Embed Size (px)
Citation preview
James Pink
Medical Device Risk Management
Requirements
The medical device industry is highly regulated and based upon a device specific risk rating for dealing with the level of regulation to be applied prior to market acceptance
All modern medical device regulations cite ISO14971:2007 as being the standard to apply for medical devices
Global Harmonisation requirements
GHTF safety and performance requirements require risk management to be used as a basis of identifying, evaluating, controlling and continuously monitoring the effectiveness of risk controls.
The need for risk management
4
Source GHTF Study Group 1
The need for risk management
5
Source GHTF Study Group 1
The need for risk management
6
Does it mean anything to me as adrug manufacturer If you have a drug delivered by means
of a combination product then you are required to ensure that the device meets all safety and performance criteria of medical device regulations. As a result you are required to ensure that devices for drug-device combinations are being designed, manufactured, supplied and used in a way that all risks are controlled and the risks are outweighed by the clinical benefit.
The need for risk management
8
Risk management process
ISO14971:2007 requirements
9
Risk Management Organisation
10
Risk management process
11
Input
New Product developmentNew Process introduction
Change to ProductChange to processSignificant Change
Adverse Incident trendsAdverse Manufacture trends
New markets / usersPMS TrendsCAPA Trends
Activity Output
Risk Management controlsManagement Review analysis
Adverse trends awarenessManufacturing limits & Controls
Supplier limits & ControlsSurgeon Training points
Post Market Clinical Follow-upComplaints investigator trainingChange control team awareness
CAPA investigator awareness
Resources
Risk Management TeamRisk Management experts
Risk Management databaseCustomers and Clinical leads
Records
Risk Management PlansRisk Management FMEA’sRisk Management Reports
Meetings, Measures and actions
PMS MeetingsProduct Review meetings
Supplier MeetingsChange control meetings
Intra project Risk Analysis meetingsRisk Management review meetings
Management Review meetingSurgeon / User feedback
Clinical Evaluation updatesNew Standards, risks and controls
Risk management process
12
Example
A new product development project is initiated. The process requires a plan, defines the information sources and identifies how clinical benefit will be derived from customers.
Risk reviews, tools and methods are all defined including the forms, procedures and records required
A Final report is written defining residual risks, controls and clinical benefit
Risk management process
13
Example
A change in Valve supplier is proposed for the MDI.
The process defines what will happen, how the change is categorised based upon importance and defines the level of process risk management, controls and reviews necessary.
Risk reviews, tools and methods are all defined including the forms, procedures and records required
Risk Management - Acceptability
ISO14971:2007 requirements
14
THIS HAS TO COME FROM A JOINT REVIEW WITH YOU AND YOUR SUPPLIER
Risk management acceptability
15
Increasing severity of HarmIncr
easi
ng p
robabili
ty o
f occ
urr
ence
of
Harm
Severity
5 = Death4 = Revision / irreversible3 = Reversible injury2 = Minor Injury1 = Inconvenience
Probability
5 = <1 in 1004 = 1 in 1003 = 1 in 10002 = 1 in 10,000 1 = >1 in 100,000
Based upon Surgical procedures
Risk management acceptability
16
Increasing severity of HarmIncr
easi
ng p
robabili
ty o
f occ
urr
ence
of
Harm
Severity
5 = Critical to safety4 = Critical to function3 = Customer Image2 = Upset the customer1 = Inconvenience
Probability
5 = <1 in 1004 = 1 in 1003 = 1 in 10002 = 1 in 10,000 1 = >1 in 100,000
Based upon Surgical procedures
Device fails to deliver appropriate uniform dose over time
Risk management acceptability
17
Risk management acceptability
18
Risk management acceptability
19
Risk management acceptability
20
Risk management acceptability
21
Risk management acceptability
22
Risk management acceptability
TipsEnsure that you are focussed on the current state of the art with relation to drug - device performance
Ensure that you are able to define hazardous situations based upon the major associated failures
Be aware that the level of acceptability will be based around your critical to safety and quality requirements. The final clinical harm will be required so that contract design suppliers and manufacturers are aware of the severity of failure.
