By Tamra Sami
PERTH, Australia – Australia’s Therapeutic Goods Administration (TGA) has undertaken a massive effort to reform its drug and device regulations, and as it pulls into the homestretch with those reforms, it is setting its sights to postmarketing efforts that include adverse event reporting, conformity assessments, patient-reported outcomes and a universal device identifier program.
In its three-part action plan released in 2019, the TGA set out to improve how devices get on the Australian market, to strengthen postmarket monitoring and to provide better information to patients about the devices they use, said John Skerritt, deputy secretary of Health Product Regulation for the TGA, during the recent Medical Technology Association of Australia (MTAA) annual conference.
“The action plan was developed because we had not come as far with devices as we have with medicines,” he said. “While there are instructions for use for devices – especially implantable ones – it’s a lot harder for patients to get access to them. There’s a lot less information available even though the implication for having a chronically implantable medical device is much greater than taking a course of a medicine for a week or two.”
To address that information imbalance, the agency set out to improve patient engagement, which originated from community concerns over adverse events with hip joints, breast implants and gynecological mesh implants.
Unlike medicines, longer-term device failures such as those seen with transvaginal mesh implants and metal-on-metal hip prostheses, are more likely to have serious clinical impacts years after implantation and would likely present in a health care setting.
Consequently, the TGA is increasing scrutiny of clinical evidence around devices, particularly medium- and high-risk devices much like Europe has done, Skerritt said.
Patient-focused initiatives include explaining how decisions are made, increasing awareness on how safety and performance are monitored, and engaging consumers in reporting adverse events.
“One of the meetings I remember most was in 2019 with a group of women affected with anaplastic large cell lymphoma from breast implants. Although the events are rare, it was valuable to work with the women who were affected, and we wanted to work with them on consumer information around better managing risk.”
Monitoring initiatives underway
Initiatives are underway for monitoring devices that include mandatory adverse event reporting, conformity assessments and a universal device identifier consultation.
“We clearly want to enhance inspections on certain sponsors to confirm they are meeting their safety and reporting requirements,” Skerritt said, and the agency is still working on mandatory reporting by health care facilities on adverse events.
At first glance, it might look like a massive regulatory burden, he said, but most states and territories have adverse event reporting requirements in hospitals, and the main issue is coordinating and collaborating better to systematically capture adverse events to spot issues sooner.
In Australia, mandatory adverse event reporting requirements exist only for device manufacturers and sponsors. Although health care facilities, health professionals and consumers are encouraged to report adverse events, this is done voluntarily, and in 2020 the TGA received roughly 6,000 medical device adverse events reports, with sponsors submitting 89% of these.
The agency is working with sponsors about how to better communicate with patients with permanently implantable devices via patient implant cards and consumer leaflets provided with their devices.
Streamlining conformity assessments
To streamline conformity assessments, the agency is now accepting device approvals from comparable regulators that include the FDA, Health Canada, and Japan’s Pharmaceuticals and Medical Devices Agency (PMDA).
“We looked at areas to strengthen regulations, but where there is evidence that there are certain levels of insurance, you try to take away regulatory burden,” he said, noting that applicants can now leverage approvals from comparable regulators, and the TGA has done at least a dozen with the FDA.
More than 1,200 Medical Device Single Audit Program quality management system reviews have been conducted, which has meant that the TGA avoided the need to inspect those facilities.
And, as TGA regulations align more closely with the European Medical Device Regulation (EU MDR), applicants won’t have to undergo mandatory TGA conformity assessments for certain devices such as class IV in vitro diagnostics.
“You can still receive a conformity assessment application, but unfortunately given backlogs in Europe with IVDs and mainstream device notified bodies, a lot of companies are coming to us because Europe is struggling. Under those regs, we realize we can accept information from an EU notified body. But if it’s from an EU notified body under the old directives, we will audit that evidence.”
Conformity assessments from EU notified bodies issuing certificates under the new EU MDR are less likely to be audited, Skerritt said, adding that the TGA has contacted companies that have lodged TGA conformity assessment requests to see if they want to proceed or withdraw those requests.
One of the big issues that remains to be addressed, he said, is the level of mutual recognition agreements (MRA). In 2013, the previous government decided that MRAs for class III and high-risk devices would no longer be allowed; however, there are discussions underway on reinvigorating MRAs with Europe across a wide range of products.
Future focus
The TGA is eyeing software that includes artificial intelligence/machine learning algorithms and is assessing them on an individual basis while consulting with international bodies like the International Medical Device Regulators Forum (IMDRF) on over-arching regulation.
For example, for an artificial intelligence (AI) device that scans for melanomas where most of the work has been done in Scandinavian countries, the data would be skewed when introduced into a market that has a more diverse population.
“The IMDRF working group feels this is an area that needs to be studied further when it comes to the learning set and the application set,” he said, noting that there are intermediate steps such as network-based learning.
The EU is overlaying AI regulation on top of device regulation, but the TGA doesn’t want to discourage applications coming to market, he said.
Another future focus is on real world evidence (RWE) both in regulation as well as in health technology assessments.
Joint replacements are an example whereby patients with hip replacements are more active than patients were years earlier. Patients today are running marathons and sailing, and the TGA has been using patient-reported outcomes as part of the submissions.
The TGA was one of the first major regulators to publish clinical evidence guidelines, he said, and as electronic health records are improved, there will be more opportunities to use RWE in Australia.
Like medicines, devices are often approved for a narrow indication, but as more RWE becomes available, those indications can then be expanded.