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Medical Devices: how to stay included Post-market reviews
Amanda Craig Technical Officer Device Vigilance and Monitoring Section Medical Devices Branch Therapeutic Goods Administration
Learning outcomes It is envisaged at the end of this session you will you be able to:
• understand the post-market review process of medical devices.
• appreciate the importance of strong working relationship between the manufacturer and sponsor.
• recognise appropriate and acceptable documentation that provides evidence of compliance with the Essential Principles.
• understand the continuum of a QMS, with the evidence informing the CER, which informs the risk assessment, which in turn informs the risk mitigation strategies, for the life of the device.
• implement processes to ensure appropriate responses to post-market vigilance and post-market reviews.
Medical Devices: how to stay included 1
Overview • The TGA’s role in post-market monitoring • Post-market monitoring
the why, who, when, and what • Quality Management System Clinical evaluation report Literature search Risk management documentation Instructions for Use Technical documentation
Medical Devices: how to stay included 2
Role of the TGA in post-market monitoring The TGA’s role is to continually monitor and evaluate the safety and efficacy or performance of therapeutic goods that are available on the market and to manage any risks associated with individual products.
Number of reviews Year # ARTG entries # completed
2014 226 168
2015 195 116
…2016 (As at24 May 2016)
186 28
We regulate therapeutic
goods throughout
their lifecycle in a number
of ways
Assess evidence
Register
Changes to product information, safety alerts, recalls
3
Enforce compliance
Monitor
Post-market monitoring
• Why are post-market reviews conducted (not an exhaustive list):
− Trends from IRIS − Recurrent advertising breaches − Unresolved/repeated recalls − Information from other regulatory
agencies − ARTG anomalies
• Who or what is reviewed: − Sponsor − Manufacturer − Ingredient − Product − Kind of device
• When: − Any point in the product’s life-cycle.
Medical Devices: how to stay included
4
Case study #1 – heart valve Signal:
• adverse events relating to leaflet breakage IRIS investigation
• same problem reported from another manufacturer’s heart valve TGA checks available data reports for other heart valves recall for heart valve
Review of all similar heart valves to determine if isolated issue or systemic
Medical Devices: how to stay included 5
Post-market review process Calling in and reviewing:
- Essential Principles checklist - Post-market data incl. supply, adverse
events and complaints - Labels - IFU - Current clinical evidence report - Risk management documentation
- Declaration of conformity & manufacturer’s certification
- Technical documentation - Ingredients and formulations of
medicated/formulated devices - Advertising material - CAPAs - Samples
Dependent on the issue under review Medical Devices: how to stay included 6
Case study #1 – heart valve
• Information requested – Clinical evidence – Technical documentation – Risk assessment documents – IFUs – Post-market data
Medical Devices: how to stay included 7
Post-market review: evidence What to submit:
- Cover letter explaining documents (Table of Contents) - All information requested in a single submission on time - Information in a clear and logical format - Linked information - Accurate data - Referenced documents - Documents in English - Electronic submission
Clinical Evidence Report
Risk assessment
Risk mitigations
Medical Devices: how to stay included 8
Post-market vigilance
Post-market review: evidence W hat NOT to submit:
- Multiple unlinked or unclear emails - Separate documents over several days - Incomplete dossier - Excerpts from documents - Data dump - Documents with data integrity issues
Clinical Evidence Report
Risk assessment
Risk mitigations
Medical Devices: how to stay included 9
Post-market vigilance
Evidence: Clinical evaluation report
Flow-through
Risk assessment documentation Risk mitigation strategies
Data Evaluation
Critical analysis and synthesis of data Risk and benefit conclusion
Data Acquisition
Literature search Clinical trial data Post-market surveillance
Authored/approved by an expert in the field, accompanied by their CV as evidence of that. Medical Devices: how to stay included 10
Evidence: Literature search • Must be unbiased and reproducible
– Period covered by search– Databases used– Search terms– Filters/criteria of inclusion– Exclusion criteria
• Number of citations from each database• List of excluded citations with justification• Full copy of all publications included, in
English• Published, peer-reviewed literature, i.e.
not newspaper or magazine article
Potential literature
Publications reviewed
Relevant literature
http://www.tga.gov.au/systematic-literature-searches-literature-based-submissions 11
• From identified search term s and inclusion criteria
Literature excluded with reasons (list provided)
•
Literature excluded from clinical evaluation with reasons
•
Evidence: Risk management Pre-market development
Post-market vigilance
Hazard identification Adverse event reporting Complaint management
Hazard recognition Sentinel event recognition
Risk evaluation Health hazard evaluation
Risk control application Corrective and Preventative Action (CAPA)
Risk control verification/validation
CAPA
Identification
Assessment
Mitigation
ISO 14971
Frequency Se
verit
y Medical Devices: how to stay included 12
Evidence: Instructions for use
– Manufacturer is responsible for packaging, labelling, instructions for use, and training
– Appropriate for product – Risk mitigation Not 1st line of risk mitigation
– Essential Principle 13 – Essential Principle Checklist – 10.2 – Information about the Sponsor
Therapeutic Goods (Medical Devices) Regulations 2002
Medical Devices: how to stay included 13
Evidence: Technical documentation Validation of evidence for relevant EPs, dependent upon
scope/issue being reviewed. For example:
• EP checklist
• Conformity report against relevant technical standards
• ISO 13485 certification for manufacturer
• Test reports demonstrating design and development changes;
verification and validation
• Verification of purchased products
• Sterilisation process records
• Useability studies
Technical standards
Conformity Report
Risk assessment –
design & manufacturing
Risk mitigation – validation & verification
of QMS Medical Devices: how to stay included 14
Case study #1 – heart valve
• Information requested – Clinical evidence – Technical documentation – Risk assessment documents – IFUs – Post-market data
• What was sent – Multiple emails with lots of journal articles – IFUs – EP checklist – Risk assessment
• When was it sent – Following a reminder s41JA letter – Emails stretched across a week or more
So, what happened
next?
