Mesh implants intended to treat patients
with pelvic organ prolapse
Market survey and quality of technical documentation

RIVM letter report 2020-0154
B. Roszek et al.

Mesh implants intended to treat patients
with pelvic organ prolapse
Market survey and quality of technical documentation
RIVM letter report 2020-0154
B. Roszek et al.

RIVM letter report 2020-0154

Colophon

© RIVM 2022
Parts of this publication may be reproduced, provided acknowledgement
is given to: National Institute for Public Health and the Environment,
along with the title and year of publication.
DOI 10.21945/RIVM-2020-0154
B. Roszek (author), RIVM
A.W. van Drongelen (author), RIVM
R.E. Geertsma (author), RIVM
J.W. van Baal (author), RIVM
Contact:
Jantine van Baal
RIVM/Gezondheidsbescherming
jantine.van.baal@rivm.nl
This investigation has been performed by order and for the account of
Dutch Health and Youth Care Inspectorate, within the framework of
project V/080168.

Published by:
National Institute for Public Health
and the Environment, RIVM
P.O. Box 1 | 3720 BA Bilthoven
The Netherlands
www.rivm.nl/en
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Synopsis

Mesh implants intended to treat patients with pelvic organ
prolapse
Market survey and quality of technical documentation
Mesh implants intended to treat patients with pelvic organ prolapse
(POP) can be implanted via two surgical approaches: via the abdomen
(transabdominal) or via the vagina (transvaginal).
The Health and Youth Care Inspectorate requested RIVM to assess the
technical documentation of mesh implants intended to treat patients
with POP. First, RIVM investigated which mesh implants were used by
physicians. Nine types of mesh implants used by physicians in the
Netherlands in 2018 were assessed. Four of these are intended for
implantation via the vagina and five for implantation via the abdomen.
The nine mesh implants are produced by six different manufacturers.
RIVM has identified major or minor shortcomings in multiple parts of the
technical documentation of all assessed products. An example of a major
shortcoming is that the safety and performance are not adequately
substantiated with data on the use of the product in humans. A minor
shortcoming is for example the lack of an adequate description of the
surgical procedure in the instructions for use in cases where it is
indicated that physicians have to be trained to perform this type of
surgery.
It is not clear whether the identified shortcomings could potentially
damage a patient’s health. Shortcomings in the technical documentation
do not necessarily imply that the actual product is of insufficient quality.
However, the safety and performance of the products have not been
substantiated properly due to the shortcomings in the technical
documentation. The regulatory system requires that manufacturers
carefully investigate and resolve the shortcomings in their technical
documentation. Manufacturers have indicated that they are improving
the technical documentation based on the results of the assessment by
RIVM. Some manufacturers have reported that they have been
reaudited by their notified bodies and that their improved technical
documentation is now compliant with European regulatory requirements.
These audits took place after the RIVM assessment was completed.
Starting in May 2021, new European regulations for medical devices will
apply. This means manufacturers will have to comply with additional and
more strict requirements, also for the technical documentation.
Keywords: mesh implant, pelvic organ prolapse, market survey,
assessment technical documentation

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Publiekssamenvatting

Bekkenbodemmatjes
Marktverkenning en kwaliteit van technische documentatie
Bekkenbodemmatjes zijn implantaten waarmee verzakkingen van
organen in het gebied van de bekkenbodem worden behandeld.
Bekkenbodemmatjes kunnen op verschillende manieren geplaatst
worden: via de buik (transabdominaal) en via de vagina (transvaginaal).
In opdracht van de Inspectie voor Gezondheidszorg en Jeugd (IGJ) heeft
het RIVM de technische documentatie van bekkenbodemmatjes
beoordeeld. Hiervoor heeft het RIVM eerst onderzocht welke
bekkenbodemmatjes er door artsen werden geplaatst. De technische
documentatie van negen typen bekkenbodemmatjes die artsen in 2018
in Nederland hebben geplaatst, zijn daarna beoordeeld. Hiervan zijn er
vier bedoeld om via de vagina te worden geplaatst en vijf via de buik.
De negen bekkenbodemmatjes zijn door zes verschillende fabrikanten
gemaakt.
Het RIVM heeft in de technische documentatie van alle beoordeelde
producten in meerdere onderdelen grote of kleine tekortkomingen
gevonden. Een voorbeeld van een grote tekortkoming is dat de
veiligheid en prestaties onvoldoende zijn onderbouwd met gegevens
over het gebruik van het product in de mens. Een kleine tekortkoming is
bijvoorbeeld dat een goede beschrijving van de operatie in de
gebruiksaanwijzing ontbreekt, terwijl er wel staat dat een arts getraind
moet zijn voor dit soort operaties.
Het is niet duidelijk of de gevonden tekortkomingen schadelijk zijn voor
de gezondheid van de patiënt. Tekortkomingen in de technische
documentatie hoeven niet te betekenen dat er iets mis is met het
product. Wel is het zo dat de veiligheid en prestaties van de producten
door de tekortkomingen in de technische documentatie niet goed zijn
onderbouwd. Regelgeving vereist dat fabrikanten de tekortkomingen in
hun technische documentatie zorgvuldig onderzoeken en oplossen.
Fabrikanten geven aan dat zij naar aanleiding van de resultaten van de
RIVM-beoordeling de technische documentatie aan het verbeteren zijn.
Sommige fabrikanten hebben gemeld dat ze sindsdien opnieuw door hun
notified bodies zijn geaudit en dat hun aangepaste technische
documentatie nu voldoet aan de Europese wet- en regelgeving. Deze
audits hebben plaatsgevonden nadat de RIVM-beoordeling was
afgerond.
Vanaf mei 2021 gelden nieuwe Europese regels voor medische
hulpmiddelen. Daardoor moeten fabrikanten zich aan meer en strengere
regels houden, ook voor de technische documentatie.
Kernwoorden: bekkenbodemmatje, marktverkenning, verzakking
bekkenbodem, beoordeling technische documentatie

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Contents

Summary — 9
1
1.1
1.2
1.3
1.4
1.4.1
1.5
1.6

Introduction — 11
Background — 11
Mesh implants in the Netherlands — 12
Mesh implants in other countries — 13
Current study — 14
Background information current study — 14
Aim of the study — 15
Guide to reading the report — 15

2

Market survey — 17

3
3.1
3.2
3.3
3.4
3.5
3.6
3.7
3.8
3.9

3.11
3.12

Assessment of technical documentation — 19
Overall quality of the technical documentation 2018 — 21
Device description — 22
Instructions for use — 23
Risk analysis — 23
Chemical composition — 23
Biocompatibility — 24
Clinical evaluation — 24
Summary and analysis of post-market surveillance data — 27
Assessment of updated clinical evaluations of transvaginal mesh
implants — 27
Assessment of updated technical documentation items of
transabdominal mesh implants — 28
Potential impact of findings on patient safety — 30
Summary of the assessment of technical documentation sets — 33

4

Conclusion — 35

3.10

References — 37
Annex 1: Characteristics of surgical mesh implants used to treat
POP in the Netherlands in 2018. — 41
Annex 2: Checklist for Dutch request gynaecological mesh
implants — 46
Annex 3: Method of the assessment of technical
documentation — 49
Annex 4: Request of the Inspectorate — 52
Annex 5: Assessment form — 54
Annex 6: Conclusions of the assessment of technical
documentation — 64

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Summary

Pelvic organ prolapse (POP) affects 30-40% of women worldwide, and
reduces their quality of life. Treatment options include reconstructive
surgical procedures using surgical mesh implants. Previous
investigations reported serious complications in patients with mesh
surgery for POP. In this study mesh implants intended to treat POP in
the Netherlands were investigated. The first part of the study was a
market survey, providing an overview of mesh implants used in the
Netherlands. The second part consisted of the assessment of technical
documentation of mesh implants. There are two surgical approaches to
treat POP using mesh implants: transvaginal and transabdominal
implantation. In this study, mesh implants for both approaches were
included. This study was performed by order of the Dutch Health and
Youth Care Inspectorate.
The market survey showed that nine types of mesh implants from six
manufacturers were used in the Netherlands in 2018. Some of the
implants were available in different variants and two of the legal
manufacturers were part of the same multinational company. From the
total of nine mesh implants, four were intended for transvaginal
implantation and five for transabdominal implantation.
The assessment indicated shortcomings in technical files of all included
mesh implants. Therefore, full conformity with the requirements in the
Medical Devices Directive (MDD) was not shown. The general description
and the instructions for use (IFU) had no or minor shortcomings in all
files. However, the file items risk analysis, biocompatibility, clinical
evaluation and summary and analysis of post-market surveillance (PMS)
data showed major shortcomings in most of the files. In a number of
cases, updated versions of one or more file items were also assessed.
Generally, improvements were seen in updated versions. Some,
however not all, identified improvements resulted in a change from
major shortcoming to minor shortcoming in the overall conclusion on a
file item.
Shortcomings in the technical file do not necessarily mean that the
device is of insufficient quality. However, the identified shortcomings
mean that there are uncertainties about impact on patient safety.
Analysis of the identified shortcomings showed that there is a potential
impact on patient safety related to shortcomings in many of the file
items.
All the shortcomings need to be adequately addressed by the
manufacturers in order to better substantiate the quality and safety of
their products as required in the regulatory system. The Inspectorate
informed RIVM that manufacturers have indicated to be working on
improvements in their technical documentation in order to comply with
the requirements for the MDD. Some of the manufacturers have
indicated that the improved technical documentation passed audits by
their notified bodies and stated that their technical documentation is
now compliant with European regulatory requirements. These audits
took place after the RIVM assessment was completed.
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Starting in May 2021, new European regulations for medical devices will
apply. This means manufacturers will have to comply with additional and
more strict requirements, also for the technical documentation.

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1

Introduction

1.1

Background
Pelvic organ prolapse (POP) is the descent of one or more of the pelvic
organs, i.e. uterus, vagina, bladder or bowel into or out of the vagina. It
may affect the anterior (bladder), middle (uterus) or posterior (rectum,
or back wall of the vagina) compartment. Although POP can affect
women of all ages, it more commonly occurs in older women and affects
30-40% of women worldwide [1, 2]. The etiology of POP is complex and
multifactorial and is linked to childbearing, obesity and advancing age
[3]. POP is not life-threatening, but it reduces the quality of life for
women [4].
There are several treatment options available for POP, depending on the
severity of the symptoms and the severity of the prolapse in
combination with age and health of the patient. For women with a mild
degree of POP, conservative treatment options are lifestyle changes,
pelvic floor physiotherapy and vaginal pessaries [5, 6]. If these
treatment options do not work or if the prolapse and symptoms are very
severe, surgery is a treatment option. A variety of reconstructive
surgical procedures are available for these women, for instance native
tissue repair and surgical mesh implantation. Scientific studies showed
that native tissue repair has a failure rate of recurrent prolapse of 1720% [3]. This resulted in embracing surgical mesh as treatment option
for POP [3]. Surgery can be performed through the abdomen
(transabdominal) or through the vagina (transvaginal) [1, 2, 7, 8].
A surgical mesh is a medical device that is permanently implanted to
provide extra support when repairing weakened tissue. Surgical mesh
can be used to treat patients for multiple different indications. Examples
of indications are urine incontinence, hernia repair and POP. Recently
RIVM provided an overview with seven of these indications [9]. Mesh
material can be synthetic or biological. It can be non-absorbable,
partially absorbable or absorbable [7, 8]. In the current report we focus
on synthetic, non-absorbable or partially absorbable surgical mesh
implants for treatment of POP.
Given that the use of surgical mesh implants in the treatment of POP
had been shown to be associated with various adverse events, the
European Commission’s Scientific Committee on Emerging and Newly
Identified Health Risks (SCENIHR) was asked to provide a scientific
opinion on the health risks of mesh implants used in urogynaecological
surgery. They outlined that clinical outcome following mesh implantation
is influenced by material properties, product design, overall mesh size,
route of implantation, patient characteristics, associated procedures
(e.g. hysterectomy) and the surgeon’s experience [10]. They also
indicated that the implantation of any mesh for the treatment of POP via
the vaginal route should only be considered in complex cases, in
particular, after failed primary repair surgery [10]. In 2018, RIVM
reviewed international literature on long-term complications of
transvaginal mesh implants. The range of long-term complications
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varied in the reviewed literature from 0-48%. The identified
complications were primarily associated with products that were not
available on the Dutch market in 2018 [11].
The transabdominal surgical approach for mesh implantation can be
carried out via laparotomy, conventional laparoscopy or robotic-assisted
laparoscopy. Recently, Le Teuff et al. reported that the incidence of
complications was similar comparing transvaginal mesh and
transabdominal mesh. This included post-operative complications and
complications one year post-operative [12]. In a recent Dutch
investigation, van Zanten et al. showed a low mesh exposure rate in
robot-assisted transabdominal pelvic floor surgery for POP [13].
Surgeon’s experience is one of the factors that influence clinical outcome
following mesh implantation [10] and thus complication rates are partly
dependent on the surgeon’s experience. Surgeon’s experience and
training differ among different countries. Therefore complication rates
can vary among different countries. The exact complication rate of
transvaginal and transabdominal mesh implantation in the Netherlands
is not known.
Surgical mesh implanted to treat patients with POP can cause serious
complications like infection, mesh shrinkage, chronic pain, including
dyspareunia, exposure and erosion into other organs [3]. This has led to
new international guidelines for the use of mesh implants that are more
stringent [3, 6, 10]. In 2017, the European Association of Urology (EAU)
and the European Urogynaecological Association (EUGA) published a
paper with a consensus statement [3]. They indicate that it is clear that
vaginally implanted mesh for POP is associated with increased risks and
its use should be restricted to experts in specialised departments and to
a special group of patients or approved clinical research. Furthermore,
that the use of transabdominal mesh should also be restricted to
specialist practice although the associated risk is considered more
acceptable. In their conclusion, however, no distinction is made between
surgical approaches: ‘synthetic mesh for POP should be used only in
complex cases with recurrent prolapse in the same compartment and
restricted to surgeons with appropriate training, working in
multidisciplinary referral centres’ [3]. In addition, importantly, it is
emphasised that patients should be adequately informed regarding the
potential success rates and mesh-related adverse events compared with
non-mesh alternatives, and should be engaged in the decision-making
process [3].
1.2

Mesh implants in the Netherlands
In 2009 and 2010, the Dutch Health Care Inspectorate, currently the
Dutch Health and Youth Care Inspectorate (hereafter Inspectorate)
received and analysed incident reports concerning transvaginal mesh
implants for the treatment of POP. In 2011, the Inspectorate started an
investigation, and media attention in December 2012 led to an increase
in reports to the Inspectorate regarding serious complications
experienced by patients after receiving a transvaginal mesh implant.
The Inspectorate published a report urging caution regarding the use of
transvaginal mesh implants [14]. Since 2013, the number of reports
received by the Dutch Inspectorate on transvaginal mesh implant
complications has decreased.

