The Access Consortium is a medium-sized coalition of regulatory authorities that work together to promote greater collaboration and alignment of regulatory requirements. This union began in 2007 with the involvement of Australia, Canada, Singapore, and Switzerland, and was later in 2021 bolstered by the addition of the United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA). The formation of ACCESS has created a harmonised regulatory framework aimed at reducing duplication and increasing each agency’s capacity to ensure patients timely access to high quality, safe and effective medicines.
Together, the consortium’s reach extends to a combined population of approximately 170 million people. Access Consortium members share information under a network of bilateral confidentiality agreements and Memoranda of Understanding to conduct their work. Information is shared through a secure collaborative document storage and management platform that is only accessible by authorised ACCESS members. Each regulatory authority retains final sovereign decisions while striving for harmonisation.This paper provides a glimpse into the collaborative endeavor that is the Access Consortium, working diligently to reshape the landscape of global healthcare access. It also provides specific recommendations for use of the ACCESS pathway where appropriate when defining the development strategy of a given medicine. It is written independent of actual experiences but based on Health Authority, vendor, and pharmaceutical input.
Regulatory Rapporteur
November 2023 | Volume 20 | No.10
Introduction
The Access Consortium mission is to facilitate collaboration and work-sharing on medicines and to reduce duplication to ensure their populations have fast access to the health products they need for better health and well-being. Guided by a shared global challenge, the consortium has gained insights into the value of harmonised efforts.[1]
One of the key challenges encountered is the cultural shift required among assessors to fully embrace the concept of collaborative work-sharing.
Consolidated question-and-answer (Q&A) sessions benefit the industry, as only one Q&A process is conducted, simplifying the information exchange. Industry also benefit from the transparent, flexible, and structured timelines set out in the pathway. For example, they can answer regulators’ issues within thirty or sixty days.
Access Consortium
Mission and vision of Access Consortium
The consortium has pioneered innovative methods to unite regulators who share a common vision, ensuring that their collective efforts yield strategic outcomes. These comprehensive processes facilitate the seamless submission, review, and approval of new medicines, ensuring a harmonious and efficient regulatory pathway.
Strategic plan 2021 to 2024
The year 2021 marked a significant milestone for the Consortium with the publication of their inaugural strategic plan which outlines key objectives to reinforce its commitment to enhance access to essential health products and promote regulatory efficiency.[1]
- The first strategic goal focuses on strengthening ACCESS work-sharing initiatives, solidifying Access as a competitive and streamlined submission pathway of choice for industry.
- The second goal revolves around the expansion of a life cycle approach, maximising continuous collaboration.
- The third goal involves increasing regulatory capacity while collaborating closely with key national health care systems partners to facilitate uptake of innovative treatments by those who need them.
The consortium journey: key milestones (2007 to 2023)
In 2007, ACCESS was established through a collaborative effort between four medium-sized regulatory agencies from Australia, Canada, Singapore, and Switzerland, aligning their goals and expertise for a common cause.[2]
From 2008 to 2015, regulatory harmonisation and work sharing emerged as key priorities.
Between 2016 and 2017, the Practical Collaboration (PC) initiative was piloted, conducting work sharing trials within the ACCESS New Chemical Entities and Generics Medicines groups from 2016 to 2018.
Access Consortium effectively applied the lessons learned from the COVID-19 pandemic, adopting best practices, and exchanging crucial information to address the evolving needs of populations worldwide. Through collaborative efforts, the consortium harnessed these learnings to ensure a responsive and effective regulatory approach in safeguarding public health.[2]
In 2021, the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) officially joined ACCESS, expanding the estimated total population served from 78 million to 150 million.[3]
In October 2021, the first ACCESS industry joint pipeline meeting was held with the following year (2022) seeing the ACCESS Clinical Trials Working Group being established to facilitate the sharing of clinical trial information amongst ACCESS members, expertise, and workload for clinical trials to facilitate consistent approaches.
In November 2022, an ACCESS statement on Good Manufacturing Practice (GMP) inspections reliance and recognition evidence Statement solidifies the Consortium’s commitment to demonstrate greater inspection reliance and accept GMP inspection outcomes. The Access Consortium is also a Participating Authorities of the Pharmaceutical Inspection Co-operation Scheme (PIC/S).[4]
As of 2023, there has been approval of 24 new active substances and eight generic medicines.[5],[6].Additionally, ACCESS published five guidance statements, including the recent ACCESS Statement on Generic Medicines Pre-Approval Inspection Reliance, further underscoring its commitment to regulatory innovation and collaboration.
Other milestones
The consortium’s commitment to regulatory excellence is evident in its ACCESS Statement on GMP Inspection Reliance, a testament to its emphasis on trust and cooperation. A pivotal step was taken in 2022 with the establishment of a sub-working group focused on New Active Substance Risk Management Plans, emphasising the consortium’s proactive approach to safety.
