The industrial process: from prototypes to medical ... · Risk assessment and management analysis for medical devices ... strength, fatigue, …) and thermal resistance, conductivity

EndoVESPA - H2020-ICT 24 - 2015- GA no. 688592

The industrial process: from prototypes to medical products

BERNARDO MAGNANI

Ekymed Srl

Risk assessment and management analysis for medical devices

February 10, 2016

Pontedera, Pisa February 10, 2016 Internal Workshop

ISO 10993 - biocompatibility of medical devices

Plastic material selection: some advices

ISO 14971: application of risk management to medical devices

Outline of the presentation


Mechanical (elasticity, strength, fatigue, …) and thermal resistance, conductivity, …

Type of medical device (…) Biocompatibility Sterilization methods Contact with other materials (drugs…) Manufacturing methods Assembly methods Partner selection Cost …

Material selection criteria


Biocompatibility testing answers two fundamental questions: – is the material safe?

– does it have the necessary physical and mechanical properties for its proposed function?

The extent to which a material needs to be characterized depends on: – Type of material

– End use of the device

– Function of the material within the device

– Availability of existing data on the material

Biocompatibility


Biocompatibility needs to be considered at the onset of design:

– use known biocompatible materials.

– individual components as well as overall packaging are important.

Material testing is performed to determine toxicity of the material, leachable substances and degradation products.

Biocompatibility


The ISO 10993 International Standard pertains to: – Surface devices on the skin, mucosal membranes,

breached or compromised surfaces.

– External communicating devices with blood, tissue, bone, dentin.

– Implantable devices.

Its purpose is to protect humans and to serve as a framework for selecting tests to evaluate biological responses.

In so doing consideration has been given to minimize the number and exposure of test animals.

ISO 10993 Standard


Identification of a materials constituents and: – Changes of the material over time, – Changes with exposure to different environments, – Lot-to-lot consistency for manufacturing purposes.

Methodologies: – Infrared spectral analysis (IR), – Thermal analysis, – Density analysis, – Molecular weight distribution, – Mechanical properties, – Surface properties, – Extract Characterization.

Characterization Methods


ISO 10993-test matrix DEVICE CATEGORIES BIOLOGICAL EFFECT

BODY CONTACT

CONTACT DURATION

Cyt

oto

xici

ty

Sen

siti

zati

on

Irri

tati

on

/In

trac

uta

neo

us

Acu

te S

yste

mic

To

xici

ty

Sub

chro

nic

To

xici

ty

Gen

oto

xici

ty

Imp

lan

tati

on

Hem

oco

mp

atib

ility

Ch

ron

ic T

oxi

city

Car

cin

oge

nic

ity

Rep

rod

uct

ive/

Dev

elo

pm

enta

l

Bio

deg

rad

atio

n

A = Limited (≤ 24 hours) B = Prolonged (24 hours - 30 days) C = Permanent (>30 days)

SURFACE DEVICES

Skin A x x x

B x x x

C x x x

Mucosal Membrane

A x x x

B x x x o o o

C x x x o x x o o

Breached or Compromised

Surfaces

A x x x o

B x x x o o o

C x x x o x x o o

EXTERNALLY COMMUNICATING

DEVICES Infusion sets,

dialyzers , laparoscopes, dental filling

materials

Blood Path, Indirect

A x x x x x

B x x x x o x

C x x o x x x o x o o

Tissue/Bone Dentin

Communicating1

A x x x o

B x x x x x x x

C x x x x x x x o o

Circulating Blood A x x x x o2 x

B x x x x x x x x

C x x x x x x x x o o

IMPLANT DEVICES

Tissue/Bone A x x x o

B x x x x x x x

C x x x x x x x o o

Blood A x x x x x x x

B x x x x x x x x

C x x x x x x x x o o

x Standard ISO evaluation tests

o

Additional tests which may be applicable

Note 1

Tissue includes tissue fluid and subcutaneous spaces

Note 2

For all devices used in extracorporeal circuits


Plastic Material Selection

No. Polymers Acronyms

Full Form

1 ABS Acrylobutadiene styrene

2 PP Polypropylene

3 PS Polystyrene

4 PC Polycarbon

5 PSU Polysulfone

6 PPSU Polyphenyl sulfone

7 PMMA Polymethyl methacrylate (Acrylic)

8 PE Polyethylene

9 UHMWPE Ultra high molecular weight polyethylene

10 LDPE Lower density polyethylene


Biocompatibility is a real requirement?

in contact with body tissues or drugs and how long?