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After the publication of the Inspectorate’s report in 2013, the
Netherlands Society of Obstetrics and Gynaecology (NVOG) took several
measures to improve transvaginal mesh implantation. They
implemented a multidisciplinary guideline, and introduced specific
indications for the treatment with the purpose of decreasing the number
and severity of complications following transvaginal mesh implantation
[15, 16]. The NVOG stated that the surgeon’s experience is important
and that therefore every surgeon would need to perform at least 10
transvaginal mesh implantations per year [15, 16].
For a medical centre that performs mesh surgery (transvaginal and/or
transabdominal), the NVOG documents included a recommendation that
at least two urogynaecology specialists or subspecialists competent in
performing mesh surgery are available. The NVOG documents stated
additional requirements for transvaginal mesh surgery, however did not
provide specific indications or requirements on surgeon’s experience for
transabdominal mesh surgery [15, 16]. Given that the EAU and the
EUGA made no distinction with regard to the surgical approach in the
conclusion of their recent consensus paper [3], it was not clear whether
the NVOG guideline still reflected current insights. The NVOG
implemented a new guideline in December 2020 [17]. In the updated
NVOG guideline no distinction is made between transabdominal and
transvaginal mesh surgery with regard to requirements on surgeons
experience.
The NVOG also has requirements and recommendations for facilities
where mesh surgery is performed, and requires that all transvaginal and
transabdominal mesh implants, together with any mesh-related
complications are registered in a central NVOG system [15, 16, 17].
Unfortunately, not all surgical mesh implanted in patients with POP in
the Netherlands are currently recorded in such a registry. Therefore the
exact number and type of mesh implanted to treat patients with POP is
not known. All surgeries can only be identified in the personal medical
files of every patient available in the handling hospital. Only medical
doctors treating these patients have access to these medical files.
In 2019, RIVM reported on the number of transvaginal mesh
reimbursement claims in 2015, 2016 and 2017. Per year 272 to 368
transvaginal mesh implants were provided. This number was based on
reimbursement claims of the Dutch Healthcare Authority [18].
Recently, NVOG performed a survey in which all Dutch hospitals were
asked to participate. The number of respondents is not known, but
NVOG informed RIVM that participating hospitals reported that 172
transvaginal mesh were implanted in 2018 in the Netherlands 1. NVOG
also performed a survey in which all Dutch hospitals were asked to
participate concerning transabdominal mesh. NVOG informed RIVM that
72 hospitals responded to this survey, reporting that 600
transabdominal mesh were implanted in 2019.
1.3

Mesh implants in other countries
Like in the Netherlands, in recent years also in France a relatively small
number of vigilance reports were filed at the Agence Nationale de
Sécurité du Médicament et des Produits de Santé (ANSM) [19]. Several
countries (for instance USA, Australia, Ireland and the UK) have
1

NVOG, Werkgroep Bekkenbodem (WBB) Nieuwsbrief November 2019
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reported that mesh implants for POP continue to cause complications
[20-24]. USA and Australia have taken transvaginal mesh implants off
their market. In several countries, the use of surgical mesh implants for
the transvaginal treatment of POP is under examination or restriction
through measures taken by their national authorities [19]. For example,
the Australian Government Department of Health, Therapeutic Goods
Administration (TGA) determined that the risks to patients from
implantation of transvaginal mesh to treat POP outweigh the potential
benefits and the supply of these products is no longer allowed [23]. In
contrast to transvaginal mesh implant procedures, transabdominal mesh
implant procedures are still allowed to be performed in several of these
countries (e.g. UK, USA and Australia) [20-24].
1.4

Current study
The Dutch Inspectorate is entrusted with market surveillance and law
enforcement of medical devices and their use, in order to address the
greatest risks for patient safety and their early identification. In order to
gain more insight on the state of affairs for mesh implants used to treat
POP in the Netherlands, the Inspectorate commissioned RIVM to perform
a study. This study included both transvaginal and transabdominal mesh
implants used to treat POP. Slings used to treat stress urinary
incontinence and abdominal implants used to treat rectal prolapse were
not included in this study. This study included the assessment of
technical documentation requested by the Inspectorate in 2018 and
2020.

1.4.1

Background information current study
RIVM identified major shortcomings in the technical documentation of
the two transvaginal mesh implants that were on the Dutch market
November 1st 2019. Therefore, RIVM decided to notify the Inspectorate
ahead of the full report. In February 2020, a summary of the
assessment of the technical documentation sets of these two
transvaginal mesh implants was reported to the Inspectorate and
published by RIVM [25]. Subsequently, the Inspectorate published their
position on this [26] and NVOG followed their position. Since then,
transvaginal mesh implant surgery is recommended to be performed
only in a clinical research setting subject to the Medical Research
Involving Human Subjects Act (WMO) [27]. As the next step, RIVM
assessed the technical documentation of the four transabdominal mesh
implants that were on the Dutch market November 1st 2019 and
identified major shortcomings. Assessment of the technical
documentation identified major and minor shortcomings. Since, the
mesh implants were still on the Dutch market November 1st 2019, RIVM
decided to notify the Inspectorate ahead of the full report. In May 2020,
RIVM reported a summary to the Inspectorate on the assessment of the
technical documentation sets of these four transabdominal mesh
implants. In the current full report, the overall results of the assessment
of technical documentation of these transvaginal and transabdominal
mesh implants are described, together with the results of three mesh
implants that were withdrawn from the Dutch market earlier in 2019.

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1.5

Aim of the study
The aim of this study was to investigate mesh implants intended to treat
POP in the Netherlands. This study consisted of the following parts:
1. Market survey to compile an overview of mesh implants used in
the Netherlands.
2. Assessment of technical documentation of selected mesh
implants.
Part one
Regarding the market survey, the following question was addressed:
- Which transvaginal and transabdominal synthetic mesh implants
are being used to treat POP in the Netherlands?
Part two
Regarding the assessment of technical documentation of selected mesh
implants, the following questions were addressed:
- Do the technical files of the selected mesh implants provide
adequate proof of conformity with the requirements of the
Medical Devices Directive (MDD) [28]?
- In case of shortcomings, do these lead to a concern for patient
safety?

1.6

Guide to reading the report
In chapter 2, the results of the market survey are presented, as well as
the products selected for technical file assessment. Chapter 3 describes
the results of the assessment of the technical files and the potential
impact on patient safety. In chapter 4, the general conclusions are
presented.

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2

Market survey

To investigate which mesh implants, intended to treat patients with POP,
are applied in the Netherlands, NVOG was contacted to obtain contact
details of two experts in the Netherlands in 2018. These experts
provided information of mesh implantation to treat patients with POP. In
addition, information showed that the transvaginal approach to treat
patients with POP was performed in a limited number of Dutch hospitals
in 2018. Detailed information regarding Dutch hospitals where the
transabdominal approach to treat patients with POP was performed was
missing. Therefore, RIVM contacted NVOG for contact information of
urogynaecologists working in hospitals where patients with POP are
treated with transvaginal mesh implantation. RIVM sent a short
questionnaire to these urogynaecologists in 2018. The questionnaire
included the following questions:
o Which surgical mesh implants (include brand names and
manufacturers), intended to treat patients with POP, do you
implant?
o Which material are the surgical mesh implants made of: nonabsorbable or partly-absorbable?
o Is the surgical mesh implanted transabdominally or
transvaginally?
RIVM received responses from urogynaecologists working in eight
hospitals. All these urogynaecologists used transvaginal and
transabdominal mesh implants.
Subsequently, web searches (www.google.com) were conducted to
identify information regarding the mesh products that were implanted in
the Netherlands in 2018. This information included: the surgical route,
mesh material, absorbability, material density, fixation methods and
specifications. In general, information was obtained using websites of
the manufacturers.
Table 2.1 and Annex 1 show an overview of all transvaginal and
transabdominal mesh identified in the questionnaire. Several mesh
products have been withdrawn from the market worldwide in 2019.
These surgical mesh implants were used in 2018. In addition to this
overview of mesh implants, one hospital reported that Parietene light
(Parietex; manufacturer: Covidien/Medtronic) was used to treat patients
for POP. This surgical mesh was not included in this study, because this
surgical mesh is intended to be used for hernia repair.

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Table 2.1 Overview of surgical mesh implants used to treat POP in the
Netherlands in 2018.

Manufacturer
A.M.I. GmbH
BD/C.R. Bard Inc 3

Name of the medical device
BSC Mesh 2
Alyte® Y-Mesh Graft 1

Surgical approach
Transvaginal
Transabdominal

BD/C.R. Bard Inc 3

Nuvia™ SI Single-Incision
Prolapse Repair System 1, 4

Transvaginal

Coloplast A/S
Coloplast A/S
Coloplast A/S
Ethicon LLC 6

Restorelle® DirectFix™ 1, 5
Restorelle® M L XL
Restorelle® Y
GYNECARE GYNEMESH™ PS
Nonabsorbable PROLENE™ Soft
Mesh
ARTISYN™ Y-Shaped Mesh 7
Calistar S 8

Transvaginal
Transabdominal
Transabdominal
Transabdominal

Johnson & Johnson Int
Promedon SA

Transabdominal
Transvaginal

These mesh implants were withdrawn from the Dutch market earlier in 2019.
November 2019: Notified body temporarily restricted CE certificate of BSC Mesh. In
September 2020, temporary restriction was removed after audit by notified body of
updated technical documentation for BSC Mesh.
3
BD (Becton, Dickinson and Company) acquired C.R. Bard Inc in 2017.
March 2019: BD announced the removal of its Women’s Pelvic Organ Prolapse and Stress
Urinary Incontinence Mesh Devices from the European market.
4
Nuvia™ SI Single-Incision Prolapse Repair System consisted of an anterior and posterior
repair system.
5
Restorelle® DirectFix™ consisted of Restorelle® DirectFix™ Anterior and Restorelle®
DirectFix™ Posterior. In May 2019, Coloplast A/S stopped selling Restorelle® DirectFix™.
6
Ethicon LLC is a Johnson & Johnson subsidiary.
7
ARTISYN™ Y-Shaped Mesh is a partly absorbable mesh.
8
March 2020: Notified body temporarily restricted CE certificate of Calistar S. In
September 2020, temporary restriction was removed after audit by notified body of
updated technical documentation for Calistar S.
Disclaimer: This information is obtained from urogynaecologists, the Inspectorate and
publicly available websites.
1
2

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3

Assessment of technical documentation

In order to show compliance with the MDD [28], manufacturers of
medical devices have to compile a file, including all relevant technical
documentation, for example on items such as risk analysis, design
verification and validation, and post-market surveillance. A selection of
seven technical documentation items, hereafter called technical
documentation set, was requested by the Inspectorate from the
manufacturers for assessment (see Textbox 1 and Annex 2).
CE-marked gynaecological mesh implants for the treatment of POP, that
were on the Dutch market in 2018, were included in this assessment.
The manufacturers and their mesh implants are shown in Table 2.1.
The method used for assessment of the documentation was adapted from
previous assessments [29-31] and is described in detail in Annex 3.
In short, a form was developed in order to enable a structured and
uniform assessment of the technical documentation sets (see Annex 5).
The form included technical documentation items (e.g. risk analysis),
which were subdivided into sub-items (e.g. risk control/mitigation). For
every sub-item, presence of adequate information was assessed. The
MDD, MEDDEV guidance documents, harmonised European standards
and state-of-the-art (EN) ISO standards as relevant, and specific
scientific opinions and guidelines from professional medical societies
were used as a basis for the assessment of the various (sub-)items [10,
15, 16, 28, 32-36]. If adequate information was missing, this was noted
on the form as a shortcoming. To facilitate a consistent assessment, two
assessors assessed the documentation independently. Assessment forms
were compared and any discrepancies were discussed and resolved,
leading to a combined assessment.
After this assessment, the manufacturers were informed about the
results and were given the opportunity to check on factual
inconsistencies. In case a manufacturer was of the opinion that the
assessment of a specific (sub-)item contained factual inconsistencies,
the manufacturer was requested to either state where the specific
information could be found in the originally submitted documentation or
to provide additional documentation, which contained the specific
information. In the latter case, only technical documentation that
existed at the time of the initial request was taken into consideration.
Two assessors reviewed the response of the manufacturer, assessed the
(additional) technical documentation and finalized the assessment.

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Textbox 1.
By order of the Inspectorate, RIVM assessed specified parts of the
technical documentation (see Annex 2 for more details) of selected
mesh implants intended to treat POP.
Requested technical documentation items:
1. Device description
2. Instructions for use
3. Risk management plan and risk analysis
4. Chemical composition
5. Biocompatibility
6. Clinical evaluation
7. Summary and analysis of post-market surveillance data
In December 2018, the Inspectorate requested technical
documentation of all selected mesh implants and ordered RIVM to
assess the technical documentation (Annex 4). RIVM performed the
assessment and manufacturers were given the opportunity to check
on factual inconsistencies. The response of the manufacturers was
reviewed by RIVM and the assessments were finalized.
In January 2020, the Inspectorate requested the latest ‘Clinical
evaluation’ of two transvaginal mesh implants and asked RIVM to
assess the latest ‘Clinical evaluation’. Manufacturers were not given
the opportunity to check on specific factual inconsistencies of the
assessment, however, they were given the opportunity to check on
factual inconsistencies of the entire current report. In February 2020,
a summary of the assessment of the technical documentation sets of
two transvaginal mesh implants that were on the Dutch market
November 1st 2019 was reported to the Inspectorate and published
[25]. This assessment included the technical documentation requested
in 2018 and the latest ‘Clinical evaluation’ requested in 2020.
In February 2020, the Inspectorate requested the latest technical
documentation of ‘Instructions for use (IFU)’, ‘Risk analysis’, ‘Clinical
evaluation’ and ‘Summary and analysis of post-market surveillance
data’ of a set of transabdominal mesh implants. The Inspectorate
asked RIVM to assess the latest technical documentation.
Manufacturers were not given the opportunity to check on specific
factual inconsistencies of the assessment, however, they were given
the opportunity to check on factual inconsistencies of the entire
current report. In May 2020, a summary on the assessment of the
technical documentation sets of transabdominal mesh implants that
were on the Dutch market November 1st 2019 was reported to the
Inspectorate. This assessment included the technical documentation
requested in 2018 and in 2020.
The Inspectorate has indicated that manufacturers and notified bodies
are currently working to address the identified shortcomings at their
request.

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The following sections of this report summarize the results of the
assessment of the technical documentation sets. A summary of the
overall conclusions on shortcomings of file items requested in 2018 per
mesh implant is given in section 3.1 in terms of major, minor or none. A
file item can contain multiple shortcomings. Whether to qualify the
combined shortcomings in a file item as major or as minor was based on
expert judgment by the assessors. Important considerations to decide
that the shortcomings were major include the amount and type of
missing information and the potential impact on patient safety of the
shortcoming. The detailed conclusions of the assessment of each
technical file item per mesh implant are presented in Annex 6. The
subsequent sections 3.2-3.8 summarise the findings per file item. In
section 3.9, the assessment of the clinical evaluation for two
transvaginal mesh implants requested in 2020 by the Inspectorate is
compared to the assessment of document versions requested in 2018.
In section 3.10, the assessment of the file items IFU, risk analysis,
clinical evaluation, and summary and analysis of post-market
surveillance (PMS) data, of four transabdominal mesh implants
requested in 2020 are compared to the assessment of versions
requested in 2018. In section 3.11, an evaluation is made of the
potential impact on patient safety of shortcomings found in the technical
documentation. A summary of the assessment of technical
documentation are provided in section 3.12.
3.1

Overall quality of the technical documentation 2018
The overall results of the assessment of the technical documentation
requested in 2018 are shown in Table 3.1. The files had major
shortcomings in three up to five file items and minor shortcomings in
one up to three file items. Five technical documentation sets had major
or minor shortcomings in all file items. Four technical documentation
sets had one or two file items without any shortcoming. Examples of
identified shortcomings for each file item are listed below.

