The Right Shot: BRINGING DOWN BARRIERs TO AFFORDABLE AND ADAPTED VACCINES
2nd Edition – January 2015
www.msfaccess.org MÉDECINS SANS FRONTIÈRES
Médecins Sans Frontières (MSF, or Doctors Without Borders) is an international, independent, medical humanitarian organisation that delivers emergency aid to people affected by armed conflict, epidemics, healthcare exclusion and natural or man-made disasters.
Each year, MSF teams vaccinate millions of people, largely as outbreak response to diseases such as measles, meningitis, yellow fever and cholera. MSF also supports routine immunisation activities in projects where we provide healthcare to mothers and children. MSF is scaling up its vaccination activities with a particular focus on improving its work in routine immunisation, as well as extending the package of vaccines used in humanitarian emergencies. In the year 2012–2013, MSF had a 60% increase in the number of doses administered in its projects.
In 1999, on the heels of MSF being awarded the Nobel Peace Prize – and largely in response to the inequalities surrounding access to HIV treatment between rich and poor countries – MSF launched the Access Campaign. Its purpose has been to push for access to, and development of, life-saving and life-prolonging medicines, diagnostics and vaccines for patients in MSF programmes and beyond.
www.msfaccess.org
www.msfaccess.org/our-work/vaccines TTableable of o fcontents Contents 1
y
Middle-income countries struggle to access affordable vaccines Middle-income countries struggle Affordability challenges for Gavi-graduating countries Affordability challenges for Gavi-graduating NGO access to affordable vaccines NGO access to affordable drops, but duopoly persists Robust competition stimulates price for newer vaccines Particularities of the vaccine market Particularities of the price transparency, Despite global initiatives to improve momentum despite negative effects on access pricing gains Tiered price information remains scarce Solutions to foster innovation: building a better vaccine Pooled procurement initiatives and associated challenges Pooled procurement initiatives and What is an ‘affordable’ price? What is an ‘affordable’ vaccine so obscure? Why are the cost components of a Summary and introduction (HPV) Human Papillomavirus Vaccines (IPV) Inactivated Poliovirus Vaccines MMR) (Measles, MR, Measles-containing Vaccines Progress in vaccine adaptation Controlled temperature chain
8 e nts o nt c o f e abl 14 13 12 27 25 10 18 39 46 52 32 36 23 16 29 T
xisting solutions to improve affordability xisting solutions to improve E and their limits Vaccine price and data opacity Vaccine Access to affordable vaccines: why price is a barrier vaccines: why price Access to affordable to immunisation Product Cards ns io Conclusion and recommendat ion ine adaptat vacc g ine pricin ility and vacc Affordab tive Summar Execu
30 Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 36 33 29
23
16 5 8 3
60 Meningococcal Vaccines
65 Pentavalent Vaccines (DTP-HepB-Hib)
72 Pneumococcal Conjugate Vaccines (PCV)
Table of contents Table 78 Oral Cholera Vaccines (OCV)
83 Rotavirus Vaccines (RV)
88 Tetanus Toxoid Vaccines (TT)
94 ANNEXES
94 Annex A: Sources and methodology for price analysis
101 Annex B: Company contacts
102 Annex C: Incoterms
103 Annex D: Abbreviations
105 Annex E: Summary of WHO position papers – recommendations for routine immunisation
106 Annex F: Notes and methodology for the graph on the price of vaccines to immunise a child
108 REFERENCES
2 Médecins Sans Frontières | The Right Shot 2nd Edition January 2015 E xecutive Summary Executive Summary
Vaccination is a cornerstone of Médecins Sans Frontières’ (MSF) work to reduce illness and death caused by preventable diseases. While global immunisation coverage reached 84% in 2013, in some places vaccination rates have stagnated, leaving behind children chronically unimmunised and unprotected. For more than 40 years, MSF has been at the forefront of vaccine delivery in crisis contexts, and in response to outbreaks of vaccine-preventable diseases. We also conduct routine immunisation in areas where health systems have failed.
Whether vaccinating refugee children crisis settings, in line with the recently the market, a lack of competition, in South Sudan, or pregnant women in developed World Health Organization various procurement strategies and Afghanistan, MSF has committed itself (WHO) guidelines on vaccinating purchasing conditions, and the business to prioritising vaccination as a core in humanitarian emergencies, the practices of the pharmaceutical health service in its operations. In 2013 challenges we face in purchasing industry. The publication consolidates alone, our programmes delivered vaccines at an affordable price have and analyses vaccine price data points more than 6.7 million doses of become acute. In addition, countries from countries, UNICEF, Pan American vaccines and immunological products, that are unable to afford these high Health Organization (PAHO), MSF, and we see the need to ramp up our prices are increasingly voicing their and pharmaceutical companies. activities even further. frustration at the inability to protect By examining the differences in pricing their children against life-threatening – strategies used by companies based However, the organisation increasingly but preventable – diseases. in emerging economies (developing- faces challenges at the field and global country manufacturers) and multinational levels in expanding capacity to address This second edition of The Right companies (industrialised-country immunisation needs. The barriers Shot outlines how the prices of 16* manufacturers), the publication explains encountered by MSF, including the fundamentally important vaccines how multinational pharmaceutical rising cost of new vaccines and the lack have evolved since their development, companies use their first-to-market of vaccine products suited for low- in some cases as far back as 2000. advantage to reap blockbuster revenues, resource settings, are also obstacles The report analyses how prices and are increasingly moving beyond for affected countries. As MSF uses are affected by the fact that a few high-income countries in seeking newer vaccines more frequently in multinational companies dominate other profitable markets. © Florence Fermon/MSF
* Human papillomavirus, inactivated poliovirus, pneumococcal conjugate, oral cholera, measles, measles-rubella, measles-mumps-rubella, meningitis A, meningitis C, meningitis ACYW-135, three diphtheria/tetanus/pertussis-containing vaccines, hepatitis B, rotavirus, tetanus toxoid.
Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 3 It also demonstrates how entry unaffordable pricing policies; some price tag. Better solutions that can of additional manufacturers with of these countries even have lower make new quality-assured vaccines WHO-prequalified vaccines, in particular immunisation coverage rates than more affordable and adapted to the developing-country manufacturers, Gavi-eligible countries. environments where children are most stimulates competition and drives vulnerable are urgently needed. Efforts Finally, while recent years have seen the down prices. to accelerate real competition in the
E xecutive Summary introduction of several new vaccines vaccines market will deliver the most An overarching challenge that MSF that offer significant potential to reduce faces in analysing the vaccine market childhood deaths, there has been little sustainable price reductions; in the is the lack of data on prices and the investment in adapting – or optimising interim, procurement strategies that notoriously opaque nature of the – vaccine products to resource-limited benefit as many countries as possible market; this lack of transparency also contexts. Most vaccines still need to be should be pursued. Collective action inhibits efforts to improve affordability. refrigerated in a rigid ‘cold chain’ until is needed to improve price transparency Price secrecy is ubiquitous in the the moment they are administered, and ensure affordable prices for quality- vaccines market, putting countries which is an immense challenge for assured vaccines in all countries, so that and other purchasers at a distinct places without electricity. Multiple doses governments can make the benefits disadvantage when negotiating are needed to fully protect children, of immunisation accessible to their with companies. and bulky products complicate populations. Shedding more light transport to remote areas. These are on the vaccine industry will benefit While Gavi, the Vaccine Alliance, some of the obstacles that annually children everywhere. has helped to lower prices of new prevent almost 22 million children and underused vaccines for its eligible under one year of age from receiving countries – originally the poorest 73 the basic package of life-saving vaccines. countries of the world – the cost to Whether in a small village in rural Congo fully immunise a child has nevertheless or a refugee camp in Iraq, vaccine skyrocketed. Even at the lowest global delivery can be extremely difficult prices, the introduction of the newest and costly to execute. A growing body vaccines against pneumococcal and of evidence, including MSF research, MSF faces increasing diarrhoeal diseases (pneumococcal “ shows that some vaccines can remain conjugate and rotavirus vaccines, challenges in offering effective outside of a strictly regulated respectively), and against cervical full immunisation temperature range, and rapid steps cancer (human papillomavirus vaccine) to re-label vaccines for their true heat to children in our has increased the cost of the full stability are needed, along with further projects. The rising vaccines package 68-fold from 2001 investments in better adapted products. to 2014 [see box, page 6], calling price of the basic into question the sustainability of Vaccine commodities themselves vaccines package immunisation programmes after account for almost half of the 57 billion means that we can't countries lose donor support. Of US dollars (US$) needed to finance afford to protect particularly serious concern is the the Decade of Vaccines – the global kids living in crisis, impact of this drastic increase on framework for expanding access to most middle-income countries immunisation from 2011 to 2020. and nor can many (MICs), which are benefitting neither In the meantime, many countries, countries who want from lower prices negotiated by especially middle-income countries, to protect their organisations such as Gavi, nor are unable to afford the newest vaccines children. from international donor support. for their populations, nor can „ Many children living in MICs are not organisations such as MSF provide Dr Greg Elder, MSF Deputy benefitting from new, life-saving these vaccines to crisis-affected Director of Operations vaccines as a result of irrational and children, because of the very high
4 Médecins Sans Frontières | The Right Shot 2nd Edition January 2015 Affordability and vaccine pricing Affordability and vaccine pricing
Unaffordable prices hinder countries from introducing new, life-saving vaccines and threaten the sustainability of immunisation programmes. Under the current paradigm, ‘affordability’ is defined by what countries and donors are willing to pay rather than a rational system that maximises access for all countries and populations.
