medical devices: how to stay included · 2016. 8. 22. · case study #1 – heart valve . signal:...

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


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

Presenter

Presentation Notes

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


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


Presenter

Presentation Notes

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


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



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


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


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?


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)


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))


Presenter

Presentation Notes

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


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


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


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


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


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?


What happened next? Case study #2 – tissue morcellators

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


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.


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


http://www.tga.gov.au/legislation-legislative-instruments

http://www.tga.gov.au/publication/australian-regulatory-guidelines-medical-devices-argmd

http://www.tga.gov.au/form/essential-principles-checklist-medical-devices

http://www.tga.gov.au/systematic-literature-searches-literature-based-submissions