Australia Considers Changes To Bioequivalence Requirements For Foreign Comparators
Executive Summary
Changing Australian requirements on showing equivalence with an overseas reference product used in bioequivalence studies, and introducing a new early scientific advice service for biowaiver proposals, are among key proposals made by the Therapeutic Goods Administration as part of reforms in the generic medicines sector.
Australia's Therapeutic Goods Administration is inviting stakeholder feedback on proposed reforms to the market authorization process for generic prescription medicines to help reduce regulatory burden, make the application process easier and promote international work-sharing. It also plans to offer incentives to generic sponsors to help address drug shortages and reduce medicine expenditure.
Two of the key changes proposed by the TGA relate to changing current data requirements for sponsors to demonstrate bioequivalence with an overseas reference product used in bioequivalence studies, and introducing a new early advice scheme for biowaiver justifications.
The TGA's reform proposals are listed in a consultation paper on which interested stakeholders can comment until March 21. While the proposals are specifically focused on generic prescription medicines, the TGA said that in the future many of these ideas could be extended to other prescription and non-prescription medicines processes, particularly those for biosimilar medicines.
On the issue of bioequivalence studies using an overseas reference product, the TGA explained that at present it accepts such studies only if the company can provide evidence that the overseas reference product is identical to the Australian reference product. However, establishing "identicality" to the overseas reference product can be challenging and not possible in some cases due to the complex nature of certain manufacturing processes and formulations.
Although the TGA's requirements on this front are comparable with overseas regulatory agencies, such as those in the EU and Canada, it noted that some agencies, for example those in Switzerland and Singapore, do not always rely on the same way of demonstrating "identicality" and, in some conditions, place less emphasis on confirming the exact quantities of the non-active ingredients.
If the TGA were to change its requirements for demonstrating equivalence between the Australian and overseas reference products, it wants to know whether this would help reduce barriers for companies seeking to register new generic medicines, or whether it could lead to potential unintended consequences.
The TGA has proposed introducing a new early scientific advice service for biowaiver justifications. At present, biowaiver requests are considered on a case-by-case basis during the market authorization process, and if the company's biowaiver justification is deemed unacceptable, the only options are for the company to withdraw its submission or for the TGA not to approve the application. At present, companies cannot seek formal advice on the appropriateness of a biowaiver justification prior to evaluation of the full dossier.
To remove uncertainty about the acceptability of a proposed biowaiver justification, the TGA has suggested introducing an optional service of allowing sponsors to seek formal scientific advice from the agency on their biowaiver proposal. This advice would be offered before the company submitted its marketing authorization application and it would operate independently from the evaluation and registration processes, the agency explained.
The new scientific advice service, it is envisaged, would initially focus on a "limited number of technical issues" specific to biowaiver justifications, with plans to extend it in the future to include issues particular to complex generics, and even more broadly to other types of medicines or applications.
Regarding the proposed new service, the TGA is yet to decide on what mechanisms are available in the current regulatory framework to offer such early advice, and what fees should be charged to companies.
Other proposals made by the TGA pertain to:
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- Adopting international templates (on submitting bioequivalence trial information and biowaiver justification) to improve opportunities for joint submissions to multiple agencies and to support work-sharing.
- Offering incentives to sponsors to address instances of drug shortages and high medicine expenditure. Australia imports over 90% of its medicines, which makes it particularly vulnerable to medicine shortages due to factors outside its control. The TGA believes diversifying supply can help and is looking at options to encourage more generic versions of medicines to be authorized, particularly those with only one supplier or manufacturer. On the issue of supporting access to cheaper medicines, the TGA is considering implementing a priority system whereby applications could be either be evaluated more quickly or go to the head of the evaluation queue to be listed as first generic medicine on the Pharmaceutical Benefits Scheme.
As the implementation of many of these proposals will require the updating of business processes and administrative requirements, and potentially regulatory changes, the TGA said that following feedback on this initial consultation it would initiate further consultation with interested parties on implementing the supported options. This would include seeking comment on more specific details for each proposed reform.
From the editors of Scrip Regulatory Affairs.