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Opinion Paper
Paul C. D. Bank, Leo H. J. Jacobs*, Sjoerd A. A. van den Berg, Hanneke W. M. van Deutekom,
Dörte Hamann, Richard Molenkamp, Claudia A. L. Ruivenkamp, Jesse J. Swen,
Bastiaan B. J. Tops, Mirjam M. C. Wamelink, Els Wessels and Wytze P. Oosterhuis
The end of the laboratory developed test as we
know it? Recommendations from a national
multidisciplinary taskforce of laboratory
specialists on the interpretation of the IVDR and
its complications
https://doi.org/10.1515/cclm-2020-1384
Received September 14, 2020; accepted October 20, 2020;
published online November 23, 2020
Abstract: The in vitro diagnostic medical devices regula-
tion (IVDR) will take effect in May 2022. This regulation has
a large impact on both the manufacturers of in vitro
diagnostic medical devices (IVD) and clinical laboratories.
For clinical laboratories, the IVDR poses restrictions on the
use of laboratory developed tests (LDTs). To provide a
uniform interpretation of the IVDR for colleagues in clinical
practice, the IVDR Task Force was created by the scientific
societies of laboratory specialties in the Netherlands. A
guidance document with explanations and interpretations
of relevant passages of the IVDR was drafted to help labo-
ratories prepare for the impact of this new legislation.
Feedback from interested parties and stakeholders was
collected and used to further improve the document. Here
we would like to present our approach to our European
colleagues and inform them about the impact of the IVDR
and, importantly we would like to present potentially useful
approaches to fulfill the requirements of the IVDR for LDTs.
Keywords: diagnostic test approval; diagnostic medical
devices regulation (IVDR); implementation; laboratory
developed test; laboratory medicine; legislation; medical
device legislation; quality assessment.
Introduction
In May 2017 the in vitro diagnostic medical devices regu-
lation (IVDR) developed by the European Union (EU) was
published as a follow-up to the in vitro diagnostic medical
devices directive (IVDD) [1, 2]. The IVDR and the accom-
panying Medical Devices Regulation (MDR) are a response
of the EU to scandals where implanted medical devices
caused serious adverse events [3]. These scandals
included harmful hip prostheses (2010), breast implants
(2012) and transvaginal pelvic floor meshes (2013) [4–6].
The aim of the EU is to guarantee patient safety as well as
*Corresponding author: Leo H. J. Jacobs, Chair Dutch Task Force IVDR,
Department Laboratory of Clinical Chemistry, Meander Medical Center
3813 TZ, Amersfoort, The Netherlands, Phone: +31 (0)33 850 5050,
E-mail: lhj.jacobs@meandermc.nl
Paul C. D. Bank, Department of Pharmacy, Amsterdam University
Medical Center, Amsterdam, The Netherlands
Sjoerd A. A. van den Berg, Department of Clinical Chemistry, Erasmus
Medical Centre, Rotterdam, The Netherlands
Hanneke W. M. van Deutekom, Department of Genetics, Section
Genomic Diagnostics, University Medical Centre Utrecht, Utrecht,
The Netherlands
Dörte Hamann, Department of Laboratory of Translational
Immunology, University Medical Center Utrecht, Utrecht,
The Netherlands
Richard Molenkamp, Department of Viroscience, Erasmus Medical
Centre, Rotterdam, The Netherlands
Claudia A. L. Ruivenkamp, Secretary Dutch Task Force IVDR,
Department of Clinical Genetics, Leiden University Medical Center,
Leiden, The Netherlands
Jesse J. Swen, Department of Clinical Pharmacy & Toxicology, Leiden
University Medical Center, Leiden, The Netherlands
Bastiaan B. J. Tops, Department of Pathology, Princess Máxima Center
for Pediatric Oncology, Utrecht, The Netherlands
Mirjam M. C. Wamelink, Department of Clinical Chemistry, Metabolic
Unit, Amsterdam University Medical Center, Vrije Universiteit
Amsterdam, Amsterdam, The Netherlands
Els Wessels, Department of Medical Microbiology, Leiden University
Medical Center, Leiden, The Netherlands
Wytze P. Oosterhuis, Department of Clinical Chemistry, Zuyderland
Medical Centre, Heerlen, The Netherlands
Clin Chem Lab Med 2020; aop
enforce transparency in the manufacturing process of
both implantable medical devices and in vitro diagnostic
medical devices (IVDs) by review by a notified body
appointed by a competent authority as well as ensure the
quality by manufacturers [2]. However, this regulation
will likely also have a large impact on (commercial) test
availability as a result of the lengthy certification process
executed by a notified body and on the ability of clinical
laboratories to create and implement laboratory devel-
oped tests (LDTs). To provide a uniform interpretation of
the IVDR for colleagues in clinical practice, the IVDR Task
Force was created by the scientific societies of laboratory
specialties in the Netherlands (Box 1). This article pro-
vides the interpretation of LDTs in the IVDR, its impact on
routine testing in clinical laboratories, the future of the
LDT under the IVDR and possible pros and cons of this
legislation.
