Combined Medical Devices: Which Classification for These

Borderline Products and Which Consequences for the

Manufacturers - About a Use Case in Skin Healing Area

Vaissière Anaïs

1,*

and Chevallier Thierry

2,3,4,†

Regentis-Pharma, 8B Rue Gabriel Voisin, Reims, France

Department of Biostatistics, Epidemiology, Public Health and Innovation in Methodology (BESPIM),

CHU Nîmes, Place du Pr. Robert Debré, 30029 Nîmes, France

UMR 1302, Institute Desbrest of Epidemiology and Public Health, INSERM, Univ. Montpellier, Montpellier, France

Tech4Health-FCRIN, France

Keywords: Medical Devices (MD), Combined Medical Devices, Combined Dressings, Cutaneous Healing, Ancillary

Substance, Peptide, Health Authorities, Classification, European Regulation 2017/746.

Abstract: Skin healing is a rapidly expanding field, especially with the growing needs of an aging population and the

increase in chronic pathologies (diabetes, venous ulcers, bedsores etc…). In order to offer ever more adapted

solutions, manufacturers are competing in ingenuity to propose innovative medical devices that meet the

expectations of patients, caregivers and the healthcare system. These developments raise many questions,

particularly with regard to the classification of devices in the various risk classes and the naming of these

wound healing devices. This article will focus on combined medical devices with the difficulties they pose

for manufacturers and health authorities in terms of development, financial investment, risk-taking and the

difficulty of classifying these so-called borderline products in the medical device universe.

1 COMBINED MEDICAL

DEVICES DEFINITION AND

EXAMPLES

A medical device (MD) is defined as “any instrument,

apparatus, equipment, material, product, except

products of human origin, or other article used alone

or in combination, […], the principal intended action

of which is not obtained by pharmacological or

immunological means or by metabolism, but the

function of which may be assisted by such means.”

(Collectif Dalloz: Jean-Paul Markus, 2010). The MD

are classified according to their destination and their

level of risk for the patient and the user according to

4 risk-categories (Class I: low-risk, IIa: moderate-

risk, IIb: elevated-risk and III: highest risk devices

(Stralin, 2020):

Combined MD are defined according to Rule 14

of Annex VIII of the European Regulation 2017/745

https://regentis-pharma.com/notre-equipe/

†

https://www.chu-nimes.fr/espace-recherche-clinique/eva

luation-des-dispositifs-medicaux-idil.html

as “All devices incorporating as an integral part a

substance which, when used separately, may be

considered a medicinal product within the meaning of

Article 1(10) of the said Directive, and whose action

is ancillary to that of the devices, are in Class III.”

According to the definition of the FDA (U.S.Food

and Drug Administration) in 2018, a combined MD is

defined as “diagnostic or therapeutic products that

combine drugs, devices, and/or biological products.”

(Morang J., 2019) (FDA, 2018).

Strictly speaking, a combined MD is a device

combining 2 elements, one of which is considered to

be a MD and the other substance is considered to be

a drug or to have a pharmacological or metabolic

action (Coronary stent with heparin coating (Biran R,

2016) or Bone substitute (hydroxyapatite) containing

an antibiotic (gentamicin) (Freischmidt H., 2020)).

The difficulty is then to prove that the main action is

brought by the device and not by the ancillary

substance. If the level of proof is not sufficient, there

Anaïs, V. and Thierry, C.

Combined Medical Devices: Which Classiﬁcation for These Borderline Products and Which Consequences for the Manufacturers - About a Use Case in Skin Healing Area.

DOI: 10.5220/0010937300003123

In Proceedings of the 15th International Joint Conference on Biomedical Engineering Systems and Technologies (BIOSTEC 2022) - Volume 1: BIODEVICES, pages 281-288

ISBN: 978-989-758-552-4; ISSN: 2184-4305

281

is a risk that the entire device will be classified as a

medicine.

These combined MD, considered as high-risk

devices because of the active substance, will be

classified in class III.

2 MEDICAL DEVICES FOR

CUTANEOUS HEALING

The cutaneous healing is currently one of the biggest

challenges for healthcare professionals. Indeed, with

the aging population, chronic wounds are more and

more frequent and lead to considerable expenses in

terms of health care costs because they are hard and

long to heal (over six weeks) and often recur (Martin

P. &. N., 2015).

The challenge of manufacturers is then to propose

new and efficient MD to improve healing without

having a strong pharmacological effect. In these

cases, the risk is to be classified as a medicine or

alternatively as a combined MD (high-risk class III)

which is by definition “A device incorporating a

substance that when used separately can be

considered a medicine” (Européenne, 2017).

