Medicines and Devices Regulation Review

The 110 page Review of Medicines and Medical Devices Regulation Discussion Paper noted here features a large number of questions in eight chapters, with a chapter on Complementary Medicine issues to be released in future.

Public submissions in response to the paper are due 5 January, with a report to the Government by 31 March.

The paper is strongly predicated on cutting what is described as "red tape" and might be construed as exacerbating the regulatory incapacity - if not regulatory capture - criticised by observers of the Therapeutic Goods Administration (TGA), ie the Australian counterpart of the FDA and the EMA.

The paper follows a succession of inquiries into the TGA and into associated matters such as pharmaceutical patents and ACCC recognition of the Medicines Australia Code, along with controversy over fraud and other problems regarding generic medicines.

Chapter Four of the paper states that "opportunities for improvement" reflect five themes:

1. There is duplication of regulatory processes, which creates an unnecessary additional burden on industry.

2. The regulatory framework lacks the necessary flexibility required to facilitate early access to innovative products.

3. Some regulatory requirements are not considered to be commensurate with the risk posed by the regulated products.

4. The regulatory framework is overly complex and poorly understood by many of those who have to interact with it.

5. Some TGA processes are considered to be overly burdensome and out of step with technology. 

Those themes determine the questions asked by the Review panel, which are as follows -

The Regulator

• How might a trusted overseas regulator be defined? Most countries assess medicines for safety and efficacy prior to approving them for market, but the nature and extent of the assessment that is undertaken can vary markedly. 
• If Australia were to register medicines based on an assessment by an overseas regulator, how is the Australian public to be reassured that this assessment will have been conducted with the same skill, depth of knowledge, and rigour as currently occurs in Australia? One option may be to develop a set of transparent criteria against which overseas regulators would be assessed in order to designate them as ‘trusted’. 
• What options are available for determining ‘trusted overseas regulators’? 
• If a criteria based approach were to be adopted, what criteria should apply in determining whether or not an overseas regulator is trusted? 
• If the TGA receives an application for registration of an NCE in Australia and the NCE has been approved by one trusted overseas regulator but rejected by another, should the submission be assessed by the TGA? If not, why not? 
• What other options would ensure that the health and safety of Australian consumers is protected? 
•  If a trusted overseas regulator rejects an application for marketing of a medicine for the same indications for which that medicine has been registered in Australia, should this spark a review by the TGA? 

Additional Requirements?

• Should the TGA approve the registration of a medicine on the ARTG on the basis that it has been approved for the same indications by a trusted overseas regulator? If not, why not? 
• What value do you believe an assessment by the TGA adds in cases where such an assessment has already been undertaken by a trusted overseas regulator? 
• Are there aspects of safety, quality or efficacy that need to be considered in the Australian context? If so, what aspects? 
• Would consideration of these aspects necessitate a full assessment of the entire application by the TGA? If so, why? 
• Should sponsors of medicines that have been approved by a trusted overseas regulator have to submit an Australian specific Module 1 of the CTD to the TGA for assessment? If not, why not? 
• What do you see as the risks and benefits of not requiring sponsors to submit an Australian specific Module 1? 
• What would be the likely quantum of savings to industry per application, if Australia was to accept assessments of trusted overseas regulators, with or without a requirement to submit an Australian specific Module 1 of the CTD to the TGA for assessment? 
• Would such an approach: Result in delayed access to new medicines by the Australian public? If not, why not? If yes, are there strategies that could be put in place to prevent this from occurring? Undermine TGA PBAC parallel processing mechanisms? If so, how might this be managed? 

