Fans watching a Premier League football match in London Stadium in lat May. Spectators were socially distanced and hygiene safety warning signs were displayed.

WHO urged high income countries in Europe and elsewhere to reconsider the reopening of mass events, and keep strict social distancing rules in place – in the wake of a surge in COVID cases almost everywhere but Latin America. 

They spoke at a press briefing on the day that the world passed the tragic milestone of four million COVID-19 deaths since the beginning of the pandemic in January 2020. 

“The world is at a perilous point in this pandemic,” said Dr Tedros Adhanom Ghebreyesus, WHO Director-General, at the WHO press conference on Wednesday.

Globally, only a slight increase in new weekly cases has been recorded over the past two weeks – but that is still worrisome after six weeks or more of declines in Europe, Asia and Africa. 

“More than two dozen countries have epidemic curves that are almost vertical right now,” said Dr Maria Van Kerkhove, WHO COVID-19 Technical Lead. 

Among those are the United Kingdom, where new cases have increased 18 fold since 20 May, and by 67% over just the past week, according to WHO. Deaths in the UK also are increasing, although much more gradually – testifying to the continued efficacy of vaccines.   

Cases on Rise in Most Parts of World 

Indeed, after sharp declines in most regions and key countries of the world over the past eight weeks, new cases are now on the increase almost everywhere – except for Latin America which had been riding an enormous fourth COVID wave, now in decline (see related HP-Watch story). 

Outside of the UK, infections were also rising fast in other European countries that have been slowly reopening this summer, with a 30% overall increase in incidence, as well as in the United States, with deaths also tilting upwards. 

This was followed by a 15% increase in cases in the African region, 11% increase in the Eastern Mediterranean region, 10% increase in the Western Pacific region, and 7% increase in the Southeast Asia region. 

In Africa, which has very low vaccine rates as well as hospital capacity, deaths per capita are approaching the all time peaks seen in January 2021, during Africa’s second wave. 

African Region Seeing Fastest Rise in Mortality  

Even more worrisome, the African region, which also lacks hospital and oxygen capacity,  has witnessed a sharp increase in mortality by 23% over just the past week, the highest out of all six WHO regions, WHO said. 

“Compounded by fast moving variants and shocking inequity in vaccinations, far too many countries in every region of the world are seeing sharp spikes in cases and hospitalizations,” said Tedros. “This is leading to an acute shortage of oxygen treatments and driving a wave of deaths in parts of Africa, Asia, and Latin America.”

Devastating Milestone – Four Million 

“Today, the world passed another devastating milestone: four million reported deaths,” said Jeremy Farrar, Director of Wellcome, in a statement. “Sadly, the true figure is undoubtedly much higher.”

“In countries with widespread vaccination coverage there thankfully appears to be a weakened link between infection rates, hospitalizations and deaths. But for large parts of the world facing a vaccine shortfall and the highly infectious Delta variant, it’s a tragically different picture,” Farrar said. 

The four major factors that are driving transmission are: the more transmissible virus variants, particularly the Delta variant; increased social mixing in reopening economies; reduced or inappropriate use of public health and social measures; and inequitable and uneven distribution of vaccines, said Van Kerkhove. 

Dr Maria Van Kerkhove, WHO COVID-19 Technical Lead, at the press conference on Wednesday.

The Delta variant, first identified in India and classified as a WHO variant of concern in mid-May, is considered 40-60% more transmissible than the Alpha variant, identified in the United Kingdom. It has been reported in 104 countries and is expected to become the dominant variant worldwide in the coming months.

WHO Urges Continued Restrictions – Despite Tourism & European Cup Pressures 

European countries have been in the process of gradually lifting public health measures for the summer months, in an attempt to revive economies, including sports summer tourism, after vaccinating a significant proportion of their populations.  

Despite the surge in new cases, the UK, which is also one of the most heavily vaccinated European countries nearly 50% of the total population fully covered, has taken the most dramatic steps towards the easing of COVID restrictions since the lockdowns were first applied last year. 

Meanwhile, European Cup matches have been played out over the past several weeks across the region in stadiums of live fans, for the first time in over a year, with the finals set for the UK’s Wembley Stadium on Sunday. However Dr Mike Ryan, WHO Head of the Health Emergencies Programme, declined to comment on whether it was wise for UK officials to permit live spectators at specific events.  

“I’m not going to comment on specific events for mass gatherings, but I would want to make sure that all of those individuals, countries, and institutions planning events in the coming months take due care and attention to managing risks,” Ryan said. 

Dr Mike Ryan, WHO Head of the Health Emergencies Programme.

On 19 July, limits on the number of people that can gather in the UK, as well as the legal obligation to wear face masks will be lifted, and all businesses still closed due to such restrictions will be allowed to reopen.

The government has made this controversial decision despite the doubling of new cases every nine days and predictions that the country could see two million individuals contract COVID over the summer.

A drop off in hospitalizations and deaths has been seen in countries with high vaccination coverage, however, the vaccination rate is not high enough to prevent transmission. In addition, the science is not yet clear on the ability of vaccinated people to transmit the virus or become reinfected, said WHO officials.

Some 49.9% of the UK’s population is fully vaccinated and 66.9% have received at least one dose. 

“The lifting of all public health and social measures [is] prudent at this time,” said Ryan.

“We would ask governments to be really careful at this moment not to lose the gains they’ve made,” said Ryan. “I would hope that in the European environment we won’t see a return to the overwhelmed hospitals and the exhausted health workers, but that’s not a given.”

He stressed the continued need for robust surveillance, active testing, and contact tracing to prevent cases from spiralling out of control again. 

“Risk management hasn’t been perfect in this pandemic, but it has saved lives, slowed down the pandemic, and kept the pressure off the health system,” said Ryan. 

“Our goal is to suppress transmission and save lives, so we need those policies in place in all countries” to meet the goal, said Van Kerkhove.

Calls for Action on Vaccine Inequity 

“Variants are currently winning the race against vaccines because of inequitable vaccine production and distribution, which also threatens the global economic recovery,” said Tedros, sounding yet another, in a series of calls to mobilise the global conscience – with mixed results.  

Dr Tedros Adhanom Ghebreyesus, WHO Director-General.

“At this stage in the pandemic, the fact that millions of health and care workers have still not been vaccinated is abhorrent,” said Tedros. 

The WHO Director General has set out a goal of vaccinating 10% of people in all countries by September, 40% by the end of the year, and 70% by mid 2022 – although at present vaccination rates, it remains entirely unclear if those targets can really be reached. 

“In this pandemic right now…protect[ing] vulnerable healthcare workers and the elderly in low-income countries before expanding into populations in high-income countries that may not suffer the same consequences of the infection,” should be prioritised, said Ann Lindstrand, WHO Head of the Essential Programme on Immunisation. 

WHO officials called upon the Group of 20 (G20) finance ministers, who will meet later this week, to take the steps necessary to end the acute phase of the pandemic, provide the funding to scale up vaccine manufacturing, and get behind Tedros’ vaccination targets.

“We have the tools we need to end this pandemic – vaccines, treatments and tests – but this will only work when they’re available to everyone, everywhere,” said Farrar. “Recent pledges from the G7 and G20 do not go far or fast enough. They are the only ones that can make vaccines available now.”

Image Credits: Wikimedia, WHO.

