The study period for this research was divided into two. The first set of articles was searched between November 2020 and November 2021. An additional set of new articles was searched between December 2021 and December 2022 to obtain more recent information. Within this period, an electronic search of 13 reputable healthcare and public databases was conducted. These were Web of Science, Science Direct, EBSCO, SCOPUS, Directory of Open Access Journals, Public Library of Science, Digital Library of the Commons Repository, Education Resources Information Center, Pro-Quest, PubMed, EMBASE (Excerpta Medica Database), Cochrane Library, PubMed Central (PMC), and UpToDate.

The study also searched for articles from major healthcare hubs, such as the databases of the Johns Hopkins University, World Health Organization, John Snow Labs, Dateva – Health Data to Health Insights, Apixio, Decision Resources Group, Optum, The Economist Intelligence Unit, Refinaria de Dados, Virtusa vLife, Medisafe, and Advera Health Analytics. The authors defined distinct and hierarchical search cluster terms to query the databases, i.e., main topic, sub-topic, and specific theme. Each article was selected through a narrative search. The key search terms were “vaccine production, pharmaceutical production, essential drug production, active pharmaceutical ingredients, global vaccine production, BRICS vaccine production, pharmaceutical patent, pharmaceutical/vaccine export, and import.” The various search terms were combined with Boolean operators AND (to narrow the search results to include only key-termed results that contain the required keywords), OR (to expand the search results to contain at least one or more of the defined key terms and phrases), NOT (to limit the search results), Quotation Marks “”, (to limit the query the system to return in results in the exact order) and Parentheses (to give priority to results containing specific keywords over other elements around it). The search terms were entered individually in English.

We further employed truncations and wildcard characters to broaden the word search and improve the sensitivity and precision of searches. The authors did not discriminate between articles based on research design (primary/secondary research, qualitative/quantitative research, essay, dissertation, or experimental/non-experimental paper). The authors limited articles of interest to those published between January 2001 and December 2022. This was to make sure that more recent information about vaccine development in the BRICS was selected and analyzed to obtain robust conclusions. The initial searches from the designated databases yielded a total of 3,928 articles. Cross-checks supplemented these from their respective reference lists and additional searches on Google Scholar and other databases to widen the article range. Through this process, 705 additional articles were retrieved and added to the selection process.

Finally, the quality of the selected articles was evaluated using the time-tested Mixed Methods Appraisal Tool (MMAT), as presented in Table 1. Pluye and Hong (10) argue that the MMAT quality appraisal indices accommodate studies undertaken with different methodologies and strategies. This is particularly important in this integrative research composed of a mix of experimental, non-experimental, qualitative, quantitative, mixed, primary, and secondary research methods. When evaluating the quality of the selected articles using the MMAT, we mainly selected the following evaluation elements to test the quality of the articles: clarity of research questions; relevance of data sources; correlation of data analysis process; how the survey result relates to the background; clarity of sampling process; correlation of sampling techniques; representativeness of samples; risk of researcher bias; reasons for research objectives; full interpretation of the results; impact risk of the contributor. By introducing the rating of each standard in detail, we can better understand the quality of the included study (16).

We set strict criteria to include and exclude articles for final analysis. The first condition was that the article must be published in the English language. This condition is necessary because it makes it easier to cross-reference with other articles that have cited it and to verify the accuracy of the article’s citation. The second criterion was that the title and theme of the article should address the topic-specific issue of vaccine production in Brazil, Russia, India, China, and South Africa. Articles that focused on the domain area of pharmaceutical production or production of active pharmaceutical ingredients were also admitted if they focused on the BRICS or compared the global production trends where the BRICS countries were discussed. Thirdly, peer-reviewed articles were prioritized, and where the article did not meet this criterion, it should have been published by a recognizable healthcare authority such as the World Health Organization (WHO), International Health Research Institutions such as Johns Hopkins University, and Centres for Disease Control (CDC), etc. The author determined whether the articles were included for full-text analysis with the assistance of trained literature search specialists based on pre-determined eligibility criteria. Publications that were disputable were further validated through a snowballing of other relevant considerations and deliberations among the research team members until a consensus was reached to accept or reject its inclusion.

For the articles that met the requirements after screening through the above process, we further adopted the full-text analysis method for testing. We first evaluated the quantitative indicators in each article. These included the analysis of observed measurable data, representative graphs, projected graphs, production and sales volumes, production and sales values, ratios, export and import values, count of production facilities, number of vaccines administered within time frames, and other quantifiable information were extracted and compared through horizontal analysis and common size analysis. The qualitative details were removed and synthesized using a four-step content analysis procedure. The articles were initially scanned for conceptual thoughts and relevant perspectives on vaccine production and pharmaceutical self-sufficiency in the BRICS. These were extracted and coded inductively by the research team.

