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Vaccine 28 (2010) 2115–2121

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Vaccine

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The role of emerging manufacturers in access to innovative vaccines of public health importanceଝ

Julie B. Milstien a,∗, Miloud Kaddar b a University of Maryland School of Medicine, Geographic Medicine, 685 West Baltimore Street, Baltimore, MD 21201-1509, United States b Department of Immunization, Vaccines and Biologicals, World Health Organization, 1211 Geneva 27, Switzerland article info abstract

Article history: The role of developing country manufacturers in assuring global access to innovative vaccines was com- Received 13 December 2009 pared to the situation in 2005. These producers now supply over 60% of traditional vaccines doses globally Accepted 14 December 2009 and an increasing value (up to 15% in 2007) of innovative products. More suppliers are now strong play- Available online 29 December 2009 ers in global market, and an even larger group has potential to do so. These manufacturers are not a homogeneous group and most of them are now at a crossroads. Decisions made by their management Keywords: and governments as well as by the international community will have a large impact on their existence Vaccine manufacturers and future and their ability to manufacture innovative vaccines at affordable prices. Vaccine market Developing countries © 2009 Elsevier Ltd. All rights reserved.

1. Introduction Recently, in a study (hereafter referred to as the Boston Con- sulting Group (BCG) study) for the Global Alliance for Vaccines Emerging vaccine manufacturers are those located in develop- and Immunization (the GAVI Alliance, or GAVI) [1], a subset of 17 ing countries and essentially owned by domestic agents, whether manufacturers in seven countries1 was selected, the members of public and/or private. Some of these manufacturers are now active which were felt to have potential as active manufacturers on the players on the global market, especially for traditional vaccines, global market. The purpose of this paper is to examine the role because of technology transfer which occurred over the years for of emerging manufacturers as players in assuring global access such products, which use decades-old technology. Several new to innovative vaccines of public health importance. We will draw vaccines have recently been added to national immunization pro- on and update the findings of the 2005 BCG study. We will also grams, and more are projected in the near future. Because of this, describe the evolution and attractiveness of emerging markets and emerging manufacturers have begun to access these new vaccine the role of emerging producers at global level with some of the technologies, and are already providing a significant percentage of more innovative products as examples. Before outlining potential newer vaccines such as hepatitis B, Haemophilus influenzae type b projections for the future, we will compare the “focus” and “capa- (Hib), and combinations of these, on the global market. bility” of emerging manufacturers today relative to the situation Although most of these manufacturers were initially constituted found in the 2005 study, illustrated by specific case reports and by as public sector organizations, many are now in the private sector. some of their main strengths and weaknesses. Even those in the public sector are being managed so as to maximize In terms of methods, the analyses, projections and case studies their ability to innovate and to assure the quality of vaccines so as to included below were based, in addition to the BCG study doc- be well-positioned in the new global marketplace. However, these uments, on our field observations as well as on published and manufacturers do not constitute a homogeneous group as will be unpublished data and reports, showed later in this paper.

1 These countries were Brazil, China, Cuba, India, Indonesia, the Republic of Korea ଝ The ﬁndings, interpretations and conclusions expressed in the paper are entirely and Mexico. Although Korea is no longer considered a developing country, two those of the authors, and do not represent the views of the World Health Organiza- Korean manufacturers were included in the study because they were supplying tion. vaccines on the global market but were not considered multinational companies. ∗ Corresponding author. One of these has since, through mergers, become part of an international company; E-mail addresses: [email protected], [email protected] however, because of its history and product lines we have continued to include it (J.B. Milstien). here.

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2. The increasing attractiveness of emerging markets

The developing country market has historically been high volume, low proﬁt traditional vaccines, and as such was not especially attractive to most vaccine-producing multinational companies (MNCs). However, with more purchases of innovative vaccines of public health priority in developing countries, both because of increasing wealth and the availability of donor funds, emerging markets have become more attractive. In fact, the emerging pharmaceutical markets, including China, India, Brazil, the Russian Federation, the Republic of Korea and Turkey, are expected to grow at 12–13% per year and to become larger than developed markets by 2020 [2]. The vaccine markets in India and China alone are expected Fig. 1. Value of UNICEF procurement for GAVI from multinational companies (MNC) to grow 16 and 17.8% respectively from 2006 to 2013 [3]. Sanoﬁ- and emerging manufacturers (EM), in millions of US dollars (Source: UNICEF Supply Division). Pasteur has reported in 2008 that emerging market sales account for almost one-quarter of total vaccine sales (D 814M of D 2.86B) [4].

