Transforming Clinical Trials: The Surging Role of Regulatory Reliance

Regulatory reliance in regulatory frameworks refers to the practice where regulatory authorities use assessments conducted by other agencies to inform their decision-making processes. This approach is designed to optimize resources and expedite patient access to innovative medicines by leveraging the work already performed by trusted regulatory bodies. At the DIA Europe 2024 conference, a session chaired by Susanne Ausborn, PhD, Global Head of International Regulatory Policy at Roche, and Martin Harvey Allchurch, LLM, Head of International Affairs at the European Medicines Agency (EMA), focused on the practical implementation of regulatory reliance.

The Role and Implementation of Reliance in Regulatory Frameworks

The session, chaired by Susanne Ausborn, PhD, Global Head of International Regulatory Policy at Roche, and Martin Harvey Allchurch, LLM, Head of International Affairs at the European Medicines Agency (EMA), focused on the fundamental role of reliance in regulatory frameworks. Ausborn emphasized the importance of regulatory reliance—where regulatory authorities use assessments from other agencies—in optimizing resources and speeding up patient access to innovative medicines. She highlighted that reliance is based on trust and transparency and trust. The session aimed to move beyond the theoretical benefits of reliance to discuss practical implementation steps, fostering a deeper understanding among global regulatory bodies.

Martin Harvey Allchurch introduced “informed reliance” as a dynamic process involving active engagement and trust between regulatory authorities. He shared examples from EMA initiatives, such as collaborations with Africa and Latin America, which significantly reduced drug approval times and improved access to medicines. The session also discussed various reliance models, including collaborative reviews and work-sharing arrangements, with Ausborn citing the European Union’s mutual recognition procedure as an effective example. Both chairs stressed the need for continuous improvement, with Ausborn mentioning EMA’s efforts to refine regulatory reliance processes based on feedback and metrics, ensuring these pathways remain efficient and effective.

Insights on Regulatory Reliance Models and Metrics

Magda Bujar, PhD, MSc, Senior Manager at the Centre for Innovation in Regulatory Science (CIRS), provided an in-depth overview of reliance models and metrics, emphasizing that reliance is not a new concept and has been utilized by various regulatory agencies for decades. She presented data from a comprehensive CIRS survey involving 29 regulatory agencies, revealing insightful trends and preferences in adopting reliance practices. The survey indicated that standalone reviews are generally not considered the ideal approach, with agencies favoring global collaboration. However, despite this preference, many agencies perceive the practical implementation of international collaboration as challenging due to differences in regulatory standards and resource constraints. Bujar highlighted several reliance models currently in use, including parallel collaborative reviews, where agencies simultaneously assess the same dossier, and work-sharing arrangements, where different assessment parts are divided among participating agencies.

Bujar provided concrete examples of successful implementations of reliance, such as the European Union’s mutual recognition procedure. This procedure allows for recognizing regulatory assessments conducted by other EU member states, thereby streamlining the approval process and reducing duplication of efforts. Additionally, Bujar discussed the importance of applying a risk-based approach to reliance, where the level of reliance is adjusted based on the product’s risk profile and the regulatory authority’s capacity. She stressed the need for continuous measurement and improvement of reliance processes through robust metrics, advocating for data collection on timelines, resource utilization, and the quality of decision-making. This approach ensures that reliance pathways are effective and beneficial for all stakeholders involved, ultimately contributing to the timely availability of medicines globally.

The Role of Reliance in Expediting COVID-19 Vaccine Approval

Jayanthi Boobalan, MBA, MPharm, RPh, Head of the Regional Regulatory Hub at Pfizer, shared an impactful case study highlighting the significant benefits of reliance during the COVID-19 pandemic. The study, which focused on the regulatory review process for the COVID-19 vaccine BNT162b2 (commonly known as the Pfizer-BioNTech vaccine), was published in Frontiers and provided a detailed analysis of how reliance strategies were employed to expedite vaccine approval across 73 countries. Boobalan’s retrospective, observational study compared traditional regulatory timelines with those implemented during the pandemic, providing concrete evidence of the efficiencies gained through reliance. She reported that 85% of the surveyed countries utilized reliance approaches during the review process, leading to a notable reduction in review timelines by approximately 11%, with pandemic-era reviews shortened to one week to three months compared to the standard 210 to 660 days.

The study identified three primary areas where regulatory flexibilities were most beneficial: Chemistry, Manufacturing, and Controls (CMC), labeling requirements, and clinical data review processes. For instance, 100% of the countries implemented flexibilities in CMC requirements, such as adjustments to stability studies and country-specific mandates, while 96% offered labeling flexibility, and there was a substantial reduction in the review burden for clinical data. Boobalan concluded by urging regulatory authorities to consider integrating some of these pandemic-era flexibilities into routine practice. She argued that the lessons learned during the pandemic provide a valuable framework for optimizing regulatory processes beyond crises. By maintaining these streamlined practices, regulatory agencies can continue improving the approval process’s efficiency for new medicines and vaccines, ensuring quicker access for patients globally.