Meaning of Product Approval

• Should a change to a medicine that has been approved by a trusted overseas regulator necessitate a further assessment by the TGA in circumstances where that change may impact safety, quality or efficacy? If not, why not? If yes, should the assessment by the TGA be limited only to those aspects of the application that are impacted by the change? 
• If Australia was to accept approvals of medicines by trusted overseas regulators, should this include conditional/provisional approvals? If not, why not? If yes, should the marketing conditions/provisions imposed by the trusted overseas regulator also apply in Australia? If not, why not? 
• Should there be capacity for Australia to impose its own conditions, either in addition to, or in place of, those imposed by the trusted overseas regulator and if so, why? Should Australia introduce an accelerated approval program(s)? 
• What are the potential risks and benefits of such programs and how might the risks be managed and the benefits maximised? 
• If Australia were to introduce an accelerated approval program: Should there be a single pathway (as per the EU model) or multiple pathways (as per the US approach) to apply? What eligibility criteria should apply to the pathway(s)? That is, under what circumstances could a sponsor apply for accelerated approval of an NCE? 
• If medicines were to be provisionally approved, based on more limited clinical data than is traditionally required for a full approval: What additional requirements, if any, might be appropriate to alert prescribers and/or consumers to the provisional approval and its implications? What requirements would need to be in place to manage withdrawal of the medicine from the Australian market if safety or efficacy concerns emerged? 

Approval of variations

• Should Australia adopt a risk based regime for variations, which allows notifications and/or annual reporting for changes that are at low risk of impacting the quality, safety or efficacy of the product? If not, why not? If yes, what might such a regime look like? 
• How might notification/reporting procedures be designed so as to minimise burden on sponsors? How might the process for minor variations for export only medicines be streamlined so as to facilitate more timely access to export opportunities without compromising health and safety? 
• Is the Special Access Scheme efficient and effective for Category A patients? Are there issues or concerns with the way in which the Scheme currently runs?
• Should the Special Access Scheme be revised to narrow the range of circumstances in which TGA approval is required for use of an unregistered medicine in a Category B patient? If yes, what criteria might be applied to determine when an approval is required? If no, why not? 
• What do you perceive as the risks of such an approach? 

Inadequate post-market surveillance?

• Does Australia’s post market surveillance of medicines need to be enhanced? If so, how might this occur? 
• What would be the features of an effective post market surveillance system? If not, why not? Why do you consider the current system effective? 

Regulatory advice to foster innovation

• Is there a role for the TGA in providing a regulatory advice service to product developers/sponsors? If yes, what should the nature and scope of this advice service be? 
• How could risks of regulatory capture be avoided? If not, why not?
•  Is current guidance material easy to locate, navigate and understand? If not, what are the main issues and concerns? 
• How might this material be improved? 
• Is the TGA website easy to navigate? If not, how might it be improved? 

Burdensome processes

• What TGA processes do you consider most burdensome and why? How might these be improved? 
• Do current regulatory requirements, costs, and timeframes act as a disincentive to the registration of additional indications for medicines? 
•  If yes, how might the regulatory framework or processes be changed to reduce the disincentives and/or provide incentives for the registration of additional indications, especially in paediatric populations? 

Trusted overseas regulators for generic medicines

• What options are available for determining ‘trusted overseas regulators’? 
• If a criteria based approach were to be adopted, what criteria should apply in determining whether or not an overseas regulator is trusted?
•  If the TGA receives an application for registration of a generic medicine or biosimilar in Australia which has been approved by one trusted overseas regulator but rejected by another, should the submission be appropriately assessed by the TGA? If not, why not? 
• What other options would ensure that the health and safety of Australian consumers is protected? 
• Should a change to a biosimilar that has been approved by a trusted overseas regulator necessitate a further assessment by the TGA in circumstances where that change may impact the comparability of the biosimilar? If not, why not? If yes, should the assessment by the TGA be limited only to those aspects of the application that are impacted by the change? 