Box 1: Dutch Task Force IVDR.
This task force consists of mandated members of the
Netherlands Society for Clinical Chemistry and
Laboratory Medicine (NVKC), Netherlands Society for
Pathology (NVVP), Dutch Society for Medical
Microbiology (NVMM), the Dutch Association of Clinical
Geneticists (VKGN)/the Association of Clinical Genetic
Diagnostic Laboratories (VKGL), Dutch Society for
Immunology (NVVI)/College of Medical Immunologists
(CMI) and the Dutch Association of Hospital Pharmacists
(NVZA).
The goal and timeline of IVDR
With the IVDR, named EU IVDR 2017/746, the IVDD 98/79/
EC has been replaced by a regulation in parallel with the
replacement of the Medical Device Directive into the formal
Regulation named EU MDR 2017/745 [1–3, 7]. Patient safety
concerns are the driving force in choosing to impose the
rules in a regulation. As such, adherence to the timeline by
the European Parliament (EP) has been strict and ambi-
tious and until recently it was unlikely that the imple-
mentation of the IVDR in May 2022 will be delayed [8, 9]. Of
course, the outbreak of Coronavirus disease (COVID-19)
and the challenges surrounding the (in-house) develop-
ment, use and availability of diagnostic tests could result in
a more cautious implementation timeline. For example, the
MDR was postponed with a year due to COVID-19 and the
fear for a shortage of medical devices [10].
Compared to the previous IVDD traceability throughout
the supply chain and greater transparency will be deman-
ded under the IVDR. Authorities and notified bodies will be
challenged, not only because the amount oftests that need a
certification will drastically increase, but also more expert
knowledge is required. Additionally, the IVDR requires
manufacturers to establish post market surveillance mech-
anisms. They will need to actively collect and evaluate
performance from the use of a device. Finally, under this
new regulation IVDs will be classified based on their related
risk on personal or public health. Although this classifica-
tion is based on the Global Harmonization Task Force
(GHTF) risk classification there currently still some ambi-
guity on the exact classification of certain assays.
Impact for manufacturers
The most significant change for manufacturers as a result
of the IVDR is the level of third-party oversight required by
a notified body appointed by the competent authority,
whereas under the IVDD the manufacturers of IVDs that
were controlled by a self-declared procedure. Approxi-
mately 20% of tests required a notified body under the
IVDD. This is a big contrast compared to the situation un-
der the IVDR, where almost 80% of IVDs on the European
market that are currently controlled by a self-declaration
procedure are estimated to require conformity assessment
by notified bodies [9, 11, 12]. Clinical evidence is likely to be
the most difficult challenge for the manufacturers. For
some manufactures this challenge might be too big and/or
too costly, and may opt not to certify their product resulting
in a diminished availability of IVD certified assays.
