CE-marking Requirements for Medical Devices
Transcription
CE-marking Requirements for Medical Devices
Medical SW #4.0 30.04.2014 Hvordan godkendes medicoteknisk udstyr med vægt på SW? Foredrag hos IDA Elteknik København 30.04.2014 – Claus Lindholt 30.04.2014 © Claus Lindholt CE-marking Requirements for Medical Devices including Software Compliance with Medical Devices Directive EN ISO 13485, EN ISO 14971, EN 62304 & EN62366 30.04.2014 – Claus Lindholt © 30.04.2014 © Claus Lindholt Indhold af foredrag 30.04.2014 • • • • • • • • Eksempler på medical SW og medical App’s MD Life-cycle og regulatoriske krav MD Definitioner, klassifikation og veje til CE-mærket Harmoniserede standarder Regulatorisk Strategi -> Plan -> Dok -> CE-mærke Krav til Medical SW - EN62304, EN62366 Dokumentation for SW i praksis Hvad med Agile (SCRUM) • (QMS ISO13485 eller Risk Management ISO14971) 30.04.2014 © Claus Lindholt © Claus Lindholt 1 Medical SW #4.0 30.04.2014 Claus Lindholt baggrund • • Akademiingeniør svagstrøm 1975 fra DIA (AUC) Ca. 35 år som projektleder: – Produktionsteknologi – Kvalitetsstyring – Produktudvikling • Indenfor produktområderne: – – – – – • • • • • • Telefoner og dataudstyr Skibsautomation EMS (Electronic Manufacturing Service) Mobiltelefoner og apps til mobiltelefoner Medicinsk udstyr (20 år) Tidligere eksportchef, salgschef, kvalitetschef, teknisk direktør og adm.direktør Medejer af Pulsemaster Ltd. UK – terapeutisk udstyr, siden 2000 Teknisk direktør (CTO) i Mermaid Care A/S, siden 2006 Certificeret lead auditor for ISO13485 kvalitetsstyringssystemer Konsulentarbejde vedr. Technical File og ISO13485 QMS for start-up’s Undervisning og foredrag i regulatoriske krav til medicinsk udstyr 30.04.2014 © Claus Lindholt Medico i Nordjylland 30.04.2014 © Claus Lindholt Mermaid Care A/S • • • • • Måleapparat for lungeparametre, Shunt og O2-tab Baseret på forskning fra AaU, Rcare Gas sensorsystem for O2, CO2 og flow samt pulsoximeter for SpO2 2 CE-mærkede produkter i MDD klasse IIa Algoritmer på Windows XP-emb. platform 30.04.2014 © Claus Lindholt © Claus Lindholt 2 Medical SW #4.0 30.04.2014 Examples Medical SW & App’s 30.04.2014 © Claus Lindholt Challenges for medical SW • Software used in a setting that does not allow the doctor sufficient time to second-guess the software. • Emergency Care Predictive Analytics Software. – This category of software may process and analyze large amounts of both structured and unstructured healthcare data and vital sign data to recommend and adjust a treatment in an emergency care setting. – Can such SW always be trusted in a hot situation? • Hospital patient monitoring software. – The problem is alarms going off so often that nurses no longer treat them as truly indicative of an emergency. – An emerging category of software is using sophisticated analytics to assess the various data related to a monitored patient, giving nurses a more meaningful notification when a patient’s health is deteriorating. – What happens when one doesn’t work, a patient crashes and the caregiver is alerted too late? 30.04.2014 © Claus Lindholt Challenges for medical SW • Software that takes a very complicated calculation and presents a result without transparently revealing the basis for the calculation. • Burn Victim Fluids Assessment. – Could use an advanced algorithm that learns how each patient responds to fluid therapy each hour. – The algorithm could use fluid in and out trend data to predict the fluid rate for the next hour that will best achieve the urine output target range. • Radiation dose calculator. – Radiation treatment planning is generally performed on dedicated computers using specialized treatment planning software. – The planner will try to design a plan that delivers a uniform prescription dose to the tumor and minimizes dose to surrounding healthy tissues. – Many factors are considered by radiation oncologists when selecting a dose, including whether the patient is receiving chemotherapy, patient comorbidities, whether radiation therapy is being administered before or after surgery, and the degree of success of surgery. 30.04.2014 © Claus Lindholt © Claus Lindholt 3 Medical SW #4.0 30.04.2014 Challenges for medical SW • Apps and other software that guide untrained users to make very complex medical decisions. • • • • SpotMole App DIABETooL Insulin Calc App Concussion Assessment&Response App Disease Management App 30.04.2014 © Claus Lindholt SpotMole App 30.04.2014 © Claus Lindholt SpotMole App Description from Google Play: SpotMole provides a simple way to have a quick check of your skin spots and moles. Take a snapshot of a mole or load a mole's photo from the phone's gallery and let SpotMole do the rest ! SpotMole may detect signs of melanoma using image processing and pattern recognition techniques. Spotmole does a scan of relevant dermatological features. Using SpotMole you first have to take a close-up and well centered snapshot of a skin spot or mole and next run an analysis. SpotMole automatic assessment software uses standard visual analysis proceedures to check spots on the skin. The features extracted are common in dermatology and widely employed in visual inspection of the skin spots. These are Asymmetry, Border, Color, Diameter and Evolution of the mole (ABCDE). Spotmole's output may be negatively influenced by images with poor contrast/brightness, color artifacts, nonuniform illumination, poor resolution, skin hairs covering the mole, etc. PLEASE, MAKE SURE YOU READ THE USAGE INFORMATION BEFORE USING THE APP: ON THE MAIN APP'S SCREEN JUST PRESS THE 'USAGE' BUTTON DISCLAIMER: SpotMole is by no means a substitute for clinical diagnostics performed by trained dermatologists. SpotMole is not a medical device and should not be considered as such. Regardless of the output of the program you are urged to seek medical advice if you have doubts with a particular skin spot - mole. SpotMole's assessment is for educational purpose only. Use SpotMole at your own risk. What happens if the app misses a potential melanoma? 