Special Section: Clinical Research in Ukraine
GCP in the Context of Global Regulatory Reliance and the Situation in Ukraine
Samvel Azatyan
World Health Organization

t is clear that good health is not possible without access to medical products, which are in this context considered to be instruments for public health, and that clinical trials are an integral and essential part of the overall product development process.

Registering clinical trials and submitting them for review by the appropriate regulatory and ethical oversight bodies ensures that their healthcare strategies are informed by scientific evidence. Article 35 of the Declaration of Helsinki states that every clinical trial must be registered in a publicly accessible database before recruiting the first subject. This registry allows scientists in different countries to know if they are duplicating research already being conducted elsewhere.

The WHO estimates that more than two billion people across the world have either no access or very limited access to essential medicines. Reasons for this situation include insufficient or inadequate regulatory capacity in member states and national regulatory authorities, or (sometimes) a lack of collaboration and work sharing between countries in medical product regulation.

Military conflicts not only cause direct loss of life on the battlefield but have other severe consequences. We have seen such consequences, from the breakdown of health services to the severe decrease of access to medical products, in Ukraine.

WHO, as a health agency of the United Nations, is very concerned with this situation and is promoting activities directed to facilitate good-quality regulatory decisions based on the concept of regulatory reliance. We first promote good governance and transparency in medical products regulation through good regulatory practices. But we also promote and facilitate building strong national regulatory systems as part of an overall health system strengthening agenda. We strongly believe that no health system in any country could be efficient and strong if it does not include a strong regulatory system. This is accomplished through the WHO global benchmarking process.

We believe that strong regulatory systems will be an important contributor to achieving overall universal health coverage and to help address public health priorities. But we also understand that regulation of medical products is something that requires strong human resources capacity. To address this issue, we are promoting development of a global competency framework and global regulatory curriculum. Work-sharing, reliance, and trust will help regulatory authorities make their national decisions much faster and with much better quality.

WHO’s formal document to describe good reliance practices was finalized in 2020, published in 2021, has been adopted by the WHO expert committee on specification for pharmaceutical preparations, and is now available for countries to implement. This document not only provides the definition of reliance but also highlights the importance of international collaboration to ensure the safety, quality, and efficacy of locally used medical products in these countries.

We commonly discuss resource constraints in WHO Member States, and this document highlights how to best use available resources and expertise to avoid duplication of efforts and concentrate regulatory resources where they are needed most. This is critically important in the context of public health emergencies, including during military conflicts. The concept of reliance is applicable to the whole product lifecycle, starting from research and development, and is applicable to all regulatory functions as the WHO global benchmarking tool describes.

For example, during the pandemic, Ukraine received COVID-19 vaccines from UNICEF through the COVAX initiative, which purchased and supplied only those COVID-19 vaccines that met WHO safety and efficacy criteria. Similarly, under the state of martial law in April 2022, the State Service of Ukraine on Medicines and Drugs Control allowed the introduction of medical devices, treatment kits, in vitro diagnostics, and active implantable medical devices, by recognizing conformity assessments carried out by foreign accredited conformity assessment bodies.

However, we must remain aware that one size doesn’t fit all. Reliance strategies should be tailored to the needs of the national health and regulatory systems in a specific country for them to be implemented. The misconception that reliance is only needed for low-resource regulatory authorities is not correct. Reliance is equally relevant for well-resourced national regulatory authorities and, we believe, should become an integral part of regulatory cooperation even in normal situations, but especially in public health emergencies, including during military conflicts.

In the area of clinical trials specifically, reliance has been instrumental in many different regions. Two good examples are the voluntary harmonization procedure in the European Union and the regulation of clinical trials in Africa through the African Vaccine Regulatory Forum (AVAREF). Experience in many different regions demonstrates that when national regulatory authorities and ethics committees are jointly assessing applications for clinical trials authorization, different participants can benefit from assessments already done by different participating countries. This will help them to facilitate and ensure robustness of the whole process of the assessment of clinical trial applications across different countries. Reliance is key to effective access and oversight of different types of medical products in case of public health emergencies, which we’ve been witnessing in the last several years during COVID-19 and can now also see in the war in Ukraine.

WHO is trying to address these issues by optimizing research and development processes for accelerated access to health products. This strategy highlights the importance of access to appropriate products to achieve WHO’s general mission, but also the importance of promotion of research and development of innovative products regardless of the situation and facilitating introduction of these products to ensure that the global community can address unmet health needs in any situation. WHO has developed an optimized process which allows for our activities in some important areas to become linked and coherent with consequent increased impact on health outcomes. These are areas of research prioritization because we must understand where to concentrate our resources first. This process also involves creating specific advice for development of these products and creating WHO guidance for local development and implementation of these products. Our prequalification program helps to assess products of local health priority.

The definition of human research in the WHO Handbook for Good Clinical Research Practice Guidance for Implementation relates to research in which various environmental factors have been manipulated in a way that would incidentally expose research participants to undue risk. The situation of military conflict is exactly what this definition considers.

The ultimate goal of all these processes is to ensure that health products are developed to address global health needs, and to accelerate in each country implementation of these strategies. The war in Ukraine reminds us all about the importance of adhering to the principles of ethical clinical trial conduct and strong assessment of benefit-risk.