Impact for clinical laboratories
The new IVDR will also have a large impact on clinical
laboratories. Clinical laboratories are mandated by the
IVDR to use IVDs marketed by manufacturers which have
received CE-IVD certification. However, the IVDR recog-
nizes the possibility of manufacturing LDTs (see Box 2) to
address the specific needs of patient groups that otherwise
cannot be met (art.29). These IVDs –when used exclusively
in the hospital laboratory where they are made–are exempt
from many of the requirements of the IVDR (see Box 3). This
also applies for IVDs that are modified and for off label use
of the IVDs. Clinical laboratories in large peripheral hos-
pitals such as laboratories for clinical chemistry, hematol-
ogy, immunology, handle large volumes of samples, often
in automated tracks which predominantly use IVDs from
2Bank et al.: Recommendations from the Dutch Task Force IVDR
commercial manufacturers. However, other clinical labora-
tories providing specialized analyses more often use LDTs,
this includes specialties such as clinical genetics, pathology,
microbiology, therapeutic drug monitoring, toxicology and
clinical laboratories in academia. For low volume, special-
ized analyses in these latter groups of laboratories commer-
cial assays were often not available in the past, forcing them
to develop and use LDTs. Once an LDT is developed, vali-
dated according to EN-ISO 15189 standards and implemented
in clinical practice there is little incentive to switch to a
commercial alternative when available. However, once the
IVDR takes effect, switching to equivalent commercial al-
ternatives will become mandatory, requiring a process of (re)
validation of new assays for analyses that are currently
already executed in routine practice. Additionally, as a result
of the mandatory switch from an LDT to a commercial assay
some laboratories probably will have to purchase new
equipment resulting in higher costs for laboratory specialties.
Finally,Vermeerschetal.haveshowninacase-studyin
preparation for the IVDR that the process of inventorying
which assays are classified conform the CE-IVD and justifi-
cation of LDT’s in a laboratory in a large academic hospital
willrequirealotoftimeandeffort[13].
Box 2: What is an LDT?
Based on the IVDR art. 5, in the following cases the test
can be considered an LDT:
1) An in-house developed and produced test;
2) Tests that are labeled “research use only”and that are used for
diagnostics;
3) A CE-IVD certified test in which adjustments are made that
change the intended use;
4) A CE-IVD certified test in which adjustments to the protocol are
made without changing the intended use
Box 3: Articles in the IVDR regarding laboratory
developed tests & interpretation by the task
force*
Art. 5a. the resources are not transferred to another
legal person.
It is permissible, and necessary, for the quality and
accessibility of healthcare, that test results and
corresponding analytical or clinical interpretations
(if applicable) can be shared with referring healthcare
providers. The LDTs cannot be transferred to other legal
entities, the results produced with the LTDs can.
Sharing relevant protocols, work instructions, clinical
validations and describing LDTs performed within the
(continued)
Art. 5a. the resources are not transferred to another
legal person.
It is permissible, and necessary, for the quality and
accessibility of healthcare, that test results and
corresponding analytical or clinical interpretations
(if applicable) can be shared with referring healthcare
providers. The LDTs cannot be transferred to other legal
entities, the results produced with the LTDs can.
Sharing relevant protocols, work instructions, clinical
validations and describing LDTs performed within the
professional discipline in scientific publications is
allowed.
Art. 5b. the devices are manufactured and used in
compliance with an appropriate quality
management system.
In general, the quality management system under EN ISO
15189 can be seen as an appropriate quality management
system. Nonetheless, there is a considerable heterogeneity
in manufacturing processes and we cannot exclude the
possibility of additional requirements.
Art. 5c. the healthcare institution’s laboratory
complies with standard EN ISO-15189 or, where
applicable, with applicable national provisions,
including national provisions regarding
accreditation.
Being EN ISO 15189 accredited is the most effective way to
comply with this part of the law.
5d) the healthcare institution justifies in its
documentation that the specific needs of the patient
target group cannot be met, or cannot be met at an
appropriate level of performance, by an equivalent
tool available on the market.
The health institution must, for each LDT, justify its use. It
will be necessary to demonstrate and prove that the
specific needs of the patient group cannot be met, or not at
the right performance level, with a comparable IVD device
available on the market.
Arguments that can be taken into consideration to
demonstrate the necessity and superiority of the LDT:
Technical:
–Working principle
–Critical performance requirements
–Required amount of patient material
–Type of (body) material
–Reliability of the device/test
–Turn-around times
Bank et al.: Recommendations from the Dutch Task Force IVDR 3
–Clinical compatibility and interdependent comparison of re-
sults from the same material (taken at the same time). For
example: a multiplex assay can measure multiple parameters
simultaneously in one analysis, instead of several indepen-
dent tests.
