he COVID-19 pandemic is a constantly evolving and debilitating outbreak and, in many ways, has been materially different from previous infectious disease outbreak experiences such as Zika and Ebola. The strain on healthcare systems (infrastructure, healthcare professionals, availability of supplies, etc.) is only the tip of the iceberg. The pandemic has led to a massive global financial and economic crisis, threatening the availability and affordability of health products and impacting health services. As the entire globe demands urgent solutions, regulatory interventions are vitally important for consolidating regulatory resources and efforts to facilitate access to safe, effective, and timely health products.

Key Takeaways

• With most pandemic solutions being driven by developed countries, efforts must focus on access to and availability of health products in Lower and Middle Income Countries (LMICs).
• Regulators play a key role in facilitating safe, effective and timely solutions and must adapt to pandemic needs for making risk-based decisions.
• Regulatory collaborations at both global and regional levels are promoting discussions and work-sharing to accelerate approval of COVID- 19-related health products.
• Regulators must work as an integral part of wider public health systems moving forward.

Focus on Low and Middle Income Countries (LMICs)

There has been tremendous progress in research to understand this pathogen and its interactions with humans and the environment. Approvals of diagnostic kits, which have uncovered a wealth of information on the virus and the disease epidemiology, have played a key role in helping healthcare workers and governments make informed decisions. In particular, the US and EU have issued a high volume of emergency authorizations for diagnostics and therapeutics trials.

Regulators must employ emergency authorities to make risk-based decisions. This involves minimizing data redundancy and review timelines without compromising scientific standards or safety. Science-driven decisions based on adequate, reliable, and transparent data are the need of the hour. Various entities, including ICMRA (International Coalition of Medicines Regulatory Authorities), AVAREF (African Vaccines Regulatory Forum) and WHO (World Health Organization), are focusing on clinical development and bringing together regulators to share resources and experiences and establish meaningful decision-making strategies.

Much of the effort invested in the development of health products is driven by developed countries with little focus on the needs in LMICs. There is lingering uncertainty regarding the availability of these products and meeting public health needs in these countries. It is important to understand if LMICs are able to use regulatory reliance practices which follow therapeutic registrations in developed countries and if there are any significant variations in the characteristics and quality of the products supplied to LMICs compared to those available in developed countries. To that end, good reliance practices using one regulator’s assessment can enable another regulator to make informed decisions that account for regional and population-specific considerations, including the type and capability of the local healthcare system.

Emerging Regulatory Policies and Collaborations

Guido Rasi (European Medicines Agency, EMA) explained the Agency’s special provisions and participation in special regulatory forums to accelerate development of COVID-19 products. EMA has initiated rolling reviews to fast-track assessments for promising COVID-19 treatments and can shorten review timelines, when robust clinical evidence is presented, from 210 to 150 days under exceptional circumstances. Furthermore, EMA is actively involved with the International Coalition of Medicines Regulatory Authorities (ICMRA) which convenes fortnightly meetings to discuss best practices and decision-making policies adopted by different regulators. These dialogues and sharing sessions help identify and address important regulatory issues across authorities. Since the outbreak, ICMRA has organized two seminars open to all regulators, with WHO as an observer, focused on potential treatments and vaccine development as well as data requirements for approvals and the feasibility of using surrogate endpoints.

Singapore was one of the region’s first countries to report SARS-CoV-2 cases. Mimi Choong (Health Sciences Authority [HSA], Singapore) described strategies employed locally to carve out its regulatory path for emergency authorization of therapeutics and diagnostics. With limited clinical data, a risk-based regulatory approach ensured safety, efficacy and quality to facilitate timely access to diagnostics and trials during the pandemic. HSA had so far approved 33 diagnostic kits based on molecular diagnostics, immunoassay, rapid serology and other assay principles. HSA has also played a significant role in ensuring adequate supply of essential products like surgical masks, PPEs, and hand sanitizers to countries such as the Philippines, approved from HSA’s emergency authorization for their local market. HSA is also actively engaged in the ACSS consortium of four regulatory authorities (Australia, Canada, Switzerland, and Singapore), a work-sharing platform that allows health product developers to simultaneously file a joint application to all four regulators and receive a consolidated set of queries, enhancing productivity and potentially minimizing time to approval.

Australia’s efforts have resulted in commendable progress in combating COVID-19 with low mortality and hospitalization rates. John Skerrit (Health Products Regulation, Department of Health, Australia) elaborated on the significance of priority pathways and nimble regulations in speeding up review and approval of diagnostic applications. Industry-regulator dialogues have been integral to regulatory innovation, especially in pandemic circumstances where broadening the scope of emergency authorization has been imperative. For example, SARS-CoV-2 diagnostic kits have received approvals in as little as 48 hours, although post-market validation steps are critical. The conditions of use of these diagnostic kits are further refined based on the performance of the kit. This ensures an uninterrupted supply of diagnostics suiting different purposes. Considerable efforts have been invested in expediting access to hand sanitizers, disinfectants, and over-the-counter medicines. Australia has also extended cooperation in regional regulatory activities with Southeast Asian countries such as Indonesia and Papua New Guinea for malaria, and these efforts continue to tackle COVID-19 in the region.

Evolving Regulatory Landscape

Work-sharing is an essential component of regulatory collaboration; hence, mutual trust among regulators must be fostered to minimize the time and resources allocated to making the same decisions. For example, confidentiality agreements within the ICMRA framework have encouraged regulators to share more information. In LMICs, pragmatism has driven work-sharing in the form of joint assessments (AVAREF) and reliance on approvals granted in developed countries. However, data must be analyzed carefully to extrapolate its utility to specific populations. Country-specific legal frameworks and cultural barriers must be overcome to facilitate interactions among regulators and eventual lead to comfort in work-sharing and confidentiality agreements.

Providing equitable access to an effective vaccine candidate to protect the entire global population is an impractical task for a single manufacturer or regulator. There is great need for collaboration beyond and across regulation. Broader and deeper cooperation among regulators and other stakeholders is essential for conquering the COVID-19 pandemic. Regulators must work as an integral component of the public health system.