52 SIMPOSIO AFI
Rimini 30-31 maggio, 1 giugno 2012
Aspetti regolatori e di progettazione nei
dispositivi medici borderline
Aggiornamenti sulle attività del Gruppo
europeo Borderline and Classification
Maria Grazia Leone
Direzione Generale dei Dispositivi Medici,
del Servizio Farmaceutico e della Sicurezza delle Cure
Ministero della Salute
([email protected])
M.G. Leone
Istruzioni per l’uso della
presentazione
ATTENZIONE
Le proposte riportate nelle prossime diapositive non
hanno ancora il marchio CE!
Costituiscono solo una base per le successive
discussioni a livello europeo e come tali potrebbe
subire sostanziali modifiche.
M.G. Leone
Agenda
Definizione di borderline
Gruppo ad hoc sui prodotti borderline farmaci
dispositivi medici
Modifiche alla linea guida MEDDEV 2.1/3 rev 3
Proposta di nuove regole di classificazione per i
dispositivi medici per os
M.G. Leone
Cosa è un prodotto borderline?
Manual on Borderline and Classification in the Community Regulatory
Framework for Medical Devices Version 1.12 (04-2012)
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.
M.G. Leone
Cosa è un prodotto borderline?
Manual on Borderline and Classification in the Community Regulatory
Framework for Medical Devices Version 1.12 04-2012
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.
M.G. Leone
APP
PRESS
COMP
EMC
SIC
GEN
PROD
AIMD
RIFIUTI e
IMBALL
M.G. Leone
Direttive 2001/83/EC e 2007/47/EC:
definizioni
Medicinale:
n ogni sostanza o associazione di
sostanze presentata come avente
proprietà curative o profilattiche
delle malattie umane; o
n 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
Dispositivo medico:
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:
n
diagnosi, prevenzione, controllo, trattamento o attenuazione
di malattie,
n
diagnosi, controllo, trattamento, attenuazione o
compensazione di una ferita o di un handicap,
n
studio, sostituzione o modifica dell’anatomia oppure di un
processo fisiologico,
n
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
M.G. Leone
Novità introdotta dalla direttiva
2007/47/EC Art. 1 comma 5c
This Directive does not apply to:
… omissis…
(c) medicinal products covered by Directive
2001/83/EC. In deciding whether a product falls
under that Directive or the present Directive,
particular account shall be taken of the principal
mode of action of the product;
M.G. Leone
D. Lgs 37/2010 Art.2 comma 3
Il presente decreto non si applica:
… omissis…
c) ai medicinali soggetti al decreto legislativo 24 aprile
2006, n. 219, che recepisce il codice comunitario sui
medicinali per uso umano. Nello stabilire se un
determinato prodotto rientri nell'ambito di
applicazione di tale decreto oppure del presente
decreto si deve tener conto in particolare del
principale meccanismo d'azione del prodotto stesso;
M.G. Leone
M.G. Leone
Ad hoc working group on borderline cases
between medical devices and pharmaceuticals
AC per dm (IT, NL, DE, SE, IR, PT, ES, UK, LV), EU
COM
AC per farmaci (GR, UK, EMA, CHMP), EU COM
1 riunione 10 marzo 2011
Meeting on demand in order to support the more complicated decisions on
borderline products by involving experts from the two sectors.
M.G. Leone
Action point
IT, DE, NL will create a working group in order to
draft
new
definitions
for
“metabolic”,
“pharmacological”, “immunological” and chemical
means.
M.G. Leone
MEDDEV 2.1/3 rev 3
In deciding whether a product falls under the MDD
particular account shall be taken of the principal
mode of action of the product
Pharmacological mean
Immunological mean
Metabolic mean
M.G. Leone
M.G. Leone
MEDDEV 2.1/3 rev 3 (December 2009)
“Pharmacological means” is understood as an interaction between the molecules of the
substance in question and a cellular constituent, usually referred to as a receptor,
which either results in a direct response, or which blocks the response to another
agent. Although not a completely reliable criterion, the presence of a dose-response
correlation is indicative of a pharmacological effect.
“Immunological means” is understood as an action in or on the body by stimulation
and/or mobilisation of cells and/or products involved in a specific immune reaction.
“Metabolic means” is understood as an action which involves an alteration, including
stopping, starting or changing the speed of the normal chemical processes
participating in, and available for, normal body function.
Note: The fact that a product is, or is not, itself metabolised does not imply that
it achieves, or does not achieve, its principal intended action by metabolic means.
M.G. Leone
M.G. Leone
Amendment to the definitions of
pharmacological, immunological and
metabolic means
as reported in the MEDDEV 3.1/3
Rev.3
M.G. Leone
MEDDEV 2.1/3 rev 3
“Pharmacological means” is understood as an
interaction between the molecules of the substance in
question and a cellular constituent, usually referred
to as a receptor, which either results in a direct
response, or which blocks the response to another
agent.
Although not a completely reliable criterion, the
presence of a dose-response correlation is indicative
of a pharmacological effect.
M.G. Leone
“Pharmacological means” (proposal)
is understood as an interaction between the molecules of the substance in
question and a constituent of a biological system (the whole human
body or any of its parts), which either results in a direct response, or
which blocks the response to another agent.