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Table 3.1 Summary of the assessment of technical documentation sets of
gynaecological mesh implants requested by the Inspectorate in December 2018.

Risk
analysis

Chemical
composition

Biocompatibility

Clinical
evaluation

S&A PMS data

Mesh
(manufacturer)
Transvaginal approach
BSC
None
(A.M.I.)
Calistar S
None
(Promedon)
Nuvia SI
Minor
(BD)
Restorelle DirectFix
Minor
(Coloplast)
Transabdominal approach
Alyte
Minor
(BD)
ARTISYN
(Johnson &
None
Johnson)
GYNEMESH PS
None
(Ethicon)
Restorelle M L XL
Minor
(Coloplast)
Restorelle Y
Minor
(Coloplast)

IFU

Device
description

Overall conclusion on shortcomings in file items

Minor

Major

Major

Major

Major

-a

Minor

Major

Major

Major

Major

Major

Minor

Major

Major

Major

Major

Minor

Minor

Major

Minor

Major

Major

Major

Minor

Major

Major

Major

Major

Major

Minor

Major

None

Major

Major

Major

Minor

Major

None

Major

Major

Minor

Minor

Major

Minor

Major

Major

Major

Minor

Major

Minor

Major

Major

Major

Abbreviations:
IFU – instructions for use
S&A PMS – summary and analysis of post-market surveillance
a
Not assessed; the manufacturer did not provide documents dating before the deadline of
the initial request by the Inspectorate despite repeated requests from the Inspectorate.

3.2

Device description
The device description of four technical documentation sets complied with
all aspects checked in the assessment. Five technical documentation sets
had minor shortcomings. Examples of identified shortcomings are:
• No separate section with a general device description as required
in the MDD. The information was scattered over multiple file items;
• Lack of information when to use the various designs of the mesh
when more than one design was available. It appeared that
choosing the appropriate mesh depends on the preference and
experience of the surgeon;
• No details on the geometry, i.e. physical dimensions of the
different parts of a mesh;
• Insufficient description of a key functional element of the mesh;
• No information on the knitting pattern of the mesh.
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3.3

Instructions for use
All instructions for use (IFU) were submitted in English and four IFUs
also in Dutch. Considering the education levels of the users, both
languages are considered acceptable. Contraindications and meshrelated risk topics were mentioned in all IFUs. However, minor
shortcomings were identified in all IFUs. Examples of identified
shortcomings are:
• The submission of a non-current version of the IFU, i.e. a version
from 2014, while a version from 2015 was referred to in another
file item;
• The IFUs of mesh implants with different designs or variants from
the same manufacturer were identical with regard to the
indications for use and the surgical procedure. More information
is needed to allow an understanding when to use which design,
and how this affects the surgical procedure;
• No specific or only brief surgical instructions for a particular mesh
were included. It was always indicated that the mesh implants
have to be implanted by trained and/or experienced surgeons.
However, more specific instructions should be included to aid
even trained surgeons with specific aspects of the mesh to be
used;
• For the transvaginal mesh implants, no reference to
recommendations from the relevant SCENIHR opinion [10]
and/or specific professional (national) guidelines was included in
any IFU. These documents recommend the use of transvaginal
mesh implants only when other surgical options are not feasible.

3.4

Risk analysis
Although the EN ISO 14971 standard was used by all manufacturers, the
overall conclusion on the risk management documentation was that it
contained major shortcomings in all cases. Examples of identified
shortcomings – not all major by itself – are:
• No (specific) risk management plan available;
• Not all general hazard categories as derived from EN ISO 14971
were addressed in the risk analysis (see Attachment II in Annex
5);
• Contraindications and their related risks were not analysed;
• Risk estimation before mitigation was missing. Risk estimation
before and after mitigation allows insights into the effect of the
mitigation action;
• Risk control was not in line with essential requirement 2 of the
MDD, as risk reduction as far as possible was not adequately
substantiated or it was not clear how risk reduction as far as
possible was achieved (e.g. whether a change in design was
considered);
• Acceptability of residual risks in relation to the benefit was
insufficiently substantiated;
• The link between risk management and PMS was not adequately
shown.

3.5

Chemical composition
Major shortcomings were found in four technical documentation sets and
minor shortcomings in three sets. In two sets, the chemical composition
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was sufficiently described. Examples of identified shortcomings – not all
major by itself – are:
• Limited information on the chemical specification of the final
product or of the raw materials, e.g. molecular weight of the
polypropylene was missing;
• No details of the chemical specification of accessories;
• No preparation protocol of the mesh.
3.6

Biocompatibility
Although the EN ISO 10993 series of standards were used by all
manufacturers, the overall conclusion on the evaluation of the
biocompatibility in all technical documentation sets was that it contained
major shortcomings. Examples of identified shortcomings – not all major
by itself – are:
• Limited chemical, physical or mechanical characterisation of the
mesh was included;
• Only a general statement of the long history of use of
polypropylene in implants was included, with limited or no
reference to literature;
• Existing toxicology and biocompatibility data were used from
other mesh implants with different physical and/or mechanical
characteristics. Manufacturers’ claims of comparability lacked
adequate substantiation for the extrapolation of data from one
product to another;
• Only standard toxicity endpoints, as specifically mentioned in ISO
10993, were considered. No additional testing related to specific
aspects of the mesh was considered; tissue in-growth, which has
been advocated as an advantage of ultralight weight mesh
implants, could be an example of such specific aspects;
• Implantation tests were performed on products with different
geometry and shape, without proper justification; this includes
using suture material instead of mesh material. ISO 10993-6
indicates that physical characteristics, such as geometry and
shape, can influence tissue response. For tests using extracts,
this could be considered less relevant. However, for tests using
the actual mesh material, e.g. implantation testing, this should
be considered;
• Insufficient justification was given on the selection of the control
sample, implantation site (type of tissue), type of experimental
animal, and the duration of the implantation period;
• Protocols for testing were not submitted;
• Either no summary of results was included or the overall analysis
was limited and results were only summarized per endpoint as
“acceptable”.

3.7

Clinical evaluation
For all documentation sets, the overall conclusion on the clinical
evaluation report (CER) was that it contained major shortcomings.
Examples of identified shortcomings – not all major by itself – are:
Structured overview on all relevant clinical data
• The CER used for initial market approval was often not included,
although it was specifically requested. In addition, several
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•

manufacturers used a system of “updated” versions of the CER,
in which a new version of the CER was covering only the period
since the previous version. The most recent version did not
provide a complete overview of all relevant literature and other
clinical data. Summarised descriptions of the clinical data as
discussed in previous versions of the CER and conclusions on the
complete clinical data set were usually lacking;
A family of transabdominal mesh implants was covered by one
CER, without clear and structured stratification of the clinical data
between the different designs. Another manufacturer covered
mesh implants intended for transabdominal as well as
transvaginal application in the same CER, again without
stratification.

Choice of clinical data types
Several CERs were not in line with the insights on the clinical data
needed according to the relevant European guidance document [32].
Examples of shortcomings are:
• Clinical data were collected in a non-structured manner;
• Clinical data were included from cases where the mesh implants
were used outside the indications for use;
• Mainly or only publications with a low level of evidence were
used, such as case reports, case series, and abstracts of
conference proceedings;
• Data were used from other mesh implants claimed to be
equivalent, without adequate substantiation of such equivalence,
see also below;
• Limited number of publications were used.
Safety and performance
• No (clinical) safety and performance claims were included in most
CERs. The following topics were indicated as claims in the reports
assessed: description of the intended use and indication for use,
promotional claims, or descriptive text on product design, or
preclinical performance. A clear description of (quantitative)
clinical safety and performance claims is needed for adequate
safety and performance analysis;
• Safety data, e.g. adverse events and complaints, as well as
performance data, e.g. clinical and patient-reported outcomes,
were included, but no analyses were performed on the
acceptability of such data. As no safety and performance claims
(thresholds) were indicated in the CER, no comparisons were
made to such thresholds. This hampered the assessment of the
appropriateness of the conclusions of the safety and performance
analyses;
• Safety and performance were only discussed on a high level,
without presenting safety data or discussion;
• Most safety and performance information was related to other
mesh implants than the subject mesh. The subject mesh and
other mesh implants were part of a product family;
• Treatment of POP using native tissue repair was not always
included for comparison.

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Equivalence
In case equivalence was claimed, adequate substantiation was lacking.
Examples of such inadequate substantiations are:
• Data from a flat mesh were used for a Y-shaped mesh. It was
claimed in a response from the manufacturer that only data were
used from cases where it was self-cut and sewn into a Y-shaped
mesh. In the CER this was not clear for all data included.
Moreover, constructing a Y-shaped mesh from a flat mesh was
not considered a reproducible process, thus still undermining the
claim of equivalence;
• Differences in physical and mechanical mesh properties, for
instance pore size, density, thickness, stiffness, pull-out strength,
knitting pattern, or shape were indicated but not discussed or a
short statement was made that differences were not relevant.
Post-market clinical follow-up (PMCF)
• PMCF was not deemed necessary by the manufacturer; sufficient
medium and long term safety and performance were considered
to be demonstrated based on a small number of publications,
including non-scientific papers;
• PMCF was not deemed necessary by the manufacturer as
sufficient clinical data were considered to be available, especially
for the “equivalent” device. However, the claimed equivalence
was insufficiently substantiated;
• PMCF was not mentioned or discussed;
• The information on PMCF in the CER and the PMCF Report was
mostly, but not entirely, the same. For example, additional
details were provided on the US Food and Drug Administration
(FDA) ordered PMS study, indicating patient enrolment since
2014. Neither in the CER, nor in the PMCF Report results of this
study were described, although it was mentioned that results
have been provided to the FDA in May 2018. A manufacturer
managed registry was being set up, but no data were yet
available.
Clinical benefit, summary and appraisal, change in benefit/risk ratio,
conclusions
• Clinical benefit was not addressed or the discussion on clinical
benefit was insufficient;
• A summary of the clinical data was not provided or limited;
• Appraisal was not performed;
• Benefit/risk ratio was not addressed;
• Conclusions focussed only on the identification of new
unanticipated risks or negative trends;
• No conclusion was provided on the performance of mesh
implants;
• Conclusions were limited to clinical data from the time period
covered by the updated version of the CER. Conclusions should
cover all available data as discussed in previous versions of the
CER, plus the additional data from the update;
• Conclusions were described in a high level manner or contained
only high level statements without sufficient underlying analysis.

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3.8

Summary and analysis of post-market surveillance data
The summary and analysis of the post-market surveillance (PMS) data
of six technical documentation sets showed major shortcomings. Minor
shortcomings were identified in two technical documentation sets,
including one set that did not include a separate technical
documentation item. Instead, the manufacturer indicated that these
data were included in the CER. Hence, the assessment was based on
information in the CER. Also, one manufacturer did not submit the
summary and analysis of PMS data dating before the deadline of this
assessment. Therefore, the summary and analysis of PMS data of this
particular mesh was not assessed. Examples of identified shortcomings
– not all major by itself – are:
• No summary of PMS data was present. Only the number of
complaints received was mentioned, with the remark that “none
of all complaints involved any situation that could affect the
safety of the patients”;
• Limited number of PMS sources, mainly complaints were used;
• No adequate analysis of PMS data was included. Criteria for the
necessity to take action with regard to the frequency of
complications were not provided;
• The results of periodic analyses, including decisions made and
actions assigned, were not present;
• The argumentation that PMCF is not necessary was not
sufficiently substantiated;
• The PMCF plan contained only limited PMCF activities.

3.9

Assessment of updated clinical evaluations of transvaginal mesh
implants
In addition to the technical file items requested in 2018, the
Inspectorate requested the current CERs of two transvaginal mesh
implants in January 2020. These two transvaginal mesh implants were
still on the Dutch market November 1st 2019. These updated CERs were
also assessed by RIVM. The overall conclusion on these updated CERs
was that they still contained major shortcomings, as was the overall
conclusion for those requested in 2018 (Table 3.2). Although part of the
sub-items of the CERs had identical shortcomings, a number of subitems were improved. However, the shortcomings were not always fully
resolved. In the text underneath, the updated CER always refers to the
CER requested in 2020.
Table 3.2 Comparison of the assessment of the clinical evaluation of transvaginal
gynaecological mesh implants requested by the Inspectorate in 2018 and 2020.

Overall conclusion on shortcomings in CER
Mesh (manufacturer)
BSC (A.M.I.)

1

Calistar S (Promedon) 2

Requested in 2018

Requested in 2020

Major

Major

Major

Major

November 2019: Notified body temporarily restricted CE certificate of BSC Mesh. In
September 2020, temporary restriction was removed after audit by notified body of
updated technical documentation for BSC Mesh.
2
March 2020: Notified body temporarily restricted CE certificate of Calistar S. In
September 2020, temporary restriction was removed after audit by notified body of
updated technical documentation for Calistar S.
1

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Examples of improvements in updated CERs (requested in 2020) are
provided below.
Choice of clinical data types
• In one of the CERs requested in 2018, a very basic literature
search was conducted, not in line with the relevant MEDDEV
guidance document. In the updated CER (requested in 2020), a
comprehensive literature search was performed, more in line with
a systematic approach. However, it was limited to a period of 5
years ending almost two years before the date of the CER and
appraisal was lacking. It contained very few references of a low
level of evidence related to the subject mesh, and also included
data from which the relevance was less clear (e.g. on mesh
implants constructed from materials different from the subject
mesh).
PMCF
• In one of the CERs (requested in 2018), PMCF was not described
or discussed. In the updated CER (requested in 2020), PMCF was
considered necessary and two PMCF studies were waiting for
approval of the ethical committee.
Equivalence
• For both mesh implants the clinical evaluation has been
performed based mainly on clinical data from other products,
without adequate substantiation of equivalence in the previous or
the updated CER;
• For one mesh implant, the CER requested in 2018 did not contain
any substantiation. The updated CER (requested in 2020) listed
an appendix on equivalence assessment in the table of contents,
however, the appendix was not present. Discussion on
equivalence or comparison with other mesh implants was not
included or referred to in the main text;
• For the other mesh, in both versions of the CER, a comparison
with other products was made on a number of relevant aspects
as required in the relevant guidance document [32]. In the CER
requested in 2018, the mesh implants were claimed to be “very
similar” despite a number of differences that were not debated.
In the updated CER, part, but not all, of the differences were
acknowledged, equivalence was not claimed. However, the data
of the compared mesh implants were still used for the clinical
evaluation of the subject mesh.
3.10

Assessment of updated technical documentation items of
transabdominal mesh implants
The technical documentation sets of four transabdominal mesh implants
requested in 2020 were assessed and compared with the technical
documentation sets requested in 2018 (Table 3.3). These four
transabdominal mesh implants were still on the Dutch market November
1st 2019. Current versions of the items IFU, risk analysis, clinical
evaluation and summary and analysis of PMS data were requested by
the Inspectorate. Not for every included item a new version was
available. In comparison to the technical documentation requested in
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December 2018, the overall conclusions on some file items were
changed from major to minor shortcomings, while others remained the
same despite the fact that improvements were observed (Table 3.3). In
the text below, updated always refers to documentation requested in
2020.
Table 3.3 Comparison of the assessment of technical documentation of
transabdominal gynaecological meshes requested by the Inspectorate in 2018
and 2020.

