banner-meds2.jpg

RUSSIAN COVID-19 VACCINES

*Research and text by Adrián Alonso Ruiz and Gurgen Tadevosyan; contributions and review by Suerie Moon, Marcela Vieira, Kaitlin Large, Yiqi Liu and Iulia Slovenski

Last Updated: 17 October 2022

KEY RESEARCH FINDINGS

Russian vaccines are primarily registered and manufactured in, and purchased by Upper-Middle Income and Lower-Middle Income Countries. Availability and access to these vaccines in Low-Income Countries seem limited.

Production and quality problems seem to have emerged in the scaling-up of Sputnik V, posing challenges in the development of a global manufacturing network and delaying vaccine deliveries.

Assessment of clinical trial results, information on vaccine deliveries, vaccine prices, and content of manufacturing and purchase agreements is challenging due to the lack of transparency.

The role of the public sector has been central in the development and financing of Russian COVID-19 vaccines. Academic research centers developed all of the Russian vaccines in this synthesis, and the Russian Direct Investment Fund (RDIF) (the State’s sovereign wealth fund) seems to have played an essential role in financing vaccine development and establishing the manufacturing network nationally and internationally.

RESEARCH GAPS

Although some patterns emerge in this synthesis, such as activities focused in Upper-Middle Income Countries (UMICs) and Lower-Middle Income Countries (LMICs), and in Eastern Europe & Central Asia, the Middle East & Northern Africa, Latin America & the Caribbean, and Eastern & Southern Africa regions, further research is needed to understand the drivers and the governance processes that directed these decisions.

A lack of transparency in regard to the status and conditions of  manufacturing and licensing agreements, vaccine pricing, and vaccine deliveries impede a more thorough analysis of the impact of Russian vaccines globally.

INTRODUCTION

This analysis aims to explore the regulatory approval status of vaccines produced in Russia, as well as the availability of data on clinical trials, manufacturing agreements, and access practices (purchases and donations). It employs the term ‘Russian vaccines’ to refer to vaccines developed by Russian entities.

The synthesis provides more information specifically about two of the vaccines developed in Russia: Sputnik V and Sputnik Light, as they have the widest presence globally. Other approved vaccines, such as EpiVacCorona and CoviVac, have a lower presence internationally and are not addressed in the same depth as the first two.

Three main resources were used for this synthesis: First, UNICEF’s COVID-19 Vaccine Market Dashboard was used to obtain data on regulatory approvals [1]. Second, the Global Health Centre’s (GHC) COVID-19 vaccine tracker was used to get data on vaccine manufacturing, purchase, and donation agreements [2]. GHC and UNICEF databases were compared to ensure that the analysis was done with the most comprehensive data. Third, data on clinical trials comes from McGill University’s COVID-19 Tracker [3]. Finally, when necessary, online searches were done to ensure that the information captured in this synthesis is as accurate as possible, given the data limitations and gaps. Data collection and cleaning was performed in April 2022. With regards to currency exchange and to ensure coherence, the rate used throughout the text is based on the historical data for January 1st, 2021.

SPUTNIK V

REGULATORY APPROVAL

Named after the first Soviet space satellite, Sputnik V is the first registered vaccine against COVID-19. It is a non-replicating viral vector-based vaccine, similar to Janssen’s Ad26.COV2.S, Oxford/AstraZeneca’s ChAdOx1, or CanSino’s Ad5-nCoV. However, it has a distinct feature, as it uses two types of adenoviruses (Ad26 and Ad5) as vectors – each dose of the vaccine consists of a different vector, whereas Janssen’s vaccine uses Ad26, CanSino’s uses Ad5, and Oxford’s uses Chimpanzee adenovirus Y25.

The vaccine was developed by the Gamaleya National Center of Epidemiology and Microbiology in Moscow (hereafter, “Gamaleya”) [4]. On August 11, 2020, the Russian Ministry of Health announced the vaccine’s registration on the State Register of Medical Products [5,6], becoming the first COVID-19 vaccine approved in the world. Outside of Russia, Sputnik V received regulatory approval first in Belarus, and by April 2022, the vaccine had received emergency or conditional use authorization in 69 countries and full licensure in seven countries[i] [7].

Sputnik V has been widely approved in Lower-Middle and Upper-Middle Income Countries (89.26% of all approvals). Eastern Europe and Central Asia (16 countries), Latin America and the Caribbean (15 countries), the Middle East and North Africa (14 countries), and Eastern and Southern Africa (8 countries) regions comprise 68.43% of the global approvals.

