A SUMMARIZED REPORT OF THE

VIRTUAL MEDTECH:

JUNE 15-17, 2021

EU MDR EXCHANGECONFERENCE

A SUMMARIZEDREPORT OF THE

Co

nten

tsIntroduction 3

First Experiences with EU MDR Submissions 4

EUDAMED - How bad can it be? 7

Artificial Intelligence (AI):

Practical Applications to Meet MDR and

IVDR Labeling Requirements 9

Identification and Evaluation of Risks 11

Pragmatic Solutions to Align Clinical Evaluation,

Risk Management, and PMS Processes 13

Bringing New Devices to Market Under the EU MDR 15

Notified Body Expectations for Clinical Evaluation Review 16

NB Feedback: Post Market Surveillance (PMS)

– How to Succeed in the First Year Under EU MDR 20

Notified Body (NB) Update:

Periodic Safety Update Report (PSUR) 21

Updates and Strategies for

Post Market Clinical Follow-up (PMCF) 24

A SUMMARIZED REPORT OF THE VIRTUAL MEDTECH: EU MDR EXCHANGE CONFERENCE 3

Introduction

MedTech 2021 provided an exciting preview into the mammoth transition that the Medical DevicesIndustry is currently experiencing with MDR/IVDR. The conference, held virtually from June 15-17, 2021, was a meeting point for all stakeholders, including the EU Commission, Notified Bodies, and various manufacturers. The interactive sessions were designed for the attendees to gain crucial knowledge about and insights into the following:

• Practical know-how, strategy, and resources needed to meet and maintain the regulatory, clinical,and PMS requirements of the EU MDR,

• First experiences with Notified Body review on submissions from both sides, • Innovative technologies and solutions to the challenges posed by MDR, and• Urgent and cautionary examples of exactly why companies should not underestimate the scope of

this transition.

Cactus Life Sciences was a proud sponsor of The Virtual MedTech: EU MDR Exchange Conference, and several team members from our Medical Device Solutions group participated in the event. Vera Edge-worth, Medical Director at Cactus Life Sciences, led a session on day 2 of the conference that centered around PMS and risks, titled “Pragmatic Solutions to Align Clinical Evaluation, Risk Management, and PMS Processes.”

Our team got a lot out of the conference, and we would like to share some of our key takeaways and insights with you in this report. The following is a compilation of summaries from some of the key sessions our team attended over the 3-day summit. We hope it serves as a helpful guide to some of the key highlights spanning the conference and all the fascinating, forward-thinking discussions you would like to revisit or possibly weren’t able to attend. Feel free to click through the table of contents to sections or sessions of particular interest for a clear glimpse of important topics related to the EU MDR.

We’d love to hear from you if you have any questions or feedback.

Happy reading!

The Cactus Life Sciences Team

Contact Us

https://lifesciences.cactusglobal.com/contact.html

First Experiences with EU MDR Submissions

Speakers:Regina Short, Program Manager, EU-MDR, Stryker;

Denise Daugert, Senior Staff Regulatory Affairs Specialist, Stryker;

Kemine Hale, Senior Manager Regulatory & Clinical Affairs, PRRC-AR, Advanced Bionics;

Elizabeth Gfoeller, Corporate Director, Regulatory Affairs, MED-EL, Austria

Denise Daugert and Regina Short, both from

Stryker, opened this session by sharing the

biggest challenges and key learnings from their

first MDR submissions. The main challenges

included management of notified body (NB)

questions, clinical review, and data remediation

or compilation. They pointed out that there are a

maximum of three allowable rounds of questions

with the NBs. The questions are very specific to

each NB, which could be a challenge if not

planned well. This challenge can be overcome by

communicating and sharing information on

strategy and approach with the NB, ensuring

there is consistency in the approach across all

technical documents, providing translation of

technical documents for suppliers from the other

countries, and gathering sufficient data for the

legacy devices.

Data Compilation / Remediation:

Scoping & Tech Doc data compilation both internally and across suppliers

Existing products having to meet Annex II Section 3b requirements & interpretation of requirements

Additional requirements for Validation, inspection and adjuvants documents.

Remediation efforts including mfg summaries, re-validations, procedure/documentation updates, resulting on occasion in the obsolescence of SKU’s.

Project Challenges


Regulatory Submission

Strategy

Communicationwith

Notified Body

Submission/ Approval


Kemine Hale, from Advanced Bionics, further

emphasized the importance of communication

with the NBs regarding the timeline, conformity,

and strategies for submission and approval. She

highlighted the challenge associated with

reclassification of all the existing AIMDD

products owing to the absence of finalized

MDCG guidance. For legacy products, gaps must

be addressed to meet the MDR requirements.

She also stressed on the internal discussions that

the manufacturers have regarding sufficient

clinical data (e.g., asking questions like ‘what is

meant by sufficient data?’) and the quality of

clinical data. Based on her experience, she

underwent 2 rounds of questions with the NBs.

She also pointed out that the question rounds are

separate for the certification board. The best

approach is to close modules one-by-one as NBs

insist on a very thorough review process.

