General themes
Positive feedback on the Therapeutic Goods Administration
5.1
Many submitters were complimentary about the Therapeutic Goods Administration ‘s (TGA’s) work in regulating medicines and medical devices. Recordati Rare Diseases Australia stated its belief that ‘the TGA is very efficient in registering medical products.’ ARCS Australia commented that ‘the TGA is an internationally recognised regulator that has been highly beneficial to our sector.’ Kyowa Kirin Australia said that it was ‘extremely pleased with the accessibility, efficiency, responsiveness and amiability of the TGA’ and that its registration processes ‘are relatively efficient, if not best practice by global standards.’ Biotronik Australia ‘commend[ed] the TGA in its desire to continually seek relevance and value’ and described it as ‘keen to engage with industry in seeking novel solutions.’
5.2
Specialised Therapeutics Australia submitted that substantial improvements to the TGA were made following the 2014 Expert Panel Review of Medicines and Medical Devices Regulation (Sansom Review), a view echoed by Bayer Australia and New Zealand, Amgen Australia, Edwards Lifesciences and Merck Sharp & Dohme Australia, the last of which described the post-Sansom Review regulatory system as ‘world class.’ In spite of this, the general view of submitters and particularly those from industry was that further improvements are still needed to enable faster and wider access to medicines and medical devices.
Use of overseas regulators
The case for more alignment with overseas regulators
5.3
The most popular ideas for TGA reform among other submitters was increased international harmonisation and cooperation. Submitters argued that products approved by reputable regulators have already been proven to be effective and safe, so reassessment by the TGA results in duplication and inefficiency. It was claimed that given Australia’s small market size, alignment with larger markets is necessary to ensure fast access to medicines and devices, particularly for rare diseases. The small United States (US) company Mirum Pharmaceuticals, for example, explained that it is submitting a rare liver disease medicine to the US Food and Drugs Administration (FDA), then taking it to the European Medicines Agency (EMA), and it would be able to bring it to Australia much faster if Australia’s process was aligned with those jurisdictions.
5.4
Submitters emphasised the need for the TGA to harmonise its systems and processes with overseas regulators. It has already made progress on this in some areas, such as Project Orbis for cancer medicines which was praised by several submitters.
5.5
AstraZeneca Australia and Bayer Australia and New Zealand commented that ‘special registration schemes’ like Project Orbis should be introduced or expanded for other diseases besides cancer, with AstraZeneca Australia giving the examples of asthma and cardiovascular diseases. Amgen Australia discussed Project Accumulus, a joint IT framework being developed by the FDA, the EMA, and the Japanese and Singaporean regulators to facilitate better data sharing, and argued that Australia needs to participate.
5.6
In the area of rare diseases, Dr Falk Pharma Australia suggested an ‘accelerated pathway’ should be available for orphan drugs that have already been registered in certain ‘reference markets.’ RESULTS International Australia, meanwhile, recommended ‘allowing access in Australia to drugs for rare and orphan diseases with WHO [World Health Organization] Prequalification quality approval.’ It explained that this would have the added benefit of ‘allowing Australia to benefit from low costs negotiated globally for such products’ by United Nations agencies.
5.7
Medtronic Australasia was generally strongly supportive of more alignment with international regulators, but argued that in aligning with European Union (EU) devices regulation:
…there needs to be a balance and caution exercised in areas where the European Regulations are not clear or the guidance documents are not made available. Should the TGA implement the changes in the absence of such explanatory documents, it can create a huge regulatory burden for sponsors.
5.8
Stryker South Pacific recommended ‘benchmarking approvals times for TGA against international best practice.’ The Medical Technology Association of Australia (MTAA) likewise recommended ‘TGA should continue improving and streamlining its internal processes to deliver consistently quick review times in line with international KPIs.’