High-risk MD necessarily entail more constraints

for manufacturers in terms of development, financial

investment, and investigation time, which can have a

major impact on the company. The aim of

manufacturers is to prove the healing efficiency and

the safety of the device. In that purpose, each step of

MD development must be carefully planned upstream

of the development phase. A concrete case of

combine device will be used to illustrate the

development process and difficulties encountered by

industrials and health authorities for the evaluation

and classification of such borderline products.

3 DRESSINGS AS COMBINED

MEDICAL DEVICES

3.1 Definition of Dressings for Skin

Healing

A dressing is a device covering a wound and

providing a physical protection against external

attacks (mechanical or bacterial). Dressings also

maintain a moist environment in contact with the

wound, promoting optimal healing. In 1962, the

British researcher George Winters demonstrated the

beneficial effects of a moist environment for healing.

Since then, this criterion is therefore considered to be

a fundamental characteristic for a twice faster healing

(Turner, 1979) and led industrials to focus on the

design of modern dressings: occlusive and

moisturizer (Chaby G., 2007) (Vaneau M., 2007)

(Werdin F., 2009).

Dressings present a high-level of risk and are

subjected to great vigilance from the manufacturers

as well as the health authorities. These dressings have

different compositions and act on different stages of

the healing process (reduction of inflammation,

improvement of tissue synthesis, intense hydration,

absorption of bad odours, elimination of cellular

debris etc…).

In general, the main functions of dressings are:

 Promote natural healing by maintaining a

moist environment and draining exudates.

 Allow gas exchange.

 Isolate the wound thermally and mechanically

from external aggression.

 Provide a bacteriological barrier by preventing

infections from the outside.

The development of dressings is vast and varied

and requires, as for any MD, a well-determined

evaluation framework as allowed by the new

European regulation 2017/746 and the

standardization of the evaluation of MD.

3.2 Classification of Dressings for

Cutaneous Healing

The classification of MD, intended for skin healing,

is complex and involves following several rules based

on dressings characteristics to correctly classify them:

 Their main action.

 The duration of use. The longer the duration of

administration, the riskier the MD will be

considered. For example, the healing of acute

wounds will take less time than chronic

wounds, which do not heal in 6 weeks. As a

result, chronic wound healing will require

treatment for more than 30 days and in

accordance with the European regulation

2017/745. “Duration of use:

o “Temporally” normally means intended

for continuous use for less than sixty

minutes.

o “Short-term” normally means intended for

continuous use between sixty minutes and

thirty days.

o “Long-term” normally means intended for

continuous use for more than thirty days.”

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 The pharmacological activity of the device:

According to Rule 8 of Annex VIII of the new

European Regulation 2017/745, “All invasive

surgical-type devices intended for long-term

use are classified as Class IIb unless:

o If they have a biological effect or are fully

or substantially absorbed, in which case

they are Class III […].

o If they are intended to administer drugs, in

which case they are Class III […].”

In addition, wound healing devices are applied on

open wounds and therefore represent a greater risk of

infection or that the carrier substances enter the

systemic circulation and induce side effects

Faced with the complexity of classification, each

device will be assessed on a case-by-case basis by

health authorities and manufacturers are responsible

for clearly defining the action of their MD and

providing a clear and precise claim. The new

European regulation 2017/746, implemented from

May 2021, brings more clarity on how to classify

MD.

3.3 Few Examples of Dressings and

Their Classification

Dressings can be classified in different risk classes

according to their characteristics. The table 1

illustrate some examples of dressings and their

repartition in the different risk-classes.

From this table, it is clear that the majority of

combined dressings are classified as Class III.

However, it is notable that combined dressings are not

automatically classified as Class III device and can be

classified in lower class risk like Prevena® or Askina

Carbosorb® dressings classified in IIa or the

Carbonet® or UrgoStart® dressings classified in IIb.

