Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - DERMAE (Clinical research for the validation of a non-invasive medical imaging device for dermatological diagnoses)

Teaser

DAMAE Medical objective is to provide dermatologists a new medical imaging device capable of producing images similar to histology images without the need for skin tissue excision and processing. As such, DAMAE Medical has developed a leading-edge optical technology capable of...

Summary

DAMAE Medical objective is to provide dermatologists a new medical imaging device capable of producing images similar to histology images without the need for skin tissue excision and processing. As such, DAMAE Medical has developed a leading-edge optical technology capable of visualizing in vivo biological tissues in situ at a cellular level, offering market-leading penetration depth while being non-invasive for the patient. Instead of the conventional long and invasive diagnosis process, this new technology enables optical biopsy for immediate and early-stage skin cancer diagnosis during clinical examinations.
During the DERMAE project (Phase 1), a first assessment feasibility regarding the scale-up of the technology was performed to demonstrate the technology in a relevant preclinical environment, and to establish and validate a pre-industrialized device for clinical trials.
First, the imagery prototype has been tested on various skin diseases thanks to collaborations with histo-pathology laboratories and allowed calibrating the technology. Then, the prototype has been applied on several human skin cancer biopsies: after the clinical examination, the tumor was removed by the dermatologist and immediately imaged to keep the in vivo structure of the tissue. That allowed optimizing the technology on more tangible clinical criteria according to the dermatologists’ feedback.
Moreover, a conception and industrialization feasibility study has been carried out to define the technical requirements associated to the functional analysis and use cases of the device. The regulatory framework of developing a medical device has also been analyzed to define the essential performance and safety requirements of the EU medical standards.
Finally, a prototype of the pre-industrialized device has then been designed and manufactured by taking into account all the constraints defined in the previous feasibility study. This work included the aesthetic design of the device, the definition of the technical solutions for providing an ergonomic kinematic and the manufacturing of the protective housing in which the optical technology is integrated.
In addition to the technical assessment feasibility, a market study was performed to investigate the international market opportunity and establish the market access strategy. Initial business plan presented in the Phase 1 proposal remains globally relevant, with slight adjustments and consolidations in terms of timing and production volumes.

Work performed

This initial phase, conducted from (April 1st 2015 to Sept. 30th 2015) enabled to transition from a TRL 4 to a TRL 6 thanks to technical feasibility assessment, which consisted of scaling-up the technology by demonstrating the prototype in a relevant preclinical environment, and to establish and validate a pre-industrialized device for clinical trials.

Pre-clinical tests: The first action was to demonstrate the technology in a relevant preclinical environment. The TRL 4 imagery prototype has then been tested through preclinical tests: first, images of a large variety of skin diseases have been performed thanks to collaborations with histopathology laboratories and allowed calibrating the technology (TRL 5). Then, the prototype has been applied on several human skin tumors, in particular basal-cell carcinoma and melanoma (TRL 6). After the clinical examination, the tumor was removed by the dermatologist and immediately imaged to keep the in vivo structure of the tissue. Those tests have been carried out in close collaboration with the Dermatology Department of Saint-Étienne Hospital, which is a French leader of non-invasive dermatological imaging research. This preclinical demonstration allowed to periodically adjust the technical developments on more tangible clinical criteria in order to converge towards an optimized technology according to the dermatologists’ feedback.

Feasibility study: The second action was to carry out a conception and industrialization feasibility study. From the general functional decomposition of the DERMAE medical device, we defined 13 essential functions which were then translated into 12 use-cases in order to specify the technical requirements in the design of the device. Then, the regulatory framework (EU directive and standards) of the project has been analyzed to define the performance and safety requirements of developing a medical device.

Design and development of prototype: The third action was to design and develop a prototype of the pre-industrialized device by taking into account all the constraints and requirements defined in the previous feasibility study. Here is the specification we have made: the device was designed as a microscope which can be rotated as required from vertical to horizontal position.
• In vertical mode, it can be used on biological tissue samples (ex vivo) or for small animals imaging (in vivo) for the study of skin pathologies in situ during preclinical research in the cosmetic or pharmaceutic industry.
• In horizontal mode, it can be used on patients (in vivo) for the non-invasive study of skin lesions during dermatology clinical trials.
First, a design study has been carried out, including in the conception the aesthetic creation of the device and the design of the protective housing in which the optical technology will be integrated, and its support. Then, a mechanical feasibility study has been performed to define the technical solutions for providing an ergonomic kinematics for the moving parts: the rotation, the translation and the precise setting of the optical unit.
Finally, an industrialization feasibility study has been made to anticipate the industrialization and large-scale production issues from the conception. For example, an analysis of the volume of the future series and the cost structures of the device allowed to define the most relevant materials and manufacturing tools and processes to use. After having achieved those studies, a prototype of the pre-industrialized device has been developed, validated and manufactured.

Market evaluation: In addition, a feasibility study of market access strategy has also been carried out. This market study consisted of identifying and interviewing worldwide key opinion leaders (Europe, USA & APAC) to challenge the targeted markets specificity and to analyze competitors’ business model, clinical development strategy and outcomes. This study has confirmed the complete relevance of the DERMAE intended m

Final results

The next steps of the DERMAE medical device development is to obtain the CE marking by the beginning of 2016 and duplicate it in a few copies. A first exploratory clinical trial will then be led with on melanoma and non-melanoma skin cancers. The objective will be to define and validate a semiology specific to the new optical imaging technology developed in the DERMAE project.
One of the main outcome of this Phase 1 has been to precise the product development strategy of the DERMAE project: the technology will be declined in two products.
The first medical device is the one described in this technical report. The technology will then be used for the study of skin pathologies in situ during preclinical research in the cosmetic or pharmaceutic industry (vertical mode) or for the non-invasive study of skin lesions during dermatology clinical trials (horizontal mode).
However, as presented in the Phase 1 proposal and in the beginning of this report, the general objective of the DERMAE project is to provide dermatologists a non-invasive medical imaging device capable of producing images similar to histology images without the need for the conventional long, invasive and unreliable biopsy process.
This objective then implies to provide a handheld device for convenient use by dermatologists and to simplify examining difficult-to-access skin regions. This will require reengineering of the design of the optical technology, which actually has a shape of a microscope, to compact the system towards a manual model, using a specific optical fiber bundle for image transport from the output of the optical unit to the detector.

The second medical device developed in the DERMAE project will then introduce an easy-to-use manual scanning device for dermatological clinical examinations and specifically claim the early-stage skin cancers diagnosis support. The device will be intended for hospitals, clinics, dermatology and general practitioner practices.
It will be constituted of a transportable trolley – in which are embedded the peripheral modules (power supplies, electronics, processor, high-end monitor etc.). The optical technology will be integrated into a hand-held device with a design optimized for direct imagery on the patient, including difficult-to-access areas.

The decision of declining the technology in two devices has emerged from the observation that the technology performances would interest some biomedical research applications, without the need of reengineering the microscope-shaped prototype into a manual model. This upcoming technical work will of course not invalidate the preclinical demonstration of the technology achieved in the Phase 1 DERMAE project.
The technical completion and clinical validation of this second medical device will be initiated in a Phase 2 SME Instrument programme.

Website & more info

More info: http://damaemedical.fr/w/.