Elizabeth Gfoeller, from MED-EL, suggested a

“holistic” approach for MDR submissions where

manufacturers must ask themselves “what do all

the device data mean?”, including design tests, the

conclusions drawn, and getting the claims right,

especially, for low-risk devices. For non-active

devices, an important question of usability must

be answered using usability engineering. While

Elizabeth described the new definitions of Class

III devices under MDR, she also enlisted the new

documents that have been made mandatory for

obtaining approval, such as UDI DI, labeling

information (like implant cards), lifetime of the

device, information on steroid components, and

mechanism of scrutiny.


The NBs are looking for or demanding

consistency in the definitions of intended clinical

benefits, intended purpose, intended user, and

target populations across technical

documentation like IFU, CER, CER, SSCP and in

how these documents should be linked with each

other. One of the important considerations now

is to ensure that all device related claims/benefits

are covered in PMS and PMCF studies, which can

be achieved if each device has its own PMS or

PMCF study, with emphasis on proactive vs.

reactive measures and volume vs. quality

measures.

The biggest learnings from the EU MDR submissionprocess included the following:

• Clear and constant communication with the

respective NB to get a clarity on the

expectations.

• Creating a strategy for submission. Hale

suggests projecting a timeline for the

submission that will

help with resource allocation for both the

manufacturer as well as the NB.

• Ensuring consistency in approach while

compiling and remediating technical

document information across the products

manufactured by suppliers and products

manufactured in-house.

• According to Stryker, translation of

documents is necessary if suppliers are in

different countries.

• Data gathering for legacy devices – gathering

and remediating manufacturing and clinical

data, including retrospective data.

• An EU-based authorized representative is

mandatory if the company is based outside

the EU.

• All fields of the submission checklist do not

need to be filled and can be completed based

on the type of device and the classification of

the device. Justification for why the element

of the list is not applicable needs to be

provided.

EXTERNAL: Reviews - good, bad & ugly?

Intended purpose - what does this mean? Is it consistentthroughout TD?Codes - are you covered? Increased importance of Codesfor you and NBNB Reviewer turnover -> not predictable / commonunderstanding yetFull reassessment of certain review modules or possibility tore-use recent AIMD recert reviews is inconsistently appliedIncreased Bureaucracy -application forms, TDdocumentation, ...

Main Learnins / Tips

EXTERNAL: Reviews - good, bad & ugly?

Technical documentation - what’s new?1. MDR Application Forms2. Classification3. GSPR checklist (e.g. CMRE)4. UDI (Basic-UDI)5. SSCP6. Manufacturing info7. PMS PLAN

TD Submission & Reviews

Richard Houlihan (CEO at Eudamed.com), in his

talk on how bad EUDAMED can be, stressed upon

the enormity of the MDR transitions and how not

to underestimate the requirements and

complexity of EUDAMED. In addition, he

cautioned that the EU is likely to provide very

limited support to the industry.

While talking about the importance and

requirement of EUDAMED due to the increased

scope of MDR compared to MDD and much

higher public transparency, Houlihan advised that

even though MDR has been delayed, the process

of registration and data upload is going to be an

uphill task.

EUDAMED - How bad can it be?

The main modules of EUDAMED requiring data submissions are as follows, and each one can

be considered a project in itself.


Speaker:Richard Houlihan, CEO, Eudamed.com

• Data uploads are in a complex format. Hence, common understanding is key, and achieving an understanding of formats and rules will require a steep learning curve.

• There are multiple data input options – web, bulk upload, and machine-to-machine (M2M).

• Each company will require a full IT and change management project.

• Data validation and business rules are extensive.

• EUDAMED UDI specifications are complete and mostly public; therefore, immediate action is required for

planning of IT strategies and building teams. This will save time and effort and avoid mistakes.

investing in training, third party tools, and support

preparing basic UDI and UDI DI groups

preparing spreadsheets and collating EUDAMED data

Some key takeaways regarding EUDAMED data submissionsinclude the following:


Speaker:Kai Simonsen, VP, Production and Quality Systems, TransPerfect Medical Device Solutions

Kai Simonsen (VP, Production and Quality

Systems, TransPerfect Medical Devices

Solutions) rightfully warned of a “content

tsunami” in this talk. This massive increase in

content due to the increased requirements from

MDR/IVDR places considerable pressure on not

only the medical device industry but also the

translation industry, as more content means more

revisions and more translations with greater need

for maintaining comprehensibility, accuracy,

consistency, and compliance. All this taken

together is likely to impact the “cost of content”

and “time to market,” unless the industry looks

toward innovative solutions to handle this.

In recent years, there has been a tremendous

growth in the application of “Automated

Language Translation” aka “Machine Translation”

(MT) with greater accessibility via apps such as

Google Translate, etc. leading to high

expectations. However, currently, the results are

mixed. MT is still considered as a useful but risky

tool - not good enough for government work! But

there is a growing temptation of cost and

turnaround reduction that is pushing the medical

devices industry toward MT adoption. Progress in

output quality has made AI neural network-based

MT commercially feasible for risky/complex

content types. Even with AI-based MT, multiple

factors must be considered for labeling content,

which is a mixed bag. See below.

