relation to its intended use, when correctly applied to appropriate subject(s). [EN ISO 14155:2011]
From the definition above, "behaviour of a medical device" related to what the device do (performance) and "response of the subject(s) to that medical device" is what happens to the patient after the device is used (benefit).

How to we verify that? We can generically separate things this way (although there my some exceptions):

To verify device performance: I may not need clinical data (I would say that most of the time you do not need clinical data to verify device performance) because I need to know what the device do (independently of what happens to the patient)

To verify patient benefit: I obviously need clinical data, because I need to know what happens to the patient, not the device

So, going back to the OP:

- If my device "clinical performance" is only related to the device performance part of the definition, in principle I would not need clinical data to verify it (an thus show compliance with ER 3)

- If my device clinical performance includes patient benefit, I do need clinical data to verify it.

One example that I've been working for some time with a client: Breast implants.

Clinical performance of a breast implant (situation 1) is historically seen as related to chest-size change and bra cup-size change, patient satisfaction, and quality of life (QOL).

All of these are related to what happens to the patient (in the first two, it's what physically happens to the patient, and the last two it's what psychologically happens to the patient). All of these need clinical data.

Now, let's say that hypothetically (situation 2) that instead of these 4 aspects of clinical performance, the only relevant aspect was the implant size (which is a characteristic of the device) - if the implant size is within x cm +- y, it's ok. I don't need clinical data to evaluate the implant size, I only need to bench measure it.

Now let's say that, instead of the 4, we have, for clinical performance (situation 3), the hypothetical implant size, but also have patient satisfaction and quality of life. So here the clinical performance would be a mix of device performance and patient benefit.

In these cases, clinical data would be needed in Situation 1 and 3, but not in 2.

This is a very simplistic view and example, and the problem is that it deals with only ER 3, not 1 and 6.

Going back to those:

Section 1 of Annex I is usually seen as the ER related to safety and to the acceptability of the benefit/risk profile

The ER related to safety includes clinical safety (defined as freedom from unacceptable clinical risk) and general safety (all other safety, such as electrical, mechanical safety, and also including aspects such as usability (use error safety)). In the case of non-clinical safety, we can usually use things like standards to show compliance. In the case of clinical safety, we need to verify what are the safety risks. If safety risks can be verified by means other than clinical data (usually in the case we can justify that for example compliance with standards alone is sufficient for clinical safety), then you can use this as part of the justification of non using clinical data

The acceptability of the benefit/risk profile depends on what the benefit of the device is - is it related to device performance only or it does include patient benefit?

This is also the reason the "Where demonstration of conformity with essential requirements based on clinical data is not deemed appropriate, adequate justification for any such exclusion has to be given based on risk management output..."

Section 3 of Annex I is usually seen as the ER related to performance

This include clinical performance and general device performance.

Clinical performance, as mentioned above, may include device performance or patient benefit.

One important note: generally, we cannot use standards for clinical OR device performance. There are some product standards that may define the full range of performance of simpler devices, but usually what we have is something like 60601, which deals with only a fraction of performance when it defines requirements for what it call "essential performance".

Sections 6 of Annex I is usually seen as ER the related to acceptability of undesirable side-effects

This also relates to something that happens on the patient, not device performance. So this is also needs clinical data. However, it may be the case that the side effects are negligible or are already historically known and the residual risk is acceptable, and in this case we usually can use a literature route.


So, for a summary of my opinion, you can justify not using clinical data if (and I may be missing some more requirements here):
- device safety can be evaluated by performance evaluation, bench testing and pre-clinical evaluation

- clinical safety can be evaluated by means other than clinical data

- benefit/risk profile does not include a benefit to patient component

- clinical performance does not include a benefit to patient component and thus can be evaluated by performance evaluation, bench testing and pre-clinical evaluation

- side-effects are either negligible or historically known, the residual risk is acceptable and thus you do not need clinical data

- your risk management shows that everything above is true

- you do not claim anything that requires clinical data
 
Last edited:

Roland chung

Trusted Information Resource
#9
Marcelo, thank you for your time and detailed input.

Generally, we can always find many cases that need clinical data. But it is really hard to find a medical device that does not provide patient benefit.

I was told that this exception is intended for well established and lower-risk devices. In this case, if harmonized standards are fulfilled, clinical data is not necessary, but other parts mentioned in the MEDDEV 2.7/1 are still required, such as PMS.
 

Marcelo

Inactive Registered Visitor
#10
Generally, we can always find many cases that need clinical data. But it is really hard to find a medical device that does not provide patient benefit.
This is not true. All IVD devices, for example, are not measured in relation to the benefit, because the real benefit (clinical outcome) dependent on further diagnostic and/or therapeutic options which could be available. That's why they measure their performance only. This is also true for most of the non-IVD diagnostic devices.

The key thinking here is "does the device use provide direct clinical benefit, or is the real benefit down the line, depending on other actions"? That's what I meant when I mention not having a benefit component.

I was told that this exception is intended for well established and lower-risk devices
Not exactly, as I mentioned most non-IVD diagnostic devices would fall into that, and they are not all well established and lower-risk devices.

In this case, if harmonized standards are fulfilled, clinical data is not necessary, but other parts mentioned in the MEDDEV 2.7/1 are still required, such as PMS.
You still have to perform the clinical evaluation, in fact. For example, you still have to perform a literature review to identify current clinical practice. You still have to justify how you fulfill the ERs, etc.
 
