Résumé

Le Brésil, la Fédération de Russie, l'Inde, la Chine et l'Afrique du Sud – les pays connus sous le nom de BRICS – ont fait des progrès considérables dans la production, la régulation et le développement des vaccins au cours des 20 dernières années. En 1993, les cinq pays fabriquaient des vaccins, mais les procédés utilisés étaient dépassés et non normalisés. Par ailleurs, peu de recherches pertinentes étaient menées et les produits ne recevaient qu'une reconnaissance internationale négligeable. En 2014, les cinq pays avaient pris des initiatives importantes en matière de développement technologique de vaccins et avaient largement amélioré leur capacité de régulation nationale. L'Afrique du Sud était alors le seul pays du groupe BRICS à ne pas produire complètement des vaccins. L'Afrique du Sud a maintenant amorcé le processus pour relancer sa production de vaccins et pour dépasser l'étape de la simple importation, formulation et conditionnement des vaccins en vrac. On a analysé les variations de prix du secteur public par dose des vaccins sélectionnés, la part du marché mondial représentée par les produits provenant de fabricants spécifiques et l'attractivité des opportunités de partenariat et d'investissement pour les multinationales dans les entreprises du groupe BRICS. Les résultats montrent que les pays du groupe BRICS ont eu un impact majeur sur le prix et la disponibilité des vaccins, et cet impact est attribuable, en grande partie, à la production des fabricants indiens de vaccins. La Chine devrait bientôt avoir un plus grand impact compte tenu du développement attendu des fabricants chinois de vaccins dans un avenir proche. Les réalisations du groupe BRICS dans le domaine du développement de vaccins devraient remodeler le marché mondial des vaccins et accélérer l'accès aux vaccins dans les pays en développement. Le défi est maintenant de transformer ces attentes en actions stratégiques et en résultats concrets.

Resumen

Brasil, la Federación de Rusia, India, China y Sudáfrica, los países conocidos como BRICS, han hecho progresos considerables en la producción, regulación y desarrollo de vacunas en los últimos 20 años. En 1993, los cinco países ya producían vacunas, pero los procesos empleados para ello estaban anticuados y sin normalizar, había poca investigación relevante y un reconocimiento internacional mínimo de sus productos. En 2014, los cinco países contaban con iniciativas sólidas para el desarrollo de la tecnología relacionada con las vacunas y habían mejorado en gran medida su capacidad normativa nacional. Sudáfrica fue el único de los BRICS que no fabricaba vacunas en su totalidad. En la actualidad, dicho país se encuentra en proceso de restablecer su propia producción de vacunas e ir más allá de la simple importación, formulación y llenado de lotes de vacunas. Se han analizado los cambios en los precios por dosis de vacunas seleccionadas del sector público, la cuota de mercado mundial de productos de fabricantes específicos y el atractivo para las empresas multinacionales de la asociación y las oportunidades de inversión en empresas de los BRICS. Los resultados indican que los países BRICS han tenido un gran impacto en el precio y la disponibilidad de las vacunas, y que una gran parte de ese impacto se puede atribuir a la producción de vacunas de los fabricantes de India. Se confía en que China tenga pronto un impacto mayor, dada la evolución prevista de los fabricantes de vacunas chinos en el futuro cercano. Se espera que los logros de los BRICS en el campo del desarrollo de vacunas remodelen el mercado mundial de las vacunas y aceleren el acceso a las mismas en el mundo en desarrollo. El desafío consiste en convertir estas expectativas en actuaciones estratégicas y resultados prácticos.