Levels of neutralizing antibodies in vaccinated individuals is a strong indicator of COVID-19 vaccine success- and this knowledge could be used to jump-start vaccine approvals and mass administration – even before large Phase 3 clinical trials are completed, suggests a new study by the University of Oxford Vaccine Group, Public Health England, and AstraZeneca. 

Knowledge of immune biomarkers could allow new vaccines to be authorised only with immunogenicity and safety data, and even before costly and time-consuming large scale efficacy trials are completed, the study published on the preprint server, Medrxiv.org, suggests. 

So using antibody biomarkers to further accelerate vaccine approvals could still help meet the huge unmet global demand that still exists, the study authors concluded, suggesting a bold new approach to vaccine approvals.  

“Understanding the relationship between immune responses to vaccines and protection against clinical outcomes is urgently needed to speed up vaccine development,” the researchers observed.

“The power of a correlate in vaccines is profound,” said Dan Barouch, Director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center in Boston, who authored an independent commentary in Nature on the new research.  

“If there’s a reliable correlate, then it can be used in clinical trials to make decisions as to what vaccines are likely to work, what form of vaccines are likely to work, or how durable the vaccines are going to be,” said Barouch. 

Even so, the science of antibody response is uneven, even with respect to the same vaccine.

“The probability of infection decreases on average with higher immune responses, but substantial variation exists between individuals,” acknowledged the authors.   

Eight vaccines have so far been recommended for use by the World Health Organization (WHO) – including the addition of two Chinese-made vaccines in June. Despite a vastly accelerated R&D timeline, approvals of other COVID vaccines in the pipeline still require many months as large-scale Phase 3 trials demonstrating efficacy must be completed. 

Study Vaccines Approved by WHO – More In Pipeline Now

Adjusted risk of primary symptomatic COVID-19 as a function of immune markers measured 28 days post second dose.
Top left: Anti-Spike IgG 28 days post boost Top right: Anti-RBD IgG 28 days post boost Bottom left: pseudovirus neutralisation antibody titres 28 days post boost
Bottom right: live neutralisation antibody titres 28 days post boost.
Grey lines show control (MenACWY) overall risk and vaccine (ChAdOx1 nCoV-19) overall risk. Blue dots show the absolute risk predicted from the model across the range of antibody values included in the analysis, adjusting for baseline exposure risk to SARS-CoV-2 infection (logit-transformed linear covariate including age, ethnicity, BMI, co-morbidities and healthcare worker status). Green shaded areas show the confidence interval around the predicted mean probability (green line) 

The Oxford and AstraZeneca study compared the immune responses of 171 vaccinated people who developed symptomatic infections to 1,404 vaccinated participants without a SARS-CoV2 infection, comparing four key biomarkers of antibody levels. 

Participants with higher levels of neutralizing antibodies tended to have stronger, although not complete protection from a symptomatic infection, the study found.

The risk of symptomatic COVID decreased with increasing levels of the following biomarkers of neutralizing antibodies: anti-spike immunoglobulin G (IgG), anti-receptor binding domain (RBD) IgG, pseudovirus neutralization titre, and live neutralization titre.  Immunoglobulin G antibodies are the basis of long-term protection.

“Finding the correlate of protection has really been a holy grail for this disease, as for others,” said Daniel Altmann, Professor of Immunology at Imperial College in a Nature commentary. “It’s surprisingly hard to do.” 

At the same time, while the antibody responses documented in the study proved to be a strong predictor for the development of symptomatic COVID infections, that was not at all the case for vaccine efficacy in terms of preventing asymptomatic infections. 

“Antibody responses did not correlate with overall protection against asymptomatic infection,” said the authors – meaning that the drivers of asymptomatic infections continue to elude researchers. 

Earlier Study Found Pfizer & Moderna Vaccines Produced More Neutralizing Antibodies that Other Vaccines 

Other studies have also demonstrated that vaccine-induced antibody levels are higher with some vaccines than others – explaining why some vaccines achieve higher levels of over all efficacy. Notably, a study in late May found induced levels of neutralizing antiboides to be highest with Moderna and Pfizer vaccines, as compared with Johnson & Johnson and AstraZeneca. 

The mRNA vaccines generated the strongest neutralizing antibody responses, and as a result were more protective. Vaccines that induced a weaker response provided lower levels of protection, said the authors. 

In the study published in Nature, researchers found a link between participants’ antibody levels recorded in early-stage trials and vaccine efficacy results from late-stage trials. 

The study estimated that a vaccine would have an efficacy of 50%, even if it induced antibody levels 80% lower than what would be found in a person who recovered from COVID-19. 

“Even low antibody levels, lower than we thought, will probably see you through,” said Altmann. 

Image Credits: WHO PAHO, Medrxiv.

Tocilizumab, manufactured by Roche.

After months with virtually no therapeutic options for people with severe COVID-19, the World Health Organization (WHO) recommended the use of a class of medicines called interleukin-6 antagonists on Tuesday.

The medicines, tocilizumab and sarilumab, reduced the risk of death and ventilation when combined with corticosteroids, according to a study published the same day in the Journal of the American Medical Association (JAMA).

Interleukin-6 is a protein or cytokine that can cause excessive inflammation, and it is a factor in rheumatoid arthritis and many cancers.

“In severely ill COVID-19 patients, the immune system overreacts, generating cytokines such as interleukin-6. Interleukin-6 blocking drugs – tocilizumab and sarilumab – act to suppress this overreaction,” according to the WHO>

The use of these drugs reduced the odds of death by 13% in severely ill and critical patients, and the odds of them needing mechanical ventilation by 28%, compared with standard care.

These are the first drugs found to be effective against COVID-19 since corticosteroids were recommended by WHO in September 2020 – but they are costly

“These drugs offer hope for patients and families who are suffering from the devastating impact of severe and critical COVID-19. But IL-6 receptor blockers remain inaccessible and unaffordable for the majority of the world,” said WHO Director-General Dr Tedros Adhanom Ghebreyesus.

Dr Tedros Adhanom Ghebreyesus, WHO Director General.

“The inequitable distribution of vaccines means that people in low- and middle-income countries are most susceptible to severe forms of COVID-19. So, the greatest need for these drugs is in countries that currently have the least access. We must urgently change this,” said Tedros.

MSF Calls on Roche to Reduce Prices

Meanwhile, Médecins Sans Frontières (MSF) called on the Swiss pharmaceutical company, Roche, the world’s only producer of tocilizumab, to lower its price “to make it affordable and accessible for everyone who needs it”.

“Even though tocilizumab has been on the market since 2009 for treatment of rheumatologic diseases, access has remained a challenge,” according to MSF. 

“Roche kept the price of this drug very high in most countries, with price tags ranging from US$410 in Australia, $646 in India to $3,625 in the USA per dose of 600mg for COVID-19.”

Julien Potet, Policy Advisor at MSF’s Access Campaign, called on Roche to “take urgent steps to make this drug accessible and affordable for everyone who needs it by reducing the price and transferring the technology, know-how and cell lines to other manufacturers”.

“Medical practitioners in many countries in Africa and Latin America, who are grappling with newer and more transmissible variants of coronavirus, are right now struggling to keep their patients alive,” said Potet.

“This drug could become essential for treating people with critical and severe cases of COVID-19 and reduce the need for ventilators and medical oxygen which are scarce resources in many places.”

Regeneron holds the patent for the second drug, sarilumab, in “at least 50 low- and middle-income countries, raising immediate challenges of ensuring uninterrupted production and supply by diverse producers in these countries”, according to MSF.