This biological constituent could be a receptor like e.g. a membrane
protein, an ion channel or an enzyme; the interaction is generally made
of different types of bindings leading to the mediation of a response at
a cellular or molecular level. They may also modify an entity or
combine with it in order to alter the interaction of the entity itself with
the body.
The principle described above also applies to the interaction between a
substance and a pathogenic organism.
Although not a completely reliable criterion, the presence of a doseresponse correlation is indicative of a pharmacological effect.
M.G. Leone
MEDDEV 2.1/3 rev 3
“Immunological means” is understood as an action in
or on the body by stimulation and/or mobilisation of
cells and/or products involved in a specific immune
reaction.
M.G. Leone
“Immunological means” (proposal)
is understood as an action in or on the body by stimulation
and/or mobilisation of cells and/or products involved in a
specific immune reaction.
Each substance, not recognized as endogenous (xenobiotic),
administered to the human body can produce an immune
response, being recognized as “non-self”. It must be clear
that a means of action can be considered “immunological”
only when the immune response is the primary intended
consequence of the administration of a substance. On the
other hand an immune response that is not the intended
consequence of administration, cannot be considered an
immunological mode of action.
M.G. Leone
MEDDEV 2.1/3 rev 3
“Metabolic means” is understood as an action which
involves an alteration, including stopping, starting or
changing the speed of the normal chemical processes
participating in, and available for, normal body
function.
Note: The fact that a product is, or is not, itself
metabolised does not imply that it achieves, or does
not achieve, its principal intended action by
metabolic means.
M.G. Leone
“Metabolic means” (1) (proposal)
is understood as an action which involves an alteration,
including stopping, starting or changing the speed of the
normal chemical processes participating in, and available for,
normal body function.
Metabolism is the set of chemical reactions, that happen in the
cells of living organisms to sustain life. It includes processes
for cell growth, reproduction, response to environment,
survival mechanisms, sustenance, and maintenance of cell
structure and integrity.
M.G. Leone
“Metabolic means” (2) (proposal)
With regard to the concept of chemical process the binding
between molecules which does not mediate, directly or
indirectly, a response within or on the human body is
considered a chemical, not a metabolic mode of action.
A typical chemical mode of action is the local pH modification
or the sequestering action of a molecule. The chemical mode
of action should be reproducible in vitro in a closed not
biological inert system.
M.G. Leone
FDA (21 U.S.C. 321(h))
In the FDA definition of a medical device instead of the concept of
pharmacological, immunological and metabolic means the term
"chemical action" as a subordinate concept is used. However, although
using a different wording, the borderline between medical devices and
medicinal products is practically the same. The FDA definition reads
as follows: "A device is: … intended to affect the structure or any
function of the body of man or other animals, and which does not
achieve any of it's primary intended purposes through chemical
action within or on the body of man or other animals and which is
not dependent upon being metabolized for the achievement of any of
its primary intended purposes."
M.G. Leone
FDA guidance
•
Classification of Products as Drugs and Devices and
Additional Product Classification Issues (Draft
guidance (06/2011)
•
Interpretation of the Term "Chemical Action" in the
Definition of Device Under Section 201(h) of the
Federal Food, Drug, and Cosmetic Act (Draft
guidance (06/2011)
M.G. Leone
Interpretation of the Term "Chemical
Action"
III. WHAT DOES “CHEMICAL ACTION” MEAN ?
Under the Agency’s interpretation, a product exhibits
“chemical action” for purposes of the device definition at
section 201(h) of the FD&C Act if:
Through either chemical reaction or intermolecular forces or
both,the product:
Mediates a bodily response at the cellular or molecular
level, or
Combines with or modifies an entity so as to alter that
entity’s interaction with the body of man or other animals.
M.G. Leone
Proposta di nuove regole di
classificazione per i dispositivi
medici per os
M.G. Leone
Medical device – medicinal product ad
hoc working group on borderlines cases
... Outcome: the members suggested qualifying the
product as a medical device. However, they strongly
recommended in parallel, a revision of the
classification rules for ingested products in the
medical device Directive.
Action point: The United Kingdom, Portugal and
Dutch's delegations will draft a proposal.
M.G. Leone
Proposta di nuove regole di classificazione
per i dispositivi medici per os
Regola 5 (attuale)
Tutti i dispositivi invasivi in relazione con gli orifizi del corpo, diversi
dai dispositivi invasivi di tipo chirurgico, che non sono destinati ad
essere allacciati ad un dispositivo medico attivo o che sono destinati
ad essere allacciati ad un dispositivo medico attivo appartenente alla
classe I:
- rientrano nella classe I se sono destinati ad un uso
temporaneo…omissis…
- rientrano nella classe IIa se sono destinati ad un uso a breve termine
…omissis…
- rientrano nella classe IIb se sono destinati ad un uso a lungo
termine…omissis…
M.G. Leone
Proposta di nuove regole di classificazione
per i dispositivi medici per os
Regola speciale? (proposta italiana)
Rule 19:
Ingested medical devices, and their products of
biotransformation, that are not systemically absorbed
are in class IIb
Ingested medical devices, and their products of
biotransformation, that are systemically absorbed,
regardless of their absorption level, are in class III.
M.G. Leone
Grazie per l’ attenzione!
M.G. Leone