The support of Gavi, which provides Gavi-eligible and required to self-finance struggle to access the lowest ‘Gavi-eligible’ countries [see box below] the vaccines, they may have to pay up global vaccine prices, being with temporary access to subsidised to six times more for PCV, according to unable to systematically access vaccines at negotiated lower prices, has what we consider to be a conservative Gavi-negotiated prices. enabled many of the poorest countries estimate by Gavi.2 There is no global consensus on the to introduce new and underused vaccines The challenge of unaffordable most effective way to improve vaccine in their immunisation programmes.1 vaccines is even more pronounced for affordability. Various actors develop However, within the next five years the range of so-called ‘middle-income and implement selected strategies, more than 25% of Gavi’s country countries’ (MICs) that have never often with different country groupings cohort will ‘graduate’, i.e. become been Gavi-eligible, nor had access to or at the regional level. Strategies to ineligible for full Gavi support, and Gavi’s lower prices. Prohibitively high enhance access to affordable vaccines it is estimated that by 2025, 29 of prices are causing many MICs to fall worldwide are urgently needed; some the original 73 eligible countries behind the Gavi-supported countries of these strategies are discussed in will have lost Gavi support entirely. in the rate of introducing PCV in their this report, and include promoting These countries will then face the national immunisation programmes price transparency and price dual challenge of meeting the higher [see Graph 3, page 14 ]. The US monitoring mechanisms, pursuing cost of new vaccines and fully self- itself is also challenged with high pooled procurement, increasing financing their national immunisation prices: the number of US physicians competition through an expanded programmes. For example, a highly offering immunisations is reported to manufacturer base, and designing donor-subsidised price for the be in decline as a result, and one- new models of vaccine development. pneumococcal conjugate vaccine third of family-practice doctors are Broader availability of predictable and (PCV) has enabled many Gavi-eligible considering ceasing vaccinations sustainable access to low-cost vaccines countries to introduce the vaccine and because of the high prices of vaccines.3 would enable more countries to afford prevent avoidable childhood mortality. Beyond countries, non-governmental to introduce life-saving vaccines into When these countries are no longer organisations (NGOs) such as MSF also their health systems.
Eligibility for Gavi support
A country’s eligibility for Gavi support is determined by its Gross National Income (GNI) per capita. Since 2011, Gavi has implemented a graduation policy, whereby when a country’s GNI per capita crosses the threshold of US$1,570, support is phased out over the next five years. During ‘graduation’, stepped country co-financing requirements increase linearly until countries are required to fully self-finance the vaccine by the end of the five-year period.1 Gavi’s graduation policy is far stricter than the eligibility threshold of the Global Fund to Fight AIDS, Tuberculosis and Malaria (Global Fund).
Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 5 The rising price of immunising a child
Several new vaccines have been For instance, according to the Pan increase their immunisation budgets. added to the WHO immunisation American Health Organization (PAHO) For example, Honduras is currently schedule since 2001 [see Graph 1, which has historically benefited from graduating and will stop receiving page 7]. Using the yearly lowest access to lower prices due to the Gavi support as of 2016. Honduras will publicly published prices (available PAHO Revolving Fund, ‘the cost have to then cover the US$5 million only to some developing countries), per child vaccinated was less than currently annually paid by Gavi for in 2001 it cost a minimum of US$0.67 US$5 [in 1979], while it is currently new vaccines, which represents a 38% to immunise a child against six approximately US$70 per child increase in the government’s present diseases (tuberculosis, measles, immunised, only taking into account expenditures for immunisation.7 diphtheria, tetanus, pertussis and the cost of the vaccines [excluding Moreover, this cost will increase more Affordability and vaccine pricing poliomyelitis); in 2014, it costs a HPV vaccine]’.4 Many countries if the country introduces the HPV minimum of US$32.09– 45.59* to outside of the PAHO region are worse vaccine in the coming years. immunise a child against 12 diseases off as they procure vaccines on their Other estimates for how much (tuberculosis, measles, rubella, own and pay much higher prices. country immunisation budgets will diphtheria, tetanus, pertussis, In some of these countries, prices can rise to cover new vaccines are hepatitis B, Haemophilus influenzae reach more than 20 times the price increases of 197% in Sri Lanka type b, poliomyelitis, pneumococcal paid by Gavi / UNICEF: for instance, between 2012 and 2018, 801% diseases, rotavirus and, for adolescent the HPV vaccine is purchased at in Congo, and up to 1,523% and girls, human papillomavirus (HPV)). EUR75 / US$100 in Macedonia, 1,547% for countries like Angola So while the number of diseases or 22 times the price paid by Gavi- and Indonesia, respectively8 [see Table against which a child is immunised supported countries.5 The price 1, ‘Select Gavi-graduating country has doubled between 2001 and increase for the newest vaccines co-financing payments for new 2014, the cost of the vaccines – HPV, pneumococcal conjugate vaccine costs,’ page 13]. Given package to fully immunise a child has vaccine (PCV) and rotavirus – is such that vaccines are only part of disproportionately multiplied 68-fold. that some MICs have deemed them the cost to fully immunise a Moreover, this estimate represents not cost effective enough to introduce child, and that other programme the theoretical best-case scenario, into their Expanded Programme on costs must still be added (human as it is based on the lowest available Immunization (EPI) schedule.6 resources, transportation, cold chain, prices for the UNICEF Supply Division Gavi-graduating countries are infrastructure, other immunisation and restricted to a select group of preparing to lose both the subsidy supplies, etc.), this escalation of developing countries, usually only to purchase vaccines and access vaccine prices seems difficult to Gavi-eligible countries. to some lower negotiated prices. absorb for many countries. The situation is particularly difficult for Even if countries can maintain their developing countries, including MICs, procurement at the lowest price, the that do not receive Gavi support. end of Gavi subsidies will drastically
* US$32.09 is the price to immunise a boy in 2014; US$45.59 is the price to immunise a girl (includes the HPV vaccine).
6 Médecins Sans Frontières | The Right Shot 2nd Edition January 2015 Affordability and vaccine pricing
Graph 1: Price to immunise a child based on lowest price available to Gavi/UNICEF
50 45.59** 45 HPV & IPV, +41% 41.09*** 40 MR & rotavirus, +14% 32.66 35 PCV, +221% 28.59 32.22 30
25 US$ x68 Hib (penta), +767% 20
15 HepB, +127% 11.43 10
5 0.67 1.28 0 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014
** Includes 3 doses of HPV vaccine. *** Includes 2 doses of HPV vaccine.
Sources: WHO routine immunisation summary tables,9 Gavi,10 UNICEF Supply Division,11 MSF The Right Shot 1st ed.12
Notes and methodology: Available in Annex F, together with the timeline on WHO recommendations and Gavi vaccine funding decisions.
Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 7 Access to affordable vaccines: why price is a barrier to immunisation
What is an ‘affordable’ price?
Who decides what is affordable of health budgets to independently 73% of the ‘intermediate’ Gavi- and what metrics are used? support the full cost of vaccines.13 eligible cohort has introduced three This estimate is within the range of or more vaccines.* The estimate Vaccine ‘affordability’ is currently global development targets that have that vaccines will cost 0.6% of defined by what countries and donors set an expectation that countries health budgets is therefore unlikely are willing to pay, and not according will spend up to 10% of their budgets to hold for countries introducing Affordability and vaccine pricing to public health need. With poor on health (short of the 15% Abuja more new vaccines. countries affording new vaccines only Declaration) and that vaccine because they are heavily subsidised by Gavi-graduating countries do not commodities will occupy no more than donors such as Gavi, and many MICs have secure access to all Gavi- 1.0% of the total health budget.13,14 struggling to introduce these same negotiated prices in the medium to This measurement has been used as products, the long-term effectiveness long term. Gavi’s negotiations with justification for the ‘affordability’ of of the current global immunisation manufacturers for guaranteed price domestically financed immunisation system is questionable. Although even continuity post-graduation are programmes. However, the underlying some Gavi countries continue to face time-limited and company-specific, assumptions in the Gavi fiscal space challenges in their ability to pay for new with procurement caveats that may analysis prove problematic for broader vaccines, Gavi has nevertheless enabled be legally and programmatically application, for several reasons. tremendous progress in access to challenging to implement. vaccines for many of the world’s poorest The model includes external Vaccine investment at country countries. Attention must now focus on resources (such as grants from level has increased more slowly sustainable solutions for all countries. the Global Fund and the World than was assumed in original Bank) within the health budget Gavi is a significant voice in the global fiscal space analyses. This could calculation, artificially inflating the debate on vaccine affordability. Gavi be attributed to under-reporting, resources available to Ministries of is trying to define the lowest available reallocation of health budgets Health for reallocation. These donor price for the vaccines it purchases, away from vaccines or simple limits funds fluctuate according to global the countries that merit the lowest on how much countries can invest economic conditions and priorities, price and the budgetary responsibility in vaccination.15 and they should not be considered of developing countries that must available for funding vaccination. fully finance their own immunisation programmes once Gavi support ends. The model uses a static estimate for the number of vaccines Gavi is trying New price reduction developments introduced. Each additional vaccine to define the have been announced for Gavi-eligible will compound the eventual cost countries, each with separate conditions. lowest price, of full immunisation for Gavi- Gavi’s threshold of US$1,570 GNI per graduated countries. The first wave the countries capita (revised each year for inflation) of graduating countries in this suggests that Gavi donors consider that merit the analysis have skipped introducing this economic indicator to represent lowest price and one of the most expensive vaccines a country’s ability to fully finance its – HPV – but future graduating the budgetary own vaccines. countries may assume the price responsibility Furthermore, a Gavi-commissioned burden for this vaccine. While 11 of of developing fiscal space analysis generated a model the 16 Gavi-graduating countries in predicting that Gavi-graduating countries the analysis have introduced two or countries. would need to allocate only 0.6% fewer vaccines with Gavi-support,