In 2005, there were at least six prequalified hepatitis B (Hep B) 3. The role of emerging manufacturers in vaccine supply vaccines, for which at least four of the producers were emerging manufacturers. There were two prequalified Haemophilus influen- 3.1. The supply of traditional vaccines zae type b (Hib) vaccines, both produced by MNCs. For DTP-Hep B and DTP-Hep B-Hib (pentavalent vaccine), there was only one pre- Vaccines for provision to national immunization programs in qualified product each, both produced by the same MNC. There was developing countries are often supplied through procurement by a second manufacturer of these two latter vaccines, an emerging large United Nations (UN) agencies. Vaccines must be prequalified manufacturer, but those products had not been proposed for pre- to be considered in these tenders. Prequalification is a procurement qualification. At that time there was a large overproduction of Hep term which refers to a process used to narrow the number of eligi- B, while the supplies of combination vaccines (about 28 M doses ble manufacturers in an open tender process. For vaccines for UN total for all combinations) were not sufficient to meet demand. agency purchase, it is WHO that devises the process and makes the Based on the data found, the study team proposed that there determination [5], and posts a list of those products which are pre- would soon be an oversupply of these combination vaccines, qualified and their manufacturers on the WHO website, updated because of the number of pipeline projects for their development. monthly. In 2005, the study team predicted that as of the end of 2007, there In 1994, the first emerging manufacturers had products pre- would be five prequalified pentavalent vaccines, of which three qualified for supply to UN agencies. That process has continued, would be from emerging manufacturers, and the available sup- with more products from emerging manufacturers being prequal- ply would exceed 250 M doses per year. In 2005, the price of the ified every year. Currently of 24 manufacturers that have products pentavalent vaccine was $3.60 per dose, and the study team also on the prequalified list, 12 are from the countries covered by the predicted a drop in the price, considering the production costs to 2005 BCG study. For traditional vaccines, excluding oral polio vac- be less than $2 per dose, and given the expected oversupply. cine, 64% of doses come from developing country manufacturers In September 2009, there were five pentavalent combination [6]. Considering products for GAVI purchase (Hep B, Hib, and their products (two from a single MNC) available and prequalified, three combinations, yellow fever vaccines), 42% of supply in volume came of which are from emerging manufacturers, plus at least three addi- from these developing country manufacturers in 2007, compared tional products that are not yet prequalified (see Table 1). to 15% in value. However, these percentages are increasing (Fig. 1), There are five prequalified DTP-Hep B combination vaccines, and as more emerging manufacturers’ products are prequalified, one of which is from an MNC. In addition, the supply of both Hib will continue to increase. and Hep B vaccines has increased, with five and nine prequalified products, respectively, manufactured mostly by emerging manu- 3.2. The supply of innovative vaccines facturers. The supply [7,8] thus should far exceed the demand, which was about 60 M doses for pentavalent and 22 M doses for One of the facets of the BCG study was an analysis of the DTP-Hep B in 2008 [9]. These manufacturers are also supplying pipelines of all the selected manufacturers. A few products of spe- other countries; for example, Panacea is supplying combination cific interest to GAVI, including DTP-based combination vaccines, vaccines to the Philippines [10]. Moreover, the price of the pen- rotavirus vaccines, and pneumococcal conjugate vaccines, were tavalent vaccine had decreased to as low as $1.90 per dose [11] chosen for particular focus. For the purpose of this paper, we will in 2009 (down from a high of $3.75 per dose in 2007). The price consider in depth the DTP-based combination vaccines, for which of DTP-Hep B was as little as $0.71 for a 10 dose vial presentation the most data are available. [12].

Table 1 Emerging manufacturers producing licensed pentavalent vaccine in 2009.

Manufacturer Country Prequaliﬁed product Volume/value on international market

Bharat Biotech International Limited India N Panacea Biotec India Y US$ 34.2M to UNICEF [7]; >15 M doses Shantha Biotecnics Private Ltd India Y 350 M doses; US$ 340M contract with UNICEF for 2010–2012 [16] Berna Biotech/Crucell Republic of Korea Y In 2008, supplied >29 M doses through UNICEF/GAVI [9] Serum Institute India N Biological E India N Author's personal copy

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Table 2 Innovative vaccine pipeline in developing countries: a selection.

