Following an initial regulatory process, NAFDAC says R21 is safe for use in Nigerian children from one year to three years, pending Phase 4 clinical trials.
By Prof Mojisola Christianah Adeyeye, DG NAFDAC
The Nigerian Agency for Drugs and Food Administration, NAFDAC, on Monday, April 17, announced the provisional approval of R21 Malaria vaccine for use in Nigeria. Below are the details:
Background – Disease Burden of Malaria in Africa
Malaria is one of the most important public health concerns in the world. According to the latest WHO World Malaria Report, there were 247 million cases of malaria in 2021 compared to 245 million cases in 2020. The estimated number of malaria deaths stood at 619 000 in 2021 compared to 625 000 in 2020.
Over the two peak years of the pandemic (2020–2021), COVID-related disruptions led to about 13 million more malaria cases and 63 000 more malaria deaths. The WHO African Region continues to carry a disproportionately high share of the global malaria burden. In 2021 the Region was home to about 95% of all malaria cases and 96% of deaths. Children under 5 years of age accounted for about 80% of all malaria deaths in the Region. Four African countries accounted for just over half of all malaria deaths worldwide: Nigeria (31.3%), the Democratic Republic of the Congo (12.6%), United Republic of Tanzania (4.1%) and Niger (3.9%)
Disease Burden in Nigeria:
Malaria is transmitted throughout Nigeria, with 97% of the population at risk of malaria. The duration of the transmission season ranges from year-round transmission in the south to three months or less in the north.
According to the 2021 World Malaria Report, Nigeria had the highest number of global malaria cases (27 % of global malaria cases) and the highest number of deaths (32 % of global malaria deaths) in 2020.The country accounted for an estimated 55.2% of malaria cases in West Africa in 2020.
Case numbers increased 5.3% between 2017 and 2020, from 298 to 314 per 1000 of the population at risk. Deaths increased 4.7%, from 0.92 to 0.97 per 1000 of the population at risk during that same period. Data from the 2018 Nigeria Demographic and Health Survey (NDHS) show that the prevalence of malaria parasitaemia in children under five years of age was 23% (a decrease from 27% in 2015 and 42% in 2010), although there are significant regional, rural-urban, and socioeconomic differences: prevalence ranges from 16% in the South and Southeast Zones to 34% in the Northwest Zone. In rural populations, prevalence is 2.4 times than in urban populations (31% vs. 13%). Compared to the highest socioeconomic group, prevalence among children in the lowest socioeconomic group is seven times higher (38% vs. 6%).
The Malaria Vaccine and Regulatory Approval Process
The National Agency for Food and Drug Administration and Control (NAFDAC) in exercising its mandate as stipulated by its enabling law, NAFDAC Act CapN1, LFN 2004 is granting registration approval for R21 Malaria Vaccine (Recombinant, Adjuvanted) manufactured by Serum Institute of India Pvt. Ltd. (SIIPL). The Marketing Authorization Holder’s (MAHs) is Fidson Healthcare Ltd in line with the Agency’s Drug and Related Products Registration Regulation 2021.
The R21 Malaria vaccine is an Adjuvanted protein vaccine presented as a sterile solution. A dose which is 0.5ml is composed of R21 Malaria antigen 5µg and Matrix-M1 50µg as an adjuvant filled in a vial as ready to use liquid formulation for intramuscular injection. The vaccine is indicated for prevention of clinical malaria in children from 5 months to 36 months of age. The storage temperature of the vaccine is 2-8 °C.
The National Agency for Food and Drug Administration and Control (NAFDAC) has several pathways for registration of vaccines. These pathways are in line with the Agency’s guideline for registration of Imported Drugs, Vaccines and IVDs under Collaborative Registration Procedure, or the Agency’s guideline for registration of imported Drug and Vaccines. The R21 Malaria Vaccine was reviewed using the later which involves full review of product dossiers.