* Using country groupings from Saxenian et al., 2011 (country grouping based on 2009 per capita GNI, with ‘intermediate’ countries having a 2009 per capita GNI of US$996–1,499, and graduating countries 2009 per capita GNI of US$1,500 or more), and vaccine introduction from ‘disbursements by program year’ from www.Gavialliance.org/results/disbursements/
8 Médecins Sans Frontières | The Right Shot 2nd Edition January 2015 Affordability and vaccine pricing
Progress towards affordable access classification. GlaxoSmithKline (GSK) from accessing vaccines at affordable has been one of the few companies to prices (e.g. Gavi prices are for Gavi- While the global community lacks a publicly disclose significant information eligible countries only); and even rational pricing system that serves all about its vaccines tiered pricing the lowest prices offered by some countries and populations, Gavi has strategy for developing countries, pharmaceutical companies are likely nevertheless had a key role in reducing categorising countries by their ability to be inadequate compared to those prices of vaccines for its group of to pay, commitment to vaccination achieved by competition between eligible countries, and the ‘Gavi price’ programmes and volumes purchased multiple manufacturers. To date, is often used as the worldwide lowest [see box ‘How do pharmaceutical high prices charged to MICs for PCV reference price. As a result of its companies set their vaccine prices?’, by GSK and Pfizer under their tiered negotiations with manufacturers and pages 20 -22].17 In late 2013, GSK also pricing strategy has led to this group special agreements, Gavi has managed published the latest results of its candidate of countries failing to adopt PCV as to secure vaccines at reduced prices – malaria vaccine (Mosquirix), publicly widely as low-income countries that often one-half to two-thirds lower than committing to selling the vaccine at no have benefitted from both lower other known public prices – although more than a 5% profit margin.18 prices and donor financial support. these agreements are negotiated on If sustainable and predictable prices an ad hoc basis and only available to Some of these efforts will, however, were available more broadly, more 16 Gavi’s limited group of countries. only benefit selected countries and countries would likely be able to afford Pooling vaccine procurement – as is populations while excluding others to introduce life-saving vaccines. practised through the PAHO Revolving Fund [see box, page 15] – allows some countries to benefit from bulk purchasing and financing mechanisms, and access low prices through high volumes and economies of scale. Affordability is not the only obstacle It also provides manufacturers with to accessing vaccines predictable and reliable demand Low prices are a critical part Adaptations can also extend the forecasts and purchases. of sustainable immunisation reach of vaccination beyond what Some manufacturers have been programmes, but weak health is achievable with conventional active in defining affordability on systems are a significant obstacle vaccines. For example, a more their terms, with several companies to successful vaccine delivery. thermostable pentavalent vaccine publicly committing to global access Vaccines ‘adapted’ for use in would be available at 97% of policies for selected new vaccines. resource-poor environments can health centres, instead of 87% For example, under a product lower programme costs by reducing using the current pentavalent development partnership including associated systems-related needs, vaccine in the cold chain; removal WHO and PATH, the manufacturer such as the constraints of the cold of the pentavalent vaccine from Serum Institute of India – an emerging chain. The key vaccine adaptations the cold chain would open up economy manufacturer – developed that MSF teams working in space for even more Expanded the Meningitis A vaccine with a developing countries need include: Programme on Immunization (EPI) specific affordability target of US$0.50 vaccines to reach health centres.19 per dose [see Meningitis Product • vaccines that are stable at high Supply-chain modelling of Card, page 60]. and freezing temperatures different product adaptations can further demonstrate the positive • simplified administration routes Pharmaceutical companies from impact of adapted vaccines. industrialised countries claim to have • fewer doses and more flexible adopted tiered pricing practices to dosing schedules In some circumstances, additional promote access and affordability for incentives may be needed to developing countries, while achieving • reduced volume and bulkiness develop better adapted products, particularly for adaptations needed large revenues with ‘blockbuster’ • improved efficacy of oral for developing countries. Possible products in high-income economies. vaccines However, these tiered pricing policies options could include development are largely not publically available • more efficacious antigen prizes, preferential procurement, and – with minimal data available combination for low-middle- fast-tracked regulatory processes, – often have no clear rationale or income countries (LMIC). or advanced purchase commitments. relation to a country’s economic
Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 9 Particularities of the vaccine market
In the vaccine market, the scarcity of publicly disclosed vaccine prices and Figure 1: MSF analysis of the new vaccine market other essential data undermines the development of effective public health MSF's analysis (based on Porter's Five Forces*) of the international market policies. Vaccine prices spiral upward for new vaccines shows that the industry is extremely attractive but seemingly unchecked and yet some well-protected, thus excluding new entrants while enabling current pharmaceutical companies claim that manufacturers to maintain strong positions and potentially high margins. vaccine profits are still insufficient to keep them in the market. Amongst some experts, low prices have been Threat of new entrants blamed for market collapse, particularly is LOW Affordability and vaccine pricing when vaccine manufacturers fled the Expanded Programme on Immunization (EPI) market in the late 1990s. Since
then, UNICEF has endeavoured to Rivalry among existing Buyers’ bargaining power mitigate risk by brokering multi-year is companies is LOW LOW/AVERAGE procurement agreements with multiple vaccine manufacturers.20
Most pharmaceutical companies do not reveal prices and many require Threat of substitute products is vaccine purchasers to sign price LOW/AVERAGE confidentiality clauses that forbid disclosure of pricing information. Information asymmetry prevents to produce a specific product and rotavirus) there are only two WHO- countries from effective negotiation to cannot readily be diverted to other prequalified products, each resulting secure lower prices, and compromises uses) and the regulatory processes in a duopoly; furthermore, the two their ability to budget appropriately required to obtain and maintain vaccines are not substitutes for one for new vaccine introduction. plant and product prequalification.22 another because of different product An analysis of the new vaccine market characteristics. When competition Buyers’ (countries’) bargaining power can be based on Porter’s Five Forces exists, originator products can be is low/average. A lack of transparency framework.* The MSF analysis replaced with cheaper, quality- and knowledge regarding existing [see Figure 1] describes the bargaining assured vaccines from low-cost products, characteristics and power of buyers, the threat of new manufacturers. prices limits the capacity of buyers entrants to the market, the threat Rivalry among existing companies of substitute products and rivalry – mostly countries – to make 23 is low. When there are only a within the industry, concluding informed decisions. With few few originator companies for a that the vaccines market favours manufacturers in the market (often 24 particular vaccine, rivalry is low and manufacturers – not purchasers. forming duopolies/oligopolies), companies tend to keep prices high buyers’ bargaining power is limited. until a lower-cost manufacturer Buyers can increase their power Threat of new entrants is low. enters the market.24 When low-cost by concentrating their demand Barriers to entry are high, manufacturers do enter the market, (e.g. by pooling procurement). because of capital-intensive and strategies such as tiered pricing time-consuming research and Threat of substitute products is low/ allow originator companies to development (R&D) and intellectual average. Vaccine substitution (within remain competitive against low-cost property (IP) restrictions, high the industry) is possible, but depends manufacturers in the low-income- sunk and fixed costs (sunk costs on the availability of competitor country segment, by securing a are those that, once committed, products and product characteristics. high margin in developed markets cannot be recovered – e.g. the For example, for each of the three while reducing their prices in low- cost of equipment that is designed newest vaccines (PCV, HPV and income countries.
* Porter’s Five Forces is a framework used to analyse the level of competition within a particular industry and inform business strategy development. The five forces analysed (threat of new entrants, threat of substitutes, bargaining power of suppliers, bargaining power of buyers and industry rivalry) define competitive intensity and the attractiveness of a market to potential entrants. For more detail, read the seminal article by Michael E. Porter ‘How Competitive Forces Shape Strategy’ in the March 1979 Harvard Business Review.21
10 Médecins Sans Frontières | The Right Shot 2nd Edition January 2015 Affordability and vaccine pricing
The concentration of vaccine would facilitate attempts to determine price of US$2.16 a dose for low-income manufacturers, combined with vaccine affordability. countries. The entrance of new and high entry barriers, significantly low-cost manufacturers since 2008 has Competition brings vaccine limits competition in this market, contributed to lowering the price per prices down so that manufacturers making dose by 38% [see Graph 2]. Among the Prices usually fall when new new vaccines operate in a highly manufacturers enter the market. newest and most expensive vaccines, protected environment. For instance, UNICEF purchased the there is currently little competition: Clear and precise information on pentavalent vaccine for Gavi-eligible the PCV, HPV and rotavirus vaccines the real costs of developing and low-income countries from a single each have only two WHO-prequalified manufacturing vaccines, which would supplier at US$3.50 a dose in 2001. manufacturers, creating de facto also clarify whether industry threats In 2012, UNICEF purchased the vaccine duopolies for the manufacturing, to exit the vaccines market are valid, from four manufacturers, at an average distribution and pricing of these vaccines.
