Il settore dei dispositivi medici a base di
sostanze: aspetti regolatori, mercato di
riferimento e nuove prospettive
Assobiomedica, Milano 9 settembre 2014
Dispositivi medici borderline:
aggiornamenti dall’Europa
Maria Grazia Leone
Direzione Generale dei dispositivi medici, del servizio
farmaceutico e della sicurezza delle cure
Agenda
• Inquadramento della questione
• Aggiornamenti dal Borderline and Classification
Expert Group
 Modifiche alla linea guida MEDDEV 2.1/3 Rev. 3
 Introduzione della definizione di diagnosi in vivo
• Aggiornamenti dal Council Working Party
 Capo 1
 Allegato VII: Regola 21
2
Inquadramento della questione
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Definizione
Cosa è un prodotto borderline?
Manual on Borderline and Classification in the Community Regulatory
Framework for Medical Devices Version 1.16 (07-2014)
I prodotti borderline sono quei prodotti che per loro natura non appartengono
con chiarezza ad un determinato settore, per i quali quindi è difficile definire
quale sia la normativa di riferimento da applicare.
In alternativa prodotti borderline sono quei prodotti che rientrano nella
definizione di dispositivo medico ma sono esclusi dal campo di applicazione
della direttiva. Quando un prodotto non rientra nella definizione di dispositivo
medico riportata nella direttiva o ne è escluso dal campo di applicazione della
direttiva stessa, si applicano altre direttive o normative di riferimento.
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APP
PRES
S
COMP
EMC
SIC
GEN
PROD
AIMD
RIFIUTI e
IMBALL
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Dispositivo medico: finalità
Finalità medica
Permette di escludere prodotti che non devono vantare
tale finalità (cosmetici, erboristici, integratori
alimentari, apparecchiature estetiche)
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L’aspetto dei borderline più discusso riguarda il
confine tra
dispositivi medici e farmaci
7
Direttive 2001/83/EC e 2007/47/EC: definizioni
Medicinale:
Dispositivo medico:
•
ogni sostanza o associazione di sostanze presentata
come avente proprietà curative o profilattiche delle
malattie umane; o
•
ogni sostanza o associazione di sostanze che possa
essere utilizzata sull’uomo o somministrata
all’uomo allo scopo di ripristinare, correggere o
modificare funzioni fisiologiche, esercitando
un’azione farmacologica, immunologica o
metabolica, ovvero di stabilire una diagnosi medica
qualunque strumento, apparecchio, impianto, software,
sostanza o altro prodotto, utilizzato da solo o in
combinazione, compresi gli accessori tra cui il
software destinato dal fabbricante ad essere
impiegato specificamente con finalità diagnostiche
e/o terapeutiche e necessario al corretto
funzionamento del dispositivo stesso, destinato dal
fabbricante ad essere impiegato sull’uomo a fini di:
•
diagnosi, prevenzione, controllo, trattamento o
attenuazione di malattie,
•
diagnosi, controllo, trattamento, attenuazione o
compensazione di una ferita o di un handicap,
•
studio, sostituzione o modifica dell’anatomia
oppure di un processo fisiologico,
•
controllo del concepimento,
che non eserciti nel o sul corpo umano l’azione
principale cui è destinato con mezzi farmacologici,
immunologici o mediante processi metabolici, ma la
cui funzione possa essere coadiuvata da tali mezzi
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Dispositivi medici e farmaci: quali differenze?
Farmaci
Dispositivi medici
• Legislazione consolidata (prima
Direttiva 65/65/EEC)
• Legislazione recente definita “Nuovo
Approccio” (prima direttiva
90/385/EEC)
• Immissione in commercio a seguito
di autorizzazione
• Autorizzazione centralizzata da
parte dell’EMA o nazionale,
decentrata o di mutuo
riconoscimento da parte degli SM
• Valutazione basata sul rapporto
rischio/beneficio
• Immissione in commercio a seguito
del rilascio del marchio CE
• Rilascio del marchio CE da parte di
Organismi Notificati (ad eccezione
della classe I)
• Valutazione basata sul rispetto dei
requisiti essenziali.
• Intervento dell’ON sempre piu’
approfondito man mano che aumenta
la classe di rischio
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Perché si tende a propendere per la classificazione come
farmaco?
