Evaluation of the review models and approval timelines of authorities participating in the East African Medicine Regulatory Harmonisation initiative: alignment and strategies for moving forward.

Introduction: Medicines regulatory harmonisation has been embraced by many national regulatory authorities (NRAs) to improve public health through faster availability of safe, high-quality, and effective medical products to patients and enhanced standardisation of technical guidelines and work sharing, leading to reduced cost to pharmaceutical companies. After ten years of implementing regulatory harmonisation by the East African Community Medicines Registration Harmonization (EAC-MRH) initiative, it is now imperative for participating NRAs to rely on each other to minimise duplication of use of limited resources. Major challenges in implementing reliance are the lack of clear registration processes and delays in the approval. The aim of this study was to compare review models, target timelines and data requirements used in assessing applications by EAC-MRH NRAs so as to align and propose strategies for improvement. Methods: A validated questionnaire that standardises and captures review processes was completed by the head of the medicine's registration division in each of the seven EAC-MRH NRAs. A country report based on the completed questionnaire was developed for each NRA and validated by the heads of the respective authorities. Results: Most applications received by all countries were for generics except Kenya, which received a significant number of new active substance applications (55 and 53 in 2020 and 2021). Mean approval times for generics using full review varied, with Tanzania's time declining for the three years. Target timelines for full review for the five countries ranged between 180 calendar days (Tanzania) to the highest 330 days (Zanzibar). The three countries (Kenya, Rwanda and Uganda) utilising the verification review model had a target timeline of 90 days. All six authorities conducted abridged reviews and fast-track assessments through a priority review track. The common technical document format was mandatory for applications in all authorities. The target timeline for key milestones in the review process varied for each country with a few similarities. Discussion: The study has provided a baseline for review models, target timelines and data requirements utilised in assessing applications for registration by EAC-MRH NRAs. Implementing the recommendations from this study will enable the NRAs to align and improve their registration processes.

Evaluation of good review practices in member authorities of the East African Medicines Regulatory Harmonisation initiative: strategies for alignment with African medicines agency.

Introduction: The East African Community Medicines Regulatory Harmonisation (EAC-MRH) programme was established to address challenges faced by national regulatory authorities (NRAs) of the region. Work sharing through joint assessments and inspections was adopted to manage limited resources and capacity; however, NRA good review practices (GrevP) are also a key determinant to success. This study evaluated GReVP among the EAC-MRH NRAs and mapped required strategies for countries to align themselves with the African Medicines Agency (AMA). Methods: A validated questionnaire (Optimising Efficiency in Regulatory Agency-OpERA) that standardises and captures review processes was completed by the head of the medicines registration division in each NRA. A country report based on the completed questionnaire was developed for each NRA and validated by the heads of the respective authorities. Results: The population and size of the NRAs vary and four of the countries have semi-autonomous authorities and three NRAs are autonomous. The Burundi and South Sudan authorities were fully government funded, Kenya and Uganda entirely from fees, while Rwanda, Tanzania and Zanzibar were partially funded from different sources. All authorities except South Sudan, which does not receive or review applications had backlogs. Authority fees varied based on the different application categories. Key milestones for standardised regulatory processes are implemented in all authorities. Queue times range from a few weeks to about one year. Three NRAs use internal technical agency staff for scientific assessments and three use both internal and external experts. Clock stop time varies and target timelines for review committee range from one day to three months. All the NRAs implement some best practices on quality measures, transparency and communication. Some have activities for transparency improvement but with minimal attention to training and education. Most employ some quality decision-making practices. Discussion: GrevP in EAC-MRH NRAs still needs to be improved and it is imperative that these authorities streamline and harmonise their practices. Increasing human resources and an investment in training and education of staff will enable the implementation of all measures for GRevP. This is vital, as the effectiveness and efficiency of the AMA will depend on the strength of these NRAs.

Pre-evaluation assessment of serological-based COVID-19 point-of-care lateral flow assays in Kenya.

