aplicação da regulamentação na cosmética e na nanomedicina · nanotechnology uses in 2008...
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Aplicação da regulamentação na Cosmética e na nanomedicina
Adriana Gamboa
Mariana Madureira
1º Encontro Nacional - Nanotecnologia: Legislar para competir, IPQ 03.04.2014
Cosmetics Legislation
REGULATION (EC) No 1223/2009 OF THE EUROPEAN PARLIA MENT AND OF THE COUNCIL of 30 November 2009 on cosmetic products
GUIDANCE ON THE SAFETY ASESSMENT OF NANOMATERIALS I N COSMETIC (SCCS/1484/12)http://ec.europa.eu/health/scientific_committees/co nsumer_safety/docs/sccs_s_005.pdf
DECREE-LAW No 189/2008 of 24 September 2008 as last ammended
Cosmetics’ Legislation – Main goals
�Functioning of the internal market (equal and immediate access to the market)
�High level of safety and protection of the human health (safe products in free circulation throughout the EU)
�Introduction of reporting of serious undesirable effects
�New rules for the use of nanomaterials
�Introduction of the notion of “responsible person”.
Definition of Nanomaterial
� “Nanomaterial ” means an insoluble or biopersistant and intentionally manufactured material with one or more external dimensions, or an internal structure, on the scale from 1 to 100 nm;
Nanotechnology uses
In 2008 there were 6193 registered patents for nanotechnology
ElectronicsStringer textilesMicroprocessorsInk-jet printersTennis balls racquetsTissues and clothesSports equipmentNew Cosmetics Sun protection
Most of the patents granted worldwide with nanotechnology are property of the cosmetic industry
Definition of Cosmetic Product
SubstanceMixture
EpidermisHair systemNailsLipsExternal genital organsTeeth Mucous membranes of the oral cavity
CleaningPerfumingChanging their
appearance Correcting body
odoursProtecting themKeeping them in good
condition
Use of nanomaterials in cosmetics
A market survey, conducted by ICCR in 2008, identified the nanoingredientsused by the cosmetic industry and their application and concluded that thefollowing ingredients were used:
Acrylates AluminaCarbon BlackCerium oxideFullereneIron OxidesPlatinumSilicaTitanium DioxideZinc Oxide
Advantages of Nanotechnology in Cosmetics
Improve properties of active molecules:� Solubility � Permeation� Bioavailability� Targeting� Stability
Improve the administration:� Reduce the dose administered� Reduce adverse effects of UV radiation� Improve the administration form
Innovation
Nano
emulsion
Macro
emulsion
Product Notification Rules
� One central EU notification (CPNP)
� Responsible Person guarantees the notification and legal compliance
� Specific rules for nanomaterials (§16):
Authorized (UV filters, Preservatives and Colorants)
Notification in EU Portal - CPNP 6 months prior to pl acing on the marketLabelling : list of ingredients with (nano) after the name of the nanoingredient
Safety Assessment
Physicochemical
Characterization
Exposure
Assessment
Hazard
Identification &
Dose – Response
Characterization
Nano-specific
Risk Assessment
No single method for the
characterization nor one suited to
fully access a nanomaterial
Intact skin and
Compromised
skin (lack of
standardised
test models)
None of the alternative in vitro validated
methods has yet been validated for
nanomaterials
Still evolving. General safety assessment
principles must be followed
(SCCS/1416/11)
Nanomaterials in study- TiO2
“SCCS has concluded that the use of TiO2 nanomateria ls at a concentration up to 25% as a UV-filter in sunscreens, can be considered to not p ose any risk of adverse effects in humans after application on healthy, intact or sunb urnt skin. However, does not apply to applications that might lead to inhalation exposure to TiO2 nanoparticles (such as powders or sprayable products).”
Purity and stability of coatings under revision by SCCS
- ZnO
“SCCS concluded that the use of zinc oxide nanopart icles (purity ≥96%, median diameter (D50: 50% of the number below this diameter) of the particle number size distribution above 30 nm, and the D1 (1% below this size) above 20 nm, coated and uncoated, solubility below 50 mg/L ), at a concentration up to 25% as a U V-filter in sunscreens, can be considered not to pose a risk of adverse effects in humans after dermal application.”
The influence of the coatings in the safety under revision by SCCS
Re-evaluation ongoing
UV Filter (nano)
ETH-50: Tris -biphenyl triazine
“The SCCS concluded that the use of ETH-50 nanomater ials (median primary particle size of 80 nm, purity ≥98%, uncoated) at a concentration up to 10% tris-biphenyl triazine, as a UV-filter in cosmetic products (except aerosols) can be consider ed safe for dermal application”
Annex VI/29
Authorisation in course
NANOMEDICINE
Pharmaceuticals
Medical Devices(including
in vitro diagnosticMD)
NANOMEDICINE
• instrument,
• apparatus,
• appliance,
• software,
• material
• article,
whether used alone
or in combination…,
intended by the
manufacturer
• Diagnosis,
• Prevention
• Monitoring,
• Treatment
• Alleviation of
disease, injury or
handicap
• Investigation,
replacement or
modification of
the anatomy or
of a physiological
process…
Medical Devices
which does not achieve its principal intended action in or on the human body by pharmacological,
immunological or metabolic means
Dec-Lei nº 145/2009
Dir 90/385/CEE
Dir 93/42/CEE
Dir 2007/47/EC
Definition
TransientShort
term
Long
term
Implantable absorvables
Implantables
Surgically invasive
Invasives - natural opening in the body or stomas.