3.4 Reflections on the Classification of

Dressings

3.4.1 Silver Dressings

In general, silver dressings are considered as risky

MD and therefore classified as class III. Silver

molecules provide an antibacterial effect, considered

as a secondary function, and they are small molecules

which can be toxic if they reach the systemic

circulation. However, Prevena® dressing, although

claimed as a silver dressing and therefore at risk, is

still classified as a class IIa. Health authorities might

have considered that a silver dosage of 0.019% was

not sufficient to induce a toxic reaction.

Table 1: List of examples of marketed dressings.

TLC-NOSF: Technology Lipide-Colloid-Nano Oligo

Saccharide Factor.

Classification Dressin

, com

osition and intended use

Class I – Not

combined

 Algoplaque® (e-pansement, e-

pansement Algoplaque, s.d.):

Hydrocolloid dressing composed of

((carboxymethylcellulose (CMC)) and

Urgo Hydrogel® (e-pansement, e-

pansement Urgo Hydrogel, s.d.):

Maintenance of a moist environment.

Class IIa –

Not

combine

 Jelonet Plus® (e-pansement, e-

pansement Jelonet Plus, s.d.): Vaseline

dressing. Drainage of exudates.

Class IIa –

Combined

 Prevena® (e-pansement, e-pansement

Prevena, s.d.): Hydrocellular dressing

with silver (0.019%). Reduction of

microbial colonization.

 Askina Carbosorb® (e-pansement, e-

pansement Askina Carbosorb, s.d.):

Active carbon dressing. Adsorption of

acteria and odours.

Class IIb –

Not

combined

 UrgoTul® (e-pansement, e-pansement

UrgoTul, s.d.) and Ialuset® (Vidal,

Vidal Ialuset, s.d.): Hydrocolloid

dressing (CMC). Maintenance of a moist

environment and management of

exudates.

 Purilon gel® (e-pansement, e-

pansement Purilon, s.d.): Hydrogel

(sodium CMC). Effective and gentle

debridement.

Class IIb -

Combined

 Carbonet® (Nephew, s.d.): Active

carbon dressing. Adsorption of bacteria

and odours.

 UrgoStart® (Vidal, Vidal UrgoStart,

s.d.): Hydrocellular dressing composed

of a TLC-NOSF matrix. Inhibition of

metallo

roteinases

(

MMP

)

Class III –

Not

combined

 Duoderm® (Vidal, Vidal Duoderm,

s.d.): Hydrocolloid dressing. Maintains a

moist environment and aids in autolytic

detersion.

Class III -

Combined

 Urgotul®Ag (Vidal, Vidal UrgoTul Ag,

s.d.): Silver dressing. Maintains a moist

and antibacterial environment.

 Promogran® (HAS, 2019): Active

dressing with anti-protease effect

composed of 55% collagen and 45%

regenerated oxidized cellulose. MMP

inhibitor.

3.4.2 Carbon Dressings

Carbon dressings are represented in all risk classes

except class III. However, carbon molecule is an

ancillary substance, not responsible for the main

action of the device (maintaining a moist

environment), but which has a supporting function in

Combined Medical Devices: Which Classiﬁcation for These Borderline Products and Which Consequences for the Manufacturers - About a

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283

wound healing (absorption of malodours). By this

definition, and also with regard to the fact that carbon,

as a small molecule, can penetrate the systemic

system, all carbon-based dressings should be

classified as class III MD.

3.4.3 Metalloproteinase Regulating

Dressings

Another special case is the MMP-regulating

dressings. These dressings contain molecules with

physiological activity since they are able to induce the

inhibition of MMP activity. However, as explained

previously, according to rule 8 of Annex VIII of the

new European regulation 2017/745, “All invasive

surgical-type devices intended for long term use are

class IIb, except: if they have a biological effect or

are fully or substantially absorbed, in which case they

are class III. […]”. This definition clearly states that

these MMP-regulator dressings should be classified

as class III. However, only the Promogran® dressing

is classified in class III. The UrgoStart® is classified

as a class IIb MD.

3.4.4 Non-combined Dressings Classified in

Class IIb or III

On the contrary of combined dressings being

classified in class IIa and IIb, it also exists some

dressings that might be considered as being at low

risk and non-combined, according to their

composition and their main action, and which still

found classified in higher risk-classes (IIb and III).

This is the case for example of the Ialuset dressing®,

whose main function is to maintain a moist

environment, and which is mainly composed of

hyaluronic acid for its strong hygroscopic power,

which is classified in class IIb. The explanation for

this high-risk classification certainly comes from the

hyaluronic acid which, depending on its size (the

smaller, the more it will be considered at risk because

of the risk of entering the systemic circulation), can

be considered as a MD or a drug.

