Sometimes, the access gap is not a scientific or economic problem.

Nearly three decades ago, Dr. Peter Mugyenyi, a leading authority on the treatment of HIV/AIDS in Africa, posed a question that has lost none of its sting today: “Where are the drugs? The drugs are where the disease is not. And where is the disease? The disease is where the drugs are not.”1

No matter how effective, a medicine cannot reach patients until it is authorized by their country’s medicines regulator. Low- and middle-income countries (LMICs) often lack the staff, infrastructure, and expertise to independently evaluate new drugs effectively. As a result, there is typically a four- to seven-year delay, on average, between a medicine first being submitted for approval in a wealthy country and its final approval in sub-Saharan Africa.2

Take Zambia as an example.3

The Zambia Medicines Regulatory Authority has roughly 150 staff members. (For comparison, Australia’s regulatory agency, which serves only a slightly larger population, has around 1,000 staff.) Within the World Health Organization’s maturity framework, ZAMRA has yet to achieve level 3 (out of 4), indicating a stable, well-functioning approach to regulating medicines.4

Over 90% of the products ZAMRA reviews are generics.

So how did Zambia approve the HIV drug lenacapavir in 12 days?

The wonder drug

To understand why the race to approve lenacapavir matters, it helps to understand what came before it.5

Pre-exposure prophylaxis — PrEP — was first approved by the U.S. Food and Drug Administration in 2012 to prevent HIV infection. The standard regimen, a daily oral tablet called Truvada, works well. The problem is that it only works when people actually take it every day, and adherence at that frequency is hard to sustain, particularly in the communities PrEP is supposed to reach. One review estimated that fewer than 30% of people who started daily oral PrEP remained protected six months later, mainly due to discontinuation or inconsistent use.6

Stigma compounds the problem, since a daily pill is visible and implies something about a person’s risk profile to anyone who sees it.

Lenacapavir, developed by Gilead Sciences, is administered as a subcutaneous injection twice a year. Results from two phase 3 trials — PURPOSE 1 and PURPOSE 2, conducted across sub-Saharan Africa, Latin America, Southeast Asia, and the U.S. — showed that more than 99.9% of participants remained HIV-negative during the one-year follow-up period. A twice-yearly injection neatly sidesteps both the adherence problem and the stigma problem in one go. By June 2025, when the FDA approved the drug for HIV prevention,7Science magazine had already awarded lenacapavir its 2024 Breakthrough of the Year.

The question was how quickly it could reach the people who needed it most. Sub-Saharan Africa accounts for 65% of all people living with HIV globally, and 86% of children with AIDS. It also had the highest rates of discontinuation of oral PrEP. Whatever the merits of the drug, it would only matter if it could get through the regulatory machinery of individual countries fast enough to make a difference.

That was not guaranteed. When it comes to regulatory capacity, Zambia is not an outlier. Over 90% of African countries have limited or no capacity to independently evaluate new drugs.8

A submission to a regulator can sit in a queue for years. Gilead needed a different approach.

Trust me, I’m a reliable regulator

A full drug assessment involves many different kinds of work, including evaluating clinical trial data, reviewing manufacturing quality, assessing pharmacovigilance systems, and considering the benefit-risk balance for a specific population in a specific disease context. Some of that work is universal. Some of it is local.

The approach Gilead used — regulatory reliance — decomposes the task. The idea is that instead of requiring every national regulator to conduct a full independent review of a drug from scratch, regulators with fewer resources draw on evaluations already performed by trusted authorities elsewhere, then cover the remaining ground, such as the locally specific questions about their own populations, disease contexts, and health care systems.

A drug that has been assessed by the FDA, then the European Medicines Agency, then Health Canada, then Australia’s Therapeutic Goods Administration, and then 20 African regulators, has had the universal portions reviewed many times over by people doing essentially the same job. Reliance collapses that redundancy while preserving the locally specific judgments that only national regulators can make.

This might sound like rubber-stamping. However, even when a regulator draws on another agency’s assessment, it makes the final decision of whether to approve a product within its own jurisdiction, and takes complete responsibility for that decision.

When reliance works, it works well. It can cut review times by half.9The limiting factor, however, is trust. How do you trust the work of others when you know it’s going to be your head on the chopping block if something goes wrong?

Trust is earned through demonstrated track records and formal vetting. The WHO maintains a List of Authorities — essentially a Michelin Guide for regulatory agencies that identifies regulators operating at an advanced level of performance. The FDA, the EMA, Australia’s TGA, Health Canada, among others are on it. These are institutions whose assessments you can rely on without having to independently validate the quality of their processes.