Mesh
(manufacturer)
ARTISYN
(Johnson &
Johnson)
GYNEMESH PS
(Ethicon)
Restorelle M L XL
(Coloplast)
Restorelle Y
(Coloplast)

Overall conclusion on shortcomings in file items
Risk
Clinical
S&A PMS
IFU
analysis
evaluation
data
Requested in
2018
2020
2018
2020
2018
2020
2018
2020

Minor

Minor1

Major

Major

Major

Major

Major

Minor

Minor

Minor1

Major

Major

Major

Major1

Minor

Minor

Minor

Minor1

Major

Minor

Major

Major

Major

Major

Minor

Minor1

Major

Minor

Major

Major

Major

Major

Abbreviations:
IFU – instructions for use
S&A PMS – summary and analysis of post-market surveillance
1
Documentation requested in 2018 and 2020 was identical, indicated by same version and date.

Examples of improvements in updated technical documentation items
(requested in 2020) are provided below.
IFU
The IFUs requested in 2018 and 2020 were identical, as indicated by
same identification of the version of the IFU and the same date of the
IFU. Thus, the overall conclusion on the IFUs did not change and all IFUs
had minor shortcomings.
Risk analysis
Improvements in the risk analysis were observed in all four cases. For
two transabdominal meshes, some sub-items of the risk analysis
improved but this did not change the overall conclusion, i.e. major
shortcomings remained for these risk analyses. However, for the other
two transabdominal meshes, the overall conclusion of the risk analysis
was changed from major to minor shortcomings. Examples of
improvement are:
• A risk management plan was submitted instead of a template for
a risk management plan. However, the plan did not differentiate
between the different designs of the various transabdominal
meshes it was covering. Different designs could lead to specific
risks, e.g. in manufacturing and surgical procedure, which should
be identified in the plan;
• Risk estimation before risk mitigation as well as post-mitigation
was shown in the risk analysis;
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•

A common shortcoming for the technical documentation
(requested in 2018) was insufficient substantiation that the risks
had been reduced as far as possible although statements
indicating this were included. This shortcoming was resolved for
two of the products.

Clinical evaluation
For one mesh, the same CER was submitted in 2018 and in 2020. The
remaining three CERs were more recent. Although some improvements
were identified, shortcomings were basically the same or the
improvements did not resolve the earlier identified shortcomings.
Examples of improvements are:
• An increased number of publications was used for the safety and
performance analysis. However, all of the data on the subject
device had the lowest level of evidence, and part of it was related
to off-label use. Another part of the data was related to a
different mesh implant, of which the equivalence was not
sufficiently substantiated;
• In the CER requested in 2018, it was stated that PMCF was not
needed. In the updated CER (requested in 2020) it was indicated
that additional PMCF activities have been planned to verify the
long term safety and performance of the mesh. However, data
from these activities were not yet available.
Summary and analysis of PMS data
The summary and analysis of PMS data of two updated technical
documentation sets (requested in 2020) showed major shortcomings.
In one case the improvements in the in 2020 requested technical
documentation sets resulted in a change in the overall conclusion from
major to minor shortcomings. For the fourth product, the overall
conclusion remained that the documentation had minor shortcomings.
Examples of improvement are:
• The number of sources used to obtain PMS data was increased;
• In two cases, the earlier documentation indicated no need for
PMCF, while PMCF activities were planned in the updated version
(data not yet available).
3.11

Potential impact of findings on patient safety
This paragraph describes whether the identified shortcomings described
above potentially affect patient safety. Shortcomings in the technical
documentation could imply that product safety and safe use of the
device are insufficiently guaranteed. This in turn could have impact on
patient safety. On the other hand, the impact of shortcomings could be
counterbalanced by available information in other parts of the file, or the
file could be poorly maintained while the device is of high quality. Thus,
while it is important that the technical documentation is providing all the
necessary information in the correct section of the file, shortcomings in
the file do not necessarily have impact on patient safety.

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Device description
The shortcomings in the device description, such as scattered
information in the files and limited information on several aspects of the
mesh implants, are not considered to have potential impact on patient
safety.
Instructions for use
Although the shortcomings for the IFU were not considered to be major,
some of these shortcomings could influence the correct use of the mesh
implants and could therefore potentially impact patient safety.
RIVM did not receive the latest version of one of the IFUs. If this is also
the case for the users, this could mean that the users do not have the
latest information on the appropriate use of the mesh or on all identified
residual risks. Limited information on the use of different designs or on
surgical procedures to be followed could hamper the correct application
of mesh implants. For trained surgeons, the potential impact on patient
safety is considered limited.
Recommendations on the use of transvaginal mesh implants only when
other surgical options are not feasible, are included in specific (national)
professional clinical guidelines, as well as in an opinion of the European
scientific committee SCENIHR [10, 15, 16]. Not referring to this in the
IFU could mean that this recommendation is insufficiently included in the
deliberations on the treatment between the surgeon and the patient. In
relation to this, given the current insights into the risk-benefit of
transvaginal mesh implants, manufacturers should consider modifying
the indications for use of their products based on these guidelines.
Risk analysis
For the risk analysis, a frequently observed shortcoming was inadequate
substantiation that all risks had been reduced as far as possible. For
example, considering a modification of the design, which is the
mandatory first risk control option in the MDD, was often not described
in the risk analysis. If the design could be improved, this could have a
potential positive impact on patient safety.
On the other hand, not addressing all general hazard categories as
derived from the harmonised standard, or insufficiently substantiating
the acceptability of residual risks in relation to the benefit has a
potential negative impact on patient safety.
Also not adequately showing the link between PMS and the risk analysis
has potential impact: during PMS new risks may be detected. If these
new risks are not fed back into the risk analysis adequately, risk
reduction will not be pursued.
Not analysing risks related to contraindications potentially has impact on
patient safety, because measures to mitigate these risks could be
missed. However, given the fact that the contraindications are provided
to an experienced user through the IFU, the potential impact is expected
to be limited.
Chemical composition
If detailed information on the chemical composition is not available,
adequate quality control on the raw materials might not be possible,
leading to potential variation in material properties. This could impact
the effect of the mesh implants in the patients, and thus patient safety.
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Information on the chemical composition is also essential for the
biocompatibility evaluation.
Biocompatibility
In a number of cases, existing data were used from other mesh implants
with different physical characteristics, for example shape, without proper
justification. This is especially relevant in relation to the implantation
tests that are performed with the actual material, rather than extracts.
As also indicated in the ISO standard for implantation testing [36], such
characteristics can influence tissue response. Furthermore, if the choices
for important parameters in these tests, like the implantation site and
the duration of implantation, have not been substantiated in relation to
the product and its intended use, it is uncertain whether the most
relevant data are available. This could have potential impact on patient
safety. If test protocols are not submitted, assessors have no insight
which choices were made.
The ISO standards require that additional testing besides the standard
endpoints is considered, in relation to specific aspects of the implant. It
is uncertain whether the lack of such considerations could have impact
on patient safety. This is also the case for just generally stating the long
history of use of polypropylene in implants, with limited or no reference
to literature.
The lack of an overall analysis and summary of results becomes
especially important if one or more test results could imply potential
toxicity. This was not observed in the submitted files. However, these
had shortcomings, as explained above.
Clinical evaluation
Clinical data are the basis for a clinical evaluation. An adequate amount
of data relevant for the device and its intended use with an acceptable
level of evidence are needed for a reliable clinical evaluation. The
shortcomings identified in relation to this can have a potential impact on
patient safety. A specific example is when manufacturers use the data
from a different device. Such data can only be used to analyse safety,
performance and clinical benefit when the devices are equivalent. If the
equivalence is not adequately substantiated, this reduces the reliability
of the clinical evaluation. The same applies to cases where the data for
mesh implants with different designs and/or different intended use are
combined in one CER without a proper stratification.
An issue in relation to the data encountered with several manufacturers
was that they use a system in which a new version of the CER is
covering only the period since the previous version of the CER. The most
recent version did not provide a complete, or even summarised
overview of all relevant literature and other clinical data from previous
CERs. Therefore, the basis for conclusions in the CER on safety,
performance and benefit-risk was not clear. The analysis and the
conclusion should cover all available data, not just the new data
presented in the CER update. Depending on the total data set the
manufacturer has available in the different versions of the CER, this may
or may not have a potential impact on patient safety.
When good clinical data are available, a proper analysis of safety and
performance with sufficient detail needs to take place. The clinical
benefit and the benefit-risk ratio have to be specifically addressed. The
absence of safety and performance claims (for example on adverse
Page 32 of 73

RIVM letter report 2020-0154

events or patient-reported outcomes) hampers the assessment of the
appropriateness of conclusions on safety and performance. The
shortcomings identified in relation to this could have a potential impact
on patient safety.
After a device is placed on the market, the manufacturer needs to
continue clinical safety and performance evaluation in the long term and
in a broader population. If no adequate PMCF takes place, new clinical
insights can be missed, which could potentially have impact on patient
safety.
Summary and analysis of PMS data
One identified shortcoming was using complaints as the only source for
PMS. Other sources, especially (pro)active ones, should be used to
obtain more comprehensive PMS data. Not using such sources means
missing the opportunity to improve the functionality and safety of the
medical device. Therefore, this shortcoming is judged to have potential
impact on patient safety. The same argument also applies for mesh
implants where only limited PMS sources were used.
Not performing an adequate analysis of the available PMS data could
lead to incorrect assessment of changes in the benefit/risk ratio or
missing opportunities for improvement. This could lead to delayed or no
actions to improve the functionality and safety of the medical device.
Therefore, this shortcoming is judged to have potential impact on
patient safety.
3.12

Summary of the assessment of technical documentation sets
The quality of the technical documentation sets varied between the
included mesh products. The general description and the IFU had no or
minor shortcomings in all files of the various mesh implants. However,
the file items risk analysis, biocompatibility, clinical evaluation and
summary and analysis of PMS data showed major shortcomings in most
of the files.
For part of the technical documentation sets, updated versions of one or
more technical documentation items were also assessed. Generally, the
updated versions showed improvements in sub-items. This did,
however, not always lead to a change in the overall conclusion with
regard to the quality of the technical documentation item.
It should be noted that the overall conclusion “major shortcomings”
does not discriminate between documentation with multiple
shortcomings and documentation with fewer shortcomings, that still lead
to the qualification “major shortcomings”. For example, a clinical
evaluation based on a limited amount of clinical data from other devices
without any substantiation of equivalence and hardly any analysis of the
data gets the conclusion “major shortcomings”. On the other hand, a
clinical evaluation based on a larger amount of data, all related to the
subject device, can still get the qualification “major shortcomings” if the
analysis of the data needs to be improved.
It is important that the technical documentation is providing all the
necessary information to show conformity with the regulatory
requirements. Shortcomings in the documentation do not necessarily
mean that the device is of insufficient quality, or that patient safety is at
stake. However, the identified shortcomings mean that patient safety is
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RIVM letter report 2020-0154

not sufficiently guaranteed by the technical documentation. An analysis
showed that there is a potential impact on patient safety related to
shortcomings in many of the file items.
Given this, and the fact that the safety and performance of medical
devices are required to be substantiated by the information in the files
according to the regulatory system for medical devices, this outcome
should be reason for manufacturers to carefully consider and resolve the
shortcomings in order to better substantiate the quality and safety of
their medical devices. The Inspectorate informed RIVM that several
manufacturers are currently working to address the identified
shortcomings in order to comply with the requirements for the MDD.

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RIVM letter report 2020-0154

4

Conclusion

POP can affect women of all ages. It more commonly occurs in older
women and affects 30-40% of women worldwide. POP is not lifethreatening, however, it does reduce the quality of life for women with
this condition. Several treatment options are available for POP, including
reconstructive surgical procedures using surgical mesh implants.
Previous investigations showed that surgical mesh implanted to treat
patients with POP can cause serious complications.
The NVOG has requirements that all transvaginal and transabdominal
mesh implants, together with any mesh-related complications are
registered in a central NVOG system. Currently, not all surgical mesh
implanted in patients with POP in the Netherlands are recorded in such a
registry. Well maintained registries are important for the collection of
real world data on the safety and performance of mesh implants.
In this study, we have compiled an overview of surgical mesh implants
intended to treat POP, as used in Dutch hospitals in 2018. We have
assessed the technical documentation sets from six manufacturers
marketing mesh implants for POP in the Netherlands at that time. All
technical documentation files contained a number of major and/or minor
shortcomings. Mesh implants that were on the Dutch market November
1st 2019 were prioritised and RIVM decided to notify the Inspectorate
about the results ahead of the full report. Summaries of the
assessments of the technical documentation sets of the two transvaginal
mesh implants (published in February 2020) and the four
transabdominal mesh implants that were on the Dutch market
November 1st 2019, were reported to the Inspectorate ahead of the full
report. The assessment showed shortcomings in the technical files of all
included mesh implants. Therefore, full conformity with the
requirements in the MDD was not shown. Although shortcomings in the
technical documentation do not necessarily mean that the device is not
safe, in many cases shortcomings in a particular file item were found to
have a potential impact on patient safety. All the shortcomings need to
be adequately addressed by the manufacturers in order to better
substantiate the quality and safety of their products as required in the
regulatory system. To arrive at this over-all conclusion, three questions
were addressed as described below.
Which transvaginal and transabdominal synthetic mesh implants are
being used to treat POP in the Netherlands?
A total of nine surgical mesh implants from six manufacturers were
identified to be used in the Netherlands in 2018. Five of these were
transabdominal mesh implants and four were transvaginal mesh
implants. Some of them had more than one variant, e.g. with different
sizes or for anterior, respectively posterior repair.

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Do the technical files of the selected mesh implants provide adequate
proof of conformity with the requirements of the Medical Devices
Directive (MDD)?
All technical files contained three or more file items with major and one
or more file items with minor shortcomings. Therefore, full conformity
with the requirements in the MDD was not shown.
In case of shortcomings, do these lead to a concern for patient safety?
The regulatory system for medical devices depends to a large extent on
the quality of the submitted technical documentation. Any shortcoming
in that documentation could imply that product safety and safe use of
the device are insufficiently guaranteed. However, shortcomings in a
technical documentation file do not necessarily mean that the device is
of insufficient quality or unsafe. An analysis of the shortcomings in the
technical documentation showed that there is a potential impact on
patient safety of shortcomings in many of the file items. Manufacturers
should carefully consider and resolve the shortcomings in order to better
substantiate the quality and safety of their medical devices as required
in the regulatory system. The Inspectorate indicated that manufacturers
are currently working on improvements in their technical documentation
in order to comply with the requirements for the MDD. Some of the
manufacturers have indicated that the improved technical
documentation passed audits by their notified bodies and stated that
their technical documentation is now compliant with European
regulatory requirements. These audits took place after the RIVM
assessment was completed.
Recently, a new regulation for medical devices was published [37]. The
date of application of this regulation is May 26th 2021. It will then
replace the MDD [28]. This is the regulatory framework under which the
mesh implants were placed on the market. The new regulation is
strengthening the requirements on medical devices and on the technical
documentation. This includes strengthened requirements for risk
management, clinical evaluation and PMS. In light of these strengthened
requirements, update of all technical documentation sets is considered
necessary.

