Regulation of Medical Devices Briefing - Italy
This article was originally published in SRA
Executive Summary
1) Which authority is responsible for overseeing the regulation of medical devices and diagnostics in Italy?
1) Which authority is responsible for overseeing the regulation of medical devices and diagnostics in Italy?
The Department for Innovation at the General Office for Pharmaceuticals and Medical Devices is responsible for overseeing medtech products, including IVDs.
2) Please give contact details for the authority.
The authority can be reached at the following address:
Ministry of Health,
Dipartimento dell’Innovazione,
Direzione Generale dei Farmaci e Dispositivi Medicali,
Pizzale dell’Industria 20,
0144 Rome,
Italy.
The contact persons are as follows:
For products within the scope of the Active Implantable Medical Devices Directive and the Medical Devices Directive:
Dr Giuseppe Ruocco at:
Ufficio III, Dispositivi Medici,
Via Giorgio Ribotta 5,
00144 Rome,
Italy.
Email:
Tel: +39 06 59943809.
For products within the scope of the IVD Directive:
Dr Giovana Nisticò
Ufficio IV, Diagnostici in Vitro,
Via Giorgio Ribotta 5,
00144 Rome,
Italy.
Email:
Tel: +39 06 59943508.
3) How are adverse incidents reported and tracked, and by whom, eg doctors, manufacturers, users?
The medical device directives require that manufacturers should report all serious incidents to the appropriate national Competent Authority on whose territory the incident occurred.
All three directives require that the following types of incidents and recalls be reported by the manufacturer to the Competent Authority:
- any malfunction of or deterioration in the characteristics and performance of a device, as well as any inaccuracies in the instruction leaflet, which might lead to or might have led to the death of a patient or to a deterioration in health;
- any technical or medical reason due to a risk of serious injury or death resulting in the recall of a device from the market by the manufacturer or the issue of an advisory notice.
New European Commission vigilance guidelines on the medical devices vigilance system, known as the “Vigilance Meddev” have been adopted to encourage all EU countries to fall more closely into line in future in the area of vigilance.
These updated guidelines, Meddev 2.12-1 rev 5, April 2007, entered into force on 1 January 2008. They are a revision of the earlier document published in April 2001 and are available on the European Commission’s medical device website at http://ec.europa.eu/enterprise/medical_devices/ meddev/2_12_1-rev_5-2007-fin2.pdf
4) Which Italian authority has the power to take defective products off the market?
The medical device directorate general within the Italian Health Ministry works together with the Istituto Superiore di Sanità, the superior health institute, which is the leading technical and scientific public body of the Italian national health service, on market surveillance and control.
5) To whom must adverse incidents be reported?
Adverse incidents occurring in Italy that involve products covered by the scope of the Active Implantable Medical Device Directive and the Medical Devices Directive should be reported to Dr Annamaria Donato. Her contact details are:
Adverse incidents concerning IVDs should be reported to Dr Giovanna Nisticò at:
The requirements to report affect all those in the system and include manufacturers and users.
6) What is the primary legal basis for medical device regulation in Italy?
The primary legal basis for medical device regulation in Italy is the EU’s medical device directives, which are part of the New Approach series of EU directives and are not as prescriptive as EU legislation for pharmaceuticals.
There are three main medical device directives: the Active Implantable Medical Devices Directive (Directive 90/385/EEC - OJ L189/ 20.7.90) and the Medical Devices Directive (Directive 93/42/EEC - OJ 169/ 12.7.93) and their revision, Directive 2007/47EC (see point 9); and the In Vitro Diagnostics Directive (Directive 98/79/EC - OJ331/ 7.12.98).
7) Is there any other EU legislation that impacts medtech products in Italy?
There is a series of six implementing legislations concerning: the Reclassification of Breast Implants (Directive 2003/12/EC - OJ L028/ 4.02.2003); Common Technical Specification on IVDs (Commission Decision 2002/364/EC - OJ L131/ 16.05.2002); Medical Devices Manufactured Utilising Tissues of Animal Origin (Directive 2003/32/EC - OJ L105/18- 26/04/2003); Medical Devices Incorporating Stable Derivates of Human Blood or Human Plasma (Directive 2000/70/EC - OJ L 313/22, 13/12/2000); Concerning Medical devices amending Commission Decision 93/42/EEC (Directive 2001/104/EC - OJ L 6/50, 10/01/2002); and the Reclassification of Hip, Knee and Shoulder Joint Replacements (Directive 2005/50/EC - OJ L 210/41, 12/08/2005).
