Risk assessment and management analysis for medical devices

Transcription

1 The industrial process: from prototypes to medical products Risk assessment and management analysis for medical devices February 10, 2016 BERNARDO MAGNANI Ekymed Srl EndoVESPA - H2020-ICT GA no

2 Outline of the presentation ISO biocompatibility of medical devices Plastic material selection: some advices ISO 14971: application of risk management to medical devices

3 Material selection criteria 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

4 Biocompatibility 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

5 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.

6 ISO Standard The ISO 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.

7 Characterization Methods 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.

8 Cytotoxicity Sensitization Irritation/Intracutaneous Acute Systemic Toxicity Subchronic Toxicity Genotoxicity Implantation Hemocompatibility Chronic Toxicity Carcinogenicity Reproductive/Developmental Biodegradation ISO test matrix DEVICE CATEGORIES BIOLOGICAL EFFECT CONTACT DURATION BODY CONTACT SURFACE DEVICES EXTERNALLY COMMUNICATING DEVICES Infusion sets, dialyzers, laparoscopes, dental filling materials IMPLANT DEVICES Skin Mucosal Membrane Breached or Compromised Surfaces Blood Path, Indirect Tissue/Bone Dentin Communicating 1 Circulating Blood Tissue/Bone Blood A = Limited ( 24 hours) B = Prolonged (24 hours - 30 days) C = Permanent (>30 days) A x x x B x x x C x x x A x x x B x x x o o o C x x x o x x o o A x x x o B x x x o o o C x x x o x x o o A x x x x x B x x x x o x C x x o x x x o x o o A x x x o B x x x x x x x C x x x x x x x o o A x x x x o 2 x B x x x x x x x x C x x x x x x x x o o A x x x o B x x x x x x x C x x x x x x x o o 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 Pontedera, x o o Pisa February 10, 2016 x o Note 1 Note 2 Standard ISO evaluation tests Additional tests which may be applicable Tissue includes tissue fluid and subcutaneous spaces For all devices used in extracorporeal circuits

9 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

10 Environmental exposure considerations 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?

11 Functional and Mechanical 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?

12 Polymer selection N. Application of medical devices Polymer selection 1 Non-contact with human body e.g. syringes, blood storage bags, glucose drip bags 2 Short-term contact with human body e.g. catheters, feeding tubes, drainage tubes, surgical instruments 3 Medium term contact with human body e.g. cultures, ligatures 4 Long term contact with human body, e.g. implants, drug delivery devices PVC, PA, PE, PS, Epoxy resins Silicone rubber, Natural rubber, PVC, Polyurethane, PE, PP, Polyester, PEEK, Polyphenylsulfone, Nylon, Teflon, PeBax Nylon, PP, Polyester PE, UHMWPE, PET, Silicone rubber, Polyurethane, PMMA, Polysulphones, Hydrogels Polyphosphazenes, Thermoplastic elastomers, Polydimethylsiloxane

13 Sterilization procedure resistance Polymer Hot air Hot air ETO Plasma Gamma Rays 120 C 130 C 180 C 60 C 45 C - PP PEEK PSU PPSU PC : very good resistance 3: good resistance 2: conditional resistance 1: No resistance

14 COMPRESSION MOLDING TRANSFER MOLDING INJECTION MOLDING EXTRUSION ROTATIONAL MOLDING BLOW MOLDING THERMOFORMING REACTION INJECTION MOLDING CASTING FORGING FOAM MOLDING REINFORCED PLASTIC MOLDING VACUUM MOLDING PULTRUSION CALENDERING Manufacturing methods MATERIAL Acetal ABS Acrylic Cellulose Nylon Polyimide Polycarbonate Polyethylene Polypropylene Polystyrene Polysulfone Polyurethane PVC Polyvinyl Tetrafluoroethylene

15 Basic information of plastic materials for MD

16 Material Selection Flowchart Market Needs Define specifications Determine function structure Seek working principles Evaluate and select concepts CONCEPT Develop layout, scale and form Model and analyze assemblies Optimize the functions Evaluate and select and layout EMBODIMENT Analyze components in detail Select processing route Optimize performance and cost Prepare detailed drawings DETAIL Product specification

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

18 ISO Process Overview 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 Risk Assessment Risk Management Post Production post production experience review of risk management experience

19 Focus on Patients Manufacturer s viewpoint: The intended use/purpose of a medical device can be depicted using an idealized functional input/output diagram Engineering World Clinical World Functional Inputs Functional Outputs Medical Benefits Medical Device Time Patient Patient User (Operator)

20 Focus on Patients Risk Management takes the idealized functional input/output diagram and identifies potential problems: Engineering World Clinical World Functional Inputs Environmental Disturbances Functional Outputs Medical Benefits Medical Device Time User Errors User (Operator) Failure Modes hazards Patient harm Patient Risk Management

21 ISO Risk Management 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 21

22 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

23 Some definitions 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

24 Examples Hazard A sharp tip Hazardous Situation Tip perforates vessel wall Inflated Balloon Blocked blood flow Catheter not sterile Infectious agents from catheter released into body Harms Vessel traumamajor Angina Infection

25 Risk Analysis 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

26 Risk Control

27 Risk concepts applied to medical devices 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?

28 Risk level 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.)

29 Probability The probability of each undesired event occurring is identified at the hazardidentification 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

30 Risk acceptability The ISO 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.

31 Cause of failure 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.

32 Increasing probability of occurrence Example of a three-region risk chart Intolerable region Broadly Acceptable region ALARP region Increasing severity of harm

33 Frequency of occurrence Results representation Frequent Severity of injury Catastrophic Critical Marginal Negligible Probable Occasional Remote Unlikely 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 reemployment 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 33. storage or operation outside of the environmental conditions prescribed 54. spikes or sharp edges 7. mobile parts Broadly acceptable region 34. incompatibility with other devices with which it is expected to be used As low as reasonably practicable region (ALARP) Intolerable region 33

34 Possible hazards and contributing factors 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). 34

35 Possible hazards and contributing factors 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 35

36 Questions to identify MD characteristics 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? 36

37 Questions to identify MD characteristics 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? 37

38 Thank you!