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RIVM letter report 2020-0154

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Page 40 of 73

RIVM letter report 2020-0154

Annex 1: Characteristics of surgical mesh implants used to treat POP in the Netherlands in 2018.

Manufacturer Name of
the
medical
device
A.M.I. GmbH
BSC Mesh 1

Surgical
approach

Material

Absorba- Material
bility
density

Fixation possibilities

Specifications

Reference

Transvaginal

Polypropylene

Nonabsorba
ble

ultralightweight
21 g/m2

Porosity 93%; hexagonal
mesh structure; surface area
of material surrounding the
vaginal wall is small: 3 cm2
of the implant has direct
contact with the vagina
(uterine cervix suspension);
u-shaped mesh (2 arms).

[38]

BD/C.R. Bard
Inc 2

Alyte® YMesh Graft

Transabdominal

Polypropylene

Nonabsorba
ble

Pore size: 2,78 x 1,33 mm
(anterior/posterior) and 1,96
x 1,06 mm (sacrocolpopexy).
Thickness: 0,29 mm
(anterior/posterior) and 0,40
mm (sacrocolpopexy). Mesh
size: 5 x 27 cm

[39], [40]

BD/C.R. Bard
Inc 2

Nuvia™ SI
SingleIncision
Prolapse

Transvaginal

Polypropylene

Nonabsorba
ble

17,67
g/m2
(anterior/
posterior)
and 35,55
g/m2
(sacrocolpopexy)
No
information

Bilateral sacrospinous
fixation with A.M.I. i-Stitch
device. The i-Stitch
facilitates the attachments
of sutures that are difficult
to reach without extensive
dissection, e.g. the mediocranial aspect of the
sacrospinous ligament.
Uterine cervix suspension
(illustration in brochure: 2
sutures for apical
suspension).
No Information

4 point fixation (anterior)
and 2 point fixation
(posterior)

No information

[41]

Page 41 of 73

RIVM letter report 2020-0154

Manufacturer Name of
the
medical
device
Repair
System

Surgical
approach

Material

Absorba- Material
bility
density

Fixation possibilities

Coloplast A/S

Restorelle®
DirectFix™
Anterior,
Restorelle®
DirectFix™
Posterior 3

Transvaginal

Polypropylene
Smartmesh®
technology

Nonabsorba
ble

No
information

Coloplast A/S

Restorelle®
M,
Restorelle®
L,
Restorelle®
XL

Transabdominal

Polypropylene

Nonabsorba
ble

Ultralightweight

Digitex® suture delivery
system, StatTack or
AbsorbaTack fixation
technologies. Digitex can be
used with non-absorbable
polypropylene sutures,
absorbable polydioxanone
sutures or absorbable
polyglycolic sutures, and
sutures sizes 0-0 or 2-0.
Single incision fixation.
Sutures anterior procedural
technique (with Digitex):
apex, bilateral SSL, bilateral
AT, bladder neck. Variations
in use occur due to
individual technique and
patient anatomy.
Digitex® suture delivery
system, StatTack or
AbsorbaTack fixation
technologies.

Page 42 of 73

Specifications

Reference

[42, 43]
[44]

NL & UK website: size not
indicated in centimetres, only
M and XL. Indicated for
anterior and posterior repair.
US website: size Restorelle M
Flat Mesh 15x10 cm,
Restorelle XL Flat Mesh
30x30 cm, Restorelle L Flat

[45, 46]
[47]

RIVM letter report 2020-0154

Manufacturer Name of
the
medical
device

Surgical
approach

Coloplast A/S

Transabdominal

Restorelle®
Y

Material

Polypropylene

Absorba- Material
bility
density

Nonabsorba
ble

No
information

Fixation possibilities

No information

Page 43 of 73

Specifications

Mesh 24x8 cm. Indicated for
sarcocolpopexy for surgical
treatment of vaginal vault
prolapse. FDA 510(k)
Summary (2013-08):
Restorelle M and Restorelle
XL are indicated for use as a
bridging material for
sacrocolposuspension and/or
sacrocolpopexy (laparotomy,
laparascopic, or robotic
approach). Where surgical
treatment for vaginal vault
prolapse is warranted. Both
are designed for the
treatment of apical vaginal
prolapse.
NL & US website: size
Restorelle Y 24x4 cm and
27x4 cm.
IFU US/CA version (201603): Restorelle Y is indicated
for use as a bridging material
for
sacrocolposuspension/sacroc
olpopexy (i.e. abdominal
placement via laparotomy,
laparascopic, or robotic
approach) where surgical

Reference

[48, 49]

RIVM letter report 2020-0154

Manufacturer Name of
the
medical
device

Surgical
approach

Ethicon LLC 4

GYNECARE
GYNEMESH
™ PS
Nonabsorba
ble
PROLENE™
Soft Mesh

Transabdominal

Polypropylene,
identical to
PROLENETM

Nonabsorba
ble

42,38
g/m2

Johnson &
Johnson Int

ARTISYN™
Y-Shaped
Mesh

Transabdominal

Polypropylene
and poliglecaprone25

Partially
absorba
ble

No
information

Promedon SA

Calistar S 5

Transvaginal

Polypropylene

Nonabsorba
ble

16 g/m2 at
central
area

Page 44 of 73

Material

Absorba- Material
bility
density

Fixation possibilities

The fixation technique and
products used should follow
current standard care. It is
recommended that sutures,
staples, or other
appropriate fixation devices
be placed at least 6,5 mm
from edge of the mesh.
The fixation technique and
products used should follow
current standard care.
When fixating with sutures
or other mechanical fixation
devices, a safe distance
from the edge of the mesh
of not less than 1 cm must
be maintained.
TAS (Tissue Anchoring
System) anchors with
sutures for fixation to
sacrospinous ligaments.
Anterior fixation arms:
fixation to obturator muscle.
Retractable insertion guide
designed for the placement
of the anchors. Retractable
insertion guide designed for

Specifications

Reference

treatment for vaginal vault
prolapse is warranted.
Mesh size: 10 x 15 cm and
25 x 25 cm.
Thickness 0,42 mm.
Pore size: 2,47 x 1,68 mm

[50, 51]
[52]

Mesh size: 27 x 5 cm

[53, 54]

Differential elasticity at
longitudinal and transversal
axis;
reinforcement for De Lancey
Level I & II;
two polypropylene
attachment arms and three
TAS anchors with their
corresponding sutures;

[55, 56]

RIVM letter report 2020-0154

Manufacturer Name of
the
medical
device

Surgical
approach

Material

Absorba- Material
bility
density

Fixation possibilities

Specifications

the placement of the
anterior attachment arms of
the implant. Knot pusher.

highly porous polypropylene
mesh.

1
November 2019: Notified body temporarily restricted CE certificate of BSC Mesh. In September 2020, temporary restriction was removed after audit
by notified body of updated technical documentation for BSC Mesh.
2
BD (Becton, Dickinson and Company) acquired C.R. Bard Inc in 2017.
March 2019: BD announced the removal of its Women’s Pelvic Organ Prolapse and Stress Urinary Incontinence Mesh Devices from the European
market.
3
In May 2019, Coloplast A/S stopped selling Restorelle® DirectFix™.
4
Ethicon LLC is a Johnson & Johnson subsidiary.
5
March 2020: Notified body temporary restricted CE certificate of Calistar S. In September 2020, temporary restriction was removed after audit by
notified body of updated technical documentation for Calistar S.

Page 45 of 73

Reference

RIVM letter report 2020-0154

Annex 2: Checklist for Dutch request gynaecological mesh
implants

1. Device description
The device description should cover the following elements:
a) a general description including its intended use/purpose;
b) the intended patient population and medical condition treated and
other considerations such as patient selection criteria;
c) the mode of action;
d) the risk class and applicable classification rule according to MDD
93/42/EEC, Annex IX;
e) an explanation of any novel features;
f) a description of the accessories, other medical devices and other
products that are not medical devices, which are intended to be
used in combination with it;
g) a description or complete list of the variants of the device;
h) a general description of the key functional elements:
• its parts/components,
• its composition,
• its functionality;
i) labelled pictorial representations (e.g. diagrams, photographs,
and drawings), clearly indicating key parts/components, including
sufficient explanation to understand the drawings and diagrams;
j) a description of the materials incorporated into key functional
elements and those making either direct contact with a human
body or indirect contact with the body;
k) the relevant CE mark certificate(s) issued by the notified body,
e.g. EC Design Examination Certificate Directive 93/42/EEC on
Medical Devices, Annex II (4).
2. Instructions for use
The instructions for use of the device as described in essential
requirement 13, including requirements 7.5 and 9.1 (MDD 93/42/EEC,
Annex I).¹
¹ For the purpose of the investigation, the instructions for use should be the ones associated with the medical
device as marketed in the Netherlands; if the device is currently not marketed in the Netherlands, at least an
English version should be provided.

3. Risk management plan and risk analysis
This documentation should contain a full report (NOT a summary) of the
risks identified during the risk analysis process and how these risks have
been controlled to an acceptable level. Preferably, this risk analysis
should be based on recognised standards, be consistent with the
manufacturer’s risk management plan, and be in English. For this
investigation, the documentation should include:
a) the risk management plan;
b) the risk analysis, containing the following elements:
• date/version number;
• reference to any standards used, e.g. EN ISO 14971;

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• all hazard categories (for example: Table Annex E of the
current standard EN ISO 14971) identified or, appropriately,
declared not applicable;
• estimates of associated risk;
• risk control, i.e. control measures that are consistently
described in line with essential requirement 2 (MDD
93/42/EEC, Annex I);
• (overall) justification/acceptability of residual risks in relation
to anticipated benefits;
c) the risk management report, ensuring that the risk management
plan is appropriately implemented, residual risks are acceptable
and appropriate methods are in place to obtain relevant
production and post-production information.
4.

Product verification and validation – relevant parts for this
investigation;
4.1. General
The documentation should summarise the results of verification and
validation studies undertaken to demonstrate conformity of the device
with the essential requirements that apply to it. For this investigation,
the information should cover the items 4.2, 4.3 and 4.4. Where no
testing has been undertaken, the documentation should incorporate a
rationale for that decision.
4.2. Chemical composition/product specification
Detailed information should be included on:
a) identify of raw materials (including chemical name);
b) chemical specification of raw materials;
c) list of suppliers of raw materials;
d) preparation protocol of the mesh;
e) chemical specifications of the mesh, including underlying
documentation on requirements of the mesh and the methods of
analysis;
f) medical substance, if applicable.
4.3. Biocompatibility
Detailed information should be included on:
a) a structured biological evaluation programme including
documented, informed decisions that assess the
advantages/disadvantages and relevance of
i. the physical, mechanical and chemical characteristics of the
medical device and its materials of construction;
ii. any history of clinical use or human exposure data (including
data in published literature);
iii. any existing toxicology and other biocompatibility data on
product and component materials, breakdown products and
metabolites (including data in published literature). For all
data, applicability to the relevant device should be shown;
iv. the selection of appropriate tests;
b) the tests conducted;
c) standards applied;
d) protocols (“standard operating procedures”) of the physical and
chemical characterisation, as well as in vitro and in vivo biological
evaluation studies conducted;
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e) analysis of data as gathered with the protocols under d);
f) summary of results and conclusion.
4.4. Clinical evaluation
The documentation should contain the clinical evidence that
demonstrates conformity of the device with the essential requirements
that apply to it. The clinical evaluation report should contain the
following elements:
a) the proprietary name of the medical device and any code names
assigned during device development;
b) identification of the manufacturer of the medical device;
c) description of the medical device and its intended application;
d) intended therapeutic indications;
e) alternative devices or treatments;
f) safety and performance claims made for the medical device;
g) context of the evaluation;
h) choice of clinical data types, i.e. clinical data used for the
evaluation can be published scientific literature, clinical
investigation(s), or a combination of scientific literature and
clinical investigations(s). These data should be supplemented with
data from the post-market phase, if applicable;
i) description of post-market clinical follow-up;
j) safety analysis of the medical device, including serious adverse
events that occurred;
k) performance analysis of the medical device;
l) summary of the clinical data and appraisal;
m) consistency of medical device literature and instructions for use
with clinical data;
n) conclusions, including possible changes to the benefit-risk ratio
and comparison with alternative treatments or devices.
The documentation should contain the evidence on which the initial
market authorization was based and the update of this information
based on data collected following placing on the market of the product,
e.g. but not limited to PMCF and PMS.
More information on the contents of the clinical evaluation report is
available in MEDDEV 2.7/1 revision 4, June 2016.
5.
Summary and analysis of PMS data
The submitted documentation should contain a PMS report of the last
four years, or the period since introduction on the market if less than
four years, containing the following elements:
a) summary of PMS data, including specification of the frequency of
separate adverse events, complaints, side effects, complications,
and description of other experiences related to the use of the
product, PMCF, patient-reported outcomes and data related to
explanted devices;
b) sources used to obtain PMS data;
c) analysis of PMS data, including trends, suitable indicators and
threshold values, substantiated decision whether any action (e.g.
FSCA) is necessary;
d) actions taken based on the analysis of PMS data.