Study involved almost 11,000 patients

The study, a meta-analysis of 27 randomised trials involving nearly 11,000 patients, was coordinated by the WHO in partnership with King’s College London, the University of Bristol, University College London and Guy’s and St Thomas’ NHS Foundation Trust.

Researchers examined the clinical benefit of treating hospitalised COVID-19 patients with interleukin-6 antagonists, compared with either a placebo or usual care. 

They combined data from 27 randomised trials in 28 countries, involving 10,930 patients, 6,449 of whom were randomly assigned to receive interleukin-6 antagonists and 4,481 to receive usual care or placebo.

“While science has delivered, we must now turn our attention to access. Given the extent of global vaccine inequity, people in the lowest income countries will be the ones most at risk of severe and critical COVID-19. Those are the people these drugs need to reach,” said Dr Janet Diaz, Lead for Clinical management, WHO Health Emergencies.

The WHO has called on companies making the medicines to issue “transparent, non-exclusive voluntary licensing agreements using the C-TAP platform and the Medicines Patent Pool, or to waive exclusivity rights”.

It has also launched an expression of interest for prequalification of manufacturers of interleukin-6 receptor blockers.

“The main patent on tocilizumab expired in 2017, yet several secondary patents remain on the medicine in a number of low- and middle-income countries that may cause uncertainties,” according to MSF.

“Several ‘biosimilar’ versions are under development, but none have been approved by a regulatory authority, meaning that despite being off-patent, Roche continue to have de facto market exclusivity.”

India has already started using tocilizumab to treat those with severe COVID-19, but supplies ran out during May, according to MSF.

“Over the last few months, we have helplessly witnessed people in South Asia scrambling to get hold of tocilizumab for patients with severe forms of COVID-19,” said Leena Menghaney, Global IP advisor for MSF Access Campaign. 

“Manufacturers based in low- and middle-income countries urgently need to register and scale up production to increase the global supply. With more than 3.9 million lives already lost to COVID-19, the world cannot wait any longer for access to treatments that can help in increasing the chances of survival.” 

 

Image Credits: Roche, WHO.

Dr Nono Simelela, WHO Assistant Director-General for Strategic Programmatic Priorities: Cervical Cancer Elimination.

At least 70% of women should be screened for cervical cancer via high-performing DNA-based tests to identify the human papillomavirus (HPV), not a visual inspection with acetic acid or a Pap smear, which are more common. 

The HPV DNA test is not only more accurate, but it is also more cost-effective, according to the World Health Organization (WHO), which launched new guidelines on screening and treatment to prevent cervical cancer on Tuesday.

“Effective and accessible cervical screening and treatment programmes in every country are non-negotiable if we are going to end the unimaginable suffering caused by cervical cancer,” said Dr Nono Simelela, WHO Assistant Director-General for Strategic Programmatic Priorities: Cervical Cancer Elimination. 

“This new WHO guideline will guide public health investment in better diagnostic tools, stronger implementation processes and more acceptable options for screening to reach more women –  and save more lives,” she told a webinar to launch the guidelines.

Last year more than half a million women contracted cervical cancer, and about 342 000 women died as a result – most in the poorest countries.

The guidelines recommend important shifts in care, including more access to self-sampling to achieve the goal of having 70% of women aged between 35 and 40 tested by 2030 and at least 90% of people who need treatment to receive it.

“Studies show that women often feel more comfortable taking their own samples, for instance in the comfort of their own home, rather than going to see a provider for screening. However, women need to receive appropriate support to feel confident in managing the process,” WHO said in a statement.

This, said WHO, paired with screening women for HPV and vaccinating girls against HPV, may help prevent more than 62 million deaths from cervical cancer in the next century.

More Research Needed to Combat Cervical Cancer

Several experts also highlighted the need for more research, training of health professionals and destigmatising the disease to combat one of the biggest killers of women, particularly those in poor countries.

They said research into HPV should not only be focused on medical objectives, but should include social and political activism if deaths are to be prevented.

Professor Lynette Denny, a South African gynaecologist and champion of cervical cancer, described cervical cancer as “a disease of poverty, but also a disease of prejudice”.

“It’s a disease of saving some lives over others,” said Denny who called on research to be extended to patients’ history and the social impacts of women post HPV-diagnosis.

“When we talk about research, we have to talk about where are our patients coming from. What are they experiencing on a day-to-day basis and what are we as researchers, and healthcare professionals hearing,” said Denny.

“There have been some studies [that show] that if a woman dies and her child is under the age of 10, the chances that that child will live to 10-years-old are about 25%. And this is what’s happening in many, many countries as well where women are dying, and have young children in communities that often are unable to take care of these children without the support of the mother.”

Responding to the Link Between HPV and HIV

And while experts called for more research into HPV, WHO said more emphasis needs to be made on the link between HPV and HIV, as women with HIV are six times more likely to get HPV than those without HIV.

With HPV being the main driver behind most cervical cancer diagnoses, this cannot be overlooked.  The guidelines state that women with HIV should start cervical cancer screening at an earlier age (25) as opposed to the general population recommendation of 30 years.

“With these new guidelines, we must leverage the platforms already developed for HIV care and treatment to better integrate cervical cancer screening and treatment to meet the health needs and rights of the diverse group of women living with HIV to increase access, improve coverage, and save lives,” said Dr Meg Doherty, Director of WHO’s Department of Global HIV, Hepatitis and Sexually Transmitted Infections Programmes.

WHO recommends that all women who test positive for cervical cancer should receive treatment soon after diagnosis.

“Cost-effectiveness of screening tests is important for scaling up programmes, but other aspects of the public health approach to eliminating cervical cancer are also vital,” said Dr. Nathalie Broutet, WHO Department of Sexual and Reproductive Health and Research and HRP. “What matters most is the coherence of every country’s programme in ensuring the continuum of care: that all women have access to screening, health care providers are informed in a timely manner about the results of the screening test and can in turn share this information with their client, and that women can access appropriate treatment or referral if needed.”

Professor Groesbeck Parham, Director of the CIDRZ Cervical Cancer Prevention Program, professor of gynaecological oncology at UNC-Chapel Hill, agreed with Denny and said that despite technological advances in trying to understand cervical cancer, “we won’t get very far unless we put this disease in the women who have it in the proper social context”

“That’s the only thing that’s going to drive this off the planet as a social movement, because it is a social disease. Women diagnosed with HPV are often stigmatised and live in shame, and this needs to be addressed, said Parham.

Image Credits: WHO.

Dr Tedros Adhanom Ghebreyesus, WHO Director General, at the ACT-Accelerator Facilitation Council Briefing on Tuesday.

As many high-income countries are relaxing restrictions for the summer months, low- and middle-income countries (LMICs) are witnessing rises in cases, deaths, and overwhelmed hospitals. 

Countries in Europe and the United States are increasingly allowing in travellers, ending mask mandates, and allowing large gatherings including football matches and concerts. 

At the same time, the third wave is intensifying in several countries, with critical oxygen shortages rising in sub-Saharan Africa, Southeast Asia, and parts of Latin America. Some 19 countries are about to run out of oxygen.

“We face a two-track pandemic,” said Dr Tedros Adhanom Ghebreyesus, WHO Director-General, at the ACT-Accelerator Facilitation Council Briefing on Tuesday. “The countries that are now opening up their societies are those that have largely controlled the supply of life-saving personal protective equipment [PPE], tests, oxygen, and especially vaccines.”