• Jargon-heavy

• Context-dependent

• Literal

• Ambiguous

• Complex

• Mechanical

Thus, AI alone will not “cut it”, and it is not a

replacement of human translation but an

enhancement, much like the robotic surgical

systems with the surgeon at the controls. Thus,

Simonsen proposes the following solution:

AI -based MT translations followed by

“post-editing” by an expert human translator.

Once feasibility is established, the productivity

gains are likely to be quite significant—as

demonstrated in the figure below—even taking

into consideration challenges posed by different

languages.


Artificial Intelligence (AI): PracticalApplications to Meet MDR and IVDRLabeling Requirements

A positive side-effect of output quality

in this system is that improving output

quality will also improve productivity,

which is generally not the case with

human translators.

Engine customization by training leads

to a tremendous improvement in

“post-editing distance” over time, as

shown in the Figure 1

Therefore, using a risk-based approach

in implementing an AI-supported

labeling translation is the way to

successful adoption of AI to meet MDR

and IVDR labeling requirements.


Improving Outputthrough Training

Feed your AI engine validated translations(TM, Glossaries)

Give your engines feedbackPED IMPROVEMENT WITHENGINE CUSTOMIZATION

*Lower PED indicates better quality

Train your translators - Post Editing is different from proofreading

Initial PED PED after customization

USE CASE 1English + French

USE CASE 2English + German

USE CASE 3English + Spanish

USE CASE 4Portuguese + English

0%

5%

10%

15%

20%

25%

30%

35%

40%

45%

Productivity goal = achieving targetlevel of accuracy with the same or lessinvestment (time/cost), compared toexpert human translation

Quality andproductivity

Example of translator productivity by language and process type

Max

imu

m W

ord

s p

er H

ou

r

0

200

400

600

Tier 1 Languages Tier 2 Languages Tier 3 Languages

800

1000

1200

Full Post-Editing Light Post-EditingHuman Translation

Figure 1

Figure 2

Manufacturers start thinking of risk

identification and management ideally while

designing the device or specifying the

requirements of the device. According to Dr.

Sood, from Valoc AG, that’s not early or often

enough. Identification of risks must begin while

conceptualizing the device(s) itself and must be

continued throughout the entire development

phase of the device(s).

It is crucial for manufacturers to differentiate

between what constitutes a hazard, harm, and

risk. A hazard is something that has the potential

to cause harm, while a risk is the likelihood of a

harm taking place, based on the exposure to the

hazard.

Common tools for preliminary risk identification include the following:• Preliminary Hazards Analysis (PHA):

“top-down approach” asking “what if”

• Failure Modes and Effects Analysis (FMEA):

“bottom-up approach”

• Fault Tree Analysis: “top-down approach”

asking “why it happened”

FMEA FMEA can be classified as either design FMEA

(i.e., identification of all possible failures in the

design, manufacturing, assembly process, and

packaging of the device) or process FMEA "(i.e.,

identification of failure modes of the process

steps to prevent the production of defective

devices)." However, FMEA does not include the

risks due to the use or risk caused by the user of

the device. It is only a reliability tool and not a risk

management system.

Dr. Sood suggests the incorporation of the device

design, process, normal use of the device, and

foreseeable misuse to create a comprehensive

hazard/risk matrix. Besides differentiating

between harms, hazards, and risks,

manufacturers gain clarity on how to ascertain

probability of occurrence and severity of harm, as

a combination of these two essential factors helps

determine the actual risk impact. Manufacturers

must consider the device risk classification,

intended use, and clinical outcomes of the device

estimating the probability of occurrence and

severity of risk.

Design FMEABe�er Design to produc�on

Process FMEAPrevent defec�ve product to market

Speaker:Dr. Shaloo Sood, Development Manager (R&D), Valoc AG

RiskIdentification

1

6

52

3 4

Concept Medical Device

Feasibility Design

V&V

User Needs User Wishes

Specs & Requ.

START DOCUMENTING

PMS7

Device Development & Risk Management


Identification and Evaluation of Risks

Some of the common mistakes thatoccur during risk evaluationare listed below:

• Identifying unambiguous or unnecessary hazards (no effect on object)• Lack of clarity for different terms and situations (hazard, harm, or risk) • Evaluation is either too simple or too complex irrespective of device classification.• Lack of documentation of hazards during the feasibility and concept phase • Lack of risk evaluation for device packaging • Not integrating risk activities in all phases of device development • Inability to distinguish between risk, residual risks, or side-effects

Dr. Sood suggests that the manufacturers must consult clinical experts or must collaborate with clinical setups wherein the device is used, to gain an understanding of the severity of the harm. Additionally, when devices are associated with high severity, it is helpful to provide clinical evidence of the same for it to be acceptable.