Another example of a careful classification is the

UrgoTul® dressing which is composed of a

moisturizing matrix (CMC, Vaseline, Paraffin) and

apart from the fact that it is used over long periods

(more than 30 days), its composition does not

represent any particular danger for the patient.

Indeed, the Algoplaque® dressing, also composed of

CMC is classified as class I MD. Moreover, the

association paraffin/vaselin/glycerol is considered as

being one of the most moisturizing mixtures and is

often used in cosmetic moisturizing cream (Mylan®,

Biogaran®, Dextopia®…). The classification of

UrgoTul® as a high-risk class (IIb) is then difficult to

understand in view of these elements, especially

considering its counterparts, UrgoStart®, which is a

combined MD also classified in class IIb.

Another example is the Duoderm® dressing,

which is a hydrocolloid dressing composed of a

matrix of pectin, gelatin, sodium CMC and a

polyurethane foam. The main function is to maintain

a moist environment. Despite a description that seems

without particular risk, this dressing is classified as

class III. It is therefore difficult to explain why this

dressing is considered to be riskier than UrgoStart®,

for example, or of equivalent risk to all silver

dressings.

These are few examples illustrating the lack of

uniformity for MD classification before the

implementation of the new European regulation.

4 CONCRETE EXAMPLE OF AN

INDUSTRIAL DRESSING,

INTENDED FOR SKIN

HEALING, CLASSIFIED AS A

COMBINED MD

4.1 Medical Device under Study

The MD used as an example to illustrate this research

is intended for skin healing of chronic wounds. This

MD consists of the association of a moisturizing

dressing with a peptide solution. The peptide included

in the solution was developed, in partnership with the

CNRS, on the basis of the activity of matrikines,

molecules derived from natural degradation of

elastin. This innovative bifunctional peptide (BFP)

has the ability to activate the synthesis of the

extracellular matrix (ECM) on one hand and to

inhibit, by a competitive mechanism, the molecule

responsible for inflammation (MMP) on the other

hand (Attia-Vigneau J, 2014) (Figure 1).

The promising performances of the peptide led the

industrials, responsible of its development, to

consider a medical application. Indeed, considering

the effects of the peptide on cellular regeneration,

proved by in vitro studies (Attia-Vigneau J, 2014),

this peptide was integrated to a phosphate buffer

solution to be applied on chronic wounds, such as

Venous Leg Ulcers (VLU), in association with a

secondary dressing to promote healing mechanisms.

Apart from pathological cases, like diabetes or

chronic wounds (ulcers), the healing process is 6

weeks. In case of chronic wounds, this healing

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process is longer because of an unbalance between

the synthesis and the degradation of the ECM

(Extracellular Matrix). This state prevents the

reconstruction of the matrix and then an impairment

of healing. The application of the BFP peptide could

bring back the balance and leads to an efficient

healing of the wound (Figure 1).

Figure 1: Healing process of wounds and schematic

representation of BFP peptide effect.

Most of the marketed MD to treat these kinds of

wounds act either on matrix synthesis, by maintaining

a moist environment (UrgoTul®, Ialuset®…), or on

the inhibition of MMP (UrgoStart® or Promogran®).

The new device uses the bifunctional effect of the

peptide and propose an innovative device able to act

on both phenomenon, synthesis of the matrix and

inhibition of MMP. This MD (peptide solution +

Secondary dressing) was therefore developed to

perform a proof-of-concept trial and to verify the

healing efficiency of the device and its safety of use.

4.2 MD Claim: Adequacy with the

Business Need

The claim of the MD is of particular importance and

consists in highlighting the main action of the

secondary dressing (hydration) in wound healing and

the supporting action of the BFP peptide which

consists in:

 Hydration of the microenvironment of the

wound, proved by in vitro RAMAN

spectroscopy and in vivo clinical trial on 10

women.

 Decrease of inflammation by a competition

mechanism of the peptide which acts as a decoy

effect for MMP and thus diverts the enzymatic

activity of this protein towards itself, leaving

the possibility for the matrix to regenerate

properly without having physiological or

metabolic effect.