“Meanwhile, countries without access to sufficient supplies are facing waves of hospitalizations and deaths,” Tedros said. 

“While some parts of the world go on to enjoy summer vacation in near normality, others brace themselves for overwhelmed hospitals and economies on the brink of collapse,” said Dag-Inge Ulstein, Norway’s Minister of International Development and Co-chair of the ACT-Accelerator Facilitation Council. 

Pandemic is in a ‘Very Dangerous Phase’

After weeks of decline, global COVID-19 cases are now on the rise in five of the six WHO regions. The African region is currently experiencing a fast-surging third wave that could pose a far greater threat to the continent than the second wave. 

“We shouldn’t be in this position 18 months into a global pandemic where all of us are exhausted and with more than 183 million confirmed cases and 3.9 million deaths,” said Maria Van Kerkhove, WHO COVID-19 Technical Lead. 

Over 20 countries globally have an exponential growth in cases and “almost vertical transmission,” said Van Kerkhove. 

The global epidemiological report separated by region, as of 5 July 2021.

This is largely being driven by the Delta variant, first identified in India and classified as a “variant of concern” by WHO in mid-May. It is considered 40-60% more transmissible than the Alpha variant, identified in the United Kingdom. 

More than 96 countries have reported the Delta variant and it is expected to become the dominant virus in the coming months. 

The pandemic “remains in a very dangerous phase,” with the continual emergence of variants, inequitable vaccinations, and overburdened health systems, said Tedros. 

“Most of the world remains susceptible to infection,” due in part to the uneven rollout of vaccines globally and the inconsistent implementation of public health and social measures around the world, said Van Kerkhove. 

“Urgent action is required, not only to redress inequitable access to health care and to vaccines, but to ensure that countries have the capacity to translate vaccines into vaccination, diagnostics into effective surveillance, and therapeutics into treatment,” said Van Kerkhove. 

The WHO identified priority actions for member states, namely to: enhance national, regional, and global surveillance, testing, clinical care, and access to oxygen and therapeutics; maintain focus on public health and social measures to suppress transmission; scale up the research, production of and equitable distribution of vaccines, diagnostics, and therapeutics; and strengthen the capacity and resilience of health systems.

Inequities are Decreasing, But Stark Disparities Remain

While a global milestone of administering three billion doses has been reached, only 0.3% of those have gone to low-income countries. Of the 2.6 billion COVID tests performed globally, less than 4% have been administered in Africa, which accounts for 17% of the world’s population.

While vaccine deployment is improving everywhere in the world, there are still stark disparities between the regions in terms of coverage.

No low-income countries have achieved more than 20% vaccination coverage nationally, compared to 80% of high-income countries.

Some 68 WHO member states have reached 20% coverage, the majority from the European region. The African region and Southeast Asian region have the lowest share of countries with coverage over 20%. 

The share of WHO member states with COVID-19 vaccine coverage over 20%.

Vaccine inequity is gradually decreasing, but high-income countries have still administered 63 times more doses per inhabitant than low-income countries. Of the 194 WHO member states, 189 have started vaccinating. 

“These persistent inequalities are translating into countless preventable deaths while the world has the tools to stop this,” said Mmamoloko Kubayi, Acting Minister of Health of South Africa and Co-chair of the ACT-Accelerator Facilitation Council.

Mmamoloko Kubayi, South Africa’s Acting Minister of Health and Co-chair of the ACT-Accelerator Council.

“We need to mobilise resources to fund medical oxygen storage and infrastructure, pay for emergency supplies, and finance the transportation of equipment and other tools needed,” said Kubayi. 

“Our only way out [of the pandemic] is to support countries in the equitable distribution of PPE, tests, treatments, and vaccines,” said Tedros.

“This pandemic is testing our ability to save lives, but also our ability to save the architecture of international cooperation that we spent so many decades building,” added Ulstein. 

Constraints on COVAX Vaccination Progress 

COVAX has shipped 95.9 million doses to 135 countries, including 69 low- and middle-income countries. Some 40 countries began their vaccination campaigns because of COVAX.

“We should have been at a much higher level of distribution by now, perhaps between 300- and 400 million doses, but because of the constraints…we have yet to touch 100 million,” said Soumya Swaminathan, WHO Chief Scientist. 

A global map of the countries that have received doses from COVAX, as of 5 July 2021.

COVAX is currently facing supply shortages primarily due to delays in clinical trials, regulatory approvals, the validation of new manufacturing sites, supply chain bottlenecks, and export controls. 

“In recognition of these risks that we are facing, we’re very much focused on having a diversified portfolio of vaccines…in terms of resilience across different manufacturing sites across the globe and having a very actively managed portfolio,” said Aurelia Nguyen, Managing Director of the COVAX Facility. 

WHO officials expect to have a “very strong increase” in vaccines available to COVAX in the fourth quarter of 2021 with additional vaccines getting WHO emergency use listing (EUL) and scale ups in vaccine manufacturing. 

The hope is also that exports of the AstraZeneca vaccine from the Serum Institute of India (SII), a major source of doses for the COVAX Facility, will resume in late 2021. 

Supplies from the SII manufacturing site were redirected to address the domestic surge in cases and deaths in April, causing delays in COVAX deliveries to low- and middle-income countries. 

Boosting the availability of vaccines immediately will require dose sharing from countries with a surplus of vaccines. Several countries have committed over 530 million doses to COVAX, with the commencement of deliveries from France, New Zealand, and the US. 

Four new manufacturers have signed up with COVAX – Moderna, Novavax, Johnson & Johnson, and Clover, a Chinese biotech firm – committing 1.5 billion doses. 

As a result of the new deal and ongoing negotiations, COVAX expects “substantial volumes” of vaccines through 2021 and early 2022, said Nguyen.

“We are forecasted to have approximately 1.9 billion doses available for delivery by the end of 2021 and of this, the advanced market commitment participants, the 92 lower-income economies, are expected to receive 1.5 billion doses of that,” said Nguyen.

The global supply forecast of the COVAX Facility for 2021 and 2022.

Appeal for Funding for the ACT-Accelerator

As of the end of June, US$17.7 billion was raised for the Access to COVID-19 Tools (ACT) Accelerator – an initiative to speed up the development, production, and access to tests, treatments, and vaccines – but a considerable gap in funding remains, said officials at the Facilitation Council meeting. 

ACT-A has a funding gap of US$16.8 billion, two-thirds of which is needed for the supply diagnostics and PPE. The rest is intended for R&D and manufacturing, the health systems connector pillar of ACT-A, and the supply of therapeutics and oxygen. 

Some 60% of the total supply need for diagnostics and therapeutics is in LMICs. 

Particularly in the context of the current surge in cases, “there is an urgency to ensure that the ACT-Accelerator’s financing needs are met,” said Michaela Pfeiffer, WHO Technical Officer of ACT-A Hub. 

As the world approaches the “sobering juncture” of four million lives lost from COVID-19, funding commitments to ACT-A are critical, said Ulstein.

WHO officials called on the Group of 20 (G-20), an intergovernmental forum for economic collaboration, to not delay financial commitments to the Accelerator. 

“Our appeal for countries to finance ACT-A is not new, but it is ever more relevant,” said Ulstein. 