30.04.2014 © Claus Lindholt © Claus Lindholt 4 Medical SW #4.0 30.04.2014 DIABETooL Insulin Calc 30.04.2014 © Claus Lindholt DIABETooL Insulin Calc Description from Google Play: Summary: - Input your medical protocol and life conditions, - Run insulin Units calc, - Check record details, - View Statistics over period of time, - Check HbA1c estimate based on your average data, - View graphs,For who ? Especially designed for Diabetes type 1 patients, also known as insulin-dependent diabetes, following “functional insulin therapy” protocols with rapid acting insulins, either with by pump or needle injections. But also meaningful for doctors, advisers and nurses. For what ? First of all, because we have been dreaming for a while about it for private usage. So we are very keen on sharing our experience with you. To compute the rapid acting insulin dose (UI) assumed to be injected according to the carbohydrates and lipid meat contents and corrective factors from your medical protocol. The input data are limited within default range values but input values keep anyway under your entire responsibility. Your data are recorded locally into your smart-phone database. You can export these data into a CSV file format (e.g. to be able to easily import your data into your PC favorite calc spreadsheet. In case of requested export (EXPORT button), the recorded CSV file will be localized onto your SD card. No data are exchanged with external devices or servers. Full detailed statistics (average, min, max values over several time periods) are available for each parameter (Blood Glucose, Insulin Units, Carbohydrates, Lipids). Every parameter is shown in a graphical view as well. The view is zoomable (in/out). The base view shows last week data and it can be slided or zoom over time©just playing with your finger ends. 30.04.2014 Claus Lindholt Concussion Assessment&Response 30.04.2014 © Claus Lindholt © Claus Lindholt 5 Medical SW #4.0 30.04.2014 Concussion Assessment&Response Description from Google Play: Sport Version app, or CARE, is a new tool that helps medical professionals and athletic trainers assess the likeliness of a concussion and respond quickly and appropriately to this potentially serious medical situation. The CARE provides instruction during the assessment of an injury; it also provides tools that can help document the injury as well as recovery. All the recorded assessment information can be shared via email with other doctors or other medical professionals. The CARE allows users to test an athlete’s readiness to return to play via a step-by-step testing regimen. This tool is an invaluable way to assess possible concussions and respond appropriately. FEATURES: ------- snip-----Return-to-Play Guide: This part of the app helps to protect children and athletes from further injury by guiding them through a daily exercise routine that tests their ability to return to play. Through a five-day, tiered workout routine, parents can ensure that their child is able to handle the added exercise without further injury or discomfort. Concussion General Information The app’s concussion information helps ensure that medical professionals are provided a comprehensive understanding of concussions as well as the assessments they will be administering via the CARE. All concussion information in this section has been provided by Gerard A. Gioia, PhD and Jason Mihalik, PhD, concussion specialists from the Children’s National Medical Center and the Matthew A. Gfeller Sport-Related Traumatic Brain Injury Research Center. Acute Concussion Evaluation (ACE) Post-Concussion Home/School Instructions Included with the app is a concussion overview page that users can share with other coaches, parents, or athletes. This overview is an excellent way to share important information about how to recognize and respond to concussions. 30.04.2014 © Claus Lindholt Disease Management App 30.04.2014 © Claus Lindholt Disease Management App Description from Google Play (abbreviated): Rapidly rising health care costs have prompted Employers and Health Plans to look to Disease Management Programs as a way to improve ones health while reducing overall healthcare costs. This app features complete health risk assessments for both men and women including Diabetes, Heart Disease, Prostate Cancer, Breast Cancer, Colorectal Cancer, Gastrointestinal, Osteoporosis, Stroke, and Lung Cancer. Multiple choice health quizzes are included to test your knowledge and increase awareness of these various disease states. Each Risk Assessment provides an in-depth look at an individual for a specific disease state and determines a level of risk. A routine visit with an individual’s primary care physician is recommended and encouraged in most situations. Ideal For Businesses (Health Plans and Employers) Disease management is one approach that aims to provide better care while reducing the costs of caring for the chronically ill. For Individuals and