Overlapping concepts, thoughts, and perspectives across articles were included once. Thirdly, the qualitative data were then extracted into a matrix and rigorously checked to ensure the uniqueness of each item entered into the matrix. The matrix also helped to determine the relationship between the different thoughts and their source of origin to ensure that single-sourced information was not duplicated unnecessarily. Finally, the articles’ research design and methodological quality were assessed.

The selection flow of the reviewed articles is presented in Figure 1. In this diagram, the number of articles selected at each stage of the research process is illustrated using the integrative research steps in tandem with the PRISMA steps to ensure a robust data collection procedure.

The first step in the screening process was to remove duplicated studies through a two-step process. The articles were extracted to four citation managers, namely Endnotes, Mendeley, Zotero, and Sciwheel, simultaneously, to reconcile the count of articles in each citation. The authors and four well-trained senior researchers in library and archival reference management systems removed all duplicated articles. After screening the articles, the content of the four citation managers was manually inspected and compared in turn by all four teams to ensure the similarity of observed content. After this stage, 2,883 duplicated articles were removed from the dataset. The remaining 1750 articles qualified to enter the next phase of the selection criteria. After that, articles without titles and abstracts were further excluded, and the remaining 898 articles that met the qualification assessment criteria were evaluated for article quality.

The screening process was conducted using the COVIDENCE software. Two authors independently screened the abstracts, and articles with absolute consensus were passed on to the full-text screening or dropped. Where there was a conflict between the authors, a third author was assigned to review the article and to break the tie to either accept or reject the abstract. The full-text screening also involved two independent reviewers. Each read the full manuscript independently and determined whether they qualified to be included in the final articles to be extracted. Where there was no consensus, a third reviewer was assigned to review it and break the tie as to whether it should be included or excluded from the final count of articles for extraction.

The MMAT score of 14 papers was above 90%, and 2 articles obtained an MMAT score of 80%. Most of the articles received a score of 100% concerning the relevance of sources, the relevance of the data analysis process, the relevance of findings to context, and the clear description of the sampling process. The weaknesses of the articles that did not obtain a full score were surrounding the potential influence of the researcher and the funding agency’s role in the study.

The characteristics of the selected articles are presented in Table 2. Approximately 11% of the articles attributed the development of the BRICS vaccine industry to the innovation policies of these countries, which are rapidly achieving global self-sufficiency in drugs and vaccines. Stretsova and others all believe that the biotechnology and related patent policies of BRICS countries are important factors in promoting the innovation and development of the vaccine industry in these regions. Chattu et al. not only recognized this point but also proposed that the outbreak of COVID-19 has also objectively promoted the innovation of the BRICS vaccine industry. Wilston et al. believe that innovation support policies from the government play an important role. The publication dates of these articles range between 2014 and 2022. The second set of articles deals with general pharmaceutical production capabilities and competencies in the BRICS. Some of the articles also compare the BRICS with the global picture.

There are also articles that focus on Pharmaceutical Production. The dates of publication of the articles range between 2014 and 2022 and constitute 19% of the reviewed articles. Bond, P. and Garcia, A believe that the national change strategies of BRICS countries are reflected in the field of drug production. According to Ezziane Z, the production level of essential medicines in BRICS countries, namely basic drug research and development and production capacity, is also an important factor in determining the development of the vaccine industry. Lee and Rahalka, among others, focus on pharmaceutical research and development, arguing that it is vital to increase the number of national laboratories and address the challenges facing the biopharmaceutical industry. Yueqin makes an interesting observation that the study sees cooperation among BRICS countries as a driving force for innovation in their vaccine industries. Articles on the vaccine supply chain accounted for 15% of the total number of articles reviewed, with one article focusing on vaccine production and supply chains in the BRICS countries and elsewhere including the largest number of publications analyzed in this study. Approximately 33% of the articles examined vaccine production in BRICS countries and how BRICS countries have become self-sufficient in vaccines over the past decade from different perspectives, including COVID-19 response, vaccine business expansion, technology transfer, investment in vaccine development, and countries’ positions in the global vaccine market. By 2023, the focus of relevant research obviously shifted to health coordination among BRICS countries, and the number of articles in this part accounts for 22%.

