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Summary In light of the increasing global burden of new HIV infections, growing financial requirements, and shifting funding landscape, the global health community must accelerate the development and delivery of an HIV cure to complement existing prevention modalities. An effective curative intervention could prevent new infections, overcome the limitations of antiretroviral treatment, combat stigma and discrimination, and provide a sustainable financial solution for pandemic control. We propose steps to plan for an HIV cure now, including defining a target product profile and establishing the HIV Cure Africa Acceleration Partnership (HCAAP), a multidisciplinary public-private partnership that will catalyse and promote HIV cure research through diverse stakeholder engagement. HCAAP will convene stakeholders, including people living with HIV, at an early stage to accelerate the design, social acceptability, and rapid adoption of HIV-cure products.

In 2018, the Bill and Melinda Gates Foundation convened over thirty subject matter experts in clinical development, manufacturing, and regulatory assessment to determine how the development and approval of medical countermeasures could be accelerated in the event of Disease X. Disease X is the result of a presently unknown pathogen with epidemic or pandemic potential. A key opportunity to accelerate the scientific assessment and regulatory approval of medical countermeasures exists within efficient navigation of facilitated regulatory pathways. It was identified that not all stakeholders will be able to skillfully navigate the facilitated pathways offered by the various regulatory agencies during a public health emergency. To democratize this knowledge, we have written an overview of the facilitated approaches which have been developed and refined by Stringent Regulatory Authorities and the World Health Organization for the primary assessment of medical products. We discuss the conditions necessary for use of these approaches, scenarios in which certain pathways may be applicable, and the pros and cons of these approaches. We also address opportunities available to developers in, or developers who wish to access, low-income countries that may have nascent regulatory frameworks.

For low- and middle-income countries (LMICs) to benefit from real-world evidence (RWE)/real-world data (RWD) in both product registration ("regulatory") decision making and in product utilization policy ("policy") decision making, they need to overcome several challenges. They need to deploy more electronic health records systems (EHRs), adjust for confounder variables, build trust between stakeholders, and create laws and regulations for local generation of data that are assented for secondary use. The role of procurers and their use of RWE/RWD in the LMIC context likewise is in a state of ongoing development. Procurers of health products are strong players currently in the "access" chain as LMICs continue to work on strengthening governmental health technology assessment (HTA) bodies. Procurers' use of RWE is presently at an early stage and is mostly indirect, leveraging RWE results that are produced by researchers in high-income countries (HICs), often under considerably different regulatory and policy objectives and constraints compared to LMICs' epidemiology and priorities. Pending wider deployment of EHRs and other RWE sources, stakeholders must realize that populations from HIC RWE (i) can be devised to closely resemble phenotypic patterns in LMIC populations and (ii) can be analyzed to align with LMICs' unmet needs.

Hiiti Sillo and colleagues reveal how the East African Community's Medicines Regulatory Harmonization initiative improves access to important medicines in Africa.

Jane H. Mashingia and colleagues reveal the progress made to date for the East African Community Medicines Regulatory Harmonization initiative.

As large numbers of candidate drugs and vaccines for potential use in the coronavirus disease 2019 (COVID-19) pandemic are being investigated, medicine regulators globally must now make urgent, informed, contextually risk-1based decisions regarding clinical trials and marketing authorizations. They must do this with the flexibility demanded by the pandemic while maintaining their core risk assessment and public safety functions. We lay out the critical role of regulators in the current crisis and offer eight "pandemic best regulatory practices." These should support both the regulatory public heath imperative and assure timely patient access to effective, safe, quality products worldwide during this emergency-thus contributing to ending this pandemic as quickly, effectively, and safely as possible.

Requiring regional or in-country confirmatory clinical trials before approval of drugs already approved elsewhere delays access to medicines in low- and middle-income countries and raises drug costs. Here, we discuss the scientific and technological advances that may reduce the need for in-country or in-region clinical trials for drugs approved in other countries and limitations of these advances that could necessitate in-region clinical studies.

Therapeutic product development, licensing and reimbursement may seem a well‐oiled machine, but continuing high attrition rates, regulatory refusals, and patients’ access issues suggest otherwise; despite serious efforts, gaps persist between stakeholders’ stated evidence requirements and actual evidence supplied. Evidentiary deficiencies and/or human tendencies resulting in avoidable inefficiencies might be further reduced with fresh institutional cultures/mindsets, combined with a context‐adaptable practices framework that integrates emerging innovations. Here, Structured Evidence Planning, Production, and Evaluation (SEPPE) posits that evidence be treated as something produced, much like other manufactured goods, for which “built‐in quality” (i.e., “people” and “process”) approaches have been successfully implemented globally. Incorporating proactive, iterative feedback‐and‐adjust loops involving key decision‐makers at critical points could curtail avoidable evidence quality and decision hazards—pulling needed therapeutic products with high quality evidence of beneficial performance through to approvals. Critical for success, however, is dedicated, long‐term commitment to systemic transformation.