Dossier Review
NAFDAC received the dossier of the R21 Malaria manufactured by the Serum Institute of India Pvt Ltd (SSPL) and was subjected to independent review at two levels. As a matured regulatory agency, it is expected as part of global benchmarking that external advisory committee is in place to advise upon invitation on certain functions of the Agency. As a new biological molecule that is being given consideration for full registration, the independent review by an external body becomes imperative as a means to further safeguard public health.
The external advisory body – NAFDAC’s Vaccine Advisory Committee (NEVAC) is made up of four highly recognized, well-published experts from Nigeria’s tertiary institutions (Nnamdi Azikwe University, Awka, Anambra State; University of Lagos, Lagos State, University of Ibadan, Oyo State and Usman Dan Fodio University, Sokoto, Sokoto State). The in-house NAFDAC’s Vaccine Review Committee is a multi-disciplinary group extracted from the following NAFDAC directorates – Drug Registration and Regulatory Affairs, Vaccines/Biologics/Medical Devices; Drug Evaluation and Research (for Clinical trial/Good Manufacturing Practices inputs; Pharmacovigilance; Post-Marketing Surveillance, Central Drug Control Laboratory, and Port Inspection.
Essentially, the dossier was reviewed by NEVAC independently using standards of the World Health Organization (WHO) across relevant domains, in addition to the ICH guidelines, European Medicines Agency guidelines (where appropriate), scientific rigor on the vaccine and the context of malaria generally and specifically to Nigeria and best research and manufacturing governance.
NEVAC members reviewed all sections independently using best review practices and met physically in plenary to assess and debate the reviews by sections, raised queries and made recommendations accordingly. Overall, the assessment was scored as: Adequate (Fully compliant with standards), and the report was submitted to the Director General.
The review of NAFDAC’s Committee has always been guided by the same international standards and best practices with the same modality of independent review by members followed by long hours of plenary where rigorous assessment of each review took place. The Committee also independently scored the assessment as Satisfactory and forwarded to the Director General.
Joint Review Committee
Upon submission of the independent reviews of both Committees, The DG called for a joint review session on Friday, April 14. The joint review process provided the opportunity for harmonising the assessments. The outcomes of the reviews were discussed, and the recommendations and queries/clarifications were consolidated to be referred to the manufacturers.
Overall, the R21 Malaria Vaccine dossier complied substantially with best international standards with which the dossier was benched-marked as mentioned above. The Joint Review Committee concluded that the data on the R21 Malaria vaccine were robust and met criteria for efficacy, safety, and quality. It was also adjudged that the vaccine’s known and potential benefits outweigh its known and potential risks, thereby supporting the manufacturer’s recommended use.
Specific instances where queries/ clarifications and or additional data were required have been duly compiled to the manufacturers. These did not affect the overall adequacy of the dossier. The Joint Review Committee recognised the importance of an effective malaria vaccine (with a 75% protection) as an additional interventional tool, as a critical need in Nigeria with the highest malaria burden. The Joint Review Committee also recommended additional phase 4 clinical trial/Pharmacovigilance study in-country in the implementation given the peculiarity and heterogeneous nature of malaria in Nigeria.
The joint Review Committee was also interested in reviewing data of the human-malaria parasite dynamics of the 25% not covered to understand issues bothering on non-protection that could inform further research. This has created a potential research collaboration opportunity between NAFDAC and the affiliated respective universities of the NEVAC members.
Recommendation
A provisional approval of the R21 Malaria Vaccine was recommended and this shall be done in line with the the WHO’s Malaria Vaccine Implementation Guideline.
While granting the approval, the Agency has also communicated the need for expansion of the clinical trial conducted to include a phase 4 clinical trial/Pharmacovigilance study to be carried out in Nigeria.
The brief on the approval of the R21 Malaria vaccine has been communicated to the Honourable Minister of Health and National Primary Health Care Development Agency for appropriate actions toward immunization in the respective population.
NAFDAC remains committed in ensuring that only products that are safe, high quality and efficacy are made available for Nigerians.