Dag-Inge Ulstein, Norway’s Minister of International Development and Co-chair of the ACT-Accelerator Facilitation Council.

In addition to financing, countries were also called upon to share vaccines, as at least 250 million doses will be needed to reach 10% vaccine coverage in all countries by September. 

The pharmaceutical industry and manufacturers have a role to play in scaling up production and facilitating technology transfer to improve the global vaccine manufacturing capacity. 

“We need manufacturers to help by sharing know-how and accelerating technology transfer,” said Tedros. 

“The stakes are high and the challenges before us are vast, but not insurmountable,” said Ulstein. “A clear message has been sent that the solutions exist, it is only that we need to have the political will to realize them and ensure that everyone everywhere has access to life saving measures.”

Image Credits: WHO.

The Swiss-based journal Vaccines has retracted a controversial paper linking deaths to COVID-19 vaccines, which prompted the resignation of six members of its editorial board last week.

The paper was titled ‘The Safety of COVID-19 Vaccinations – We Should Rethink the Policy’, and it attracted massive support from anti-vaxxers who question the safety of vaccines.

Prior to its retraction, the journal issued an “expression of concern” flagging that “serious concerns have been raised about misinterpretation of the data and the conclusions” in the paper, particularly that three deaths reported to be linked to vaccinations is “incorrect and distorted”.

The paragraph that attracted the most controversy argued: “The number of cases experiencing adverse reactions has been reported to be 700 per 100,000 vaccinations. Currently, we see 16 serious side effects per 100,000 vaccinations, and the number of fatal side effects is at 4.11/100,000 vaccinations. For three deaths prevented by vaccination we have to accept two inflicted by vaccination.”

The  paper based its statistics on adverse effects and deaths on data from Netherlands Pharmacovigilance Center, called Lareb. However, anyone can report an adverse effect or death on the database without independent medical verification. After the paper was published, Lareb’s head of science and research, Eugène van Puijenbroek, wrote to the journal and requested that it retract the paper.

The paper listed as its corresponding author the controversial German psychologist Harald Walach. In 2012, he received the Goldene Brett vorm Kopf  (golden blockhead) ‘prize’ for promoting pseudo-science from the German Society for the Scientific Investigation of Pseudosciences.

Walach and co-authors medical physicist Rainer Klement and data analyst Wouter Aukema, responded to Retraction Watch about the retraction of their paper by saying: “We used imperfect data correctly. We are not responsible for the validity and correctness of the data, but for the correctness of the analysis. We contend that our analysis was correct.”

Editorial board resignations include virologist Florian Krammer, from Icahn School of Medicine at Mount Sinai; Oxford University immunologist Katie Ewer, who helped to develop the Oxford-AstraZeneca COVID-19 vaccine; New Zealand vaccinologist Helen Petousis-Harris; epidemiologist Diane Harper from the University of Michigan; Australian immunologist Paul Licciardi from Murdoch Children’s Research Institute and virologist Andrew Pekosz from the Johns Hopkins University Bloomberg School of Public Health, according to Science magazine.

 

 

 

Image Credits: International Monetary Fund/Ernesto Benavides.

A COVID-19 outreach program in Karnataka state, India.

Despite a series of controversies, Bharat Biotech, which produces Indian homegrown vaccine Covaxin, hopes for World Health Organization (WHO) emergency use listing (EUL) soon, following last week’s publication of its promising Phase 3 results.

The vaccine was given emergency authorisation by the Indian government in early January – even before it had concluded a Phase 3 trial or published its Phase 2 results.  It has since been accused of irregularities during its Phase 3 trial and of being involved in a corrupt deal in Brazil.

However, Bharat finally published a preprint of its Phase 3 trial results via the BMJ’s reputable preprint service last week, which showed that Covaxin had 93.4% protection against severe COVID-19, and 65.2% protection against the Delta variant. 

The trial involved 25,798 people between the ages of 18 to 98 years in 25 sites across India. But trialists at the Bhopal site reported that they had been paid $10 to take part and some had been unable to read the consent form as they were illiterate, according to media reports. 

While these results still have to be peer-reviewed, the company is in the process of submitting “rolling data” to the WHO, according to the WHO EUL status report.

Over the weekend, Bharat company chairperson and managing director Dr Krishna Ella said that that the trial results had established India and developing world countries’ ability to “focus on innovation and novel product development”.

The Indian Council of Medical Research (ICMR) has worked with the company to develop the vaccine, and Balram Bhargava, ICMR Director and India’s Secretary of the Department of Health Research, welcomed the results.

Describing the trial as India’s largest COVID-19 Phase 3 clinical trial, Bhargava said that Covaxin “has consolidated the position of Indian academia and industry in the global arena”.

Corruption Allegations in Brazil

However, the company has also been embroiled in a corruption scandal in Brazil, which resulted in the suspension last week of a 20 million-dose order of the vaccine worth $324-million pending the outcome of investigations. The allegations of irregularities reach as high as President Jair Bolsanaro, according to Quartz.

The issue was raised by India’s opposition Congress Party last Friday, which accused the Modi government of being “conspicuously silent” about the deal with Brazil despite the fact that public money had been used to develop the vaccine.

“Taxpayers’ money was put into this and which is why we have a right to question: what has happened with that money and why is the government conspicuously silent on it?” according to Congress spokesperson Supriya Shrinate, who claimed that the ICMR was to get 5% from the sale of the vaccine.

Part of the Brazilian scandal centres on a company linked to Bharat, which is apparently tried to act as a ‘broker’, selling the vaccines on to the Brazilian government at the vastly inflated price of $15 per dose. This is more expensive than the Pfizer vaccine, which has WHO EUL.

A whistleblower in the Brazilian Health Department told a Senate panel that he was facing pressure from an aide of a close ally of Bolsonaro to sign a contract for the vaccines at a massively inflated price, according to the Guardian

Ministry head of imports Luis Ricardo Miranda, told the panel that he had not approved an import license for the vaccine because an invoice for the first shipment asking for upfront payment had been sent by a company not mentioned in the contract.

Wagner de Campos Rosário, of the federal office of the comptroller general, said in a press briefing reported by CNN Brasil last week that the deal had been suspended “as a simple preventive measure, since there are complaints that could not be explained well by the complainant”. He expected the investigation to take around 10 days.

However, both Bharat and Bolsonaro have denied wrongdoing.

Image Credits: Flickr – Trinity Care Foundation, Flickr – Trinity Care Foundation.

Antibiotics are commonly used in animals to boost their growth and keep them from picking up infections.

Their consensus was inevitable. As the 74th World Health Assembly (WHA) discussed a solution in May to contain the grave and growing threat of antimicrobial resistance (AMR), one mandate emerged: any action must take a multisectoral One Health approach to human, animal, and environmental health. 

Antibiotics are commonly used in animals – often without the input of veterinarians – to boost their growth and keep them from picking up infections. Estimates indicate that more than 70% of the antimicrobials sold globally are used in animals, and in some countries up to 80%, mostly for growth promotion. This indiscriminate antimicrobial use fuels resistance. 

Drug-resistant germs can cross over from animals to humans through direct contact with farm animals or through meat handling or consumption. Inappropriate antimicrobial use in animals is now recognized as a major contributor to drug resistance. 

Some 700,000 people already die due to antimicrobial resistance each year, and that may increase to millions per year if we don’t do more to stop inappropriate use of antibiotics. Meanwhile, rising incomes and growing urban populations throughout the world have increased the demand for meat, which means more livestock farming.