ملخص

أحرزت البرازيل والاتحاد الروسي والهند والصين وجنوب أفريقيا – البلدان المعروفة بتجمع "بريك" (BRICS) – تقدماً كبيراً في إنتاج اللقاحات وتنظيمها واستحداثها على مدار العشرين سنة المنصرمة. وفي عام 1993، كانت جميع البلدان الخمس تنتج اللقاحات ولكن العمليات المستخدمة قد عفا عليها الزمن وغير موحدة المعايير، ولم تكن هناك سوى بضعة أبحاث ذات صلة، وكان الاعتراف الدولي بالمنتجات ضئيلاً جداً. وبحلول عام 2014، أطلقت جميع البلدان الخمس مبادرات قوية لاستحداث تكنولوجيا لقاحات وقامت بتحسين قدراتها التنظيمية على الصعيد الوطني. وكانت جنوب أفريقيا في هذا الوقت البلد الوحيد في تجمع "بريك" الذي لم يكن ينتج اللقاحات بشكل كامل. وتقوم جنوب أفريقيا الآن بإعادة تأسيس إنتاج اللقاحات الخاصة بها وتجاوز مرحلة استيراد اللقاحات السائبة وتركيبها وتعبئتها. وتم تحليل التغيرات في سعر القطاع العام للجرعة بالنسبة للقاحات المحددة وحصة السوق العالمي ممثلة بالمنتجات من جهات تصنيع معينة وجاذبية فرص الشراكة والاستثمار، للشركات متعددة الجنسيات، في شركات تجمع "بريك". وتشير النتائج إلى تحقيق بلدان تجمع "بريك" لأثر كبير على سعر اللقاحات وتوافرها، ويعزى معظم هذا الأثر إلى حصائل مصنعي اللقاحات في الهند. ويتوقع أن يكون للصين قريباً أثر كبير، نظراً للتطوير المتوقع لمصنعي اللقاحات في الصين في المستقبل القريب. ويتوقع أن تؤدي إنجازات تجمع "بريك" في مجال استحداث اللقاحات إلى إعادة تشكيل سوق اللقاحات العالمي وتسريع الوصول إلى اللقاحات في العالم النامي. ويتمثل التحدي في تحويل هذه التوقعات إلى إجراءات استراتيجية وحصائل عملية.

摘要

在过去20多年中，被称为金砖五国（BRICS）的巴西、俄罗斯联邦、印度、中国和南非在疫苗生产、管制和开发方面取得相当大的发展。1993年，五国都在生产疫苗，但使用的是过时和非标准化的流程，几乎没有相关的研究，产品的国际认可也微乎其微。到2014年，所有五个国家都有开发疫苗技术的强有力行动方案出台，并极大地提高其国家监管能力。这样就只有南非一个不完整生产疫苗的金砖国家。南非正在重建自身的疫苗生产，已经不再止步于仅仅是散装疫苗进口、配苗和分装的阶段。本文分析了公共部门每剂选定疫苗的价格、以具体厂商产品为代表的全球市场份额、金砖国家公司合作和投资机会对跨国公司的吸引力等所有方面的变化。结果表明，金砖国家已经对疫苗价格和可用来源产生重大影响，其中大部分影响归因于印度疫苗生产商的产量。鉴于中国疫苗制造商在不久将来的预期发展，预计中国将很快产生更大的影响。金砖国家在疫苗开发领域的成绩可望重塑全球疫苗市场，加快发展中国家对疫苗的获得速度。而面临的挑战是把这些期望转变成战略行动和实际的结果。

Резюме

Бразилия, Российская Федерация, Индия, Китай и Южная Африка — страны, известные как БРИКС, — добились значительных успехов в производстве, регулировании качества и разработке вакцин за последние 20 лет. В 1993 году все пять стран занимались производством вакцин, однако используемые процессы были устаревшими и нестандартизированными, с малым объемом соответствующих исследований и незначительным международным признанием продукции. К 2014 году все пять стран значительно продвинулись в разработке технологий для производства вакцин и значительно улучшили свои национальные системы регулирования данной отрасли. К этому времени Южная Африка являлась единственной страной БРИКС, которая еще не имела полноценного производства вакцин. В настоящее время Южная Африка находится в процессе восстановления собственного производства вакцин и перехода от простого импорта, составления рецептур и расфасовки вакцин. Были проанализированы изменения в ценах государственных закупок на дозу отдельных вакцин, доля мирового рынка, представленная продукцией отдельных производителей, и привлекательность партнерства и инвестиций в компании стран БРИКС для транснациональных компаний. Результаты показывают, что страны БРИКС оказали существенное влияние на цены и доступность вакцин на рынке, причем в основном это относится к продукции индийских производителей вакцин. Ожидается, что Китай также будет наращивать свое влияние, учитывая ожидаемое развитие китайских производителей вакцин в ближайшем будущем. Ожидается, что достижения стран БРИКС в области разработки вакцин приведут к изменению мирового рынка вакцин и ускорению доступа к вакцинам в развивающихся странах. Задача состоит в том, чтобы воплотить эти ожидания в стратегические действия и практические результаты.