Clinical:
–Is the device used for the same clinical condition or purpose?,
including:
–the same severity and stage of the disease
–in the same place in the body
–in a comparable population, including age, anatomy and
physiology
–comparable relevant critical performance in view of the
expected clinical effect for a specific intended purpose.-
Substantiation of the above can be based on (but is not
limited to):
–National guidelines from professional associations/ interna-
tional guidelines
–Scientific literature
–Expert opinion e.g. clinical utility cards Clarification: The IVDR
does not specify when the lack of an alternative for the device
must be justified. An appropriate moment is at the start of the
LDT’s development process, when the functional requirements
and the patient target group are known. Subsequently, a -
re-assessment will have to be performed at the end of the
life cycle of the LDT or when the LDT is changed. For medical
devices (LDTs) that are produced without a clear (end of) life
cycle or that are not subject to change, market orientation
needs to be performed at a reasonable frequency to check
for the availability of equivalent, commercially available
alternatives. The information published in EUDAMED is
leading for this.
5e. the healthcare institution shall provide its
competent authority with information on the use of
such devices, including justification for their
manufacture, modification and use.
All previously mentioned items must be documented and
must be able to be handed over to the competent
authorities upon request.
5f) the healthcare institution draws up a statement
that makes it public and contains the following
elements: i) The name and address of the
manufacturing healthcare institution, ii) data
identifying the devices, iii) a statement that the
devices comply with the general safety and
performance requirements set out in Annex I to this
regulation and, where applicable, information on
requirements that are not fully met, with a reasoned
justification for that.
(See Supplementary Document I for example
explanation).
5g) for devices classified in class D according to the
rules of Annex VIII, the healthcare institution shall
prepare documentation explaining the production
facility and the production process, design and
performance data of the devices, including the
intended purpose, which is sufficient detailed to
enable the competent authority to assess whether
the general safety and performance requirements
set out in Annex I to this Regulation are being met.
Member States may also apply this provision to
devices classified as class A, B or C in accordance
with the rules set out in Annex VIII.
For the time being, the Task Force assumes that this
requirement only applies to class D.
5h) the healthcare institution takes all measures
necessary to ensure that all devices are
manufactured in accordance with the
documentation referred to in point g), and i) The
healthcare institution evaluates the experience
gained with the clinical use of the devices and takes
all required corrective actions.
Here too, EN-ISO 15189 accreditation provides assurance,
in particular on the basis of Section 4.14 Evaluation and
Audits.
* Quoted elements from the IVDR are bolded and
interpretations from The IVDR taskforce are displayed in
italics.
The call for a task force
As the scientific societies of laboratory specialties in The
Netherlands envisioned that the European IVDR legislation
will have large consequences for the use, availability and
costs of in vitro diagnostic tests, a multidisciplinary task
force was convened to meet the possible challenges of the
IVDR (see Box 1).
The main goal of this Task Force was to aid the imple-
mentation of the IVDR by providing a practical interpreta-
tion for their members of this legislation and to provide
clarity on the impact on the field in daily practice. With this
interpretation of the regulation the Task Force aims to
harmonize the interpretation of the articles in this regulation
by professionals in the field. Additionally, the Task Force
aimed at maximizing the possibility for laboratory special-
ists to develop diagnostic procedures to address unmet
needs within the limits of best practices, current standards
and legislation. During multiple meetings the text of the
IVDR was discussed until a consensus on the interpretation
4Bank et al.: Recommendations from the Dutch Task Force IVDR
was reached and a draft document was developed con-
taining the interpretation by the Task Force of article 5.5 of
the IVDR which encompasses LTDs and other relevant ar-
ticles for clinical laboratories. In the next step multiple
stakeholders and interested parties, including the Dutch
Ministry of Health Welfare and Sport (VWS) and Health and
Youth Care Inspectorate (IGJ) (who are likely to fulfill the
role as competent authority in the Netherlands), were con-
sulted to check whether they agreed on the interpretation
and to provide feedback on the document. The consulted
stakeholders greatly valued the proactive initiative taken by
the taskforce and welcome the input from the medical lab-
oratory experts. Of course, our recommendations are only
one of several considerations that have to be taken into
account and at this stage our guidance document should be
considered as a non-binding practical advice for laboratory
professionals.
