IBADAN, Nigeria – There are high hopes that the R21/Matrix-M malaria vaccine recently approved by Ghana and Nigeria will be manufactured in Africa in the not-to-distant future – a brighter-than-usual prospect for this World Malaria Day (25 April).

Earlier this month, Ghana’s Food and Drugs Authority (FDA) approved the R21/Matrix-M malaria vaccine manufactured by the Serum Institute of India (SII) for use in children aged from five months to three years, the age group at the highest risk of death from malaria. 

This was despite the vaccine not yet being given World Health Organization (WHO) prequalification approval. 

SII, the manufacturing and commercialisation license holder for the vaccine, described Ghana’s approval as the “first crucial step [that] will enable the vaccine to help Ghanaian and African children to effectively combat malaria”.

“The licensure of the R21/Matrix-M Malaria Vaccine for use in Ghana is a significant milestone in our efforts to combat malaria around the world. We remain steadfast in our commitment to scaling up production of the vaccine to meet the needs of countries with high malaria burden and to support global efforts towards saving lives,” said Adar Poonawalla, SII CEO.

Shortly afterwards, Nigeria’s National Agency for Food and Drug Administration and Control (NAFDAC) also granted a “registration approval” for the vaccine to SII. The agency said it had received the dossier of the vaccine and it had been subjected to independent review at two levels. 

The agency added that the vaccine’s dossier substantially complied with best international standards, and that its Joint Review Committee had concluded the vaccine data was robust and met the criteria for efficacy, safety, and quality. 

Local production?

Ghana’s regulator announced that the application for regulatory approval had been submitted by SII’s ‘local agent’, DEK, which expects to eventually manufacture the vaccine locally.

“The status of the [Ghana] FDA Lab creates a great advantage for the local agent who hopefully will be manufacturing the malaria vaccine in Ghana in the near future,” the agency stated.

A few days after the regulatory approval, a ground-breaking ceremony of the DEK Vaccines Limited’s vaccine fill-and-finish plant was held. The company is a private sector-led consortium of Ghanaian pharmaceutical companies.

At the ceremony, Ghanaian President Nana Addo Dankwa Akufo-Addo, said it “will help our nation realise the dream of becoming self-sufficient in the manufacture of vaccines”.

Meanwhile, Nigeria’s regulator announced Fidson Healthcare Ltd, a major local bourse-listed player in the country’s pharmaceutical industry, as the vaccine’s Marketing Authorization Holder (MAH). This authorizes the Nigerian firm licensed to distribute, sell and commercialize the vaccine in Nigeria.

The Nigerian government also revealed in September 2022 that it had signed a local vaccine manufacturing agreement involving Biovaccines Nigeria Limited (a joint venture between the Federal Government of Nigeria and May & Baker Nigeria Plc), and SII.

“The government has approved 15% of the vaccines that UNICEF normally supplies to Biovaccines to supply through contract manufacturing with the Serum Institute of India. With that, the institute will now be comfortable enough to come and join Biovaccines Nigeria in building its manufacturing plant here in Nigeria in Ota,” Nigerian health minister, Osagie Ehanire said.

From Oxford to West Africa via India

Designed and developed at the University of Oxford, the vaccine has been tested in the United Kingdom, Thailand, and several African countries. 

A Phase Three trial that is underway in Burkina Faso, Kenya, Mali and Tanzania has enrolled 4,800 children and the results are expected later this year. 

While the regulator in Nigeria has also recommended an in-country Phase Four clinical trial or pharmacovigilance study in the implementation, given the peculiarity and heterogeneous nature of malaria in Nigeria, it noted that the efficacy results from the vaccine’s clinical trials contributed to its decision to approve it.

Last year, the Oxford researchers and their partners reported from a Phase 2B trial that a booster dose of R21/Matrix-M at one year, following a primary three-dose regime, maintained high efficacy against malaria, and continued to meet the WHO’s Malaria Vaccine Technology Roadmap goal of a vaccine with at least 75% efficacy. 

This followed 2021 results from the Phase 2B trial reporting that R21/Matrix-M demonstrated high-level efficacy of 77%. Recent data from the large phase III trial also show high levels of efficacy and a reassuring safety profile. 

Prof Adrian Hill, chief investigator for R21/Matrix-M programme, and Director of the Jenner Institute at the University of Oxford, described the regulatory approval of the vaccine as the culmination of 30 years of malaria vaccine research at Oxford. 