Introduction

Through their vaccine manufacturers, Brazil, the Russian Federation, India, China and South Africa have a substantial and increasing role in the global vaccine market. Together, these countries known as BRICS are increasing the production capacity for vaccines with a high global demand and vaccines that are required specifically in the developing world. BRICS are also generally replacing multinational corporations as sources of traditional vaccines – i.e. the five vaccines originally included in the World Health Organization’s (WHO) Expanded Programme on Immunization¹1 State of the world’s vaccines and immunization. 3rd ed. Geneva: World Health Organization; 2009. – and enhancing competition and lowering prices in the United Nations’ and national vaccine markets.

In this paper, we analyse the growth of vaccine production, vaccine regulation and development in BRICS over the past 20 years. We evaluate the impact of that growth on the global vaccine market, by comparing vaccine production in each of the five countries in 1993 and 2013, analysing the relevant technology sources and collaborations, following the evolution of national regulatory authorities, and determining temporal trends in the numbers of vaccines prequalified by the WHO that were produced. We also identify some of the current limitations of BRICS’ vaccine-related strategies and explore ways in which the international community might help reduce those limitations.

BRICS’ role in the global vaccine market

The vaccines needed for the Expanded Programme on Immunization¹1 State of the world’s vaccines and immunization. 3rd ed. Geneva: World Health Organization; 2009. and the subsequent national immunization programmes were initially sourced from both national and international manufacturers. Recombinant hepatitis B and Haemophilus influenzae type b vaccines became available in the 1980s but their production was felt too complex for many vaccine manufacturers. Three major developments subsequently influenced the global vaccine market. One was the introduction, in 2001, of highly profitable products such as the conjugate pneumococcal vaccine, which produced profits measured in billions of United States dollars (US$).²2 With US backing Prevnar 13 aims for blockbuster status [Internet]. London: EP Vantage; 2010. Available from: https://www.epvantage.com/Universal/View.aspx?type=Story&id=207307&isEPVantage=yes [cited 2013 Nov 15].
https://www.epvantage.com/Universal/View... The second major development was the growth of funding initiatives to introduce new vaccines nearly simultaneously throughout the developing world.³3 Muraskin W. The Global Alliance for Vaccines and Immunization: is it a new model for effective public–private cooperation in international public health? Am J Public Health. 2004;94(11):1922–5. doi: http://dx.doi.org/10.2105/AJPH.94.11.1922 PMID: 15514228
https://doi.org/10.2105/AJPH.94.11.1922... The third major development was the emphasis placed on quality control and assurance standards for all vaccines used worldwide. This emphasis was mainly the result of the establishment of WHO’s programme of vaccine prequalification in 1987⁴4 A system for the prequalification of vaccines for UN supply [Internet]. Geneva: World Health Organization; 2013. Available from: http://www.who.int/immunization_standards/vaccine_quality/pq_system/en/index.html [cited 2013 Nov 15].
http://www.who.int/immunization_standard... and that programme’s collaboration with large vaccine procurement agencies such as the Supply Division of the United Nations Children’s Fund (UNICEF) and the Revolving Fund of the Pan American Health Organization (PAHO). Vaccine production has become a research-based global business with high industrial standards for quality and the potential for substantial profits. In the early days of the Expanded Programme on Immunization, the prices of the traditional vaccines used in the developing world were low because multinational corporations could produce the vaccines using existing capacity that the corporations did not need to supply their more usual, higher-priced markets. As new more-profitable vaccines became available, however, most of the multinational corporations stopped producing the older vaccines. Fortunately, the growth of vaccine manufacturing in some of the BRICS countries has helped to keep the prices of traditional vaccines relatively low.