Medical Devices: how to stay included 15
Post-market review outcomes
• Closure of review • Not in scope • Sufficient and satisfactory evidence
provided • Amendment to Instructions for Use
• With or without recall action • Recall of devices or safety notice
• Additional conditions of inclusion (s41 FP) • Suspension (s41 GA & GF) • Cancellation (s41 GK, GL, GM, & GN) • Referral to:
• Advertising Compliance (s42 DL), or • Regulatory Compliance
Uniform Recall Procedure for Therapeutic Goods (www.tga.gov.au/industry/recalls-
urptg)
Medical Devices: how to stay included 16
What happened next? Case study #1 – heart valve • Proposal to Cancel (s41GN(2))
– Failure to provide information after a s41JA letter
(s41GN(1)(c)); and – Failure to comply with the Conditions of Inclusion (s41GN(1)(b)) sufficient information is provided that shows compliance with
the Essential Principles; and – The safety and performance of the device is unacceptable
(s41GN(1)(d))
Medical Devices: how to stay included 17
What happened next? Case study #1 – heart valve
• Sponsor provided response within 20 workings days
– did not include the required information
– assessment of the material supplied still did not alleviate TGA’s concern about the safety and performance of the device
• A letter cancelling the device based on the previous three provisions
• Cancellation was published on TGA’s website
Medical Devices: how to stay included 18
Post-market review statistics Year #ARTG entries #completed Cancelled by
Sponsor Cancelled by TGA
2014 226 168 34 13
2015 195 116 18 10
…2016 (as at 24 May 2016)
186 21 9 0
TGA cancellations Reason # 2014 # 2015 #2016…
Not replying to a s41JA request for information
6 0 0
Non compliance with automatic conditions of inclusion
7 10 0
Medical Devices: how to stay included 19
Reasons for Sponsor cancellations Reason #
2014 # 2015
# 2016 (as at 24 May)
Change of sponsor 5 1 0
Change in manufacturer 1 0 0
No device supplied under entry 5 2 1
Device no longer supplied 6 10 1
Information not provided 11 3 1
Incorrectly classified 1 0 6
Model superseded 2 1 0
No longer the distributor 3 0 0
No longer making medical claims
0 1 0
Medical Devices: how to stay included 20
Key messages • Post-market reviews
– Read the request for information carefully
– Provide considered answers to the questions, making links between the information provided and the issue being explored
– Ensure documentation is current, relevant, and appropriately labelled
– It is not the responsibility of the TGA to decipher the dossier; it is the manufacturer's responsibility to put two and two together
– If the submission is complex or contains multiple documents, add a flow chart, table of contents, and/or narrative to guide the reviewer
– If a document is referred to in your submission it should also be supplied
– If in doubt, contact the TGA
Medical Devices: how to stay included 21
Case Study #2 – tissue morcellators Signal:
• Information from FDA TGA checks available data clinical report request feedback from Sponsors
Review of all tissue morcellators on the ARTG
Medical Devices: how to stay included 22
Case study #2 – tissue morcellators • Information requested
– IFUs – Post-market data
• What was sent – IFUs – Supply and adverse event data
• When was it sent – Within the specified timeframe by all Sponsors
So, what happened
next?
Medical Devices: how to stay included 23
What happened next? Case study #2 – tissue morcellators
• Amended IFUs distributed through recall sections with new black box warning
Medical Devices: how to stay included 24
Learning outcomes At the end of this session it is envisaged that you will:
• Have an understanding of the post-market review process of medical devices.
• Appreciate the importance of strong working relationship between the manufacturer and sponsor.
• Recognise appropriate and acceptable documentation that provides evidence of compliance with the Essential Principles.
• Understand the continuum of a QMS, with the evidence informing the CER, which informs the risk assessment, which in turn informs the risk mitigation strategies, for the life of the device.
• Implement processes to ensure appropriate responses to post-market vigilance and post-market reviews.
Medical Devices: how to stay included 25
Further information • Therapeutic Goods Act 1989 • Therapeutic Goods (Medical Devices) Regulations 2002
– http://www.tga.gov.au/legislation-legislative-instruments • Australian regulatory guidelines for medical devices
– http://www.tga.gov.au/publication/australian-regulatory-guidelines-medical-devices-argmd • Essential Principles checklist
– http://www.tga.gov.au/form/essential-principles-checklist-medical-devices • Systematic literature searches for literature based submissions
– http://www.tga.gov.au/systematic-literature-searches-literature-based-submissions • Draft clinical evidence guidelines – Medical devices
– https://www.tga.gov.au/consultation/consultation-draft-clinical-evidence-guidelines-medical-devices • International Medical Device Regulators Forum
– www.imdrf.org
Medical Devices: how to stay included 26