8) What are the Italian legal instruments that transpose these Directives?
The Italian decree of 24 February 1997 n 46 transposes the Medical Devices Directive, the decree of 14 December 1992, n 507 transposes the Active Implantable Medical Device Directive and decree No 332/2000 transposes the In Vitro Diagnostics Medical Devices Directive.
9) Are any changes imminent to the Italian law?
A review of the Medical Devices Directive and the Active Implantable Medical Devices was adopted by the European Council and Parliament in September 2007 and published in the Official Journal of the European Union on 21 September 2007.
Italy, as with all other EU member states, had until 21 December 2008 to transpose the revised Directives into its national law, and has until 21 March 2010 to ensure that its measures are implemented nationally.
Other changes are dealt with in point 13.
10) Are any other bodies involved in assessing the safety of medical devices in Italy?
While the Competent Authority, the Department for Innovation at the General Office for Pharmaceuticals and Medical Devices, is responsible for overseeing the market, under the EU Directives, the Notified Bodies audit the products or manufacturing procedures against the requirements of the directives. These are third-party certification bodies, which are independent of the regulatory authority, or at least of the statutory regulatory department.
In Italy, there are 10 Notified Bodies under the Medical Devices Directive, one under the Active Implantable Medical Device Directive and none under the IVD Directive.
11) Where are the Italian notified bodies based and what products do they audit?
The AIMD Directive
Under the AIMD Directive, there is only one Notified Body, the Istituto Superiore di Sanità. The ISS is notified to test all AIMDs to Annexes, II, III, IV and V of the AIMD Directive. It is based at the following address:
Istituto Superiore di Sanità
Notified Body number 0373
Viale Regina Elena, 299,
00161 Rome
Italy
Tel: +39/649901
The Medical Devices Directive
The ISS is also notified to test all products covered under the scope of the MDD to Annexes II-VI of the Medical Devices Directive.
The other nine notified bodies in Italy which are notified to test products under the Medical Devices Directive, are as follows:
IMQ, Istituto Italiano del Marchio di Qualità Spa
Notified Body number 0051
Via Quintiliano, 43,
20138 – Milan,
Italy,
Phone: +39 02 50731.
Fax: +39 02 50991500.
Email:
Website: www.imq.it
IRCM Istituto di Ricerche e Collaudi Masini srl
Notified Body number 0068
Via Moscova, 11,
20017 - Rho (MI),
Italy
Tel: +39 02 9301517
Email :
Website: www.istitutomasini.it
CPM – Istituto Ricerche Prove ed Analisi srl
Notified Body number 0398
Via Artigiani, 63
25040 - Bienno (BS)
Italy
Phone: +39 0364 300342
Email:
Website: www.cpmapave.it
ICIM – Istituto di Certificazione Industriale per la Meccanica Spa
Notified Body number 0425
Piazza A. Diaz, 2
20123 – Milan,
Italy
Tel: +39 02 725341
Email:
Website: www.icim.it
Consorzio Italcert
Notified Body number 0426
Viale Sarca, 336,
20126 – Milan,
Italy
Tel: +39 02 66104876
Email :
Cermet
Notified Body number 0476
Via Cadriano, 23,
40057 - Cadriano-Granarolo Emilia (BO),
Italy
Tel: +39 051 764811
Fax: +39 051 763382
Email:
Website: www.cermet.it
Biolab Spa – Centro di Analisi e Ricerche Biologiche
Notified Body number 0477
Via Bruno Buozzi, 2,
20090 Vimodrome,
Italy.
Tel: +39 02 2507151
Istituto di Certificazione della Qualità
Notified Body number 0546
Via G Giardino, 4,
20123 – Milan,
Italy
Tel: +39 02 8069171
Email:
Website: www.certiquality.it
TUV Rheinland Italia srl
Notified Body number 1936
Via Mattei, 10
20010 - Pogliano Milanese (MI)
Italy
Tel: +39 02 9396871
Email:
Website: www.tuvitalia.com
There are no Italian bodies notified to test under the IVD Directive.
Some of the Italian bodies notified under the MDD are notified to test a very wide range of products against all possible annexes, while for others the scope of their notification is much more narrow. The exact types of products that these bodies audit and the method of audit that they provide are listed in the European Commission’s “Nando” website at: http://ec.europa.eu/enterprise/newapproach/nando/
12) Who oversees the Italian Notified Bodies?