Many countries are eager to contain AMR. According to a WHA-related report, 144 countries now have a national action plan to do so. However, sectors differ in the amount of progress they’ve made. While there is general awareness and progress in the human health sector, work in the animal sector is lagging, and work in the environmental sector has only begun.

As the WHA affirmed, six years after it launched a Global Action Plan on AMR, we need collaborative, multisectoral coordination to address public health threats at the intersection of humans, animals, and the environment. It’s the only way to effectively address this widespread issue. 

The global health nonprofit I work for is supporting Global Health Security Agenda (GHSA) activities aimed at improving multisectoral coordination on AMR as part of the USAID Medicines, Technologies, and Pharmaceutical Services Program. We’ve worked in multiple countries, using WHO-recommended benchmarks to improve their capacity to detect, assess, report, and respond to public health events per International Health Regulations.

As my colleagues and I explained in a paper, “Strengthening multisectoral coordination on antimicrobial resistance: a landscape analysis of efforts in 11 countries,” it’s critical to help countries establish national multisectoral task forces and ensure that they function effectively. They must include high-level governmental officials and other stakeholders from both human and animal health, along with the agricultural, environmental, and food sectors.

Multi-sectoral Collaboration Needed to Tackle AMR

In some countries, these coordinating bodies lacked adequate political support and the authority to act. Ethiopia had weak coordination among its AMR stakeholders, no monitoring and evaluation capability to measure progress, no central reporting mechanism on AMR-related activities, and no functional technical working groups in line with One Health to actually implement activities against AMR. We convened national stakeholders to address these issues and improve overall functionality of the multisectoral coordination body on AMR and its technical working groups.

Countries need enabling environments such as administrative and financial support, adequate human resources, and practical know-how on the process and parameters of how these multi sectoral bodies operate. They also need ways to gather, analyze, and monitor data.

Support pays off: with our collaboration, the human, animal, agriculture, and environmental sectors in Cameroon collaborated on a plan to execute the country’s national action plan on AMR. Bangladesh and Kenya developed multisectoral monitoring and evaluation frameworks to track their action plans.

In Uganda, the Ministry of Agriculture, Animal Industry and Fisheries released its first-ever guidelines in February for antimicrobial use in animals.

Previous efforts by stakeholders to address AMR have largely been siloed. To get diverse sectors and disciplines to the table at the central level and to form mutual trust, frank discussions about why collaboration is critical, explaining the science, and finding common ground among sectors are needed.

The private sector has a stake in outcomes, too, especially as they relate to maintaining the effectiveness of medicines or protecting livestock.

Increasing drug resistance in E. coli, Salmonella, and other bacteria prompted Côte d’Ivoire to embark on an ambitious multi sectoral antimicrobial stewardship plan. Health and vet facilities began to monitor drug prescribing and  infection prevention and control procedures, while another committee looked into the sale of medicines without prescriptions and the sale of fake or substandard drugs. Greater attention to hygiene and prescribing also helped health facilities deal with the COVID-19 pandemic.

Every country needs the same inclusive approach. It is a big undertaking, and many lower-income countries are just beginning to achieve liftoff in implementing their national AMR plans. However, as we struggle to contain the COVID-19 pandemic, we cannot take our eyes off of the creeping global problem of AMR, which threatens to claim even more lives.

Dr Mohan P. Joshi

Mohan P. Joshi is a physician and senior principal technical advisor at the global health nonprofit Management Sciences for Health, where he is the technical lead for issues related to antimicrobial resistance and global health security.

Image Credits: Commons Wikimedia.

Gaston Browne, Prime Minister and Minister for Finance and Corporate Governance of Antigua and Barbuda, has called on wealthier countries to assist SIDS with a multitude of challenges, including on issues of climate change and COVID-19 vaccine sharing.

Small island states need more help to deal with the effects of climate change as well as the new challenges brought on by the COVID-19 pandemic, the first World Health Organization (WHO) Small Island Developing States (SIDS) Summit concluded this week.

Following a two day virtual SIDS Summit: For a healthy and resilient future in Small Island Developing States, heads of state, ministers of health, and other stakeholders released an outcome statement prioritising actions that would help them deal with the “acute and existential health and development threats” that they face.

The 25-point statement focuses on needed measures to battle COVID as well as other longstanding health threats, promote sustainable environments, as well as addressing the social and economic impacts of the pandemic – including the critical need to revive island state economies, often built around international tourism as well as trade.

The action plan also calls for more robust emergency preparedness, as well as healthy and sustainable food systems for the island nations beset by more extreme weather, rising sea levels, and related to that, the loss of beaches and mangroves rich in aquatic resources, cultivable land, as well as fresh water resources.

Addressing a WHO briefing on Friday to unpack the outcome statement, Gaston Browne, Prime Minister and Finance Minister of Antigua and Barbuda, said SIDS have been confronting climate challenges with limited resources, now exacerbated by the COVID pandemic.

“While we can list a few accomplishments, the world sometimes turns its back on us. This is happening perhaps a little too often and the pandemic is a typical example as to how the international community has failed to assist SIDS in equal ways…” said Browne.  

“This outcome statement requires action by all, and hinges on urgent interventions in addressing the unique vulnerability of SIDS and the inequalities that stand as obstacles to development.”

Vaccine Equity Paramount to Help Defeat the COVID-19 Pandemic

Browne took a swipe at the United States government which was recently asked to clarify whether sanctions against Cuba extend to collaborations on COVID-19 vaccine R&D – as the island nation develops two promising vaccine candidates, Abdala and Soberana 2. 

He applauded Cuba as a “small state that continues as a leader in healthcare and medicines”. Cuba, like many other SIDS, “are promoting the concept of universal health care with significant success despite the fiscal constraints,” he added.  

Browne also raised concerns about COVAX, the global vaccine-sharing facility, saying that small island states can’t get access: “Despite the good efforts of the COVAX facility, development partners are not doing enough,” he said. “Seems like we still have a problem with vaccine nationalization.”

“And that’s compounded by the fact that travel and trade have been curtailed, thereby inflicting red wounds on our economies. So, we now run the risk of disintegrating into what I consider to be economic sclerosis, eroding decades of hard won gains, and that should not be allowed to happen.Our tourism industry is all but at a standstill, said Brown, referring to the tourism trade which has long been a mainstay of many island states. 

“Our economies are shattered and there’s much anxiety among SIDS of the possibility of a protracted pandemic which means that we are left in lockstep with each other in global solidarity in order to effectively defeat this pandemic.”

The outcome statement notes that SIDS are vaccinating at lower rates than the global average and called on the G20 and others to share vaccine doses, testing equipment and other medical tools.

“The COVID-19 pandemic is not over. SIDS must not be left behind in the race to administer vaccines; support to date has been essential, but SIDS need wealthier countries to share more vaccine doses now ideally through COVAX,” reads the statement.

Less Words, More Action Backed by Financial Resources

WHO Director-General Dr Tedros Adhanom Ghebreyesus

WHO Director-General Dr Tedros Adhanom Ghebreyesus echoed Brown’s sentiments on countries working together on issues of climate change and further highlighted concerns around vaccine equity.

“Their (SIDS) very existence is at risk as (Brown) noted. The same is true for vaccine equity. In many respects many small island developing states have succeeded in preventing widespread transmission of COVID-19 in their communities.”