Graph 2: Number of manufacturers (by type) and price, pentavalent vaccines purchased for Gavi-eligible countries
3.80 6 3.62 3.62 3.61 3.61 3.60 3.54 3.50 3.50 3.39 5 3.40 3.37 3.20 4 3.00 3.00 3 2.80 US$ PER DOSE 2.60 2 2.48 2.40 1 NUMBER OF MANUFACTURERS IN UNIT 2.20 2.16 2.00 0 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012
Number of multinational manufacturers (IFPMA) Gavi/UNICEF average price per dose, pentavalent vaccine
Number of emerging economy manufacturers (DCVMN)
Sources: UNICEF Supply Division 25,26
Notes and methodology: to UNICEF for each year between to UNICEF at any time between • For Gavi-eligible countries only. 2001 and 2012. 2000 and 2012: Biological E, • Volume and value data have been Panacea Biotec, Serum Institute • Price per dose is calculated by updated with the latest figures of India and Shantha Biotechnics dividing the total value spent by from May 2013. (emerging manufacturers); UNICEF to purchase pentavalent Crucell/Berna Biotech Korea and vaccines by the total number of • Manufacturers listed below have GSK (industrialised manufacturers). doses purchased and donated supplied pentavalent vaccines
Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 11 NGO access to affordable vaccines
MSF is one of several non-governmental years of negotiations, neither Pfizer nor negotiations, MSF will make a short-term organisations that vaccinate children and GSK have been willing to sell MSF the exception to its non-donation policy and struggle to access affordable vaccines for vaccine at the lowest global price; both accept a donation for a limited supply of their programmes; high prices limit the have offered MSF donations instead. PCV over the next few years. The serious use of new vaccines such as PCV, HPV or Donations have a short-term affordability delays in providing life-saving vaccines rotavirus, for example, by reducing the benefit, but they are unsustainable for children living in crisis have forced number of children that it is possible to and often complicated by company- MSF to make this pragmatic, though target for immunisation. imposed restrictions on geographic unsustainable, decision. or population use and volume limits, MSF believes that humanitarian A sustainable mechanism is urgently organisations and NGOs should be able and can undermine recipients from needed for MSF and other humanitarian
Affordability and vaccine pricing to purchase vaccines at the lowest global transparently communicating about actors to quickly and affordably access new price – currently the Gavi price – for their procurement challenges. Furthermore, vaccines for the world’s most vulnerable medical operations. Gavi is finally publicly vaccine donations create long-term children, regardless of where they live. supporting this notion.27 However, MSF harm by undercutting the market and and others still cannot systematically stifling competition, as smaller companies purchase vaccines at Gavi prices,28 and cannot match donation offers, even “ Refugee children are MSF believes the commercial price that if such companies offer low prices. incredibly vulnerable Gavi pays is still too high. Organisations such as WHO, UNICEF to vaccine-preventable and Gavi have institutional policies MSF has been in negotiations with diseases...and urgently against accepting donations.29,30 Pfizer and GSK since 2008 to access need access to the PCV at the lowest global price. PCV In principle, donations are not a newest vaccines. „ could protect thousands of refugees strategy that MSF favours as a means Dr Greg Elder, MSF Deputy and people living in hard-to-reach areas of dealing with affordability challenges; Director of Operations from pneumonia. However, after five however, after many years of failed price
Vaccinating in HUMANITARIAN emergencies Emergencies can quickly disrupt a (PCV) to protect refugee children’s to purchase approximately 24,000 country’s health system – particularly lives. However, policy obstacles and doses of PCV10 from GSK. The high in already fragile states with weak manufacturer refusal to extend Gavi vaccine price forced MSF to scale back health systems – thereby impacting prices to NGOs have prevented vaccination of the originally planned the country's ability to maintain high rapid implementation of recent older age range as it could only afford immunisation coverage even for basic WHO guidelines recommending to immunise children aged up to 23 vaccines. The most recent coverage immunisation programmes in months. The vaccination campaign estimates by WHO demonstrate humanitarian emergencies. was carried out in three rounds from declining vaccine coverage in July through September 2013. In 2013, a retrospective survey countries experiencing emergencies. documented childhood mortality For example, the coverage rate in in Yida refugee camp, South Sudan, Central African Republic fell from 47% at levels above the emergency to 23% between 2012 and 2013, and threshold. Having determined that in Syria the rate fell from 72% to 41% pneumonia was a frequent cause between 2011 and 2013.31 of child deaths in the Yida refugee Children caught in emergencies are population, MSF decided to vaccinate among the world’s most vulnerable, children with PCV and pentavalent yet are not routinely receiving vaccines. At the time of this decision, protection from life-threatening MSF had already been in negotiations diseases, such as pneumonia and with GSK and Pfizer for upwards of diarrhoea. In refugee camps where five years to purchase PCV at the MSF works, pneumococcal diseases lowest global price. After continued are a major cause of morbidity and refusals by each company, with mortality and MSF has recognised donation offers extended to MSF
the significant potential of the instead, MSF decided to pay US$7 Libessart/MSF © Yann pneumococcal conjugate vaccine per dose – double the Gavi price –
12 Médecins Sans Frontières | The Right Shot 2nd Edition January 2015 Affordability and vaccine pricing
Affordability challenges for Gavi-graduating countries
While Gavi currently subsidises vaccine the GNI eligibility threshold (currently are already facing.8 Several have sought purchases in almost all of its originally at GNI US$1,570 per capita), 20 Gavi- external donor support to help finance eligible countries, more than a quarter graduating countries are experiencing their immunisation programmes of its country cohort is ‘graduating‘.8 an aggressive increase in co-financing post-Gavi; another will become the 8 Some of these countries will lose Gavi obligations through the graduation recipient of a vaccination trust fund. 32 support entirely starting from 2016. process. Some graduating countries The expected budget increases for previously-supported Gavi new vaccines Countries receiving Gavi support for have expressed concern that their are listed in Table 1. The table excludes new vaccines are required to finance increasing immunisation costs cannot other non-Gavi-supported vaccines that a portion of the vaccine cost with be sustainably financed as they lose countries have to also finance. non-Gavi funds; this ‘co-financing’ Gavi subsidies. Saxenian et al. have requirement is based on a country’s reported on the affordability challenges GNI per capita. Triggered by reaching that some of these graduating countries
Table 1: Select Gavi-graduating country co-financing payments for new vaccine costs (in US$)
Increase Country 2012 2018 2012 – 2018 (%)
Angola 2,267,799 34,542,500 1,523%
Armenia 193,804 1,082,000 558%
Azerbaijan 1,224,450 3,028,500 247%
Bhutan 39,068 133,500 342%
Bolivia 730,675 5,134,000 703%
801% Congo 563,712 4,513,500 “ When Nigeria Georgia 239,941 1,710,000 713% exits from Guyana 36,447 365,000 1,001% Gavi support,
Honduras 1,088,385 3,365,000 309% it needs to be able to get 1,547% Indonesia 2,088,500 32,314,500 vaccines at Gavi Kiribati 15,475 60,000 388% prices or lower Moldova 154,092 1,116,000 724% to continue to
Mongolia 129,985 676,000 520% afford them. „
Sri Lanka 943,752 1,860,500 197% Professor Muhammed Ali Pate, former Minister of State Total 7,627,585 89,901,000 1,179% for Health, Nigeria
Source: Saxenian et al.8
In addition to losing the Gavi subsidies, current prices – which will already stretch a variety of conditions, rendering these Gavi graduates have only time-limited health system budgets – once Gavi ad hoc deals, like short - term donations, access to the lower negotiated Gavi subsidies conclude. Gavi has secured unsustainable in the long term.33 Some prices, and only for specific vaccines. an extension of some of its discounts companies that also supply Gavi, such as Without long-term assured price access for graduating countries from some Merck (for rotavirus and HPV vaccines), or new low-cost competitors entering manufacturers. These agreements – with have yet to make similar commitments the market, vaccine prices for Gavi- Crucell, Sanofi Pasteur/Shantha, GSK for Gavi-graduating countries. graduates could spike far higher than the and Pfizer – are time-limited and with
Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 13 Middle-income countries struggle to access affordable vaccines
For countries that are considered middle- to access new vaccines at affordable Vietnam found that the introduction income economies – MICs currently prices. Twenty-one of the 54 countries of new vaccines would increase the number more than 100 – introducing categorised as lower-middle-income government’s budgetary costs by more new vaccines is an immense challenge (LMIC) are Gavi-eligible; the remainder, than 100%.37 Given that vaccines are only from an affordability standpoint. The and all of the upper-middle-income part of the cost to immunise a child – for MICs, with a combined population countries (UMIC) are either unable instance in Honduras, total vaccine costs of about five billion, a birth cohort to access Gavi support or will be for a immunised child are US$39.93, but 36 of approximately 96 million,34 and ‘graduating’ soon. comprehensive implementation costs US$136.62 – the escalation in vaccine where 75% of the world’s poor live,35 Higher vaccine costs are difficult to prices has become prohibitive.38 have diverse public health needs and absorb in many MIC budgets, as these
Affordability and vaccine pricing economic realities. Achieving the countries already self-finance a costly Countries excluded by Gavi often ‘middle-income’ economic threshold immunisation budget. A 2006 study have few sources of external support has paradoxically limited their ability of comprehensive vaccine costs in for vaccine introduction. Bilateral price
Graph 3: Proportion of LICs and MICs that have introduced or plan to introduce Pneumococcal Conjugate Vaccines (PCV)
90%
78% 80% 76% 70% 70%
60% 54% 54% 56% 50% 55% 46% 40% 34% 32% 30% 27%
20% 16% 22% % OF TOTAL NO. LICS AND MICS 9% 10% 4% 5% 5% 0% 0% 2008 2009 2010 2011 2012 2013 2014 2015 2016
Low-income countries (LICs) Middle-income countries (MICs)
Sources: WHO,44 World Bank45
Notes and methodology: • Year of introduction (and planned • Classification of countries as low-income • MICs (include LMICs and UMICs): introduction for 2013, 2014, 2015 and (LIC) or middle-income (MIC) is done GNI of US$1,036 –12,615 2016) as registered by WHO as of 31 using 2012 GNI per capita, calculated Dec 2012. WHO draws the data from the using the World Bank Atlas method:45 • Number of LICs in 2012: 37 most recently received Joint Reporting • LICs: GNI of US$1,035 or less • Number of MICs in 2012: 100 Form. Latest update: 17 Jan 2014 (47 LMICs and 53 UMICs)
14 Médecins Sans Frontières | The Right Shot 2nd Edition January 2015 Affordability and vaccine pricing
negotiations with vaccine manufacturers between 2009 and 2016 being 47% it the country with the second highest place these countries, which may for LICs compared to 30% for MICs proportion of unimmunised children in have lower volumes and lack expertise [see Graph 3, page 14 ]. Despite the high the world. Other MICs similarly suffer in price negotiations, at a distinct pneumonia burden, MICs have been from poor health service performance disadvantage. Where certain vaccines slow to adopt this expensive new vaccine and disproportionately high disease have not been introduced into EPI, [for prices, see the PCV product card, burdens. The Republic of South Africa individuals may purchase them privately, page 72]. By 2016, it is expected that has a vaccination coverage of 65% and sometimes at prices comparable to 78% of LICs will have introduced PCV in an HIV prevalence rate of 17.9%,43 those in high-income countries. For their routine immunisation programmes, illustrating that despite its positive instance in 2014, the PCV13 vaccine versus 56% of MICs. The high cost is general economic achievement the was available for US$63.74 per dose in even altering the cost-effectiveness country’s public health indicators hospitals in Morocco, while in France analyses of these life-saving vaccines: remain dire. Countries like South the manufacturer price was US$58.43 Thailand found that, at the current price, Africa benefit neither from donor per dose. Many children – 77% of the PCV was not cost-effective enough to assistance (for immunisation) nor from MIC cohort – are vaccinated in countries be integrated into EPI.41 pricing mechanisms that can increase undertaking self-procurement for some affordability and accelerate availability of Economic indicators alone do not or all of their vaccines; these countries vaccines for the public. The HPV product encapsulate societal development, are paying higher prices than pooled card [see page 39] shows how the price nor do economic indicators necessarily procurement could yield.39 In some of of HPV introduction in South Africa is correspond to the ability of a country’s these countries, prices of vaccines can affecting the government budget. health system to reach its population reach more than 20 times the price paid with essential health services. Relying To understand how arbitrary the by Gavi / UNICEF. For instance, the HPV solely on crude economic thresholds economic indicators that are used to vaccine is purchased at EUR75/US$100 is too unsophisticated a method for divide countries are, consider that in Macedonia, or 22 times the price paid establishing a country’s ability to pay. in 2013 there were 28 countries that by countries supported by Gavi.40 For example, Nigeria is categorised as have never been Gavi-eligible that had By 2011, low-income countries (LICs) a LMIC, with a 2013 GNI per capita of a GNI per capita lower than that of had surpassed MICs in PCV introduction, US$2,760.42 Nigeria, however, has a the Gavi-graduating country with the annual growth rate of introduction vaccination coverage of 58%, making the highest GNI.39
PAHO’s Revolving Fund: a regional pooled procurement and financing mechanism for vaccines and related supplies
The Americas region has a diversity countries in the region to better The Revolving Fund has also of countries at various levels of plan for their immunisation negotiated with companies to economic development and health budgets, resulting in higher rates obtain most favoured nation status, system performance. Established of national financial self-sufficiency; whereby manufacturers agree to in 197746 as part of the Expanded 95% of vaccines costs are financed offer the Revolving Fund the lowest Program on Immunization (EPI) with national funds. More than global price for a specific vaccine of the Americas, the Pan-American 180 million vaccine doses (worth product. However, this is changing US$512 million) were purchased in Health Organization’s (PAHO) as companies that practise tiered 2012 for PAHO’s participating 35 Revolving Fund is a pooled pricing and some international countries and six territories.46 procurement and financing donors dislike the most favoured mechanism for vaccines and The Revolving Fund establishes nation clause and argue that MICs related supplies. The PAHO annual and multi-year tenders in the PAHO region – such as Brazil Revolving Fund has been credited for vaccines and makes use of or Ecuador – should pay higher prices with Latin America and the a credit line financed by PAHO than those offered through Gavi to Caribbean’s high immunisation member states. Historically, PAHO’s the region’s poorer countries. While rates, disease eradication and Revolving Fund has negotiated there were originally six Gavi-eligible elimination successes, early vaccine with manufacturers and obtained countries in the PAHO region, five introduction, and access to some the lowest prices by pooling of these countries are currently of the lowest vaccine prices in demand and offering the vaccine losing Gavi support through the the world.47 The predictability of at the same single price per vaccine graduation process. supply/demand and the lower for the region, independent of a prices negotiated have enabled country’s economic classification.
Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 15 Vaccine price and data opacity
The vaccine pricing landscape is introducing new vaccines and raises important element: the price the notoriously opaque, and prices paid concerns as to whether Gavi-graduating country will be charged for the vaccine. for the same vaccine vary significantly countries will be able to sustain their An evaluation of cost-effectiveness from one country to another. This is in full immunisation programmes when analyses of HPV concludes that, “in contrast to the availability of price data they can no longer access the Gavi- the end then, the key determinant of for other public health commodities. negotiated prices.49 cost effectiveness is the only factor that Prices for HIV antiretroviral (ARV) cannot be evaluated, even though it Without price comparison mechanisms, medicines, for example, are published will be important when deciding on countries cannot fully understand on the WHO’s Global Price Reporting the vaccine to be used in a national the vaccine market and are unable Mechanism, allowing a modest prevention scheme.”52 Affordability and vaccine pricing comparison of costs across countries, to determine if they are paying an companies and time – although the affordable price for their vaccines. The growing demand from countries lack of generic competition for new Governments and policy makers are to have access to reliable price and ARVs, and the increasing use of tiered increasingly using cost-effectiveness procurement data23,51 has prompted pricing for these drugs, is significantly analyses to inform decision-making the international community to obscuring ARV prices across countries.48 when planning the purchase and start developing initiatives on price The opacity of vaccine pricing hinders introduction of new vaccines.50,51 transparency, but information remains countries, especially MICs, from However such studies often lack an scarce [see page 18].
Why are the cost components of a vaccine so obscure?
The cost components for vaccines however, little of this information that are too high; for example are challenging to understand, is communicated publicly. PhRMA, Pharmaceutical Research and as most associated costs are not Manufacturers of America, states that Myths and opacity publicly available. Vaccine costs total development costs can reach behind R&D costs should depend upon governments’ close to US$1 billion.53 But in a 2009 and pharmaceutical companies’ The R&D investment required for a new article in the journal Vaccine, Light et investment choices in research and vaccine varies widely and companies al. estimated that rotavirus vaccine development (R&D), cost of goods, themselves cite wildly different figures. development costs were US$167– 508 manufacturing, regulatory approvals Often the pharmaceutical industry million for Merck’s product and and marketing, among other factors; provides R&D investment estimates US$150–466 million for GSK’s
Table sources: GSK, Merck and Table 2: Total worldwide revenues of HPV, Pfizer annual reports 2006 – 2013; PCV and rotavirus vaccines, published research note.62 by companies (in US$ million) Notes: Exchange rate based on Oanda.com and xe.com, using yearly July rates. Total cumulated Average sales sales, in US$ per year, in US$ Sales time period * These amounts do not reflect million million vaccines sales in major European countries made through the joint 2010 – 2013 Pfizer, Prevnar 13 15,905 3,976 venture Sanofi Pasteur MSD. However, amounts reflect supply Merck, Gardasil* 9,896 1,237 2006 – 2013 sales to Sanofi Pasteur MSD.
Merck, Rotateq* 4,282 535 2006 – 2013
GSK, Synflorix 2,240 448 2009 – 2013
GSK, Rotarix 3,038 380 2006 – 2013
GSK, Cervarix 2,046 292 2007 – 2013
16 Médecins Sans Frontières | The Right Shot 2nd Edition January 2015 Affordability and vaccine pricing
product (in 2008 US$), acknowledging for a product: through their R&D Nevertheless, Merck and GSK’s public that the Phase III clinical trials were investment and by paying high prices. statements that the price of their HPV unusually large; GSK cited them as vaccines to Gavi represents the cost of The opacity of the ‘largest infant vaccine trials ever manufacture, at US$4.50 and US$4.60 manufacturing costs conducted’.54 This aligns with the per dose, respectively, demonstrates the findings of André et al. that costs to bring Opacity in manufacturing costs is significant profit margin that is derived a new vaccine to market ranged from also a challenge to making informed from sales to other countries, such as the US$200 to US$500 million.55 While public health decisions. It gives US, where the government is charged private sector investment in R&D rise to uncertainty regarding some US$121.03 and US$103.85 per dose, has been overstated, public sector pharmaceutical companies’ statements respectively. MSF is undertaking a study contributions to vaccine development that vaccines are being sold ‘at cost’ to explore the actual manufacturing costs are often under-reported. For the to Gavi-eligible countries. Without for HPV vaccine. HIV vaccine, in 2012 the public sector independent verification, it is unclear contributed approximately 83.4% whether profits are still being made off Without verifiable information on the of the overall investment, with the sales to the world’s poorest countries. real cost of manufacturing and other commercial sector contributing only In 2013, the president of Merck Vaccines cost data, it is impossible to accurately 3.5% in early-stage research and noted that the price of HPV vaccine at assess company profits. Nevertheless, development.56 Likewise for one HPV US$4.50 per dose to Gavi represented the high prices of these vaccines in vaccine, two Australian research Merck’s manufacturing cost, excluding developed markets have enabled centres alone are credited with 13% research, marketing or other costs.58 manufacturers to earn tremendous of research and development costs.57 A GSK representative also claimed that returns estimated to be at least 12 to 16 The US National Institutes of Health profit could not be made at their price times the cost of manufacture (based and US universities also contributed of US$4.60 per dose to Gavi.58 As no on the assumption that the Gavi price significant public resources to the independent group has been allowed represents the vaccine manufacturing development of the HPV vaccine. Such to verify the manufacturing costs cited cost) for Cervarix and Gardasil.58–61 investments are not factored into the by Merck and GSK, it is unknown Revenues as reported by the companies end price of the vaccine, meaning that whether this price represents the producing the newest vaccines are listed governments are often paying twice actual per-dose manufacturing cost. on page 16 [see Table 2, opposite].