5.9
ARCS Australia raised the specific issue of the TGA’s regulation of manufacturing, which it said ‘seems to be moving away from international harmonisation,’ in contrast to the TGA’s approach in other areas. It argued that ‘this will increasingly present a roadblock for companies, and reverse the progress and advances’ made by the other international initiatives. In response to these issues, it recommended that ‘the TGA rely more wholly on overseas [Good Manufacturing Practice] accreditation and not insist on additional evaluation of audit reports or request review of technical agreements between manufacturers. ‘
The case for caution in alignment with overseas regulators
5.10
While a strong majority of submitters who raised the issue of alignment with overseas regulators supported increasing it, some others urged caution. The Western Australian Department of Health (WA Health) highlighted the importance of the TGA being careful in deciding which regulators its designates as Comparable Overseas Regulators (CORs) commenting that:
It is vital that the TGA regularly monitor any changes to approval processes for research and development across the CORs to ensure that standards remain of a suitable high level. Additionally, robust data capture and post market surveillance across a mandated period should be required.
5.11
The Centre for Law and Genetics, University of Tasmania and Sydney Health Law and Sydney Health Ethics, University of Sydney advocated for careful consideration of any increase in reliance on international regulators, noting ‘the current state of flux in acceptable safety and efficacy thresholds, and the recent controversy that has surrounded a number of medical devices approved for use in Australia through these pathways.’
5.12
The Australian Commission on Safety and Quality in Health Care (ACSQHC) noted the problems with medical devices are heavily dependent on CORs for their approval. They commented:
… processes which ensure appropriate attention to the quality and relevance of international assessments and approval processes to local circumstances are imperative.
5.13
Dr Bruce Baer Arnold and Dr Wendy Bonython, acting in a private capacity, raised the medical devices issues, and noted that regulatory failures that result in patient injuries place ‘avoidable burdens on the public/private health systems.
5.14
The Royal Australian and New Zealand College of Radiologists (RANZCR) drew the Committee’s attention to the specific problems that can arise in aligning regulation of software that uses Artificial Intelligence (AI), in its case in clinical radiology. It submitted that:
It has been well documented that performance of AI systems is related to the population of individuals on which it has been trained.
…there need to be mechanisms in place to ensure that machine learning devices are trained and tested on individuals appropriate for the Australian demographic. Such devices are clearly labelled to ensure that they are able to be used in a clinically appropriate context. When relying on the assessment of overseas regulators, it is also imperative that the TGA has mechanisms in place to be alerted to all changes to AI systems.
The Government’s position
5.15
In response to the possibility of the TGA simply ‘rubber stamping’ decisions by overseas regulators, the Department of Health (the Department) told the Committee:
A key reason for the Government’s decision in 2016 that Australia should continue to make sovereign decisions regarding medicines approvals, rather than ‘rubber stamp’ decisions of other regulators, was that there was often significant discordance between these decisions. In individual cases, this is thought to be due to differences between regulators in the data submitted by the applicant, differences in clinical practice or risk appetite between countries or differences in opinions between respective advisory committees. There have been some cases where absolute differences in regulatory outcome (acceptance versus rejection) occurred but much more common are significant differences in the approved indication (intended use) between regulators for a given medicine.
5.16
On the issue of whether such ‘rubber stamping’ would be beneficial for provisional approval for rare disease therapies in particular, Adjunct Professor John Skerritt, Deputy Secretary, Health Products Regulation, Department of Health (Adjunct Prof Skerritt), commented:
In provisional approval, it's even more important to know where the risks and uncertainties are. You could argue that's a case where you actually want to have information on what gaps you need to fill in the coming period. There could be safety issues. Remember, with provisional approval, you're going back to the company and saying, 'We need answers to A, B, C, D, E, F.' In order to shape those questions, you'd argue that the exact opposite should apply; you should actually know more about those drugs and what's not known and what is known about them.
5.17
Adjunct Professor Skerritt argued that the most important consideration is ‘to continue to have an environment and actively encourage Australia to be a tier 1 market; in other words, for submissions to Australia to be made as soon as possible after the European and North American submissions.’
Length of review versus risk
5.18
Beyond the issue of alignment with overseas regulators, some submitters insisted on a more general need for caution in speeding up the regulatory process. Miss Jessica Pace emphasised that ‘attempts to speed up regulatory processes can have impacts on quality.’ She said that her research of the views of clinicians and patients showed that they are ‘largely satisfied with our current systems of medicines funding and regulation,’ although they acknowledge there are areas that need improvement, particularly for rare diseases. Dr Arnold and Dr Bonython likewise submitted that ‘weakening of Australia’s therapeutic goods regime will result in harms without substantive benefit to consumers of medical products.’