“We’re in a very dangerous period of this pandemic in those countries with low vaccination coverage, terrible scenes of hospitals overflowing are again becoming the norm, but no country on Earth is out of the woods yet,” said Dr Tedros.

He said the pandemic has “hit you hard in other ways”, in referring to declining revenues from tourism, significantly compounded by more transmissible variants like the Delta variant.

Tedros said “the time for lofty words is over” and called for “concerted action, backed by financial resources to mitigate the consequences of climate change, while we work to keep temperatures down and scale green innovations in terms of the small islands.”

SIDS Challenges to be Advocated at Global Meetings

The SIDS outcome statement also calls for:

  • SIDS health to be  addressed fully in the climate change movement – “One-Point-Five-to-Stay-Alive” – referring to the aspiration to keep average global temperatures below 1.5 C 
  • Healthy, sustainable and resilient food systems that focus on the preservation of biodiversity and deliver healthy diets are essential in SIDS;
  • Better access to COVID vaccines and others pandemic tools; and beyond the pandemic, support for fighting deepseated issues in maternal and child health, communicable and non-communicable diseases (NCDs);
  • More access to digital health technology and other tools for rapid data collection and analytic capacity; and
  • Access to development finance, including finance for the prevention and control of NCDs and climate change action.

Brown  however stressed the need for bolder action to achieve those objectives: 

“Recognizing the interconnectedness of human health and sustainable development requires tackling the social determinants of health while promoting economic resilience,” he said. 

With regards to COVID-19, the outcome statement also highlighted the impact the pandemic has had on mental health, including increased harmful use of alcohol, substance abuse, and gender-based violence, which increases needs for treatment services, social support and rehabilitation. 

To address these issues, the SIDS recommend the advancement of the updated Comprehensive Mental Health Action Plan 2013-2030 and expanded community-based mental health care.

The statement looks forward to upcoming global gatherings, including the UN Food Systems Summit, planned for September, the UN Framework Convention on Climate Change, Conference of Parties (COP26), in Glasgow 31 October-12 November,  and the Nutrition for Growth Summit, planned for December as venues where their agenda can be taken up more directly. Along with that, there is a planned SIDS high-level and ministerial meetings on NCDS in 2022 is another forum where countries will be able to advocate for more awareness and action. 

Image Credits: WHO.

India’s Stelis Biopharma manufacturing site, where the Russian Sputnik V vaccine will be produced

Despite the emergence of new WHO concerns over quality control at Sputnik V’s domestic production facilities, the Russian Direct Investment Fund (RDIF) is pushing ahead with a massive international “open-license” manufacturing effort for its Sputnik V vaccine – which breaks the traditional model of vaccine production and leverages existing capacity in poorer countries, desperate for doses.

As such, RDIF has “broken the model of closed intellectual property” and adopted a vaccine scale-up model that is “fundamentally different” to most vaccine developers, Leena Menghaney, Global IP Advisor for MSF’s Access Campaign, told Health Policy Watch in an interview.

But at the same time, a recent WHO review of manufacturing practices at one of the vaccine’s nine Russian plants identified a number of substandard manufacturing practices – illustrating how challenging quality control may be for the wider Russian model. 

The WHO review is not the only one to have found issues. 

Earlier this year, Brazil’s medicines regulator rejected Sputnik V’s request for approval, due to the contamination of some batches of the adenovirus vector, among other issues. 

Meanwhile, Slovakia’s regulator also has voiced concerns that the batches of Sputnik V it received did “not have the same characteristics and properties” as the version of Sputnik V reviewed in a Lancet study, which published favourable Phase III trial results for the vaccine earlier in February – with an efficacy of 91 % against symptomatic COVID-19 disease and 100% against severe COVID.

And the European Medicines Agency (EMA) has delayed Sputnik V’s approval following the RDIF’s failure to submit additional clinical trial data by a deadline that was initially set for early June.

At the same time, low- and middle-income countries, desperate for vaccines, have largely ignored such concerns. Since Russia’s own approval last August, almost seventy, mostly low- and middle-income countries have greenlighted the vaccine, which features a low price and easy storage requirements – and is even more attractive after India’s Serum Institute halted its AstraZeneca vaccine exports via the Global COVAX facility in March.

Even more significantly, a number of countries, including India, Serbia, Argentina, and Iran, have already begun their own mass production of Sputnik V vaccines. That includes half a dozen manufacturers in India, which are set to produce 65%-70% of Sputnik V’s global supply, or about 850 million doses or more a year, according to RDIF projections. 

Should those aims indeed be reached, the RDIF and its partners could potentially produce nearly 10% of the world’s total vaccines for 2021.


Non-Exclusive Deals With Multiple Manufacturers 

“The RDIF did what most vaccine developers and global health actors like the Bill and Melinda Gates Foundation should have done, which is to adopt a non-exclusive and open approach to vaccine manufacturing,” said Menghaney.

Instead of sealing exclusive licenses with a handful of manufacturers, the RDIF has shared its vaccine technology and know-how with some 27 manufacturers, predominantly based in India or upper middle income countries, according to the Geneva Graduate Institute’s COVID Vaccine Manufacturing Tracker.

That sets the RDIF apart from most other major pharma vaccine developers, which are primarily manufacturing, as well as distributing, vaccines in high-income countries – according to the Geneva Graduate Institute’s COVID Vaccine Manufacturing Tracker.

Pfizer and Moderna, for instance, have signed a total of 6 and 9 agreements, respectively, with manufacturers. All are based in high-income countries like France, Switzerland, or Germany – except for one deal between Pfizer/BioNTech and China’s Shanghai Fosun Pharmaceutical Group. Even Johnson & Johnson, which recently struck an expanded manufacturing deal with Aspen Pharmacare in South Africa, is primarily producing vaccines in the US and Europe.  And in the case of AstraZeneca, which has been the most aggressive in licensing production in low- or middle-income countries, including the Serum Institute of India, those licenses are exclusive.  

“The RDIF did not limit itself to one manufacturer,” added Menghaney. “If anyone wants [to produce] Sputnik V, they can go to RDIF and get it.”

The RDIF has sealed deals with manufacturers from upper middle income countries, in contrast to the rest of Western vaccine developers, which are primarily manufacturing, as well as distributing vaccines in high-income countries

Sharing Regulatory Dossiers within Countries

Another aspect of RDIF’s approach, also evidenced in India, has involved the sharing of the same vaccine “regulatory dossier” with multiple manufacturers. In India, those companies include: Dr. Reddy’s; Panacea Biotech; Stelis Pharma (Strides arm); Hetero; Gland Pharma; Virchow; and the Serum Institute of India, said Menghaney.

Sharing of dossiers is rarely done, due to trade secret and non-disclosure issues, Menghaney noted: “Instead of making manufacturers compete with each other, the RDIF encouraged them to produce the same common technical dossier and to work together to improve the yield of the vaccine.” 

The use of a common dossier not only hastened India’s regulatory approval of multiple new manufacturing facilities, but it has also allowed manufacturers to work together to optimise the yield of Sputnik V and to address quality control issues, such as contamination, which are common bottlenecks in the mass-production of adenovirus-based vaccines like Sputnik V. 

“The RDIF took a collaborative approach to manufacture the vaccine but also to scale it up,” said Menghaney, adding that no other company has adopted such a collaborative regulatory process for a COVID vaccine to date.