Key takeaways:

1. Risk identification must begin at the concept stage of the device by PHA, followed by FMEA and fault tree analysis.

2. It is essential to remember that FMEA is only a tool to identify hazards and not a risk management system. FMEA entails risks related to device failures only.

3. Risk is a combination of the severity of a harm and the probability of its occurrence. Good risk analysis is not possible if the identification and evaluation of risks are not optimal.


Vera Edgeworth, Medical Director for the

Medical Device Solutions team at Cactus Life

Sciences, and Ronak Dunung, Manager—Risk

Management at Cook Medical, discussed safety

and performance of a subject device, specifically

within the context of how the S&P data are

recorded and analyzed within standard quality

management processes, such as design and

usability, labeling, production, clinical evaluation,

and post-market surveillance.

Speakers:Vera Edgeworth, Medical Director, Cactus Life Sciences;

Ronak Dunung, Risk Management, COOK Medical

Key points:

1.

Clinical Evaluation: S&P measures for clinical

evaluation can be pre-determined or defined

using methods like think terms (generally

reported in clinical literature), grouping of

similar terms, level of event (device vs.

procedure), sample size, consistency in units of

measure, and time points. For evaluation, the

workflow is suggested to go from

pre-determining the measures, then state of the

art (SOTA) literature, defining SOTA-based

acceptance criteria, and finally, to comparison

of the S&P obtained from clinical literature of

the device(s) under evaluation with the

SOTA-based range and criteria.

Clinical Evalua�on


Pragmatic Solutions to AlignClinical Evaluation, Risk Management,and PMS Processes

Labeling: The labeling contains

user-related information. All

the data set here link and

extract data from other

processes; for example,

intended use corroborated

with design validation studies,

precautions with usability

studies and design verification

studies, and side-effects with

risk management files.

3.

Post-market surveillance

(PMS): PMS studies can be

reactive or proactive. Reactive

studies can arise from

complaints, registries, clinical

literature, and vigilance,

whereas proactive studies can

be taken up via clinical studies,

registries, surveys, and expert

user groups (user feedback).

4.

2. Production and Design and Usability: SOTA must be quantified to act like a benchmark even in product development to make sure risks are acceptable.

Design &Usability

Produc�on

SAFETY PERFORMANCE

N/A N/A SOTA

Residual Risk:Adverse Event

Side-EffectRisk Controls:

WarningsContraindica�on

On-Device Marking

Indica�on for UseIntended Purpose

Intended UseBenefit

Precau�onUse-Task

DUE

SAFETY PERFORMANCE

HarmAdverse Event

Serious IncidentUser Feedback Reac�ve

Adverse EventSide-Effect

Clinical OutcomeUser Feedback Proac�ve


SAFETY PERFORMANCE

MAUDE (Device Problem Code; Event Type)

Performance Standards (e.g., ISO 10993) SOTA

Effect of Failure Mode/Harm(Risk)

Design: Verifica�on Tes�ngUsability: Summa�ve Evalua�ons

Process: Test Method Valida�ons/Process Valida�ons

DUE

Bringing New Devices toMarket Under the EU MDR

Speaker:Marianna Luppi, Independent

This presentation focused on the achievement of the first Conformité Européenne (CE) mark under Medical Devices Regulation (MDR) 2017/745. The Medical Device Directive (MDD) requirements largely remain the same under MDR. However, the shift to MDR is met with stricter changes, which are divided into the following:

• Stricter conformity assessment • Stricter clinical evaluation requirement • Stricter traceability • Stricter transparency

Stricter conformity assessment

• Sponsors and manufacturers should determine the list of applicable standards and common specifications that reflect the state of the art. • Ensure expertise to determine the adequate list of standards.• GSPR conformity depends on the compliance strategy developed for the device.

Stricter clinical evaluation requirement (new rules governing the clinical trial)

• Collection of available clinical literature • Equivalence with other devices (if any) for which clinical data already exist and are

accessible to the manufacturer • Implantable medical devices and Class III medical devices must be subjected to brand new clinical trials (with exceptions in a few cases) • Credible Clinical Evaluation Plan is essential to ensure clinical validation of the MDR requirements.

Stricter traceability

• Per Article 27 of the MDR, a new system of Unique Device Identification (UDI) is required for the identification and traceability of the medical devices. • The quality system should support the UDI database creation.• Each medical device needs a label with its unique code placed on it or the packaging.

Stricter transparency

• Information on products and the tests are to be made public on the EUDAMED database. • The aim of the EUDAMED is to provide the public and the health professionals with the information related to medical devices. • Ensure enough resources to compile the technical documentation of the medical devices to populate the EUDAMED.


ConclusionWith the MDR coming into effect, the manufacturers should plan and construct their strategy to meet the stricter requirements in terms of conformity assessment, clinical evaluation requirement, traceability, and transparency.