While the FDA and EMA are world-class regulators, their mandate stops at their borders. When they approve a drug, they approve it for their populations. Their benefit-risk assessments do not account for the disease burden and health care contexts of people outside the United States or the European Union. That’s why there exist specific pathways designed to build off their expertise and incorporate the needs of low- and middle-income countries. These mechanisms not only enable reliance on existing assessments, but generate assessments shaped around the populations that matter most. The EMA’s EU-Medicines for All (EU-M4all) procedure is one such approach. The WHO Prequalification Programme is another option. Between them, they formed the backbone of lenacapavir’s route to Zambia.

The relay

Gilead’s regulatory strategy for lenacapavir was, in essence, a carefully designed relay. Each step leveraged the work of the previous one.

Step one: the FDA. A submission to the U.S. regulator is the starting point for most drugs. In December 2024, the FDA placed lenacapavir under priority review, accelerating the standard 10-month assessment timeline to six. However, the reliance chain that would eventually reach Zambia began not with the FDA in Washington, D.C., but in Amsterdam with the EMA.10

Step two: the EMA. After submitting lenacapavir to the FDA, Gilead then went to the European Medicines Agency in February 2025, both for the right to market it in the EU and for an assessment under the EU-M4all procedure, previously known as Article 58.

EU-M4all exists specifically to provide rigorous scientific evaluation for medicines intended for markets outside the EU. The same committee that reviews medicines for European patients reviews the drug with the populations of target countries in mind, including local disease burden and health care system constraints. It is the same standard of assessment, applied with a different frame of reference.

A medicine’s benefit-risk profile is not context-free. A drug’s particular side-effect profile might be a better trade-off against a backdrop of higher disease mortality, or present different risks in a population with different comorbidities. For example, sub-Saharan Africa has extremely high rates of TB-HIV coinfection. This is an issue far less salient to a European reviewer evaluating a drug for European patients, but central to any benefit-risk assessment for the region where lenacapavir is most needed.

The EU-M4all process also brings non-EU regulators into the room before any downstream decision is required of them. For lenacapavir, experts from the WHO, Uganda, Zambia, Kenya, Nigeria, Zimbabwe, South Africa, Thailand, and Vietnam all participated in the assessment. They signed confidentiality agreements that entitled them to see Gilead’s unredacted trial data, the same data the EMA committee members themselves were reviewing.

A positive EU-M4all opinion is a signal to every downstream regulator in the chain. It tells them that a rigorous, internationally credible body has looked at this data with their populations explicitly in mind, and found it favorable. It is also an asset. The EMA committee publishes a full assessment report of EU-M4all’s opinion (lenacapavir’s was a juicy 206 pages), which becomes a shared resource that any regulator can draw on, rather than proprietary knowledge locked inside the walls of any single institution.

The EMA recognized lenacapavir’s urgency and reviewed it in 120 days rather than the standard 210. In July 2025, it issued a positive opinion.

Step three: WHO prequalification. Next, Gilead submitted to the WHO Prequalification Programme in August 2025.

WHO prequalification is a gateway to procurement. Most international purchasing agencies, like UNICEF and the Global Fund to Fight AIDS, Tuberculosis and Malaria, typically require a product to be WHO-prequalified before they will buy it. Getting on the WHO list is therefore not just a regulatory milestone, but often a commercial prerequisite for reaching patients at scale in low- and middle-income countries. Without prequalification, the drug may be nationally approved but still practically unreachable because the organizations with the purchasing power to distribute it at scale won’t buy it.

There are two routes to WHO prequalification. The first is the full prequalification pathway, in which the WHO conducts an independent scientific review of the complete dossier from scratch. This is the path for products without any prior approval from a recognized agency. Products approved via this route are eligible for the full Collaborative Registration Procedure, through which the WHO shares its assessment and inspection reports with participating national regulators and allows them to ask questions of the WHO during their own review.

The second is the abridged prequalification pathway. This is a streamlined WHO assessment for products already approved by a recognized agency, resulting in full prequalification status and the same Collaborative Registration Procedure eligibility. Until recently, this pathway was only available to medicines approved for use within the recognized agency’s region. This changed in March 2025, when new WHO guidance expanded the abridged pathway to include products only approved for use outside the recognized agency’s region (i.e., export-only), meaning those that had received a positive opinion via EU-M4all could now be included.11

Lenacapavir was the first product to use the expanded abridged prequalification pathway.

The abridged review does not reevaluate the clinical data. Its focus is confirming that the product submitted for WHO prequalification is identical in all material respects to the product assessed by the recognized agency. Is it the same formulation? The same specifications? The same packaging? To help answer these questions, the manufacturer submits the reference regulator’s assessment report (the European public assessment report in lenacapavir’s case) alongside product samples, quality documentation, batch records, and a letter from the agency authorizing the WHO to share its unredacted assessment and inspection reports with national regulators via the Collaborative Registration Procedure.