Non Invasives
InvasibilityDuration of contact
Classification
Medical Devices
CONFORMITYESSENTIAL
REQUIREMENTS
COOPERATION
ASSESSMENT/RISK• Classification criteria
• Assessment
procedures
STANDARDIZATION
INTERVENIENTS• Manufacturers
• Notified Body
• Competent Authority
• Users
• Standardization Bodies
SURVEILLANCE• Market
• Notified Body
Medical Devices
Me
dic
al
De
vic
es
-C
on
form
ity
Mil
est
on
es
Medical Devices
New challenges…
� Innovation occurs at increasing speed
• Better Prevention AND diagnosis AND therapy
• Huge impact on delivery of health care
� Drivers:
• ICT developments
• Nanotechnologies
• Diffusion of high tech care to less controlled environments
� New generations increasingly result from “Converging technologies”
combination of different technologies which leads to the crossing of
borders between traditional categories of medical products such as
medical devices, pharmaceutical products or human tissues
- growing number of borderline and combination products
New challenges…
RE Geertsma, ACP de Bruijn, ESM Hilbers-Modderman, ML Hollestelle, G Bakker, B Roszek. New and Emerging Medical Technologies:
A horizon scan of opportunities and risks - report 65/07 RIVM, 2007.
New challenges…
� New technologies also bring new risks:
• New materials, unknown properties
• Increasingly complex – higher risk of failure
• Combination of technologies: failure to interact
• Combination of technologies: unintended interaction
• Higher risk after diffusion to less controlled environment
• Specific training for N&ET is not included in education of clinicians,
while most technologies show a clear learning curve
• Technology gap for clinicians – language problems with engineers
� New technologies are also a challenge to the regulatory system
New challenges…
New challenges…
Nanotechnologies
There is scientific uncertainty about the risks and
benefits of nanomaterials used for medical devices.
NP caracteristics:Size
Distribution
Aggregation/agglomeration
Surface area
� Conventional surgical tools (reduction of physical adhesion to tissues and
chemical inertness)
• Suture needles with steel nanocrystals (1-10 nm)
• Surgical blades with diamond nanolayers (20-40 nm)
� Dressings with silver nanoparticles
(antibacterial activity)
� Minimally Invasive Surgery/Delivery devices• Nanoneedles for surgery and cellular delivery
• Reinforced catheters with Carbon Nanotubes
� Cancer Therapy• Combining functional modalities
(Targeting, Imaging, Therapy, Monitoring)
Nanotechnologies
� Materials / implantable devices • Bone replacement materials - Orthopedic
(Hydroxyapatite nanoparticles (HA) and calcium phosphate (TCP)
• Coating of implants - Orthopedic
Nano-structures of HA for knee replacements, hip and dental
Nanocrystalline metal-ceramic coatings
• Vascular Stents coating
(Nanoporous alumina and hydroxyapatite (increasing biocompatibility))
� In vitro diagnostic• Lab-on-a-ship
(allows diagnosis of multiple parameters simultaneously)
• Early diagnostic tests
Biochips and gene chips diagnosis and detection in a very earlier phase -colon,
breast and prostate cancers
Nanotechnologies
MD Legal Framework
Publications (Nano)
• “Report on Nanotechnology to the medical devices expert group - Findings and
Recommendations”, N&ET WORKING GROUP - JULY 2007
(http://ec.europa.eu/enterprise/medical_devices/net/entr-2007-net-wg-report-nano-final.pdf)
• “Commission recommendation 2011/696/EU on the definition of nanomaterial”, 18 October
2011
• “Proposal for a Regulation of the European Parliament and the Council on medical devices” -
COM(2012) 542 final, 26.09.2012 (http://ec.europa.eu/health/medical-
devices/files/revision_docs/proposal_2012_542_en.pdf)
“…In the design and manufacture of medical devices, the
manufacturers should take special care when using
nanoparticles that can be released to the human body and
those devices should be subject to the most severe conformity
assessment procedure…”
MD Legal Framework
* Whereas 13 - Revision of the MDDs – COM Proposal (http://ec.europa.eu/health/medical-devices/files/revision_docs/proposal_2012_542_en.pdf)
ANNEX I*
GENERAL SAFETY AND PERFORMANCE REQUIREMENTS
(…)
II. Requirements regarding design and construction
7. Chemical, physical and biological properties
“…The devices shall be designed and manufactured in such a way as to reduce to a
minimum the risks linked to the size and the properties of particles used. Special care
shall be applied when devices contain or consist of nanomaterial that can be released
into the patient’s or user's body.”
* Revision of the MDDs – COM Proposal (http://ec.europa.eu/health/medical-devices/files/revision_docs/proposal_2012_542_en.pdf)
MD Legal Framework
Information on the label
“Where applicable, an indication that the device incorporates or consists of
nanomaterial unless the nanomaterial is encapsulated or bound in such a
manner that it cannot be released into the patient’s or user's body when the
device is used within its intended purpose.”
(…)
Special Classification Rule
Rule 19
– All devices incorporating or consisting of nanomaterial are in class III unless
the
– nanomaterial is encapsulated or bound in such a manner that it cannot be
release.
* Revision of the MDDs – COM Proposal (http://ec.europa.eu/health/medical-devices/files/revision_docs/proposal_2012_542_en.pdf)
MD Legal Framework
Adriana Gamboa
Health Products Directorate
Tel + 351 21 7987264
Fax + 351 21 7987281
Thank you for your attention
Mariana Madureira
Adviser to the Executive Board
Tel + 351 21 7987241