Requirements MDD MDR

CEP

CDP

CER

CIP & CIR

PMS Plan

PMCF Plan

PMCF Report

PSUR

CECP

Implant Card

Literature Plan & Report

*Not an exhaus�ve list

MDD vs

MDR

SSCP

This session was presented by Dr. Yvonne Ndefo

of the National Standards Authority of Ireland

(NSAI). Dr. Nfedo stressed on the longer review

period from the beginning of the session due to

there being more documents compared to MDD,

the involvement of an external expert panel, the

validation of the SSCP and uploading it to

EUDAMED, and the involvement of external

clinical experts if in-house experts are not

available.

As a Notified Body (NB), they

• Verify the adequacy of the clinical evidence

and clinical evaluation

• Ensure that all new claims are supported by

clinical data and risk analysis

• Check the suitability and adequacy of the

equivalence data, if equivalence is claimed

• Verify the adequacy of the manufacturer

conclusions and conformance with the GSPRs

• Verify the adequacy of the benefit-risk

determination, risk management, IFU, user

training, and the post-market surveillance

(PMS) plan

• Review the need for a post-market clinical

follow-up (PMCF)

• Ensure the clinical evaluation is updated with

PMS and PMCF data

• Review all clinical evidence presented by the

manufacturer

• Document the impression of its review of the

manufacturer’s clinical evaluation in the

Clinical Evaluation Assessment Report (CEAR)

• Prepare the CEAR template as per MDCG

2020-13

Notified Body Expectationsfor Clinical Evaluation Review

Speaker:Dr. Yvonne Ndefo, Chief Clinical Evaluator for Medical Devices, NSAI

Figure 1: Mandatory documentsFigure 1 presents all the mandatory documents that are required to be submitted to the NB. Each document is inter-related, and the NB expects that there is traceability and alignment among each one of the documents.


Figure 2: Review stakeholders

Table 1 lists the data that must be provided in the Clinical Evaluation Plan (CEP), Clinical Evaluation Report (CER), and the

Clinical Investigation Plans (CIP)/Clinical Investigation Reports (CIR).

Table 1: Relevant documents

CEP

• Intended purpose of the

device

• GSPRs that require suppor

from clinical data

• Intended target population

• Clear indications and

contra-indications

• Clinical benefits to patients

with clinical outcome

parameters

• Methods to examine

qualitative and quantitative

aspects of clinical safety with

reference to determination of

residual risks and side-effects

• Acceptability of the

benefit-risk ratio

• Must have a Clinical

Development Plan (not

optional for legacy devices)

• Confirm the clinical

evaluation methodology

CER

• Clinical background

• Current knowledge and state

of the art

• Specify chosen route of

clinical evaluation

• Clinical data held by the

manufacturer

• Preclinical data and test

results

• Favorable and unfavorable

data

• Version controlled

• Signed and dated

CIP/CIR

• Meets requirements of

EN ISO14155

• CIP and all versions

submitted

• CIP is signed by the principal

investigator

• Clinical investigation

performed as per the CIP

• Ethics committee approval

• Letter of “No Objection” from

the CA

• Was an expert panel

consulted (MDR article 61,

section 2)?

• Is the investigation publicly

registered?

• Investigator brochure is

provided

• Informed consent is adequate

Figure 2: The CEAR is used by the NB to document the

conclusions of its assessment of a particular medical device

submission. Harmonization of this document supports a clear

documentation of the NB assessment and allows for the

manufacturer to specify additional requirements (based on the

device) as well as facilitate reviews by designating authorities.

Who Gets to Review the CEAR?

Expert Panel Annex IX, chapter II

(5.1)

ManufacturerAnnex IX, chapter II (4.2)

Competent Authori�esAr�cle 54 (3)


Under the MDR, the PMS (Annex III; Articles 83-86) and PMCF (MDR Annex XIV; part B) plans and

reports are highly critical and must be up to date.

Figure 3: Components of a PMS plan

Figure 4: Components of a PMCF plan

Figure 3 presents the components of a PMS plan. A PMS is

carried out to obtain safety and performance data of the

device in scope in a proactive manner. This helps to identify

if any corrective or preventive actions need to be

undertaken for the device. Under the MDR, the PMS plan

includes the PMCF plan as well.

Figure 4 presents the components of a PMCF plan. A PMCF

must be considered wherein CE-marking for legacy devices

is based solely on equivalence; where there is a design

change, intended use change, a new target population, etc.;

when it is requested by the NB (MDR article 56, MDCG

2020-7-Section C); for legacy devices where the PMS data

(including PMCF) are not adequate (MDCG 2020-6, Section

6.4), etc.

• Device name and model and other equivalent devices • Literature sources must use multiple database (not just one) • Search terms • Search start and end dates • Inclusion and exclusion criteria

• Previous literature reviews • Aim of the review and the literature review question • How the literature relates to the risk management • Methods used to identify and select articles • Appraisal method

The NB will assess the technical document’s literature search basedon the following aspects:

PMS Plan PSUR Literature

Undesirable side effects

Trend repor�ng,

FSCAs, FSNsInfo on Similar devices

Feedback/ complaints

Serious incidents/

Non serious incidents

PMCF Plan

PMCF plan Evalua�on of equivalent or

similar devices

Monitor known side effects and

contraindica�ons

Systema�c misuse or off

label use

Iden�fy and analyse emerging

risks Acceptability of

risk benefit

Safety and performance

life�me of device

Ra�onale for methods used

Iden�fy unknown side

effects


Figure 5 presents the issues commonly faced while evaluating a PMCF.