Vaccine manufacturers and markets in emerging economies

Some manufacturers in low- and middle-income countries have been included in WHO’s vaccine prequalification programme since the programme was established. Examples include the Pasteur Institute of Senegal and some manufacturers in the formerly communist states of central and eastern Europe – represented by the Canada-based buying group, Conpharma. By 2007, nearly 50% of the manufacturers of prequalified vaccines were based in emerging economies.⁵5 Milstien J, Costa A, Jadhav S, Dhere R. Reaching international GMP standards for vaccine production: challenges for developing countries. Expert Rev Vaccines. 2009;8(5):559–66. doi: http://dx.doi.org/10.1586/erv.09.23 PMID: 19397413
https://doi.org/10.1586/erv.09.23... Around that time, such economies also became key importers of new vaccines.⁶6 Worldwide major vaccine manufacturers in figures. Brussels: European Vaccine Manufacturers Association; 2004. Available from: http://www.vaccineseurope.eu/wp-content/uploads/2012/12/Worldwide-Major-Vaccine-Manufacturers-in-Figures-2004.pdf [cited 2013 Nov 15].
http://www.vaccineseurope.eu/wp-content/...

Special characteristics of BRICS

In the early 1990s, the Children’s Vaccine Initiative performed assessments in countries that could possibly play an enhanced role in vaccine supply. All five BRICS countries were included in these assessments. Recently, the BRICS group has attracted increasing attention as a market and development force – and not just for vaccines.⁷7 Harmer A, Xiao Y, Missoni E, Tediosi F. ‘BRICS without straw’? A systematic literature review of newly emerging economies’ influence in global health. Global Health. 2013;9(1):15–26. doi: http://dx.doi.org/10.1186/1744-8603-9-15 PMID: 23587342
https://doi.org/10.1186/1744-8603-9-15...

The main functional areas of vaccine development and supply comprise clinical studies and vaccine research, development, regulation and production. Four of the BRICS countries are undertaking all of these activities and the exception – South Africa – is engaged in all but production.

Vaccine production

We examined vaccine production in each of the BRICS countries between 1993 and 2013. There are no data available on the general quality of the vaccines produced in 1993 (Table 1), although a measles vaccine produced by the Serum Institute of India was prequalified by WHO. In 1995, yellow fever vaccines produced in Brazil and the Russian Federation came from laboratories that were approved by WHO for the production of such vaccines.⁸8 WHO Expert Committee on Biological Standardization. Laboratories approved by WHO for the production of yellow fever vaccine. Annex 1 (discontinued) [Technical Report Series No. 872]. Geneva: World Health Organization; 1998.

Table 2 tracks the development and production of WHO-prequalified vaccines by the BRICS countries between 1986 and 2013. The number of prequalified products from manufacturers in BRICS – and other emerging economies – has increased over the last two decades but appears to have levelled off in recent years.

Over our study period, vaccines from manufacturers in BRICS represented a major proportion of the purchases made via the UNICEF Supply Division (Table 3) and the PAHO Revolving Fund (Table 4) from manufacturers in low- and middle-income countries – in terms of both volume and value. In 2012, just four Indian manufacturers supplied over 95% of the vaccines bought from manufactures in BRICS by the Revolving Fund – again in terms of both volume and value.

The share of vaccines purchased via PAHO and UNICEF from vaccine manufacturers in low- and middle-income countries decreased after 2005, probably as the result of the introduction of new vaccines. For PAHO, for example, this share fell from 56.42% of vaccine doses in 2005 to 31.27% in 2010. Although the general trend in the size of this share has been downwards, peaks have occurred when vaccine manufacturers in low- and middle-income countries have supplied vaccines needed for particular mass vaccination campaigns. There is also some evidence to suggest that the share of vaccines purchased via PAHO and UNICEF from vaccine manufacturers in low- and middle-income countries began to increase after 2010.

By 2013, manufacturers in BRICS were producing many types of vaccines (Table 5). Although most of the vaccines might be considered traditional, some were more innovative products, such as a meningococcal type A conjugate vaccine and a genetically engineered Japanese encephalitis vaccine from India and a live attenuated Japanese encephalitis vaccine from China. A novel cholera vaccine manufactured by Shantha Biotechnics in India was created using technology that was developed in Sweden before being transferred – by the International Vaccine Institute – to Viet Nam and then to India. Although not WHO-prequalified, the world’s first hepatitis E vaccine – a recombinant Escherichia coli-based virus-like particle vaccine – was recently launched in China.