These articles examine global vaccine production (including in the BRICS) before and during the COVID-19 pandemic and predictions beyond COVID-19. Approximately 38% of the articles used qualitative research methods, whereas 9% employed quantitative research methods. The remaining articles were conducted with a mixed methodology. Most of the studies were conducted based on the analysis of secondary data or a review of previous studies. This is a common practice in the healthcare sector, where official sources are trusted sources for official data. Approximately 66% of the studies were focused on the BRICS, whereas 34% had a global focus. Even though the settings of the studies were largely BRICS countries, the backgrounds of the authors widely varied across all continents.

The proportion of pre-qualified vaccines produced in a particular country is a perfect measure of vaccine self-sufficiency. This pre-qualification requires the new vaccines to thoroughly evaluate relevant data testing of samples and WHO-pertinent manufacturing inspection locations. If it is satisfied with the process, it declares a vaccine to meet the responsible WHO unit’s safety, quality, and efficacy standards. It also indicates that the vaccines meet the operation specifications for the packaging and presentation of United Nations institutions that want to procure vaccines. Table 3 shows the percentage of pre-qualified vaccines produced in the BRICS by 2013. This table shows that by 2012, pre-qualified vaccine production in the BRICS had picked up. At that point, the BRICS was home to nearly 40% of the global population. In 2020, the BRICS regions produced the highest number of pre-qualified vaccines worldwide. In 2020, 46 manufacturers of pre-qualified vaccines bought the World Health Organization, of which the BRICS regions are home to 17, and they represent 37% of the total manufacturing base of the global production of pre-qualified vaccines.

Figure 2 provides details of the ranking of top countries and regions in the vaccine production industry between 2017 and 2019, just before the COVID-19 pandemic. Together, these countries (regions) produce approximately 95% of global vaccines, and the EU bloc leads with an average production capacity of 15.65 million vaccines per annum. India closely follows this, with a production capacity of 14.7 million vaccines, alongside China, which was shown to have produced 10.05 million vaccines on average each year from 2017 to 2019. The United States produced approximately 4.85 million vaccines within the period, while Indonesia and the Russian Federation produced 1.65 million vaccines and 1.05 million vaccines, respectively. Japan and the Republic of Korea follow, respectively, with the production of 1 million vaccines and 0.95 million vaccines. Supposing the vaccine production capacity among the BRICS members is accumulated, it is revealed that the BRICS (China, India, and Russia) produced a total of 25.8 million vaccines, which is more than half of the countries that produce 95% of global vaccines.

Figure 3 presents the percentage locations of Active Pharmaceutical Ingredients Manufacturing Facilities for all drugs in the US healthcare market. Active Pharmaceutical Ingredients are important because they are the substances used in the production of finished pharmaceutical products with the intent of furnishing pharmacological activity or otherwise having a direct effect on the diagnosis, cure, mitigation, treatment, prevention, correcting, modifying, and restoring health in one form or another. Historically, the production of medicine for the US market has been done domestically, but this trend has changed, and major drug manufacturing companies have relocated their production hubs to other destinations for both business and practical reasons. This is particularly the case for active pharmaceutical ingredients. Again, the BRICS countries have been a significant contributor to the active manufacturing of pharmaceutical ingredients, as shown above. For example, while the EU manufactures 26% of active pharmaceutical ingredients consumed in the US, India ranks second with a percentage manufacturing rate of 18%. China (13%), Canada (2%), and the rest of the world (13%) follow in that order. This implies that the BRICS members represented in the chart (China and India) produce 31% of all Active Pharmaceutical Ingredients consumed in the US, which outperforms those produced in the north (America, USA, and Canada, 30%), the EU (26%), and the rest of the world (13%).

The number of registered patents is a test of the innovation capability of a country or a firm. In Figure 4, the top 10 patent registration industries in the health sector globally are presented. Medical technology, pharmaceuticals, and biotechnology patents are the fastest registered patents within the period. The top 10 countries registering these patents are shown in Figure 4. China and Russia are the only BRIC countries represented and account for nearly 25% of biotechnology patent registration, 35.7% of pharmaceutical patent registration, and 18.3% of medical technology. This information affirms that the geography of medical innovation is shifting, though moving toward emerging economies such as China, India, and Mexico.

Figure 5 shows the production and export of COVID-19 vaccines for respective countries and blocs. The analysis shows that as of October 2021, China alone has produced and exported more vaccines than the combined production of the US, the EU, and even India. If considered in a bloc, the contribution of the BRICS in this data (China and India) is far greater than the production and export of COVID-19 vaccines. This information further testifies to the vaccine production leadership of the BRICS.