Vaccine Potential manufacturer Country Comments

Pneumococcal conjugatea Partnership with GSK Singapore Production facility to be operational 2011 [18] Oswaldo Cruz Foundation (BioManguinhos)/GSK Brazil Production of 10-valent Synﬂorix® [19] Chengdu Institute/PATH China Three year project starting June 2009 [20]

Rotavirus Bharat Biotech International Limited India Received strains from NIH; in phase 3 clinical trials [21] Shantha Biotecnics Private Ltd/PATH India Received strains from NIH; not yet in clinical trials [22] Biological E, and Serum Institute India Received strains from NIH Instituto Butantan Brazil Received strains from NIH; various collaborations Chengdu and Wuhan Institutes China Received strains from MIH

Measles-mumps-rubella Serum Institute India Prequaliﬁed, $1.50/dose for single dose presentation in 2009

Meningitis A conjugate Serum Institute/Meningitis Vaccine Project India Expected product license and prequaliﬁcation in 2010 [23]; projected production 25 M doses/year, prices from $0.40/dose

Rabies Novartis subsidiary India Prequalified Zydus Cadila India Prequalified [24] Serum Institute India Licensed, not prequalified Vabiotech Viet Nam Licensed, not prequalified

Japanese encephalitis Chengdu Institute/PATH China SA-14-14-2 live attenuated vaccine, licensed in 7 countries and exported to 4 Asian countries, not prequaliﬁed [25] Biological E/Intercell India IC-51 inactivated strain derived from SA-14-14-2; partnership for production in India and distribution in south and southeast Asia [26] Vabiotech Viet Nam Japanese mouse brain technology, 3 M doses per year [27]

Cholera Crucell-SBL Sweden Prequaliﬁed, on sale for $7.12/dose in developing countries Shantha/International Vaccine Institute/Vabiotech India South–South technology transfer, licensed in India, expected to be sold at $6/dose there [28]

Seasonal and pandemic influenza Vabiotech Viet Nam Avian flu vaccine proceeded to phase 1 trials [29] GPO Thailand Russian strains and Live-attenuated influenza virus technology from Nobilon license, seed virus developed [30] Neptunus Interlong Bio-Technique/GSK China Seasonal and pandemic vaccines to be developed [13] Instituto Butantan/Sanofi-Pasteur Brazil In production for seasonal vaccine Birmex/Sanofi-Pasteur Mexico Technology transfer agreement [31] Sinovac China Vaccine A(H1N1) produced and used in China [32]

Anthrax and other bioterror vaccines Panacea/PharmAthene Inc India Strategic alliance to develop anthrax vaccine [33]

a Price is expected to be $3.50 per dose under the Advanced Market Commitment versus the industrialized country price of about $70 [17].

3.3. Vaccines for the future 2005 BCG study, and a few manufacturers, in Vietnam, Thailand, and Egypt, who were not in either category. The two subsidiaries In the countries being considered, there are a large number of MNCs, Chiron India and Shenzhen Sanofi Pasteur, were omitted. of innovative vaccines in the pipeline, some of which are already The characteristics used to assess focus were: licensed and prequalified. Table 2 presents a selection. Where available, prequalification status, price and quantity have been included; • percentage and number of pipeline products of interest to the the availability of some of these products at very low prices com- developing world; pared to some current products is striking. • percentage of vaccine sales to global public agencies; • percentage of total sales from vaccines portfolio; • extent to which manufacturer has invested in and prepared for 4. Focus and capabilities of emerging manufacturers prequalification; • manufacturer’s flexibility to invest in vaccines for export. 4.1. Comparison with 2005 situation

To be able to assess more quantitatively the potential of emerg- Those characteristics assessed for capacity were: ing manufacturers, the same assessment of focus versus capacity was done as in the 2005 BCG study [1]. The manufacturers consid- • previous experience with WHO prequaliﬁcation; ered in 2009 were those included in the 2005 BCG study, as well as • appropriate production facilities; those manufacturers of prequaliﬁed products not included in the • access to investment; Author's personal copy

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4.2. Case studies

To illustrate the evolution of these manufacturers since 2005, a few case studies are useful.