5.19
Australian Prescriber submitted that ‘it is important that rapid approval does not compromise the safety of new drugs.’ It noted that ‘adverse effects tend to emerge over time and, if efficacy has been based on surrogate outcomes, there can be uncertainty whether new drugs will be effective in practice.’ It nonetheless did not call for any reduction in the current use of accelerated approval pathways. The Sydney Children’s Hospital Network and Children’s Medical Research Institute kept their submission on this issue general, stating that ‘the focus must be on patient safety’ but that ‘risks should be balanced against potential benefits of early access to novel therapeutics.’ The ACSQHC made the same broad point, submitting:
The argument is sometimes made, that assessment and approval processes are extended and more immediate availability of a new drug or device would save lives. The risks and benefits of ‘early’ introduction should always be considered objectively.
Resourcing
5.20
Currently, the TGA’s activities are primarily cost recovered from industry fees and charges, however, a small amount of appropriation funding is provided for other activities. For example, in the 2019-20 Mid-Year Economic and Financial Outlook statement, the Government provided $33 million over four years (including $6.6 million in 2020-21) for work on improvement of patient safety through regulatory measures for opioids and to partially defray the costs of the TGA Special Access Scheme, Orphan Drugs Program and mandatory reporting of shortages of critical medicines.
5.21
A related concern was the question of whether the TGA is adequately resourced. The Association of Australian Medical Research Institutes (AAMRI) submitted that ‘[approval] timelines could be decreased by increasing the TGA budget so expedited reviews can be implemented.’ Novo Nordisk Australia recommended that there be ‘additional funding allocated to the TGA to strengthen the TGA’s ability to regulate new and innovative therapeutic goods, ensuring that sufficient effort is directed to the development and exploration of novel therapeutic classes.’ Dr Arnold and Dr Bonython argued that the TGA’s current funding is insufficient for it to ‘fulfil its responsibilities on a timely proactive basis’ and ‘attract and retain expertise.’
5.22
Australian Prescriber explained that the TGA publishes Australian Public Assessment Reports (AusPARs) to provide information about newly approved medicines, but that there is often a delay between the registration of medicines and their publication. It submitted that:
The rapid approval of new drugs in Australia must be accompanied by a rapid release of the information supporting those approvals. The TGA should be given the resources to ensure that an AusPAR is available at the same time a new drug is launched.
5.23
ARCS Australia emphasised the need for ‘resources at the TGA being sufficient to maintain a strong focus on continuous improvement and strategic focus.’ It added that ‘initiatives such as the Advanced Therapies Unit are critical to success’ and ‘IT infrastructure at the TGA needs a major overhaul.’ Johnson & Johnson seconded this, and stated:
We would advocate for sufficient resources to address current TGA limitations, including in relation to information technology. In that regard, we support the recent announcement in the Federal Government’s October Budget to provide additional resources to the TGA.
5.24
Medicines Australia submitted that the TGA’s IT infrastructure is not ‘fit-for-purpose’ and it welcomed the funding announced in the 2020 Federal Budget. It further asserted that, in contrast to the FDA and European EMA, the TGA does not have sufficient internal resources to conduct its clinical evaluations and consequently must rely on external evaluators. It explained that:
Quality of external clinical evaluations can be poor due to lack of experience …or failure to understand regulatory requirements. This creates additional burden for Sponsors in having to address erroneous requests…and can result in delays to approval.
5.25
The MTAA raised concerns about the TGA’s resources, and specifically its IT resources, asserting that ‘long review timelines are often caused by a lack of specialist reviewers and outdated IT systems.’ It recommended that the Government ‘ensure that TGA has the human and IT infrastructure resources to fulfil its mission.’ Pathology Technology Australia delivered one of the most forthright criticisms of the TGA’s resourcing, submitting that:
Improvement in the TGA is more likely to come from changing either the resourcing or the funding model. The current fee-for-service model is a nonsense when the TGA cannot staff to workload (under the public service staffing limits imposed by the Department of Finance). If this service is to remain fully fee-for-service, then it needs to be free to staff-to-workload. If TGA remains tethered to public service staffing ratios, then product assessment and registration services need to be federally funded.
