Concurrent Submission of In Vitro Devices and Drug Applications in Multiple Countries
In 2019, the WHO outlined the principles and considerations for reliance on the work of other regulators in the regulation of medical products. This practice aims to leverage existing regulatory work to improve the efficiency, effectiveness, and quality of national regulatory authorities (NRAs).
Reliance on other regulators' work is supported by the World Health Organization (WHO) as a means to optimize resource use and expertise. It allows NRAs to focus on activities that add significant value locally, such as vigilance, market surveillance, and oversight of manufacturing and distribution.
Principles and Considerations
The WHO details the principles of good reliance practices (GRelP), which include:
Universality: Applicable to all NRAs, regardless of resources or maturity.
Sovereignty: NRAs retain final decision-making authority.
Transparency: Clear, open processes and criteria for reliance.
Legal Basis: Reliance must align with national and regional legal frameworks.
Consistency: Reliance practices should be predictable and consistently applied.
Competence: Both the relying and referenced NRAs must maintain high competence levels.
Key Concepts
Reliance vs. Recognition: Reliance involves using another regulator's work to inform decisions, while recognition involves accepting another's regulatory decisions directly.
Risk-Based Approach: Tailoring reliance strategies based on product risk, local needs, and regulatory capacity.
Regional Reliance Mechanisms: Encouraging collaboration and mutual reliance within regions.
Implementation
Strategic Integration: Embedding reliance practices into national regulatory strategies and policies.
Cultural Change: Promoting understanding and acceptance of reliance practices among stakeholders.
Investment: Initial resource investment is required to establish effective reliance mechanisms.
Sameness of Product: Ensuring the product is identical to that assessed by the reference regulator.
Enablers and Barriers
Trust: Building trust between NRAs through transparency and shared standards.
Convergence and Harmonization: Aligning standards and guidelines to facilitate reliance.
Information Sharing: Effective communication and data sharing among regulators.
Stakeholder Engagement: Involving industry, healthcare professionals, and the public to build support for reliance practices.
Project Orbis
Project Orbis, led by the FDA, aims to expedite the approval of oncology drugs through simultaneous submissions and collaborative reviews among multiple international regulators. The principles and practices outlined in the WHO's GRelP document align closely with the goals of Project Orbis.
Project Orbis is an initiative led by the U.S. Food and Drug Administration (FDA) aimed at accelerating the approval process for oncology drugs among multiple countries. The project facilitates collaborative review of promising cancer treatments, allowing for simultaneous submission and review of oncology products among international regulatory agencies.
Key Features and Benefits of Project Orbis:
Collaborative Review Process:
Multiple Agencies: Project Orbis involves collaboration among several international regulatory agencies, including the FDA, the European Medicines Agency (EMA), Health Canada, the Australian Therapeutic Goods Administration (TGA), and others.
Simultaneous Submissions: Pharmaceutical companies can submit their drug applications concurrently to participating countries, which enables regulatory agencies to conduct reviews in parallel rather than sequentially.
Accelerated Approvals:
Reduced Approval Times: By aligning review processes, Project Orbis can significantly reduce the time it takes for a cancer drug to receive approval across multiple countries. This is particularly important for providing patients with faster access to new and potentially life-saving treatments.
Shared Insights: Agencies share insights and findings during the review process, which can lead to more efficient and comprehensive assessments of the drug’s safety and efficacy.
Harmonization of Standards:
Consistency: The collaborative approach helps harmonize regulatory standards and requirements across participating countries, making it easier for companies to meet the necessary criteria for drug approval.
Global Impact: With more streamlined and consistent regulatory processes, patients worldwide can benefit from quicker access to innovative cancer therapies.
Examples of Project Orbis in Action:
Dostarlimab Approval: In August 2020, dostarlimab, a treatment for endometrial cancer, was approved under Project Orbis in the United States, Australia, and Canada. This marked a significant step in providing patients with access to new treatments more quickly across these countries.
Ripretinib Approval: In May 2020, ripretinib, a drug for gastrointestinal stromal tumors (GIST), received simultaneous approvals in the United States, Canada, and Australia through Project Orbis.
In 2023, there were 20 approvals under Project Orbis, 13/20 were approved in both the US and other countries. 8 of these were biomarker driven studies and therefore would require a companion diagnostic.
In 2024 so far, there have been 4 approvals under Project Orbis in the US, all of which are still under review in other countries.
Participating Agencies:
FDA (United States)
Health Canada (Canada)
Therapeutic Goods Administration (Australia)
Swissmedic (Switzerland)
Medicines and Healthcare products Regulatory Agency (MHRA, United Kingdom)
Pharmaceuticals and Medical Devices Agency (PMDA, Japan)
Project Orbis exemplifies international cooperation in drug regulation, aiming to expedite the availability of oncology treatments. By reducing approval times and harmonizing regulatory standards, it helps ensure that cancer patients around the world can access new and effective therapies more quickly.
UK statement to extend this reliance on other regulators to IVDs
In May 2024, the MRHA released a draft policy outlining how the UK will recognize international regulators' approvals for medical devices, aiming to streamline the approval process in Great Britain.
This move aims to leverage the work of international regulators to expedite approvals and improve access to high-quality medical devices. Currently, the UK recognizes CE certifications from the EU, with this arrangement lasting until June 30, 2030.
Intended Approach
The Medicines and Healthcare products Regulatory Agency (MHRA) will recognize medical device approvals from regulatory authorities in Australia, Canada, the EU, and the USA. To qualify, devices must comply with specific criteria, including relevant legislation in these countries, English labeling, and adherence to UK-specific requirements. This policy aims to reduce redundant assessments and focus resources on innovative products, benefiting patient health.
Proposed Access Routes
The draft policy details various access routes for different device classifications, including self-registration, reliance on EU approvals, and specific requirements for approvals from Australia and the USA. Certain devices, such as custom-made devices and some Software as a Medical Device (SaMD), are excluded from this framework.
By recognizing approvals from established regulatory bodies, the UK aims to reduce approval times and improve patient access to new medical technologies.
Project Orbis has shown that collaborative international reviews can lead to more efficient regulatory processes for oncology drugs. The UK's draft policy for medical devices follows this model, leveraging international expertise to streamline and expedite the approval process.
Benefits
Faster Access: Patients gain quicker access to quality-assured medical devices.
Reduced Duplication: Minimizes redundant regulatory assessments, allowing focus on innovation.
Global Standards: Aligns UK regulations with international standards, promoting consistency and safety.
By adopting a framework akin to Project Orbis, the UK may be able to review both drug applications and their companion diagnostics much more rapidly and efficiently.