For single use application?

Sterilization method? How often?

Will the device be painted/electroplated /glued?

Humidity, temperature and exposure time?

Does the device need to be visible under a fluoroscope or X-ray?

Is the color of the material is an important factor?

UV resistance?

Environmental exposure considerations


Dimensional stability Loads, how long they will be applied? Continuous or

intermittent? Is toughness or impact resistance critical during use? Electrical isolation? What are the manufacturing processes/options available? Several molding tecniques are available:

– micro molding, – over molding, – insert molding, – gas assisted molding

Target cost of the component? Life time? Aging?

Functional and Mechanical Considerations


Polymer selection

N. Application of medical devices

Polymer selection

1 Non-contact with human body e.g. syringes, blood storage bags, glucose drip bags

PVC, PA, PE, PS, Epoxy resins

2 Short-term contact with human body e.g. catheters, feeding tubes, drainage tubes, surgical instruments

Silicone rubber, Natural rubber, PVC, Polyurethane, PE, PP, Polyester, PEEK, Polyphenylsulfone, Nylon, Teflon, PeBax

3 Medium term contact with human body e.g. cultures, ligatures

Nylon, PP, Polyester

4 Long term contact with human body, e.g. implants, drug delivery devices

PE, UHMWPE, PET, Silicone rubber, Polyurethane, PMMA, Polysulphones, Hydrogels Polyphosphazenes, Thermoplastic elastomers, Polydimethylsiloxane


Sterilization procedure resistance

Polymer Hot air Hot air ETO Plasma Gamma Rays

120 °C 130 °C 180 °C 60 °C 45 °C -

PP 4 4 1 2 3 2

PEEK 4 4 4 4 4 4

PSU 4 3 1 3 3 3

PPSU 4 4 2 4 4 4

PC 2 1 1 3 3 2

4: very good resistance 3: good resistance 2: conditional resistance 1: No resistance


Manufacturing methods

MATERIAL

CO

MP

RES

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N

MO

LD

IN

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TR

AN

SFER

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LD

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G

IN

JEC

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OLD

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EX

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BLO

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TH

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NJEC

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CA

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FO

RG

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AM

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LD

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G

REIN

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RC

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PLA

STIC

M

OLD

IN

G

VA

CU

UM

MO

LD

IN

G

PU

LTR

US

IO

N

CA

LEN

DER

IN

G

Acetal • • • • • • • •

ABS • • • • • • •

Acrylic • • • • • • •

Cellulose • • • • •

Nylon • • • • • • • • •

Polyimide •

Polycarbonate • • • • •

Polyethylene • • • • • • • • •

Polypropylene • • • • • • • • •

Polystyrene • • • • • • • • •

Polysulfone • • • • •

Polyurethane • • • • • • •

PVC • • • • • • • • • • •

Polyvinyl • • • • • • • • •

Tetrafluoroethylene • • • • •


Basic information of plastic materials for MD


Material Selection Flowchart

CONCEPT

EMBODIMENT

DETAIL

Product specification

• Define specifications • Determine function structure • Seek working principles • Evaluate and select concepts

• Develop layout, scale and form • Model and analyze assemblies • Optimize the functions • Evaluate and select and layout

• Analyze components in detail • Select processing route • Optimize performance and cost • Prepare detailed drawings

Market Needs


ISO 14971 provides manufacturers with a framework to manage the risks associated with the use of medical devices.

ISO 14971 specifies a process for a manufacturer to:

– identify the hazards associated with medical devices,

– estimate and evaluate the associated risks,

– control these risks,

– monitor the effectiveness of the controls.

ISO 14971


ISO 14971 Process Overview

Risk A

ssessm

en

t

Risk Analysis

• determining user needs / intended uses • hazard identification • risk estimation

Risk Evaluation

• risk acceptability decisions

Risk Control

• option analysis • Implementation • residual risk evaluation • overall risk acceptance

Post Production

• post production experience • review of risk management experience

Risk M

anage

me

nt


Focus on Patients

Manufacturer’s viewpoint: The intended use/purpose of a medical device can be depicted using an idealized functional input/output diagram

Patient

User (Operator)

Functional Inputs

Functional Outputs

Patient

Time

“Engineering World” “Clinical World”

Medical Benefits

Medical Device


Focus on Patients

Risk Management takes the idealized functional input/output diagram and identifies potential problems:

Patient

User (Operator)

Functional Inputs

Functional Outputs

Patient

Time

“Engineering World” “Clinical World”

Environmental Disturbances

Medical Benefits

User Errors

Medical Device

hazards harm

“Risk Management”

Failure Modes


Risk management principles should be applied throughout the life cycle of medical devices and used to identify and address safety issues. The current approach to device safety is to estimate the potential of a device becoming a hazard that could result in safety problems and harm. This estimate is often referred to as the risk assessment.