5.26
When asked by the Committee about whether the TGA’s current cost recovery model provides it with sufficient resources, Adjunct Prof Skerritt replied:
So consumer expectations have changed. Profiles have changed. There's a list of other things and services that we provide that can't be attributed to an individual company. There's also a greater expectation on compliance…So the dilemma I have, as I've seen the nature of expectations of regulators change, is whether we have the model that can actually service that.
5.27
The Department added:
While the TGA’s activities are primarily cost recovered from industry fees and charges, a small amount of appropriation funding is provided for other activities. For example in the 2019/20 Mid-Year Economic and Financial Outlook statement, the Government provided $33 million over four years (including $6.6 million in 2020/21) for work on improvement of patient safety through regulatory measures for opioids and to partially defray the costs of the TGA Special Access Scheme, Orphan Drugs Program and mandatory reporting of shortages of critical medicines.
There are some activities that may not be appropriately cost recovered under Australian Government Cost Recovery Guidelines because they cannot be attributed to individual TGA sponsors, or it would be unreasonable or inefficient to cost recover (e.g. from individual terminally ill patients in the case of SAS A).
5.28
The Department went on to note a series of examples of costs that may not be appropriately cost recovered, some of which are of particular interest to this inquiry. These include ‘horizon scanning on new medicines and medical technologies,’ ‘provision of early scientific advice for new and emerging technologies,’ ‘regulatory policy development for new and emerging technologies,’ ‘community and healthcare practitioner education and communications’ and the ‘Orphan Drugs Scheme.’ It concluded by stating that:
It would be a decision for government, and not for officials, to determine whether changes to TGA’s funding model are appropriate, and if so how these activities should be funded.
Technical aspects of regulation
Molecular indications
5.29
One overseas development that attracted particular interest from some submitters was the recent FDA approval of larotrectinib, an NTRK inhibitor. AAMRI explained that this drug:
…was recently approved in the US for a molecular indication rather than the more usual disease indication. This means that rather than a drug being approved for the treatment of a specific cancer, such as breast, lung, bowel etc., it is approved for every cancer where an NTRK fusion is found, and in both adult and paediatric populations.
5.30
AAMRI suggested that a ‘routine, standard approval pathway for therapeutics with molecular indications’ be created. It did however acknowledge that:
Safety risks need to be considered due to cross reactions and dose alterations, or administration route in conjunction with pharmaceutical development requirements. However, if these considerations are considered, expedited approvals should be possible.
5.31
The Luminesce Alliance and one of its members, the Children’s Cancer Institute, both noted the US example. They argued that ‘in an era of molecularly and genetically targeted drugs [the current system] creates artificial access restrictions,’ and that it should be changed ‘to facilitate the broadening of indications sharing the same molecular and genetic drivers of disease.’ The Victorian Comprehensive Cancer Centre referred to the US example above in the context of rare cancers, and put forward a proposal for a ‘fast-tracked approval program for tumour agnostic treatment of rare cancers.’
5.32
Similarly, the Australian and New Zealand Children’s Haematology/Oncology Group submitted that:
…increasingly it is recognised that there may be rare childhood cancers which are driven by the same molecular mechanisms as more common adult cancers and that the drugs developed to treat those adult cancers may be effective in childhood cancers.
5.33
Accordingly it suggested that a ‘mechanism of action approach should…be extended to the conduct of clinical trials and the registration and approval process for new drugs and other novel therapies.’
Advisory Committee on Medicines
5.34
ARCS Australia raised concerns about the TGA’s Advisory Committee on Medicines (ACM), submitting that there is ‘a trend in significant divergence between ACM positions and that of local medical practice.’ It went on to say:
TGA has recognised that the constitution of the ACM could benefit from renewal or the TGA could further explore other mechanisms for obtaining independent scientific/medical advice (as is routinely done for oncology products for instance). We acknowledge this plan which needs to be adequately funded and be agile in responsiveness for specific expertise to support new product registration.
5.35
Medicines Australia commented on the ACM that there should be ‘alignment of committee membership with therapeutic area of relevance.’ Novartis Australia and New Zealand noted that while the Pharmaceutical Benefits Advisory Committee (PBAC) requires a positive Delegate’s Overview from the ACM before it will recommend an application for reimbursement through the parallel process, the meetings schedules of the ACM and PBAC are not coordinated.