The Advanced Market Commitment model: making profits FROM developing country markets
A precedent of deriving profits multinational manufacturers reap profits in excess of 20% from from developing-country vaccine (Pfizer and GSK) that had already the subsidy.65 The evaluation’s markets was established by the committed to producing a profitable conclusions noted that the AMC did Gavi Advance Market Commitment vaccine.65 In a 2012 evaluation not contribute to the development of (AMC) for pneumococcal vaccines. of the AMC, Dalberg Global the existing PCV products, and that The AMC concept was proposed as Development Advisors found “the substantial revenue potential of a means of spurring investment in that one of these manufacturers the Gavi market therefore may have vaccines for diseases concentrated expanded its manufacturing capacity been enough to attract low-cost in low-resource countries and of in response to the AMC (the other manufacturers without additional promoting rapid vaccine uptake in had already decided to expand subsidies [of US$1.5 billion from the 63,64 the most affected countries. It was for a global market).65 Despite AMC]”. While a third manufacturer hypothesised that a donor-subsidised the limitation of manufacturers is expected to enter the market in ceiling price and demand quantities being unwilling to share their 2019, the AMC was not a critical would incentivise a range of vaccine factor in this investment decision, costing information, the evaluation manufacturers to open new lines though a fourth company tripled nevertheless determined that the two of research that would not have their research investment in PCV manufacturers were earning returns otherwise been developed. after the AMC announcement.65 at or above the 10–20% mark To date, 73% of the AMC donor funds The Gavi AMC for PCV provided a typically referenced as incentivising (US$1.095 billion) for Gavi have been late-stage public- and philanthropic- suppliers in the vaccines/ committed to Pfizer and GSK. funded subsidy of US$1.5 billion pharmaceutical industry. The AMC that to date has benefitted two manufacturers may ultimately
Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 17 Despite global initiatives to improve price transparency, price information remains scarce
Price transparency is rare in the On country-specific data, some national vaccines market, with both countries websites provide public- and private- and pharmaceutical companies often sector vaccine prices, but the sites “ To the extent that reluctant to share price information. are typically difficult to navigate and we know what lack descriptive information about Some manufacturers have taken other countries are the products and price components, steps towards articulating their limiting the usefulness of the data and paying, that would global pricing strategy; for instance, accurate cross-country comparisons strengthen our arm both GlaxoSmithKline (GSK) and (see Annex A for methodology and [in negotiations with
Affordability and vaccine pricing the International Federation of difficulties encountered). To develop the companies]. „ Pharmaceutical Manufacturers & Vaccine Product Cards in this report, we Associations (IFPMA) published tiered- sought country price points to conduct Dr Yogan Pillay, Deputy Director General, pricing papers in 2013 that provide analyses across different economic Department of Health, South Africa some information on their pricing development levels. As concluded by 17,66 strategies for developing countries. S. van Dongen in a comparative analysis There is, however, little will to increase of websites reporting medicine prices transparency about prices themselves, in 2010, the utility of identified national as companies fear price erosion as price data was limited by missing in the public sector using tax payer a result of competition and publicly information such as the components of monies, it is reasonable for citizens available price references. For the each price, and the comprehensiveness to have access to the prices paid and purposes of preparing this report, MSF of the price information.69 to expect government and industry contacted nine companies to request accountability for the prices negotiated. Reasons cited by countries and information on their vaccine prices; companies for concealing vaccine all of the multinational manufacturers Developments in vaccine price prices include the fear that data could declined to share their prices. data availability and price be wrongly interpreted and concern For more information, see the box monitoring about parallel trade.70 These concerns ‘How do pharmaceutical companies have for instance pushed the once Outside of the prices published by the set their vaccine prices?’, pages 20-22 . publicly accessible Common European PAHO Revolving Fund and UNICEF, On the buyers’ side, the PAHO Drug Database (CEDD, called Euripid there are few initiatives to enhance Revolving Fund67 has been publishing since 2010), which was created “to price transparency.74 its prices for many years, but data make prices of pharmaceuticals easily At country level, initiatives exist to are limited to the weighted average available for the public of Europe”,71 enhance decision-making based on to now restrict its access to officials price by product presentation; the cost and price analysis. ProVac – a from its member countries. information does not include the programme-costing model developed manufacturer price per product, nor The availability of pricing information by the PAHO region in 2006 – was born volumes purchased, and historical for other public health commodities out of the need to strengthen economic prices are difficult to access. In 2011, such as ARVs for HIV,72 contraceptives evaluation and increase the use of UNICEF Supply Division for the and artemisinin combination therapy economic evidence to inform national first time retroactively published (ACT) for malaria, indicates that EPI decision-making. While not a price ten years of price information for vaccine price opacity does not need transparency mechanism per se, ProVac all its low-income country vaccine to exist. An analysis of six medicine enables countries to share economic purchases.11,68 UNICEF’s move to price-information mechanisms showed evaluations and costing studies, which increase transparency was a milestone that positive effects on access to benefit vaccine pricing decisions in vaccine price discussions, further medicines – such as uptake of higher- in other countries.75,76 The ProVac adding to the information base quality medicines, improved contract initiative has provided evaluation that has enabled the comparison negotiation outcomes, changes in support to 14 countries in the PAHO of prices across various regions and national pricing policies and lowered region for introduction of HPV, PCV by countries at different levels of prices – are seen when mechanisms and rotavirus vaccines. Following the economic development; those data that increase data quality and price success of the initiative, PAHO received sets inspired publication of the first transparency exist.73 As vaccines are requests for ProVac support from edition of the this report.68 largely purchased by governments countries outside of the region. Since
18 Médecins Sans Frontières | The Right Shot 2nd Edition January 2015 Affordability and vaccine pricing
its founding, ProVac has compiled data did not see clear commitments from differential pricing that offers the from more than 130 countries to assist countries to purchase the vaccines.77,35 ‘right’ price to a country, they use national decision-makers. publicly available information on The most promising initiative in the At a global level, the importance price information domain could be countries to classify them and justify of price transparency is gaining the WHO Vaccine Product, Price and a price at which to sell their vaccines. momentum as countries increasingly Procurement (V3P) project, a mechanism But as manufacturers maintain total articulate high prices as a barrier to that can have a critical role in fostering opacity on their R&D, production vaccine access. Almost half of the international data transparency costs and prices, it is significantly more US$57 billion budget of the Decade [see box below]. complicated for countries to negotiate of Vaccines (DoV) – the global Increased price transparency will help fair prices that can be defended against framework for expanding access to to fill the data gap and reduce the industry’s oft repeated statements immunisation from 2011 to 2020 – will current asymmetry of information that prices paid do not sustain future be absorbed by the cost of vaccine between purchasers and suppliers. investments in R&D and do not even commodities alone, and in 2012 MSF When manufacturers claim to use cover their operating costs. advocated price monitoring over the course of the DoV. At the 2013 World Health Assembly, a proposed framework for monitoring, evaluation The WHO Vaccine Product, Price and and accountability of the Global Procurement (V3P) Project Vaccine Action Plan (GVAP) included Launched in 2011, the WHO Vaccine Global Price Reporting Mechanism the addition of a report on trends in Product, Price and Procurement (GPRM)72 on HIV drugs. The project vaccine prices, with the development (V3P) project aims to develop a has started collecting pricing of indicators to monitor prices over mechanism to collect, assemble data and had a soft launch with 74 the decade. Monitoring prices is now and disseminate “reliable, accurate select country data in June 2014 considered a measure of success for and neutral information and [Objective 4 from Figure 2 ]. the GVAP, “a challenging task, but an data on vaccine product, price 77 The V3P could be critical to important priority”. and procurement, allowing for achieving improved international increased price transparency and In 2012, UNICEF Supply Division price transparency. As it moves more informed decision making in launched a middle-income country into implementation, sustained the vaccine implementation and pooled procurement pilot mechanism WHO and government political procurement processes”.80 for new vaccines, with one objective will and commitment to share being increased price transparency. The mechanism should be used price information will be key to the As part of the pilot, UNICEF asked collaboratively by countries, development and success of the V3P manufacturers to share prices especially self-procuring low- and mechanism. For more information, for countries participating in the middle-income countries and Gavi- visit the V3P website: www.who.int/ mechanism and reference pricing graduating countries, with the end immunization/programmes_systems/ for countries electing to self- product a web-based tool linked to procurement/v3p/platform/en/ procure.78,79 In the initial forecasting, the database, similar to the WHO 19 countries (with a birth cohort of 7.2 million) expressed interest in joining the initiative.78 At the time of this publication, UNICEF had not announced any awarded contracts Figure 2 from this pilot. No information on Phases of the V3P project why this procurement mechanism has so far not worked has been PHASE ONE PHASE TWO made public. It has been argued that few manufacturers responded Objective 1 Objective 2 Objective 3 Objective 4 to the tender, as they were unwilling Objective 5 to provide public reference prices, Information Consensus Testing & utility Implementation which companies see as potentially gathering & analysis & development assessment & roll out Impact evaluation undermining their capacity to sell at higher prices to other markets; another hypothesis is that companies
Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 19 Equipping countries with accurate Additionally, having access to the volumes, duration of contract) and reliable price information would terms and conditions by which other would assist governments in better assist decision making and lead countries manage to secure lower understanding product options to quicker and more sustainable prices (e.g. manufacturer, product, available and how to lower the adoption of new vaccines.51 presentation, procurement terms, cost of introducing vaccines.49,51
How do pharmaceutical companies set their VACCINE prices?
In an effort to better understand Out of the nine companies Emerging manufacturers from vaccine pricing, we contacted nine contacted: developing countries were more Affordability and vaccine pricing pharmaceutical companies* and • four shared their prices (Bio transparent and willing to share asked them to share their prices and Farma, Biological E, Panacea their prices and other pricing pricing strategies for this report. and Serum Institute of India); strategy and product information. Findings are presented below, • seven shared some information including companies’ responses.** regarding their pricing PRICING STRATEGY TRANSPARENCY strategy or vision (the four Pricing strategies are influenced by listed above and Crucell, the particularities of each market and Vaccine prices are difficult to GSK, Merck and Pfizer); the power of its actors. Please refer find. Companies usually do not • one did not reply within to the page 10 analysis of the new publish them, considering the the requested time period vaccines market and the forces active information to be proprietary (Sanofi Pasteur). in the industry. and confidential. Pricing reports published by the MSF Access Large multinational companies In the vaccines market, two groups Campaign, such as Untangling are not inclined to improve price of manufacturers emerge, each with the Web of Antiretroviral transparency as it is perceived to distinct pricing strategies. While Price Reductions, use price increase price referencing and each manufacturer will have its information voluntarily shared thus weaken their negotiating own particular strategy, two broad by pharmaceutical companies position with governments and models can be identified: or listed in searchable public other purchasers. One company Cost-plus pricing strategies databases, but our efforts cited price transparency as to secure vaccine price increasingly compromising its Value-based and differential information from companies ability to offer low prices to the pricing strategies were far less successful. poorest countries.
Group 1: Cost-plus pricing strategies82 price is mainly fixed on costs (e.g. costs of production)
The emerging manufacturers we contacted largely do not apply differential pricing strategies, selling their vaccines at similar prices to all countries, with price variation mainly attributable to differences in Incoterms,*** transportation costs and regulatory costs.
This strategy allows manufacturers to compete on price and use their low cost structure and ability to reduce costs to sell vaccines at a much lower price than other manufacturers.
* Details on company contacts available in Annex B. ** Research methodology presented in Annex A. *** See definition of Incoterms in Annex C.
20 Médecins Sans Frontières | The Right Shot 2nd Edition January 2015 Affordability and vaccine pricing
Group 2: Value-based and differential pricing strategies82 price is fixed on the basis of what buyers are willing/able to pay
This strategy is especially used in non-competitive markets (e.g. for newer vaccines) where manufacturers do not have to compete on price.
In this strategy, the price of the product is not evidently linked to costs; the manufacturer seeks the best price that the buyer is willing to pay, even if it means applying different prices to different buyers. This differential pricing or market segmentation strategy is often referred to as ‘tiered-pricing’.