BACKGROUND: Timely testing is a key determinant of management outcomes of coronavirus disease 2019 (COVID-19). Real-time reverse transcription polymerase chain reaction tests are currently the mainstay for COVID-19 testing. However, serological point-of-care tests (PoCTs) can be useful in identifying asymptomatic and recovered cases, as well as herd immunity. OBJECTIVE: The aim of this study was to assess COVID-19 PoCTs in Kenya to support the emergency use authorisation of these tests. METHODS: Between March 2020 and May 2020, 18 firms, of which 13 were from China, submitted their PoCTs to the national regulatory authority, the Pharmacy and Poison Board, who in turn forwarded them to the Kenya Medical Research Institute for pre-evaluation assessment. The tests were run with real-time reverse transcription polymerase chain reaction COVID-19-positive samples. Pre-COVID-19 plasma samples that were collected in June 2019 were used as negative samples. The shelf lives of the PoCTs ranged from 6 to 24 months. RESULTS: Only nine (50%) tests had sensitivities ≥ 40% (range: 40% - 60%) and the ability of these tests to detect IgM ranged from 0% to 50%. Many (7/18; 38.9%) of the kits had very weak IgM and IgG band intensities (range: 2-3). CONCLUSION: Serological-based PoCTs available in Kenya can only detect COVID-19 in up to 60% of the infected population.

Safety and Tolerability of Mass Diethylcarbamazine and Albendazole Administration for the Elimination of Lymphatic Filariasis in Kenya: An Active Surveillance Study.

Preventive chemotherapy with diethylcarbamazine citrate (DEC) and albendazole (ALB) is the core intervention strategy to eliminate lymphatic filariasis (LF). We conducted a large-scale prospective active safety surveillance study to identify the incidence, type, severity, and risk factors for adverse events (AEs) following mass drug administration (MDA) of single-dose DEC and ALB in 10,010 participants from Kilifi County, Kenya. AEs were actively monitored and graded at 24 h, 48 h, and on day 7 Post-MDA. Out of 10,010 enrolled study participants, 1621 participants reported a total of 3102 AEs during a seven-day follow-up. The cumulative incidence of AEs was 16.2% (95% CI, 15.5-16.9%). The proportion of participants who experienced one, two, or ≥three types of AEs was 9.2%, 4.6%, 2.4%, respectively. AEs were mild (87.3%), moderate (12.4%), and severe (0.3%) and resolved within 72 h. The five most common AEs were dizziness (5.9%), headache (5.6%), loss of appetite (3.3%), fever (2.9%), and drowsiness (2.6%). Older age, taking concurrent medications, ≥three tablets of DEC, and type of meal taken before MDA were significant predictors of AEs. One in six participants experienced systemic mild-to-moderate severity grading and transient AEs. DEC and ALB co-administration for the elimination of LF is generally safe and well-tolerated.

Legal and institutional foundations for universal health coverage, Kenya.

Kenya's Constitution of 2010 triggered a cascade of reforms across all sectors to align with new constitutional standards, including devolution and a comprehensive bill of rights. The constitution acts as a platform to advance health rights and to restructure policy, legal, institutional and regulatory frameworks towards reversing chronic gaps and improving health outcomes. These constitutionally mandated health reforms are complex. All parts of the health system are transforming concurrently, with several new laws enacted and public health bodies established. Implementing such complex change was hampered by inadequate tools and approaches. To gain a picture of the extent of the health reforms over the first 10 years of the constitution, we developed an adapted health-system framework, guided by World Health Organization concepts and definitions. We applied the framework to document the health laws and public bodies already enacted and currently in progress, and compared the extent of transformation before and after the 2010 Constitution. Our analysis revealed multiple structures (laws and implementing public bodies) formed across the health system, with many new stewardship structures aligned to devolution, but with fragmentation within the regulation sub-function. By deconstructing normative health-system functions, the framework enabled an all-inclusive mapping of various health-system attributes (functions, laws and implementing bodies). We believe our framework is a useful tool for countries who wish to develop and implement a conducive legal foundation for universal health coverage. Constitutional reform is a mobilizing force for large leaps in health institutional change, boosting two aspects of feasibility for change: stakeholder acceptance and authority to proceed.