Additional requirements re generics

• Should the TGA approve the registration of a generic medicine on the ARTG on the basis that: a trusted overseas regulator has assessed it as being bioequivalent to a reference product available in the overseas market; and the sponsor provides evidence that the overseas reference product and the Australian reference product are identical or interchangeable? If not, why not? 
• What value do you believe an assessment of bioequivalence by the TGA would add in such circumstances? Could work sharing initiatives between regulators improve timeframes for approval of generic medicines? If so, how? 
• In what ways could TGA processes for assessment of generic medicines be better harmonised with international practice? 
• Should the TGA approve the registration of a biosimilar on the ARTG on the basis that: a trusted overseas regulator has assessed it as being biosimilar to a reference product available in the overseas market; and the sponsor provides evidence that the overseas reference product and the Australian reference product are identical? If not, why not? 
• What value do you believe an assessment of biosimilarity by the TGA would add in such circumstances? 
•  Should Australia adopt a risk based regime for variations, which allows notifications and/or annual reporting for changes that are at low risk of impacting the quality, safety or efficacy of the product? If not, why not? If yes, what might such a regime look like? 
• How might notification/reporting procedures be designed so as to minimise burden on sponsors? 

Variations for Export

•  How might the process for minor variations for export only medicines be streamlined so as to facilitate more timely access to export opportunities without compromising health and safety? 

Burdens on registration of generics

•  Do you consider the timeframes for assessing applications for registration of new generic medicines to be unreasonable? 
• How do they compare with timeframes achieved by overseas regulators such as the FDA and the EMA? What do you think are the main factors impacting TGA timeframes for assessment of generic medicines and how might these factors be addressed? 
• Would the creation of a separate registration pathway for generic medicines achieve more timely approvals and more appropriately align regulatory processes with risk? If not, why not? If yes, what would the generic approvals pathway look like? How would it differ from the process for NCEs? 
• Should an update to the indications for a generic medicine which is in line with the originator medicine, be treated as a variation, rather than as creating a separate and distinct good? 
• What are the risks and benefits of this approach? 

Generics trade names

•  Do you believe that the process for applying for an additional trade name is burdensome? If yes, how do you propose it could be modified? 
• What do you think would be a reasonable statutory assessment timeframe for consideration of an application for an additional trade name? 

Risks re OTC medicines

• Do Australian decisions regarding the scheduling and/or rescheduling of medicines appropriately balance risk and benefit? If not, why not? 
• Are the current scheduling classifications and factors suitable for appropriately assessing substances based on risk? If not, in what way could they be improved? 
• What would be the advantages/disadvantages of adopting a formal methodology for assessment of risks and benefits to inform scheduling decisions? 
• What might such a methodology look like? How could the transparency of the scheduling process be improved? 
• What are the risks and benefits of allowing direct to consumer advertising of Schedule 3 Medicines? 
• How might any risks be managed? 

Risks re therapeutic goods

•  Is the threshold at which some products are classified as medicines too low? If so, what criteria could be used to determine which types of products were more suited to regulation as consumer goods? 
• What are the advantages and disadvantages of excluding some low risk products from the Therapeutic Goods Act 1989? 

Variations re OTC medicines

• Should Australia adopt a risk based regime for variations, which allows notifications and/or annual reporting for changes that are at low risk of impacting the quality, safety or efficacy of the product? If not, why not? If yes, what might such a regime look like? 
• How might notification/reporting procedures and mechanisms be designed so as to minimise burden on sponsors? 
•  How might the process for minor variations for export only medicines be streamlined so as to facilitate more timely access to export opportunities without compromising health and safety? 

Burdens re OTC Trade names

•  Do you believe that the process for applying for an additional trade name is burdensome? If yes, how do you propose it could be modified? 
• What do you think would be a reasonable statutory assessment timeframe for consideration of an application for an additional trade name? 

 Scheduling burdens

• Are scheduling and registration processes poorly aligned? If so, what approach could be adopted to achieve better harmonisation? 
• Would efficiency be improved and complexity reduced by introducing parallel processing of: scheduling and registration applications?; and rescheduling applications and related labelling alterations? 
• What are the advantages/disadvantages of such an approach? 

Recognition of overseas device regulators?

• Should the TGA undertake its own assessment of the competency of EU notified bodies? If yes, how might this occur? If not, why not? 
• Alternatively, given the concerns with the EU system, should Australia look to recognise other international regulators as ‘trusted’ for the purpose of device approvals? If yes, what criteria should apply in determining whether or not an overseas regulator is trusted? 
• Should any criteria take into account different device classifications? For example, a regulator could be designated trusted for some classes of devices but not others. 