Multinational manufacturers that replied to our request reported that they apply differential pricing strategies; however when asked for more information, most provided little or no or detail on how their tiered pricing policies are defined. Company responses follow:
• Crucell, a subsidiary of Johnson & Johnson, applies a tiered-pricing strategy, aligned with Johnson & Johnson’s Credo,83 and believes that tiered pricing is the best solution in markets with limited suppliers, and that preventing companies from tiering prices would lead to higher vaccine prices in developing countries. However, little information is publicly available on how tiers and prices are set.
• GSK operates a tiered-pricing approach, describing it as “based on a country’s development level and ability to pay”. GSK does not share further pricing information but has published a publicly available position paper on tiered pricing that details its seven-tier approach to differential pricing.17
• Merck details its pricing position as “a worldwide differential-pricing framework that takes into account many factors including countries’ level of economic development, public health priorities, volume and duration of procurement and economical value for the local health care system”. However, little information is publicly available on how tiers and prices are set.
• Pfizer does not share its pricing policy with third parties, but supports principles of tiered pricing, as developed in the 2012 IFPMA position paper on tiered pricing.66
EFFECT ON PRICES
These two different pricing strategies might decide to exit the market a similar price to all countries, are reflected in vaccine prices. when prices become too low while manufacturers from (e.g. Crucell exited the measles- Group 2 apply value-based and Pricing strategies influence the rubella UNICEF market in 2013, differential pricing strategies. In price set by manufacturers for citing the fact that pricing Graph 4, page 22, we see that a similar product. Companies trends were incompatible with the highest price paid (that from Group 1 above compete the company’s strategy), or to could be identified through on prices, and usually offer their concentrate on high-margin and public information sources) for vaccines at a lower price than more profitable markets (e.g. newer PCV by a MIC is 1,471% higher manufacturers from Group 2 vaccines, high-income markets). than the price to Gavi countries. [see Table 3, overleaf ]. As originator manufacturers claim that their Pricing strategies influence cost structure typically does not the price paid across buyers. allow them to compete on low- Manufacturers from Group 1 price competitive markets, they tend to offer their products at
Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 21 Table 3: Comparison between the highest and lowest available price to UNICEF for selected vaccines for low-income countries (Gavi-eligible countries only), in US$ per dose
Table sources: UNICEF SD,11 Vaccine Lowest price Highest price % difference Bloomberg News 201384
PCV, 2014 and SII* GSK * Price commitment from Serum Institute 73% forecasts of India (SII) to produce PCV and sell it $2.00 $3.40 – 3.50 at US$2 per dose.84
MMR (10-dose), SII Sanofi Pasteur ** Price commitment from Bharat 84% 2014 Biotech to produce a rotavirus $1.02 $1.89 vaccine (Rotavac) and sell it to the public sector at US$1 per dose.85 Measles (10-dose), Bio Farma Sanofi Pasteur 105% 2014 $0.22 $0.45 Affordability and vaccine pricing DTP (10-dose), Bio Farma Sanofi Pasteur 175% 2012 $0.16 $0.44
Rotavirus, 2014 Bharat Biotech** Merck 400% and forecasts $1.00 $5.00
Graph 4: Examples of vaccine price differences between countries, illustrating distinct pricing strategies (see also box on pages 20 & 21) 1,600 1,471 Group 1: Group 2: 1,400 Prices are similar Prices are diverse for all buyers. across buyers. 1,200 Price range is small. Price range 1,000 is substantial.
800
600 403 425 400 PRICE PER DOSE (base 100)
200 163 100 100 116 100 105 110 100
0 Serum Institute of India, Panacea, pentavalent GSK, pneumococcal conjugate measles-rubella (10 - dose vial) (10 - dose vial) vaccine, PCV10 (1- or 2 - dose vial) Group 1 Group 2
MICs, highest MICs, lowest PAHO Gavi/UNICEF (base 100)
Sources: UNICEF Supply Division,86 PAHO Revolving Fund,67 country price analysis (see Annex A for details on methodology and sources), communication with manufacturers.
Notes and methodology: • If the Gavi / UNICEF price for the • For SII and Panacea, price range Serum Institute of India (SII) vaccine for MICs was obtained through • Data are for 2013 or 2014. was US$100, the highest price communication with the companies. observed for the same product in • Group 1: companies operating • For GSK, prices represent the lowest a MIC would be US$163, or 1.63 cost-plus pricing strategies. and highest national prices found via times the UNICEF price. For GSK’s public information. • Group 2: companies operating PCV10, the highest price observed value-based and differential in a MIC is 14.71 times the price • Sources and definitions detailed pricing strategies. offered to Gavi / UNICEF. in Annex A.
22 Médecins Sans Frontières | The Right Shot 2nd Edition January 2015 Affordability and vaccine pricing Existing solutions to improve affordability and their limits
Pooled procurement initiatives and associated challenges
Existing solutions to improve economic indicators. As part of its mechanism, see ‘Developments vaccine affordability market-shaping strategic goal, Gavi in vaccine price data availability uses pooled procurement via UNICEF and price monitoring‘, page 18. Pooled procurement of vaccines – SD to negotiate lower prices on behalf a strategy whereby several countries The Gulf Cooperation Council, of the donors that pay for new and aggregate their individual volume established in 1978, includes six underused vaccines for Gavi-eligible participating countries that pool their needs, to their mutual benefit – can countries.88 The PAHO Revolving vaccine needs, aggregating demand help to reduce prices by leveraging Fund uses pooled procurement for and standardising specifications across economies of scale and streamlining a geographic zone, whereby any countries.89,90 Countries in the group heavy procurement processes by country in the Americas region can use the mechanism differently, with centralising vaccine tenders, contracts use its procurement mechanism to some countries using it occasionally and payment. It is an effective access the prices negotiated by the while others use it to supply the strategy to lower vaccine prices for Revolving Fund secretariat [see box: majority of their vaccines. the purchaser and lessen procurement PAHO's Revolving Fund, page 15]. 87 capacity requirements for countries. Countries of the PAHO region primarily At the request of its member states, For example, countries with small self-finance their own immunisation the WHO Eastern Mediterranean Region populations may have difficulty budgets, with more than 95% of the (EMRO) began work on a Pooled Vaccine negotiating affordable prices because cost of vaccines bought through the Procurement (PVP) initiative in 2011.39 of their limited profitability for suppliers Revolving Fund paid by national funds. The initial phase of the initiative received and resulting lack of market power. The Revolving Fund has, however, been interest from Egypt, Iraq, Jordan, under pressure to alter its principles of ‘Pooling’ demand from multiple Lebanon, Libya, Morocco, Syrian Arab regional solidarity and the availability purchasers benefits both purchasers Republic and Tunisia, and was ready to of one price for all countries [see box supply interested MICs with pentavalent and suppliers. Larger vaccine volumes overleaf: Two public health organisations vaccine, PCV, rotavirus vaccine and HPV mean greater negotiating power for with different price models]. vaccine as of October 2013.91,92 As of purchasers, such as governments, mid-2014, tenders had not yet been while pooled procurement provides UNICEF Supply Division developed released for the PVP initiative. manufacturers with more predictable the pilot Middle Income Country volumes for manufacturing plans, New Vaccine Procurement Initiative in In a 2010 analysis on pooled procurement allows improved forecasting and 2012, in response to growing concern mechanisms for vaccines, the World Bank reduces transactional costs through for Gavi-graduating countries and and Gavi highlighted the value of pooled simplified contracting and purchasing for other MICs left out of any other procurement mechanisms as: processes. Pooled procurement is existing pricing or pooled procurement predictability (stable flow of funds) used by the PAHO Revolving Fund, structures. The initiative was established UNICEF Supply Division (SD), by Gavi to pool demand among MICs for the equitability (especially for three newest and most expensive through the UNICEF SD, by the Vaccine participating low-income and small vaccines – PCV, HPV and rotavirus Independence Initiative for the Pacific countries that would otherwise vaccines – and aggregate forecasts for Islands (also managed by UNICEF SD), probably pay higher prices) 78 and the Gulf Cooperation Council. companies. No awarded contracts from this pilot have been published, efficiency (more efficient use of Countries and organisations that however, and information on why the resources and lower vaccine cost) practise pooled procurement vary mechanism has so far not worked is not feasibility (requires investment in their characteristics. For example, public; it is likely that few manufacturers and agreement on procurement Gavi’s eligibility policy (country GNI responded to the tender, as they were legislation) per capita Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 23 Two public health institutions with different price models Gavi / UNICEF and the PAHO Revolving Companies generally do not wish paid by the region for these newer Fund both use pooled procurement to offer MICs in the PAHO region – vaccines, in October 2013 PAHO’s strategies to leverage economies such as Brazil or Ecuador – the same member states agreed to a PAHO of scale for price negotiations with price as that offered to the poorest Directing Council resolution reaffirming manufacturers, but each has a different countries, such as those financed by the principles of the Revolving Fund philosophy on what is considered an Gavi. Some companies have even and requesting a review of the waivers affordable price. Gavi advocates tiered side-stepped the LPC by developing provided so far.94 In its reaffirmation, pricing,93 and uses donor support and different product presentations PAHO noted that past LPC exceptions its mandate of purchasing new and specifically for the Gavi and PAHO had been provided in good faith, but underused vaccines for only selected markets. For example, in the case of that prices for the Revolving Fund did developing countries as the basis for its PCV and HPV vaccines, GSK created not significantly decline subsequent negotiations with manufacturers. Gavi to the granted LPC exemptions.95 a two-dose vial specifically for sales Affordability and vaccine pricing promotes the concept that the lower to Gavi while continuing to offer the In 2014, Sanofi-Pasteur and Gavi prices it receives should be subsidised single-dose vial for the PAHO market announced new prices for inactivated by higher-income countries, which at a higher price. poliovirus vaccine (IPV)96 through a should be expected to pay more. four-tier pricing system. In refusing The PAHO Revolving Fund operates on PAHO has been facing significant to lower the price for its IPV vaccine principles of regional solidarity and the pressure from pharmaceutical to the PAHO Revolving Fund, and philosophy that pooled procurement companies, Gavi and Gavi donors with PAHO’s resistance to grant should lower prices for all purchasers, that support tiered pricing strategies, another waiver, Sanofi-Pasteur thereby establishing one price for such as the Bill & Melinda Gates decided to cease supplying PAHO any country that wishes to use the Foundation, to abandon its lowest region countries with its IPV vaccine. mechanism. PAHO