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Annex 3: Method of the assessment of technical
documentation

Identification and selection of manufacturers and devices
For the identification of manufacturers and mesh implants used for the
treatment of POP, information was used from an RIVM questionnaire
sent to urogynaecologists performing transvaginal mesh surgery
affiliated to Dutch hospitals. Urogynaecologists were asked which mesh
(brand name and manufacturer) they implanted. The survey resulted in
an overview of manufacturers and their CE-marked gynaecological mesh
implants for the treatment of POP, that had been used in Dutch hospitals
in 2018. All listed mesh implants were selected for the assessment of
technical documentation (Table 2.1).
Request of technical documentation and manufacturer’s check on factual
inconsistencies
In December 2018, the Inspectorate requested a relevant part of the
technical documentation of the selected mesh implants from the
accompanying manufacturers (see Annex 4 for a copy of the letter).
With the letter requesting the technical documentation, a checklist was
enclosed which described details on the items to be submitted (see
Annex 2). The checklist was developed by RIVM and was largely based
on the Summary Technical Documentation (STED) from the Global
Harmonisation Task Force 2, modified in some places to better fit with
the requirements of the MDD. The following information was requested
from the manufacturers:
• Device description;
• Instructions for use;
• Risk management plan and risk analysis;
• Product verification and validation – relevant parts for this
investigation:
o General;
o Chemical composition/product specification;
o Biocompatibility;
o Clinical evaluation;
• Summary and analysis of PMS data.
Following receipt, the technical documentation set was checked for
completeness by RIVM and the manufacturer was asked by the
Inspectorate to provide any missing documentation. The submitted
documentation was accepted for assessment if dated on or before the
deadline of the initial request.
In October 2019, manufacturers received the results of the assessment.
For more information on the method of assessment see below. In case a
manufacturer was of the opinion that the assessment of a specific (sub-)
2 The Global Harmonization Task Force (GHTF) was the predecessor of the current International Medical Device

Regulators Forum (IMDRF). IMDRF aims to accelerate international medical device regulatory harmonization
and convergence. GHTF final documents are still current and can be accessed on the IMDRF website. As the
work of IMDRF progresses, these documents will be reviewed and published as IMDRF documents. For more
information, see http://www.imdrf.org/index.asp.
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item contained factual inconsistencies, the manufacturer was requested
to either state where the specific information could be found in the
originally submitted documentation or to provide additional
documentation which contained the specific information and was dated
on or before the deadline of the initial request. Upon reviewing the
manufacturer’s response, the assessment of the technical
documentation set requested in 2018 was finalized.
In January 2020, the Inspectorate requested the most recent CERs of
two transvaginal mesh implants. In February 2020, the Inspectorate
requested recent technical documentation of four transabdominal mesh
implants. The following information was requested:
• Instructions for use;
• Risk management plan and risk analysis;
• Clinical evaluation;
• Summary and analysis of PMS data.
Following receipt, the check for completeness was performed.
Manufacturers were not given the opportunity to check whether the
assessment of the technical documentation set requested in 2020
contained factual inconsistencies. Manufacturers were given the
opportunity to check whether the full report contained factual
inconsistencies.
Method of assessment
RIVM developed an assessment form (see Annex 5) in order to enable a
structured and uniform assessment of the documentation sets. For each
section of the checklist from Annex 2, a file item was included. For each
of these items, a set of sub-items was listed (largely based on the subitems listed in the STED). The MDD, the MEDDEV guidance document
2.7.1/Rev4 on clinical evaluation, harmonised European standards and
state-of-the-art (EN) ISO standards as relevant were used as a basis for
the assessment of the particular (sub-) items on risk management and
biocompatibility [28, 32-36].
The device description was mainly used as background information for
the assessment. For the IFU, it was checked whether specific meshrelated risks (see Annex 5, Attachment I) were mentioned. For the
assessment of the risk analysis, it was checked whether these meshrelated risks were addressed as well as whether general hazard
categories (see Annex 5, Attachment II), as derived from the
harmonised standard for risk management of medical devices were
covered [33]. For the item product verification the documentation
should summarise the results of verification and validation studies
undertaken to demonstrate conformity of the device with the essential
requirements that apply to it. For this assessment, the information
should at least cover the following items: chemical composition,
biocompatibility, and clinical evaluation. For chemical composition, it
was checked whether chemical product specifications of raw materials
and the mesh were described. For biocompatibility, it was checked
whether the evaluation was performed in line with the standards. For
the clinical evaluation, a list of mesh-related topics to be covered was
drawn up and checked (see Annex 5, Attachment III). For the summary
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and analysis of PMS data it was checked whether PMS was adequately
performed.
To facilitate a consistent assessment, two assessors assessed the
(additional) documentation and reviewed the manufacturer’s response
independently. Assessment forms were compared, any discrepancies
were discussed and resolved, and forms were finalized. This method has
also been used for previous assessments, such as silicone breast
implants, dermal fillers, and transcatheter aortic valves [29-31].
Quality of technical documentation items
In general, the quality of the technical documentation was based on the
presence or adequate description of each particular sub-item. Only a
shortcoming was noted in the assessment form. Several sub-items are
associated with patient safety, while for other sub-items, such a link is
not the case. Using expert judgement of the RIVM assessors, the overall
conclusion (indicated by no/minor/major shortcomings) for the technical
documentation items was obtained. Important considerations to decide
that the shortcomings were major include the amount and type of
missing information and the potential impact on patient safety of the
shortcoming.
Two kinds of factual inconsistencies were considered:
- The manufacturer submitted information but it did not appear to
be taken into account for a specific file item or sub-item. The
manufacturer was requested to specify the name of document
and page number(s);
- The appropriate documentation to cover a specific item of the
assessment did exist at the time, but was not submitted. As the
study was based on the situation at the moment of the
submission request, any documentation dating from after
deadline of the initial request for the technical documentation
items was not taken into consideration during the re-assessment.

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Annex 4: Request of the Inspectorate
> Return address Postbus 2518 6401 DA Heerlen

<Name manufacturer>
Sent by email

Date
Subject

20 December 2018
Request for technical documentation

Stadsplateau 1
3521 AZ Utrecht
Postbus 2518
6401 DA Heerlen
T 088 120 5000
www.igj.nl
Information
<Name Inspector>

Our reference
<Reference number>

Dear Sir/Madam,
The Dutch Health and Youth Care Inspectorate (Inspectorate) is the
competent authority for the European Directive on Medical Devices
93/42/EEC in the Netherlands. As such the Inspectorate is charged with
the surveillance and law enforcement of this Directive.
According to the information known to the Inspectorate your company
markets mesh implants to treat pelvic organ prolapse in the
Netherlands. By request of the Inspectorate, the National Institute for
Public Health and Environment (RIVM) will perform a study on mesh
implants.
Request for technical documentation
Part of this study involves an assessment of the technical documentation
of mesh products for the treatment of pelvic organ prolapse. Therefore,
we request you to follow the steps below and provide the following
information to the Inspectorate by e-mail to
_Die nstpostbusIGJMedischetechnologie@igj.nl (please note the
underscore _ at the beginning of the address).
1. After receipt of this letter: please provide the contact details
(including name, e-mail address and telephone number) of the
person who will be in charge of handling our request on behalf of
your company on January 7th, 2019 at the latest;
2. Additionally, please include an overview of the product names /
types of the marketed mesh implants and distributors in/for the
Netherlands;
3. Start collecting the documentation for the product(s) mentioned
below, according to the attached checklist. Please, mark the
documents as ‘confidential’ and provide them in such a format
that it clearly refers to the items as listed in the attached
checklist, in order to prevent misinterpretation during
assessment.
The request under item 3 concerns your product(s): <product
name(s)>.
In the week of January 7th, 2019 and after receipt of the contact details
of the person in charge of our request, we will send this contact person
information on how to provide us with the documents by secured
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means. In order to be able to start the assessment in time, we kindly
request you to forward the information before, but no later than
January 21st, 2019.
Please note that additional documentation may be requested, if
information is considered to be incomplete or assessment of provided
information indicates a need for more information.
Upon finalisation of the assessment, I will inform you regarding the
findings concerning your product(s). The results of this study will be
published by RIVM in a publicly available report.
If you have any questions regarding this letter or study, please do not
hesitate to contact me at the letter head address or at:
_DienstpostbusIGJMedischetechnologie@igj.nl.
Yours sincerely,

<Signing and name inspector dep. of Medical Technology>
Enclosure(s): Documentation required

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Annex 5: Assessment form

Manufacturer
Medical device (code – name – type of mesh)
Notified body (code – name)
1
1.a
1.b
1.c
1.d
1.e
1.f
1.g
1.h
1.i

1.j
1.k

Device description
General description, including intended use / purpose
Intended patient population and medical conditions treated and
other considerations such as patient selection criteria
The mode of action
The risk class and applicable classification rule according to MDD
93/42/EEC, Annex IX
An explanation of any novel features
A description of the accessories, other medical devices and other
products that are not medical devices, which are intended to be
used in combination with it
A description or complete list of the variants of the device
A general description of the key functional elements: its parts /
compartments; its composition and its functionality
Labelled pictorial representations (e.g. diagrams, photographs,
and drawings), clearly indicating key parts / components,
including sufficient explanation to understand the drawings and
diagrams
A description of the materials incorporated into key functional
elements and those making either direct contact with a human
body or indirect contact with the body
The relevant CE mark certificate(s) issued by the notified body,
e.g. EC Design Examination Certificate Directive 93/42/EEC on
Medical Devices, Annex II (4)

Shortcomings

Reference

Conclusion:

Manufacturer
Medical device (code – name – type of mesh)
Notified body (code – name)
2
2.a
2.b
2.c
2.d

IFU
Indications for use
Important aspects of the use of the mesh (trained user)
Contraindications and mesh-related risk topics (Attachment I)
IFU in Dutch or English
Reference to SCENIHR opinion and/or Dutch guideline regarding the
use of meshes only when other surgical options are not feasible

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Shortcomings

Conclusion:

Reference

RIVM letter report 2020-0154

Manufacturer
Medical device (code – name – type of mesh)
Notified body (code – name)
3

3.a
3.b

3.c

Risk analysis
This documentation should contain a full report (NOT a
summary) of the risks identified during the risk analysis process
and how these risks have been controlled to an acceptable level.
Preferably, this risk analysis should be based on recognised
standards, be consistent with the manufacturer’s risk
management plan, and be in English. For this investigation, the
documentation should include:
Risk management plan
Risk analysis, containing the following elements:
Date / version number risk analysis;
Reference to any standards used, e.g. EN ISO 14971;
All hazard categories of EN ISO 14971 (Attachment II)
identified or, appropriately, declared not applicable;
Contraindications and mesh-related risk topics addressed
(Attachment I);
Adequate estimation of associated risk;
Risk control, i.e. control measures that are consistently
described in line with essential requirement 2 (MDD
93/42/EEC, Annex I);
Acceptability of residual risks addressed in relation to
anticipated benefits
Conclusions: the risk management report (RMR), ensuring that
the risk management plan is appropriately implemented, residual
risks are acceptable and appropriate methods are in place to
obtain relevant production and post-production information

Shortcomings

Reference

Conclusion:

Manufacturer
Medical device (code – name – type of mesh)
Notified body (code – name)
4
4.1

4.2
4.2.a
4.2.b
4.2.c
4.2.d

Product verification and validation – relevant parts for this
investigation
The documentation should summarise the results of verification
and validation studies undertaken to demonstrate conformity of
the device with the essential requirements that apply to it. For
this investigation, the information should cover the items 4.2,
4.3 and 4.4.
Where no testing has been undertaken, the documentation
should incorporate a rationale for that decision.
Chemical composition / Product specifications
Identity of raw materials (including chemical name)
Chemical specification of raw materials
List of suppliers of raw materials
Preparation protocol of the mesh

Shortcomings

Reference

Shortcomings

Reference

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4
4.2.e
4.2.f

Product verification and validation – relevant parts for this
investigation
Chemical specifications of mesh, including underlying
documenta-tion on requirements of the mesh and the methods of
analysis
Medicinal substance, if applicable

Shortcomings

Reference

Conclusion:

Manufacturer
Medical device (code – name – type of mesh)
Notified body (code – name)
4.3
4.3.a

4.3.b
4.3.c
4.3.d
4.3.e
4.3.f

Biocompatibility
A structured biological evaluation program including
documented, informed decisions that assess the advantages /
disadvantages and relevance of
i. the physical, mechanical and chemical characteristics of the
medical device and its materials of construction;
ii. any history of clinical use or human exposure data
(including data in published literature);
iii. any existing toxicology and other biocompatibility data on
product and component materials, breakdown products and
metabolites (including data in published literature). For all
data, applicability to the relevant device should be shown;
iv. the selection of appropriate tests
Tests conducted
Standards applied (ISO 10993-series)
Protocols (“standard operating procedures”) of the physical and
chemical characterisation, as well as the in vitro and in vivo
biological evaluation studies conducted
Analysis of data as gathered with the protocols under d)
Summary of results and conclusion

Shortcomings

Reference

Conclusion:

Manufacturer
Medical device (code – name – type of mesh)
Notified body (code – name)
4.4

4.4.a
4.4.b
4.4.c
4.4.d
4.4.e
4.4.f

Clinical evaluation
The documentation should contain the clinical evidence that
demonstrates conformity of the device with the essential
requirements that apply to it. The clinical evaluation report
should contain the following elements:
The proprietary name of the medical device and any code
names assigned during device development
Identification of the manufacturer of the medical device
Description of the medical device and its intended application
Intended therapeutic indications
Alternative devices or treatments
Safety and performance claims made for the medical device
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Shortcomings

Reference

RIVM letter report 2020-0154

4.4
4.4.g
4.4.h

4.4.i
4.4.j
4.4.k
4.4.l
4.4.m
4.4.n

Clinical evaluation
Objective of the CER clearly documented
Choice of clinical data types, i.e. clinical data used for the
evaluation can be published scientific literature, clinical
investigation(s), or a combination of scientific literature and
clinical investigations(s). These clinical data should be
supplemented with data from the post-market phase, if
applicable
Description of post-market clinical follow-up
Safety analysis of the medical device, including serious adverse
events that occurred
Performance analysis of the medical device
Summary of the clinical data and appraisal
Consistency of medical device literature and instructions for use
with clinical data (Attachment I & III)
Conclusions, including possible changes to the benefit-risk ratio
and comparison with alternative treatments or devices.
State of the art addressed?
Equivalence used for CER? Has the equivalence been
adequately substantiated, see also MEDDEV 2.7/1 rev 4
Comparison with other devices documented?
Risks addressed consistently throughout relevant documents
(Attachment I)?
Literature: same device / same indications / patient population
if other devices included
Clinical benefit addressed?

Shortcomings

Reference

Conclusion:

Manufacturer
Medical device (code – name – type of mesh)
Notified body (code – name)
5

5.a

5.b
5.c
5.d

Summary & analysis of PMS data
The submitted documentation should contain a PMS report of the
last four years, or the period since introduction on the market if
less than four years, containing the following elements:
Summary of PMS data, including specification of the frequency of
separate adverse events, complaints, side effects, complications,
and description of other experiences related to the use of the
device, PMCF, patient-reported outcomes and data related to
explanted devices
Sources used to obtain PMS data
Analysis of PMS data, including trends, suitable indicators and
threshold values, substantiated decision whether any action (e.g.
FSCA) is necessary
Actions taken based on the analysis of PMS data
Actions taken adequate in relation to deficiencies observed?
PMCF part of PMS?