Communication with sponsors
5.36
Bristol Myers Squibb (BMS) proposed that the ‘TGA should provide early guidance on major and minor issues raised during the regulatory review, to enable Sponsors to begin to respond sooner, expediting the regulatory process.’ Medicines Australia provided a list of seven aspects of the TGA’s ‘Evaluation Process’ and four aspects of its ‘Advisory/Expert Committee Process’ that it said are out of step with the equivalent processes of the FDA and EMA, together with recommendations to resolve these discrepancies.
5.37
Many of these suggestions were technical issues relating to improving communication between the TGA and sponsor, although they did include their concern with the ACM membership. The MTAA raised similar concerns, commenting that questions are issued to the sponsor from different review sections at different times rather than all at once, and the process for requests for additional information means different sections often request the same information.
Status of real world evidence
5.38
Submitters had various comments to make relating to the TGA’s approach to evidence. The Australasian Sleep Association recommended that the TGA ‘use a case-based rather than formulaic approach to making decisions’ where a medicine has been shown to be effective in comparison to a placebo, even if its efficacy against comparator medicines has not yet been established.
5.39
ARCS Australia noted that the TGA already accepts real world evidence (RWE) as part of application dossiers, but submitted that it should develop ‘guidance for accepting and evaluating’ dossiers that contain such evidence, aligned with guidance from overseas regulators such as the TGA. BMS made a similar recommendation, saying that this would ‘improve predictability and transparency for the sponsor, reducing the need for resubmissions and delays in patient access.’ Roche Australia stated ‘there is a lack of formal guidance on how sponsors should develop and frame this type of evidence.‘ It noted that such guidance had been developed by the FDA and EMA.
5.40
Medical technology submissions touching on the TGA’s approach to evidence were strongly supportive of a greater role for RWE. Stryker South Pacific commented that:
In relation to the introduction of innovative technology (without adequate clinical evidence or potentially without an adequate comparator) the ability to commit to an ongoing post-market clinical follow-up in lieu of excessive pre-market evidence generation is important to enable access in both the public and private sectors. This should include maintaining reporting requirements and the ability to halt access should early issues be identified.
5.41
Abbott Diabetes Care suggested that the TGA’s evidence guidelines are ‘focused and heavily weighted on double-blind randomised controlled trials, in which patients do not know what therapy they are receiving, but that while these work well for drugs they these are impossible to run for many devices. It emphasised that the shorter ‘product cycles’ for devices compared to drugs – meaning they are developed and made outmoded more quickly - together with ‘ethics issues in device trials’ and smaller patient populations mean that RWE is even more important than it is for medicines.
5.42
The TGA acknowledged the thrust of these comments on its approach to evidence, as Adjunct Prof Skerritt told the Committee:
…a number of the submissions also said that we should provide clearer regulatory guidance around the use of real-world evidence in submissions. We've actually commenced a project and public consultations which will probably lead to more specific and detailed guidance and engagement with patient groups in the industry about how we can better incorporate real-world evidence.
Post-market surveillance
5.43
The potential of more use of RWE in TGA decision-making was discussed in the context of post-market surveillance, as noted by Stryker South Pacific which suggested:
…utilising the early adoption of medical technology in Australia’s private health sector to collect post-market surveillance and performance data to inform policy, regulatory and funding decisions.
5.44
The MTAA suggested that lessons can be learned from the TGA’s response to the COVID-19 pandemic in this respect, and that the TGA’s Priority Review pathway could be improved by ‘combining a fast-track premarket review with a rigorous post-market oversight to ensure both fast access and patient safety.’
5.45
WA Health argued for the need for post-market surveillance where the efficacy or safety (particularly long-term safety) of a new therapeutic good is uncertain. It used the UK and EU’s black triangle scheme as an example of a surveillance system, and suggested that surveillance could be incorporated into the TGA’s schemes for access to medicines and devices not on the ARTG.
5.46
Miss Pace reported that the clinicians and patients participating in her research ‘expressed a desire for greater use of post-market data collection in order to provide faster access to new medicines,’ but she cautioned that such collection is ‘more difficult than many imagine.’ She said this was because of difficulty in collecting the raw data and insufficient funding or expertise for the regulator to analyse it properly. Drs Arnold and Bonython criticised Australia’s current approach to post-market surveillance and called for the introduction of ‘a mandatory public fault reporting scheme for therapeutic goods,’ including prompt publication of information about faults by the TGA.