Table 1. Sputnik V registrations by region and number of countries

Table 1 - Sputnik V registrations by region and number of countries

The vaccine has not been submitted for approval to the US Food and Drug Administration (FDA). In Europe, the European Medicines Agency (EMA) communicated the start of the rolling review process in March 2021 [8], but press reports in July 2021 mentioned that Gamaleya failed to provide standard packages of regulatory and manufacturing data in time, leading to the suspension of the review process [9,10]. Despite this, two EU Member States, Hungary and Slovakia, granted emergency approval status to the vaccine [1].

Figure 1 - Distribution of Sputnik V's regulatory approvals (Emergency use and Licensure) per country's income level group

In February 2021, Gamaleya submitted an Expression of Interest (EOI) to start the Emergency Use Listing (EUL) process for Sputnik V. This procedure was created by the World Health Organization (WHO) to expand the availability of unlicensed vaccines in preparation for, or during Public Health Emergencies (PHE), based on a set of quality, safety, and efficacy data. UNICEF’sACT-Accelerator relies on the EUL process to purchase and distribute vaccines [11,12].

KP_figure_2.PNG

Figure 2 - Geographic distribution of Sputnik V's regulatory approvals

 

After the submission of the EOI, the process was put on hold during the summer of 2021 by WHO, after a series of inspections in Gamaleya’s  manufacturing facilities raised concerns about data integrity and test results, risk of cross-contamination, and sterility [13,14]. In October 2021, WHO restarted the review process, and as of May 2022, it was still awaiting the submission of Corrective and Preventive Actions to address the inspection’s observations [15,16].

CLINICAL TRIALS

As mentioned before, Sputnik V ​​combines two different types of human recombinant adenovirus-based vectors: adenovirus serotype 26 (Ad26) for its first dose and serotype 5 (Ad5) for the second dose. Each vector bears genetic fragments that encode the SARS-CoV-2 spike glycoprotein, which are the proteins that trigger the immune response.

 

An interim analysis of a Phase 3 trial of Sputnik V was published in The Lancet on February 2, 2021 [17]. According to the publication, Sputnik V showed a 91.6% efficacy against COVID-19. Although more results have been announced on Sputnik V’s webpage [18–20], no further studies have been published in peer-reviewed journals, raising concerns from experts regarding the transparency of safety results from clinical trials [21,22].

 

Overall, seventeen clinical Sputnik V trials have been tracked as of April 2022. Five Phase 1/2, six Phase 2, two Phase 2/3 and four Phase 3 trials took place. Trials took place in Russia (6), Argentina (4), UAE (2), Belarus (2), Azerbaijan, Belarus, India, and Venezuela [3].

Table 2. Number and geographical distribution of clinical trials.PNG

Table 2 - Number and geographical distribution of clinical trials

Source: https://covid19.trackvaccines.org/

 

VACCINE MANUFACTURING

In addition to Medgamal (the manufacturing branch of the Gamaleya Institute, with a claimed manufacturing capacity of sixty million units per year), Gamaleya and the Russian Direct Investment Fund (RDIF), expanded the national manufacturing capacity through agreements with six companies [23]. These companies were Binnopharm, R-Pharm, Biocad and Generium (with an alleged capacity of 120 million doses per year), Lekko (91 million per year), and Pharmstandart-UfaVITA (200 million per year) [23–25]. As of April 2022, no further centers have joined the manufacturing network.

In addition to this national network, RDIF and Gamaleya started developing a wide international network of manufacturing agreements. As of April 2022, the GHC database has tracked 37 manufacturing agreements with international partners to manufacture Sputnik V. The vast majority of these agreements are signed with companies based in Upper and Lower-Middle Income Countries (18 and 14 agreements respectively), with only five manufacturers based in High-Income Countries reported. Companies based in India (nine agreements), Eastern Europe & Central Asia (nine agreements), and East Asia & the Pacific (eight agreements) represent 69% of all agreements, followed by companies based in the Middle East & Northern Africa (five agreements), Latin America & the Caribbean (four agreements), and

Western Europe (two agreements).

KP_figure_3.PNG

Figure 3 - Number of manufacturing agreements by income level of manufacturer's country

Although the agreements are not publicly available, many are reported to include the full manufacturing process and longer-term collaborations that include the phased expansion of capacity from fill and finish, including technology transfer, biomaterials, knowledge, and regulatory dossiers [26].