Families A simple and convenient way to determine your risk for developing one the following major diseases: Diabetes, Heart Disease, Prostate Cancer, Breast Cancer, Colorectal Cancer, Gastrointestinal, Osteoporosis, Stroke, and Lung Cancer. Disease Management programs empower individuals, in collaboration with physicians and other health care professionals, to effectively manage their conditions and associated risk factors and co-morbidities. Our risk assessments are designed by experienced healthcare professionals to ensure accurate and dependable information is made available to you or a loved one. -This app does not diagnose or suggest treatment for any disease state. A visit to your primary care physician is 30.04.2014 © Claus Lindholt highly recommended. © Claus Lindholt 6 Medical SW #4.0 30.04.2014 Life-Cycle for Medical Devices Direktiver og standarder 30.04.2014 © Claus Lindholt MDD Life-Cycle for Medical Devices Intended use Clinical Trials Clinical Reports & Articles Research From Product Requirements Intended Use & Performance Risk Analysis Controlled Processes Verification & Validation Clinical Evaluation Project- QMS – Process Control - GMP Training Calibration CAPA System Change Control Final Control Develop- Produc- Changes Refurbishment Archiving Vigilance De-commissioning Marke-- ting& idea –Approval which requirements? planto end-of-life ment tion Sales Service & End-of-Life Regulatory Requirements Plan for Regulatory Requirements incl.: • Strategy • Time Schedule • Resources • Economics 30.04.2014 MDD Classification MDD Essential Req. Risk Management Standards e.g. EMC and Safety Clinical Rationale Quality Management Process Validation Brochures and Web-site Manuals National Language Dealer Contracts Post Market Surveillance Vigilance Reporting Recalls © Claus Lindholt Definition på medicinsk udstyr • Se direktivet på www.medicinskudstyr.dk link til Lovgivning – Bek.1263 – 1) » Medicinsk udstyr «: Ethvert instrument, apparat, udstyr, materiale, utensilie (éngangsudstyr), anordning, hjælpemiddel eller enhver anden genstand anvendt alene eller i kombination, herunder edb-programmel, der hører med til korrekt brug heraf, som af fabrikanten er beregnet til anvendelse på mennesker med henblik på: • a) Diagnosticering, forebyggelse, overvågning, behandling eller lindring af sygdomme, • b) diagnosticering, overvågning, behandling, lindring af eller kompensation for skader eller handicap, • c) undersøgelse, udskiftning eller ændring af anatomien eller en fysiologisk proces, eller • d) svangerskabsforebyggelse, • og hvis forventede hovedvirkning i eller på det menneskelige legeme ikke fremkaldes ad farmakologisk, immunologisk eller metabolisk vej, men hvis virkning kan understøttes ad denne vej. – 2) » Tilbehør «: Ethvert produkt, der af fabrikanten er bestemt til at blive anvendt sammen med medicinsk udstyr, for at det medicinske udstyr kan anvendes som planlagt af dets fabrikant. I bekendtgørelsen betragtes tilbehør som selvstændigt medicinsk udstyr. 30.04.2014 © Claus Lindholt © Claus Lindholt 7 Medical SW #4.0 30.04.2014 Relevante Direktiver • Medicinsk Udstyr direktivet (MDD) 93/42 + 2007/47 omfatter alt medicinsk udstyr og SW til diagnosticering, forebyggelse, overvågning, behandling eller lindring af sygdomme og handikap mv. In Vitro Diagnostic direktivet (IVDD) 98/79 omfatter alle typer testsystemer, som anvender biologisk materiale udenfor kroppen (in vitro), f.eks. Glucosetest apparater, herunder beslutningsstøttesystemer (SW) baseret på IVD data • • Aktiv Implantat direktivet (AIMDD) 90/385 omfatter alle typer aktivt medicinsk udstyr, som er beregnet til at bruges i kroppen i længere tid, f.eks. pacemakers Waste of Electrical and Electronic Equipment (WEEE) omfatter kontrolleret bortskaffelse af AL elektronik – også medicinsk udstyr, men ikke B2B Reduction of Hazardous Substances (RoHS) regulerer brugen af f.eks. bly i elektronik og bromholdige brandhæmmere i plast. Al medicinsk udstyr er pt. undtaget, men RoHS 2 (2011/65) træder i kraft for MD d.22.07.2014, IVD d.22.07.2016 og AIMD i 2019! • • 30.04.2014 © Claus Lindholt MDD Bilag I - Væsentlige Krav De generelle krav: De specifikke krav: Højt sikkerhedsniveau Indbygget beskyttelse Egnethed Stabilitet i ydeevne Transportsikkerhed Afvejning af fordele mod ulemper De specifikke krav findes i de harmoniserede standarder. 30.04.2014 Elektrisk sikkerhed Elektromagnetisk kompatibilitet (EMC) Krav til brugbarhed (usability) Risikoanalyse Mærkningskrav Krav til brugsanvisning Alarmfunktioner Materialesikkerhed Bioforligelighed Sterilitetssikkerhed Mekanisk sikkerhed Brand- og eksplosionssikkerhed Nøjagtighed og stabilitet Strålebeskyttelse Klinisk evaluering © Claus Lindholt Klassificering af medicinsk udstyr MDD bilag IX • Medicinsk udstyr opdeles i 3 klasser – Klasse I med underklasser Is og Im • Ikke elektrisk udstyr (klasse I), sterilt udstyr (klasse Is) og udstyr med målefunktion (klasse Im) – Klasse IIa (romertal 2a) • Det meste elektriske udstyr – Klasse IIb • Udstyr med høj risko – Klasse III • Udstyr i forbindelse med centralnervesystemet • • • • • MDD bilag IX afsnit III har 18 regler til klassificering EU MEDDEV 2.4 /1 part 1 & part 2 indeholder guidelines Dokumentationen for klassificeringen skal indeholde rationale for fabrikantens valg af klasse Klassificeringen gælder alene vejen til CE-mærket – de tekniske krav er de samme for alle klasser – afhængig af udstyret Eksempler: – – ALPE er klasse IIa i henhold til regel 10 (active device