Additional requirements re devices?

• Should the TGA approve the inclusion of a medical device on the ARTG on the basis that it has been approved for the same purpose by a ‘trusted’ overseas regulator?  If yes: ­ should this occur regardless of the class of the device? 
• ­ How could concerns about the quality of some overseas conformity assessments be managed? If not, why not? 
• What value do you believe an assessment by the TGA adds? Are there aspects of safety, quality or efficacy that need to be considered in the Australian context? If so, what aspects? 
• Where there are differences in device classification between Australia and the EU, should sponsors be required to meet additional conformity assessment requirements? If not, why not? 
• Should Australia adopt the EU classification system? If not, why not? 
• What are the strengths of the Australian device classification system that cannot be found in the EU system? 
• Should Australia maintain Australian specific requirements with respect to labelling and post market monitoring? If not, why not? If yes, what value do these requirements add? 

Device approval

• Should a difference in a medical device that has been approved by a trusted overseas regulator necessitate a further assessment by the TGA in circumstances where that difference may impact safety, quality or performance? If not, why not? If yes, should the assessment by the TGA be limited only to those aspects of the application that are impacted by the difference? 
• Would this approach apply to all classes of medical devices? 
• If Australia was to accept approvals of medical devices by trusted overseas regulators, should this include conditional/provisional approvals? If not, why not? 
• Would this approach apply to all classes of medical devices? If yes, should the marketing conditions/provisions imposed by the trusted overseas regulator also apply in Australia? If not, why not? 
• Should there be capacity for Australia to impose its own conditions, either in addition to, or in place of, those imposed by the trusted overseas regulator and if so, why? 
• Should Australia introduce an accelerated approval program(s) for higher risk medical devices? If yes:  What eligibility criteria should apply to the accelerated approval pathway? That is, under what circumstances could a sponsor apply for accelerated approval of a device?  What are the potential risks and benefits of such programs and how might the risks be managed and the benefits maximised? 
•  If higher risk medical devices were to be provisionally approved, based on more limited clinical data than is traditionally required for a full approval:  What additional requirements, if any, might be appropriate to alert clinicians and/or consumers to the provisional approval and its implications? 
• What requirements would need to be in place to manage withdrawal of the device from the Australian market if safety or efficacy concerns emerged?
• What additional post market surveillance would need to be in place for medical devices that were provisionally approved? 

Flexibility

•  Is the current regulatory framework and classification system flexible enough to accommodate new and emerging medical device technologies? If not, why not? How could it be improved? 

Device risk and regulatory burdens

• Does the current regulatory framework for medical devices in Australia provide an appropriate balance between managing risk and minimising unnecessary regulatory burden? If not, why not?
• Should low risk medical devices that are not subject to an independent conformity assessment be included on the ARTG? If not, why not? 
• Are there any risks involved in not including such products on the ARTG? If yes, why? 
• What are the benefits of these products being included on the ARTG? 
• Should Australia adopt a risk based regime for variations, which allows notifications and/or annual reporting for changes to medical devices that are at low risk of impacting the quality, safety, or performance of the device? If yes, what might such a regime look like? 
• How might notification/reporting procedures be designed so as to minimise burden on sponsors? If not, why not? 

Post-market surveillance

• Does Australian have the balance right between pre market and post market regulation of medical devices? If not, why not? How could it be improved?
•  What are the features of an effective post market surveillance system? 

Access to unapproved devices

•  Is the Special Access Scheme efficient and effective for Category A patients? Are there issues or concerns with the way in which the Scheme currently runs? 
•  Should the Special Access Category B and the Authorised Prescriber schemes be revised to narrow the range of circumstances in which TGA approval is required for use of an unregistered medical device?  If yes, what criteria might be applied to determine when an approval is required? If no, why not? 
• What do you perceive as the risks of such an approach? 