The lack of publicly available information on manufacturing capacity estimates, contracted capacity, or the current status of some of the agreements, makes the analysis of this manufacturing network challenging. However, publicly available information seems to point to the emergence of technical difficulties when scaling up the production of the Ad5 vector for the second dose of the vaccine [27–29]. These problems could be linked to delays in vaccine deliveries to different countries and might have influenced the decision of launching Sputnik Light, the single-shot vaccine consisting of Sputnik V’s first dose [30,31].

Figure 4 - Geographic distribution of manufacturing agreements.

In addition, quality concerns related to the second vector of Sputnik V were raised by the Brazilian Regulatory Agency, ANVISA, after the detection of self-replicating Ad5 viruses in all of the batches received in April 2021 [32–34]. According to media reports, Slovak regulators also raised concerns regarding the quality of the vaccines delivered, as they found discrepancies between the specifications of the vaccines received and the ones published in clinical trials, such as different presentations and properties in batches from different manufacturers [35,36].

VACCINE ACCESS

The GHC’s most recent data notes that at least 52 countries (54 agreements) have announced publicly the purchase of Sputnik V doses. However, given the lack of publicly available data to track deliveries, the status of many purchase agreements remains unclear, especially given the technical problems associated with vaccine manufacturing and delays in deliveries mentioned before.

Consequently, this section analyzes the doses committed in the agreements, acknowledging that the number of doses delivered can differ substantially. Assessing the geographic scope and doses committed can offer a picture of Gamaleya’s original approach for Sputnik V.

Out of the 54 agreements tracked by the GHC (excluding eight agreements that were terminated and seven in which the finalization of the deal is unclear), 85.19% were reported to be signed with Lower- and Upper-Middle Income Countries, accounting for 98.79% of the total doses committed.

Table 3. Distribution of purchase agreements by country's income level. Source GHC.PNG

Table 3 - Distribution of purchase agreements by country's income level.

Source GHC

Countries from South Asia, Latin America and the Caribbean, the Middle East and North Africa, and Eastern Europe and Central Asia account collectively for 87.97% of the total Sputnik V doses committed. Of special interest is the case of India, who purchased 67.48% of the total doses in the South Asia region. Similarly, Iran and Egypt represent 91.94% of the doses in the Middle East and North Africa Region; and Turkey and Uzbekistan represent 51.55% of the doses in the Eastern Europe and Central Asia region.

Table 4. Distribution of doses committed by region.PNG

Table 4 - Distribution of doses committed by region

Source GHC

Countries from South Asia, Latin America and the Caribbean, the Middle East and North Africa, and Eastern Europe and Central Asia account collectively for 87.97% of the total Sputnik V doses committed. Of special interest is the case of India, who purchased 67.48% of the total doses in the South Asia region. Similarly, Iran and Egypt represent 91.94% of the doses in the Middle East and North Africa Region; and Turkey and Uzbekistan represent 51.55% of the doses in the Eastern Europe and Central Asia region.

Figure 5 - Geographic distribution of Sputnik V’s purchase agreements.

Note: given the state-ownership of Gamaleya, Russia is not highlighted as a purchaser country, although Russia is the primary market for Sputnik V vaccines.

In February 2021, Gamaleya offered 300 million doses to the African Union, but the agreement was never finalized due to pricing concerns, according to news reports [37,38]. Without this agreement, the regions of Eastern & Southern Africa and Western & Central Africa accounted for 2.94% of the total Sputnik V doses committed by Gamaleya. In other cases, such as in Italy, the purchase of the vaccine was conditional on the approval of the regulatory authority.

Regarding price, Sputnik V’s website announced that the vaccine would cost less than $10 USD per dose [39]. However, other publicly available sources show certain inconsistencies with this claim. For example, whereas there were announcements of a special $3 USD for Latin America, Argentina has reported two different prices ($9.95 USD and $12.61 USD), and public sources reported a price tag of $19 USD in Ghana. Table 4 provides a summary of the publicly available prices paid by different countries according to UNICEF and GHC.