The Competent Authority, the Department for Innovation at the General Office for Pharmaceuticals and Medical Devices, is responsible for overseeing the notified bodies, although the notifying authority, which designates the Italian notified bodies, is the Industry Ministry’s Directorate General for Development and Competiveness.
13) What is the legal basis in Italy for the regulation of medtech products on the borderline with pharmaceuticals and of combinations of medical devices and pharmaceutical products?
Once again, the legal basis resides in EU legislation. If the product administers a medicinal product within the meaning of Council Directive 2001/83/EC, medicinal products, then the device part must meet the requirements of device legislation and the medicinal part will be governed by Directive 2001/83/EC.
Where the device and medicinal product form a single integral unit, intended exclusively for use in the given combination and which is not reusable, then that single-unit product is governed by Directive 2001/83/EC.
But where a device incorporates substances which, if used separately, may be considered to be a medicinal substance within the meaning of Directive 2001/83/EC; if the substances incorporated in the medical devices are liable to act upon the body with action ancillary to that of the device, the placing of the devices on the market is governed by the Medical Devices Directive but the safety, quality and usefulness of the substances must be verified by analogy with the appropriate methods specified in Council Directive 75/318/EEC of 20 May 1975 on the approximation of the laws of the Member States relating to analytical, pharmaco-toxicological and clinical standards and protocols in respect of the testing of proprietary medicinal products.
14) Do companies need to register in Italy prior to marketing?
The are complex and controversial registration requirements in Italy, against which a complaint was filed at the European Commission in April 2008. The Ministry of Health has been creating a database for information on new medical devices and those already on the Italian market for purchasing, vigilance and post-market surveillance purposes.
There is a requirement for all those responsible for placing medical devices onto the Italian market to notify electronically information on their products through the Health Ministry website: www.ministerosalute.it.
Upon notification, which is charged for, the Italian Health Ministry provides the manufacturer, authorised representative, or other party responsible for placing the product on the market with an identification number.
The database is divided up into 22 principal categories and 144 subcategories, closely aligned with the Global Medical Device Nomenclature (DMDN).
The notifications to the Health Ministry must include the following:
- general information on the medical device, including details such as identification code, brand name and model;
- medical device classification details, including risk class, and the Italian and GMDN classifications codes;
- information relating to the CE-marking certificate such as the number, expiry date and notified body used;
- technical information, for example: sterilisation method used; types of material in the device; whether there are biological tissues or animal-derived substances and if so which; whether there are medicinal products present; and information relating to the primary packaging materials;
- technical documentation, including information on labels and instructions for use; and
- commercial and sales information, including price and volume.
Currently, these changes do not apply to in vitro diagnostic products and custom-made medical devices. However, a new system for notifying these products will be established in the near future.
15) Do manufacturers need to register low-risk medical devices in Italy prior to marketing?
Yes, as explained in 14).
16) Do manufacturers need to register high-risk medical devices in Italy prior to marketing?
Yes, as explained in 14).
17) Are there any additional forms that must be completed by medical device manufacturers in Italy?
No
18) Which laws regulate clinical trials in Italy?
The requirements regulating clinical trials in Italy are contained in a variety of laws in Italy, including the following laws: No 507/92 for active implantables and No 46/97 for medical devices. They are also contained in the ministerial decree of 2 August 2005 which explains the ways of fulfilling documentation requirements for clinical trials. Post-market trial requirements are dealt with in the ministerial note of 26 February 2007; and there is also an explanatory ministerial note of 5 December 2007. More information is available at: www.ministerosalute.it/dispositive/paginainterna.jsp?id=248menu=sperimentazione
19) What procedures must be followed in Italy by sponsors wishing to carry out clinical trials?
Under the EU medical device directives, the manufacturer, or Authorised Representative, must notify the Competent Authorities of the Member States in which the clinical trials are to be conducted and also obtain a favourable opinion from the relevant Ethics Committee.
In the case of devices falling within Class III and implantable and long-term invasive devices falling within Class IIa or IIb, the manufacturer may commence the relevant clinical investigation at the end of a period of 60 days after notification, unless the Competent Authority has notified the manufacturer within that period of a decision to the contrary based on considerations of public health or public policy.