Ragioni storiche
“Il farmaco è piu’ sicuro”
Contengono sostanze
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Proanthocyanin Content in Cranberry CE
Medicinal Products
Abstract
The CE marking is a statutory marking for certain products sold within the European
Economic Area. Medicinal products with a CE label are not regulated by the European
Medicines Agency but are licensed according to the directives of the European
Community. We have analysed the proanthocyanin (PAC) content of four cranberry
CE products by both a photometric (DMAC method using 4-dimethylamino-cinnamicaldehyde as colouring reagent) and a high-performance liquid chromatography assay
and have compared the daily dosages recommended for the products by their
manufacturers with benchmark doses obtained from the literature. For all CE products,
the identified DMAC values for the PAC content per unit were below those declared.
For two of the CE medicinal products, not even the manufacturers’ maximum daily
dosages have type A PAC contents that would have any chance of providing the health
benefits promised on the product information sheets; the other two might have some
chance, but only at maximum dosage (nine capsules per day for one of them). CE
medicinal products should be better controlled by regulatory authorities to
prevent consumers from buying and taking doses that are inadequate to provide
the benefits claimed.
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Aggiornamenti dal
Borderline and Classification Expert Group
Modifiche alla linea guida MEDDEV 2.1/3 Rev. 3
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Pharmacological means (bozza)
• “Pharmacological means” is understood as an interaction between, or an
indirect effect of, the molecules of the substance in question or its active
metabolites and a constituent of the human body (including any of its
parts, or an organism or other pathogens within or on the body) through
any type of chemical binding which results in initiation, enhancement,
mitigation or blockade of physiological or pathological characteristics.
• Although not a completely reliable criterion, the presence of a doseresponse correlation is indicative of a pharmacological effect.
• Examples of constituents of the human body may include: cells, receptors,
membrane proteins, ion channels, enzymes.
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Immunological means (bozza)
• “Immunological means” is understood as an action mediated or exerted
(including e.g. stimulation, modulation, replacement) by immunecompetent cells (e.g. lymphocytes, phagocytes, macrophages, dendritic
cells) and/or by molecules involved in overall immunological response (e.g.
toll-like receptors, complement factors, cytokines, antibodies).
• A means of action can be considered “immunological” only if the induction
or blocking of the immune response is the principal intended consequence
of the administration of a substance.
• Examples: vaccines, antibodies, antivenoms and certain therapies which
depend on an immunological means to target therapy
15
Metabolic means (bozza)
• “Metabolic means” is understood as an action which involves an alteration,
including stopping, starting or changing the rate, extent or nature of the
chemical processes (whether normal or pathological) participating in, and
available for, function of the human body or an organism or pathogen
within or on the body.
• Metabolism is the set of chemical reactions that happen in living
organisms. It includes processes for growth, reproduction, response to
environment, survival mechanisms, sustenance, and maintenance of body
structure and integrity.
16
Modifiche alla linea guida MEDDEV 2.1/3 Rev. 3 (bozza)
•
Note 1: The fact that a substance is itself metabolised does not necessarily imply that it
achieves its principal intended action by metabolic means.
•
Note 2: Definition of substance (Directive 2001/83/EC)
Substance: Any matter irrespective of origin which may be:
— human, e.g. human blood and human blood products;
— animal, e.g. micro-organisms, whole animals, parts of organs, animal secretions,
toxins, extracts, blood products;
— vegetable, e.g. micro-organisms, plants, parts of plants, vegetable secretions,
extracts;
— chemical, e.g. elements, naturally occurring chemical materials and chemical
products obtained by chemical change or synthesis.
•
Note 3: A chemical binding is any type of binding (e.g. electrostatic interactions, van der
Waals forces, H-bonds, covalent binding).
17
Introduzione della definizione di
diagnosi in vivo
nella linea guida MEDDEV 2.1/3 Rev.3
18
Introduzione della definizione di diagnosi in vivo (bozza)
A medicinal product is defined in Article 1(2) of Directive 2001/83/EC (MPD),
as follows:
“2. Medicinal product:
(a) Any substance or combination of substances presented as having properties
for treating or preventing disease in human beings; or
(b) Any substance or combination of substances which may be used in or
administered to human beings either with a view to restoring, correcting or
modifying physiological functions by exerting a pharmacological, immunological
or metabolic action, or to making a medical diagnosis.”
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Introduzione della definizione di diagnosi in vivo (bozza)
•
It appears from this legal definition that a substance shall be considered to be a medicinal
product when having the purpose to making a “medical diagnosis”. It is therefore important
to understand and clarify the meaning of what a “medical diagnosis” is. Based on the existing
definitions, and in particular the definition of an in vitro medical device according to Directive
98/78/EC, it could be said that a “medical diagnosis” is the demonstration or visualisation of
the anatomy/morphology, the condition or the functions of the human body irrespective if
these are physiological or pathological.
