medical devices - clinical research - registration strategies dr. n. haraszkiewicz-birkemeier

Medical Devices. From idea to implementation. Clinical research.

Strategies for marketing of new medical devices.

Dr Natalia Haraszkiewicz-Birkemeier

Medical devices - Dr. N. Haraszkiewicz-Birkemeier

Medical Devices – definition, directives, guidelines,

classification


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.


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


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.


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


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.


IVD Medical DeviceAn 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


IVD Medical DeviceClassification

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


EU Medical Devices Markets


EU Medical Device Markets


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”


EU market challenges


Registration of Medical Devices & Clinical Data


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


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.


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.


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.


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."


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.


Examples of Medical Devices


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


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.


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.


MammaPrintThe 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.


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.


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


HER-2 DNA Probe Kit


Herceptin (trastuzumab)PATHVYSION HER-2 DNA Probe KitDevice 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/


Pharmaceutical and diagnostic development

Source: Biomarkers strategies for oncology drug development , N.Haraszkieiwcz, LinkedIn blog


Source: http://www.pmlive.com/blogs/digital_intelligence/

Clinical Trials mobile


Clinical Trials mobileLilly 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


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.: [email protected]. mobile: (+31) 0641883606

mailto:[email protected]

medical devices - clinical research - registration strategies dr. n. haraszkiewicz-birkemeier

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