4.2.1. An innovative large volume public sector manufacturer partnering with an international public health group For this first case study, we have selected Chengdu Biological Products, one of the large public sector vaccine manufacturers in China which is part of the Chinese National Biotec Group. All of these manufacturers (there are seven, plus two additional companies in the group) have as a primary focus, to fill the public health needs of the Chinese population for basic vaccines, and they are required to produce certain amounts of the traditional vaccines and sell them at a fixed price, which is widely regarded as lower than the cost of production. Thus, most of these manufacturers have taken steps to discover and produce vaccines against a wider range of diseases that they can sell at higher prices to the wealthier provinces in China, as a way of staying financially afloat. One of these products is the live SA-14-14-2 vaccine against Japanese encephalitis developed by Chengdu, and grown on primary hamster kidney cells. Through a long history of international assistance, most recently through PATH’s Japanese Encephalitis

Fig. 2. (a) Focus on the GAVI market and capacity to serve that market in 2005 (17 Vaccine Project, Chengdu has built new facilities and has received manufacturers). (b) Focus on the global market and capacity to serve that market in much training in GMP and quality assurance. To date, however, 2009 (25 manufacturers). none of this support has been validated by the prequalification of this product, although that is the ultimate goal. Prequalification will likely depend on (1) continued upgrading of the Chinese regulatory authority, and (2) a continued culture of GMP at the Chengdu • record of production scale-up; facility, which would include control of raw materials, processes, • ability to bring a product quickly to market; testing, facilities, and packaging. Nevertheless, Chengdu has suc- • access to components, technologies, know-how and intellectual ceeded in exporting this product to a number of countries in South property rights (IPR); Asia, including Thailand, Nepal, India, and Sri Lanka, due to its low • ability to acquire missing elements through partnering with a price and demonstrated efficacy. manufacturer of prequalified products; Chengdu has now entered additional agreements for develop- • functional national regulatory authority in the country of produc- ment of vaccines such as the pneumococcal conjugate vaccine (also tion; with PATH) and rotavirus vaccine (using the NIH Kapikian technol- • robust quality assurance system. ogy). One of the aspects of the Japanese encephalitis virus vaccine agreement with PATH is the requirement to sell a certain number of doses at a price that is below the Chinese market price in exchange The results are shown in Fig. 2, along with the results from the for PATH assistance – a requirement that is not particularly attrac- previous study. tive to Chengdu. However, this agreement has provided Chengdu It can be seen in both analyses that there is a group of man- with much vaccine production hardware and software that they ufacturers with high capacity and high focus, another group with would not ordinarily have, and thus gives them an advantage on a lower level of capacity and/or focus, and finally, a group which the international market, even if they cannot control the sales price. is neither interested in nor capable to supply the UN agencies Such agreements are allowing Chengdu to improve its production procurement market. The results in 2009 show a maturing of the facilities and processes, and may be important in raising the quality emerging manufacturers as a group. Compared to 2005, there is a of products on the Chinese national market as well. group tightly focused on this market and highly capable to serve it. These are all manufacturers of prequalified products, and they 4.2.2. An innovative large volume private sector manufacturer are homogeneous in character. These manufacturers are all pri- partnering with or acquired by an MNC vate sector, all capable of large volume production, have access to Of all the private sector manufacturers in India, Shantha has ready financing, and have managed to access necessary technolo- been the one that has attracted the attention of investment gies, through a combination of in-house research and development analysts. Originally set up by Dr Varaprasad Reddy to make recom- (R&D) and strategic alliances. It should be noted that even though binant hepatitis B vaccine as a humanitarian effort, Shantha has Berna Biotech/Crucell has been a member of this group, being been heavily research-based, with ample funding, state of the art located in an emerging market, it is also part of the MNC, production facilities, knowledgeable staff, many recruited from Crucell. other successful Indian vaccine manufacturers, and a variety of pri- The second group as well includes a majority (9/13) of manu- ority products. Shantha’s recombinant hepatitis B vaccine was the facturers who produce at least one prequalified product; however, first Indian hepatitis B vaccine to be prequalified; likewise for its this group tends to be comprised of national or public sector man- pentavalent vaccine, which has a large share of the global mar- ufacturers, many of which have less well developed R&D capacity, ket. Most analyses of successful vaccine manufacturers in India put GMP compliance, or ability to consistently supply large volumes Shantha near the top of the list. through UN agencies. The third group is larger, and of higher capa- However, a few years ago, the majority stake in Shantha was bility than the equivalent group in 2005, but is slightly less focused acquired by Bio-Mérieux. In July 2009, this stake was acquired by on this market. Sanofi Pasteur so that the French vaccine manufacturer would have Author's personal copy