Table 5. Sputnik V price per dose.PNG

Table 5 - Sputnik V's price per dose (based on publicly available information)

Apart from purchase agreements, donations have been another route to deliver Sputnik V vaccines. On a smaller scale compared to other vaccines, the GHC database tracks 1.08 million doses donated or announced to be donated to at least 24 countries. Following a similar pattern to the country approvals, manufacturing, and purchase agreements, the donations tracked focus on Lower- and Upper-Middle Income countries (98.42% of the total doses donated or committed to donate), with Eastern Europe and Central Asia as the main recipients of vaccines donated (55.31%), followed by Eastern and Southern Africa (26.03%).

Table 6.PNG

Table 6 - Doses of Sputnik V committed or donated by recipient region

Regarding vaccine donors, 55.81% of the doses were donated by Russia directly to another country, followed by Serbia (28.90%). Two Russian private companies, Alrosa and Rusal, have also donated doses (100,000 and 10,000 doses respectively).

R&D FINANCING

The GHC tracker has not captured any investments made to develop Sputnik V. However, RDIF seems to have played a key role in its development. According to the Fund’s Director, Kyril Dmitriev, the total investments are equal to approximately $ 295 million USD  September 2021, although it is not clear whether these investments were dedicated to research and development, manufacturing, or other aspects of Sputnik V’s production and development [40,41]. The media also reported that between April and June 2020, Gamaleya received $4.04 million USD from the Ministry of Health as part of an “experimental scientific development” [42]. The Moscow City Health Department and Sberbank seem to have contributed as funders to the vaccine’s R&D, as reported by Luganov et. al [43].

SPUTNIK LIGHT

REGULATORY APPROVAL

Sputnik Light is a single-dose vaccine consisting of the first dose of Sputnik V, therefore based on the “recombinant human adenovirus serotype number 26 (rAd26)” only [44]. It was registered in Russia on May 6, 2021, and since then it has been approved in 24 additional countries [6]. Following the same pattern as Sputnik V, 20 out of the 25 countries are Upper-Middle and Lower-Middle Income Countries, mostly in the Middle East and North Africa region (six registrations), Eastern Europe and Central Asia (six registrations), and East Asia and the Pacific (four registrations). In all countries where Sputnik Light has been approved, Sputnik V had also previously been approved.

Table 7.png

Table 7 - Sputnik Light registrations by region and number of countries

KP_figure_6.PNG

Figure 6 - Distribution of regulatory approvals (Emergency use and Licensure) of Sputnik Light per country's income level

Figure 7 - Geographic distribution of Sputnik Light registrations.

CLINICAL TRIALS

Although Gamaleya claims that Sputnik Light has an 80% efficacy against infection, we found no peer-reviewed publications with results of Phase 3 trials for Sputnik Light [44]. One Phase 1/2 study was published in The Lancet, indicating that Sputnik Light has a good safety profile and a good humoral and cellular immune response.

According to McGill University’s tracker, there have been five clinical trials conducted for Sputnik Light: two Phase 3 studies conducted in Russia and India, one Phase 2 study in Argentina, one Phase 1/2 study conducted in Russia, and another Phase 1/2 study with no location stated.

VACCINE MANUFACTURING

The GHC has tracked nine agreements that are specific to the manufacture of Sputnik Light. However, given that Sputnik Light consists of the first dose of Sputnik V, and the technical difficulties producing the second dose of the vaccine, there is the possibility that some manufacturers that were contracted as Sputnik V manufacturers turned to produce the single dose shot. In fact, there seems to be a total overlap between Sputnik V and Sputnik Light manufacturers, as all the companies manufacturing Sputnik Light were also included in the database as Sputnik V manufacturers.

VACCINE ACCESS

Sputnik Light’s purchase agreements have not been as widely announced as Sputnik V’s. The GHC database tracks ten agreements, adding up to 9 million doses. The geographic distribution follows the same pattern as Sputnik V, focusing on Upper- and Lower-Middle Income Countries (80.08% and 19.88% of the total doses purchased respectively) and one agreement with a High-Income Country (San Marino, which purchased 400,000 doses). 62.29% of the doses have been purchased by Venezuela alone, and some Eastern European and Central Asian countries (Belarus, Kazakhstan, and Uzbekistan) represent 14.55% of the doses purchased. Interestingly, India, which purchased 67.48% of the total Sputnik V doses in the South Asia region, has not purchased any Sputnik Light doses.

Regarding vaccine donations, the GHC has tracked donation announcements for 580,000 doses: 100,000 doses donated to Benin, 200,000 to the Kyrgyz Republic, 250,000 to Syria, and 30,000 to the Lao People’s Democratic Republic[ii].