23
Risk management plans
ISO14971:2007 requirements
24
Risk management plans
25
Lifecycle phases
If a drug manufacturer uses a device they must develop risk management plans that will ensure all elements of risk are covered from design through to manufacture
Risk management plans
26
Hazardous Situation
Hazard Harm Design Feature Probability Severity
Valve affects Dose plume
Mechanical fatigue Too much drug
Valve and Actuator Fatigue ?3
5
Step 1 - Undertake literature reviewStep 2 - Review previous designsStep 3 - Undertake Design VerificationStep 4 - Undertake Design ValidationStep 5 - Assign probability valueStep 6 - Include in Clinical Evaluation
Risk management plans
27
Hazardous Situation
Hazard Harm Design Feature Probability Severity
Valve affects Dose plume1
Mechanical fatigue Too much drug
Valve and Actuator Fatigue2 ?33
5
Risk Verification Report
Risk Management Meeting date 21/12/2009
Summary1 Verified information source from Clinical
evaluation report C01989 issue 22 Design FMEA conducted 21/12/2008
verified3 Test report T18786 revision 1 verified4 Reviewed Test report and confirmed risk
control acceptable
ConclusionRisks identified in the risk analysis coincide with the original information sources and risk management activities defined within the RM Plan document D001 revision 3Controls within Design have been reviewed and reduction of probability is consistent with the control
Signed ____________Date 21/12/2009
Risk management file
ISO14971:2007 requirements
28
Risk management file
29
Risk Management Plan
Clinical Evaluation – PHA*
Identification of Characteristics
Design FMEA
Application FMEA
Requirement
Process / Supplier FMEA
Risk Management Report
Risk Analysis
ISO14971:2007
30
Risk analysis
31
Annex G activities
MDI
Preliminary Hazard Analysis
MDI
Preliminary Hazard Analysis
MDI
Clinical / Scientific
evaluation Preliminary
report
MDI
Clinical / Scientific
evaluation Preliminary
report
MDI
DFMEARevision 1
MDI
DFMEARevision 1
MDI
DFMEARevision 3
MDI
DFMEARevision 3
MDI
PFMEARevision 1
MDI
PFMEARevision 1
MDI
PMCFRevision 1
MDI
PMCFRevision 1
Risk analysis
32
Preliminary Hazard Analysis
Review of FDA Guidance provides the following summary of requirements....
33
Characteristic Hazardous Situation Potential Harm Severity
Dose content uniformity Insufficient Dose uniformity- Design characteristic failure / Actuator / Valve
insufficient dose deliveredtoo high dose delivered
depends on customer / drugdepends on customer / drug
Dose content uniformity Degradation of Dose uniformity over time – Design characteristic failure of actuator / valve over the lifetime of uses
As above As Above
Aerodynamic particle size Particle size is > 5Microns- Design characteristic failure of the MDI (Size and shape of expansion chamber / stem
insufficient dose delivered As above
Spray Pattern and Plum geometry
Inappropriate spray pattern and or plume geometry – Design characteristic failure / Actuator / Valve
As above As above
Leaching Drug chamber / contact materials leaching - polynuclear aromatics (PNAs), nitrosamines, monomers, plasticizers, accelerators etc.
Toxicological effects depends on customer / drug and patient contact
The preliminary clinical / Scientific report Description of the intended performance
Describe reasonable performance expectations
Describe indications and claims if known
Standards and Regulatory guidance review
Literature review based upon common features / exclusion and inclusion criteria
Summary of current methods and their limitations including current techniques, instrumentation and surgical technique, current outcomes and expected clinical benefit
Evaluation of your experiences from similar devices
Confirmation from your customer relating to some of the most important aspects for their Drug Master file.
= Compilation of Hazards / Hazardous situations to be included in future risk analysis
= Consideration relating to risk acceptability
34
The preliminary clinical report
Ensure that previous risk analysis are reviewed.
Review of Design failures (Where output could not be achieved)
Review of failed validations
Review of limitations – Technology, Process, Supply chain or Drug delivery
Review of customer complaints relating to similar designs or similar intended use
35
Risk analysis – PHA for MDI.
Hazard Forseeable sequence of events Hazardous situation Information Source
Harm
MechanicalDose content uniformity
After several actuations the dose content uniformity is compromised
Design
[See Design FMEA for Valve and actuator design]
Process
See Process FMEA
Use
[See usability / AFMEA]
FDA GuidanceDesign and Test data on file
Insufficient doseOverdoseNo dose
ChemicalLeaching
Unintended leaching of toxic compounds from the container / plastic components enter into the drug and are delivered to the patient
Design
[Selection of the material and manufacturing method – See DFMEA]
Process
[See PFMEA – Inappropriate moulding parameters – incorrect material spec]
Use
[See usability / AFMEA]
FDA GuidanceDesign Data on file
Toxicological / Poisoning
36
Risk management in Design
Tip
Ensure that there are regular reports relating to the design progress but ensure that risks identified and their references are reported within the phase as this concentrates the minds of the people undertaking the design project
37
Risk management documentation in design Risk Management Plan
Clinical / Scientific Reports
R&D Reports
Process Validation reports
Supplier qualification reports
Design Validation reports
Usability reports
Identification of characteristics affecting safety Design FMEA
Process FMEA
Application FMEA
Risk management summary
Post market clinical follow up and risk reviews
Transfer to manufacture risk management control plans
38
Risk management in design
39
PrelimHazard Analysi
s
PrelimHazard Analysi
s
Risk Analysi
s
Risk Analysi
s
Clinical literature
Design StandardsCompetitor products
Recalls and advisory
Previous RA
Intended Use
Characteristics
Hazard identification
Outcomes
Reliability dataCustomer feedback
Manufacturing data
Risk Report
Risk Report
Risk Mgt Plan
Risk Mgt Plan
Typical Controls in Design.