Harmonizing and Streamlining Reliance Pathways

Isabelle Colmagne-Poulard, PharmD, MBA, MSc, Head of International Global Regulatory & Scientific Policy at Merck, presented findings from an EMA Focus Group on Reliance survey. This survey explored the use of the EMA as a reference agency and highlighted the diverse documentation required for reliance applications. The survey showed that the EMA is used as a reference agency in 71% of cases. However, companies often face variability in document requirements, needing up to 13 different documents, such as the Certificate of Pharmaceutical Product (CPP), approval letters, detailed assessment reports, Good Manufacturing Practice (GMP) certificates, and inspection reports.

Colmagne-Poulard advocated harmonizing and streamlining regulatory reliance pathways to enhance efficiency and sustainability. She proposed prioritizing key documents like the GMP certificate, approval letter, and European Public Assessment Report (EPAR), readily available on public platforms such as the EMA and EudraGMDP websites. She suggested that the CPP could be an alternative to more detailed documents in many cases. She referenced an EMA pilot project demonstrating the effectiveness of using a standardized set of key documents, significantly reducing the time and resources needed for reliance applications without compromising review thoroughness. This approach aims to create a more efficient regulatory environment, facilitating faster global access to new and innovative medicines.

Panel Discussion: Global Perspectives on Regulatory Reliance

The panel discussion at the DIA Europe 2024 conference featured representatives from regulatory agencies worldwide, each sharing their experiences and insights on implementing regulatory reliance. This global perspective highlighted the diverse approaches and challenges different regions face in adopting reliance pathways.

• Egyptian Drug Agency (EDA) reported significant reductions in regulatory timelines and increased industry satisfaction through their reliance practices. By relying on assessments conducted by other regulatory authorities, the EDA has expedited the approval process for new drugs, ensuring quicker patient access. The agency highlighted that its industry partners appreciated the streamlined processes, which allowed for more efficient resource allocation and faster market entry.
• ANVISA (Brazil) shared the successful outcomes of its unilateral reliance pilot project, which demonstrated remarkable efficiency gains. This project, which has been running for two years, involved over 400 submissions and reduced approval timelines by a factor of five. ANVISA’s experience emphasized the importance of clear guidelines and robust communication with the industry to address initial challenges, such as understanding product sameness and dealing with redacted reports. The pilot’s success paved the way for a permanent reliance framework.
• Saudi Food and Drug Authority (SFDA) emphasized the importance of flexibility in its reliance approach and expressed its ambition to transition from unilateral reliance to becoming a reference agency. The SFDA has applied a bridged verification pathway since 2016, initially facing documentation and industry engagement challenges. However, through continuous dialogue and adaptation, the SFDA has refined its processes, ensuring that it can meet the needs of both local and multinational companies.
• Jordan Food and Drug Administration (JFDA) highlighted the necessity of submitting complete and standardized dossiers for practical reliance. The JFDA stressed that for reliance to be successful, the regulatory dossiers submitted by companies must be identical to those reviewed by the reference agencies. This includes ensuring that the formulation, manufacturing sites, and all relevant data are consistent. The JFDA is considering allowing electronic submission of the CPP to streamline the process further and reduce administrative burdens.
• HALMED (Croatia) discussed its smooth transition to reliance practices as part of its EU accession process. By aligning its national legislation with EU regulations well before its accession, HALMED could implement reliance seamlessly. This alignment included adopting simplified procedures for authorizing medicinal products already approved in the EU, thereby leveraging the comprehensive assessments other EU member states conducted.
• Medicines and Medical Devices Agency of Serbia noted their progress in digitalizing regulatory processes to facilitate reliance. The agency is harmonizing its application forms with EU standards, simplifying the submission process for companies and enhancing the efficiency of reliance pathways. The digitalization initiative is expected to reduce administrative burdens and improve the overall transparency and effectiveness of the regulatory process.
• African Union Development Agency-NEPAD outlined their efforts to harmonize standards and build national systems to support reliance across Africa. The agency has been working on harmonizing regulatory standards through regional economic communities and joint assessments. These efforts aim to create a more cohesive regulatory environment across the continent, enabling smaller and less resourced agencies to rely on the evaluations conducted by more established authorities. NEPAD emphasized that building trust, capacity, and robust national systems are critical to successfully implementing regulatory reliance in Africa.

The diverse experiences shared by the panelists highlighted the universal benefits of reliance, such as reduced timelines and enhanced regulatory efficiency, while emphasizing the need for ongoing dialogue, capacity building, and adaptability to local contexts.

Summary

The panel discussion at the DIA Europe 2024 conference illustrated the universal advantages of reliance, such as reduced regulatory timelines and enhanced efficiency, through diverse global perspectives. Representatives from various regulatory agencies shared their experiences, highlighting successful regulatory reliance implementations and the associated challenges. From Egypt’s expedited drug approval processes to Brazil’s efficient reliance pilot projects, the discussion showcased the importance of clear guidelines, robust communication, and continuous adaptation. Additionally, the session highlighted the need for harmonization of documentation requirements, as advocated by Isabelle Colmagne-Poulard, and the potential benefits of integrating pandemic-era flexibilities into routine practice, as presented by Jayanthi Boobalan. Ultimately, the insights shared reinforced that reliance is a critical tool for improving global health outcomes by facilitating faster access to safe and effective medicines.