The pivotal role of the Access Consortium in addressing global health challenges was unmistakably seen during the COVID-19 pandemic, with its involvement in assessing vaccines and therapeutic products. The Pharmacovigilance (PV) Working Group highlights the consortium’s dedication to patient safety, underscoring the holistic nature of its mission.[7]
Consortium successes and future ambitions
Several key success factors contribute to the effectiveness of the ACCESS initiative:
- Speeding up filings to ACCESS regulators: Swift submission of regulatory filings to ACCESS regulators accelerates the evaluation and approval process.
- Reduction in approval timelines: By implementing streamlined review processes, optimised for efficiency and clarity, member countries can facilitate quicker approvals.
- GMP inspection reliance: A significant hallmark of the ACCESS initiative is the commitment to mutual reliance on good manufacturing practice (GMP) inspections, which was the first guidance document issued in November 2022.[4] As a result, if a manufacturing facility has been inspected and approved by one ACCESS country, fellow member countries will refrain from re-inspecting the same manufacturing plants.
- Reduced regulatory burden on industry stakeholders: When member countries mutually recognise each other’s approvals and inspections, it eliminates redundant administrative tasks and costs for companies.
The uniqueness of the Access Consortium lies in its concerted efforts to overcome regulatory divergence and delays, facilitating a fast-track procedure akin to priority reviews, tailored to the specific procedures of member countries.
Access Consortium has pioneered three distinct authorisation procedures: the New Active Substance, the Biosimilar and the Generic Medicine Initiative.
Access Consortium recognises the significance of life-cycle management for approved products. Also worth mentioning, the International Coalition of Medicines Regulatory Authorities (ICMRA) supports the principle of reliance and promotes its application in the regulatory landscape.[8] Momentum is being gained in the PAC (Post-Approval Changes) Pilot program, with various companies participating and submitting post-approval changes for evaluation. However, the speed at which changes are being reviewed and assessed remains an aspect that needs ongoing assessment and improvement.
Discussion and recommendations
ACCESS lessons learned from the pandemic and ACCESS key challenges
Work-sharing, while a cornerstone of ACCESS, presents its own set of challenges. The goal of achieving faster and broader access to the same high-quality medicines necessitates seamless collaboration between member countries. The challenge also stretches across to navigating the co-ordination of the national Health Technology Assessment (HTA) following an ACCESS approval. The administrative burden of collaboration with independent authorities and alignment on questions and decisions is also experienced by ICRMA.
Leveraging the Health Canada collaboration environment, ACCESS is “at the forefront of piloting artificial intelligence (AI) and other cutting-edge technologies. These initiatives hold the potential to revolutionise regulatory practices, making them more efficient, accurate, and adaptive.”[9] A prime example is the literature search application piloted during the PV Pilot. This innovative tool not only streamlines processes but also strengthens the quality of regulatory decisions.
Access has introduced language models, enabling AI systems to comprehend and process complex textual information. In the realm of drug safety, AIs within ACCESS capabilities shine in the recognition of safety signals and active substances.[9]
Regulators (NAWSI; GMWSI) and industry experience of access
NASWI – the New Active Substances Working Share Initiative
The ACCESS New Active Substance (NAS) Working Group are responsible for new medicines registrations (small molecules & biologics) and new clinical indications. The ACCESS NAS is a regulatory information/work-sharing process with a standard 12-month targeted review timeline with an option for an accelerated review under a priority designation where criteria is met for the participating authorities. With regulatory innovation increasing in its complexity, there is a greater need for global regulatory agility and sharing of scientific resources and expertise. ACCESS regulatory authorities are able to co-ordinate regulatory reviews and thereby support timely patient access to high quality, safe and effective medicines.[10]
The New Active Substances Working Share Initiative (NASWSI) has successfully completed 25 new active substance work-sharing applications, and eleven applications currently under way, reflecting a robust commitment to collaborative regulatory efforts. This initiative reached a significant milestone in 2022 with the introduction of the first two five-way work-sharing applications, marking a significant stride towards enhanced cooperation among regulatory bodies.
GMWSI – the Generic Medicines Work Sharing Initiative
The Generic Medicines Work Sharing Initiative (GMWSI) has established a solid foundation for collaborative efforts among regulators. As of now, ACCESS has successfully completed eight generics work sharing applications, and has two applications currently under review.
GMWSI revisions were guided by insights gained from practical implementation, enhancing internal processes and the effective utilisation of foreign assessment reports.[11]
Promise Pathway
A recent initiative is the introduction of the ‘Promise Pathway,’ which emphasises teamwork among ACCESS member countries to ensure a seamless and streamlined regulatory process that benefits all stakeholders. Promise Pathway is the consortium’s priority work sharing procedure. Currently, sponsors can take part in the PROMISE pilot when requesting priority review for their dossier in the Expression of Interest
The Promise Pathway has specific eligibility criteria for new substances seeking accelerated review. Firstly, a company must express its interest in undergoing this priority work-sharing procedure. Furthermore, eligibility for the PROMISE Pilot requires thorough assessment which involves a comprehensive evaluation of the potential benefits and risks associated with the substance (see Figure 1).