In general, risk management can be characterized by phases of activities: – determination of levels of risk that would be acceptable in the device, – risk analysis, – risk evaluation, – risk control and monitoring activities.

The risk analysis starts with identifying hazards that may occur due to characteristics or properties of the device during normal use or foreseeable misuse

ISO 14971 - Risk Management

21


What is Risk Management ?

The systematic application of management policies, procedures and practices to the tasks of

analyzing, evaluating and controlling risk

** Courtesy of ISO 14971:2007 “Medical Devices -= Application of risk management to medical devices”, Terms and Definitions, 2.22


harm: physical injury or damage to the health of people, or damage to property or the environment

hazard: potential source of harm hazardous situation: circumstance in which people, property or the environment are

exposed to one or more hazard(s) risk: combination of the probability of occurrence of harm and the severity of that

harm risk analysis: systematic use of available information to identify hazards and to

estimate the risk risk assessment: overall process comprising a risk analysis and a risk evaluation residual risk: risk remaining after protective measures have been taken risk control: process through which decisions are reached and protective measures

are implemented for reducing risks to, or maintaining risks within, specified levels risk evaluation: judgment, on the basis of risk analysis, of whether a risk which is

acceptable has been achieved in a given context based on the current values of society risk management: systematic application of management policies, procedures and

practices to the tasks of analyzing, evaluating and controlling risk

Some definitions


Examples

Hazard Hazardous Situation

Harms

A sharp tip Tip perforates vessel wall

Vessel trauma-major

Inflated Balloon Blocked blood flow

Angina

Catheter not sterile

Infectious agents from catheter released into body

Infection


Document both the intended use and foreseeable misuse of the device

Identify known and foreseeable hazards associated with the device

Hazard + Sequence of events = Hazardous Situation

Severity × Probability = Risk

Risk Analysis


Risk Control


Risk estimation: the concept of risk is the combination of the following two components: – the probability of occurrence of harm, that is, how

often the harm may occur;

– the consequences of that harm, that is, how severe it might be.

Probability estimation: – Does the hazard occur in the absence of a failure?

– Does the hazard occur in a failure mode?

– Does the hazard occur only in a multiple-fault condition?

Risk concepts applied to medical devices


The concept is in reality a continuum, however in practice a number of discrete levels can be used. In this case, the manufacturer decides how many categories are needed and how they are to be defined. The levels can be descriptive: 1. incredible 2. improbable 3. remote 4. occasional 5. probable 6. frequent

or symbolic – (P1, P2, etc.)

Risk level


The probability of each undesired event occurring is identified at the hazard-identification stage. Three approaches are commonly employed to estimate probabilities, as follows: – use of relevant historical data,

– prediction of probabilities using analytical or simulation techniques,

– use of expert judgment

They can be used individually or jointly but must be coherent

Probability


The ISO 14971 does not specify acceptable risk!

Risks can be categorized into the following three regions: – broadly acceptable region: the risk is so low that it is

negligible in comparison with other risks and in view of the benefit of using the medical device

– ALARP (As Low As Reasonably Practicable) region: any risk associated with a medical device would be acceptable if the patient’s prognosis were improved; BUT this cannot be used as a rationale for the acceptance of unnecessary risk. Practicability refers to the ability of a manufacturer to reduce the risk. Practicability has two components:

• a) technical practicability, and

• b) economic practicability.

– intolerable region.

Risk acceptability


A hazardous situation can result from the failure of a system. There are two possible types of failure: – random failures: statistical probability. e.g. the

probability of failure of an assembly can be estimated from the failure probabilities of the components

– systematic failures examples: a) An incorrectly rated mechanical part fails to prevent a hazardous

situation. The part could be incorrectly designed, incorrectly assembled during manufacture, or incorrectly replaced during repair.

b) The use of incorrect material: the material might have been incorrectly specified, or incorrectly used during manufacture (e.g. the incorrect material is ordered from the supplier).

c) A software does not provide a correct information to the HMI. A possible consequence is that the surgeon can decide a therapy instead of a different one.

