Summary
In the past few years, accelerated by research and investment during the COVID pandemic, a group of technologies based on synthetic mRNA and nanoparticle delivery mechanisms has reached the stage of clinical application. These initiatives include improved vaccines for endemic and emerging diseases, immunotherapeutic approaches to cancer, and the potential for therapies for some genetic conditions.
The Therapeutic Goods Administration, along with international regulators, recognises the importance of ensuring timely access to products that arise from these new technologies, at the same time developing appropriate regulatory guidelines and evaluation pathways to ensure public safety.
There has been discussion within the pharmaceutical industry, the research community and among regulators of a potential ‘platform’ approach to assessing mRNA products. There is, however, currently no consensus on what constitutes an mRNA ‘platform’.
In principle, a ‘platform’ approach to regulation would allow Sponsors to use data between products and thus reduce the need to generate new information for each application, as well as make some changes to an existing product with minimal regulatory oversight. Given the similarity between some mRNA products (e.g. vaccines manufactured using the same method and delivery particle) there is merit to this approach.
At this stage the TGA feels that adopting a platform approach is premature given the mRNA technology is relatively new. There is currently insufficient regulatory experience with mRNA products to know what elements of a regulatory dossier can be applied between different products, and what specific components of a product are of potential significance for its efficacy and safety.
Furthermore, although mRNA technologies are similar in some respects there are different ways this technology can be applied. The breadth of current mRNA technologies does not easily allow a definition of what is captured by a ‘platform’ use of data. It is expected that guidance will be developed on these matters as more regulatory experience is gained to identify common features of mRNA technologies, with ‘case-by-case’ approach being applied in the interim.
The TGA recognises that the regulatory management of emerging mRNA technologies is a rapidly evolving policy environment. Several comparable overseas regulators acknowledge ‘prior knowledge’ from applications can be leveraged by Sponsors in future applications, and this is consistent with the TGAs case-by-case approach.
TGA will seek to align its approach with overseas Regulators although specific interpretation will be on a case-by-case basis.The TGA’s position will remain under active review as a regulatory consensus on the management of mRNA platform technology emerges.
Specific positions on key issues
Position on platform assessment of mRNA products
The TGA does not currently recognise a category of ‘platform’ mRNA technologies, applications or application pathways for evaluation and registration purposes.
All registration applications for mRNA based products will be assessed on a ‘case-by-case’ basis on their own merits.
In an application, Sponsors are able to refer to previously submitted data which may be of relevance. This use of ‘prior’ knowledge is consistent with the current approach to mRNA applications by international regulators.
If an application relies on previously submitted data, this data must be referenced in the application. A Sponsor cannot assume TGA will automatically identify to previously submitted data.
Previously submitted data may require re-evaluation, and additional questions may be raised regarding these data, in the context of evaluation of a new application.
The fact a product uses mRNA technology does not remove the requirement to comply with any established quality guidance applicable to a class of products, such as validated batch-release testing and potency assays for vaccines.
Obtaining TGA guidance on applications relating to mRNA products
There is currently no standing TGA guidance on a ‘platform’ approach to the assessment of mRNA-based products.
Sponsors are encouraged to seek TGA advice before lodging an application for approval of an mRNA based product (e.g. a pre-submission meeting).
At a pre-submission meeting TGA can share its experience with the evaluation of similar applications (whilst respecting commercial confidentiality). This experience forms the evolving body of guidance that the regulator has currently developed for mRNA products.
All TGA advice at pre-submission meetings is made without prejudice to the final decision regarding an application. However, advice is provided to Sponsors in good faith and should be taken as indicative of the TGA’s likely approach to an application.
Considerations in risk-benefit assessment of mRNA based products
The potential application of mRNA technology spans a large range of medical conditions, from preventive immunisation to the treatment of acute medical conditions (e.g. cancer).
When referring to previously submitted data, TGA will consider the appropriate risk context for the proposed use of an mRNA product.
It may not be possible for Sponsors to rely entirely on data obtained in one risk setting to support an application in another.
Safety data for an mRNA product in adult cancer patients would not, for example, be sufficient to address the safety of a vaccine given to pregnant women at a population level.
Conversely, data for lethal conditions for which existing therapies also carry significant risks may require less data than for a preventative treatment to support use.
Provisional registration may be an option for treatments with promising preliminary clinical data.