ACSMD meeting statement, Meeting 10, 26 August 2015

Advisory Committee on the Safety of Medical Devices

11 December 2015

Role of the Advisory Committee on the Safety of Medical Devices in the TGA's regulatory decision making process

The ACSMD is a statutory advisory committee established by the Therapeutic Goods Regulations 1990.

The TGA currently has ten statutory advisory committees from which it can obtain independent expert advice on specific scientific and technical matters to aid the TGA's regulatory decision making and other regulatory processes.

The ACSMD provides advice to the TGA on, amongst other things, matters relating to the safety, risk assessment, risk management and performance of medical devices supplied in Australia.

How this statement should be read

The advice provided by the ACSMD is an important element in the undertaking of the regulatory functions of the TGA. However, it forms only one part of the total body of information that is available to, for instance, a TGA delegate making a regulatory decision under the Therapeutic Goods Act 1989 ("the Act"). Therefore, while appropriate consideration will be given to such advice, it is important to note that neither the TGA nor a TGA delegate is obliged to follow it.

It should also be noted that details of the committee's advice may not become publicly available for some time after the committee has provided that advice. The purpose of this Meeting Statement is to describe in general terms the matters considered by the committee at each meeting and for it to be available as soon as reasonably practical after the relevant meeting.

Additionally, following publication of this statement, it is most likely that further work will be undertaken by the TGA to investigate, monitor and / or evaluate the medical devices considered by the ACSMD; and this will continue for some time into the future. It is therefore possible that further information about the medical devices will become publicly available at a later time and this will be pursuant to a regulatory decision under the Act being made and following further consultation with the device's sponsor and / or manufacturer.

Overview of the medical devices referred for advice

The TGA continually monitors medical devices supplied in Australia to ensure their ongoing safety, quality and performance (as the manufacturer intended). As part of this process, the TGA routinely undertakes safety reviews of medical devices, seeks advice on proposed safety reviews and Risk Management Plans and also undertakes post-market monitoring of medical devices.

Safety / Post-market surveillance reviews

No safety / post-market surveillance reviews were considered at this meeting.

Proposed safety reviews

No proposed safety reviews were considered at this meeting.

Risk management plans and post-market monitoring

A Risk Management Plan (RMP) is a set of pharmacovigilance activities and interventions designed to identify, characterise and/or manage risks relating to a therapeutic good. No RMPs were considered at this meeting.

At this meeting, the committee’s advice was sought on the need for post-market monitoring of the Essure contraceptive device.

Essure contraceptive device

The Essure contraceptive device is indicated for women who desire permanent birth control (female sterilisation) and is the only medical device of its type available in Australia. The device was referred to the ACSMD as the TGA was seeking advice on recent information published by other regulators and the media which raised concerns about the number and unusual types of adverse events being reported within Australia and worldwide. The committee noted that there has been an increase in device incidents reported both in Australia and world-wide since 2013: the TGA received four reports from 1999 to 2012 and nine reports since 2013.

These 13 cases included common and known adverse events such as cramps (most common), pelvic pain, pregnancy, ectopic pregnancy, discharge, perforations, and migration of the device. Although the majority of the reported adverse events are noted in the device’s Instructions for Use (IFU) document, the TGA has also observed a number of Device Incident Reports (DIR) containing what appear to be unusual adverse events including fatigue, weight gain, headache, nausea and alopecia.

The committee was asked if it accepted the sponsor’s/manufacturer’s explanation for the increase in adverse event reports across 2013 and 2014. The committee noted that the sponsor has stated that the increase in adverse event reports since 2013 reflects the implementation of an improved post-market surveillance system internationally, following the change of manufacturer.

The committee also noted that the 13 DIR in Australia were of variable quality. The unusual adverse events were few in number and describe a broad range of generalised symptoms that are difficult to define as being specifically related to the Essure device. It was also noted that such events are also reported for many devices, medicines and placebos. As such, the committee agreed that there was no obvious link between the underlying performance of the device and the number and types of unusual adverse events reported.

The committee noted that the TGA has currently not received any evidence to suggest an issue related to the risk management processes which are in place for the device and advised that the explanation for the increase in adverse event reports across 2013 and 2014 was acceptable.

The committee was asked whether additional reporting requirements would be an appropriate method to monitor the rate and pattern of occurrence of adverse events associated with the device. While the committee was not convinced that there was an urgent safety signal that needed to be addressed, the committee advised that additional requirements on the sponsor to regularly report would be an appropriate method to monitor the rate and pattern of occurrence of adverse events associated with the Essure device. More medically confirmed data will give a more accurate indication of trends. The committee supported the collection of additional information from patients/reporters to assist in the future analysis of the safety of the Essure device and advised that reanalysis should occur in three to five years or sooner if the situation warrants it. The committee was asked whether it had any additional suggestions on future investigations by the TGA, with regard to both the observed increase in adverse event reports including the more unusual adverse events. The committee suggested that information on the time between insertion of the Essure device and the emergence of an adverse event was relevant to analysis of the data.