Cause of failure


Example of a three-region risk chart

Intolerable region

ALARP region

Broadly Acceptable

region

In

creasin

g p

ro

bab

ilit

y o

f o

ccu

rren

ce

Increasing severity of harm


Results representation

33

Severity of injury Catastrophic Critical Marginal Negligible

Fre

qu

ency

of

occ

urr

en

ce

Frequent

Probable

Occasional 7. mobile parts

Remote

Unlikely

33. storage or operation outside of the environmental conditions prescribed 54. spikes or sharp edges

34. incompatibility with other devices with which it is expected to be used

Incredible

16. bioincompatibility 18. toxicity 25. pyrogenicity 26. inability to maintain hygienic safety 35. accidental mechanical damage 46. specific inadequate use of preliminary checks 48. use by personnel with no skills / untrained 49. reasonably foreseeable misuse

15. biocontamination 17. Incorrect chem. formulation 19 allergenicity 24. re-infection and/or cross infection 43. inadequate labeling 44. operating instructions inadequate 51. inadequate warning of the dangers likely with the re-employment of disp. disposable 53. incompatibility with consumables / accessories / other medical devices 69. Lack of end of life of the medical device 70. Loss of mechanical integrity 71. inadequate package 72. improper reuse

Broadly acceptable region

As low as reasonably practicable region (ALARP)

Intolerable region


Energy hazards and contributory factors – electricity, – heat, – mechanical force, – ionizing radiation, – non-ionizing radiation, – moving parts, – unintended motion, – suspended masses, – failure of patient-support device, – pressure (e.g. vessel rupture), – acoustic pressure, – vibration, – magnetic fields (e.g. MRI).

Possible hazards and contributing factors

34


Biological hazards and contributory factors: – bio-contamination, bio-incompatibility, toxicity,…etc.

Environmental hazards and contributory factors: – electromagnetic fields, inadequate supply of power,…etc.

Hazards resulting from incorrect output of energy and substances: – electricity, radiation, pressure, … etc.

Hazards related to the use of the medical device and contributory factors: – inadequate labeling, inadequate operating instructions, … etc

Inappropriate, inadequate or over-complicated user interface (man/machine communication): – mistakes and judgement errors, lapses and cognitive recall errors, … etc.

Hazards arising from functional failure, maintenance and ageing and contributory factors: – erroneous data transfer, lack of, or inadequate specification for maintenance

including inadequate specification of post-maintenance, functional checks, inadequate maintenance,… etc

Possible hazards and contributing factors

35


What is the intended use/intended purpose and how is the medical device to be used? Is the medical device intended to contact the patient or other persons? What materials and/or components are incorporated in the medical device or are used

with, or are in contact with, the medical device? Is energy delivered to and/or extracted from the patient? Are substances delivered to and/or extracted from the patient? Are biological materials processed by the medical device for subsequent re-use? Is the medical device supplied sterile or intended to be sterilized by the user, or are

other microbiological controls applicable? Is the medical device intended to be routinely cleaned and disinfected by the user? Is the medical device intended to modify the patient environment? Are measurements taken? Is the medical device interpretative? Is the medical device intended for use in conjunction with medicines or other medical

technologies? Are there unwanted outputs of energy or substances? Is the medical device susceptible to environmental influences?

Questions to identify MD characteristics

36


Does the medical device influence the environment? Are there essential consumables or accessories associated with the medical device? Is maintenance and/or calibration necessary? Does the medical device contain software? Does the medical device have a restricted shelf-life? Are there any delayed and/or long-term use effects? To what mechanical forces will the medical device be subjected? What determines the lifetime of the medical device? Is the medical device intended for single use? Is safe decommissioning or disposal of the medical device necessary? Does installation or use of the medical device require special training? Will new manufacturing processes need to be established or introduced? Is successful application of the medical device critically dependent on human factors

such as the user interface? – Does the medical device have connecting parts or accessories? – Does the medical device have a control interface? – Does the medical device display information? – Is the medical device controlled by a menu?

Is the medical device intended to be mobile or portable?

Questions to identify MD characteristics

37


Thank you!

Documents

The industrial process: from prototypes to medical ... · Risk assessment and management analysis for medical devices ... strength, fatigue, …) and thermal resistance, conductivity