Vaccine innovation

For each of the BRICS countries, we investigated vaccine products in the pipeline and the partnerships for vaccine innovation that have been set up (Table 6). The capability of each country to master intellectual property provisions that relate to vaccine development has been discussed in earlier publications.¹⁹19 Milstien JB, Gaulé P, Kaddar M. Access to vaccine technologies in developing countries: Brazil and India. Vaccine. 2007;25(44):7610–9. doi: http://dx.doi.org/10.1016/j.vaccine.2007.09.007 PMID: 17913312
https://doi.org/10.1016/j.vaccine.2007.0... ^–2121 Milstien JB, Kaddar M, Kieny MP. The impact of globalization on vaccine development and availability. Health Aff (Millwood). 2006;25(4):1061–9. doi: http://dx.doi.org/10.1377/hlthaff.25.4.1061 PMID: 16835187
https://doi.org/10.1377/hlthaff.25.4.106...

Pipeline products

There are some important and innovative vaccines in the pipeline in the BRICS countries, such as the conjugate vaccines being developed in India, an influenza vaccine made from virus-like particles being developed in the Russian Federation, a dengue vaccine – based on technology from the United States National Institutes of Health – being developed in Brazil, and pneumococcal conjugate vaccines being developed in both China and India. Chinese manufacturers have developed their own technologies for rotavirus, live Japanese encephalitis, human papillomavirus and hepatitis vaccines.

Partnerships

Over the study period, many partnerships between vaccine manufacturers and multinational corporations in BRICS have been established. In India, agreements with five multinational corporations account for an estimated 22% of pipeline vaccine products.¹⁹19 Milstien JB, Gaulé P, Kaddar M. Access to vaccine technologies in developing countries: Brazil and India. Vaccine. 2007;25(44):7610–9. doi: http://dx.doi.org/10.1016/j.vaccine.2007.09.007 PMID: 17913312
https://doi.org/10.1016/j.vaccine.2007.0... Five partnerships to support technology transfer in Brazil in 2006¹⁹19 Milstien JB, Gaulé P, Kaddar M. Access to vaccine technologies in developing countries: Brazil and India. Vaccine. 2007;25(44):7610–9. doi: http://dx.doi.org/10.1016/j.vaccine.2007.09.007 PMID: 17913312
https://doi.org/10.1016/j.vaccine.2007.0... included agreements for the transfer of knowhow but no licences for patents rights. Conversely, an agreement for the transfer of dengue vaccine technology, from the United States National Institutes of Health to the Instituto Butantan in Brazil, included a licence for patent rights but no explicit authorization for the transfer of knowhow. In October 2013, Brazil’s government-funded Oswaldo Cruz Foundation announced that it was going to develop an affordable measles and rubella vaccine with the support of the Bill & Melinda Gates Foundation. The Brazilian Ministry of Health is allocating funds to support this plan, including US$ 727 million for the construction of a plant at the Bio-Manguinhos site to produce the vaccine.

Two vaccine manufacturers – Bio-Manguinhos in Brazil and Biological E. in India –illustrate the use of partnerships to assess innovative technologies. Bio-Manguinhos is a state-supported institution that has been charged with providing general access to any vaccine that the national health authorities consider to be a priority, as soon as possible. To help achieve this goal, Bio-Manguinhos is using agreements with GlaxoSmithKline, complemented by its own development activities and many collaborative activities with several universities.¹⁹19 Milstien JB, Gaulé P, Kaddar M. Access to vaccine technologies in developing countries: Brazil and India. Vaccine. 2007;25(44):7610–9. doi: http://dx.doi.org/10.1016/j.vaccine.2007.09.007 PMID: 17913312
https://doi.org/10.1016/j.vaccine.2007.0... Bio-Manguinhos has already had several technology transfer agreements with GlaxoSmithKline, relating to the development of H. influenzae type b conjugate, rotavirus and pneumococcal conjugate vaccines, as well as straight bulk-filling agreements for oral polio, measles, mumps and rubella and measles, mumps, rubella and varicella vaccines. The partnership agreement for the H. influenzae type b conjugate project specified a reference price, which was the PAHO Revolving Fund’s price minus a discount for the cost of the bulk. In return, Bio-Manguinhos received technical assistance. The agreement also specified maintenance of secrecy and knowhow for 10 years and limited export to the Mercosur countries. In addition, the agreement stipulated that Bio-Manguinhos would be charged a 4–5% running royalty for 5 years from the start of selling its own product.¹⁹19 Milstien JB, Gaulé P, Kaddar M. Access to vaccine technologies in developing countries: Brazil and India. Vaccine. 2007;25(44):7610–9. doi: http://dx.doi.org/10.1016/j.vaccine.2007.09.007 PMID: 17913312
https://doi.org/10.1016/j.vaccine.2007.0...

