Clinical Researcher—June 2024 (Volume 38, Issue 3)

INTERNATIONAL INTERLUDE

Piety Rocha

 

 

 

As companies seek ways to bring their products to multiple markets, understanding those markets and their regulatory approval process is imperative. Choosing the most appropriate pathway can reduce the burden on both the sponsor and on the health authorities, and potentially expand access to more patients.

One such pathway is the Access Consortium, which was formed in 2007 by four health authorities: Australia’s Therapeutic Good Administration (TGA), Health Canada, Singapore’s Health Sciences Authority (HSA), and Swissmedic.{1} In 2020, following Brexit, the United Kingdom’s Medicines and Healthcare products Regulatory Agency joined the Access Consortium.

The Access Consortium was established amid increased globalization and, with it, a growing push toward greater harmonization by aligning regulatory policy approaches, providing joint scientific advice and work-sharing, reducing duplication and the burden on health authorities, and accelerating access to high-quality medicines.{2,3}

Access Consortium Developments

While the Access Consortium has been in place for 17 years, there are signs that interest in the pathway is gaining momentum. According to the TGA, the first two submissions to all five agencies were approved through the New Active Substances Work-Sharing Initiative (NASWSI) in 2022–23.{3} In 2023, the TGA approved seven new medicines through the NASWSI. As of June 2023, NASWSI had approved 25 applications.{4}

In recent years, there have been a number of developments to further strengthen the process. Access now has several active working groups in place to support a range of activities across active substances, generics, information technology architecture, and, most recently, a group dedicated to advanced therapy medicinal products (ATMPs).{5}

In late 2023, Access created the Promise Pilot Pathway to establish a common approach to the criteria for priority review. The pathway applies to products that treat a serious, life-threatening, or severely debilitating condition or where no other treatment is registered or marketed in participating regions. The pathway will be further reviewed after the pilot. Assessment of an application is carried out by one agency with peer review by all participating agencies.{6}

The Agency Review Process

The way the agencies manage work-sharing is to have different agencies than the originating one review each Module within the electronic Common Technical Document (eCTD) submission, depending on capability, experience, and capacity. The other agencies will review and discuss the assessment reports for these modules and a consolidated list of questions, which are then sent to the marketing authorization holder (MAH) for Modules 2 to 5.{4} The country assigned to specific modules will evaluate the responses and, if necessary, the agencies may prepare an additional list of questions for further clarification, and any remaining country-specific questions will be treated on a national level.{6,7}

Differences between Modules 2 to 5 are accepted, though MAHs are asked to outline any differences in the information they provide to each authority. These will be discussed by participating members to determine if the application is suitable for a work-sharing arrangement.{5}

Module 1 (not part of the CTD) will be reviewed separately by each participating agency, given that it contains country-specific administrative information. At the end of the review period, each authority issues its decision on marketing authorization independently.{4}

Sponsors also can take advantage of predictability of evaluation timelines, which are agreed to by all participating health authorities before commencing the evaluation.{8} This, together with a consolidated set of questions, provides MAHs with a clearer timetable of the process from start to finish, helping teams to plan and prepare their organizational strategy.

The Access pathway also gives companies the potential to consider submission to the five markets concurrently with submissions in other markets, which our experience has found would otherwise put too great a burden on busy global pharmaceutical teams that are often faced with competing deadlines, making prioritization challenging.

However, it is important to consider the approach carefully, since as our experience shows, some authorities, for example Singapore’s HSA and the TGA, have in the past rejected applications through Access for products approved in the European Union (EU), choosing instead to use other reliance (whereby one national authority takes into account assessments performed by another authority) or comparable overseas pathways.{9}

Therefore, companies should take time to understand what is expected. In addition to an Expression of Interest submitted to each participating health authority, companies interested in the Access pathway can take advantage of technical and logistical pre-submission meetings with the health authorities to clarify expectations.{6}

Planning the Regulatory Pathway

We have seen examples where different evaluation outcomes by each regulator can significantly delay approval when an MAH submits national applications in each country, rather than through the Access Consortium. For example, a pharmaceutical company obtained registration from one of the Access regulators with a post-approval commitment to submit impurity-related information once it became available. However, for the same product, another regulator put a stop clock on the submission until the data were generated, resulting in an 18-month delay to approval. Had the application gone through the Access Consortium, experience would suggest the likelihood of the health authorities coming to an agreement, for example on post-approval commitment, therefore reducing the delay to approval in one Access market.

For the sponsor or MAH, another advantage of the pathway is it reduces the burden on global teams. If applying separately, each team—chemistry/manufacturing/controls, clinical, preclinical—will face different sets of questions from each jurisdiction, which can result in a constant flow of questions throughout the year, depending on the submission plan. By way of example, one large pharmaceutical company that took a combination product through the Access pathway found that the reduced burden on the global teams—in terms of not having to respond to multiple identical requests for information—allowed them to focus their attention on other priority products. This provided predictability in relation to their internal resourcing needs.

For small companies that don’t have large teams, being able to answer just one set of questions can be hugely advantageous.