“I congratulate our superb clinical trial partners in Africa who have generated the dataset supporting the safety and efficacy of the vaccine in children,” Hill said. 

The vaccine contains Novavax’s Matrix-M which is a saponin-based adjuvant that enhances the immune system response, making it more potent and more durable. The Matrix-M adjuvant stimulates the entry of antigen-presenting cells at the injection site and enhances antigen presentation in local lymph nodes. This technology has also been used successfully in Novavax’s COVID-19 vaccine and is a key component of other development-stage vaccines.

An approval without a WHO prequalification

Unlike the developments surrounding the approval of the COVID-19 vaccines in the African countries that largely followed a prequalification approval by the WHO, both Ghana and Nigerian regulators went ahead to approve the vaccine without any WHO approval. 

In addition to affirming their regulators’ competence and authorization to undertake such approvals, Dr Franklin Asiedu–Bekoe, Director of Public Health in Ghana, told Health Policy Watch that the vaccine – the second malaria vaccine that the country is rolling out – will be closely reviewed by the country’s team of scientists.

“In Ghana, we have 93 districts that are now using the TRS,S. There are a number of districts that are yet to be using it. So if we have a vaccine, which is good, I think nothing stops us from using it,” he argued.

Moreover, Prof William K. Ampofo, Secretary of the Presidential Committee on Vaccine Manufacturing and Development, Ghana, added that the approval was in response to the manufacturer’s application.

“The vaccine was approved based on the application by the manufacturer Serum Institute. It was not an independent decision by the Ghana FDA. It was in response to the application by the Serum Institute for the R21 vaccine based on the data that had been accumulated,” Ampofo told Health Policy Watch.

Local manufacturing elements of both approvals

In the weeks before regulatory approval for the R21 vaccine, Ghana officially expanded access to the WHO-approved RTS,S malaria vaccine. Four years on, more than 4.5 million doses of the vaccine have been administered through the countries’ routine immunization programmes. 

“Community demand for the vaccine is high and the vaccine is well accepted in African communities, even when additional visits to vaccination clinics are required to receive the four-dose schedule,” WHO revealed. 

But RTS,S rollout has been plagued with concerns regarding its comparatively minimal efficacy, high cost and limited supply. 

In sharp contrast, R21’s demonstrably higher efficacy (more than 75% over 12 months) and comparatively lower cost ($3 compared with RTS,S’ $5 per dose) made it even more attractive to African countries – along with the manufacturer’s announcement of potential manufacturing capacities of more than 200 million doses annually.  

But beyond these essential factors are also considerations for local manufacturing from the outset of the vaccine’s introduction in Africa.

WHO and Gavi falling in line

Even though the WHO prequalification certification has not yet approved the R21 vaccine, the WHO has expressed its support for the vaccine, acknowledging on its website that a second malaria vaccine may be coming forward.

“The WHO prequalification process is also underway. WHO will continue the thorough and efficient review of the R21 vaccine and awaits the submission of additional analyses by the vaccine developer,” the global health body said.

Dr Phionah Atuhebwe, New Vaccines Introduction Officer at WHO AFRO Regional Office, added that the WHO is already evaluating the vaccine’s safety, efficacy, quality and programmatic suitability.

“Ghana and Nigeria have not jumped the gun because it is expected that, at national level within their jurisdiction, the national regulatory authorities can also review data once they have received information from different vaccine developers,” she said.

Aurelia Nguyen, Chief Programme and Strategy Officer for Gavi, the Vaccine Alliance, also told Health Policy Watch that the alliance is prepared to provide funding for the R21 malaria vaccine. 

“It is a hugely exciting development with the approvals that we’ve seen in Ghana and Nigeria. This is all moving us forward towards having a second vaccine,” Nguyen said. 

She noted that the restricted supply of the RTS,S made it “really important” to have several tools, in addition to affordability.

“It’s not just about the volumes, it’s also about the affordability. Serum Institute has made a very important public commitment in terms of keeping the cost of the vaccines to $3 or less. So we really look forward to them honoring that commitment because ultimately, it will mean that more people are protected,” Nguyen concluded.

Image Credits: WHO/Fanjan Combrink, WHO/M. Nieuwenhof, WHO.