Notification is required for all clinical trials and the application to the Competent Authority (CA) must be in Italian. Notification must be made to the Ethics Committee and then to the CA on a specific notification form. There is a 60-day waiting period before the clinical investigation can commence once notification has been given to the CA. The 60-day waiting period is mandatory but if CA notification has been given and the EC approval occurs within the 60-day period the investigation can commence immediately.
Ethics Committee approval is applicable to all clinical trials in Italy. Submission to the Ethics Committee of the hospital where the investigation is to take place must be made and when it is a multi-centre trial one submission must be made per site. The submission will take approximately one month to process.
20) Can you be more specific about how this works in practice in Italy?
With regards to clinical investigation documentation, all information dedicated to the patient, specific instructions for use, patient informed consent etc, should be translated into Italian. In addition, instructions for use for people outside the immediate investigation team, for example instructions for sterilising and cleaning equipment, should also be translated. For CE-marked devices, the user has to be provided with a translation of the instructions for use in Italian.
A notification is required for any studies of CE-marked devices that have undergone substantial changes or that will be studied for a new indication or intended use. In this case, the notification procedure is the same as that for non-CE-marked medical devices. However, in some cases a notification is required even for CE-marked devices being studied with the same intended use for which they were CE-marked.
It is easier to conduct clinical investigations in public hospitals in Italy, but it is possible to conduct them in private hospitals as long as they have Competent Authority approval. Also they must follow Italy’s good clinical practice laws.
If the study is conducted in public hospitals, which are part of the National Health System, no notification is needed. However, if the study is conducted in private centres or clinics, the conduct of the study must be authorised by the Ministry of Health and a notification needs to be filed. The accreditation of private centres with the National Health Service is not sufficient for performing clinical investigations without the formal, written authorization from the Ministry of Health.
This authorisation must be requested for each clinical study; it needs to be in Italian, and must be submitted to the MoH along with all the necessary documentation, including a favourable opinion of the Ethics Committee and payment of some €1,900 The timeframe for MoH review of the dossiers is 90 days.
Specific insurance is required by law in Italy to cover the sponsor of clinical trials and it provides cover for two years after the termination of the trial.
21) What are the requirements concerning the reporting of adverse incidents during a clinical trial?
All adverse incidents must be fully recorded and notified to the Competent Authority, as is stated in the medical device directives.
22) How are products regulated in Italy which are a combination of medical devices and advanced therapy medicinal products or are devices which contain non-viable human tissues?
The text of the Advanced Therapy Medicinal Products Regulation, which regulates healthcare products containing human tissues or cells where the cells or tissues are viable and their action is primary, as well as gene and somatic cell therapy, was published in the Official Journal of the European Union on 13 November 2007 and came into force on 30 December 2008. This text essentially covers products that meet the definition of a medicinal product, but many are used in combination with medical devices.
For combination products, manufacturers will have to ensure that their products are in compliance with the medical device regulations and the ATMP regulations, with the same type of rules applying as to which requirements take precedence, as with drug/device combinations (see point 13).
Manufacturers should also be aware that the drug authorities and European Medicines Agency (EMEA) are legally bound to examine the results of the notified body as far as an assessment of the device is concerned, and can seek a notified body assessment of the device element of the combination if one is not already available. In either case, there will be occasions when the notified body will be called upon to justify its decision in front of the drug authorities.
Manufacturers of any new ATMPs covered by the scope of the Regulation will have to meet its requirements as soon as the Regulation enters into force. But for manufacturers of tissue engineered products covered by the ATMP Regulation that are already on the market, they will have until December 2012 to obtain a new marketing licence for their products. This is one year longer than for manufacturers of cell and gene therapy products.
Since the requirements are being introduced via a Regulation, rather than a Directive as is traditional in the medical devices regulatory field, implementation will be much swifter.
Work is now ongoing at the medical devices unit of the European Commission on the future regulation of medical products containing non-viable human tissues where the action of these tissues is ancillary. It is envisaged that these products will be regulated under the medical devices regulatory regime, although with requirements that reflect the level of risk inherent in these products.
EU cell therapy requirements have so far heavily influenced the regulatory approach in many countries. These will continue to apply until the ATMP Regulation takes effect.
Other Directives that impact this area are the following:
- 2004/23/EC - Quality and safety for donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells, which was due to be transposed into member state national law by 7 April 2006;
- 2006/17/EC - Technical requirements for donation, procurement and testing of human tissues and cells, due for transposition by 1 November 2006; and
- 2006/86/EC - Traceability requirements, notification of SAEs and events and technical requirements for coding, processing, preservation, storage and distribution of human tissues and cells, which was transposed on 1 September 2007 and the coding system of which was due to be in place by 1 September 2008.
