Medical devices - classification - clinical trials - registration strategies - market analysis

1. Medical Devices. From idea to
implementation. Clinical research.
Strategies for marketing of new
medical devices.
Dr Natalia Haraszkiewicz-Birkemeier

2. Medical devices - Dr. N. Haraszkiewicz-Birkemeier
Medical Devices – definition,
directives, guidelines,
classification

3. Medical devices - Dr. N. Haraszkiewicz-Birkemeier
What is a Medical device according
to World Health Organization
(WHO)?‘Medical device’ means any instrument, apparatus, implement, machine, appliance, implant,
reagent for in vitro use, software, material or other similar or related article, intended by the
manufacturer to be used, alone or in combination, for human beings, for one or more of the
specific medical purpose(s) of:

diagnosis, prevention, monitoring, treatment or alleviation of disease,

diagnosis, monitoring, treatment, alleviation of or compensation for an injury,

investigation, replacement, modification, or support of the anatomy or of a
physiological process

supporting or sustaining life,

control of conception,

providing information by means of in vitro examination of specimens derived
from the human body; and
does not achieve its primary intended action by pharmacological, immunological or
metabolic means, in or on the human body, but which may be assisted in its
intended function by such means.

4. Medical devices - Dr. N. Haraszkiewicz-Birkemeier
Medical devices – articles for medical
purpose
Medical devices are defined as articles which are
intended to be used for a medical purpose. The
medical purpose is assigned to a product by the
manufacturer. The manufacturer determines
through the label, the instruction for use and the
promotional material related to a given device its
specific medical purpose.
Source: Directive 93/42/EEC, Guidelines MEDDev2.1/1

5. Medical devices - Dr. N. Haraszkiewicz-Birkemeier
Regulation of Medical Devices
in Europe – Directives
There are three European Medical Devices Directives:
• the Active Implantable Medical Device (AIMD) Directive - 90/385/EEC
• the Medical Device Directive (MDD) – 93/42/EEC
• the In Vitro Diagnostic Device Directive (IVD) – 98/79/EC
These three main directives have been supplemented over time by
several modifying and implementing directives, including the last
technical revision brought about by Directive 2007/47/EC.

6. Medical devices - Dr. N. Haraszkiewicz-Birkemeier
Regulation of Medical Devices
in Europe – MEDDEVs Guidance

The European Commission provides a range of guidance documents to assist
stakeholders in implementing directives related to medical devices.

The guidelines are not legally binding. However, due to the participation of the
aforementioned interested parties and the experts from competent authorities, it is
expected that the guidelines be followed, ensuring the uniform application of
relevant directive provisions.
Source: https://ec.europa.eu

7. Medical devices - Dr. N. Haraszkiewicz-Birkemeier
Classification (MDD Anex IX)
Classification according to MDD Annex IX by manufacturer, e.g.
Class 1 non-sterile, non-measuring (low risk, non-invasive devices)
Class 1 sterile, measuring (low risk, non-invasive devices)
Class 2a (Medium-risk, short-term invasive devices)
Class 2b (Higher-risk, often longer-term surgically invasive)
Class 3 (Highest-risk devices, including all active implantable devices)
- Classification is determined based on device’s duration of contact and
degree of invasiveness
- As part of the Essential Requirements, a clinical evaluation in
accordance with Annex X must be conducted for all medical devices.

8. Medical devices - Dr. N. Haraszkiewicz-Birkemeier
IVD Medical Device
An IVD Medical Device is defined as a device which, whether used
alone or in combination, is intended by the manufacturer for the
in-vitro examination of specimens derived from the human body
solely or principally to provide information for diagnostic,
monitoring or compatibility purposes. This includes reagents,
calibrators, control materials, specimen receptacles, software,
and related instruments or apparatus or other articles.
Note: International reference materials (e.g. WHO) and materials
used for external quality assessment schemes are excluded.
Source: Principles of IVD Medical Devices Classification, SG1 Proposed Document SG1(PD)/N045R12

9. Medical devices - Dr. N. Haraszkiewicz-Birkemeier
IVD Medical Device
Classification
There are four risk classes of devices. The manufacturer must apply
the classification rules to each IVD Medical Device according to
its intended use.
Source: Principles of IVD Medical Devices Classification,
SG1 Proposed Document SG1(PD)/N045R12

10. Medical devices - Dr. N. Haraszkiewicz-Birkemeier
EU Medical Devices Markets

11. Medical devices - Dr. N. Haraszkiewicz-Birkemeier

12. Medical devices - Dr. N. Haraszkiewicz-Birkemeier
EU Medical Device Markets

13. Medical devices - Dr. N. Haraszkiewicz-Birkemeier
EU Market - The Big Three and
Second-Tier Markets
- Markets such as Italy, Spain, Switzerland, Poland and the Czech Republic may not be
as wealthy as the big three, but these markets are often underserved when it comes to
medical devices.
- The Netherlands and Scandinavian countries are viewed as the “early adapters”

14. Medical devices - Dr. N. Haraszkiewicz-Birkemeier
EU market challenges

15. Medical devices - Dr. N. Haraszkiewicz-Birkemeier
Registration of Medical Devices
& Clinical Data

16. Medical devices - Dr. N. Haraszkiewicz-Birkemeier
Registration of a device

Registration of device with Competent Authorities if necessary.