for diagnosis) Respirator er klasse IIb efter regel 9 + potentiel farlig 30.04.2014 © Claus Lindholt © Claus Lindholt 8 Medical SW #4.0 30.04.2014 Vejen til CE-mærket - MDD Klassificeringen gælder alene vejen til CE-mærket – de tekniske krav er de samme for alle klasser – afhængig af udstyret Klasse I anmeldes til CA – Lægemiddelstyrelsen Klasse Is og Im kræver NB assistance Klasse IIa kræver NB assistance og dokument kontrol Klasse IIb og III kræver NB’s granskning af dokumentationen og der er begrænsning i valget af kvalitetsstyringsomfang 30.04.2014 © Claus Lindholt Vejen til CE-mærket – MDD 30.04.2014 © Claus Lindholt Direktiver og Harmoniserede Standarder Direktiver EU Kommissionen Regeringen Folketinget Sundhedsministeren Sundhedsstyrelsen Virksomheden Standarder EU Direktiv Standardiseringsorganisation Forslag til EN standard Dansk lov EU Kommissionen EU Tidende Harmonisering af EN standard Dansk Standard National DS/EN standard Bekendtgørelse MDD nr.1263 af 15.12.08 IVDD nr.1269 af 12.12.05 Væsentlige krav Kvalitetsstyring Bemyndiget Organ Overensstemmelse Bemyndiget Organ Sundhedsstyrelsen Virksomheden Medicinsk Udstyr iht. EN standarder Akkrediteret Laboratorium Testrapporter Overvågning 0543 30.04.2014 © Claus Lindholt Find Dir. & Harm.Std. på www.medicinskudstyr.dk © Claus Lindholt 9 Medical SW #4.0 30.04.2014 Nogle harmoniserede standarder • EN62304:2006 - Medical device software - Software life-cycle processes • EN 62366:2008 - Medical devices - Application of usability engineering to medical devices • EN ISO 14971:2012 - Medical devices - Application of risk management to medical devices • EN 60601-1:2006 - Medical electrical equipment -- Part 1: General requirements for basic safety and essential performance • EN 60601-1-2:2007 - Medical electrical equipment -- Part 1-2: General requirements for basic safety and essential performance Collateral standard: Electromagnetic compatibility - Requirements and test 30.04.2014 © Claus Lindholt EN60601-x-y Horisontale og Vertikale standarder EN60601-1 Generic EN60601-1-2 EMC • EN60601-1 Generic EN60601-1 Generic EN60601-1 Generic EN60601-2-12 Lungeventillatorer 30.04.2014 • • EN60601-1-6 Usability EN60601-1-8 Alarms EN60601-1-x Horisontale (collateral) std. gælder alle typer udstyr EN60601-2-x Veritkale (particular) std. dækker særlige krav eller fortolkninger for specifikt udstyr (EN80601-2-x) Se en samlet liste via Lovgivning link på www.medicinskudstyr.dk © Claus Lindholt EN 60601-1:2006 - Indhold 1 Scope, object and related standards 2 * Normative references ( * Rationale in Annex A) 3 * Terminology and definitions 4 General requirements 5 * General requirements for testing ME EQUIPMENT 6 * Classification of ME EQUIPMENT and ME SYSTEMS 7 ME EQUIPMENT identification, marking and documents 8 * Protection against electrical HAZARDS from ME EQUIPMENT 9 * Protection against MECHANICAL HAZARDS 10 * Protection against unwanted and excessive radiation HAZARDS 11 * Protection against excessive temperatures and other HAZARDS 12 * Accuracy of controls and instruments and protection against hazardous outputs 13 * HAZARDOUS SITUATIONS and fault conditions 14 * PROGRAMMABLE ELECTRICAL MEDICAL SYSTEMS (PEMS) 15 Construction of ME EQUIPMENT 16 * ME SYSTEMS 17 * Electromagnetic compatibility of ME EQUIPMENT and ME SYSTEMS 30.04.2014 © Claus Lindholt © Claus Lindholt 10 Medical SW #4.0 30.04.2014 8 * Protection against electrical hazards • Krav: – – – – • Means of Patient Protection MoPP (x2) Means of Operator Protection MoOP (x2) Applied Part B, BF eller CF [pdf s. 217] Bestemt ved Risk Manangement proces Metoder: – – – – • Isolationsafstande og –materialer Krybe-luft afstande Transformatorer Beskyttelsesjord Vigtigste tests: – Lækstrøm < 100µA (touch current) – Højspændingstest > 4kV – Jordslutningsstrøm >25A 30.04.2014 © Claus Lindholt EN60601-1-2:2007 EMC • Emissions – Protection of radio services – Protection of PUBLIC MAINS NETWORK • Harmonic distortion • Voltage fluctuation and flicker • IEC 61000-3-2 IEC 61000-3-3 Immunity – – – – – – – • • CISPR 11 ESD – ElectroStatic Discharge Radiated RF Electromagnetic Fields Electrical fast transients and bursts Surges Conducted disturbances, induced by RF fields Voltage dips and variations Magnetic fields IEC61000-4-2 IEC 61000-4-3 IEC 61000-4-4 IEC 61000-4-5 IEC 61000-4-6 IEC 61000-4-11 IEC 61000-4-8 EMC oplysninger i brugermanualen, f.eks. afstand til mobiltelefoner Brug et akkrediteret laboratorium og få en testrapport 30.04.2014 © Claus Lindholt EN60601-1-8:2007/AC2010 Alarm systemer • • • • Elektromedicinsk udstyr – Del 1-8: Generelle sikkerhedskrav – Kollateral standard: Generelle krav, prøvninger og vejledninger for alarmsystemer i elektromedicinsk udstyr og elektromedicinsk systemer Marking of Controls – 6.3 Instruction for Use – 6.8.2 Technical Description – 6.8.3 Alarm Condition – 201.1 – Alarm Groups – 201.1.1 – Alarm Condition Priority – 201.1.2 • • Intelligent Alarm System – 201.2 Alarm Signal Generation – 201.3 – Visual Alarm Signals and Displays – 201.3.2 – Auditory Alarm Signals – 201.3.3 30.04.2014 © Claus Lindholt • • • • • • • • • Alarm System Delays – 201.4 Alarm Presets – 201.5 Alarm Limits – 201.6 Alarm System Security – 201.7 Alarm Signal Inactivation States – 201.8 Alarm Reset – 201.9 Alarm Latching Properties – 201.10 Distributed Alarms – 201.11 Alarm Condition Logging – 201.12 © Claus Lindholt 11 Medical SW #4.0 30.04.2014 Regulatorisk Strategi & Plan Hvordan kommer man fra alle kravene til en