From the industrial point of view, the peptide can

be considered as an ancillary molecule, making the

proposed device a MD that has been claimed as such

by the health authorities.

4.3 Classification of the Developed MD

and State of the Art

The French health authorities considered that the

claimed device was in fact a medicine. Considering

the definition of a medicine by the Public Health

Code (Article L. 5111-1) as “Any substance […]

exerting a pharmacological, immunological or

metabolic action.”, an argument was developed to

respond to the health authorities by comparing the

proposed MD to those already on the market such as

UrgoStart® or Promogran®, which are protease

regulators and can therefore also be considered as

having a pharmacological or physiological effect.

Despite this comparison, the French authorities

remained on their position because they considered

the peptide solution alone as a medicine. They also

stated that the dressing is not an impregnated dressing

(MD dressing incorporating as an integral part a

substance with an accessory pharmacological action)

and the peptide release on the wound cannot be

evaluated. This lack of safety on peptide release as

well as the lack of hindsight of the health authorities

regarding this new molecule made it impossible to

classify it as a MD.

Another example of MD more comparable to the

“Peptide solution + Secondary dressing” is the

Cacipliq20®. This Cacipliq20® is a spray,

considered as a MD of class III, offering protection of

growth factors by decoy effect and whose mode of

action can be compared to that of the BFP peptide,

which also acts as a decoy for MMP (Barritault,

2020). Additional expertise was therefore requested

from another European health authority who stated on

this particular case that the Cacipliq20® is accepted

as a device but similar products may be considered

pharmaceutical. This statement demonstrates the

variability of classification that can be obtained from

one country to another.

The opinion of other European health authorities

is quite unanimous and in agreement with that of the

French health authorities. Only the Czech health

authorities (SUKL) considered the device presented

as a combined device of class III. As a risk device this

MD is subject to great vigilance in terms of

Combined Medical Devices: Which Classiﬁcation for These Borderline Products and Which Consequences for the Manufacturers - About a

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traceability and monitoring and consequently, a GMP

synthesis of the peptide has been required by the

health authorities in order to carry out a clinical

trial.DM. This GMP synthesis not originally planned

by the industrial and that will have heavy

consequences for the future of the project.

5 IMPACT OF A

CLASSIFICATION AS A

COMBINED MD OF CLASS III

A device classified in class IIb or III is considered as

high-risk class by health authorities and a GMP

synthesis would been required in any case. The debate

is not about the classification of the MD but about a

wrong evaluation of the project in its entirety and a

poor knowledge of the field. How this wrong

estimation impacts the project and its budget

according to the development stage of the MD?

5.1 MD Conception

The MD conception stage is an essential step

determining the whole project technically and

financially. A correct calibration is essential to avoid

budget expense and project delay. The longer is a

project and the more expensive it will be. The correct

definition of the MD is possible with a deeper

knowledge of the field of MD. Indeed, a MD

classified in class IIb or in class III as a combined MD

present risk and although the safety and innocuity

proof are high. Health authorities will not take any

chances to propose a product on which they do not

have hindsight and without strong, recorded and

tracked guarantees on the safety. Moreover, with the

sanitary scandals of the past few years, health

authorities are extra careful regarding new devices.

5.2 Clinical Phases

A poorly estimated project at the outset will have the

greatest impact during the clinical phases. The

acceptance of the clinical trial is submitted to the

approbation of health authorities that will request the

GMP synthesis. As the budget allocated for the trial

is not sufficient to cover this additional expense, the

project will inevitably fall behind schedule.

For clinical trial, the quantity of necessary peptide

(or molecule) is rather small, and the costs are

extremely high due to the tracking system to

implement, and the documentation requested for a

GMP synthesis (Figure 2).

Figure 2: Impact of unplanned GMP synthesis on clinical

phase of a project.

 Produce a small amount of peptide, just

enough for the trial, pending verification that

the clinical trial is providing the expected

results.

 Produce a larger amount of peptide in

anticipation of the continuation of the project

and the commercialisation of the MD after the

clinical trial.

The 2 options of production will have an

equivalent price and difference will not be significant.

A larger production of peptide during the clinical

phase can save valuable time for the

commercialization phase where important quantity of

peptide will be requested. It is then important to

correctly estimate the financial costs and benefits of a

larger molecule production upstream.

It is necessary to be well trained and advised by

experts of the field to avoid taking decision urgently

and make bad choices for the project.