Biological E. is a private sector company that strives to develop and introduce standard and innovative vaccines in a manner consistent with their financial viability, using partnerships to access new technologies. One such partnership was set up with a public sector organization – the former Netherlands Vaccine Institute²²22 Serum Institute of India Ltd. acquires Bilthoven Biologicals of Netherlands [Internet]. Pune: Serum Institute of India; 2012. Available from: http://www.seruminstitute.com/content/news_9.htm [cited 2014 Apr 15].
http://www.seruminstitute.com/content/ne... – to develop a pentavalent combination vaccine.¹⁹19 Milstien JB, Gaulé P, Kaddar M. Access to vaccine technologies in developing countries: Brazil and India. Vaccine. 2007;25(44):7610–9. doi: http://dx.doi.org/10.1016/j.vaccine.2007.09.007 PMID: 17913312
https://doi.org/10.1016/j.vaccine.2007.0... For this vaccine, Biological E. used innovative methods to circumvent the patent-obstructed steps in the standard production process. Biological E. now has a WHO-prequalified pentavalent product that has been brought to market at the lowest price to date and is expected to capture a large share of the global pentavalent market for 2013–2015.²³23 Product menu for vaccines supplied by UNICEF for the GAVI Alliance. New York: United Nations Children’s Fund; 2013. Available from: http://www.unicef.org/supply/files/Product_Menu_July_2013.pdf [cited 2013 Nov 15].
http://www.unicef.org/supply/files/Produ... Biological E. has also licensed technologies – from Intercell – for the development of a Japanese encephalitis virus vaccine, for which it has the rights to market in low- and middle-income countries. In August 2013 this vaccine was prequalified by WHO for use in adults, and Biological E. expects it to be licensed soon for use in children.²⁴24 Biological E, JEEV vaccine prequalified by WHO – Hyderabad [Internet]. Hyderabad: Biological E. Limited; 2013. Available from: http://www.biologicale.com/pdf/JVEE.pdf [cited 2014 Apr 15].
http://www.biologicale.com/pdf/JVEE.pdf...

Vaccine regulation

A vaccine manufacturer’s success on the global market depends on the market’s perception of the quality – or likely quality – of that manufacturer’s products.²⁵25 Hendriks J, Liang Y, Zeng B. China’s emerging vaccine industry. Hum Vaccin. 2010;6(7):602–7. doi: http://dx.doi.org/10.4161/hv.6.7.11933 PMID: 20523120
https://doi.org/10.4161/hv.6.7.11933... Much of that perception relies on an effective system of vaccine regulation. For each of the BRICS countries, we therefore investigated the functionality of the relevant national regulatory authority – as assessed by WHO, the judgements of consumers or other regulatory authorities as to the suitability for procurement of vaccines from the country, and the regulation of clinical trials of vaccines.