The DIR reports did not provide information on how recently the patient had discontinued hormonal contraceptives. The committee highlighted that adverse events attributed to the presence of the device may actually reflect the discontinuation of a hormonal contraceptive. Details on the temporal relationship between this discontinuation, insertion of the device and the emergence of adverse events should be sought from patients/ reporters.

The committee affirmed that insertion of the Essure device should only be performed by a doctor who has completed an approved training program. Regular review of the adequacy of the training program is appropriate to minimise procedural complications and also to optimise counselling practices.

The committee also advised that the sponsor should consider inclusion of follow-up questions that specifically relate to the Essure device and that this may be facilitated via questionnaires that are already in place and being used as required, when incidents are reported.

The committee was asked whether it had any general comments regarding the Essure device and the issues highlighted above. The committee advised that whilst the reported unusual adverse events are hard to explain and could be related to other medical conditions, they should not be entirely discounted. Quality data collection over time should hopefully clarify the picture.

The serious adverse events of pregnancy, including ectopic pregnancy, and perforations are more clinically concerning and the rates of these events should be closely monitored. Health practitioners and the sponsor should be reminded to report these in order to assess how the rates of these events in the ‘real world’ compare to clinical trial situations. It was commented that generalised symptoms such as fatigue, weight change and rash could be associated with autoimmune disease.

The committee also advised that patient counselling is critical for all contraceptive choices. A patient who does not receive adequate counselling about potential adverse events is more likely to be worried by such events, should they occur. Any possible effects of simultaneous withdrawal from hormonal contraceptives need to be addressed in patient counselling and in the IFU document.

Stakeholder engagement

From time to time representatives from other statutory committees and international regulators are invited to attend a TGA statutory advisory committee meeting.

In this context, it is a standing arrangement for representatives from New Zealand’s Medicines and Medical Devices Safety Authority (MEDSAFE), to participate in ACSMD meetings as observers.

Subcommittee update - Orthopaedic Subcommittee (OSC)

The ACSMD also considered a report from the two most recent (7th and 8th) meetings of its Orthopaedic Subcommittee (OSC).

The OSC's functions are to advise the ACSMD and the TGA on prostheses which have been identified in the Australian Orthopaedic Association's National Joint Replacement Registry (AOANJRR) Annual Report as having a higher than anticipated revision rate. This includes:

  • assessment of clinical data and other relevant information (including submissions from the sponsor) and provision of advice on whether the revision rates associated with the joint replacement are acceptable;
  • consideration of possible reasons for the higher than anticipated rates of early revision for the identified implants, including if there is a link between implant design or manufacture and the revision rates; and
  • providing advice on the strength of the evidence to support the benefit of joint replacement compared with the higher risk of a possible early revision.

The OSC also provides the TGA with advice in relation to orthopaedic issues in general.

The OSC generally convenes three (3) times per year and each new 'review cycle' commences following publication of the latest AOANJRR Annual Report in October each year. Once that report is released, the OSC then usually meets in December each year to firstly consider those orthopaedic implants that have been 'newly identified' in that year's AOANJRR Annual Report as having higher than anticipated rates of revision.

The second meeting is then usually held in March the following year and gives further consideration to some of the 'newly identified' implants which were first considered at the previous December meeting. These are generally implants for which sufficient concern was initially raised by the OSC at its December meeting to warrant further consideration of the most recently available AOANJRR data, rather than waiting for a full 12 month period to elapse before further review occurs.

The third yearly OSC meeting is usually held two months later, in May, to give further consideration to orthopaedic implants (and / or implant combinations) which are still used and have been "re-identified" in the AOANJRR Annual Report as having higher than anticipated revision rates. The implants considered at this meeting have already been identified in one or more of the earlier AOANJRR Annual Reports and previously referred to the OSC (and its predecessor) for advice (and the advice at those previous meetings, was that the TGA should 'continue to observe' these implants and 'revisit them at a future meeting if necessary').

When the OSC advises the TGA to 'continue to observe' an implant, this implies that the OSC's view is that the TGA should not be considering regulatory action1 in relation to the product at that time. However, such advice does not infer any definitive committee view as to the current safety and performance of that device.

OCS Meeting 7

The 7th (and third yearly) meeting was held on 26 May 2015. There were 12 ‘still used and re-identified’ implants / implant combinations considered at this meeting and the OSC’s advice to the TGA is tabulated below.

Implant / Implant Combination Sponsor OSC advice / outcomes
Bipolar (Partial) Hip Prosthesis: Tandem Bipolar Head when used with Basis Femoral Component Smith & Nephew Surgical Pty Ltd

The OSC advised that the revision rate of the Tandem Bipolar Head when used with Basis Femoral Component should continue to be closely observed and that the implant combination is revisited in the future when updated data from the AOANJRR becomes available.

Total Conventional Hip Replacement: CPT Femoral Component when used with the Low Profile Cup Acetabular Component Zimmer Australia Pty Ltd

The OSC advised that the revision rate of the CPT Femoral Component when used with the Low Profile Cup Acetabular Component was high and of concern.

While it appears that the two components work well when used in other combinations, the OSC also advised that the revision rate of the CPT Femoral Component when used with the Low Profile Cup Acetabular Component should continue to be observed and that the implant should be revisited in the future when updated data from the AOANJRR become available.