The final document includes a list of the paragraphs of
the IVDR which are relevant for clinical laboratories and
provides an explanation of the text and directive for the
members of the associations on how to implement the
relevant paragraphs of the IVDR. Additionally, the Task
Force provided interpretation in linking Appendix I of the
IVDR to sections of the EN-ISO 15189:2012, which helps
clinical laboratories to create a gap analysis. Finally, the
document provides support to prepare for the introduction
of the IVDR by an active assignment to its members to start
to investigate which LDTs are used in their clinical labo-
ratories and if they comply with the IVDR validation re-
quirements (see Supplementary Document 1).
Although the document created by the Task Force
currently holds no legal value, as of today, the content of
the document and associated files is supported by all
scientific societies of diagnostic specialties in the
Netherlands. As mentioned above, the IVDR prohibits the
use of LDTs when equivalent commercial alternatives are
available. However, abiding article 5 of the IVDR (see
Box 3) LDTs are exempt from the IVDR when used on a
non-industrial scale and no equal or superior performing
commercial CE-IVD diagnostic test is available. The major
caveat is currently that precise definitions of the limits,
and criteria when a use-case is defined as industrial are
still open for interpretation. In a general sense, it is the
Task Force’s view that any test developed in-house and
used for patient care, is not applied on an industrial scale.
This is especially the case in clinical laboratories in an
academic setting, where many specific assays are not
commercially available and laboratories should have the
possibility to help clinicians in their process of diagnosis
and patient monitoring and by fulfilling the EN-ISO 15189
requirements.
Furthermore, minor modifications should be possible
without the test being considered an LDT. This includes
dilutions, reaction times, etc. Such an adaptation shifts the
responsibility from supplier to laboratory and the labora-
tory is required to substantiate the adjustment by per-
forming a validation (in particular according to EN-ISO
15189) of the aspects that could reasonably be assumed to
be influenced by the adaptation. Finally, there are situa-
tions where adjustments are made only by exemption in
individual cases. These are often ad hoc decisions that
require adjustments to answer an urgent, specific clinical
question. In those cases it could be necessary to indicate
that the reported results have been generated using an
unvalidated analysis not covered by EN-ISO 15189.
Discussion
As a result of multiple scandals, the EP has provided
Europe with a new regulation which aims to protect
patients from harmful medical devices including IVDs.
As medical laboratory specialists we aim to provide high
quality and safe in vitro diagnostic testing procedures to
clinicians in our hospitals and associated primary care
centers to diagnose and monitor patients. To ensure that
our laboratory tests are of high quality and results are
reproducible we hold ourselves to strict quality control
procedures and require this from our colleagues as well.
With the arrival of the IVDR the implementation of a quality
management system (EN-ISO 15189 or equivalent) is
mandatory for clinical laboratories, a decision that we fully
support [9, 12].
The IVDR forces the manufacturers to provide trans-
parency in the manufacturing process by certification
through a notified body appointed by the competent au-
thority, for the majority of products used by clinical lab-
oratories. The removal of the option of self-certification
and implementation of obligatory certification by trusted
third parties for most products will likely result in the
removal of IVD products from the market which do not
uphold their quality claims. Moreover, the requirement
for the manufacturers to gather clinical data as part of the
certification will likely result in a further increase of the
quality of the IVDs and will result in an easier imple-
mentation procedure. The manufacturers will have to
provide the majority of the data necessary for validation
as part of the certification process by the notified body.
Post marketing surveillance of the assays will result in
continuous monitoring of the IVD in clinical practice as a
requirement in the certification process and prevent
Bank et al.: Recommendations from the Dutch Task Force IVDR 5
possible tampering with the IVD by the manufacturer
once certification has been granted by the notified body.
With the implementation of the IVDR an international
database (EUDAMED) will become available which will
provide an overview of the commercial CE-IVDs for various
platforms possibly including the specifications of the as-
says so laboratory specialist can make a more informed
choice on which assay to use on their platform. Instead of a
laborious validation from scratch, a verification of the as-
say’s claims will be sufficient for implementation in clin-
ical practice [14].