Shortcomings

Conclusion:

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Reference

RIVM letter report 2020-0154

Attachment I
Contraindications and risks based on literature for mesh (x = addressed)
Note: this is not an exhaustive list of contraindications and risks
IFU

RA

CER

IFU

RA

CER

1. Contraindications
Pregnant women, women that are considering / planning
future pregnancy
Potential of future / for further growth (e.g. infants,
children, adolescents)
Patients undergoing anticoagulant therapy
Patients with known sensitivity or allergy to polypropylene
products
Presence of known or suspected cancer of the vagina,
cervix, or uterus
(Active / pre-existing / latent) Systemic or local infection,
especially genital or related to the urinary tract
Blood coagulation disorder
Renal insufficiency and upper urinary tract obstruction
Autoimmune connective tissue disease
Any pathology that would limit blood supply and compromise
healing (e.g. decreased blood supply to organs due to
treatments such as radiation therapy, chemotherapy)
Any pathology, including known or suspected uterine
pathology, which would compromise implant placement
Pathology of soft tissue into which the mesh is to be placed
Patients with pre-existing conditions that pose an
unacceptable surgical risk
Planned intraoperative or accidental opening of the
gastrointestinal tract
Mesh should be used with precaution in diabetic women

2. Complications / side effects / adverse events
Abscess
Adhesion formation
Allergy, hypersensitivity or other immune reaction
Bladder damage
Bleeding, including haematoma, haemorrhage
Bowel damage
Contracture
Discomfort
Fistula formation
Granulation tissue formation
Infection / potentiation of existing infection
Inflammation
Mesh exposure, erosion or extrusion
Mesh migration
Necrosis
Nerve damage
Pain
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-

Pain during intercourse (dyspareunia)
Painful urination (dysuria)
Recurrent prolapse
Reoperation / resurgery
Scarring / vaginal scarring
Seroma
Ureteral obstruction
Urethra damage
Urinary incontinence (stress urinary incontinence, urge
incontinence)
Urinary retention / obstruction
Vaginal wall damage
Vessel damage
Voiding dysfunction
Wound dehiscence
IFU

RA

CER

IFU

RA

CER

3. Operational risks
Missing information on intended device delivery approach
Insufficient specification of all relevant dimensions
Inadequate device preparation
Disregard of expected device lifetime
Use beyond expiry date
Inadequate adherence to shipping / storage conditions
Warnings regarding handling and implanting the device
Inadequate or missing instruction for re-sterilisation method
/ max number (if applicable)
Incompatibility with physiological environment in which it is
intended to function

4. Risk factors, other than side effects
Bio-incompatibility
Adverse reaction to breakdown product of absorbable
materials (if applicable)
Package opened or damaged
Inability to complete implant procedure
Unintended anatomical interactions

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Attachment II
This appendix provides a selection of categories of risks and subsequent
examples, and is based on hazards described in the standard EN ISO
14971:2007, corrected 2012, Medical devices – Application of risk
management to medical devices. The list of examples is not exhaustively
(x = addressed).
Biocompatibility
- Allergenicity / irritancy
- Sensitization
- Cytotoxicity
- Carcinogenicity
Chemical hazards
- Acids and alkalis
- Residues, e.g. cleaning
- Contaminating agents
- Manufacturing additives or adjuvants
Use error
- Use by unskilled / untrained personnel
- Inadequate equipment
- Incorrect instrument operation
Hazardous phenomena linked to inadequate labelling
- Incomplete instructions for use
- Inadequate description of performance characteristics
- Inadequate specification of intended use
- Inadequate disclosure of limitations
Hazardous phenomena linked to inadequate operating instructions
- Inadequate specification of accessories to be used with the medical
device
- Inadequate specification of pre-use checks
- Over-complicated (operating) instructions
Hazardous phenomena linked to insufficient warnings about
- Of complications / side effects
- Of reuse of single-use medical devices
Incomplete requirements
- Inadequate specification of:
• design parameters
• performance requirements
• end of life
Manufacturing processes
- Insufficient control of changes to manufacturing processes
- Insufficient control of materials / materials compatibility
information
- Insufficient control of manufacturing processes
- Insufficient control of subcontractors
Transport and storage
- Inadequate packaging
- Contamination or deterioration
- Inappropriate environmental conditions
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Environmental factors
- Physical, e.g. heat, pressure, time
- Chemical, e.g. corrosions, contamination
Cleaning, disinfection and sterilization
- Lack / inadequate specification for, validated sterilization
procedures, if applicable cleaning / disinfection
- Inadequate conduct of cleaning, disinfection and sterilization
Disposal and scrapping
- No or inadequate information provided
Formulation
- (Bio)degradation
- Inadequate warning of hazards associated with incorrect
formulations
Potential for use errors triggered by design flaws, such as
- Missing instructions for use
- Ambiguous or unclear device state
- Ambiguous or unclear presentation of settings, measurements or
other information
Failure modes
- Unexpected loss of mechanical integrity
- Deterioration in function, as a result of ageing
- Loss of sterility

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Attachment III
Clinical evaluation of urogynaecological mesh implants for the treatment
of pelvic organ prolapse
Note: these lists are not exhaustive (x = addressed)
1. Indications
- Indicated for tissue reinforcement and stabilization of fascial
structures of the pelvic floor in vaginal wall prolapse, where
surgical treatment is intended, either as mechanical support
or bridging material for the fascial defects
- Indicated for use as a bridging material for
sacrocolposuspension / sacrocolpopexy (i.e. abdominal
placement via laparotomy, laparoscopy, or robotic approach)
where surgical treatment for vaginal vault prolapse is
warranted
- Intended for the surgical treatment of the anterior and
posterior prolapse by means of tissue reinforcement and
stabilization of the soft tissues of the female pelvic floor
- Intended for the surgical treatment of the posterior and apical
prolapse by means of tissue reinforcement and stabilization of
the soft tissues of the female pelvic floor
- Intended to provide surgical support, act as a bridging
material and/or provide reinforcement for the body's natural
structures
- Indicated for use as a bridging material for
sacrocolposuspension / sacrocolpopexy (laparotomy or
laparoscopic approach) where surgical treatment for vaginal
vault prolapse is warranted
- Indicated for use as a bridging material for apical vaginal and
uterine prolapse where surgical treatment (laparotomy or
laparoscopic approach) is warranted
2. Contraindications
- Pregnant women, women that are considering/planning future
pregnancy
- Potential of future / for further growth (e.g. infants, children,
adolescents)
- Patients undergoing anticoagulant therapy
- Patients with known sensitivity or allergy to polypropylene
products
- Presence of known or suspected cancer of the vagina, cervix,
or uterus
- (Active / pre-existing / latent) Systemic or local infection,
especially genital or related to the urinary tract
- Blood coagulation disorder
- Renal insufficiency and upper urinary tract obstruction
- Autoimmune connective tissue disease
- Any pathology that would limit blood supply and compromise
healing (e.g. decreased blood supply to organs due to
treatments such as radiation therapy, chemotherapy)
- Any pathology, including known or suspected uterine
pathology, which would compromise implant placement
- Pathology of soft tissue into which the mesh is to be placed
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RIVM letter report 2020-0154

-

Patients with pre-existing conditions that pose an
unacceptable surgical risk
Planned intraoperative or accidental opening of the
gastrointestinal tract
Mesh should be used with precaution in diabetic women

3. Safety
- Abscess
- Adhesion formation
- Allergy, hypersensitivity or other immune reaction
- Bladder damage
- Bleeding, including haematoma, haemorrhage
- Bowel damage
- Contracture
- Discomfort
- Fistula formation
- Granulation tissue formation
- Infection / potentiation of existing infection
- Inflammation
- Mesh exposure, erosion or extrusion
- Mesh migration
- Necrosis
- Nerve damage
- Pain
- Pain during intercourse (dyspareunia)
- Painful urination (dysuria)
- Recurrent prolapse
- Reoperation / resurgery
- Scarring / vaginal scarring
- Seroma
- Ureteral obstruction
- Urethra damage
- Urinary incontinence (stress urinary incontinence, urge
incontinence)
- Urinary retention / obstruction
- Vaginal wall damage
- Vessel damage
- Voiding dysfunction
- Wound dehiscence
4. Performance (anatomical success, efficacy outcome)
- Anatomical success, i.e. pelvic organ prolapse quantification
(POP-Q)
- Subjective success, e.g. quality of life (QoL)
- Sexual function score, e.g. pelvic organ/urinary incontinence
sexual questionnaire 12 (PISQ-12)

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Annex 6: Conclusions of the assessment of technical
documentation

BSC Mesh (A.M.I.) - transvaginal mesh
File item

Year 1 Conclusion

Device
description

2018

No shortcomings. The device is sufficiently described.

IFU

2018

Minor shortcomings. Specific (local) guidelines on the use of transvaginal
meshes are not mentioned, the physician is encouraged to discuss the matter
with the patient. The above mentioned guidelines should be taken into
consideration during this discussion. Given the current insights into the risk /
benefit of transvaginal meshes, it is recommended by the assessors that the
manufacturer also considers modifying the indications for use based on these
guidelines.

Risk analysis

2018

Major shortcomings. The risk management plan is not specific enough. The
link to PMS should be improved. For warnings, no risk reduction could be
estimated. The risk analysis does not adequately substantiate why no other
risk control measures were possible, e.g. in the design.

Chemical
composition

2018

Major shortcomings were observed. Limited information has been supplied,
lacking insight into chemical specification of both the mesh and the
accessories. More in-depth information is considered necessary.

Biocompatibility

2018

Major shortcomings. Only test reports for biocompatibility have been
provided, where it is not always clear if the samples tested were related to
the BSC Mesh. No rationale for the tests selected, no discussion of available
information. A literature review on existing data should be performed in order
to take account of the existing knowledge and the generally acknowledged
state of the art, regarding the evaluation of biocompatibility of particular
products.

Clinical
evaluation

2018

Major shortcomings The CER, dated December 2014, is of poor quality,
providing mainly high-level information on the use of mesh products in POP
procedures and containing nearly no clinical data or analysis of such data. No
clinical investigations with the BSC mesh product were performed, and
substantiation of equivalence with other mesh products is lacking. However, it
is stated that safety and performance are substantiated.

2020

Major shortcomings. Clinical evidence is mainly based on clinical data of
competitor meshes. Discussion on equivalence or comparison with other
meshes to substantiate extrapolation of results to the BSC Mesh, or the other
A.M.I. meshes, is not included or referred to in the main text. In the table of
contents an Annex on equivalence was mentioned, which was not submitted.
Clinical data of the BSC Mesh is limited, only three references are included
with few patients and short-term follow-up.

2018

No assessment. The summary and analysis of PMS data were dated after the
deadline for this study.

Summary &
analysis of PMS
data
1

2018 and 2020 – year of request

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RIVM letter report 2020-0154

Calistar S (Promedon) - transvaginal mesh
File item

Year 1 Conclusion

Device
description

2018

No shortcomings. The device is sufficiently described.

IFU

2018

Minor shortcomings. Specific (local) guidelines on the use of transvaginal
meshes are not mentioned, the physician is encouraged to discuss the matter
with the patient. The above mentioned guidelines should be taken into
consideration during this discussion. Given the current insights into the
risk/benefit of transvaginal meshes, it is recommended by the assessors that
the manufacturer also considers modifying the indications for use based on
these guidelines.

Risk analysis

2018

Major shortcomings. Risks analysed, risk reduction, acceptability of risks in
relation to benefit, and conclusions are insufficiently addressed.

Chemical
composition

2018

Major shortcomings were observed. The chemical specifications and
information on preparation of the mesh need to be elaborated upon.

Biocompatibility

2018

Major shortcomings were observed. The applicability of existing data from
other products for Calistar S is not sufficiently shown.

Clinical
evaluation

2018

Major shortcomings. No clear safety and performance claims were made.
Equivalence was used to show safety and performance. However, as Calistar
S is composed of two types of mesh (low density and high density), which is
not the case for the other meshes used for the comparison, equivalence is
not adequately substantiated. There are some other differences as well.

2020

Major shortcomings. Only preliminary data from Calistar S were available.
Candidates for equivalence were selected, i.e. the Calistar A from Promedon
and the Elevate Anterior from AMS/Astora. Although equivalence of the two
other devices with Calistar S was not claimed, the data on these two devices
were used as the basis for conclusions on safety and performance of the
Calistar S. This is not in line with the MEDDEV guidance.
The indications for the Calistar S were narrowed by the manufacturer to
surgical treatment of recurrent prolapse and primary prolapse with high risk
for recurrence.
The manufacturer is sponsoring a PMCF study to address the gaps about
gaining clinical evidence from Calistar S device itself and to gather long-term
clinical follow-up. This study will use the narrowed indication.

2018

Major shortcomings. PMS is only briefly mentioned in the CER. The assessors
consider the extent of PMS too limited to allow sufficient insight into the
experiences gained with the use of the mesh.

Summary &
analysis of PMS
data
1

2018 and 2020 – year of request

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Nuvia™ SI Single Incision Prolapse Repair System (BD) - transvaginal mesh
File item

Year 1 Conclusion

Device
description

2018

Minor shortcomings. Information expected in the general description was
scattered over multiple file items. The information needs to be included in a
separate section, especially for a complex system as the Nuvia SI.
Description of the functional elements "needle tip" or "ferrule" should be
clarified and description plus pictorial representation of the knitting pattern
should be included.

IFU

2018

Minor shortcomings. Specific (local) guidelines on the use of transvaginal
meshes are not mentioned, nor the recommendation to use transvaginal
meshes only when other surgical options are not feasible. Given the current
insights into the risk/benefit of transvaginal meshes, it is recommended by
the assessors that the manufacturer also considers modifying the indications
for use based on these guidelines.

Risk analysis

2018

Major shortcomings. It is not clear how risk reduction in line with essential
requirement 2 was achieved in practice. No risk management plan was
submitted. Due to the uncertainty on the risk control and the substantiation
of the benefit in the CER, it is uncertain if the conclusions on the benefit-risk
acceptability are valid.

Chemical
composition

2018

Major shortcomings. The specific information on the chemical specification
of the various polypropylene materials, e.g. molecular weight, is lacking.
The preparation protocol and the chemical specification of the mesh are
lacking.

Biocompatibility

2018

Major shortcomings. The biological evaluation is based on tests performed
on other Bard products with insufficient substantiation that this is a valid
approach. Especially the relevance of an implantation test on a product with
a different shape or mesh knit pattern should be discussed. Tests performed
on the other Bard products are listed and it was stated that they had been
passed, but protocols and results were not provided. No other endpoints
specific for the product were considered besides standard endpoints. The
duration of the implantation test was very short for a permanent implant. A
literature review on existing data should be performed in order to take
account of the existing knowledge and the generally acknowledged state of
the art, regarding the evaluation of biocompatibility of particular products.

Clinical
evaluation

2018

Major shortcomings. This update of the CER is discussing only data from the
period covered by the update. Summarised description of the data as
discussed in previous versions of the CER and conclusions on the complete
data set are lacking. The use of equivalence is not adequately substantiated.
Specific safety and performance claims are lacking, hampering the
assessment of the safety and performance analysis. Safety and performance
analysis, and discussion on clinical benefit need to be improved. Data for
the different devices covered by the CER should be stratified per device
consistently.

Summary &
analysis of PMS
data

2018

Minor shortcoming. PMCF is planned. The plan contains limited PMCF
activities.

1

2018 – year of request

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RIVM letter report 2020-0154

Restorelle® DirectFix™ Anterior, Restorelle® DirectFix™ Posterior (Coloplast)- transvaginal mesh
File item

Year 1 Conclusion

Device
description

2018

Minor shortcoming. CE certificate submitted is not covering the Restorelle
DirectFix Anterior and Restorelle DirectFix Posterior mesh. Moreover, the
certificate was dated August 2019, while the certificate at the time of the
original file submission was requested.

IFU

2018

Minor shortcomings. The recommendation to use a transvaginal mesh only
when there is no viable alternative should be addressed more explicitly,
preferably by including this in the indications for use. Furthermore, more
specific information on the indications for use of the anterior, respectively the
posterior variant, or both concurrently, should be included. A description of
the shape of each variant could also be useful.