COVIVAC

APPROVAL

CoviVac is an inactivated whole virion vaccine, developed by the Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products (hereafter, Chumakov Center). The center was established in 1955 in response to the growing concern over the spread of Polio in the USSR. In 1959, in collaboration with Albert Sabin, it became the first in the world to commence large-scale manufacturing of oral poliomyelitis vaccine from Sabin strains [45–47]. Its technology is similar to the ones used by Sinovac’s CoronaVac, Sinopharm’s BBIBP-CorV, Bharat Biotech’s Covaxin, and Valneva’s VLA2001 [48,49].

As of April 2022, the vaccine has been approved or has received emergency use listing only in Russia, Belarus, and Cambodia [1,50]. However, data on Phase 3 clinical trials is not available at the moment. McGill University’s tracker captures two clinical trials, one Phase 1/2 trial and one Phase 2, both in Russia.

MANUFACTURING​

Apart from the Chumakov Center (which has capacity to produce more than 20 million doses of the vaccine in 2022, according to media), two more producers are currently manufacturing or are performing trials to manufacture CoviVac [51]. These include Nanolek ( the capacity to produce 10 million doses of CoviVac per year according to news releases), and the Mechnikov Institute of Biotechnology in Nicaragua, which is a scientific institution created under the auspices of the Nicaragua-Russian collaboration [52].

ACCESS

Although sources claim that CoviVac has applied for regulatory approval in countries such as South Korea, there is no evidence to suggest that CoviVac has been approved or administered to the public outside of Russia and Belarus, where the Ministry of Health announced the reception of 300,000 doses in December 2021 [53,54].

R&D FUNDING

In a paper detailing the preclinical trials, the researchers at Chumakov Center declare the Ministry of Science and Higher Education of the Russian Federation as well as the Russian Foundation for Basic Research (RFBR) as main funders. The RFBR “is a self-governed state nonprofit organization in the form of a federal organization controlled by the Government of the Russian Federation” [55]. Although the RFBR does not indicate on its website any collaboration with the Chumakov Institute, the 2020 report of the RFBR highlights that they have granted 418 million Rubles to 109 COVID-19-related projects [56].

EPIVACCORONA

 

APPROVAL

 

EpiVacCorona is a Russian two-dose, peptide-based vaccine developed by the Vector State Research Center of Virology and Biotechnology. It contains chemically synthesized spike proteins that induce the immune response.

The State Register of Medical Products registered EpiVacCorona on October 13, 2020, and EpiVacCorona-N on August 26, 2021 [6]. According to the CEO of Vector, Rinat Maksyutov, the manufacturing techniques of EpiVacCorona had to be amended for large-scale production, which gave rise to EpiVacCorona-N [57]. Outside Russia, the vaccine was first authorized for emergency use in Turkmenistan and is currently authorized in Venezuela and Cambodia as well [58,59].

CLINICAL TRIALS

The three clinical trials tracked (one Phase 1/2 and two Phase 3 trials) have been performed in Russia. As with other vaccines in this synthesis, the results have not been published, but some media reports claim that the vaccine has a high potential to induce an immune response [60].

MANUFACTURING

The vaccine has been manufactured by Vector-BiAlgam, Geropharm, and the Vector Center [61]. Geropharm is the only fully private manufacturer of this vaccine, while the others are at least partially state-sponsored. According to Russian media sources, EpiVacCorona’s production has decreased since November 2021 and no further manufacturing is scheduled for 2022 [62].

MANUFACTURING ABROAD

There has also been evidence of a willingness to expand EpiVac Corona’s manufacturing capacity outside Russia. One of Brazil’s pharmaceutical companies, Uniao Quimica, announced an agreement to first import the vaccine and then transfer the technology from Russia [63]. Venezuela too expressed an intention to purchase and manufacture the vaccine locally [64]. While there is evidence of manufacturing agreements with these countries, it is unclear if the agreements have been realized and the manufacturing has commenced.

R&D FINANCING

There is limited availability of data to assess the costs of the vaccine. However, according to Russian media outlets, by Summer 2021 vaccine development cost were estimated in $47 million USD [65].

REFERENCES

Access the full list of references HERE

NOTES

[i] According to UNICEF Market Dashboard, as of October 1st, 2022, the situation remains the same.

[ii] The GHC Database does not capture doses delivered, but announcements of vaccine donations in media reports. In some cases, the announcement was made at the time of delivery.

 
 
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.