Enhanced collaboration among authorities is key to ensuring timely access to high quality health products worldwide

Medicines regulators, while performing a vital public health activity, are often perceived as both negative cost centers for governments and as impediments to innovation and economic development. The Mexican government recently undertook a regulatory optimization program focused on transforming the Mexican medicines regulatory pathway into one that is efficient, value-added, aligned with international norms, resource accountable, and one that protects and promotes public health, while also facilitating economic development.To facilitate the implementation of a new national access to medicines policy, the national government and the Mexican medicines regulatory agency instituted a multifaceted series of regulatory and legal reforms, which are described in this paper. These reforms encompassed multiple aspects of the regulatory oversight of medicines: administrative processes, clinical trials oversight, reliance on market authorization information and reports (ie, "work products") of other trusted regulators, and validation of activities by both Pan American Health Organization (PAHO) and WHO.These reforms have resulted in a marked positive impact on the availability of safe, effective, quality medicines at lower costs for Mexicans, both in the private and public sectors, while simultaneously facilitating expansion of the Mexican pharmaceutical industry.The regulatory optimization approach undertaken by Mexico could be a useful model for other countries that are trying to provide appropriate public health protection to their citizens, facilitate access to needed quality medicines, and encourage local economic development.

After nearly a decade of discussion, analysis, and development, the Medicines Adaptive Pathways to Patients (MAPPs) initiative is beginning to see acceptance from regulators, industry, patients, and payers, with the first live pilot project initiated under the guidance of the European Medicines Agency in 2014. Although it is a significant achievement to see the first asset being placed into human trials under an adaptive pathway, there is much to be learned regarding the multinational and multi-stakeholder effort that has driven the growing acceptance of MAPPs as a methodology and concept, as well as the need for continued and increasing international collaboration to foster the wider adoption of MAPPs. Changes in available science and technology, as well as a number of challenges in the current system, outlined in this paper, are transforming approaches to medicines development and approval. It is these challenges that have led directly to the groundbreaking MAPPs collaboration between the Massachusetts Institute of Technology Center for Biomedical Innovation’s New Drug Development Paradigms Initiative, the EMA, patient, payer and health technology assessment groups, the European Federation of Pharmaceutical Industries and Associations, and the Innovative Medicines Initiative—a European public-private partnership. This article examines the development of MAPPs, from inception of the concept, to the establishment of this trans-Atlantic initiative, and examines challenges for the future.

The concept of adaptive licensing (AL) has met with considerable interest. Yet some remain skeptical about its feasibility. Others argue that the focus and name of AL should be broadened. Against this background of ongoing debate, we examine the environmental changes that will likely make adaptive pathways the preferred approach in the future. The key drivers include: growing patient demand for timely access to promising therapies, emerging science leading to fragmentation of treatment populations, rising payer influence on product accessibility, and pressure on pharma/investors to ensure sustainability of drug development. We also discuss a number of environmental changes that will enable an adaptive paradigm. A life-span approach to bringing innovation to patients is expected to help address the perceived access vs. evidence trade-off, help de-risk drug development, and lead to better outcomes for patients.

Background Advances in pharmaceuticals offer improved health outcomes for a wide range of illnesses, yet medicines are often inaccessible for many patients worldwide. One potential barrier to making medicines available to all is the cost of product registration, the fees for regulatory review and licensing for the sale of medicines beyond the cost of clinical trials, if needed. Methods and findings We performed a cross-sectional analysis of pharmaceutical registration fees in low-, middle-, and high-income countries. We collected data on market authorization fees for new chemical entities and for generic drugs in 95 countries. We calculated measures of registration fee size relative to population, gross domestic product (GDP), and total health spending in each country. Each of the 95 countries had a fee for registering new chemical entities. On average, the ratio of registration fees to GDP was highest in Europe and North America and lowest in South and Central America. Across individual countries, the level of registration fees was positively correlated with GDP and total health spending, with relatively few outliers. Discussion We find that, generally speaking, the regulatory fees charged by medicines regulatory authorities are roughly proportional to the market size in their jurisdictions. The data therefore do not support the hypothesis that regulatory fees are a barrier to market entry in most countries.

The removal of 5 pharmaceuticals from the market in a 12-month period because of unexpected adverse events raised concerns about the adequacy of the drug review process at the US Food and Drug Administration (FDA). Specifically, concerns were raised about improvements in drug review efficiency that significantly reduced FDA review times. We have reviewed the circumstances of the 5 removals to determine whether there was any relationship to the increased efficiencies in the drug review process. When the removed drugs were analyzed by date of approval, no increase in the number of drugs taken off the market was seen, demonstrating that reduced review processing time was not the reason for the cluster of removals. We conclude that the agency's drug review procedures and postmarketing surveillance system after a drug has been marketed are currently adequate but must continually adjust to future challenges.

1. The FDA is in the process of developing good review practice (GRP) guidance for use within CDER and CBER in order to facilitate the review process and ensure consistency in approach and quality across divisions. 2. In particular, the goal of GRP track VIII is to produce a guidance document for the clinical/statistical reviewer, detailing all the steps in the review process. These fall within three elements, the internal (or reactive) review, the external (or creative) review, and the documentation and conclusion. 3. Each individual study review is composed of three separable but related tasks, the description, auditing and checking, and analysis and evaluation. The track VIII GRP will provide guidance on how to draw such information into an integrated analysis and conclusion regarding safety and efficacy. 4. Once finalised, the GRP documents will be a considerable aid to reviewers and will enhance the quality of the review process.

In a study reported herein, the marketing approval dates of 214 drugs newly introduced into the world market from January 1990 through December 1994 were compared in 4 countries. The analysis reveals that the United States and the United Kingdom have similar patterns of drug availability, although the United States has a number of therapies with significant public health benefits that are not yet available in the United Kingdom. The findings also show that the United States outpaces both Germany and Japan in approving important new drugs. Various strategies adopted by the Food and Drug Administration to expedite its pharmaceutical review process, including the use of industry user fees, are described.