In late June, the Federal Government released the Stage 1 report on the Review of Medicines and Medical Devices Regulations, conducted by Emeritus Professor Lloyd Sansom AO, Mr Will Delaat AM and Professor John Horvath AO. We take a look at what the experts would have TGA do with devices.
Premarket – Taking Harmonization to the Next Level
The expert review was strongly in flavour of flexibility of approach in premarket review, calling for multiple review pathways and an eclectic approach to acceptance of international reviews.
Expanding the Options
The review recommended that a multiplicity of options should be available for Australian approval of devices including:
- Direct assessment by TGA
- Assessment by an Australian designated third party
- Assessment by an international 3rd Party (e.g. Notified Body)
- Approval based on review and acceptance by a comparable overseas Authority
All well and good to provide maximum flexibility. The review also clearly recommended that TGA retain the capacity to do assessments. However there are challenges to ensuring that all of these things can actually coexist in practice.
TGA has accepted CE certificates since 2012 – and recently extended this acceptance to local manufacturers. However there’s been no enthusiasm for European Notified Bodies to establish substantial presences in Australia. Those that are here have sales offices and one a small number of local auditors – with most of the assessors being flown in on demand. If the acceptance of CE is to continue (and it’s hard to imagine otherwise) then the business case for establishment of Australian 3rd party organisations is likely to be weak.
Are we so different?
The proposal to accept regulatory reviews from comparable agencies challenges TGA’s insistence that the only international review that can be accepted is CE, because the Australian and European systems are essentially equivalent in requirements and assessment processes. However there’s long been an argument that the decisions of other leading regulators with different processes, but arguably just as robust systems, should also have currency with TGA. It’s particularly compelling that regulatory reviews by Health Canada and the Japanese PMDA should be acceptable to TGA. Although they are not as closely aligned as Europe – the classification systems and requirements in Canada and Japan are similar and by any reasonable assessment the agencies are just as capable as TGA.
A bigger challenge exists with US FDA approvals, as there is considerable misalignment in device classifications which results in many devices apparently receiving more – or less regulatory review in the US than equivalent devices in Australia. Yet even then differences may be less than expected. For example devices containing animal origin materials such as wound dressings with collagen based hydrogels are Class III in Australia and require direct TGA conformity assessment. Similar reviews are made by European Notified Bodies. In the USA these same devices are subject to 510(k) clearance – which is frequently criticized as a lesser standard of review. Yet the reality is that in all three reviews, the regulators will focus on the primary risk of controls over sourcing and processing of the animal origin materials, and all three will base their reviews on the requirements of ISO 22442 – the risk management standard for animal origin materials. In this era of widespread use of consensus international standards for regulatory reviews, the outcomes are likely to be similar in competent agencies, irrespective of the precise regulatory review process.
Lets be clear (about 3rd parties)
TGA has long struggled with acceptance of 3rd party reviews, maintaining the application audit program to double–check European reviews TGA has assessed many thousands of devices since the current regulations were established in 2002, but that body of experience has apparently not allowed the agency to establish sufficient confidence in Notified Bodies to reduce application audits. Indeed until recently TGA was seeking to strengthen further the application audit process for higher risk devices. This past year TGA has been undertaking renewed “confidence building” by actively reviewing the larger Notified Bodies serving the Australian market. It’s not been completely clear what exactly has been involved in this process. The 2014 amendments to the European MRA give some hint in that they speak )of sharing of information, exchange of documents and observation of each other’s audits, but there’s precious little detail.
Given all this lack of clarity, the expert review makes a very welcome call for TGA to establish transparent criteria and processes for designation of 3rd parties as acceptable to TGA. Whenever there’s a high profile device failure, commentators are quick to point fingers at suspect international reviews and there are calls for strengthening regulation. Clear processes and acceptance criteria, published for all to see, should go a long way to supporting public confidence in TGA and fostering a more rationale discourse on what’s possible and reasonable in internationally harmonised regulation.
The expert review calls for development of an expedited pathway for novel technologies. THis mirrors similar initiatives overseas. It’s a common accusation that regulations are most burdensome on small companies developing new technologies and that the inevitable consequence is stifling of innovation. International regulators, including both the US and Chinese FDA have introduced expedited pathways for new technologies. However it’s not clear that these programs are particularly effective, and there are nagging doubts about risk. The problem with novelty is precisely that it’s less well understood and by definition more risky. The only safe way to expedite review of new technologies at the necessary level of rigour is to throw much more resource at the review.
Registries for all
The review calls for all high risk implantables to be included in a registry. It goes further to say that TGA should should actively monitor and analyse data from registries and be responsible for the correct operation of registries. There are two real challenges here, of funding and control. The most obvious example is the well established National Joint Replacement Registry (NJRR). TGA takes a keen interest in the annual reports of the NJRR, working closely with the registry and issuing “Please Explain” letters to manufacturers of joints identified by the registry as having unusually high revision rates . The NJRR is funded by the industry – by a levy on prosthesis reimbursements. Yet the registry is operated by the Orthopaedic Association and both TGA and industry have limited access to its database and no influence over the registry operations or reporting. The review recommendations are likely to increase enthusiasm amongst clinician groups for establishment of registries – but expect robust debate about the way they are established and operated and how they should be funded.
It says what?
The Therapeutic Goods Act has changed enormously since its first draft in 1989, with 61 revisions undertaken in the past quarter century. It’s expanded each time and has grown to over 550 pages of primary legislation and more than 200 pages of devices regulations and 300 pages of medicines regulations. It seems reading the Act kept the expert reviewers awake at night (or perhaps not) and they make a clear call for a total rewrite to simplify the legislation, make it more flexible (including introduction of more graduated penalties) and most importantly – to recognise that devices are different to medicines.
Stand aside Sir Humphrey – time for some plain English.
TGA – here to stay
The review makes a very clear statement that TGA should retain an independent capability for regulatory review. All well and good, but it’s a reality that TGA is a small agency in international terms and that necessarily limits the breadth of capability especially for extensive premarket review. Expansion of acceptance of international approvals brings with it the inevitable potential for reduction in TGA capabilities.
Perhaps the more important question is not how much regulation is done by TGA, but what kind.
To that end,using the resources freed by greater reliance on international reviews to support a shift to stronger postmarket regulation is an obvious way forward. Strengthening postmarket has been a long running theme at TGA and the review is vocal about upgrading TGA’s postmarket capabilities. It puts forward some concrete suggestions for how to achieve more with little. In particular, implementing more comprehensive postmarket monitoring programs, sharing data with registries, moving adverse vent reporting to electronic means (TGA actually already does this to some extent) and by better international sharing of information.
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