A Period Safety Update Report (PSUR) must

include the conclusion of the benefit-risk

determination, the main findings of PMCF, the

volume of device sales, an estimate evaluation of

the size and other characteristics of the

population using the device, and the usage

frequency of the device.

After the completion of all technical documents, the expectations during the auditing of the clinical evaluation are listed below:

• Clinical evaluation planning, conduct,

assessment, reporting, and update

• PMS and PMCF

• Interface with the risk management process

• Appraisal and analysis of the available data

and their relevance to demonstrating

conformity with the GSPRs

• Analysis of the conclusions on the clinical

evidence and drawing up a CER

Figure 5: Common issues with PMCF

Common Issues seen with PMCF× Different device used for PMCF

× PMCF not performed within intended use of device, under normal condi�ons of use

× Complaints in PMCF study were not fed into the complaints data

× Reportable incidents during the PMCF study was not reported as per MEDDEV 2.12.1 to CA

× New risks generated from PMCF has not been assessment during risk management ac�vi�es

× PMCF was not performed as per PMCF plan

× PMCF devia�on or amendments to PMCF plan was not documented in report

× IFU not updated with residual risks discovered from PMCF

× Poorly reported PMCF results

× PMCF results not fed into CER, SSCP & PSUR, IFU & Risk

× PMCF objec�ves/endpoints do not match results in report


NB Feedback: Post Market Surveillance(PMS) – How to Succeed in theFirst Year Under EU MDR Speaker:Daniele Bollati, Product Conformity Assessment, IMQ

This presentation focused on outlining the post-market surveillance (PMS) requirements from start to finish and comparing the PMS, periodic safety update report (PSUR), and the post market clinical follow-up (PMCF) requirements.

Three main takeaways from this pre-sentation were the following: • MDR requirements on the PMS system:

For each device, manufacturers shall plan, establish, document, implement, maintain, and update a PMS system in a manner that is proportionate to the risk class and appropriate for the type of device (Article 83, MDR).

The PMS system must update the benefit-risk determination; the design and manufacturing information, the instructions for use, and the labeling; the clinical evaluation; and the summary of safety and clinical performance.

The PMS system must identify the need for preventive, corrective or field safety corrective action and the options to improve the usability, performance, and safety of the device.

The PMS system must contribute to the PMS of other devices and detect and report trends in accordance with Article 86 of the MDR.

• The PMS Plan should be prepared in reference to ISO/TR 20416:2020 (sources and data analysis) and the PMCF in reference to MDCG 2020-7 and MDCG 2020-8.

• The one-year postponement of MDR can be used for collecting useful data in line with the MDR (also for legacy devices)

to support the term “sufficient clinical evidence” per MDCG 2020-6

to test and challenge the various company departments involved

How to take advantage of the postponement of MDR

Description of the general

methods used to build up the

specific PMS plans

Explanation of the interface

between PMS process and the

other processes

Identification of the documents to

be updated with PMS output

(PSUR, PMCF report etc..)

Definition of the methods of

communication/transmission

(EUDAMED, NB etc..)

Definition of the general criteria

used to update PMS plan

Gap analysis

Build up general procedures for PMS in accordance with Articles 83-86

Build up specific PMS plans in accordance with article 84


Speaker:Nicolas Corbier, Post-Market Surveillance Process Manager, GMED

This presentation focused on the following:

• Outlining what NBs are looking for in Periodic

Safety Update Reports (PSURs)

• Addressing NB workloads associated with

PSURs

• What is meant by “State of Art”?

PSURs

The PSUR should contain the summary of the

results and conclusions of the analyses of the

post-market surveillance (PMS) data gathered as

a result of the PMS plan (Article 84, Medical

Devices Regulation [MDR]), with a rationale and

description of any preventive and corrective

actions taken. In addition, it should also present

the conclusions of the benefit/risk determination;

main findings of the post market clinical follow-up

(PMCF); the volume of sales of the device; an

estimate evaluation of the size and other

characteristics of the population using the device;

and where practicable, the usage frequency of

the device collected throughout the lifetime of

the device.

The PSUR is prepared for Class III, Class IIb, and

Class IIa devices. It is updated annually for Class

IIb and Class III devices and at least every two

years for Class IIa devices. It is submitted to the

NB involved in the conformity assessment for

evaluation (for Class III and implantable devices).

The PSUR is a part of the Technical

Documentation (TD; according to Annexes II and

III, MDR). It reflects the defined PMS plan (Article

84, MDR), which explains what data should be

collected and how these data should be collected

(Annex III, MDR). It is also linked to risk

management, PMCF, and clinical evaluation.