Total Conventional Hip Replacement: ML Taper Femoral Component when used with the Fitmore Acetabular Component Zimmer Australia Pty Ltd

The OSC advised that the revision rate of the ML Taper Femoral Component when used with the Fitmore Acetabular Component was high and of concern.

While it appears that the two components work well when used in other combinations, the OSC also advised that the revision rate of the ML Taper Femoral Component when used with the Fitmore Acetabular Component should continue to be observed and that the implant should be revisited in the future when updated data from the AOANJRR become available.

Total Conventional Hip Replacement: Excia Cementless Femoral Component B Braun Pty Ltd The OSC advised that the revision rate of the Excia Cementless Femoral Component should continue to be observed and that the implant should be revisited in the future when updated data from the AOANJRR become available.
Total Conventional Hip Replacement: Furlong Femoral Component Orthotech Pty Ltd The OSC advised that the revision rate of the Furlong Femoral Component should continue to be observed and that the implant should be revisited in the future when updated data from the AOANJRR become available.
Total Conventional Hip Replacement: Trabecular Metal Femoral Component Zimmer Australia Pty Ltd The OSC advised that the revision rate of the Trabecular Metal Femoral Component was of concern and that the surface material appeared to be implicated in the higher than anticipated revision rate. The TGA should raise with the sponsor/ manufacturer the concerns regarding the rate of revision and investigate what can be done to reduce the risk of revision associated with the use of this device.
Partial Knee Replacement: PFC Sigma Patella when used with the Sigma HP Trochlear Component Depuy Synthes Pty Ltd The OSC advised that the revision rate of the PFC Sigma Patella when used with the Sigma HP Trochlear Component should continue to be observed and that the implant combination should be revisited in the future when updated data from the AOANJRR become available.
Total Knee Replacement: Advance Femoral Component when used with the Advance Tibial Component Surgical Specialties Pty Ltd The OSC advised that the revision rate of the Advance Femoral Component when used with the Advance Tibial Component should continue to be observed and that the implant combination should be revisited in the future when updated data from the AOANJRR become available.
Total Knee Replacement: Genesis II CR (cementless) Femoral Component when used with the Genesis II CR (cementless) Tibial Component Smith & Nephew Surgical Pty Ltd The OSC advised that the revision rate of the Genesis II CR (cementless) Femoral Component when used with the Genesis II CR (cementless) Tibial Component should continue to be observed and that the implant combination should be revisited in the future when updated data from the AOANJRR become available.
Total Knee Replacement: Trekking Femoral Component when used with the Trekking Tibial Component Orthotech Pty Ltd The OSC advised that the revision rate of the Trekking Femoral Component when used with the Trekking Tibial Component should continue to be observed and that the implant combination should be revisited in the future when updated data from the AOANJRR become available.
Total Knee Replacement: Vanguard PS Femoral Component when used with the Regenerex Tibial Component Biomet (Australia) Pty Ltd The OSC advised that the revision rate of the Vanguard PS Femoral Component when used with the Regenerex Tibial Component should continue to be observed and that the implant combination should be revisited in the future when updated data from the AOANJRR become available
Total Shoulder Prosthesis (Conventional and Reverse): SMR Humeral Component when used with the SMR L1 Glenoid Component Lima Orthopaedics Australia

The OSC advised that the revision rate of the SMR Humeral Component when used with the SMR L1 Glenoid Component was high and that this was due to design features of the implant.

However, in appropriately selected patients (e.g. where it is anticipated that there may be future surgery to augment the glenoid with a bone graft), use of this implant combination at the primary procedure does offer benefits for the patient that counterbalance the higher risk of revision.

The implants should continue to be observed and the combination should be revisited in the future when updated data from the AOANJRR becomes available.

OCS Meeting 8

The 8th (and additional yearly) meeting of the OSC was held on 21 July 2015 and gave consideration to a pre-market submission applying for the inclusion of a knee replacement orthopaedic implant in the Australian Register of Therapeutic Goods.

The outcomes of these OSC meetings were noted by the ACSMD. The subcommittee's advice is now being considered as part of the TGA's regulatory decision making processes.

OCS Meeting 9

The next meeting of the OSC is scheduled to be held on 7 December 2015.

Further information

Meeting statements are made publicly available after each meeting.

For further information on the ACSMD, please visit the ACSMD webpage or contact the ACSMD Secretary, Mr Craig Davies on 02 6232 8641 (telephone) or via email: acsmd.secretariat@tga.gov.au.


Footnotes

  1. 'Regulatory action' by the TGA involves one or more of a wide range of actions which can include working with the product sponsor to improve product labelling, amending details within the Instructions for Use or Surgical Technique documents and improvement to education and training material for both healthcare professionals and patients. Regulatory action can also include the publication of Safety Advisories / Alerts, recall actions and the cancellation of products from the Australian Register of Therapeutic Goods (ARTG). All Safety Advisories / Alerts, Recall actions and ARTG cancellations are published on the following pages of the TGA website - Safety information and Cancellations.