Adoptée en 2010, la Constitution du Kenya a entraîné une série de réformes dans tous les secteurs afin de les adapter aux nouvelles normes constitutionnelles, notamment à la décentralisation et à une charte détaillée des droits. La Constitution sert de tremplin pour faire progresser les droits en matière de santé et restructurer les cadres politiques, juridiques, institutionnels et réglementaires en vue de réduire les disparités chroniques et d'améliorer les résultats cliniques. Toutefois, ces réformes de santé prévues dans la Constitution sont complexes. Toutes les composantes du système de santé évoluent en même temps, de nombreuses lois inédites sont promulguées et des organismes de santé publique sont créés. L'emploi d'approches et d'outils inadaptés a entravé la mise en œuvre de ces changements si complexes. Pour mieux appréhender l'étendue des réformes de santé entreprises au cours des 10 premières années de la Constitution, nous avons développé un cadre sanitaire sur mesure, inspiré des concepts et définitions de l'Organisation mondiale de la Santé. Nous avons appliqué ce cadre afin de récolter des données sur les organismes publics et les lois relatives à la santé qui ont d'ores et déjà été édictées ou sont en cours d'élaboration, et avons comparé l'ampleur des transformations avant et après la Constitution de 2010. Notre analyse a révélé de multiples structures (lois et organes publics de mise en œuvre) réparties dans l'ensemble du système de santé, avec plusieurs nouvelles structures de gestion conformes à la décentralisation mais une fragmentation au niveau de la sous-fonction de régulation. En décomposant les fonctions normatives du système de santé, le cadre a permis d'établir une cartographie globale des différentes caractéristiques de ce système (fonctions, lois et organes de mise en œuvre). Nous sommes convaincus que notre cadre représente un outil utile pour les pays qui souhaitent développer et instaurer des bases juridiques propices à la création d'une couverture maladie universelle. La réforme constitutionnelle possède un pouvoir de mobilisation capable de faire progresser le changement institutionnel dans le domaine de la santé. Et ce, en renforçant deux aspects qui favorisent sa réalisation: l'acceptation de la part des intervenants, et l'autorité nécessaire pour agir.

La Constitución de Kenia de 2010 generó una serie de reformas en todos los sectores para ajustarse a los nuevos estándares constitucionales, incluida la transmisión y una amplia carta de derechos. La constitución representa una plataforma para promover los derechos sobre la salud y reestructurar los marcos jurídicos, institucionales y normativos con el fin de revertir las deficiencias crónicas y mejorar los resultados de la salud. Estas reformas de la salud, establecidas por mandato constitucional, son complejas. Asimismo, todas las áreas del sistema de salud se están transformando de manera simultánea, ya que se han promulgado varias leyes nuevas y se han establecido organismos de salud pública. Sin embargo, la falta de herramientas y métodos adecuados limitó la implementación de estos cambios tan complejos. Se elaboró un marco adaptado del sistema sanitario, que se guía por los conceptos y las definiciones de la Organización Mundial de la Salud, para tener una idea del alcance de las reformas sanitarias en los primeros 10 años de la constitución. En este contexto, se aplicó el marco para documentar las leyes sanitarias y los organismos públicos ya promulgados y en curso, en el que se comparó el grado de transformación antes y después de la Constitución de 2010. El análisis realizado reveló que se habían formado múltiples estructuras (leyes y organismos públicos de ejecución) en todo el sistema sanitario, que tenían muchas estructuras de gestión nuevas alineadas con la transmisión, pero que estaban fragmentadas dentro de la subfunción de reglamentación. Al desestructurar las funciones normativas del sistema sanitario, el marco permitió realizar un mapeo completo de los diversos atributos del sistema sanitario (funciones, leyes y organismos de ejecución). Se considera que el marco que se propone aquí es un instrumento útil para los países que quieren elaborar e implementar un fundamento jurídico propicio para la cobertura sanitaria universal. La reforma constitucional es una fuerza de movilización que permite obtener importantes avances en el cambio institucional del sector sanitario, lo que fomenta dos aspectos de la viabilidad del cambio: la aceptación de las partes interesadas y la autoridad para proceder.

Eight years of the East African Community Medicines Regulatory Harmonization initiative: Implementation, progress, and lessons learned.

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

Optimizing the East African Community's Medicines Regulatory Harmonization initiative in 2020-2022: A Roadmap for the Future.

Margareth Ndomondo-Sigonda outlines future challenges for the East African Medicines Regulatory Harmonization initiative.

Coming together to improve access to medicines: The genesis of the East African Community's Medicines Regulatory Harmonization initiative.

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