Companies should understand that Access is a work-sharing initiative, not a harmonized process like the Centralized Procedure in the EU, where there is an agreed assessment report to which all EU member states must adhere. Rather, Access facilitates the review process in the five countries, or however many countries members participate in a given application. Ultimately, each regulator will make its own decision. Indications and final product labeling could be slightly different in each country, but the core evaluation is common.{6} This has similarities to Europe’s Decentralized Procedure, where one agency acts as a reference regulatory agency and will evaluate Modules 2 to 5.{10}

Companies considering the Access pathway will also need to allow for the preparation time. While, overall, the process can reduce the burden on global teams, there is an administrative burden to consider since potential applicants will first need to seek permission to begin the process through an Expression of Interest application to participate in work-sharing.{6} The form will need to be sent simultaneously to at least two Access members for their approval in order to adopt the Access pathway.{11} Although Modules 2 to 5 might be harmonized, MAHs may also need to meet country-specific requirements before initiating the process—for example, obtaining an establishment license from Swissmedic to distribute a product in Switzerland or a Good Manufacturing Practice clearance from the TGA for all sites involved.{12,13}

A Triple Advantage

A recent survey found that MAHs that did participate in the Access pathway were largely satisfied with the experience. Participating affiliates surveyed cited several benefits to the process, with 76% saying it helped them gain experience with a work-sharing pathway, 73% saying it led to near simultaneous approval in multiple countries, 61% saying the review process was shorter compared to national timelines, and 61% saying there were fewer overall questions from the health authorities.{4}

While most health authorities now have reliance programs in place, these are not work-sharing initiatives.{9} It is this work-sharing approach with the potential for simultaneous assessment and approval timelines to allow access to all the markets involved—potentially five different jurisdictions—that separates Access from the reliance programs. This is an advantage both to the individual health authority, reducing workload, and to the MAH, by way of being able to submit one version of the dossier to all participating countries.

This can lead to a vast time saving for busy regulatory affairs teams, which would otherwise have to adapt multiple country-specific dossiers—a process that experience shows can take several months.

Besides the work-sharing benefits, data from the Centre for Innovation in Regulatory Science shows that the median submission gap and median approval time for new active substances approved through Access was faster than for those approved by the individual health authorities.{14}

Conclusion

Work-sharing is a clear benefit to the health authorities, helping to reduce resource pressures. Additionally, products are becoming more complex, which requires specific expertise to handle more innovative biologics and ATMPs. Being able to leverage expertise from other health authorities can help to address some of the skills and staffing gaps.

Most importantly, Access benefits patients by giving them earlier access to medicines that otherwise might take longer to get to the relatively smaller markets that make up the Access Consortium.

Disclaimer

The information provided in this article does not constitute legal advice. PharmaLex and its parent Cencora, Inc., strongly encourage readers to review available information related to the topics discussed herein and to rely on their own experience and expertise in making decisions related thereto.

References

1. Australia-Canada-Singapore-Switzerland-United Kingdom (Access) Consortium, TGA. https://www.tga.gov.au/international-activities/australia-canada-singapore-switzerland-united-kingdom-access-consortium
2. Access Consortium, Strategic Plan 2021–2024. https://www.tga.gov.au/sites/default/files/2022-09/access-consortium-strategic-plan-2021-2024.pdf
3. TGA Performance Report 2022–23. https://www.tga.gov.au/sites/default/files/2023-12/tga-performance-report-2022-23.pdf
4. Industry Perceptions and Experiences with the Access Consortium New Active Substance Work-Sharing Initiative (NASWSI): Survey Results and Recommendations, Therapeutic Innovation and Regulatory Science, March 2024. https://link.springer.com/article/10.1007/s43441-024-00624-7
5. Guidance Access Consortium, Gov.UK. https://www.gov.uk/guidance/access-consortium
6. Access Consortium: Operational procedures for New Active Substances Work-Sharing Initiative (NASWSI). https://www.tga.gov.au/sites/default/files/access-naswsi-operational-procedures.pdf
7. ACCESS – NAS work sharing initiative: Q&A, TGA. https://www.tga.gov.au/resources/resource/guidance/access-nas-work-sharing-initiative-qa
8. Evaluation Plan Estimators, TGA. https://www.tga.gov.au/resources/resource/guidance/evaluation-plan-estimators
9. TRS 1033 – Annex 10: Good reliance practices in the regulation of medical products: high level principles and considerations, World Health Organization. https://www.who.int/publications/m/item/annex-10-trs-1033
10. Authorisation procedures – The decentralised procedure, European Commission. https://health.ec.europa.eu/other-pages/basic-page/authorisation-procedures-decentralised-procedure_en
11. Access Consortium New Active Substance (NAS) work-sharing initiative, TGA. https://www.tga.gov.au/access-consortium-new-active-substance-nas-work-sharing-initiative
12. Licensing of medicinal and transplant products, Swissmedic. https://www.swissmedic.ch/swissmedic/en/home/humanarzneimittel/bewilligungen_zertifikate.html#:~:text=Companies%20that%20manufacture%20or%20distribute,successful%20inspection%20or%20other%20evaluation
13. Good Manufacturing Practice clearance guidance, U.S. Food and Drug Administration. https://www.tga.gov.au/resources/resource/guidance/gmp-clearance-guidance
14. New drug approvals in six major authorities 2013–2022: Focus on orphan designation and facilitated regulatory pathways. https://cirsci.org/wp-content/uploads/dlm_uploads/2023/07/CIRS-RD-Briefing-88-6-agencies-v.1.2.pdf

Piety Rocha is the Director, Head of Regulatory Affairs & Country VDC Head at PharmaLex, Australia. She has more than 20 years of experience in the Australian and New Zealand pharmaceutical industry. Piety is a seasoned regulatory affairs professional, with extensive knowledge and expertise covering innovative and generic prescription medicines across multiple therapeutic areas.