Although the IVDR will likely result in a step forward in
the quality assurance and control in medical laboratories
(in the future possibly by uptake of the IVDR in the ISO
guideline), some concerns must be addressed too. As a
result of a lack of notified bodies and the large number of
medical devices currently marketed in clinical practice
there is a worry that products critical for the processes in
daily practice will not receive certification in time. This
could result in certain IVDs, required for daily clinical care,
being withdrawn from the market. Additionally, the pro-
cess of certification by a notified body is a laborious,
expensive and time-consuming process. Smaller enter-
prises that currently provide a high quality assay for a
niche in laboratory medicine might not have the resources
to follow through with the certification process. Similarly,
American companies that currently also sell their products
on the European market might opt out of providing their
products to clinical laboratories in European countries.
The REACH (Registration, Evaluation, Authorization and
Restriction of Chemicals), an area of EU regulation, has had
a similar result. Both scenarios might have implications for
the diagnostic process and monitoring of specific groups of
patients.
Another major concern regarding the IVDR is its
impact on innovation. With the strict regulation regarding
the use of LDTs, laboratories in academia and large pe-
ripheral hospitals are less likely to develop new assays for
use in clinical practice to respond to (rapid) changes in
healthcare (see Box 4). The investment of a time-
consuming and expensive process of developing a new
assay can be undone after the introduction of a newly
marketed commercial CE-IVD alternative. This could result
in an increase of the costs of medical care. Due to the funds
and manpower required for the certification process, clin-
ical laboratories are unlikely to have their own LDTs
certified by a notified body. This might also reduce the
pressure on manufacturers to improve upon their regis-
tered products. For example, in the past it has become clear
that LDTs developed on a mass-spectrometer platform
used for the quantification of tacrolimus were significantly
better than a commercial product based on an immuno-
assay available at the time [15]. This has resulted in the
development of commercial mass-spectrometer assays for
immunosuppressants which are currently available for
multiple mass-spectrometers platforms. A downside
experienced by Le Goff et al. is the ability to troubleshoot
with commercial ready-to-use mass-spectrometry assays
as the kit has become a black box [14].
Box 4: The use of LDTs in a global emerging health
emergency.
In December 2019 an outbreak of the novel SARS-CoV-2
coronavirus in Wuhan, China was recognized. The virus
spread rapidly and caused the current global COVID-19
pandemic [16]. Reliable laboratory diagnosis of the
SARS-CoV-2 virus is an important requisite for both
public and clinical healthcare. Due to international
collaboration between WHO reference laboratories,
diagnostic assays for the detection of the novel
SARS-CoV-2 were designed and validated despite the
absence of samples or virus isolates [17]. These LDTs
provided hospitals and public health institutions with
tools for clinical care and public health response in the
absence of commercial assays.Although the first
commercial CE-IVD marked assays for this novel virus
became available in March-April, unprecedented market
failure resulted in scarcity of these CE-IVD assays as well
as general reagents and consumables which forced
laboratories to modify procedures or switch assays
multiple times.Fortunately, this situation benefited from
experience that laboratories maintained through
development of LDT’s in general. However, with the
introduction of (article 5.5) of the IVDR, this experience
will decrease and this will likely impede the future
responses to rapidly evolving health emergencies and
may severely impair clinical care and public health
response.
In conclusion, the IVDR will likely improve the overall
quality of IVDs, result in a higher uptake of commercial
CE-IVD products and diminish the use of LDTs by clinical
laboratories. However, there are also concerns regarding
the availability of certified products, the impact on inno-
vation of novel diagnostics and possible barriers to
respond to changing (public) health challenges. Addi-
tionally, for the diagnosis and monitoring of disease in
specific patient groups the use of LDTs will still be neces-
sary. With the provided document the Task Force aims to
provide an instrument for our colleagues to act upon the
IVDR in clinical practice.
6Bank et al.: Recommendations from the Dutch Task Force IVDR
Research funding: None declared.
Author contributions: All authors have accepted
responsibility for the entire content of this manuscript
and approved its submission.