5.47
Both the Pharmacy Guild of Australia and the Pharmaceutical Society of Australia advocated for enhanced post-market surveillance for medicines, which they described as pharmacovigilance; the latter stated that ‘it is important that a holistic, nationally-coordinated and outcomes-focussed approach to undertaking pharmacovigilance activities is implemented.’ They emphasised the important role that pharmacists play in pharmacovigilance currently and the scope for it to be increased; the Guild, for example, proposed ‘a standardised service model in community pharmacy that fitted in with the re-supply (repeat) arrangements for new and novel medicines.’
Other areas of interest
General engagement with industry
5.48
AstraZeneca Australia recommended that the TGA promote its Priority Review pathway to industry ‘for other disease indications in addition to oncology.’ It suggested that this would be assisted ‘by periodic reporting of the number of applications’ rather than the current practice of only publishing successful applications. The MTAA suggested that the pathway be the subject of ‘a sustained, dedicated education and training program aimed at Australian MedTech companies developing or aiming to distribute novel/ breakthrough technologies. The TGA’s Priority Review pathway is discussed further in Chapter 3.
The role of the states and territories
5.49
The MTAA expressed unhappiness with the role that state and territory governments currently play in the regulation of medical devices, stating that:
State and Territory governments need to eliminate red tape and duplicative requirements for medical devices that increase the cost and burden to industry with no added benefit to patient safety, such as compulsory registration to commercial databases Recall Health and National Product Catalogue. TGA regulations, systems and processes should be adopted uniformly across Australia without duplication by State and Territory departments of health.
5.50
It welcomed the ‘recognition of the need for change’ in the 2020 Addendum to the National Health Reform Agreement, and recommended that to implement that change ‘a national list of novel health technologies recently approved should be created’ and:
State and territory governments should be required under their reporting responsibilities for the National Health Reform Agreements to transparently outline their processes for evaluating and funding new technologies included in the novel list, what decisions have been taken and progress in uptake of the new technology.
The independence of the regulator
5.51
Dr Arnold and Dr Bonython recommended that consideration should be given to ‘re-establishing it as an independent body that reports direct to Parliament,’ as opposed to the current model under which it forms part of the Department.
Breakthrough status
5.52
There was strong interest from the medical devices industry in the FDA’s Breakthrough Devices Program. Edwards Lifesciences submitted that:
The goal of the Breakthrough Devices Program is to provide patients and health care providers with timely access to these medical devices by speeding up their development, assessment, and review, while preserving the statutory standards for premarket approval.
The Breakthrough Devices Program offers manufacturers an opportunity to interact with the FDA's experts through several different program options to efficiently address topics as they arise during the premarket review phase, which can help manufacturers receive feedback from the FDA and identify areas of agreement in a timely way.
5.53
Edwards Lifesciences suggested that the Government establish a similar program. Medtronic Australasia explained the difference between this program and the TGA’s existing Priority Review in the following terms:
The priority review designation criteria that the TGA has established is different to that of the [FDA] and requires the requisite evidence to be available at the time of the submission rather than working in a partnership approach modelled by the [FDA], who get involved from the early stages of design, development and evidence gathering requirements such as design of clinical trials.
5.54
Medtronic Australasia argued that establishing a similar program in Australia would particularly assist in ensuring breakthrough devices are quickly adopted in public hospitals, by establishing ‘a more strategic national approach to patient access.’ It recommended ‘enabling the TGA to have market entry discussions and better alignment to accept [FDA] breakthrough designations.’
5.55
AusBiotech discussed the FDA program, in which it said ‘the regulator effectively works with companies at early development stage to co-design study protocols and requirements, and undertakes real time assessment of manufacturing quality, effectively leading to approval at the time of reporting of trials. BioScience Managers meanwhile submitted that ’breakthrough device or similar designation would help development of [digital therapeutics] in Australia.’