National regulatory authorities

The national regulatory authority of each BRICS country has been successfully assessed by WHO and four of the authorities – all but that of South Africa – have been judged as functional in their role as overseers of WHO-prequalified vaccines.²⁶26 National regulatory authorities (NRAs) and National Control Laboratories (NCLs) in countries producing vaccines prequalified for purchase by UN agencies [Internet]. Geneva: World Health Organization; 2012. Available from: http://www.who.int/immunization_standards/national_regulatory_authorities/offices/en/ [cited 2013 Nov 22].
http://www.who.int/immunization_standard... After WHO first judged its national regulatory authority to be functional in this role, in March 2011, China sought WHO prequalification for many Chinese products. Some of the necessary assessments by WHO are now under way. India’s national regulatory authority most recently received a positive assessment by WHO in December 2012²⁷27 Sinha K. Indian vaccine industry passes WHO quality test with flying colours. The Times of India. 2012; Dec 15. – after an exceptional review that was triggered by the withdrawal or delisting of several Indian products from WHO’s list of prequalified vaccines.

In a country that has never exported its locally produced vaccines – such as South Africa – WHO will only assess the national regulatory authority if such an assessment is requested. In such cases, it is left to the regulatory authority to publish or not to publish the results.

The national regulatory authorities of four of the BRICS countries – Brazil, China, India and South Africa – were included as founding members of WHO’s Developing Country Vaccine Regulators Network, along with those of Cuba, Indonesia, the Republic of Korea and Thailand. By May 2012, the national regulatory authority of the Islamic Republic of Iran joined the Network.²⁸28 Nishioka SA, Southern J, Dominguez R, Dellepiane N. Helping each other regulate clinical trials: a network of vaccine regulators from developing countries. Clin Investig. 2013;3(2):113–7. doi: http://dx.doi.org/10.4155/cli.12.151
https://doi.org/10.4155/cli.12.151... ^,2929 Immunization standards [Internet]. Geneva: World Health Organization; 2013. Available from: http://www.who.int/immunization_standards/vaccine_regulation/dcvrn_members/en/index.html [cited 2013 Nov 22].
http://www.who.int/immunization_standard...

Other regulatory groups

Brazil, China, the Russian Federation and South Africa are members of the European Pharmacopoeia.³⁰30 South Africa joins the European pharmacopoeia [Internet]. Amsterdam: International Plasma Fractionation Association; 2013. Available from: http://www.ipfa.nl/nieuws/south-africa-joins-the-european-pharmacopoeia [cited 2013 Nov 15].
http://www.ipfa.nl/nieuws/south-africa-j... South Africa’s Medicines Control Council also participates in the Pharmaceutical Inspection Co-operation Scheme.³¹31 Participating authorities [Internet]. Geneva: Pharmaceutical Inspection Co-operation Scheme; 2013. Available from: http://www.picscheme.org/members.php [cited 2013 Nov 15].
http://www.picscheme.org/members.php... Brazil is a member of PAHO’s Pan American Network for Drug Regulatory Harmonization network.³²32 Fitzgerald J. Report to the 15th ICDRA from PAHO/WHO: advances in the strengthening of national regulatory authorities, regulatory networks and convergence in the Americas. In: 15th International Conference of Drug Regulatory Authorities; 2012 Oct 23-26; Tallinn, Estonia. Geneva: World Health Organization; 2012. Available from: http://www.icdra.ee/attachments/article/17/1-James-Fitzgerald.pdf [cited 2013 Nov 15].
http://www.icdra.ee/attachments/article/... South Africa is a member of the African Vaccine Regulatory Forum, which participates in the joint clinical review of applications for clinical trials in African countries.³³33 The African vaccine regulation forum. Washington: Global Health Technologies Coalition; 2013. Available from: http://www.ghtcoalition.org/files/AVAREFguide-final-formattedforrelease.pdf [cited 2013 Nov 15].
http://www.ghtcoalition.org/files/AVAREF...

Oversight of clinical trials

Each of the BRICS countries has a system for the registration of clinical trials carried out within its borders. The latest available data on the number of vaccine trials conducted (Table 7) indicate that most of the recent vaccine trials in BRICS involved new vaccines. This indicates both the dynamism of the national regulatory authorities in BRICS and the high level of innovation involved in vaccine production in most of the countries – particularly in China and India.

Impact on vaccine prices

Table 8 and Box 1 document the impact of the BRICS manufacturers – notably Indian manufacturers – on the global vaccine market.

