WHO Facilitated Regulatory Pathways

Every country's National Regulatory Agency (NRA) has the responsibility to oversee the safety, efficacy, and quality of the medical products available to its citizens. Since there are more than 190 NRAs in the world, each going through a version of the same process - and in many cases reviewing the exact same products - there is a lot of duplication built into the system, which can lead to lengthy delays in clinical trials authorization and product approval, and to the proliferation of substandard and falsified medicines.

One promising way to address these challenges is to establish "facilitated regulatory pathways." These pathways are based on the principle of "reliance," whereby NRAs leverage the scientific assessment documents and inspection reports created by other trusted agencies to inform their own decision-making rather than repeating the assessments and inspections.

Facilitated pathways for medicines date to the height of the HIV/AIDS epidemic in the 1990s, and for vaccines to the meningitis crisis in the 1980s, when the WHO developed the medicines Prequalification (PQ) program to make it easier for people in low- and middle-income countries to receive lifesaving drugs. Under the PQ program, the WHO acts in the de facto role of a medical products regulator (primarily for products which have not gone through a reference NRA), determining whether the product meets international standards for safety, efficacy, and manufacturing quality. If it does, WHO PQ will "list" the product, giving the manufacturer the ability to apply to large procurement tenders from UNICEF, UNITAID, the Global Fund, and other global procurers.

The PQ designation expedites the process of getting lifesaving, quality-assured medicines to people, but it is not a formal regulatory authorization in the country where the product will be used, because only the local NRA has that authority.

To build on this work, and with support from the Gates Foundation, the WHO developed the Collaborative Registration Process (CRP) in 2012. If a manufacturer wishes to market its prequalified product in a country where the NRA is a participant in the CRP, the country's NRA can use the WHO's assessment and inspection reports in its own regulatory decision-making. As part of the CRP, NRAs commit to deciding on marketing authorization applications in 90 days after receiving the WHO reports. While they retain authority over the final decision, they do not duplicate expensive, time-consuming assessment work. In recent years, the number of countries engaged in the CRP has increased from 15 to 71, including most of sub-Saharan Africa.

Variations of reliance-based facilitated pathways have increasingly become best regulatory practice around the world.

• The PQ program is primarily focused on assessing the bioequivalence of generic versions of innovator medicines, not novel and innovative products. It also focuses on high-priority vaccines for LMICs. When that kind of analysis is required, the WHO relies on reviews done by trusted regulatory agencies, such as the European Medicines Agency (EMA) through its Medicines for All procedure. NRAs that participate in the CRP can rely on WHO's reliance on the EMA, SwissMedic, or other trusted regulatory authorities.
• The WHO has certified some NRAs as WHO Listed Authorities (WLA), which means they have the capacity, capabilities, and track record to be reference agencies upon which other NRAs and WHO can rely.