5.56
The MTAA submitted that the criteria for the TGA’s Priority Review are ‘similar to criteria used by other regulatory agencies such as the US FDA and its Breakthrough Devices Program.’ When asked about the difference between this program and the TGA’s Priority Review, it told the Committee that:
TGA insists on evidence up-front, whereas the FDA is more inclined to look at real-world evidence. We believe this is important…you can glean a lot of clinical evidence up-front. You would still be on top of it to make sure, but you have equity of the availability.
5.57
MTAA commented that ‘we hope to see…continued alignment between the TGA priority review pathway and the US FDA Breakthrough Devices Program.’
5.58
Noxopharm Limited drew the Committee’s attention to similar FDA initiatives for medicines. It submitted that ‘providing the equivalent of the FDA breakthrough (fast-track) approval, especially for orphan drugs would bring forward revenues, again making investment in Australian drug development a more attractive option.’
The Special Access Scheme
5.59
RESULTS International Australia informed the Committee that ‘important drugs’ for the treatment of tuberculosis currently have to be accessed through the Special Access Scheme (SAS). It explained that the process for a doctor to get approval under the SAS is ‘long and cumbersome,’ and if not treated as soon as possible the patient can infect others, develop drug-resistant tuberculosis, and even die.
5.60
The Australasian Association of Nuclear Medicine Specialists and the Australian and New Zealand Society of Nuclear Medicine (AANMS and ANZSNM) drew attention to another problem relating to the SAS, writing that:
The difficulty and expense of change of sponsor of an existing listed drug should be minimised. In recent years, existing listed drugs have dropped off the ARTG when a new sponsor elects not to seek change of registration. This results in nuclear medicine practices having to use the SAS pathway to use a proven drug which was once, but is no longer, on the ARTG.
Nuclear medicine
5.61
The AANMS and ANZSNM made the following suggestions for radiopharmaceuticals:
… a separate ARTG class should be created for them given their unique nature; evidence requirements for diagnostic radiopharmaceuticals should be reduced commensurate with the extremely low safety threat they pose; application costs should be reduced in recognition of the level of evidence required and the lack of commercial sponsors under the current pricing; and restrictions on interstate and intrastate supply of radiopharmaceuticals manufactured under exemption from TGA manufacturing regulation should be lifted given the low safety risk they pose.
Digital technology
5.62
One area of emerging technology that attracted submitter attention was digital technology. Sleepfit Solutions focused its submission on digital therapeutics (DTx), which it described as ‘evidence-based behavioural treatments delivered online that can increase accessibility and effectiveness of health care.’ It noted that these differ from ‘”consumer grade” health-related software applications’ as they ‘deliver defined therapeutic interventions rather than general wellness tracking services,’ and are distinct from other ‘digital healthcare services’ such as ‘adherence, diagnostics tools or telemedicine platforms.’
5.63
Sleepfit Solutions explained that current medical device regulation is ‘ill-suited to DTx innovations’ as ‘digital therapies can be developed more quickly than pharmacological products, and benefit from agile development practices with ever faster feedback loops.’ It called for the creation of a ‘formal approval pathway’ for DTx, and suggested that it could be modelled on one introduced by Germany in 2020. BioScience Managers addressed DTx, submitting that:
By their very nature, DTx are “data-intensive”….Artificial intelligence, machine learning and novel algorithms are now and will continue to be central to DTx. It is imperative that regulatory agencies like TGA build internal data science and software coding skills to evaluate and approve DTx.
5.64
As mentioned above in the discussion of alignment with overseas regulators, the RANZCR commented on some of the issues surrounding AI. It explained that it has been ‘working on AI in radiology since 2016,’ and outlined eight ‘Regulatory Principles’ it has developed for the regulation of such AI. It noted that unlike traditional medical devices ‘machine learning systems and artificial intelligence tools are not static and can learn post release and change.’ It therefore argued that they should be regulated ‘more robustly’, with a level of evidence required commensurate with the level of risk of the particular device, and it noted the problem with alignment with overseas regulators discussed above. The RANZCR argued that any substantial modifications to the AI model must require fresh authorisation from the TGA, and that ongoing monitoring of AI devices is even more important than for regular devices.