She contrasts that with AstraZeneca, which signed about a dozen exclusive deals with manufacturers, including the Republic of Korea and the Serum Institute of India, effectively blocking other manufacturers in the same country from bidding to produce the vaccine. 

The problems around such exclusivity, became more evident last spring, when the Serum Institute of India halted its exports of the AstraZeneca “Covishield” vaccine to over 100 low-income countries in Africa and elsewhere participating in the WHO co-sponsored COVAX vaccine facility after Indian COVID cases began to skyrocket. That, in turn, set off a domino effect, stalling vaccine campaigns that had only just begun in LMICs around the world, and leaving them more dependent than ever on vaccine donations from rich countries, or alternatively vaccines from China or Russia.

“The Serum Institute has an exclusive deal with AstraZeneca, and not just for India,” she said. “This probably means that these countries won’t be receiving any doses of the Oxford vaccine from other sources unless the agreement between AZ and SII is reviewed.”

The RDIF’s approach, she said, is all the more welcome to access advocates against the backdrop of still limited vaccine sharing pledges to the global COVAX facility and continuing reluctance by the big mRNA pharma firms, like Pfizer and Moderna to freely share their vaccine know-how.

RDIF Refuses To Reply On Manufacturing Quality Control Issues 

Despite that bright assessment, the preliminary WHO report, published last week, unearthed a number of concerning contamination issues at the Russian “Ufa Vitamin Plant” which manages the domestic Sputnik vaccine’s “fill and finish” process – where vaccine active ingredient is transformed into an injectible product.

WHO voiced six concerns with the plant, including: “integrity of data and test results”; potential “cross-contamination” of the batches; and poor hygiene standards. The report followed a WHO-led inspection between the 31st of May and the 4th of June. 

The Ufa Vitamin Plant asserted in a statement on June 23 that the WHO concerns were addressed “within 48 hours”. 

“Following the receipt of the comments from WHO, Ufa VITA responded to all the questions and concerns raised within 48 hours,” the firm announced last week. “We invite WHO for another inspection. We remain fully transparent and will continue with the WHO prequalification process.”

RDIF, however, has so far remained mum on the quality control issues raised by WHO – including non-response to queries by Health Policy Watch. 

And the WHO-reported concerns still remain outstanding, according to the public WHO dossier on the vaccine. 

WHO’s prequalification team flagged six concerns following its inspection of the Russian Ufa Vitamin Plant – a “fill-and-finish” facility

Sputnik V Approval Process: “Additional Data Required”

In response to a Health Policy Watch’s query, WHO declined to provide further clarifications, pointing only to its latest EUL update, dated 29 June, which continues to state, with respect to Sputnik V: 

“Additional data (Non-CLIN, CLIN, CMC) Required. Following up on inspection observations; Anticipated date [of approval] will be set once all data is submitted and followup of inspection observations completed.”

“Subject to certain requirements being met, WHO will continue to assess Sputnik V vaccines from different manufacturing sites and will publish decisions on their EUL status when all the data are available and the review is concluded,” WHO’s latest news update on Sputnik also stated.

Contamination Is a Common Concern 

Contamination is a common challenge faced by manufacturers of adenovirus-based vaccines, Ian Jones, Professor of Virology at the University of Reading in the UK, told Health Policy Watch. Potentially such contamination can make the adenovirus, which is supposed to remain non-infective, “replication-competent.” 

“The Sputnik V vaccine technology is basically just growing a virus,” he said. “However, it is not as trustworthy as the RNA as it is a biological, as opposed to chemical process. There are issues with yields, the risk of contamination and, for the adenovirus vectors [which deliver the vaccine], the need to measure the levels of ‘real’ adenovirus, a small amount of which is generated as part of the process. So, in many ways the older technology is a less good technology than mRNA technology.”

Ensuring high hygiene standards in all vaccine production facilities, including fill-and-finish facilities, remains “very important”, emphasized Jones, to avoid contamination of batches with other pathogens as well.

“High hygiene is very important in all such facilities to avoid bacterial contamination. The material will be injected, so passes the skin that normally acts as a barrier to pathogen entry,” he observed.

Contamination is a common issue in the scale-up of adenovirus-based vaccines

Pharma Manufacturers Say RDIF Issues Illustrate Challenges They Face 

Pharma leaders have repeatedly asserted that quality control issues, such as the ones identified by WHO at the RDIF plant, are illustrative of the challenges that they would face were they to issue open licenses as a means of scaling up vaccine production – as per the RDIF model.   

“It’s a very complex sector, with complicated science, very complicated manufacturing processes, we have to be very careful to whom we transfer the know-how, in particular because of the imperative of safety and quality,” said Bharat Biotech’s Executive Director of Quality Operations Sai Prasad, who is also President of the Developing Countries Vaccine Manufacturers’ Network (DCVMN), at an IFPMA-hosted webinar in late April. Bharat Biotech developed India’s first indigenous COVID vaccine – although that, too, has yet to gain WHO approval.  

“…. Don’t underestimate the requirements of standardized, manufacturing, quality control, and quality assurance,” Thomas Cueni, Director General of the International Federation of Pharmaceutical Producers (IFPMA), told Health Policy Watch in a recent interview.  

Stephane Bancel, CEO of Moderna

Speaking at an April 2021 event, Moderna’s Stephane Bancel noted that technology transfers are a “matter of trust – trust between the partners but also patient trust: 70% of vaccine manufacturing is about quality control and quality assurance.” 

“That is why we should not get lost into thinking that intellectual property is the bottleneck. The limiting step is manufacturing know-how and capacity, ability to find skilled workers who can take part in the complex manufacturing process, as well as the raw materials.”

“Basically companies have the responsibility for the quality of their products….Companies really need to have the ability to pick their partners on the basis of checklists, which is really about quality, quality, quality…”

RDIF’s Has Little To Lose from Open Approach 

The Sputnik V vaccine uses twenty-year-old adenovirus technology, which lacks substantial intellectual property protections

In fact, the RDIF has significant built-in incentives to try the open license approach – which western manufacturers may often lack, Knowledge Ecology International’s Director James Love told Health Policy Watch.

“The RDIF lacks significant manufacturing capacity, does not think it is protecting a highly proprietary manufacturing platform, and sees a political benefit if having its vaccine being used,” emphasized Love.

That is in contrast to companies such as Pfizer, Moderna, and other vaccine front runners, which already have significant manufacturing capacity – as well as novel technologies that they wish to protect, he said.  

And RDIF’s open license approach clearly has its limits as well. For example, the company has not shared its vaccine recipe to the WHO-backed COVID-19 Technology Access Pool (C-TAP), Love noted. Even though C-TAP was launched over a year ago, it remains empty to date of vaccine recipes from pharma developers in east or west, north or south.

The RDIF also has given no signal, to date, about whether it would join the WHO co-sponsored global COVAX facility should its vaccine finally be approved by the WHO.  

“I don’t think the RDIF has suddenly become cuddly and philanthropic,” added Jones. “They want the hard currency the sales will bring…I think they also want to demonstrate that they can be a world player in the vaccine business [to become] a more permanent global supplier.”

“Had they [Russia] invented a novel technology, it is not clear to me their current stance would have been taken.”

-Elaine Ruth Fletcher contributed to this story.

Image Credits: RDIF, Stelis BioSource, Wikimedia Commons.