The information in Figure 6 compares the number of vaccinated people among the BRICS (Brazil, Russia, India, China, and South Africa) countries against those in the European Union, United States, and G7. This helps determine vaccine self-sufficiency’s production and vaccination delivery capacity components. The figure shows that the BRICS countries together have vaccinated 1,717.49 million people as of December 2021, whereas the European Union vaccinated 306.65 million people within this period. Similarly, the United States has vaccinated 202.65 million people, just as the G7 together had vaccinated 456.72 million people by the end of December 2019. In each case, most of the vaccines produced in the BRICS were home-based as opposed to those in the European Union, but generally, the information affirms the fact that the BRICS countries do not just have the production capacity, they also have a well-established vaccine distribution network that commensurates with the needs and challenges created by COVID-19.

In Figure 7, the largest global exporters in the pharmaceutical industry are presented in terms of value and volume. The EU exports 27.44% of global vaccine needs, accounting for 27.60% of global pharmaceutical export value. India exports 24.65% of the global volume of pharmaceutical exports, representing 22.47% of the pharmaceutical export value. The other representative of the BRICS in this analysis is China, responsible for 1.93% of global pharmaceutical exports. Together, the BRICS countries are only accountable for approximately 24.64% of global vaccine exports but receive only 2.08% of their value.

Ezziane (21) traced the history of vaccine production in BRICS countries, claiming that vaccine self-sufficiency in BRICS countries does not have a long history, but considerable progress has been made over the past 20 years. According to Allen (25), this change is due to the fact that the BRICS countries have been extremely brave in changing themselves in order to promote self-sufficiency in vaccines and drugs. Zhou (42) revealed that the need to achieve vaccine self-sufficiency in BRICS countries was planned and implemented through public-private partnerships at the level of individual countries and inter-group cooperation. The public sector invests heavily in innovation by creating the conditions for innovation for proactive pharmaceutical entrepreneurs and large corporations.

This cooperation between the state and the private sector has helped individual countries to develop pharmaceutical entrepreneurs and companies willing to accept and introduce new pharmaceutical products and services through the innovation process and investment in research and development (6). Small pharmaceutical companies in the BRICS countries, in particular, have seen particularly significant growth by transferring ideas and inspiration from their contacts with the global pharmaceutical industry to investing in new technologies, supporting innovative practices, stimulating creative ideas, stimulating novelty, and persisting in experimentation to bring about new drug opportunities and new solutions to existing and new health challenges (28).

In some cases, BRICS governments have preferential purchase policies for domestic manufacturers and occasionally threaten compulsory licensing of medicines deemed essential for public health (33). These market and benchmark scientific risks for developing innovative health products in BRICS countries slow the rate at which large pharmaceutical companies make significant investments to push early-stage compounds through clinical trials and roll-out (43).

The application of artificial intelligence to pharmaceutical products is one of the key factors that have grounded pharmaceutical production capability in the BRICS. Since 2005, several countries, including China, India, and Russia, have invested heavily in artificial intelligence and machine learning techniques to accelerate drug discovery (23). Both startups and large-scale pharmaceutical enterprises were encouraged to adopt AI-assisted automation, an optimization process for drug manufacturing, and marketing design to AI algorithms, which allow pharmaceutical companies in the BRICS to identify and recruit patients for clinical trials faster and more efficiently, which is a key step in the drug discovery and development process (29).

The growth of drug data analysis has also created pharmaceutical startups in China, India, and, in particular, Russia to analyze small and noisy data sets using different machine learning techniques (active learning, small amount learning, reinforcement learning, presentation learning), as well as deep learning solutions to predict and optimize potential drug candidates (24). This further eliminates the need for large data sets. As a result, AI technology simplifies and shortens the identification and eligibility criteria for clinical trials for vaccine production. The recruitment process for clinical trials has become faster, more rigorous, and less expensive, reducing lead time to the administration process without compromising on quality (34).

Another crucial innovative capability in the BRICS that supports the drive for vaccine and pharmaceutical self-sufficiency is the application of Big Data and Analytics in the drug development process. Several modeling companies have emerged in the BRICS to take advantage of the volume of data generated during the drug discovery and development process (44). For example, between 2010 and 2020, 27 companies were registered in China and India to properly analyze data and derive value from drug manufacturing processes with high-performance systems to support new and existing drug manufacturing companies (45).

