IL RUOLO DELL’ISTITUTO SUPERIORE DI SANITA’ COME ORGANO TECNICO: IL CONTRIBUTO DEL DIPARTIMENTO DI MALATTIE INFETTIVE, PARASSITARIE, ED IMMUNOMEDIATE.

IL RUOLO DELL’ISTITUTO SUPERIORE DI SANITA’ COME ORGANO TECNICO: IL CONTRIBUTO DEL DIPARTIMENTO DI MALATTIE INFETTIVE, PARASSITARIE, ED IMMUNOMEDIATE Dr. Maria Rapicetta Dirigente di ricerca – DIRETTORE DEL REPARTO EPATITI VIRALI DIP. MIPI 1° CORSO DI AGGIORNAMENTO SUI DISPOSITIVI MEDICI: ASPETTI REGOLATORI E APPLICATIVI ROMA, MAGGIO 2009 ISTITUTO SUPERIORE DI SANITA’ Department of Infectious, Parasitic and Immunomediated Diseases

RIFERIMENTI NORMATIVI
DPR 13/3/1986, n. 128 – Regolamento di esecuzione delle norme di cui all’art.189 del testo unico delle leggi sanitarie, approvato con regio decreto 24/7/1934, n. 1265, e successive modificazioni, in materia di produzione e commercio dei presidi medico-chirurgici. G.U. Serie Gen. n. 98 del 29/4/1986. DM 3/3/1987, n Assoggettamento alla disciplina dei presidi medico-chirurgici dei Kit per la rilevazione di anticorpi anti HIV. G.U. Serie Gen. n. 80 del 6/4/1987. DM 12/12/ Assoggettamento dei reagenti per il rivelamento di HBsAg ed anti HCV alla disciplina dei presidi medico-chirurgici. G.U. Serie Gen. n. 41 del 19/2/1992. DPR 6/10/1998, n Regolamento recante norme per la semplificazione dei procedimenti di autorizzazione alla produzione ed all’immissione in commercio di presidi medico-chirurgici, a norma dell’art. 20, comma 8, della legge 15/3/1997 n. 59. G.U. Serie Gen. n. 266 del 13/11/1998. Provvedimento ministeriale 5/2/1999 – Approvazione dei requisiti della domanda e relativa documentazione da presentare ai fini dell’autorizzazione all’immissione in commercio ed alla variazione di autorizzazioni già concesse per i presidi medico-chirurgici. G.U. Serie Gen. n. 34 del 11/2/1999. Circolare ministeriale 30/10/2000, n. 17 – Adeguamento dei livelli di sicurezza trasfusionale in presenza di metodiche atte alle indagini sui costituenti virali per HCV. G.U. Serie Gen. n. 258 del 4/11/2000. Circolare ministeriale 19/12/2001, n. 14 – Indicazioni integrative alla Circolare 30/10/2000 n. 17, recante: “Adeguamento dei livelli di sicurezza trasfusionale in presenza di metodiche atte alle indagini sui costituenti virali per HCV”. G.U. Serie Gen. n. 300 del 28/12/2001. DL 9/5/2003, n Disposizioni urgenti relative alla sindrome respiratoria acuta severa (SARS). G.U. Serie Gen. n. 108 del 12/5/2003. Direttiva 98/79/CE del Parlamento Europeo e del Consiglio del 27/10/1998 relativa ai dispositivi medico-diagnostici in vitro. G.U. C.E. n. L.331 del 7/12/1998. DL 8/9/2000, n. 332 – Attuazione della Dir. 98/79/CE relativa ai dispositivi medico-diagnostici in vitro. G.U. Serie Gen. n. 269 del 17/11/2000. ISTITUTO SUPERIORE DI SANITA’ Department of Infectious, Parasitic and Immunomediated Diseases

NATIONAL CONTROLS OF HIV AN HEPATITIS TEST KITS IN EC MEMBER STATES*
National control authority licensing control and/or evaluation National control authority batch release Monitoring of kits in use and other evaluation systems None Austria Belgium Denmark Finland France Germany Greece Ireland Italy Luxembourg Netherlands Portugal Spain Sweden UK X ISTITUTO SUPERIORE DI SANITA’ Department of Infectious, Parasitic and Immunomediated Diseases * from CPMP Biotechnology working group