plan for gennemførelse – og får det hele med? 30.04.2014 © Claus Lindholt MDD Life-Cycle for Medical Devices Intended use Clinical Trials Clinical Reports & Articles Research Activities Product Requirements Intended Use & Performance Risk Analysis Controlled Processes Verification & Validation Clinical Evaluation Project Plan QMS - GMP Proces Control Training Calibration CAPA System Change Control Final Control Design & CEDevelopmarking ment ProducTion Changes Refurbishment Archiving Vigilance De-commissioning Service Marketing & End-of& Sales Life Regulatory Requirements Plan for Regulatory Requirements incl.: • Strategy • Time Schedule • Resources • Economics 30.04.2014 MDD Classification MDD Essential Req. Risk Management Standards e.g. EMC and Safety Clinical Rationale Quality Management Process Validation Brochures and Web-site Manuals National Language Dealer Contracts Post Market Surveillance Vigilance Reporting Recalls © Claus Lindholt 2 Strategi for CE-mærkning Hvad skal udstyret bruges til? + Er det er medicinsk udstyr? + Hvilket direktiv? + Hvilken klassificering? + Hvilken vej til CE-mærket? + Hvilke krav til kvalitetsstyring? + Hvilke standarder gælder? + Hvilke medicinske krav? + Hvordan dokumenteres det hele? = LAV EN PLAN! 30.04.2014 © Claus Lindholt © Claus Lindholt 12 Medical SW #4.0 30.04.2014 Regulatory Strategy for CE-marking Costumer Requirements Intended Use definition No Medical device? Other rules & standards? e.g. EPJ or LIS Yes Applicable Directive MDD or IVDD (AIMDD) Directive Requirements: Essential Requirements Clinical Rationale IVD Performance Eval.. Product properties e.g. includes SW Device Classification: MD: I, Im, Is, IIa, IIb, III IVD: Other, Selftest, List A, B Harmonized Standards List of applicable Route to CE-mark CA application or NB Other directives to consider: RoHS, Reach, WEEE etc. Technical File Content DHF + DMR Scope & content of QMS QM+QOP+WI+QF+QR CE Conformity doc. PMS & Vigilance Project Plan including Regulatory Strategy and Deliverables Develop Product Documentation Develop MDD/IVDD Conformance Documentation Establish QMS Directive + EN ISO13485 30.04.2014 © Claus Lindholt Documentation for CE-marking Project Plan including Regulatory Strategy and Deliverables Develop Product EN62304 EN62366 EN/ISO14971 EN60601-1 Develop QMS Directive + EN/ISO13485 Clinical Performance doc. EN14155 EN13612 Verify Product Safety & EMC test DHF Implement QMS Quality Records Essential Requirements Product Lifetime Validate Product Transfer to Production DMR + DHR Internal Audit QMS + all doc’s MD Clinical Rationale IVD Performance Val. Decl. of Conformance Notified Body Audit (Annex ? + ISO 13485) Review of ALL documents xxxx Product Changes 30.04.2014 Quality Records Management review Clinical Improvement PMS & Vigilance © Claus Lindholt EN62304 Software for medicinsk udstyr Livscyklusprocesser for medicinsk software 30.04.2014 © Claus Lindholt © Claus Lindholt 13 Medical SW #4.0 30.04.2014 Is the SW a medical device? Meddev 2.1/6 page 9 30.04.2014 © Claus Lindholt 30.04.2014 © Claus Lindholt Is the SW MDD or IVD? Meddev 2.1/6 page 9 30.04.2014 © Claus Lindholt © Claus Lindholt 14 Medical SW #4.0 30.04.2014 Livscyklusprocesser for SW? Input Output SW dokumentation Brugerkrav SW Udvikling Projektplan Standarder Eksekverbar kode Verifkationsdokumentation Proceskontrol Proceskrav Livscyklus EN62304 30.04.2014 QA-Dokumentation © Claus Lindholt MDD Life-Cycle for Medical Devices Intended use Clinical Trials Clinical Reports & Articles Research Activities Product Requirements Intended Use & Performance Risk Analysis Controlled Processes Verification & Validation Clinical Evaluation Project Plan QMS - GMP Proces Control Training Calibration CAPA System Change Control Final Control Design & CEDevelopmarking ment ProducTion Changes Refurbishment Archiving Vigilance De-commissioning Service Marketing & End-of& Sales Life Regulatory Requirements MDD Classification MDD Essential Req. Risk Management Standards e.g. EMC and Safety Clinical Rationale Quality Management Process Validation Plan for Regulatory Requirements incl.: • Strategy • Time Schedule • Resources • Economics 30.04.2014 Brochures and Web-site Manuals National Language Dealer Contracts Post Market Surveillance Vigilance Reporting Recalls © Claus Lindholt From MDD Life Cycle to EN62304 SW-Development MDD Product Life cycle Research ISO13485 Design Concept Control Business Plan Design & Devel. Costumer Requirements Design Production Marketing & Sales Service & EoL Develop- Verificament tion Validation Transfer CE-mark Product Risk Management Process 30.04.2014 © Claus Lindholt © Claus Lindholt 15 Medical SW #4.0 30.04.2014 From MDD Life Cycle to EN62304 SW-Development MDD Product Life cycle Research ISO13485 Design Concept Control Business Plan Design & Devel. Costumer Requirements Design Production Marketing & Sales Service & EoL Develop- Verificament tion Validation Transfer CE-mark Product Risk Management Process EN62304 5.1 SW Design Planning 5.2 5.3 Req. Analysis Architecture Design 5.4 5.5 5.6 5.7 Detailed Unit Impl. Integrat. Design & Test & Test 5.8 System Release Test 7. SW Risk Management Process 8. SW Configuration Management Process 9. SW Problem Resolution Process 30.04.2014 © Claus Lindholt From MDD Life Cycle to EN62304 SW-Development MDD Product Life cycle Research ISO13485 Design Concept Control Business Plan Design & Devel. Costumer Reqirements Design Production Marketing & Sales Service & EoL Develop- Verificament