Through state-negotiated deals, pharmaceutical companies opened up their critical data to third parties with capabilities in advanced analytical techniques. This has turned historical and real-time data hitherto unused, underused, abused, or misused in the drug delivery process into critical competitive descriptive diagnostic, predictive, and predictive weapons for analyzing the collection of all medical data (patient records, hospital data, and medical imaging) to speed up and eliminate inefficiencies in drug development (6).

The third source of innovation that has transformed the vaccine and pharmaceutical industry in the BRICS is the development of innovative solutions for flexible pharmaceutical production (46). From 2005, several BRICS countries began exploring new pharmaceutical manufacturing strategies like batches of precision medicine in response to changing market dynamics. Some IT companies emerged to offer single-use technology to eliminate complex steps, such as cleaning and validation between stages of production to reduce downtime and increase production (27).

Another innovative technology introduced into the drug manufacturing processes in the BRICS is continuous manufacturing optimization technologies (26, 30, 47). For example, microfluidic droplet generators are emerging Microstructured elements that optimize and tailor the drug manufacturing process equipment down to an ideal scale. This technology improves and speeds up the intensified core pharmaceutical processes, such as crystallization, pervaporation, micro-encapsulation, and chemical synthesis (22).

Precision medicine is one area that has also been enhanced in the quest to achieve vaccine and pharmaceutical self-sufficiency through efficient drug manufacturing practices in the BRICS. The concept of precision medicine helps to develop customized drugs to treat patients with unique pharmaceutical needs (32, 48). With advanced Omic studies and data analysis, new insights can be captured to better understand how an individual’s body reacts and responds to drugs. This is particularly helpful in additive manufacturing, which depends on drug exposure models to determine the pharmacodynamic and pharmacokinetic properties of drugs (49).

This further helps to settle on the accurate drug dosage for different clinical parameters such as age, gender, and comorbidities, as well as make real-time predictions on drug efficacy and interaction in specific individuals and groups of people, etc. This innovative capability is currently being explored to develop drug-specific exposure models for alternative vaccine formulas to cure COVID-19, which is currently being investigated in laboratories in BRIC countries (50). The innovative capacity of additive manufacturing is another important area that BRICS countries are exploring to achieve vaccine self-sufficiency (12).

Since 2017, Chinese, Indian, and Russian pharmaceutical entrepreneurs have made a breakthrough in precision medicine research to launch advanced 3D bioprinters for printing tissues or cells. This initiative is critical in the drug development process, regenerative medicine, and organ engineering. This technology can facilitate the development of precision bills and medical formulations that depend on age and physiology (51). With these bio-printers, innovations in tissue engineering, bio-inks, and microfluidics can be scaled up.

These technologies are capable of making tissues have the desired structure and feature with a good cell survival rate, which was a major limitation in previous techniques used in testing new pharmaceutical products (50). Through electro-hydrodynamic printing techniques, new 3D bioprinters help deliver higher cell survival rates and tissues with micro and nano-scale features (12, 51–56). Thus, through pharmaceutical innovation, the BRICS countries have asserted their autonomy, boosting the quest for self-sufficiency (55).

Yueqin (56) explains that rejuvenated state support continues to play a significant role in the accelerated growth of the pharmaceutical manufacturing market in the BRICS. Aware of the changing dynamics of human society, each member of the bloc has developed and launched a national pharmaceutical innovation strategic plan to encourage innovation in the sector by the private sector (31). Most often, these strategies have arisen due to consistent, open, and frank public-private dialog and partnership. Despite the differences (timetable) in the depth and breadth of these policies, obvious similarities suggest that policymakers across the bloc have been learning from each other (36). Drug innovation at the 6th BRICS Summit (Brazil, 2014) was discussed and prioritized as a key feature of the drive for vaccine self-sufficiency (20, 37–40). At the summit, the unified geopolitical bloc discussed a mechanism to consciously leverage a new set of ideas, products, and values to capture the attention of the global health community (57). The parties agreed to challenge the status quo and lay the foundation for the systematic design of a range of innovative capabilities and opportunities for pharmaceutical companies and individuals to flourish through new market niches and product designs (38).

In addition, national regulatory authorities in these countries have been equipped with new technologies and experts to strengthen the vitality of national regulatory systems to monitor the production of more accurate drugs and vaccines, especially in China and India. For example, in 2011, the WHO successfully evaluated national regulatory authorities for vaccine clinical trials and certified them (5, 58). Recently, with the exception of South Africa, four regulatory authorities in BRICS countries have revised their regulatory functions to ensure compliance with WHO-prequalified vaccine targets. This assessment has facilitated the acceptance of many drugs produced in China on the international market and helped the development of the vaccine industry.