ATTIVITA’ DI CONTROLLO E CONSULENZA DEL DIPARTIMENTO MIPI DELL’ISS NEL SETTORE DEI KIT DIAGNOSTICI IN VITRO ● Controllo di kit di tipo immunometrico per determinazioni qualitative e quantitative di marcatori di infezioni ● Controllo e validazione di kit per determinazione qualitativa e quantitativa di acidi nucleici (NAT) quali marcatori di infezioni ● Controlli di kit diagnostici post-marketing su segnalazione ● Allestimento di pannelli sierici e Preparazioni Standard per controlli interni di qualità ● Attuazione di programmi nazionali di valutazione esterna di qualità (VEQ) per laboratori del SSN ● Partecipazione a commissioni EU ed a Comitati Tecnici associati alla Direttiva 98/79/CE ● Organizzazione di convegni sulle specifiche tematiche rivolti a personale tecnico del SSN ISTITUTO SUPERIORE DI SANITA’ Department of Infectious, Parasitic and Immunomediated Diseases

SISTEMA DI GESTIONE DELL’AUTORIZZAZIONE (SGA)
Gruppo di lavoro CdG/DMDV - Direttiva 98/79/CE (7 dicembre 1998) SISTEMA DI GESTIONE DELL’AUTORIZZAZIONE (SGA) Il sistema è articolato in modo da definire, per le varie fasi delle attività: Politica e conduzione della certificazione; Organizzazione tecnica, amministrativa e delle risorse umane; Pianificazione delle attività interessate, ivi comprese l’assegnazione delle risorse e la documentazione; Misura delle prestazioni conseguite con l’adozione del sistema, ivi incluse le verifiche ispettive (audit); Verifica e riesame del sistema. La struttura generale dell’ SGA risponde allo stato dell’arte in materia ed è schematizzabile nel seguente modello logico: Politica per la Certificazione di dispositivi medico-diagnostici in vitro Verifica delle soluzioni adottate Miglioramento continuo Pianificazione delle attività Controlli e azioni correttive Attuazione dell’ SGA ISTITUTO SUPERIORE DI SANITA’ Department of Infectious, Parasitic and Immunomediated Diseases

ARTICOLAZIONE DEL SISTEMA DI GESTIONE DELL’AUTORIZZAZIONE
Gruppo di lavoro CdG/DMDV - Direttiva 98/79/CE (7 dicembre 1998) ARTICOLAZIONE DEL SISTEMA DI GESTIONE DELL’AUTORIZZAZIONE L’ SGA è articolato nelle seguenti Sezioni e Sottosezioni: Rif. SEZIONI Cod. SOTTOSEZIONI 1. Politica dell’Istituto 1.1 Politica per la certificazione 1.2 Piano di attuazione della politica 2. Controllo dell’organizzazione 2.1 Organizzazione 2.2 Personale 3. Controllo delle valutazioni di conformità 3.1 Richiesta di valutazione 3.2 Preparazione della valutazione 3.3 Conduzione della valutazione 3.4 Rapporto sulla valutazione 3.5 Modifiche ai requisiti della valutazione 3.6 Sorveglianza e rinnovo della certificazione 4. Controllo delle prestazioni 4.1 Analisi e valutazione delle non conformità 4.2 Verifiche ispettive interne 4.3 Reclami 5. Revisione del sistema 5.1 Misura delle prestazioni del sistema 5.2 Riesame del sistema ISTITUTO SUPERIORE DI SANITA’ Department of Infectious, Parasitic and Immunomediated Diseases

Direttiva 98/79/CE (7 dicembre 1998)
ORGANIGRAMMA NOMINATIVO DEI RESPONSABILI DEL COMITATO DI GESTIONE DEI DMDV (CdG/DMDV - Dipartimento Malattie Infettive, Parassitarie ed Immunomediate - MIPI) Direttiva 98/79/CE (7 dicembre 1998) ISTITUTO SUPERIORE DI SANITA’ Department of Infectious, Parasitic and Immunomediated Diseases

