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Presentation: Session 3: Post-market reviews

Workshop: Medical devices: how to stay included

24 August 2016

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Presentation

  • Presented by: Amanda Craig
  • Presented at: Workshop: Medical devices: how to stay included
  • Presentation date: Workshops were held on 19 May 2016, 2 June 2016, 23-24 June 2016, 21 July 2016 and 27 July 2016
  • Presentation summary: This presentation discusses the post-market review process of medical devices

Transcript

Medical Devices: how to stay included

Post-market reviews

Amanda Craig
Technical Officer
Device Vigilance and Monitoring Section
Medical Devices Branch
Therapeutic Goods Administration

Slide 1 - 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.

Slide 2 - 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

Slide 3 - 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 at 24 May 2016) 186 28

We regulate therapeutic goods throughout their lifecycle in a number of ways

  • Register
  • Monitor
  • Changes to product information, safety alerts, recalls
  • Enforce compliance
  • Assess evidence

Slide 4 - 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.

Slide 5 - 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

Slide 6 - 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

Slide 7 - Case study #1 - heart valve

  • Information requested
    • Clinical evidence
    • Technical documentation
    • Risk assessment documents
    • IFUs
    • Post-market data

Slide 8 - 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

Cycle Diagram of evidence - Clinical evidence report - Risk assessment - Risk mitigations - Post-market vigilance.

Slide 9 - Post-market review: evidence

What 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

Cycle Diagram of evidence - Clinical evidence report - Risk assessment - Risk mitigations - Post-market vigilance.

Slide 10 - Evidence: Clinical evaluation report

Data Aquisition
Literature search Clinical trial data Post-market surveillance
Data Evaluation
Critical analysis and synthesis of data Risk and benefit conclusion
Flow-through
Risk assessment documentation Risk mitigation strategies

Authored/approved by an expert in the field, accompanied by their CV as evidence of that.

Slide 11 - 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 - From identified search terms and inclusion criteria

Publications reviewed - Literature excluded with reasons (list provided)

Relevant literature - Literature excluded from clinical evaluation with reasons

Systematic literature searches for literature based submissions

Slide 12 - 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

Diagram listing risk management cycle - mitigation - identification - assessment.

Risk Management Matrix - severity on y axis - frequency on x axis

ISO 14971

Slide 13 - 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

Slide 14 - 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

Process Diagram: technical standards, conformity report, risk assessment - design & manufacturing, risk mitigation - validation and verification of QMS.

Slide 15 - 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?

Slide 16 - 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

Slide 17 - 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))

Slide 18 - 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

Slide 19 - Post-market review statistics

Post-market review statistics
Year #ARTG entries #completed Cancelled by Sponsor Cancelled by TGA
2014 226 168 34 13
2015 195 116 118 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

Slide 20 - Reasons for Sponsor cancellations

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

Slide 21 - 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

Slide 22 - 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

Slide 23 - 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?

Slide 24 - What happened next? Case study #2 - tissue morcellators

  • Amended IFUs distributed through recall sections with new black box warning

Slide 25 - 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.

Slide 26 - Further information

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