Risk analysis

2018

Major shortcomings. A specific risk management plan dated before the
deadline for this study is missing. Risk estimation before mitigation is
missing. Risk reduction as far as possible and the acceptability of the benefitrisk ratio are insufficiently substantiated.

Chemical
composition

2018

Minor shortcomings. The specific information on the chemical specification of
polypropylene, e.g. molecular weight, is lacking.

Biocompatibility

2018

Major shortcomings. The selection and specific methodology of appropriate
tests, as well as the choice to use the data obtained with tests on Restorelle
DirectFix Posterior for the Restorelle DirectFix Anterior were not adequately
substantiated. History of clinical use or human exposure data were not
included in the biological safety evaluation.

Clinical
evaluation

2018

Major shortcomings. The submitted CER provides an update covering new
information from 2017-2018. As no previous versions are available, it is not
clear on which data the benefit-risk is based. No safety and performance
claims are included. Data from PMCF studies are not provided. Safety and
performance analysis, appraisal and discussion on clinical benefit need to be
improved.

Summary &
analysis of PMS
data

2018

Major shortcomings. Decisions on acceptability of PMS results and actions
taken are not included in the documentation. The results of the monthly PMS
review process and meetings including the actions should be incorporated in
an overall PMS report.

1

2018 – year of request

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RIVM letter report 2020-0154

Alyte® Y-Mesh Graft (BD) - transabdominal mesh
File item

Year 1 Conclusion

Device
description

2018

Minor shortcomings. Information expected in the general description was
scattered over multiple file items. Limited information on construction /
knitting pattern of the mesh.

IFU

2018

Minor shortcoming. Instructions should be included on training specific for the
Alyte Y-Mesh Graft.

Risk analysis

2018

Major shortcomings. It is not clear how risk reduction in line with essential
requirement 2 was achieved in practice. No risk management plan was
submitted. Due to the uncertainty on the risk control and the substantiation
of the benefit in the CER, it is uncertain if the conclusions on the benefit-risk
acceptability are valid.

Chemical
composition

2018

Major shortcomings. The specific information on the chemical specification of
monofilament polypropylene, e.g. molecular weight, is lacking. The
preparation protocol and the chemical specification of the mesh are lacking.

Biocompatibility

2018

Major shortcomings. The biological evaluation is based on tests performed on
3D MAX Mesh with insufficient substantiation that this is a valid approach.
Especially the relevance of an implantation test on a product with a different
shape should be discussed. Tests performed on the Bard 3D MAX Mesh are
listed and it was stated that they had been passed, but protocols and results
were not provided. No other endpoints specific for the product were
considered besides standard endpoints. The duration of the implantation test
was very short for a permanent implant. A literature review on existing data
should be performed in order to take account of the existing knowledge and
the generally acknowledged state of the art, regarding the evaluation of
biocompatibility of particular products.

Clinical
evaluation

2018

Major shortcomings. This update of the CER is discussing only data from the
period covered by the update. Summarised description of the data as
discussed in previous versions of the CER and conclusions on the complete
data set are lacking. The use of equivalence is not adequately substantiated.
Based on these two findings, it is uncertain that no PMCF is needed, as
claimed by the manufacturer. Specific safety and performance claims are
lacking, hampering the assessment of the safety and performance analysis.
Safety and performance analysis, and discussion on clinical benefit need to be
improved.

Summary &
analysis of PMS
data

2018

Major shortcoming. PMCF is not needed according to the manufacturer. It is
uncertain whether this statement is correct because the complete data set
needed to substantiate this is not used in the analysis, and because it is
partly based on inadequately substantiated equivalence with a competitor
product.

1

2018 – year of request

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RIVM letter report 2020-0154

ARTISYN™ Y-Shaped Mesh (Johnson & Johnson International) - transabdominal mesh
File item

Year 1 Conclusion

Device
description

2018

No shortcomings. The medical device is sufficiently described.

IFU 2

2018
2020

Minor shortcomings. More specific instructions for the surgical procedure
should be included. According to the CER a more recent version of the IFU
exists.

Risk analysis

2018

Major shortcomings. The reduction of risks as far as possible, as required in
the MDD, is not adequately substantiated. No specific risk management plan
was submitted, although this should have been drawn up according to the
harmonised European standard and the manufacturer's risk management
procedure. Improvement is considered necessary.

2020

Major shortcomings. The reduction of risks as far as possible, as required in
the MDD, is not sufficiently substantiated. This needs improvement. No
specific risk management plan was submitted; the manufacturer indicated
this was under development with a target date of 20 March 2020. A
shortcoming in the risk estimation is also indicated as being resolved with a
target date of 20 March 2020.

Chemical
composition

2018

No shortcomings. Chemical composition is sufficiently described.

Biocompatibility

2018

Major shortcomings. Comparability of devices used in the actual testing and
the selection of appropriate tests were insufficiently substantiated. Overall
analysis should be more elaborate, discussing whether results from one
endpoint might be outweighed by results for another endpoint.

Clinical
evaluation

2018

Major shortcomings. In the current CER equivalence is claimed to ULTRAPRO
Mesh (flat mesh) cut and sewn into a Y shape. This claim of equivalence is
not considered sufficiently substantiated. No specific safety and performance
claims have been made, leading also to shortcomings in the safety and
performance analysis. Limited data of ARTISYN Y-Shaped Mesh are available.
Safety and performance are insufficiently substantiated. A more in-depth
technical assessment of the adequacy of the available clinical data set is
beyond the scope of this assessment. The manufacturer indicated that he is
working on setting up PMCF.

2020

Major shortcomings. In the current CER equivalence is claimed to ULTRAPRO
Mesh (flat mesh) cut and sewn into a Y shape. This claim of equivalence is
not considered adequately substantiated. No specific safety and performance
claims have been made, leading also to shortcomings in the safety and
performance analysis. Limited data of ARTISYN Y-Shaped Mesh are available.
Safety and performance are insufficiently substantiated. PMCF data from a
clinical database have been analysed; additional necessary PMCF activities
have been planned to verify the long-term safety and performance. Data
resulting from these activities are not yet available.

2018

Major shortcomings. Information from another product, for which the claim of
equivalence is not acceptable, is used to state that PMCF is not needed. The
number of sources is limited.

2020

Minor shortcomings. No trend report was included. PMCF activities are
described, results not yet available.

Summary &
analysis of PMS
data

1
2

2018 and 2020 – year of request
IFUs requested in 2018 and 2020 were identical

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RIVM letter report 2020-0154

GYNECARE GYNEMESH™ PS Nonabsorbable PROLENE™ Soft Mesh (Ethicon) - transabdominal mesh
File item

Year 1 Conclusion

Device
description

2018

No shortcomings. The device description was adequate.

IFU 2

2018

Minor shortcomings. More specific instructions for the surgical procedure
should be included. According to the CER, a more recent version of the IFU
exists.

2020

Minor shortcomings. More specific instructions for the surgical procedure
should be included. According to the CER and two HLMR forms, a more
recent version of the IFU / other IFU documents exists.

2018

Major shortcomings. The reduction of risks as far as possible, as required in
the MDD, is not adequately substantiated. Two hazard categories are not
addressed in the risk analyses submitted. No specific risk management plan
was submitted, although this should have been drawn up according to the
harmonised European standard and the manufacturer's risk management
procedure. Improvement is considered necessary.

2020

Major shortcomings. The reduction of risks as far as possible, as required in
the MDD, is not sufficiently substantiated. This needs improvement.

Chemical
composition

2018

No shortcomings. The chemical composition is sufficiently addressed.

Biocompatibility

2018

Major shortcomings. Biocompatibility risk assessment indicates that data
from other devices are used. Comparability of devices used in the actual
testing and the selection of appropriate tests were insufficiently
substantiated, especially Proceed is sterilized using another method and
contains other additional materials. Overall analysis should be more
elaborate.

Clinical
evaluation 3

2018
2020

Major shortcomings. In the current CER, no clear safety and performance
claims have been used to substantiate adequate safety and performance.
Improvement is needed, as clear safety and performance claims should be
included in the assessment of safety and performance. Moreover, the
analysis of the available data should be improved to allow a conclusion on
the safety and performance of GYNEMESH PS in relation to other treatments
and other devices used for the same indication. It could be debated whether
data on off-label use and lowest quality data on on-label use should be
included in the analysis. In-depth technical assessment of the adequacy of
the data set formed by the seven Level III studies plus the additional nongraded studies is beyond the scope of this assessment.

Summary &
analysis of PMS
data

2018

Minor shortcomings. The need for PMCF should be re-evaluated.

2020

Minor shortcomings. No trend report was included. PMCF is mentioned, but
not yet executed and therefore results are not available.

Risk analysis

2018 and 2020 – year of request
IFUs requested in 2018 and 2020 were identical
3
Clinical evaluation reports requested in 2018 and 2020 were identical
1
2

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RIVM letter report 2020-0154

Restorelle M L XL (Coloplast) - transabdominal mesh
File item

Year 1

Conclusion

Device
description

2018

Minor shortcomings. Additional information is needed on when to apply which
of the various designs. In their response document the manufacturer
provides more information on the use of the two designs. This information is
not provided in the general description or elsewhere in the submitted
technical documentation. This kind of information shall be made available in
an unambiguous manner.

IFU 2

2018
2020

Minor shortcomings. The IFUs of Restorelle M, L, XL and Restorelle Y are
identical with regard to the indications for use and the surgical procedure. For
two types of products with different designs, some difference would be
expected in the surgical procedure. More information is needed to allow an
understanding when to use which design.
In their response document the manufacturer does provide more information.
This kind of information shall be made available in the IFU.

Risk analysis

2018

Major shortcomings. A risk management plan dated before the deadline for
this study was missing. Risk estimation before mitigation is missing.
Contraindications are not included. Risk reduction as far as possible and the
acceptability of the benefit-risk ratio are insufficiently substantiated.

2020

Minor shortcomings. Risk management plan does not differentiate between
Restorelle M, L, XL and Restorelle Y. In the risk analysis it is, however,
indicated whether risks are applicable to Y, flat or both. A more detailed
benefit risk analysis is needed.

Chemical
composition

2018

Minor shortcomings. The specific information on the chemical specification of
polypropylene, e.g. molecular weight, is lacking.

Biocompatibility

2018

Major shortcomings. The selection and specific methodology of appropriate
tests, as well as the choice to use the data obtained with tests on Restorelle
DirectFix P for the Restorelle M, L, XL were not adequately substantiated.
History of clinical use or human exposure data were not included in the
biological safety evaluation.

Clinical
evaluation

2018
2020

Major shortcomings. No description is included on differences in indications
and surgical procedures between the two different designs of Restorelle M, L,
XL and Restorelle Y and no stratification is made in the data analysis. Safety
and performance claims were not adequate. Part of the literature data
concerned applications that were not in line with the indications for use or
concerned concomitant procedures, which hampers the assessment of the
safety and performance. Safety and performance analysis, and discussion on
clinical benefit need to be improved.

Summary &
analysis of PMS
data

2018

Major shortcomings. Decisions on acceptability of PMS results and actions
taken are not included in the documentation. The results of the monthly PMS
review process and meetings including the actions should be incorporated in
an overall PMS report.

2020

Major shortcomings. Decisions on acceptability of PMS results and actions
taken are not included in the documentation. The results of the monthly PMS
review process and meetings including the actions should be incorporated in
an overall PMS report.
The numbers of complaints and units sold differ markedly between version 3
and 5 of the CER. This should be elaborated upon.

1
2

2018 and 2020 – year of request
IFUs requested in 2018 and 2020 were identical

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RIVM letter report 2020-0154

Restorelle Y (Coloplast) - transabdominal mesh
File item

Year 1 Conclusion

Device
description

2018

Minor shortcomings. Additional information is needed on when to apply which
of the various designs and on the geometry of Restorelle Y. In their response
document the manufacturer provides more information on the use of the two
designs. This information is not provided in the general description or
elsewhere in the submitted technical documentation. This kind of information
shall be made available in an unambiguous manner.

IFU 2

2018
2020

Minor shortcomings. The IFUs of Restorelle Y and Restorelle M, L, XL are
identical with regard to the indications for use and the surgical procedure. For
two types of products with different designs, some difference would be
expected in the surgical procedure. More information is needed to allow an
understanding when to use which design.
In their response document the manufacturer does provide more information.
This kind of information shall be made available in the IFU.

Risk analysis

2018

Major shortcomings. A risk management plan dated before the deadline for
this study was missing. Risk estimation before mitigation is missing.
Contraindications are not included. Risk reduction as far as possible and the
acceptability of the benefit-risk ratio are insufficiently substantiated.

2020

Minor shortcomings. Risk management plan does not differentiate between
Restorelle Y and Restorelle M, L, XL. In the risk analysis it is, however,
indicated whether risks are applicable to Y, flat or both. A more detailed
benefit risk analysis is needed.

Chemical
composition

2018

Minor shortcomings. The specific information on the chemical specification of
polypropylene, e.g. molecular weight, is lacking.

Biocompatibility

2018

Major shortcomings. Only the standard tests to be included in the risk
assessment for long-term implants according to ISO 10993-1 were discussed.
No additional testing related to specific aspects of the mesh was considered,
e.g. tissue in-growth which has been advocated as an advantage of ultralight
weight meshes. Also, all tests were performed on Restorelle DirectFix P,
which is a flat mesh for transvaginal use with different shape compared with
the transabdominal flat and Y meshes and also some differences in thickness,
surface area and mass. The potential effect of the different geometry of
Restorelle Y versus the Restorelle DirectFix P mesh and of differences in other
properties was not discussed; they were just declared equivalent. For tests
using extracts this could be considered less relevant, however, for tests using
the actual mesh material, e.g. implantation testing, this should be
considered. As also indicated in ISO 10993-6, physical characteristics such as
shape can influence the character of tissue response. Furthermore,
insufficient justification was presented on the selection of the control sample,
implantation site (type of tissue), type of experimental animal and duration of
the implantation period (13 weeks is the shortest duration of generally
accepted periods for long-term studies).

Clinical
evaluation

2018
2020

Major shortcomings. No description is included on differences in indications
and surgical procedures between the two different designs of Restorelle Y and
Restorelle M, L, XL and no stratification is made in the data analysis. Safety
and performance claims were not adequate. Part of the literature data
concerned applications that were not in line with the indications for use or
concerned concomitant procedures, which hampers the assessment of the
safety and performance. Safety and performance analysis, and discussion on
clinical benefit need to be improved.

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RIVM letter report 2020-0154

Restorelle Y (Coloplast) - transabdominal mesh
File item

Year 1 Conclusion

Summary &
analysis of PMS
data

2018

Major shortcomings. Decisions on acceptability of PMS results and actions
taken are not included in the documentation. The results of the monthly PMS
review process and meetings including the actions should be incorporated in
an overall PMS report.

2020

Major shortcomings. Decisions on acceptability of PMS results and actions
taken are not included in the documentation. The results of the monthly PMS
review process and meetings including the actions should be incorporated in
an overall PMS report. The numbers of complaints and units sold differ
markedly between version 3 and 5 of the CER. This should be elaborated
upon.

1
2

2018 and 2020 – year of request
IFUs requested in 2018 and 2020 were identical

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RIVM
Committed to health and sustainability