Functional Testing / Bench Testing
Testing against a Standard – Validation i.e. ISO11137, ISO11607, ISO7206-4, IEC 60601-1 – FDA Guidance
Simulation – Finite Element – Wear performance
Hand Calculation
Prototype study
Choice of Materials
Choice of processes and Technology
Focus Group (Human Factor Analysis)
Clinical Literature Searches
Concept Reviews (Focus Group) – Surgeon / Clinical / User opinion
CAD Assembly / Tolerance Study
Design of Experiments
Tolerance Stack Analysis
Assembly Testing
Scientific / Engineering Constant
Review of Similar Designs
Measurement Systems analysis
Clinical Investigations
Validations
MTBF – Stability testing
40
REMEMBERThe control will be usedin order to give you assurancewhen you are doing a test that you have covered a risk........
Typical controls in Design
ISO Standards
FDA Guidance
Customer Testing methods
Bespak Testing methods
41
Risk Management in process
42
Risk Management in process
43
Validation activities should be initiated
with risk management
Process hazards should derive from
the DFMEA
Risk Management in process
44
Hazards How Moulding can initiate the hazard
Leaching
Inappropriate materialIncorrect Heat and
pressureIncorrect additives
Inappropriate mould time ?????
Sequence of events
inappropriate cross linking of polymer leads to plasticiser free radicalinappropriate material
formulation / ingredient selected
Moulding controls
Material verificationProcess Validation of Moulding parameters
Goods inwards Verification of raw
materialsQC Sampling for
Leaching
Typical Controls in Process.
Testing Points
Trained in a SOP
Gauge R&R
Process Validation
Monitoring and Measurement (SPC Process or product parameters)
Poke Yoke Settings
Checkmate Verifications / Closed Loop Systems
Software validation
5S / Line Clearances
Identification and Traceability
Physical Location controls
Start up verifications
In process verifications
Routine Maintenance
Calibration
ISO13485:2003 / Ordinance or FDA Control requirements.
Supplier Evaluation – First Article / PPAP
Routine Audits
45
Risk Controls – Risk benefit
ISO14971:2007 requirements
46
Risk controls – risk benefit
ISO14971:2007 requirements
47
Risk Management Report
48
Typical Risk Management Report
Summarises the Way you did risk management
Summarises that the risk controls have been implemented (And verified)
Summarises where you got the information
Provides a succinct summary of the results of the activities and how controls will be reviewed on an ongoing basis
49
Keeping risk management alive
Concept diagram - MDI
51
Define the Scope of Project
Area MDI
Operator / User
COPD Patient
Delivery method
Valve / Actuator
Intended Use
Particle SizeNumber of usesDrug type
Indications for use
Critical to quality requirements
Technology Moulding / Machining
Develop the ProductDefine the need
Select the Risk Management Plan to use
Define the Scope of the Project
Generic
RM PlanDev
Lifecycle
Generic
RM PlanDev
Lifecycle
CustomRM PlanDev
Lifecycle
CustomRM PlanDev
Lifecycle
Develop the ProductDevelop the ProductImplement Process
Develop the ProductPlace on Market
PHAPHA
DFMEADFMEA
PFMEAPFMEA
PHAPHA
Customer Acceptabilit
y
Customer Acceptabilit
y
Risk control
Verification
Risk control
Verification
Define the need
Design Validatio
n
Design Validatio
n
ProcessValidatio
n
ProcessValidatio
n
change to risk?
Risk controls effective?
YES
NO
What the clinical benefit
would be
Reasonable expected performan
ce
Hazards relating to the current
use, Technology
Risk Manag
eReport
Risk Manag
eReport
Clinical Benefit
V Risk
Clinical Benefit
V Risk
On Market
RM Plan
Lifecycle
On Market
RM Plan
Lifecycle
Change
RM Plan
Lifecycle
Change
RM Plan
LifecycleDatabas
e