Current limitations

Currently, of the vaccine manufacturers in BRICS, the Indian ones are the most globally active. The Brazilian manufacturers are also quite active but those in the Russian Federation are currently more focused on upgrading facilities – to improve production capacity and compliance with international standards – than on vaccine exports. The potential impact of Chinese manufacturers, who are now entering the global market, is immense but has yet to be realized. In South Africa, vaccine manufacturing has been slow to develop and may have greater potential regionally than globally.

The focus of vaccine manufacturers in BRICS has been on the domestic market, the United Nations’ market or both. These manufacturers are yet to make a substantial impact on several broader and potentially more profitable vaccine markets – such as those involving new vaccines and the vaccine demands and needs of wealthier countries and the private sector within their own countries and of many middle- and high-income countries. Full exploitation of such markets is likely to push the manufacturers in BRICS into harder competition with each other for supply agreements. For each such manufacturer, the risk of loss of a substantial market share to a new supplier and the frequent lack of a large portfolio of vaccines and other products – that would allow the flexibility of easy diversification – may be major challenges to the sustainability of turnover and profit.

Given the relatively low returns from their vaccines – in absolute values – and the limited markets in which they are currently active, the vaccine manufacturers in BRICS must invest a greater percentage of turnover to research and development than the multinational corporations that also produce vaccines.

With increasing links through technology transfer, outsourcing and restricted supply arrangements, the more innovative vaccine manufacturers in BRICS are becoming ever more attractive targets for mergers and acquisitions by multinational manufacturers. They are therefore at increasing risk of a loss of autonomy and national and regional focus.

Conclusion

Most of the BRICS countries are having substantial impacts on the global vaccine market, albeit to varying degrees. The production of important traditional vaccines within BRICS is contributing to the achievement of Millennium Development Goal 4. Such production is a key component in increasing access to affordable vaccines of good quality, as it allows large-scale supplies to domestic and United Nations’ markets. Through collaborations with universities, donors, international partners and multinational corporations, vaccine manufacturers in BRICS have not only provided increased production capacity for important underutilized vaccines but also developed novel vaccines for specific use in low- and middle-income countries. These manufacturers rely heavily on public sector arrangements and supply agreements with United Nations’ agencies. Such reliance could stop manufacturers in BRICS from reaching their full economic potential and full sustainable impact.

The same manufacturers face several other weaknesses and challenges. These include low levels of financial and technical investment in vaccine research, the need to innovate, a dependence on limited markets, and low levels of diversity in product portfolios. Among manufacturers in BRICS, the emphasis is generally more on competition – for the same limited markets and product segments – than on cooperation. The five countries represented by the BRICS acronym are far from being a coherent group. There is a real risk of the absorption and acquisition of vaccine production facilities by multinational firms and the subsequent loss of autonomy.

In general, vaccines from the BRICS countries are currently competitively priced because the manufacturing costs in BRICS are relatively low. The prices of such vaccines may have to rise, however, to allow greater investment in vaccine research and development and the use of new processes and updated facilities to produce more complex vaccines. The prices may also have to rise as the mean income per capita in the emerging economies and, therefore, the living standards expected by the workforce increase.

It is expected that China will soon emerge as a major player in the global vaccine market and that there will be increasing differentiation between the national vaccine manufacturers that have sufficient capacity to compete with the multinational corporations and the ones who lack the capacity. Vaccine manufacturers in BRICS could either enter into fierce competition with the multinational corporations, for an adequate share of the global vaccine market, or focus on a niche market, such as the vaccines that have more local importance.

The international public sector could help strengthen vaccine production in BRICS, perhaps by exploiting the Global Vaccine Action Plan’s Decade of Vaccines Strategy. Under certain conditions, the United Nations’ procurement agencies could perhaps provide targeted support to vaccine manufacturers in BRICS, so as meet global needs for specific vaccines. Support from donors like the Bill & Melinda Gates Foundation could be focused on more upstream areas, such as research and development, technology platforms and intellectual property rights. More cooperation between academia, biotechnology firms and public health institutions should also be encouraged.

Acknowledgements

The authors would like to acknowledge and thank all the peer reviewers for their valuable feedback and suggestions. Thanks also to Michael Hinsch for his assistance in the data mapping.

References

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