The fact that the WHO participated directly in the EU-M4all process helped considerably. By the time Gilead knocked on the WHO’s door with the prequalification dossier, the WHO’s assessors were not encountering lenacapavir for the first time.

Under the new procedure, the WHO can still request additional data specific to the safe use of the product in relevant regions beyond what the EU-M4all assessment covered. In the case of lenacapavir, the WHO asked Gilead for stability data demonstrating the product maintains its quality throughout its stated shelf life under Zones III, IVa, and IVb conditions: the high-heat, high-humidity storage conditions typical of much of sub-Saharan Africa and Southeast Asia, which fall outside the climatic zones the EMA routinely requires data for.12

This all resulted in the WHO prequalifying lenacapavir on October 6, 2025. It only took it 36 days — roughly one-fifth of the FDA’s and a quarter of the EMA’s priority review.

The 12 days

At this point, it probably will not come as a surprise that Zambia’s regulatory agency did not review over 100,000 pages of technical data from scratch in 12 days.

The reliance architecture described above made it possible to sidestep that constraint without abandoning regulatory rigor. Zambia’s own experts had already participated in the EU-M4all process. They likely had already formed views on lenacapavir’s benefit-risk profile for the Zambian population. The EU-M4all process had, in effect, done a substantial portion of ZAMRA’s analytical work for them, months in advance.

When the WHO prequalification package arrived, it included not just the WHO’s own abridged assessment report but the unredacted EMA assessment and inspection reports. ZAMRA received everything it needed to make an informed decision without having to generate any of it itself.

So what exactly did ZAMRA do during those 12 days?

It verified. Gilead would have provided a declaration of “sameness” (that the product submitted for national approval was the same as what the WHO had prequalified) and a cover letter justifying any difference, which ZAMRA reviewed against the reference dossier. This is a repeat of the verification process that happened earlier in the chain. Each link requires its own check because the product could, in theory, differ between submissions.

ZAMRA’s own submission requirements also mandate that applicants submit physical product samples alongside a certificate of analysis, so a sample of lenacapavir would have arrived on ZAMRA’s desk.13

Furthermore, Gilead’s application needed to fulfill local requirements, which would include at a minimum local labeling review and any country-specific administrative or postmarket surveillance obligations. These tasks were answerable by a small team with access to the right documents in less than two weeks, precisely because the foundational work had already been done elsewhere.

On November 4, 2025, after 12 working days, ZAMRA approved lenacapavir for HIV prevention. ZAMRA’s approval time for new drugs via verification is usually over a year, but in this case it took one-third of the time the WHO itself took to prequalify it.

Regulatory reliance is working when each step in the chain takes less time than the previous one. In the case of lenacapavir, the gap between first submission and approval in Zambia was under 11 months.

The accumulation of trust

There is a managerial instinct, when faced with a decision that will be yours to own, to redo the underlying work yourself. The instinct is understandable, particularly when you are a regulator in a poor country, acutely aware of the consequences of substandard drugs. But the instinct, followed rigidly, is also what produces the access gap. Every redundant full review is a tax on patients who are waiting.

In regulatory reliance, the question moves from “Did we independently evaluate this drug thoroughly?” to “Do we trust the institution whose evaluation we are leveraging, and have we verified that what we are approving is the same thing it approved?”

The first question is unanswerable for national regulators that lack the resources to conduct their own thorough evaluation. The second is tractable when good reliance practices are followed, and the reliance machinery that supported Zambia’s approval of lenacapavir has been decades in the making.

The WHO has been the biggest driver of reliance mechanisms to support access to medicines in developing countries. The first such tool was implemented in 1969, when the WHO launched its Certification Scheme for pharmaceutical products, which allowed exporting countries to voluntarily issue certificates attesting to a product’s quality and manufacturing standards.14

This gave countries with limited regulatory capacity assurance about the quality standards of the medicines entering their markets.15

In 1987, the WHO created the Prequalification Programme, initially to help UNICEF with its vaccine procurement, before expanding to medicines in 2001. The EU-M4all procedure followed in 2004.

While the results of these programs have been meaningful, they are also uneven, and quantitative data on the adoption of regulatory reliance in sub-Saharan Africa and LMICs more broadly is extremely limited, partly because regulatory agencies in LMICs often lack the capacity to maintain data transparency around their approval processes.

The WHO has prequalified around 1,500 health products, and its Collaborative Registration Procedures, established in 2015, had facilitated 59 approvals across 23 countries by mid-2021, with 69 countries participating as of early 2026.16

However, the products eligible for prequalification are limited, likely due to limited capacity: The department overseeing prequalification had the same number of staff (approximately 115) in 2022 as it did in 2019, despite a substantially heavier workload.