5.3 Marketing and Post Marketing

An unplanned GMP synthesis at the marketing phase

can have a financial impact mainly according to the

decision taken at the previous steps. During the

marketing phase, there is 2 possibilities:

 The peptide quantity produced at the previous

step was just sufficient to complete the trial. In

that case an additional budget and time increase

is to plan for the production of GMP synthesis.

 The peptide quantity produced at the previous

step was increased in anticipation for the

marketing. In that case, the manufacturing of

the device can be launch immediately.

However, a reflexion is to be considered for the

future of the project and according to the marketing

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plan of the industrial. Indeed, either the industrial is

the exclusive manufacturer and seller of the MD, in

which case it will be necessary to provide a budget

for the GMP synthesis throughout the marketing and

life cycle of the MD. Or the industrial commercializes

its devices in the form of licensing by granting

licenses for the exploitation of its product. In this

case, the manufacturer does not have to budget the

GMP synthesis for the marketing part.

However, it is important to highlight that the

greater the quantity of GMP synthesis, the lower the

price per kilo will be. Therefore, for 10 kg of GMP

peptide produced, the price per kilo is equivalent to

that of a non-GMP synthesis (Figure 3).

Figure 3: Impact of unplanned GMP synthesis on marketing

phase of a project.

Therefore, the impact of a GMP synthesis not

foreseen by the industrial during the design of the

project will have no financial impact for the later

phases of the project, if the GMP synthesis is very

important (equivalent to about 10 kilo).

6 CONCLUSION

The classification of MD and in particular combined

devices is a very complicated process, hardly

harmonized before the implementation of the new

European regulation 2017/746. Some examples of

dressings classifications that do not comply with the

new European regulation can be cited as UrgoStart®

(a combined MD classified as class IIb) or Prevena®

dressing (a combined MD containing silver classified

as class IIa) or a product like Cacipliq20® that can be

considered as a medicine and yet is positioned as class

III MD under the old directive. In this logic, the

mechanism of action of the UrgoStart® dressing,

whose main function is the inhibition of proteases by

the NOSF molecule, could be considered as a

pharmacological activity (Européenne, 2017)and

then classified as a combined MD of class III. To

understand this classification, an expert opinion has

been requested from European health authorities who

stated that, in their opinion and according to the

regulation in force, the substance NOSF meets the

status of a medicine. According to the regulation,

combined MD are defined following the rule 14 of

Annex VIII of the European Regulation 2017/746 as

“All devices incorporating as an integral part a

substance which, when used separately, may be

considered as a medicinal product within the

meaning of Article 1(10) of the said Directive, and the

action of which is ancillary to that of the devices, fall

within Class III.” On this basis, the UrgoStart® MD

could therefore be considered as a combined MD.

The status of combined MD is not clear, and it was

noted through this article that:

 Combined MD dressings are not clearly

defined as such on the contrary of combined

MD as stent or injector pens.

 Combined MD dressings are widely

represented within the different risk classes,

and they are not systematically classified in

class III as they should be as high-risk MD.

As part of the evaluation of a MD, it is currently

essential to carry out one, or even several, clinical

trials to demonstrate efficiency and safety of the

device. In this case, the balance benefit-risk is very

important and cannot be unbalanced in one direction

or the other under penalty of considering the device

as a drug. Indeed, in the case of a combined MD, the

main objective is to prove the ancillary action of the

associated molecule compared to the main MD.

Although the manufacturer transmits all the safety

information and considers the benefit-risk to be well

balanced, the health authorities will tend to perceive

an unbalanced in the direction of risk.

Those combined MD are considered as

“borderline products”, they are indeed, at the frontier

between the MD and the medicine, it is then a

question of claim and most of all to prove the effect

of the ancillary substance, associated with the main

MD. Moreover, an associated and innovative

substance will always be considered at risk by health

authorities who will not take any risk and will

systematically classify it as a high-risk MD. It is also

clear that regardless of the classification of the device,

in class III as a combined MD or in class IIb, such as

UrgoStart®, a GMP synthesis will be requested for

the associated molecule in order to have a better

traceability.

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The debate is therefore not about being classified

as a class IIb MD or as class III combined MD, but

really about avoiding being classified as a medicine.

The aim is then to provide as much proof of safety as

possible and to make a good claim that will avoid

being classified as a medicine by health authorities.

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