PROCEDURES FOR DIAGNOSTIC KITS CONTROL IN ITALY
(Decrees: 3 March 1987 (anti-HIV), 12 December 1991 (HBsAg, Anti-HCV) Licensing after the evaluations of technical documentation and of sample kit by the Istituto Superiore di Sanità and by the Ministry of Health* Batch release procedure by the Istituto Superiore di Sanità External quality control (NEQAS) by the Istituto Superiore di Sanità * Any variation of components, expire date and production procedure must be authorised ISTITUTO SUPERIORE DI SANITA’ Department of Infectious, Parasitic and Immunomediated Diseases

REQUIREMENTS FOR TECHNICAL DOCUMENTATION
THE TECHNICAL DOCUMENTATION PROVIDED BY THE MANUFACTURERS MUST BE BASED, FOR LICENSING PROCEDURE ON: biological principles of methodology production methods & characterization of each reagent type of reagents and their shelf life including their assessment description of testing procedures adapted procedures for result assessment sensitivity, specificity and accuracy (with description of the assessment methods) information sheet, also in Italian, as an integral part of the kit, reporting the elements listed above, handling precautions and limitation on the physical, biological and clinical aspects, and the list of necessary but not provided materials FOR BATCH RELEASE PROCEDURE, ON: series number of the batch and of the individuals components expire date of the batch and the individual reagents (which must comply with the registration documentation) the number of kits in the batch quality control certificate and quality control assays performed by the manufacturer ISTITUTO SUPERIORE DI SANITA’ Department of Infectious, Parasitic and Immunomediated Diseases

ANTI-HIV TESTING KITS (VEQ 2004)
Tradename Brand Screening tests Method Manufacturer AXSYM HIV 1/2 gO EIA VIDAS HIV DUO HIV COMBI EIA COBAS CORE VITROS ANTI HIV 1+2 ENZYGNOST ANTI HIV 1/2 PLUS ORTHO HIV-1/HIV-2 Ab CAPTURE ELISA TEST BIOTEST ANTI-HIV TETRA ELISA GENSCREEN HIV 1/2 versione 2 VIRONOSTIKA HIV UNI-FORM II PLUS O ImX HIV-1/HIV-2 III PLUS ACCESS HIV-1/2 NEW ENZYGNOST HIV Integral MUREX HIV- 1.2.O COBAS CORE ANTI HIV 1-2-O EIA ABBOTT HIV 1/2 gO EIA MEIA 3 Gen ELFA (FluorescenzaI Indirect sandwich 4 Gen ECLIA (ElettroChemiLunescenza) sandwich 4 Gen Immunometric luminescence 3 Gen ELISA 3 Gen ELISA (sandwich) 3 Gen ChLIA (Immunometrico Chemioluminescenza) ELISA (sandwich) 4 Gen ABBOTT BIOMERIEUX ROCHE ORTHO DADE BEHRING BIOTEST BIO-RAD ORGANON ISTITUTO SUPERIORE DI SANITA’ Department of Infectious, Parasitic and Immunomediated Diseases

ANTI-HCV and HBsAg TESTING KITS (VEQ 2004)
Tradename Brand Screening tests Method Manufacturer AXSYM HCV COBAS CORE ANTI-HCV EIAS ORTHO HCV 3.0 ELISA Test System with Enhanced SAVe VITROS HCV ARCHITECT ANTI HCV IMX HCV v.3.0 INNO-TEST HCV Ab IV ABBOTT HCV EIA 3.0 MONOLISA ANTI-HCV PLUS ACCESS HCV PLUS AXSYM HBsAg V. 2 COBAS CORE HBsAg EIA II VIDAS HBsAg VITROS HBsAg ARCHITECT HBsAg ELECSYS HBsAg ETI MAK 4 ORTHO ANTIBODY TO HBsAg ELUSA TEST SYSTEM 3 ENZYGNOST HBsAg 5.0 IMX HBsAg HEPANOSTIKA HBsAg UNIFORM II SUPERMIK HBsAg MONOLISA Ag HBs PLUS ACCESS HBsAg MEIA ELISA (indirectI ELISA Immunometric luminescence CMIA ELISA (indirect) Enzyme Immunoassay (chemiluminescence) MEIA 3 Gen ELISA sandwich ELFA (Enzyme Linked Fluorescent assay) CMIA (chemiluminescent microparticle immunoassay) ECLIA (ElettroChemiLuminescenza) ELISA direct sandwich ELISA 3 Gen ABBOTT ROCHE ORTHO INNOGENETICS BIO-RAD BIOMERIEUX DIASORIN DADE BEHRING ORGANON MED. SYSTEM ISTITUTO SUPERIORE DI SANITA’ Department of Infectious, Parasitic and Immunomediated Diseases