All manufacturers must prepare a Declaration of Conformity stating their
device is in compliance with all applicable Directives. Upon completion of
Declaration of Conformity, CE Marking to the product may be affixed.

All EU member states require device labeling in their official languages
and they may require labeling information be made available in another
European Community language to patients and users. Label information
in Technical File should only appear in one language.

Systematic records of Post-Market Surveillance (PMS) and Vigilance PMS
findings must be kept
Source: http://ec.europa.eu/health/medical-devices/regulatory-framework/legislation/index_en.htm

17. Medical devices - Dr. N. Haraszkiewicz-Birkemeier
Technical File/Design Dossier
All Class I, IIa and IIb device manufacturers must prepare Technical Files
containing data to demonstrate MDD 93/42/EEC compliance.
• Class III device manufacturers must prepare Design Dossiers to
demonstrate compliance to MDD.
• All manufacturers must have clinical data to demonstrate compliance
to MDD.

18. Medical devices - Dr. N. Haraszkiewicz-Birkemeier
What is clinical data?
Clinical Data is an important component of the CE Marking process. It is defined and
included in Article 1.2 (k): "The safety and/or performance information that is
generated from the use of a device.
(Annex I part I, 6a, Directive 93/42/EEC)
Clinical data are sourced from:

clinical investigation(s) of the device concerned

clinical investigation(s) or other studies reported in the scientific literature, of a
similar device for which equivalence to the device in question can be demonstrated

published and/or unpublished reports on other clinical experience of either the
device in question or a similar device for which equivalence to the device in
question can be demonstrated.

19. Medical devices - Dr. N. Haraszkiewicz-Birkemeier
Clinical Evaluation Summary
Reports
Even simple Class I device requires a CER! The Clinical
Evaluation is exactly what it sounds like – an
evaluation of research done on the safety and
efficacy of the device. That research might have
been done by your company, or published by others,
and depending on the risk category of your device it
can be fairly simple or quite extensive.

20. Medical devices - Dr. N. Haraszkiewicz-Birkemeier
Clinical Evaluation Summary
Reports
European Directive 2007/47/EC, which amends the EU
Medical Devices Directive MDD 93/42/EEC (and Active
Implantable Medical Devices Directive AIMDD 90/385/EEC),
places greater emphasis on clinical data and a Clinical
Evaluation Report (CER). Recital 8, which is in the preamble
of Directive 2007/47/EC, makes the statement "clinical data,
even for Class I devices, is generally required." Also, Annex I,
Essential Requirements now states: "Demonstration of
conformity with the Essential Requirements must include a
clinical evaluation in accordance with Annex X."

21. Medical devices - Dr. N. Haraszkiewicz-Birkemeier
Auditing of Quality System and
Technical File or Design Dossier by
chosen Notified Body

Following appointment of the EC REP, quality system and Technical
File/Design Dossier must be audited by a Notified Body. Upon successful
completion of the audit, the Notified Body will issue a CE Certificate

Manufacturers of Class I Non-sterile/Non-measuring devices self-declare
MDD conformity and do not require CE Marking certificates.

22. Medical devices - Dr. N. Haraszkiewicz-Birkemeier
Examples of Medical Devices

23. Medical devices - Dr. N. Haraszkiewicz-Birkemeier
Examples of MD and IV MD

Genetic/DNA tests:
- MammaPrint, - 23andme

Glucose sensors

Companion diagnostics/combination products:
- Therapies (e.g. Mab + genetic tests)

Wearables

Apps

24. Medical devices - Dr. N. Haraszkiewicz-Birkemeier
Tumor genomic assays/tests
Genomic tests are used to help make decisions about whether
more treatments after surgery would be beneficial.
While their names sound similar, genomic testing and genetic
testing are very different.
Genetic testing is done on a sample of your blood, saliva, or
other tissue and can tell you if you have an abnormal
change (also called a mutation) in a gene that is linked to a
higher risk of breast cancer.