Patient-matched medical devices
5.65
3DMediTech, a manufacturer of ‘patient-matched 3D printed devices,’ made a submission on the regulation of patient-matched devices. These devices, known as personalised medical devices, are defined as a device that:
(a) is manufactured by the manufacturer, within a specified design envelope, to match:
(i) either or both of the anatomical and physiological features of a particular individual; or
(ii) a pathological condition of a particular individual; and
(b) is designed by the manufacturer (even if the design is developed in consultation with a health professional); and
(c) is manufactured using production processes that are capable of being:
(i) either or both validated and verified; and
(ii) reproduced.
5.66
3DMediTech noted the TGA’s creation of a new registration pathway for such devices, implemented in 2021, which separates them out from the ‘custom-made’ medical device category which is ‘subject to a less prescriptive regulatory regime.’ It praised this reform as striking ‘an extremely effective balance’ between protecting patient safety and supporting business. It asked however that the transitional arrangements for the new pathway be altered so that the list of devices allowed to remain regulated as custom-made devices as a transitional measure be made public, to allow for more transparency.
Medicinal cannabis
5.67
MedReleaf Australia submitted that the current regulatory system ‘does not have the structure or ability to appropriately review medicines that are whole plant cannabis,’ as opposed to a single chemical compound. It recommended that ‘a new class of registration be implemented that is more appropriate in assessing medical cannabis.’
Committee Comment
5.68
The Committee wishes to record its appreciation for the work the TGA and its staff have undertaken during the COVID-19 pandemic, and thanks it for continuing to engage well with the inquiry despite being under increased pressure.
5.69
The Committee is satisfied that the TGA is performing well in many aspects of its regulatory role, particularly those relating to medicines and medical devices for common diseases. The Committee believes that this is in large part due to two factors: the reforms made following the Sansom Review, and a proactive approach to reforming itself further, including actively seeking the views of those affected by its regulatory activities.
5.70
The Committee agrees that the TGA should not adopt a whole scale ‘rubber stamping’ approach to overseas regulatory approvals. While the Committee acknowledges that much of the evidence it received supported much greater alignment with overseas regulators, it believes that the risks of major change need to be weighed against the potential benefits. However, the Committee does see scope for increased collaboration with Comparable Overseas Regulators (CORs) and an expansion of Project Orbis arrangements for disease consortiums other than cancer.
5.71
The Committee acknowledges that there are access problems for many rare diseases, and encourages the TGA to work on improving those through increasing its alignment with international regulators where relevant. In particular, the Committee believes it is an unsatisfactory situation that cancer patients have the benefit of Project Orbis, but patients of non-cancer rare diseases have no equivalent. It therefore urges the TGA to try to remedy this disparity.
5.72
The Committee urges the Australian Government to reconsider the current cost recovery funding model for the TGA within the Department of Health. The Committee sees merit in increasing funding for staffing levels and expertise within the Department of Health to ensure the TGA can manage an increasing number of submissions in the near future and to expand competencies in horizon scanning for new medicines and technologies. The Committee welcomes the extra funding the Australian Government has recently provided, and urges the Australian Government to provide further funding to ensure that the TGA’s workforce is staffed sufficiently to meet workloads and that the IT system is able to deal with an increased number of submissions in the future.
5.73
The Committee acknowledges that the cost recovery model works well for therapies for more common diseases, and believes that it could be used to support the publication of Australian Public Assessment Reports (AusPARs) at the same time as the launch of a medicine, to ensure clinicians and their patients are as well informed as possible.
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The Committee believes there is merit in the suggestions that the TGA should adapt its processes to enable the approval of therapeutic goods by molecular indication as well as by disease indication. The Committee acknowledges that this is a highly complex issue, that such a change may involve substantial effort on the part of the TGA and that it will have repercussions for other elements of the development and approval process such as clinical trials and reimbursement. However, the Committee believes this will be an area of growing importance into the future and the TGA should adapt its processes accordingly.
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The Committee recommends the TGA aligns its processes with the PBAC’s for parallel processing purposes and its communication with sponsors during the assessment process. The Committee notes the growing importance of Real World Evidence (RWE) and welcomes the TGA’s commitment to produce more detailed guidance on its use.
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The Committee noted the FDA’s Breakthrough Devices Program. The Committee supports this idea and recommends that the Australian Government establish a similar program in Australia to support the domestic medical technology sector.