tion Validation Transfer CE-mark Product Risk Management Process EN62304 5.1 SW Design Planning 5.2 5.3 Req. Analysis Architecture Design 5.4 5.5 5.6 Detailed Unit Impl. Integrat. Design & Test & Test 5.7 5.8 System Release Test 7. SW Risk Management Process 8. SW Configuration Management Process 9. SW Problem Resolution Process 30.04.2014 © Claus Lindholt EN 62304 - SW Dev. Life Cycle • MDD, Bilag I, væsentlige krav 12.1.a. – For udstyr, der inkorporerer software, eller i sig selv er medicinsk software, skal softwaren valideres i overensstemmelse med det aktuelle tekniske niveau, idet der tages hensyn til principperne for udviklingslivscyklus, risikostyring, validering og verificering. • Annex I, ER 12.1.a. – “For devices which incorporate software or which are medical software in themselves, the software must be validated according to the state of the art taking into account the principles of development lifecycle, risk management, validation and verification.” 30.04.2014 © Claus Lindholt © Claus Lindholt 16 Medical SW #4.0 30.04.2014 Life-cycle model for softwareudvikling iht. EN62304 • • • Et framework – processer, aktiviteter og opgaver Identificerer krav for hvad der skal gøres og hvad der skal dokumenteres Specificerer en SW klassifikation metode • • • Beskriver ikke hvordan kravene opfyldes Kræver ikke en specifik SW life-cycle model Specificerer ikke dokumenter 30.04.2014 © Claus Lindholt SW Development Processes – Documented life-cycle with: • • • • Development Plan Milestones Activites Documentation – Development life-cycle must include: • • • • • Requirements specification Architecture specification Sub-system design and test specifications Verification PEMS Validation 30.04.2014 © Claus Lindholt EN62304 - Vigtige koncepter • • • • • Kvalitetsstyring og risikostyring er nødvendig SW klassificeres iht. fareniveau (severity of potential harm) Der er forskellige krav baseret på SW klassifikationen Forskellige moduler kan have forskellig klasse Segregering – adskillelse af kritiske funktioner – også variabler • SW life-cycle ender ikke med produktfrigivelsen, den fortsætter med vedligeholdelse Guidelines for risikostyring af medicinsk software: – AAMI TIR32:2004 Medical device software risk management – IEC/TR 80002-1 Guidance on the application of ISO14971 to medical device software • 30.04.2014 © Claus Lindholt © Claus Lindholt 17 Medical SW #4.0 30.04.2014 EN62304 Klassifikation af software • • • • • Risk Management Proces efter EN ISO 14971 A: No injury possible B: non-serious injury C: death or serious injury Validering afhænger af klasse • De-klassificering ved HW risk control SW risk control samme klasse som kontrollerede hazard Segregering skal dokumenteres • • 30.04.2014 © Claus Lindholt SW i et medicinsk udstyr 30.04.2014 © Claus Lindholt Medical SW funktionstyper 30.04.2014 © Claus Lindholt © Claus Lindholt 18 Medical SW #4.0 30.04.2014 Særlige risiko egenskaber ved SW • • • • SW kan ikke i sig selv påføre skade – derfor kan risikoanalyse ikke gennemføres på SW alene – HW platform og tilkoblet udstyr samt kommunikation skal med SW er systematisk af natur og fejler ikke tilfældigt – derfor bruges sandsynlighed ikke. Risiko = 100% Alle årsager må derfor undersøgers og imødegås, hvis de er kritiske. Funktionen af SW er afgørende for dybden af risikoanalysen og valg af kontrolmetoder ved SW fejl: – Life supporting – respirator – Terapeutisk – strålekanon – Dianostisk eller monitorering – ALPE eller patientmonitor 30.04.2014 © Claus Lindholt Kæder af årsager i SW 30.04.2014 © Claus Lindholt SW Risk Management 30.04.2014 © Claus Lindholt © Claus Lindholt 19 Medical SW #4.0 30.04.2014 Kontrol af farlige situationer 30.04.2014 © Claus Lindholt SOUP • • • • • Software of Unknown Provenance Også kaldet ”tredje parts software” Styresystemer, udviklingsystemer (biblioteker), run-time fortolker (Java), kommunikations SW, drivere etc. Hvis der skiftes version af udviklingssystem, kan det betyde ny komplet SW-test og SW-validering Hvis SOUP bruges, skal det altid være under kontrol og enten valideres, overvåges eller isoleres 30.04.2014 © Claus Lindholt ALPE essential – System Architecture Inspired atmospheric air ALPE-1 Control Unit ALPE Trolley N2 O2 10L or 20L Gas Cylinders w. Pressure Regulators to 5 Bar Gas Supply System 4 HW systems: • ALPE-1 Trolley • ALPE-1 Controller Unit • ALPE Respiration Unit • ALPE Notebook PC ALPE Respiration Unit Flow Meter O2 Analyzer Embedded Controller w. ALPE-1 Firmware USB I/F Power Supply & Isol.Trafo Public Mains Patient Pulse Oximeter Isolated Mains Status Display Function buttons Alarm Beeper Windows Notebook PC w. ALPE Console SW WLAN SOUP håndtering af Windows XP og Embedded Linux Operator Gas Flow Data/Electrical 30.04.2014 © Claus Lindholt 2 SW Systems: • ALPE-1 Firmware w. Alarm System • ALPE Console SW w. Algorithm and Operator Interface • Opdelt på flere processorer • Alarmsystem - segregering • FPGA og HW-watch-dog • Sikker USB kommunikationsprotokol © Claus Lindholt 20 Medical SW #4.0 30.04.2014 SW Risk Management • • • • • • Brug vejledninger i anvendelse af EN ISO 14971 (risikostyring) i forbindelse med software til medicinsk udstyr (TIR 32 og IEC TR80002-1) Find alle farer på systemniveau og identificér dem, der kan have SW som grundlæggende årsag Lav en tabel pr. identificeret fare (hazard) og grad af alvorlighed (severity) List alle årsager og kæder af årsager Opstil kontrolmetoder (Methods of Control – ikke mitigations) List sporbarhed for kontrolmetoder med krydsreference til system specifikation, design og alle testniveauer (og kode for Class C) 30.04.2014 © Claus Lindholt Risk Management EN/ISO14971 • Hvis tiden tillader? 