J.B. Milstien, M. Kaddar / Vaccine 28 (2010) 2115–2121 2119 a “manufacturing and research base” in India, to “allow Sanofi to holder and the government to allow them to export their products provide important vaccines at affordable prices around the world” on the global market at prices which will allow them to stay in [13]. It is not clear how this acquisition will impact the future viabil- business. ity of Shantha, nor its place as a key supplier of innovative vaccines Currently, the successful emerging manufacturers have the fol- on the global emerging market. lowing characteristics which may aid them to supply the global public market: 4.2.3. An innovative moderate volume public sector manufacturer partnering with an MNC • Large volume production capability. The Brazilian manufacturers, BioManguinhos and Butantan, • A public health focus. have invested in R&D, have knowledge of intellectual property • Relatively lower infrastructure costs than MNCs, despite an concerns, are supported by a well-functioning national regula- increasing requirement for investment in GMP [15]. tory authority, and are together providing the majority of Brazil’s • Generally a lighter regulatory burden than the MNCs, although public sector vaccines. This success has been based on a long this is increasingly stringent for all products on the international history of manufacturing, plus a strong government interest in market. strategic planning. Although only BioManguinhos currently pro- duces prequalified products (yellow fever vaccine and meningitis On the other hand, they have disadvantages which could inhibit AC polysaccharide vaccine – in collaboration with Cuba’s Findlay such success, particularly for innovative vaccines, such as less abil- Institute, another example of South–South cooperation), both have ity to spread investments and risks over a wide range of products. attracted the attention of large vaccine MNCs, who have transferred An important disadvantage is the lack of R&D. Even for those man- vaccine production technology starting from filling of imported ufacturers who have invested in R&D, the breadth and depth of bulk vaccines. BioManguinhos has had such an agreement in force the research efforts for the emerging manufacturers is limited. The with GlaxoSmithKline for many years for filling of oral poliovirus 2005 BCG study found that the most innovative emerging man- vaccine, and recently concluded one for measles-mumps-rubella ufacturers spent up to $6M per year on R&D, or 4–14% of sales, vaccine. Also through a GSK agreement, they have progressed to while MNCs in contrast spent from $22M (for the smaller man- full scale production of Hib vaccine, and will shortly commence fill- ufacturers) to >$200M per year for the same time period. For ing of imported pneumococcal conjugate bulks as a step towards example, emerging manufacturer R&D may be focused on one a full technology transfer of that vaccine. Sanofi Pasteur has had a or two products, but generally not on a cross-cutting advance similar arrangement with Butantan, which is now starting full scale such as a new adjuvant. Other disadvantages include the follow- influenza vaccine production. The advantages of such agreements ing: are that they allow the country to benefit from a new vaccine technology sooner, and will eventually result in national ownership of • Lack of access to technologies and processes, as well as to vaccine the technology. However, the disadvantages are that the prices may seeds and strains, cell substrates, other raw materials that may be higher than could eventually be attained by these national man- be protected by patents. ufacturers, and they are not able to be offset by export sales, which • Lack of experience with bringing a totally new product to market. are controlled by the MNC. • Lack of experience in dealing with products and processes that may be under patent. 4.2.4. An innovative low volume quasi-private sector • Limited experience in dealing with increasing regulatory barriers. manufacturer partnering with an international public health • Lack of experience in conducting clinical trials and managing IPRs. group Vabiotech is a company formed in 2000 as part of the National Institute of Hygiene and Epidemiology in Vietnam. Its mission is to It is evident that these manufacturers are at a crossroads, and make vaccines for the national domestic program, but its strategic the decisions they make now will impact their ability to move for- directions may include exporting some of their larger volume and ward in this new market. Decisions made at the global level by the more desirable vaccines on a global level. One of these is likely their international community will also have an impact on their ability oral cholera vaccine, the technology of which has been improved to strengthen their current efforts and overcome some of the main and standardized through collaboration with the International Vac- identified obstacles and weaknesses. cine Institute, and was recently transferred to Shantha, whose Moreover, outcomes have not always been positive for man- product has now been licensed in India. Through international ufacturers, generally in the public sector, in developing countries. assistance, the company has been improving its GMP compliance, Despite concerted effort, domestic manufacture in Egypt, Iran, Thai- and plans to increase its production volumes, which are now land, Vietnam and South Africa has not developed to the same fairly low (4 million doses for the largest volume product) [14]. level as the more successful public sector manufacturers mentioned However, without strong regulatory oversight and a significant here. Several other facilities in Bangladesh, India, and some coun- infusion of cash, the future of this company on the global market is tries in South America, have closed their doors. unclear. Table 3 summarizes the innovation status of manufacturers in three key countries, Brazil, China, and India. All are moving towards 5. Strengths and weaknesses of emerging manufacturers the ability to fully access innovative technologies; the future will allow an assessment of these efforts. The previous section provides some idea of what will be the prerequisites for emerging manufacturers to be successful on the 6. Possible directions and outcomes global market. Aside from being large volume, GMP-compliant and research-based manufacturers, they will need regulatory oversight What are the options available to emerging manufacturers on at least to a level sufficient to allow their products to be pre- the global market? Some of them will choose to remain as produc- qualified, and ideally, to a level that allows them to compete on ers of the traditional vaccines. To the extent that they can become internationally regulated markets. They will need access to suffi- high volume manufacturers on the global market, this route could cient funding to maintain the facilities, product technologies and be sustainable. However, for those manufacturers that are supply- processes current, and sufficient autonomy from the technology ing only a limited domestic market, no matter how large it is, with Author's personal copy