HIV, HBV, HCV CONFIRMATORY TESTS
HIV, HBV, HCV NAT TESTS Tradename Brand Screening tests Manufacturer COBAS AMPLISCREEN HCV TEST v. 2.0 COBAS AMPLISCREEN HIV-1 TEST v. 1.5 COBAS AMPLISCREEN HBV TEST PROCLEIX HIV-1/HCV PROCLEIX ULTRIO ASSAY HIV, HBV, HCV CONFIRMATORY TESTS CHIRON RIBA HCV 3.0 SIA INNO-LIA HCV Ab III UPDATE DECISCAN HCV PLUS HIV BLOT 2.2 NEW LAV BLOT I Ac Ab Ak CHIRON RIBA HIV-1/HIV-2 SIA INNO-LIA HIV K1036 IT INNOLIA HIV CONFIRMATION BIOBLOT HIV-1 PLUS ELECSYS HBsAG CONFIRMATORY COBAS CORE HBsAg II CONFIRMATORY EIA ROCHE CHIRON INNOGENETICS SANOFI-PASTEUR ALFA BIOTECH BIO-RAD ORTHO ONNOGENETICS INSTRUMENTATION LAB. ISTITUTO SUPERIORE DI SANITA’ Department of Infectious, Parasitic and Immunomediated Diseases

DISTRIBUZIONE CENTRI PARTECIPANTI NEL 1994 E NEL 2003
ISTITUTO SUPERIORE DI SANITA’ Department of Infectious, Parasitic and Immunomediated Diseases

TIPOLOGIA DEI CAMPIONI POSITIVI INVIATI

DISTRIBUZIONE GEOGRAFICA E PERCENTUALE DI COPERTURA DEI CENTRI PARTECIPANTI

CHARACTERISTICS OF POSITIVE SAMPLES OF EACH SHIPMENT PANEL, BY YEAR

ISTITUTO SUPERIORE DI SANITA’ Department of Infectious,
Parasitic and Immunomediated Diseases

EU IVD DIRECTIVE Directive 98/79/EC of the European Parliament and of the Council on in vitro Diagnostic Medical Devices - adopted on 5 October published in Official Journal of EU Committees on 7 December published in Italian GU n. 269 on 17 November 2000 ■ has introduced at EU level common regulatory requirements for safety quality and performance of IVDs ■ applies to: reagents and reagent products, calibrator materials or instruments including specimen receptacles intended by the manufacturer for the in vitro examination of human tissue, blood or fluid samples for the purpose of providing information about a patient’s state of health ISTITUTO SUPERIORE DI SANITA’ Department of Infectious, Parasitic and Immunomediated Diseases

Directive 98/79/CE (7 December 1998) ANNEX I ESSENTIAL REQUIREMENTS
The manufacturer has to demonstrate that the in vitro diagnostic medical devices: ■ do not compromise the health and safety of patients and users ■ are designed and manufactured to be suitable for the stated medical purpose, taking into account of the generally acknowledged state of the art ■ are able to achieve the performance, where appropriate, in terms of: analytical sensitivity, diagnostic sensitivity, analytical specificity, diagnostic specificity, accuracy, repeatability, reproducibility, including control of known relevant interferences, and limits of detection. ■ possess the elements of traceability, i.e.: a - The values assigned to calibrators and/or control materials, are assured through available reference measurement procedures and/or available reference materials of a higher order. b - are designed, manufactured and packed in such a way that their characteristics and performances during their intended use will not be adversely affected under storage and transport conditions c - labeling information and instructions for use, both for devices intended for professional use and for self-tests are addressed to lay persons. ■ Is characterized by risk analysis including the identification and demonstration of acceptability of risks related with their use. ISTITUTO SUPERIORE DI SANITA’ Department of Infectious, Parasitic and Immunomediated Diseases