25. Medical devices - Dr. N. Haraszkiewicz-Birkemeier
Genetic/DNA Tests
There are several tests used to analyze the genes in a
breast cancer to help predict whether the breast
cancer will come back (recurrence). All of the tests
can be done on a sample of preserved tissue that
was removed from the breast during the original
biopsy or surgery.

26. Medical devices - Dr. N. Haraszkiewicz-Birkemeier
MammaPrint
The MammaPrint test analyzes 70 genes to see how active they are and then
calculates either a high-risk or a low-risk recurrence score.
Research suggests the MammaPrint test eventually may be widely used to
make treatment decisions based on the recurrence risk of early-stage,
hormone-receptor-positive or hormone-receptor-negative disease.

27. Medical devices - Dr. N. Haraszkiewicz-Birkemeier
Companion Diagnostic Devices with In
Vitro and Imaging Tools
A companion diagnostic device can be in vitro diagnostic device or an
imaging tool that provides information that is essential for the safe
and effective use of a corresponding therapeutic product. The use of
an IVD companion diagnostic device with a particular therapeutic
product is stipulated in the instructions for use in the labeling of both
the diagnostic device and the corresponding therapeutic product, as
well as in the labeling of any generic equivalents and biosimilar
equivalents of the therapeutic product.

28. Medical devices - Dr. N. Haraszkiewicz-Birkemeier
Herceptin and HER-2+test
Herceptin is a humanized monoclonal antibody (also called a biologic therapy). Antibodies
are part of the body's normal defense against bacteria, viruses and abnormal cells
such as cancer cells. Therapeutic monoclonal antibodies are created and produced in
a laboratory through a complex and resource-intensive process. Their name comes
from the fact that they are produced from a single cell.
Herceptin works on both the extracellular and the intracellular domains of the HER2
receptor:

Continuously suppresses HER2 activity that may lead to tumor proliferation

Leads to cell stasis and death

Herceptin provides constant inhibition of the HER2 receptor

Extended half-life enables Herceptin to maintain constant exposure

29. Medical devices - Dr. N. Haraszkiewicz-Birkemeier
HER-2 DNA Probe Kit

30. Medical devices - Dr. N. Haraszkiewicz-Birkemeier
Herceptin (trastuzumab)
PATHVYSION HER-2 DNA Probe Kit
Device manufacturer: Abbott Molecular Inc.
The PathVysion HER-2 DNA Probe Kit (PathVysion Kit) is designed to detect amplification of the HER-
2/neu gene via fluorescence in situ hybridization (FISH) in formalin-fixed, paraffin-embedded human
breast cancer tissue specimens. Results from the PathVysion Kit are intended for use as an adjunct
to existing clinical and pathologic information currently used as prognostic factors in stage II, node-
positive breast cancer patients.
The PathVysion Kit is further indicated as an aid to predict disease-free and overall survival in patients
with stage II, node positive breast cancer treated with adjuvant cyclophosphamide, doxorubicin, and
5-fluorouracil (CAF) chemotherapy. The Pathvysion Kit is indicated as an aid in the assessment of
patients for whom herceptin (trastuzumab) treatment is being considered (see herceptin package
insert).
Source: http://www.fda.gov/

31. Medical devices - Dr. N. Haraszkiewicz-Birkemeier
Pharmaceutical and diagnostic
development
Source: Biomarkers strategies for oncology drug
development , N.Haraszkieiwcz, LinkedIn blog

32. Medical devices - Dr. N. Haraszkiewicz-Birkemeier
Source:
http://www.pmlive.com/blogs/digital_i
ntelligence/
Clinical Trials mobile

33. Medical devices - Dr. N. Haraszkiewicz-Birkemeier
Clinical Trials mobile
Lilly Oncology is committed to providing resources that support
and enrich the cancer community. Part of that commitment is
making sure oncology professionals have access to the trial
information they need. The Lilly Oncology Clinical Trials
Resource application provides healthcare professionals free
access to trial information for a wide variety of cancer
indications. Key Features:
- Clinical Trials: Find Lilly Oncology and non-Lilly Oncology clinical
trials
- Sortable Filters: Locate trials based on cancer type, country,
state, drug, phase, and/or title
- Save and Share Trials: Save trials for fast and easy future
reference, and share saved content with colleagues
- Other Resources: Find links to additional resources, such as the
American Cancer Society, based on audience, service, and/or
category
- Events: Locate congresses and events based on category,
location, and/or date

34. Medical devices - Dr. N. Haraszkiewicz-Birkemeier
Interested and need more info?
For more information and a complete
presentation don't hesitate to contact me.
Presentations in different languages: English,
German, Polish, Dutch are available.
Email.: natalia.haraszkiewicz@gmail.com
Tel. mobile: (+31) 0641883606