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Table 3 Country innovation statistics.

Country # Biotechs # Vaccine manufacturers IPR facility Products

Brazil 181 companies: 39.4% health, 2, public sector, since 1900 Where relevant, tend to license in Prequalified yellow fever; prequalified 21% human health technology through joint technology meningitis AC polysaccharide; supply transfer agreements; limited number 83% of Brazilian national immunization of products being developed through program demand; produce a total of own patented R&D [34] 215 M doses, of which 150 M used nationally; $550M [35] China 500 companies 8 institutes and 43 To date not much affected by IPR. 41 vaccines; more than 1 B doses, manufacturers Innovation in vaccines is generally $735M [36] using classic approaches India 325 companies At least 14 Quite innovative in accessing needed Total sales D 263.6 in 2006; 2 technology through combination of manufacturers, Serum and Panacea, technology held by Indian institutes, account for 83% of global sales [37] licensing in, and partnerships, particularly with international organizations or non-profit or developing country manufacturers

vaccines that are becoming less and less expensive, it is doubtful www.gavialliance.org/resources/BCG 24 June.pdf. Note that although this ref- that this will be a viable option. erence provides the summary of the study, both authors were intimately involved in the study, and this paper thus provides information from the study Other manufacturers, notably those in Mexico and Brazil, as that is heretofore unpublished. well as in other countries not traditionally associated with vaccine [2] IMS, MIDAS 2006 sales data, Total Pharmaceutical Market, as quoted by Murray production, will opt for partnerships with MNCs to access newer Aitkin of IMS. [3] Renub Research. World Vaccines Market 2008–2013: Future Fore- technologies. This route will normally not result in their develop- cast, Critical Trends and Developments, April 2009, available at ment as innovative producers of vaccines; however, it can be seen http://www.researchandmarkets.com/research/6d84fc/world vaccines mar. as the best route to assure newer vaccines to their countries. An [4] Sanofi-Aventis. Emerging Markets IR-Seminar. 2009 July 2, available at anomaly here is Shantha, which finds itself as part of a MNC while http://en.sanofi-aventis.com/binaries/IR Seminar-Emerging markets tcm28- 25561.pdf. developing innovative products for the Indian market. It will be [5] World Health Organization. Procedure for assessing the acceptability, important to follow how this arrangement plays out, and its impact in principle, of vaccines for supply to United Nations agencies. WHO on the affordable supply of innovative vaccines, not just for India, document WHO/IVB/05.19, available at http://www.who.int/vaccines- documents/DocsPDF06/812.pdf. but on the global market. [6] Jadhav SS, Gautam M, Gairola S. Emerging markets & emerging needs: devel- Finally, there are some vaccine manufacturers who are pre- oping countries vaccine manufacturers’ perspective & its current status. pared to develop innovative products through various technology Biologicals 2009;37(3):165–8. [7] Panacea Biotec’s award in 2008 was estimated at 10–15 M doses: Panacea access agreements, who are prepared to license these products Biotec, Panacea Biotec bags award (USD 34.2 million) for Pentavalent Vac- on the global market, and who thus may find themselves facing cine, Easy Five, from UNICEF. Press release 12 August 2008, available at a cost structure that is increasingly like that faced by the MNCs, http://www.panacea-biotec.com/press