EU-M4all has been slower to take hold. By 2020, only 10 positive opinions were issued. A 2015 EMA review of the procedure found that manufacturers doubted the pathway actually accelerated downstream approvals, maintenance fees were burdensome, and many national regulators either weren’t aware of it or treated it as a second-tier assessment. Coordination between the EMA and the WHO was also deemed suboptimal.17

Adoption has also faced structural obstacles on the part of the relying agencies. For example, certain countries still lack the domestic legal basis to formally practice reliance in the first place: You cannot build a review process around another agency’s work if your own legislation does not permit it. The African Union’s Model Law on Medical Products Regulation is one ongoing effort to give member states a legal template for doing so.

A subtler constraint is that effective reliance requires a sufficient degree of regulatory competence in the relying agency — verification is not an unskilled task. It is also worth noting that after approval, agencies must independently conduct postmarket surveillance, monitor local adverse events, and oversee national labeling and product information requirements. This points to a broader criticism: Reliance alone will not help agencies develop the capacity and local expertise needed in the long term, leaving them dependent on external assessments and ill-equipped to respond to domestic regulatory challenges. This is why the current WHO guidance on good reliance practices makes clear that reliance and sustained investment in local capacity must go hand in hand.

As this history attests, lenacapavir’s success was far from guaranteed. Lenacapavir benefited from an unusual convergence of factors. It had exceptional clinical trial results that made regulatory hesitation difficult to justify. It had a manufacturer with the resources and experience to navigate reliance pathways effectively. It had a preexisting access infrastructure built up over decades of HIV/AIDS advocacy. Not every drug will enjoy these benefits. The four- to seven-year average will not immediately become 11 months across the board.

But it is worth being clear about what the lenacapavir case demonstrates. It shows that the access gap is not primarily a scientific problem or an economic problem. The science was done. The manufacturing capacity exists. The gap, when it closes this fast, closes because of unglamorous institutional design. Because someone decided that WHO representatives should be in the EU-M4all room, because someone decided that unredacted assessment reports should flow from the EMA to national regulators via a formal procedure, because someone revised a guidance document in March 2025 to enable a pathway that hadn’t existed before.

None of this is visible from the outside. None of it makes headlines. All of it is what makes 12 days possible.18

At a time when the global medical establishment doubted that Africans would comply with antiretroviral regimens, Dr. Mugyenyi was an early and vocal dissenter — a position history has since validated.

The FDA had approved lenacapavir in December 2022 as a treatment option for people living with multidrug-resistant HIV, before it was discovered to also be effective as a prevention tool.

Whereas the FDA’s approval didn’t initiate the regulatory reliance relay that ultimately enabled Zambia’s approval, it was a prerequisite for procurement under the President’s Emergency Plan for AIDS Relief, which requires drugs to be FDA-approved or tentatively approved to be eligible for purchase under the program. In September 2025, Gilead announced a partnership with PEPFAR to procure and distribute lenacapavir to up to 2 million people in low- and middle-income countries.

Before then, products approved by trustworthy regulators specifically for use outside their home region could only achieve “alternative listing” status, which enables a product to be recognized by the WHO quickly, but does not constitute full prequalification.

Climatic Zone IVb (mean temperature 30 degrees Celsius, relative humidity 75%) covers much of sub-Saharan Africa, South and Southeast Asia, and parts of Latin America. Drug stability testing under the EU guidelines typically covers Zone II (temperate climates).

Whether ZAMRA independently tested that sample in its laboratory or relied on Gilead’s certificate of analysis and the quality assessment already conducted by the WHO cannot be established from publicly available sources because ZAMRA does not publish summary assessment reports.

A year prior, the WHO had adopted the first draft text on Good Manufacturing Practices, which was then built into the certification scheme.

The certificate attests to certain facts about the product, like whether the product is authorized for sale in the exporting country and whether the manufacturing facility meets Good Manufacturing Practice standards and includes a copy of the approved product information (e.g., labeling).

Following the review of EU-M4all, in 2021 it became possible for manufacturers to undertake parallel submission for EU marketing authorization as well as a positive opinion under EU-M4all, increasing its appeal. Gilead chose this parallel option for lenacapavir.

I’m very glad to say Zambia’s story isn’t unique. In October 2025, the South African Health Products Regulatory Authority became the first African national regulator to approve lenacapavir for preventing HIV. In November, Zimbabwe approved it in 18 working days. December brought approvals in Botswana, Rwanda, Tanzania, Malawi, and others. By January 2026, Kenya, Uganda, Namibia, and Mozambique had followed.