Fast drugs: accelerating the regulatory approval pathway for COVID-19

7 minute read  27.03.2020 Simone Mitchell, Jonathan Kelp, Kristi Geddes, Jaimie Wolbers, Helaena Short

As the COVID-19 crisis continues to take hold globally, attention is increasingly turning to the tireless work being done by medical researchers to address the effects of the pandemic. What are the options for fast-tracking regulatory approval for vaccines, diagnostic tests and treatments for COVID-19 and when are we likely to see results?

In Australia, the Doherty Institute is working on a new test for COVID-19 that reportedly delivers results in 30 minutes. Funding is presently being sought for clinical trials of certain drugs that might be used to treat COVID-19. Many research institutes and companies in Australia and around the world have commenced researching potential vaccines that they hope will confer immunity against COVID-19.

As a general rule, any vaccine, medicine or medical device must be approved by the Therapeutic Goods Administration (TGA) before it can be supplied in Australia. A test, treatment or vaccine for COVID-19 is no different. However, while the TGA has an important role to play in ensuring quality, safety and efficacy, there are some fast-track mechanisms that may apply in light of the public health emergency we are presently facing.

Importantly, the options available differ depending on whether they are being asked to consider a vaccine that might provide immunity and hence prevent people contracting COVID-19 in the first place, a diagnostic test for COVID-19, or a new or existing drug used as treatment for COVID-19 patients.

How quickly can we bring a vaccine to market?

Any one of the potential vaccines currently being researched, or a number of them together, may prove to provide immunity against COVID-19. Presently, some are being tested in laboratories (for example, tests on cell-cultures or animals), while others are progressing to Phase 1 clinical trials in humans.

Clinical trials form an important part of the data reviewed by the TGA or equivalent regulators overseas when deciding whether to approve a vaccine for supply and use in humans.

Phase 1 clinical trials involve administering the vaccine to between 10-100 healthy adult human volunteers to assess the vaccine's safety profile and potential side-effects. Assuming no safety issues arise, Phase 2 and Phase 3 clinical trials involve larger groups of volunteers for a closer analysis of the efficacy of the vaccine, identifying the most effective dose and assessing the risk-benefit balance. For a standard vaccine development process, each phase of these trials can last anywhere between many months to years.

It is possible for the TGA to approve a new vaccine on the basis of more limited data, for example, if immunological data from a phase 1 or phase 2 trial can be used to predict vaccine efficacy (that is, the likely extent of protection against infection) that would otherwise be assessed in a phase 3 trial. In those cases the TGA would require efficacy to be monitored after the vaccine has been launched.

However, the clinical trial process simply cannot be bypassed in the rush to have a vaccine available.

In the spirit of international co-operation to combat the COVID-19 pandemic, the TGA is a lead member of a group of regulatory authorities who will undertake and prioritise coordinated reviews of relevant vaccines (and medicines) for COVID-19.

Given the TGA's announcement that it will give medicines and vaccines relating to COVID-19 the highest possible priority, we expect that Australia will be in the best possible position to promptly access any new vaccine once the necessary clinical trials have concluded and been evaluated.

Even with that prioritisation, and cooperation between regulators globally, the earliest we are likely to see an approved COVID-19 vaccine in Australia is mid-2021.

Can we use the seasonal flu vaccine model for COVID-19?

A seasonal flu vaccine is available each year, and is approved by the TGA under a simplified approval pathway.

However, the quicker pathway only applies on the basis of:

  • The manufacturing process is the same as a previously approved vaccine, with the only change being the strains of virus included in the vaccine;
  • There are many years of safe and effective use of seasonal flu vaccines in several million people globally; and
  • The TGA in any event evaluates the safety and quality of each batch lot of vaccine before it can be released.

Because any COVID-19 vaccine would be novel and will not have extensive pre-existing safety or efficacy data, unlike the seasonal influenza vaccine, it is unlikely to be a candidate for an abbreviated pathway of this type.

Do COVID-19 diagnostic tests need approval?

The TGA has greater flexibility to facilitate the rapid approval of diagnostic medical devices used to detect COVID-19 infection.

First, the TGA has committed to expediting review of the information and performance data for any COVID-19 test as a matter of priority, with further requirements that will assist the TGA to monitor ongoing safety and performance of the tests as we learn more about COVID-19. Between 19 and 26 March, the TGA, through that expedited review process, approved 13 COVID-19 diagnostic tests.