Thread starter Similar threads Forum Replies Date
T ISO 9001 Auditor Career without Quality Background? Career and Occupation Discussions 6
T With a Quality background, How high (designation) can you go in an organization? Career and Occupation Discussions 24
S How to Train People who have no ISO 9001:2000 Background (managerial level)? Training - Internal, External, Online and Distance Learning 1
G Question on Historical Background on ISO 10012 General Measurement Device and Calibration Topics 2
J CAPA History/Background Required - MSc Thesis on a CAPA System - Medical Devices Nonconformance and Corrective Action 5
S Shainin DOE - Paired Comparison? Background of this theory? Binomial distribution? Six Sigma 16
A Cell Manufacturing - The background and use of "manufacturing cells" presentation Lean in Manufacturing and Service Industries 5
H No background/training at all with TS 16949 - How do I get started? IATF 16949 - Automotive Quality Systems Standard 7
G What Is Your Company's Head Honchos Background - Poll Misc. Quality Assurance and Business Systems Related Topics 28
V Background of people in SQA (Supplier Quality Assurance) Supplier Quality Assurance and other Supplier Issues 5
D Is PMCF really a continuous activity per Annex XIV,Part B? EU Medical Device Regulations 4
R MDR, Annex I, 23.1 Interpretation - IFU on the website EU Medical Device Regulations 0
L EN 62368 (In an Annex - M.4.2.1) Secondary Lithium Battery Charging Safeguards CE Marking (Conformité Européene) / CB Scheme 2
P MDR/IVDR Annex III - Technical documentation on PMS EU Medical Device Regulations 1
D ISO 14971:2019 vs MDR Annex 1, Requirement #4 - "Manufacturers shall inform users of any residual risks" ISO 14971 - Medical Device Risk Management 5
K Applicability of Cybersecurity EU MDR 2017/745 Annex 1 23.4(ab), 14.2(d) CE Marking (Conformité Européene) / CB Scheme 3
K Applicability of eIFU as per EU MDR 2017/745 Annex 1 23.1 CE Marking (Conformité Européene) / CB Scheme 0
I IVD - 98/79EC - class IIa - Annex to the EC from the NB states the CM as one of the facilities? CE Marking (Conformité Européene) / CB Scheme 2
R Identify Medical Device characterstics as Annex C of ISO 14971 Risk Management ISO 14971 - Medical Device Risk Management 5
K EU MDR Annex 1 Chapter III: Information in the Instructions for Use-23.4 (e) the performance characteristics of the device; EU Medical Device Regulations 1
Rincewind MDR - GSPR - Annex I - Chapter II EU Medical Device Regulations 2
R An indication that the device is a medical device (MDR, Annex 23.2q) - applicable for accessories? EU Medical Device Regulations 5
S Difference between EU-MDR Annex IX and the Annex-combo X&XI EU Medical Device Regulations 2
A EN ISO 14971:2019 does not include the Annex Zs ISO 14971 - Medical Device Risk Management 4
S EU MDR Annex XIV - Clinical Evaluation Plan - What do these methods mean? EU Medical Device Regulations 12
K Annex XVI Device Transition Timeline under the MDR EU Medical Device Regulations 2
M EU MDR - Annex II 3b - What documents fall under this requirement? EU Medical Device Regulations 3
C IEC 60601-1-8, difference between table 4 and annex D IEC 60601 - Medical Electrical Equipment Safety Standards Series 2
A EU MDR Annex I section 11.3 - Medical Devices labelled as having a specific microbial state EU Medical Device Regulations 7
J MDR Annex VIII, Rule 6 Classification - Implication for lower risk CV products? CE Marking (Conformité Européene) / CB Scheme 3
Z 21 CFR and Annex 11 mapping document Pharmaceuticals (21 CFR Part 210, 21 CFR Part 211 and related Regulations) 1
A EU-MDR Annex I Requirement 10.1(d) EU Medical Device Regulations 3
T Post-Market Surveillance Plan - Requirements outlined in Annex III (1.1b) EU Medical Device Regulations 2
D Applicable MDR Annex's for Class IIa Medical Devices EU Medical Device Regulations 0
J MEDDEV 2.12/1's new MIR & IMDRF terms & codes (IMDRF Annex) EU Medical Device Regulations 1
M MDR Annex IX Chapter I, 2.2 (c) - Device identification procedures during manufacture. EU Medical Device Regulations 1
D Example for Accessories of "Annex XVI non-medical devices" and how to classify it now with respect ot EU MDR Other Medical Device Regulations World-Wide 1
P Performance evaluation (IVDD Annex VIII) & Design and Development Validation Studies EU Medical Device Regulations 1
H Critical Supplier Agreement acc. to NBOG 2010-1 Annex II EU Medical Device Regulations 5
L EU-MDR-Annex I - 10.4 (CMR & Endocrine-disrupting properties) - Labeling Content EU Medical Device Regulations 5
T EU-MDR-Annex I - 10.4 (CMR & Endocrine-disrupting properties) EU Medical Device Regulations 0
M Annex II - Technical Documentation. V&V, Performance and Safety EU Medical Device Regulations 3
S MDR Annex II Design & Manufacturing info - 'Adjuvants' definition EU Medical Device Regulations 3
J IVDR and MDR ANNEX I Requirements Template EU Medical Device Regulations 5
M Annex I - General Safety and Performance Requirements. Precise identity - how provided EU Medical Device Regulations 6
S Class II Medical Device Conformity Assessment Route according to Annex V only CE Marking (Conformité Européene) / CB Scheme 7
F IMDRF opened a Consultation on Annex E & F and the link to ISO 14971 ISO 14971 - Medical Device Risk Management 4
Douglas E. Purdy ISO/IEC 17025:2017 Clause 8 & Annex B ISO 17025 related Discussions 9
W EU GMP Annex XI - What is an "appropriate QMS"? Other Medical Device Related Standards 2
C Annex II EU MDR gap analysis EU Medical Device Regulations 7

Similar threads

Top Bottom