In vitro diagnostics

• Has the regulatory framework for IVD’s resulted in a reduced emphasis on clinical best practice? If so, how.
• Should there be statutory timeframes for assessment of applications for inclusion of an IVD on the ARTG? 

Process burdens

• What TGA processes do you consider most burdensome and why? How might these be improved? 
•  How might the processes required to include a device family on the ARTG be streamlined without undermining public health and safety? 
•  Are there other concerns with the inclusion of devices on the ARTG? How might these be addressed? 
• Should the TGA allow a broader range of permissible formats for instructions for the use of medical devices? If not, why not? 
• Do current regulatory requirements, costs, and timeframes act as a disincentive to the registration of additional intended purposes for medical devices? If yes, how might the regulatory framework or processes be changed to reduce the disincentives and/or provide incentives for the registration of additional intended purposes? 

Classification of devices

•  Is the classification system for medical devices too complex? If yes, how might it be simplified without impacting public health and safety? 
• Do manufacturers require assistance, such as online decision tools, to assist them to correctly classify medical devices? If not, why not? If yes, what sorts of assistance would be most effective? 
•  Is the pre market assessment of medical devices considered overly complex in other ways? If yes, in what way? 
• What are the major pressure points and how might these be addressed? Is there a role for the TGA in providing a regulatory advice service to product developers/manufacturers/sponsors? If not, why not? If yes, what should the nature and scope of this advice service be? 
• How could risks of regulatory capture be avoided? 
• Is current guidance material easy to locate, navigate and understand? If not, what are the main issues and concerns? How might this material be improved? 
• Is the TGA website easy to navigate? If not, how might it be improved? 

Transparency

•  Should information about regulatory decisions in respect of medical devices be publicly available? For example, an evaluation report or other relevant information. If not, why not? 
• What do you see as the risks? If yes, how would this benefit consumers, clinicians and industry? 
• How could any risks be managed? 
• Should other regulatory findings relating to medical devices be made public, for example, reports on audits or post market reviews?  If not, why not? What do you see as the risks?  If yes, how would this benefit consumers, clinicians and industry? How could any risks be managed? 
• Could the regulation of medical devices be made more transparent in other ways? If so how, and what would be the risks and benefits of the proposed approach? 

Interaction with other frameworks (eg the GTR)

•  Is the system overly complex for manufacturers/sponsors of devices using hybrid/convergent/ co dependent technologies? If yes, how could the process be streamlined without undermining public health and safety? 

Consumer understanding

• Is the regulation of medical devices transparent enough in terms of informing health professionals and consumers about the level of scrutiny that a device has undergone? If not, how could it be improved? 
• Should there be a system for medical devices similar to the AUST R and AUST L system for medicines? If not, why not? 

Advertising Framework

• Should Australia allow advertising of prescription medicines to the general public? If not, why not? If yes, what risks might this create and how could these be mitigated? 
• What are the risks and benefits of allowing direct to consumer advertising of Schedule 3 medicines? How might any risks be managed? 

Co-regulation

•  Should Australia continue to require compulsory pre vetting of medicines advertised direct to consumers or should it move towards a self regulatory, or combined statutory and self regulatory, model? 
• If Australia was to adopt a self regulatory model or a model which combined risk based regulation with self regulation (such as the UK) what key elements would need to be in place to ensure that public health and safety was protected, while minimising regulatory burden? 

Advertising enforcement

• Should there be a single authority for receiving complaints about the advertising and marketing of therapeutic products? If yes, which agency would be best placed to act in this capacity? 
• Does the current regulatory framework for advertising medicines direct to consumers: Provide adequate incentives to promote compliance with requirements? If not, why not. What additional incentives should be included? Contain adequate sanctions and penalties for non compliance? If not, what additional sanctions and penalties should be available? 
• Should the TGA have the power to take immediate action to suspend an advertisement that it considers places at risk public health and safety? 
•  If yes, why and how might any risks be mitigated? If not, why not? 
• Is the current self regulatory scheme for advertising of medical devices effective? If not, why not? Please provide examples of where the system has failed.