Directive 98/79/CE (7 December 1998) CLASSIFICATION OF IVDS INTO CATEGORIES
1 - Devices listed in Annex II-List A Reagents and reagent products for detection of infections by HIV 1 and 2, HTLV-I and II or by hepatitis B, C and D viruses. Reagents for determination of ABO system, Rhesus-C, c, D, E, e, anti-Kell Devices listed in Annex II-List B Reagents and reagent products for determination of anti-Duffy, anti-Kidd, irregular anti- erythrocytic antibodies, tumor marker PSA, HLA tissue groups DR, A, B, detection of phenylketonuria, detection of the infectious diseases: rubella, toxoplasmosis, cytomegalovirus and chlamydia, detection of trisomy 21. Self-testing devices for the measurement of blood glucose Devices for self-testing All other devices not listed in Annex II and not intended for self-testing ISTITUTO SUPERIORE DI SANITA’ Department of Infectious, Parasitic and Immunomediated Diseases

Document GHTF/SG1/N045: 2008 PROPOSED GENERAL CLASSIFICATION SYSTEM FOR IVD MEDICAL DEVICES

Directive 98/79/CE (7 December 1998) CONFORMITY ASSESSMENT ROUTES FOR IN VITRO DIAGNOSTIC MEDICAL DEVICES LISTED IN ANNEX II-LIST-A ISTITUTO SUPERIORE DI SANITA’ Department of Infectious, Parasitic and Immunomediated Diseases

Directive 98/79/CE (7 December 1998) CONFORMITY ASSESSMENT ROUTES FOR IN VITRO DIAGNOSTIC MEDICAL DEVICES LISTED IN ANNEX II-LIST-B ISTITUTO SUPERIORE DI SANITA’ Department of Infectious, Parasitic and Immunomediated Diseases

Directive 98/79/CE (7 December 1998) CONFORMITY ASSESSMENT ROUTES FOR IN VITRO DIAGNOSTIC MEDICAL DEVICES TO BE USED FOR SELF-TESTING ISTITUTO SUPERIORE DI SANITA’ Department of Infectious, Parasitic and Immunomediated Diseases

Directive 98/79/CE (7 December 1998) CONFORMITY ASSESSMENT ROUTE FOR GENERAL IN VITRO DIAGNOSTIC MEDICAL DEVICES ISTITUTO SUPERIORE DI SANITA’ Department of Infectious, Parasitic and Immunomediated Diseases

Document GHTF/SG1/N045: CONCEPTUAL ILLUSTRATION OF REGULATORY REQUIREMENTS INCREASING WITH DEVICE RISK CLASS ISTITUTO SUPERIORE DI SANITA’ Department of Infectious, Parasitic and Immunomediated Diseases

COMMON TECHNICAL SPECIFICATIONS (CTS) 2009/108/EC amending 2002/364/EC SCREENING ASSAYS: ANTI-HIV 1 AND 2, ANTI-HTLV I AND II, ANTI-HCV, HBSAG, ANTI-HBC ISTITUTO SUPERIORE DI SANITA’ Department of Infectious, Parasitic and Immunomediated Diseases

COMMON TECHNICAL SPECIFICATIONS (CTS) 2009/108/EC amending 2002/364/EC NAT ASSAYS FOR HIV 1, HCV, HBV, HTLV I/II (QUALITATIVE AND QUANTITATIVE; NOT MOLECULAR TYPING) 1 ISTITUTO SUPERIORE DI SANITA’ Department of Infectious, Parasitic and Immunomediated Diseases

COMMON TECHNICAL SPECIFICATIONS (CTS) 2009/108/EC amending 2002/364/EC

COMMON TECHNICAL SPECIFICATIONS (CTS) 2009/108/EC amending 2002/364/EC
For quantitative NATs a study shall be performed on at least 100 positive specimens reflecting the routine conditions of users (e.g. no pre-selection of specimens). Comparative results with another NAT test system shall be generated in parallel. For qualitative NATs a study on diagnostic sensitivity shall be performed using at least 10 seroconversion panels. Comparative results with another NAT test system shall be generated in parallel. ISTITUTO SUPERIORE DI SANITA’ Department of Infectious, Parasitic and Immunomediated Diseases