•
Hence substances like x-ray contrast media, NMR enhancing agents, SPECT- and PETradiopharmaceuticals are medicinal products.
•
It should also be emphasised that a diagnostic medicinal product is to be composed of
substances or combination thereof and used in vivo and not consist of instruments, apparatus,
appliances, software, materials or other articles so to differentiate it from a medical device.
•
Finally, the mode of action is not a criterion in this case.
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Aggiornamenti dal Council Working Party
PROPOSAL FOR A
REGULATION OF THE EUROPEAN PARLIAMENT AND OF THE
COUNCIL
ON MEDICAL DEVICES, AND AMENDING DIRECTIVE 2001/83/EC,
REGULATION (EC) NO 178/2002
AND REGULATION (EC) NO 1223/2009
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Chapter I, Article 1 Scope
This Regulation establishes rules to be complied with by medical devices and accessories to medical devices that are placed on the market or
put into service in the Union for human use.
For the purposes of this Regulation, medical devices and accessories to medical devices shall hereinafter be referred to as ‘devices’.
2. This Regulation shall not apply to:
(a) in vitro diagnostic medical devices covered by Regulation (EU) […/…];
(b) medicinal products covered by Directive 2001/83/EC and advanced therapy medicinal products covered by Regulation (EC) No
1394/2007. In deciding whether a product falls under Directive 2001/83/EC or Regulation (EC) No 1394/2007 or under this Regulation,
particular account shall be taken of the principal mode of action of the product;
(c) human blood, blood products, plasma or blood cells of human origin or devices which incorporate, when placed on the market or used in
accordance with the manufacturer's instructions, such blood products, plasma or cells, except for devices referred to in paragraph 4;
(d) cosmetic products covered by Regulation (EC) No 1223/2009;
(e) transplants, tissues or cells of human or animal origin or their derivatives, or products containing or consisting of them, unless a device is
manufactured utilising tissues or cells of human or animal origin, or their derivatives, which are non-viable or are rendered nonviable.However, human tissues and cells that are non-viable or are rendered nonviable and that have undergone only non-substantial
manipulation, in particular those listed in Annex I of Regulation (EC) No 1394/2007, and products derived from such tissues and cells, shall
not be considered devices manufactured utilising tissues or cells of human origin or their derivatives;
(f) products that contain or consist of biological substances or organisms other than those referred to in points (c) and (e) that are viable,
including living micro-organisms, bacteria, fungi or virus;
(g) food covered by Regulation (EC) No 178/2002.
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Proposta del Parlamento EU 9/10/2013
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Chapter I Article 3 Regulatory status of products
1. The Commission may, at the request of a Member State or on its own initiative,
by means of implementing acts, determine whether or not a specific product, or
category or group of products, falls within the definitions of 'medical device' or
'accessory to a medical device'. Those implementing acts shall be adopted in
accordance with the examination procedure referred to in Article 88(3).
2. The Commission shall ensure the sharing of expertise between Member States
in the fields of medical devices, in vitro diagnostic medical devices, medicinal
products, human tissues and cells, cosmetics, biocides, food and, if necessary, other
products in order to determine the appropriate regulatory status of a product, or
category or group of products.
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Una decisione della Corte di Giustizia europea
Case C-109/12, Laboratoires Lyocentre v Lääkealan turvallisuus,
3 ottobre 2013:
La qualificazione di un prodotto come dispositivo medico in uno
Stato membro non preclude che possa essere differentemente
qualificato in un altro Stato membro
La proposta della Commissione contiene elementi che tendono ad
assicurare una più uniforme applicazione della normativa
La Commissione può prendere decisioni con atti di esecuzione.
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Proposta del Parlamento EU 9/10/2013
26
Annex VII Rule 21
Devices that are composed of substances or combination of substances intended to
be ingested, inhaled or administered rectally or vaginally and that are absorbed by
or dispersed in the human body are in class III.
Nella proposta di Regolamento discussa dal Parlamento europeo la Regola 21 è
stata cancellata (Emendamento 306 del Testo del 9/10/2013)
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Un corretta applicazione delle regole
si basa su solidi dati scientifici
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Supporre va bene, ma approfondire è meglio
Mark Twain
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Grazie per l’attenzione!
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