Notified Body (NB) Update:Periodic Safety Update Report (PSUR)

Outlining what NBs are looking for in PSURs

• A PSUR is part of the TD, as specified in

Annexes II and III; the NB will evaluate the

PSUR as part of the TD assessment

• For Class III and implantable devices, PSUR will

also be transmitted to the NB involved in the

conformity assessment; the NB will also

evaluate the PSUR outside the scope of the TD

assessment

• New “operational” role of NBs in PMS and

vigilance of manufacturers:

reinforces the role of the NB in its

surveillance activities and post-certification

monitoring for the devices for which it has

issued a certificate

need to analyze whether the manufacturer’s

conclusions regarding benefit/risk ratio are

justified from the point of view of the

gathered data and the manufacturer’s

analysis while making the link with the

vigilance data (Article 92 [2] and [9], MDR)

• Per the MDR requirements, a PSUR must

be in line with the scope of the TD(s)

submitted for conformity assessment

reflect the evolution of the benefit/risk ratio

according to the data collected and analyzed

contain all the information requested in

Article 86 of the MDR (and when necessary,

a justification should be provided if the data

are not available)

• The Medical Device Coordination Group

(MDCG) has set up a task force to develop a

guidance for PSURs (management, guidelines,

and evaluation of NB), which might be expected

in the coming weeks.

Addressing NB workloads associated with PSURs

• Objectives of the NB organizations: To define a

common approach between all NBs and to

harmonize practices

• Most important impact in terms of workloads:

PSUR for legacy devices

• Need to have a pragmatic approach (Article

120, MDR - "the requirements of this

Regulation relating to post market

surveillance, market surveillance, vigilance,

registration of economic operators and of

devices shall apply in place of the

corresponding requirements in those

Directives”)

• For medical devices with an MDR certificate,

use the issuance date of the MDR

certificate/the date of signing the Declaration

of Conformity (DoC) to

spread the submission of PSURs by the

manufacturer

spread the assessment of PSURs by NBs


What is meant by “State of Art”?

• PSUR is a living and stand-alone document

that aggregates and summarizes the activities

carried out during the entire lifetime of the

device (as defined in the TD by the

manufacturer), which reflects the evolution of

the benefit/risk ratio of the device and the

state of the art (data from PMCF studies) to

identify any safety and performance concerns.

• The following data are to be collected and

analyzed in accordance with the PMS

plan/PMCF plan:

relevant data on similar devices, relevant

scientific and clinical data, and data from

PMCF studies

in particular, a comparison with the available

information of other devices with the same

intended use and state of the art

data that must also be summarized and

included, as necessary, in accordance with

the PMCF Evaluation report

the possible differences in the safety and

performance of the device and any possible

change(s) in relation to the state of the art

from PMCF activities - “PSUR shall set out

the main findings of the PMCF” (Article 86

[1b], MDR)

• After collecting and analyzing the data, if

concerns have been identified, this gathered

information will be used

to re-evaluate the benefit/risk ratio

to update the state of the art of the medical

device


Conclusion

The NBs look forward to the clear representation of the device’s PMS results and conclusion, as a

result of the PMS/PMCF plan, which work together to connect benefit/risk determination, PMS,

PMCF, and risk management. With a pragmatic approach, NBs strive to define a common approach

among all NBs and to harmonize practices for the evaluation of PSURs.

Updates and Strategies forPost Market Clinical Follow-up (PMCF)

Speaker:Bassil Akra, CEO and Co-Owner, QUNIQUE

This presentation focused on assessing what

manufacturers need to do to perform compliant

post market clinical follow-up (PMCF) activities

and the best practices for completing PMCFs.

Assessing what manufacturers need to do to perform compliant PMCF activities

Manufacturers “of devices shall implement and

keep up to date the post-market surveillance

system” - Article 10[10] of the Medical Devices

Regulation [MDR] and Article 10[9] of the In

Vitro Diagnostic Regulation [IVDR]. “The

manufacturer shall specify and justify the level

of clinical evidence necessary to demonstrate

compliance with the relevant general safety and

performance requirements which shall be

appropriate to the characteristics of the device

and its intended purpose.” - Annex I, MDR. In case

of no clinical data, the manufacturers should

collect PMCF data, where the PMCF plan is also

deemed necessary.

The clinical development plan (CDP) indicates

progression from exploratory investigations, such

as first-in-man studies and feasibility and pilot

studies, to confirmatory investigations, such as

pivotal clinical investigations, and a PMCF (Annex

XIV, MDR). The MDCG 2020-6 can be referred

for the analysis of these clinical data.

Demonstration ofcompliance with the

GSPR, relevant forthe device in

question have to bebased on:

The usage of reliable, justified and soundanalytical methods (whereapplicable qualitative, quantitative, or both);

Results of performedcomprehensive analysis;

Identification of any missingdata and/or gaps;

Determination of PMCF needs.