Secondly, at the end of January 2020, Health Minister Greg Hunt formally made an exemption under the Therapeutic Goods Act that allowed the supply of unregistered COVID-19 diagnostic tests to a member of the Public Health Laboratory Network, and which has subsequently been expanded to include all accredited pathology laboratories.

How broad is the Minister's power to make exemptions?

The power used by Minister Hunt allows medical devices to be exempt from the regulatory approval provisions under the Act if he satisfied that, in the national interest, it is necessary so that the devices can be made available urgently in Australia in order to deal with an actual threat to public health caused by an emergency that has occurred. In light of significant concerns regarding the availability of ICU ventilators, it is possible that novel or repurposed ventilator medical devices will be exempt from some or all of the standard regulatory requirements if adequate manufacturing and supply capability is demonstrated.

A similar power applies to medicines. Therefore, it is theoretically possible that the Minister might make an exemption for a COVID-19 vaccine.

However, it is unlikely that a vaccine would be permitted to enter the market without appropriate clinical trial data adequately establishing, at the very minimum, the safety profile of the new vaccine. The potential for widespread and significant patient harm arising from an unapproved vaccine is far greater that for unapproved medical devices.

How quickly can we bring a medicine for treating COVID-19 to market?

Many of the medicines being assessed for their potential use in treating COVID-19 have already been approved by the TGA, albeit for treating other conditions. Where these anti-viral medicines have been available on the market for a significant period of time, their safety profile is very well established. Therefore, the concerns that apply for a novel vaccine are less likely to arise, and the TGA may be more willing to expedite regulatory approval.

In any event, where a medicine is registered and available in Australia, medical practitioners may prescribe or dispense most medications for any purpose considered appropriate and necessary in their reasonable clinical judgement (described as 'off-label use'). This would allow most approved medicines to be used for the treatment of COVID -19 if a medical practitioner considers it clinically justified. However, in light of increased off-label prescribing of hydroxycholoroquine, the TGA recently amended the Poisons Standard so that only a subset of medical specialists may prescribe hydroxychloroquine to patients in the first instance. The Poisons Standard, including the recent amendment, is automatically adopted most Australian States and Territories. Therefore, it is possible that off-label use of certain medicines may become increasingly more restricted during the pandemic to address the risk of shortages.

Another important consideration is that off-label use of an existing medicines is usually not eligible for subsidy under the Pharmaceutical Benefits Scheme.

Other medicines under investigation for use against COVID-19 have been previously subject to clinical or pre-clinical testing but have never obtained regulatory approval.

Even if a medicine is not registered and available in Australia, its use may nevertheless be permitted under a scheme that allows for the import and supply of unapproved medicines to a single patient on a case-by-case basis (described as the 'Special Access Scheme'). Depending upon how ill the patient is, this requires either advance approval from the TGA, or notification to the TGA within 28 days of the medicine being administered.

Key takeaways

  • The options available to the regulator differ depending on whether they are being asked to consider a vaccine, a diagnostic test for COVID-19, or a new or existing drug used as treatment for COVID-19 patients.
  • It is possible for the TGA to approve a new vaccine with more limited data and it is theoretically possible that the Health Minister might make an exemption for a COVID-19 vaccine. However, it is unlikely that a vaccine would be permitted to enter the market without appropriate clinical trial data adequately establishing, at the very minimum, the safety profile of the new vaccine. The earliest we are likely to see an approved COVID-19 vaccine in Australia is mid-2021.
  • Diagnostic tests are being expedited for approval by the TGA (with 13 tests approved in the last week) and the Health Minister has formally made an exemption under the Therapeutic Goods Act that allowed the supply of unregistered COVID-19 diagnostic tests in certain circumstances.
  • Many of the medicines being considered for their potential use in treating COVID-19 have already been approved by the TGA for treating other conditions. Where a medicine is registered and available in Australia, medical practitioners may exercise reasonable clinical judgement to prescribe or dispense the medication for another purpose. Where a medicine is not registered and available in Australia, its importation and use may nevertheless be possible under the "Special Access Scheme". However, efforts by the TGA to curb off-label use of some medicines may have an increasing impact on these supply mechanisms as the pandemic progresses.

If you would like to discuss the regulatory approval pathway for vaccines, medical devices or medicines, whether COVID-19 related or not, please do not hesitate to contact us.

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