releases.html. [8] Singh Seema. Shantha’s story is that of Indian biotechnology, 15 July 2009, although their overall costs may still be lower. Should this result available at http://www.livemint.com/shantha.htm. in higher prices, as seems likely, the advantages on the global [9] Figures from UNICEF Supply Division website, http://www.unicef.org/ market of sourcing vaccines from emerging manufacturers may supply/index gavi.html. [10] Panacea Biotec. Panacea Biotec signs agreement with Family Vaccines to be relatively mooted, and it will be of considerable interest to supply combination vaccine in Philippines. 4 October 2007, available at follow the ability of these manufacturers to act in the interest http://www.Panacea-Biotec.com/press releases/Family-Vaccines-4Oct07.pdf. of global public health by manufacturing innovative vaccines at [11] UNICEF forecasting tool, provided to countries in 2009. affordable prices. This may become increasingly difficult as time [12] Product menu for vaccines supplied by UNICEF for the Global Alliance for Vaccines and Immunization (GAVI), updated 23 September 2008, available at goes by. http://www.unicef.org/supply/files/Product Menu 23 Sept 2008.pdf. Decisions made by their management and governments as [13] BS Reporter. Sanofi buys Shantha in offshore deal. 2009 July 28. Available at well as by the international community will have an impact http://www.business-standard.com/india/storypage.php?autono=365140. [14] Vabiotech website, available at http://www.vabiotechvn.com/english/?act= on their future ability to manufacture innovative vaccines at info&id=2. affordable prices. Should innovative vaccines become unafford- [15] Milstien J, Costa A, Jadhav S, Dhere R. Reaching international GMP standards for able, this would mean that the current paradigm has failed. New vaccine production: challenges for developing countries. Expert Rev Vaccines 2009;8(5):559–66. strategic thinking and effort and enhanced international surveil- [16] United Nations Agency Awards $340m Contracts To Shantha Biotechnics, lance will be necessary to ensure that this failure does not take 2 September 2009, available at http://contractservices.pharmaceutical- place. business-review.com/news/united nations agency awards 340m contracts to shantha biotechnics 090901. [17] Center for Vaccine Ethics and Policy. First Advance Market Commitment Acknowledgements (AMC) pilot project formally launched, pneumococcal disease for developing countries. 15 June 2007, available at http://www.gavialliance.org/ The authors are pleased to acknowledge the helpful sugges- resources/7 Advanced Market Commitment.pdf. [18] Macdonald Gareth. GSK grows in Asia vacc market. 2009 June 10, tions and review by colleagues, including Michel Zaffran, Thomas available at http://www.in-pharmatechnologist.com/Industry-Drivers/GSK- Cherian, Marie-Paule Kieny, Sarah Schmitt, Carsten Mantel, Nora grows-in-Asia-vacc-market. Dellepiane, and Suresh Jadhav. We particularly appreciate the assis- [19] GSK and Brazil’s Fiocruz form partnership for new R&D effort and increased vaccine access. 17 August 2009, available at http://www.gsk.com/media/ tance of Robert Matthews, UNICEF Supply Division, for indicating pressreleases/2009/2009 pressrelease 10085.htm. data sources on developing country vaccine supplies. [20] PATH. China National Biotec Group/Chengdu Institute of Biological Products and PATH announce collaboration to accelerate pneumococcal vaccine development. 2000 June 22. Available at www.path.org/ References news/pr090622-cdibp.php. [21] Mehta Nina. 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