For any device, manufacturers shall plan,

establish, document, implement, maintain, and

update a post-market surveillance (PMS) system

in a manner that is proportionate to the risk class

and appropriate for the type of device

throughout the lifetime of the device. Some

regional regulatory requirements differ among

the expected lifetime, entire lifetime, and lifetime

of a device. The expected lifetime is to be defined

during the design input phase by considering the

current state of the art for a specific intended use

and indication of a device. The entire lifetime is to

be understood as the period from the first placing

on the market after initial market approval till the

last patient is treated with the device and

followed-up for the predefined expected lifetime

by the manufacturer. The lifetime of a device is to

be understood as the validated expected lifetime

according to real world evidence. A schematic

representation of PMS is shown in the figure

below:

Figure 2 —Example schematic representation of post-marketsurveillance

Examples of processes providing inputs to post-market surveillance (Outside the scope of ISO TR 20416)

Design and development

Risk management

Clinical / performance evaluation

Regulatory compliance Improvement Marketing

and sales

5.2 Scope of the post-market surveillance plan

5.3 Objectives of the post-market surveillance plan

5.4 Responsibilities and authorities 5.5 Data collection

Examples of data sources are provided in Annex A

5.6 Data analysis Examples of methods for data analysis are provided in Annex B.

5.7 Reporting on data analysis

5. P

lann

ing

of p

ost-

mar

ket

surv

eilla

nce

6. R

evie

w o

f the

pos

t-m

arke

t sur

veill

ance

pla

n

Post-market surveillance process

5.8 Interface with other processes

Examples of decisions or actions to take based on the post-market surveillance process (Outside the scope of ISO TR 20416)

• Design and development changes• Maintenance of the risk management file

• Maintenance of the clinical evaluation file• Maintenance of the marketing strategy

• Reporting of adverse event• Corrective action or preventive action

• Issuance of advisory notice


Best practices for completing PMCFs

PMCF is a continuous process to update the

clinical evaluation and is part of the PMS plan.

The PMCF plan includes the general methods and

procedures of PMCF (i.e., gathering clinical

experience, collecting feedback from users,

screening of scientific literature, and of other

sources of clinical data) along with the specific

methods and procedures of PMCF to be applied

(i.e., evaluation of suitable registries or PMCF

studies). The MDCG 2020-7 is the guidance

document for the PMCF plan template. The

PMCF plan should link to the CER, connecting the

methodologies selected and the methods

employed.

The different procedures that are to be used as

part of a PMCF include screening of scientific

literature and other sources of clinical data,

post-market studies, collecting data from

registries, surveys of health care professionals,

surveys of patients/users, and reviews of case

reports that may reveal misuse or off-label use.

The PMCF might not always be a study. For

instance, reporting of a system misuse/off-label

use cannot be found by a PMCF study, but it can

rather be found via a survey or customer

feedback. The rationale for the appropriateness

of the chosen methods/procedures should also be

discussed.

The proactive and reactive methods are shown in the figure below:

Proactive: written or electronic surveys or

questionnaires; interviews of users; literature search; use of medical device

registries; post-market clinical follow-up

studies (or post-market performance follow-up studies, IVDs);

recall information and other information released from regulatory agencies.

Reactive:• review of complaints

(including incident reports);

• review of non-solicited observations by healthcare professionals or observations by the organization's sales and marketing team members;

• review of service reports or maintenance reports;

• review of regulatory compliance notifications.


The specific timeline for the PMCF activities should be provided; a detailed and adequately justified time

schedule for PMCF activities, such as the analysis of PMCF data and reporting, should be described. A

summary table of the different PMCF activities foreseen by the manufacturer is provided below:

The applicable common specification(s), harmonized standard(s), or applicable guidance document(s)

should be referenced, and the estimated date of the PMCF report should be mentioned in the PMCF

plan. In addition, the relevant parts of the technical documentation should also be clearly referenced.

The PMCF plan should align with the RMR and the clinical evaluation.

Number of activity

Description of activity Aim of the activity Rationale and known limitations of the activity

Timelines of the activity


Conclusion

An ideal PMCF plan, with reference to MDCG 2020-7, presents the general and specific methods

and procedures of the PMCF activities. The PMCF report should reflect as an output of such a

PMCF plan and align with the instructions for use, clinical evaluation, summary of safety and

clinical performance, and risk management documentation to form a holistic picture.


AcknowledgementThis report was made possible with the collaboration

and contribution of the following members of the

Cactus Life Sciences Team:

Eisha Shaw, Scientific Writer

Sindhuja DE, Scientific Writer

Nandini Dhiman, Scientific Writer

Srinidhi Ragunathan, Scientific Writer

Kwisha Shah, Senior Content Associate

Amit Pattar, Senior Visual Designer


Cactus Life Sciences is a non-traditional, fully integrated

scientific communications agency. We disseminate

science while focusing on stakeholder personalization,

workflow efficiencies, and technology-led innovation.

Who we are

Contact Us

Digital and CreativeSolutions

ScientificPublications HEOR

MedicalCommunications

MedicalInformation

MedicalDevice Solutions

https://lifesciences.cactusglobal.com/contact.html

Documents

A SUMMARIZED REPORT OF THE