Directive 2004/23/EC will apply to final manufactured human tissue engineered products (hTEPs) until the Advanced Therapy Products Regulation takes effect. It will then still apply to hTEPs, as far as the donation, procurement and testing is concerned.
It will apply fully to the unregulated products containing non-viable human tissues and cells until further regulatory advances are made.
23) How are nanomedicine devices regulated in Italy?
These are regulated according to the EU legislation that impacts the product sector in which the product falls. So the requirements of the medical device legislation would apply to any product which fell under the scope of the definition of a medical device, and the requirements of pharma legislation to any product which fell under the scope of the definition of a pharmaceutical. The same would apply to nanotech and drug/device combination products as with any other drug/device combination products.
The European Commission issued a code of conduct to govern research in this field in February 2008 and was then working on a review of regulation relevant to nanotechnology.
24) Are there any other legal or guidance documents which impact the way medtech products are regulated or controlled in Italy?
There are many additional aids and guidance documents to regulation which are drafted at EU level. These include: EU consensus statements, drafted by the European Commission’s European Medical Device Expert Group (MDEG); European Commission guidelines relating to the medical device directives, known as meddevs; harmonised standards (which give a presumption of conformity with the essential requirements of the medical device directives to any manufacturer that has fully complied with them); and Notified Body recommendations.
All these documents can be found via the website on medical devices of the European Commission’s Directorate General Industry and Enterprise at: http://ec.europa.eu/enterprise/medical_devices/index_en.htm
These texts do not have a legal status per se, but they provide a clear expectation of what is required, and any manufacturer which did not follow this guidance may be called upon, in the case of non-compliance or an incident, to explain why they did not follow these documents.
There are also a series of documents that have been drafted and agreed by the medical device Global Harmonisation Task Force (GHTF). The GHTF aims to encourage convergence in regulatory practices related to ensuring the safety, effectiveness/performance and quality of medical devices, via the publication and dissemination of harmonised guidance documents on basic regulatory practices. These are available at: www.ghtf.org.
25) Are there any other important contact points within the Competent Authority for medical devices?
The national TSE/BSE contact point, under Article 5(4) of Commission Directive 2003/32/EC, which introduces detailed specifications as regards the requirements laid down in the MDD with respect to medical devices manufactured utilising tissues of animal origin, is Dr Giuseppe Ruocco at the address in point 2).
26) Which Italian agencies are involved in giving approval so that a medical device can benefit from reimbursement?
Since January 2006, diagnoses and procedures have been coded using the Italian version of the US 2002 ICD-9-CM DRG classification, 9th revision, which contains a total of 15,327 codes: 11,745 codes for diagnoses and 3,582 for procedures.
When it comes to the approval of a price, there are special situations where companies can achieve higher prices than are set out in the DRG payments: the regions may give higher reimbursement rates than the national ones as long as they make up the difference themselves. In 2004, 11 regions out of 21 granted extra-DRG reimbursement rates for specific procedures.
There are major problems with late payments in Italy.
27) Does the application procedure differ according to whether the product is intended for the ambulatory (out of hospital) or hospital settings?
Separately to the DRG system for hospitals, there is a specific tariff list for prosthetics and other aids, plus another tariff list that defines the reimbursable cost of outpatient, ambulatory and laboratory services, including surgery, rehabilitation and diagnostics procedures. These are also grouped according to product type.
28) How is it possible to have new medical procedures recognised for reimbursement listing?
Regions can update their DRG lists by adding new procedure codes to reflect the uptake of new technologies in their areas. To accommodate these changes, they can either increase the corresponding DRG tariff or allow extra-DRG reimbursement. In all cases, these additional costs cannot be passed on to the SSN (Servizio Sanitario Nazionale) and must be covered by the regional budget.
However, hospital reimbursement of additional tariffs is an exception and applies to some implants, with the tariffs varying according to the individual decisions taken by the Regions.
29) Are there any influential health technology assessment agencies in Italy?
Decentralisation of healthcare management in countries such as Italy and Austria mean further fragmentation at regional level, and companies must be ready to work closely with patients, doctors, hospital buyers and, where relevant, buyers in the insurance companies in each of these markets, to understand what is really needed, and then tailor their HTA and health economics data accordingly.