Competing interests: Authors state no conflict of interest.
References
1. Directive 98/79/EC of the European Parliament and of the Council
of 27 October 1998 on in vitro diagnostic medical devices. Off J
European Union L 1998;331:1–37.
2. Regulation (EU) 2017/746 of the European Parliament and of the
council of 5 April 2017 on in vitro diagnostic medical devices and
repealing directive 98/79/EC and commission decision 2010/227/
EU. Off J Eur Union 2017;117:176–332.
3. Regulation (EU) 2017/745 of the European Parliament and of the
Council of 5 April 2017 on medical devices, amending directive
2001/83/EC, regulation (EC) No 178/2002 and regulation (EC) No
1223/2009 and repealing council directives 90/385/EEC and 93/
42/EEC. Off J Eur Union 2017 L 117: 1-175, eur-lex. europa. eu/eli/
reg/2017/745/ 2017 [Accessed 10 Apr 2020].
4. Steele GD, Fehring TK, Odum SM, Dennos AC, Nadaud MC. Early
failure of articular surface replacement XL total hip arthroplasty. J
Arthroplasty 2011;26:14–8.
5. Berry RB. Rupture of PIP breast implants. J Plast Reconstr Aesthetic
Surg 2007;60:967–8.
6. Wise J. Permanent mesh has “limited utility”for vaginal prolapse
repair, review finds. BMJ 2016;352:i822. Clinical research ed.
7. COUNCIL DIRECTIVE 93/42/EEC of 14 June 1993 concerning
medical devices. 1993.
8. Spencer S. The essential IVDR and the challenges it presents
rockville: regulatory affairs professionals society; 2019. Available
from: https://www.raps.org/news-and-articles/news-articles/
2019/9/the-essential-ivdr-and-the-challenges-it-presents.
9. Cobbaert C, Smit N, Gillery P. Metrological traceability and
harmonization of medical tests: a quantum leap forward is needed
to keep pace with globalization and stringent IVD-regulations in
the 21st century! Clin Chem Lab Med 2018;56:1598–602.
10. Haahr T. Parliament decides to postpone new requirements for
medical devices; 2020. Available from: https://www.europarl.
europa.eu/news/en/press-room/20200415IPR77113/parliament-
decides-to-postpone-new-requirements-for-medical-devices.
11. van Drongelen A, de Bruijn A, Pennings J, van der Maaden T. The
impact of the new European IVD-classification rules on the
notified body involvement; a study on the IVDs registered in the
Netherlands. Bilthoven: National Institute for Public Health and
the Environment; 2018.
12. Heinzelmann E. The new, stringent MDR and IVDR
regulations: viewing this change as an opportunity. Chimia
2018;72:430–1.
13. Vermeersch P, Van Aelst T, Dequeker EMC. The new IVD
Regulation 2017/746: a case study at a large university
hospital laboratory in Belgium demonstrates the need for
clarification on the degrees of freedom laboratories have to
use lab-developed tests to improve patient care. Clin Chem
Lab Med 2020.
14. Le Goff C, Farre-Segura J, Stojkovic V, Dufour P, Peeters S,
Courtois J, et al. The pathway through LC-MS method
development: In-house or ready-to-use kit-based methods? Clin
Chem Lab Med 2020;58:1002–9.
15. Ko DH, Cho EJ, Lee W, Chun S, Min WK. Accuracy evaluation of
Roche and Siemens tacrolimus and cyclosporine assays in
comparison with liquid chromatography-tandem mass
spectrometry. Scand J Clin Lab Invest 2018;78:431–8.
16. Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. A
pneumonia outbreak associated with a new coronavirus of
probable bat origin. Nature 2020;579:270–3.
17. Corman VM, Landt O, Kaiser M, Molenkamp R, Meijer A, Chu DK,
et al. Detection of 2019 novel coronavirus (2019-nCoV) by real-
time RT-PCR. Euro Surveill 2020;25. https://doi.org/10.2807/
1560-7917.es.2020.25.3.2000045.
Supplementary Material: The online version of this article offers
supplementary material (https://doi.org/10.1515/cclm-2020-1384).
Bank et al.: Recommendations from the Dutch Task Force IVDR 7