30.04.2014 © Claus Lindholt EN62366:2007 Medicinsk udstyr – Indbyggelse af anvendelighed i medicinsk udstyr Medical devices – Application of usability engineering to medical devices 30.04.2014 © Claus Lindholt © Claus Lindholt 21 Medical SW #4.0 30.04.2014 Categories of user actions Indblanding Smutter Utilsigtet Huskefejl Tilsigtet 30.04.2014 © Claus Lindholt Usability conceptual design 30.04.2014 © Claus Lindholt Risk Analysis 30.04.2014 © Claus Lindholt © Claus Lindholt 22 Medical SW #4.0 30.04.2014 Dokumentation af medicinsk SW 30.04.2014 © Claus Lindholt Mermaid Care QMS BRD DM R 7 P Design Control Process Phase V-Model and Controlled Documents se P ha se ha 1 VaTP VaTR P 6 CRS 2 Ph as e se ha VeTP VeTR em ag an P ro ce ss M 3 k is Ph as e e as Ph R ITP ic at io n ITR & P 3 ha se e as 4 Ph V er if SDS ss ce ro tP en 4 M TP M TR Ph as e 4 Legend : P h ase 1: P h ase 2: P h ase 3: P h ase 4: P h ase 5: P h ase 6: P h ase 7: 4 xDD RM F e as Ph Legend: BR D – Bu sin ess R ation ale D ocu m en t C RS – C u stom er R equ irem en t S pecification VaTP – V alidation Test Plan VaTR – Validation Test R eport SR S – System R equ irem en t Specification VeTP – V erifictaion Test Plan SD S – System D esign Specification ITP – In tegration Test P lan ITR – In tegration Test R eport x DD – D esign Docu m en t (x = S for SW , H for H W, U for U sability & M for Mech an ics) MTP – Modu le Test P lan MTR – Modu le Test Report R MF = R isk Man agem en t File D H F – D esign H istory File D MR – Dev ice Master R ecord DHF 5 SRS Produ ct Proposal Produ ct R equ iremen ts D esign D evelopm en t System Verification System Validation Produ ct R elease V.1.1 / 07.12.06 / CL 30.04.2014 © Claus Lindholt 10 Technical File for CE-marking of Stand-alone SW MDD Product Life cycle Research • Clinical Articles (optional) EN13485 Design Control Business Plan CE-mark • • • • Classification Essential Req. Standards Clinical Rationale • Declaration Costumer Requirem. Concept • Proof of Concept • Clinical Articles • (optional) Design & Develop. • Business Rationale (optional) Development Design Production • Final Test • Final Control Verification CRS Marketing & Sales Validation VaTR Planning PMP 30.04.2014 © Claus Lindholt Transfer DMR: • SW-executable • SW Configuration • Manuals • Labels • Packaging • Work Instructions RMF VaTP VaTPr 5.1 EN62304 SW Design Service & End-of-Life • Brochures • Web-site 5.2 5.3 5.4 5.5 5.6 5.7 Requirem. Analysis Architecture Design Detailed Design Unit Implem. & Test Integration & Test System Test SRS SAS SDD’s SW-RMF SDS MTPr’s VeTPr ITPr MTP’s VeTP ITP MTR’s ITR VeTPR 5.8 Release SWC © Claus Lindholt 23 Medical SW #4.0 30.04.2014 Required QMS Procedures – MDD Annex VI+VII MDD Product Life cycle Research Business Plan Design & Develop. CE-mark Production CE-marking Process Marketing & Sales Service & End-of-Life Post Marketing Surveilance Vigilance EN13485 Design Control Costumer Requirem. Concept Development Design Verification Validation Risk Management 5.1 EN62304 SW Design Planning SW Design Control EN62304 Transfer Sub-contracting of Production 5.2 5.3 5.4 5.5 5.6 5.7 5.8 Requirem. Analysis Architecture Design Detailed Design Unit Implem. & Test Integration & Test System Test Release SW Risk Management Configuration Management Problem Resolution Document Control 30.04.2014 © Claus Lindholt Required Quality Records MDD Product Life cycle Research Business Plan Design & Develop. CE-mark Production Management Reviews DHR: • P/O Records • Test Records • Control Records Standards EN13485 Design Control Costumer Requirem. Concept Development Design Verification Marketing & Sales Service & End-of-Life Complaints Accident Reports Validation Transfer Sub-contracting of Production 5.1 EN62304 SW Design Planning Phase Reviews 5.2 5.3 5.4 5.5 5.6 5.7 Requirem. Analysis Architecture Design Detailed Design Unit Implem. & Test Integration & Test System Test Document Reviews Training Records Configuration Records 5.8 Release Release Notes Problem Reports 30.04.2014 © Claus Lindholt Manifesto for Agile Software Development We are uncovering better ways of developing software by doing it and helping others do it. Through this work we have come to value: Individuals and interactions over processes and tools Working software over comprehensive documentation Customer collaboration over contract negotiation Responding to change over following a plan That is, while there is value in the items on the right, we value the items on the left more. 30.04.2014 © Claus Lindholt © Claus Lindholt 24 30.04.2014 AAMI TIR 45:2012 AGILE Practices in the development of medical Device SW Fig 4, p.23 Medical SW #4.0 30.04.2014 © Claus Lindholt Spørgsmål og diskussion Kontakt: [email protected] mobil: 40 25 35 33 LinkedIn: dk.linkedin.com/in/clauslindholt/ 30.04.2014 © Claus Lindholt Kvalitetsstyring ISO 13485 30.04.2014 © Claus Lindholt © Claus Lindholt 25 Medical SW #4.0 30.04.2014 ISO 13485 • Medicinsk udstyr – Kvalitetsstyringssystemer – Krav til lovmæssige formål • Standard for kvalitetsstyringssystemer indenfor medicinsk udstyr • Konstrueret med henblik på opfyldelse af lovmæssige krav – Harmoniseret i EU i forhold til MDD+AIMDD – Stort overlap med FDA’s Quality System Regulations (21 CFR part 820), men dækker ikke alle QSR krav 30.04.2014 © Claus Lindholt