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
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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)
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© Claus Lindholt
© Claus Lindholt
1
Medical SW #4.0
30.04.2014
Claus Lindholt baggrund
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Akademiingeniør svagstrøm 1975 fra DIA (AUC)
Ca. 35 år som projektleder:
– Produktionsteknologi
– Kvalitetsstyring
– Produktudvikling
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Indenfor produktområderne:
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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
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© Claus Lindholt
Medico i Nordjylland
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© Claus Lindholt
Mermaid Care A/S
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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
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© Claus Lindholt
© Claus Lindholt
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Medical SW #4.0
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Examples Medical SW & App’s
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© Claus Lindholt
Challenges for medical SW
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Software used in a setting that does not allow the doctor sufficient time
to second-guess the software.
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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?
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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?
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© Claus Lindholt
Challenges for medical SW
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Software that takes a very complicated calculation and presents a result
without transparently revealing the basis for the calculation.
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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.
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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.
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© Claus Lindholt
© Claus Lindholt
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Medical SW #4.0
30.04.2014
Challenges for medical SW
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Apps and other software that guide untrained users to make very
complex medical decisions.
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SpotMole App
DIABETooL Insulin Calc App
Concussion Assessment&Response App
Disease Management App
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© Claus Lindholt
SpotMole App
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© 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?
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© Claus Lindholt
© Claus Lindholt
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Medical SW #4.0
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DIABETooL Insulin Calc
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© 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.
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Claus
Lindholt
Concussion Assessment&Response
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© Claus Lindholt
© Claus Lindholt
5
Medical SW #4.0
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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.
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© Claus Lindholt
Disease Management App
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© 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
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© Claus Lindholt
highly
recommended.
© Claus Lindholt
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Medical SW #4.0
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Life-Cycle for Medical Devices
Direktiver og standarder
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© 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
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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.
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© Claus Lindholt
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Medical SW #4.0
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Relevante Direktiver
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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
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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!
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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
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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
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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:
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ALPE er klasse IIa i henhold til regel 10 (active device for diagnosis)
Respirator er klasse IIb efter regel 9 + potentiel farlig
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© Claus Lindholt
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Medical SW #4.0
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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
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© Claus Lindholt
Vejen til CE-mærket – MDD
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© 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
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© Claus Lindholt
Find Dir. & Harm.Std. på
www.medicinskudstyr.dk
© Claus Lindholt
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Medical SW #4.0
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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
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© Claus Lindholt
EN60601-x-y Horisontale og Vertikale
standarder
EN60601-1
Generic
EN60601-1-2
EMC
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EN60601-1
Generic
EN60601-1
Generic
EN60601-1
Generic
EN60601-2-12
Lungeventillatorer
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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
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Medical SW #4.0
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8 * Protection against electrical hazards
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Krav:
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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:
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Isolationsafstande og –materialer
Krybe-luft afstande
Transformatorer
Beskyttelsesjord
Vigtigste tests:
– Lækstrøm < 100µA (touch current)
– Højspændingstest > 4kV
– Jordslutningsstrøm >25A
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EN60601-1-2:2007 EMC
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Emissions
– Protection of radio services
– Protection of PUBLIC MAINS NETWORK
• Harmonic distortion
• Voltage fluctuation and flicker
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IEC 61000-3-2
IEC 61000-3-3
Immunity
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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
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EN60601-1-8:2007/AC2010
Alarm systemer
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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
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Intelligent Alarm System – 201.2
Alarm Signal Generation – 201.3
– Visual Alarm Signals and Displays –
201.3.2
– Auditory Alarm Signals – 201.3.3
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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
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Regulatorisk Strategi & Plan
Hvordan kommer man fra alle
kravene til en plan for gennemførelse
– og får det hele med?
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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!
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Medical SW #4.0
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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
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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
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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
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© Claus Lindholt
© Claus Lindholt
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Medical SW #4.0
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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
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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:
claus@lindholt.dk
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.
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© Claus Lindholt
© Claus Lindholt
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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
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© 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
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© Claus Lindholt
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Medical SW #4.0
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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