Rigorous evaluation of the NAS application’s clinical data and quality assurance measures are essential to ascertain its eligibility for the Promise Pathway.
It can take 60 days for the sponsor to understand whether its request to use the Promise Pathway will be approved so that its dossier can be submitted for review (see Figure 2).
Recommendations
While as usual, sponsors would need to identify as early as possible the most appropriate strategy to have their products be registered in more than one jurisdiction, we believe the following recommendations should be considered by the Access Consortium:
- Apply lessons learned including pandemic lessons learned.
- Measure key performance indicators including measures for patient access to medicines.
- Articulating the benefits of work-sharing trust and reliance. Leveraging other experiences such as MHRA work-sharing with peers pre-Brexit for mutual recognition procedures and decentralised procedures.
- Investigate improvements for transparency, predictability, and consistency of NASWI with Access objectives.
- Share experience of the PROMISE pilot, of the pilot use of AI tools for PV, and of new tools and methods (e.g., digital tools, RWD/RWE) used in dossiers submitted for review to the Access Consortium.
- New frontiers need to be explored. For example, the coordination of post-marketing pharmacovigilance and use in paediatrics.
Conclusion
Access Consortium has achieved notable successes, particularly in the domains of new active substances, generic medicines, and of some lifecycle procedures (current lifecycle is limited to line extensions, GMP reliance and PV for COVID-19 therapies, and safety but not CMC variations as yet). With its focus on addressing delays, embracing real-world experiences, the Consortium aims to facilitate post-approval adjustments highlights its dedication to promoting swift, safe, and effective access to innovative medicines. Work-sharing in the Consortium enhances convergence, increases reliance, and reduces duplication. The joint review / partnership avoids unnecessary duplication of work. Data packages can be generated once and used for different purposes.
The Consortium is dedicated to continually enhance their technological expertise, embrace a state-of-the-art approach to assess the risk and benefits of new medicines. With a steadfast focus on collaboration, innovation, and the well-being of our populations, the Consortium strives to shape a healthier and more accessible future for all.
Noteworthy positive response from the member of ACCESS include:
- The synergy between Australia and its ACCESS counterparts is evident in their commitment to optimising collaborative practices.
- Swissmedic representatives noted the division of access to reviews provided faster access to safe and effective and high-quality medicines for all their populations using organisation, process, guidance and technology.
There has been at least one decision by a sponsor to not use the ACCESS Consortium due to the nature of the therapy being reviewed, in that the consortium had not yet assessed a radioligand therapy (RLT,) so it was decided to work through just the MHRA in the hopes of a faster review time.[12] The ACCESS Strategic Plan 2021-2024 aims to further develop the pathway as a competitive and efficient submission pathway of choice for industry, supported by regulators. Proposals include an increase in product scope and further expansion of its use throughout the product’s lifecycle e.g., Pharmacovigilance and GMP inspection. Guidance to streamline the submission process is being looked at to enhance predictability and efficiency for both industry and agencies alike as well as overall strengthening the pathway.[1]
References
[1] UK MHRA (2023) Access Consortium Strategic Plan 2021-2024.(Accessed: 19 Sep 2023).
[2] Australia Therapeutic Goods Administration (2021) Points to consider for strain changes in authorised COVID-19 vaccines in an ongoing SARS-COV-2 Pandemic. (Accessed: 19 Sep 2023).
[3] Australia Therapeutic Goods Administration (2023) Australia-Canada-Singapore-Switzerland-United Kingdom (Access) Consortium.(Accessed: 19 Sep 2023).
[4] UK MHRA (2022) Notice - Access Consortium Good Manufacturing Practice (GMP) Statement.(Accessed: 19 Sep 2023).
[5] Schofield, F. (07 Sep 2022) Faricimab & Asciminib Are First Products To Be Approved By All Access Consortium Regulators. The Pink Sheet. [online] (Accessed: 19 Sep 2023).
[6] Swissmedic (2022) Access Consortium work-sharing authorisations.(Accessed: 19 Sep 2023).
[7] Singapore HSA (2021) Access Consortium statement on COVID-19 medicines.(Accessed: 19 Sep 2023).
[8] EMA (2023) Partners & Networks - International Coalition of Medicines Regulatory Authorities (ICMRA).(Accessed: 19 Sep 2023).
[9] Raine, June; Choong, Mimi May Ling; Schlapfer, Jorg; Aung-Thin, Pamela. ACCESS Consortium: What’s Next? DIA 2023 Global Annual Meeting Regulatory Collaboration Forum. 29 Jun 2023.
[10] Singapore HSA (2023) Access Consortium.(Accessed: 19 Sep 2023).
[11] UK MHRA (2022) Guidance Access Generic Medicines Work Sharing Initiative. (Accessed: 19 Sep 2023).
[12] Bruce, F. (08 Sep 2022) Why Novartis Rejected Access Consortium In Favor Of Direct UK Radioligand Filing. The Pink Sheet. [online] (Accessed: 19 Sep 2023).