Proces- og produktstandarder • Produktstandarder beskriver, hvad produktet skal kunne/gøre/være. Eksempelvis kravene i IEC 60601-1-2 • Processtandarder beskriver hvordan fabrikanten skal udføre en opgave. Eksempelvis ISO 13485 og ISO 14971 • Fordele: Muliggør tilpasning til fabrikantens egne vilkår, undgår ”micro-management” fra lovgivernes side • Men – en processtandard er en større ledelsesopgave at implementere end en produktstandard, da den griber ind i større dele af organisationen, ikke kun R&D og produktion 30.04.2014 © Claus Lindholt Kvalitetsstyringssytem (QMS) • Specificerer de processer som skal til for at organisationen kan levere produkter/services, der lever op til krav fra lovgivere, kunder og andre Input 30.04.2014 © Claus Lindholt Sæt af sammenhængende aktiviteter Output © Claus Lindholt 26 Medical SW #4.0 30.04.2014 Interaktion mellem processerne 4. Quality Management System Plan 6. Resource management processes Act Do 5. Management responsibility processes 7. Product realization processes Check 8. Measuring, monitoring, and improvement processes 30.04.2014 © Claus Lindholt 4. Quality Management System • Etablere kvalitetsstyringsystemet: Identificere processer og hvad de behøver for at kunne køre effektivt, forpligte sig til at udføre og følge op på disse processer • Establish er nøgleordet: Processerne skal være dokumenterede og følges i praksis • Dokumentationskrav: Kvalitetsmanual, kvalitetspolitik, kvalitetsmål, documents og records. • Alle har et medansvar – men det overordnede QMS-ansvar er ledelsens 30.04.2014 © Claus Lindholt 5. Management responsibility • Organisationsdiagram: Definere ansvarsområder • Management representative: – Ansvarlig for implementering – Rapporterer til ledelsen om QMS’ tilstand – Skaber bevidsthed om lovmæssige krav i organisationen • Management review: Ledelsen mødes for at diskutere QMS. 30.04.2014 © Claus Lindholt © Claus Lindholt 27 Medical SW #4.0 30.04.2014 6. Resource management • Organisationen skal identificere de ressourcer, der er nødvendige for at kunne drive kvalitetsstyringssystemet i overensstemmelse med kravene, og sikre at disse er til stede • Ressourcer kan være mennesker, maskiner, bygninger, værktøjer osv. 30.04.2014 © Claus Lindholt 7. Product realization • Udstyrets vej fra idé til kunde Specifikke krav til et indkøb Kunden: Customer requirements Sales (7.2 Customer related processes) Generelle krav til nyt udstyr Design control (7.3) Purchasing Tegninger, specifikationer, arbejdsinstruktioner Production and service provision (7.5) Tegninger, specifikationer, arbejdsinstruktioner Færdigt udstyr 30.04.2014 © Claus Lindholt 7.3 Design control 30.04.2014 © Claus Lindholt © Claus Lindholt 28 Medical SW #4.0 30.04.2014 8. Measuring, monitoring, and improvement • Forbedring er ikke et krav i 13485 – kravet er maintain the effectiveness • Korrigerende og forebyggende handlinger Nonconformance: Noget er ikke, som det bør være Corrective action: Root cause analysis-> forhindre at problemet opstår igen Correction: Man reparerer det umiddelbare problem 30.04.2014 © Claus Lindholt 8. Measuring, monitoring, and improvement Control of Nonconforming Product Corrective and Preventive Action Feedback til ledelsen Analysis of Data Customer complaints/feedback Internal audits 30.04.2014 © Claus Lindholt Dokumentation • Documents – kendetegnes ved et revisionsnummer, udvikler sig og opdateres – – – – Kvalitetsmanual Procedurer Skabeloner Arbejdsinstruktioner • Records – arkivmateriale – Training records: Certifikater, CV’er, eksamensbeviser – Purchasing records: Ordrer, følgesedler – Device History Record • ”Hvis det ikke er dokumenteret, skete det ikke.” • Nogle dokumenter og records er direkte krævet af ISO 13485 – andre er bare gavnlige at have • Papir eller elektronisk? Underskrifter er et nøgleelement. – Praksis på området er høje krav til dyr og tidskrævende validering af software til elektroniske underskrifter 30.04.2014 © Claus Lindholt © Claus Lindholt 29 Medical SW #4.0 30.04.2014 ISO 13485 og andre standarder • Andre processtandarder kan have yderligere krav til bestemte processer i QMS – EN 62304: Software life cycle processes – EN 14971: Risk management for medical devices • Da mange sådanne standarder forudsætter et kvalitetsstyringsystem, kan det være nødvendigt at have et, selvom MDD ikke kræver det for udstyrets klasse • ISO 13485 binder andre processtandarder sammen – Ansvarsdefinition – Dokumentationskrav – Ledelse 30.04.2014 © Claus Lindholt ISO 13485 og andre standarder • ISO 13485 kræver, at man sætter sig ind i de lovmæssige krav til udstyret og følger dem: – En af kvalitetsstyringsystemets opgaver er at sørge for, at relevante produktstandarder følges 30.04.2014 © Claus Lindholt Notified Bodies + audits • EU: Notified Body påtager sig mod betaling opgaven med at sikre, at fabrikanters kvalitetsstyringsystem lever op til relevante krav (ISO 13485) • Certificering (3-årig), med årlige opfølgningsaudits • Dokumentationsgennemgang og interviews • Frit valg blandt akkrediterede Notified Bodies – der er forskel! • Vær opmærksom på: ISO 13485 er ikke altid konkret. NBs kan finde på at komme med krav, der bunder i deres praksis, ikke i 13485 (dem kan man modsætte sig!) • Afsæt god tid til audit, også i ledelsen. Det er en let måde at vise, at ledelsen tager ansvar for kvalitetsstyringsystemet. 30.04.2014 © Claus Lindholt © Claus Lindholt 30 Medical SW #4.0 30.04.2014 Spørgsmål og diskussion 30.04.2014 © Claus Lindholt © Claus Lindholt 31