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Italy has
implemented the GCP Directive 2001/20/EC by the Legislative Decree
N° 211 of June 24, 2003 (G.U. N° 184 of August 9, 2003, S.O.
130/L). The Regulation came into force since 1 January 2004. All the
clinical trials are covered by the Directive, from Phase I to Phase
IV. An exemption is provided for non-interventional trials. Compliance
with the principles of GCP was already mandatory for all the clinical
trials; the new Directive confirms this point. The Ministry of Health
has issued a new programme to make more frequent the inspections of
Sponsors, clinical centres and CROs.
All the clinical trials must be authorized by the competent Ethical
Committee(s). In the case of a monocentre clinical trial, the Ethical
Committee shall have a statutory limit of 60 days from the date of
receipt of a valid application to give its reasoned opinion (this
60-day limit was only recommended formerly). Within the period of
examination, the Ethical Committee may send only one request of additional
information (there was no limit formerly). In the case of multicentre
clinical trial, the application must be presented simultaneously to
the Ethical Committees of all the concerned clinical centres. The
experimental protocol will be examined by the Ethical Committee of
the coordinator centre (First EC) within 30 days since the date of
the application. An extension to the time limits for examination is
allowed only for the First EC (formerly, the application was presented
to the EC of the coordinating centre and, then, to each additional
centre). The Ethical Committee will examine the relevance and importance
of the clinical trial, the balance between risks and benefits for
the patient, the protocol, the suitability of the investigator and
his co-workers, the suitability of the clinical centre, the investigator
brochure, the cost of the clinical trials, etc.
The Legislative Decree N° 211/2003 (GCP Directive) has definitively abrogated the so-called "Giudizio di Notorietà", i.e. the examination by the central Istituto Superiore di Sanità or, alternatively, the possibility of the Ethical Committee to exempt a drug from the safety evaluation by the I.S.S. This examination was formerly mandatory for all products.
Now, a central authorization by the Istituto Superiore di Sanità (I.S.S.) and Ministry of Health is needed for Phase I clinical trials on new chemical entities, as well as for products aimed to genetic and somatic cells therapy (D.P.R. 439 of September 21, 2001; D.M. of March 18, 1998; D.M. of March 2, 2004), and drugs containing GMO.
The authorization concerns mostly the safety of use of the product with refer to the proposed indication and doses, while the experimental clinical protocol is authorized by the Ethical Committee(s) of the clinical centre(s) involved in the trial.
The ISS is required to communicate the receipt of the application within 5 days, while the Commission is required to decide within 60 days. The Commission may require further documentation or may invite the Company to an audit; in such a case, the 60-day limit is suspended. Amendments to the proposed clinical experimental protocol may be applied after the authorization; the time limit for examination is 30 days.
The authorization is released directly by the Ethical Committee for Phase II to Phase IV clinical trials with all the other products.
According to the national data protection legislation all personal
data will be handled with strictest confidence following the provisions
of the respective Italian law. "Articolo 13 del Decreto Legislativo
30 giugno 2003, n. 196" ("Codice in materia di protezione dei dati
individuali")"
The application of GMP to clinical trial supplies is now on a statutory basis.
Persons intending to manufacture, assemble and/or import IMPs are now required to hold a specific authorization of the Ministry of Health.
The holder of the authorisation is legally obliged to comply with the principles and guidelines of good manufacturing practice (GMP). Batches require release by a qualified person. GMP inspections are conducted.
The GCP Directive 2001/20/EC will be fully implemented by a series
of specific decrees of the Ministry of Health on each different topic
(format of application, documents to be present for IMP import, etc).
TRANSITORY NORM. While waiting for coming decrees that will fully implement the Directive, the Ministry of Health suggested with a Circular Letter of December 4, 2003 to apply for clinical trials authorization by making reference to the previous norms for all the points that are not specified in the Directive (Letter N° 800.II/S.AA.GG.40/9940).
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ITALY
Regulatory and Ethical Procedures