COMMON TECHNICAL SPECIFICATIONS (CTS) 2009/108/EC amending 2002/364/EC RAPID TESTS: ANTI- HIV 1 AND 2, ANTI-HCV, HBSAG, ANTI-HBC, ANTI-HTLV I AND II ISTITUTO SUPERIORE DI SANITA’ Department of Infectious, Parasitic and Immunomediated Diseases

SEROTYPING AND GENOTYPING ASSAY: HCV
COMMON TECHNICAL SPECIFICATIONS (CTS) 2009/108/EC amending 2002/364/EC HIV 1 ANTIGEN SEROTYPING AND GENOTYPING ASSAY: HCV ISTITUTO SUPERIORE DI SANITA’ Department of Infectious, Parasitic and Immunomediated Diseases

DEFINITION OF THE “STATE OF ART” FOR HIV DETECTION DEVICES INCLUDING HIV AG/AB COMBINATION ASSAYS, ANTI-HIV-1/2 ASSAYS AND HIV RAPID TESTS Common Technical Specifications (CTS, 3 February 2009 amending Decision 2002/364/EC) “diagnostic tests sensitivity during the early infection phase (sero-conversion) has to represent the state of art”. Furthermore, two categories of samples are defined: Early sero-conversion HIV samples: p24 antigen and/or HIV RNA positive and; not recognised by all of the antibody screening tests and; indeterminate or negative confirmatory assays Sero-conversion HIV: p24 antigen and/or HIV RNA positive and; recognised by all of the antibody screening tests and; positive or indeterminate confirmatory assays HIV tests shall identify all sero-conversion HIV samples as positive; and at least 40 early sero-conversion HIV samples shall be tested. Results should conform to the state of the art. ISTITUTO SUPERIORE DI SANITA’ Department of Infectious, Parasitic and Immunomediated Diseases

SERO-CONVERSION PANELS USED

DETECTION DELAY IN RECOGNITION OF HIV INFECTION RELATIVE TO NAT (DAYS)

DETECTION DELAY OF HCV INFECTION (DAYS)

DETECTION DELAY OF HBSAG INFECTION (DAYS)

SUMMARY RESULTS OF THE SERO-CONVERSION STUDY HIV 1/2, Ab TEST KIT

ISTITUTO SUPERIORE DI SANITA’ Department of Infectious,
Parasitic and Immunomediated Diseases

Directive 98/79/CE (7 December 1998) ANNEX III sect
Directive 98/79/CE (7 December 1998) ANNEX III sect. 3 TECHNICAL DOCUMENTATION Must include: General description of the product 2 - Documentation of the quality system 3 - Design information including origin of material; drawings and diagrams and the operation of the product; description of the procedures used for sterile products; labels and instructions for use 4 - Results of the risk analysis 5 - Results of the design calculations and of the inspections carried out 6 - The test reports 7 - The results of stability studies ISTITUTO SUPERIORE DI SANITA’ Department of Infectious, Parasitic and Immunomediated Diseases

SUMMARY RESULTS OF THE SERO-CONVERSION STUDY HIV 1/2 Ag/Ab TEST KIT

IL RUOLO DELL’ISTITUTO SUPERIORE DI SANITA’ COME ORGANO TECNICO: IL CONTRIBUTO DEL DIPARTIMENTO DI MALATTIE INFETTIVE, PARASSITARIE, ED IMMUNOMEDIATE.

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IL RUOLO DELL’ISTITUTO SUPERIORE DI SANITA’ COME ORGANO TECNICO: IL CONTRIBUTO DEL DIPARTIMENTO DI MALATTIE INFETTIVE, PARASSITARIE, ED IMMUNOMEDIATE.

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Presentazione sul tema: "IL RUOLO DELL’ISTITUTO SUPERIORE DI SANITA’ COME ORGANO TECNICO: IL CONTRIBUTO DEL DIPARTIMENTO DI MALATTIE INFETTIVE, PARASSITARIE, ED IMMUNOMEDIATE."— Transcript della presentazione:

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