Global Regulators Embrace Collaborative Initiatives

Efforts to build greater harmonization between global regulators are gathering momentum, partly due to changes brought about by COVID. This growing trend is likely to continue as regulatory authorities gain increasing confidence in collaborative initiatives that are still in their infancy.

The pandemic accelerated the level of collaboration among regulators, driven by the urgent need to find a vaccine to combat the deadly virus worldwide. The outcome demonstrated what can be achieved when drug approval processes are streamlined to improve timely access for all without compromising safety. Global collaboration is likely to grow in the future as regulatory authorities seek to build greater efficiencies into the review process.

There has long been a tradition of regulators in different regions sharing information, but this did not necessarily translate into work sharing. The unnecessary duplication of evaluation processes impeded the release of life-saving drugs, with some markets waiting more than two years after initial approval in the United States, for example.

Breaking down barriers

With its rapid and deadly spread, COVID-19 was a game changer for the pharmaceutical industry, and its regulators, worldwide. While drug companies worked collaboratively across regions to develop effective vaccines, regulators also had to show a willingness to break down traditional barriers to approval. Collaboration was essential to ensure all regions had access to the vaccines at the same time.

The groundwork for fast-tracked approvals in Australia was laid in 2018 when the Therapeutic Goods Administration (TGA) reviewed the way it assessed dossiers for new registrations. Previously, the regulator had performed a full assessment to determine the safety, efficacy and quality of medicines before allowing their release onto the market.

However, the TGA recognized the need to reduce duplication of evaluation processes to prevent unnecessary delays in getting medicine to those who need it most.

Traditionally, a new drug would have sought approval in the United States first, via the Food and Drug Administration (FDA), and in the European Union, before making its way to Australia for evaluation.

With drugs taking years of research and clinical trials to get to the approval stage, this jurisdictional delay could prevent Australians with life-threatening conditions such as cancer from getting access to critical medicine in a timely manner.

The TGA introduced more flexible pathways to approval for prescription medicines, depending on the drug and the circumstances. Under the standard pathway, it could take the regulator up to a year to review the evidence of a drug that had already been approved in the US or the EU.

To ensure patients with serious conditions are not waiting unnecessarily for potentially life-saving drugs, sponsors can apply to fast-track the process – either via the priority review pathway or the provisional review pathway.

Under priority review, the TGA can complete an evaluation up to three months earlier by adopting a more flexible approach including, for example, asking the sponsor questions as they arise rather than waiting to send a consolidated list of questions on completion of the assessment round.

Under the provisional approval pathway, a sponsor can apply to the TGA to approve medicine for a serious or life-threatening condition for a limited period while the pharmaceutical company completes final clinical trials – making a drug available up to two years earlier than normal.

The COVID vaccines fell into this approval category because of the urgency of the situation. The TGA approved them on the basis that the clinical data was evident and the real-world data to validate the safety of the products would follow.

This collaboration was a great example of global harmonization, not just in drug development but in getting the medicines reviewed and approved.

This flexible approach to approvals benefits the pharmaceutical industry and the regulator. It gives sponsors an opportunity to release medicines in different regions at the same time and enables the TGA to leverage other health regulators’ evaluation. Most importantly, it benefits patients who gain quicker access to new medicines – or new uses for established medicines.

Maximize expertise, minimize duplication

In recent years, collaboration has become more formalized through various initiatives.

The Access Consortium, which is made up of the TGA, Health Canada, Health Sciences Authority of Singapore, Swissmedic and the UK’s Medicines and Healthcare products Regulatory Agency (MHRA), was established to promote collaboration among regulators, as well as better alignment of requirements for drug approvals.

Recognizing the need to maximize the use of new technologies and reduce duplication, as well as ensure each agency provides timely access to consumers, the coalition is committed to information and work sharing.

Each authority retains its autonomy over the approvals process, but such collaboration enables the parties to reduce the duplication of essential evaluation and, therefore, the delivery timeline. Four submissions were approved through the Access Generic Medicine Work Sharing Initiative in 2021-2022.

The TGA is also a partner in Project Orbis, which was established in 2019 by the FDA Oncology Center of Excellence to help improve access to new treatments for patients with cancer. The Australian regulator joined the FDA and Health Canada in the first collaborative review of two products, enabling simultaneous decisions in all three countries, with only minor differences between their drug labels. The TGA used its provisional approval pathway to bring the drugs to market.

In 2021-2022, there were 22 submissions approved through Project Orbis, up from 11 the previous year.

Project Orbis acknowledges that clinical trials internationally play an increasingly important role in investigating the safety and efficacy of cancer drugs. This work sharing could also have long-term benefits, with uniformity of global standards to improve the design of clinical trials and, ultimately, the drugs developed.

Regulatory collaboration helps alleviate internal pressures, as well as external. With senior TGA reviewers retiring or exiting, for example, the regulator can draw on the expertise of partners to fill gaps in the evaluation process. Similarly, when Brexit forced the European Medicines Agency (EMA) to move from London to Amsterdam, the regulator lost many of its experts who did not want to relocate. These situations have made global partnerships all the more important.

Collaboration will also help regulators navigate the legacy of COVID, including disruptions to manufacturing and supply of medicines. The TGA has been working closely with its global counterparts to prevent, or at least limit, shortages.

There is no doubt that the pharma landscape is changing, including the type of products and the supporting technology. The medicines being proposed for registration are also getting more complex.

With these changes comes greater demand for regulatory scientists and evaluators who need to be upskilled to ensure the continued efficacy, quality and safety of approved medicines. One of the best ways to do this is to connect globally and leverage the expertise of others.

The response to the pandemic from the pharma industry and its regulators has created a blueprint for the future whereby collaboration is the norm, rather than the exception.

About the author

Piety Rocha is the director, head of Regulatory Affairs Team & country head VDC at Pharmalex. She has more than more than 20 years’ experience in the Australian and New Zealand pharmaceutical industry and has managed regulatory affairs team locally and internationally.