therefore does not price clause. The pressure increased treat countries of different economic in 2009 when the price for PCV Price negotiations for HPV vaccine levels differently, and instead passes vaccine was being negotiated between the two suppliers (Merck the benefit of its bulk negotiations under the Gavi Advance Market and GSK) and the PAHO Revolving onto any country in the region that Commitment. In a bid to pressure Fund continue. At the time of wishes to participate in the mechanism. the PAHO Revolving Fund to provide publication, an affordable price had an exemption to the LPC so that not been agreed upon between the The principles governing each Gavi could purchase PCV for a lower companies and the PAHO region. mechanism and its associated price without companies being Manufacturers, aspiring to extract policies have, however, affected the required to lower the price for greater profits from MICs markets, implementation options of the other. PAHO countries as well, PAHO was have deployed various tactics While both PAHO and UNICEF have forced to waive its LPC for the prices to undermine the principles of established ‘lowest price clauses’ (LPC) offered to Gavi / UNICEF through the solidarity of the regional purchasing with companies in their procurement AMC. Since then, PAHO has issued mechanism. The PAHO Revolving contracts, it has been PAHO that has two additional exemptions for the Fund remains under immense faced international pressure to issue procurement of rotavirus and HPV pressure as companies move towards exemptions to this agreement.94 vaccines by Gavi / UNICEF. Expressing pricing strategies that aim to maximise The LPC clause – otherwise known concern over the higher prices profit in MICS. For more information as the most-favoured nation (MFN) clause – contractually requires manufacturers to provide the lowest global price to that purchasing entity; if a lower price is provided to another country, procuring agency or third party, then the company must reduce the price to the same level for the original purchaser. The LPC is disliked by companies that practise tiered pricing and market segmentation in an effort to extract as much profit as possible [see box: ‘How do pharmaceutical companies set their © Jean-Mark Gibou vaccine prices?,’ pages 20-22]. 24 Médecins Sans Frontières | The Right Shot 2nd Edition January 2015 Affordability and vaccine pricing on HPV prices, see HPV Product PAHO region countries – that struggle at a crossroads of different models Card, page 39. to afford the escalating prices of new for pricing and vaccine affordability. vaccines. With Gavi advocating a tiered In the absence of a global solution As countries ‘graduate’ from Gavi pricing approach and expecting that benefits the countries served by support and begin to assume the to receive the lowest global prices both Gavi and PAHO, pharmaceutical full cost of new vaccines introduced for its purchases, while the PAHO companies are moving forward with substantial Gavi donor subsidies, Revolving Fund continues to work for country by country, trying to divide and to face the unpredictable prices the best possible price for member and segment markets and to lock in that will be set by some companies, states in its region by pooling country the highest prices they can secure they will find themselves in a similar volumes, these two public health from governments. situation to other MICs – including institutions have found themselves Tiered pricing gains momentum despite negative effects on access Tiered pricing, also known as differential Pharmaceutical companies are not are covered by each tier and how pricing, is presented by multinational transparent in their tiered pricing prices are set within tiers. Even though pharmaceutical companies and some policies which are usually implemented GSK has articulated its tiered pricing global health actors as the solution for by companies unchecked and without strategy, it has not publicly disclosed improved access to vaccines. Under appropriate government oversight. prices charged in each tier, which the tiered pricing approach, companies What few data points are available on tier countries are assigned to and the charge different prices in different tiered pricing strategies show that, precise formula the company applies markets for the same product: in theory aside from Gavi prices, pharmaceutical to establish tiers, country classification the highest price is set in higher-income companies with a monopoly or duopoly and prices charged. Companies cite the countries, and relatively lower prices in in the newer vaccines (GSK, Pfizer, concern that any transparency regarding lower-income countries. The premise Merck) are pricing these vaccines with their pricing formulas threatens their of tiered pricing is that companies no clear rationale or relation to a advantage in the market; they also offer price discounts to countries of country’s economic classification level, bemoan any initiatives to increase lower economic status because they as illustrated by the prices paid by availability of country price data for fear cannot afford to pay the same price countries for Pfizer’s Prevnar 13 that it will be used by other countries as high-income countries, such as [see Graph 5, overleaf]. Morocco, for reference in price negotiations. the US; however, the expectation is a LMIC, is paying more for Prevnar that as countries become richer, the 13 (PCV13) than France, Hungary price charged to them increases. and the Czech Republic, all countries Intuitively and to the general public, with higher economic levels. Likewise, tiered-pricing may sound like a Tunisia and Lebanon are paying more rational approach for establishing than France for the vaccine, despite prices across a range of countries having substantially lower GNI levels. Tiered at different levels of development. pricing allows A few companies have taken steps to In practice, however, tiered pricing is better articulate the rationale of their manufacturers a pharmaceutical company-promoted tiered pricing business strategy – GSK, to set prices at strategy that allows manufacturers for example, published a statement on whatever the to set prices as high as the purchaser a seven-tier pricing system in October market will will tolerate, frequently without 2013, noting the inclusion of criteria tolerate, without considering public health needs and beyond country economic development impact, and in fact acting as a market – but most multinational companies considering public segmentation strategy that can delay decline to give further details on how health needs. the entrance of competition. their prices are set, which countries Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 25 Graph 5: Pfizer's Pneumococcal Conjugate Vaccine (PCV13) price per dose for countries by GNI per capita, 2014 160 60,000 135.8 140 50,000 120 99.0 40,000 100 80 78.0 30,000 67.3 Affordability and vaccine pricing 61.5 63.7 58.4 GNI PER CAPITA US$ PER DOSE 60 49.4 20,000 40 15.7 10,000 20 3.3 0 0 Gavi/ PAHO Czech France Hungary Morocco Tunisia Lebanon Belgium USA UNICEF Rep. LMIC UMIC HIC UN org. GNI/capita 2012 Sources: World Bank,45,97 Gavi,14 country price analysis (see Annex A for details on methodology and sources) Notes and methodology: to hospitals. See Annex A for more • GNI per capita for Gavi is the threshold 14 • Manufacturer price for all countries information on definitions and sources. for graduation (US$1,570). except for Morocco and Tunisia, • GNI per capita for PAHO was estimated • GNI per capita for countries is based where the price used here is the price at US$7,500.98 on World Bank Indicators 2012.45,97 26 Médecins Sans Frontières | The Right Shot 2nd Edition January 2015 Affordability and vaccine pricing Robust competition stimulates price drops, but duopoly persists for newer vaccines Genuine and sustainable price decreases with only two manufacturers for each to WHO PQP and national regulatory will be stimulated by real competition of the new and much more expensive authorities’ queries. in the market. The vaccine market vaccines – PCV, rotavirus, HPV – and differs substantially by antigen; some the inability to use the two available Steps to accelerate the antigens like the pentavalent vaccine products interchangeably, companies entrance of additional have healthy markets which benefit are enjoying near monopolies. manufacturers to harness from proper competition among a There are a variety of strategies the price decreases delivered broad manufacturer base, while others that governments, donors, vaccine by real market competition like the rotavirus, PCV and HPV vaccines manufacturers and others can employ to – rather than relying on are duopolies. As has been seen in the promote vaccine competition. Reducing the tiered pricing strategy pentavalent market, the entrance of the barriers to entry and facilitating promoted by multinational additional manufacturers – a total of diversity in the manufacturing supply pharmaceutical companies – seven companies now sell prequalified by promoting technology transfer to will be critical in promoting pentavalent vaccines – has led to steep new manufacturers are critical tools to availability of affordable price declines. In 2008, when Shantha accelerating competition. Simplification vaccines. In the absence of Biotech entered the pentavalent of the regulatory processes for product competition, transparency market it undercut the previous lowest prequalification – while maintaining the initiatives to avail price and price (offered by GSK) by 17%. The highest level of quality assurance – would procurement information introduction of other company products also facilitate and speed up market entry for use by countries and (with more affordable multidose vial for lower-cost follow-on and adapted procurement agencies in sizes) in 2011 and 2012, specifically vaccines. Simplification could come from their negotiations with from emerging manufacturers,99 further the WHO prequalification programme pharmaceutical companies are lowered the price: the lowest price (PQP) itself and from initiatives to critical. Aggregating volumes available decreased by 56% , from harmonise regional regulations, such through pooled procurement US$2.70 per dose in 2010 (Shantha as the African Vaccine Regulatory Forum to leverage market weight Biotech, one-dose presentation) to (AVAREF).100 Vaccine manufacturing by country groups will also be US$1.19 per dose in 2013 (Biological companies can also shorten the a powerful tool in reducing E, ten-dose presentation). However, approval process by responding swiftly the price of vaccines. © Samantha Maurin /MSF Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 27 Opportunities to stimulate competition: Chinese manufacturers enter the global market The most effective driver to increase ventures and seven are state run. where a duopoly currently keeps vaccine affordability is competition In March 2011, WHO certified China’s prices high in the international between manufacturers. Entry of National Regulatory Authority (CNRA) market, such as PCV, rotavirus additional manufacturers to the for meeting WHO standards for and HPV vaccines. In addition to global market will help to bring regulatory oversight. This milestone, contributing follow-on products, down prices and ensure adequate repeated in July 2014 when WHO Chinese companies are developing supply to meet global needs. renewed the CNRA certification, entirely new vaccines, such as means that Chinese companies can the vaccine against hepatitis E The emergence of Chinese vaccine submit prequalification applications by Xiamen Innovax Biotech. Affordability and vaccine pricing manufacturers in the global market to WHO for international review. – with the first WHO-prequalified The promise of increased competition, vaccine by a Chinese company, China’s largest company is state- new products and improved supply Chengdu Institute of Biological owned Sinopharm’s subsidiary security that Chinese companies Products (for Japanese encephalitis China National Biotechnology represent could be a game changer vaccine), achieved in 2013 – could Group (CNBG), which comprises for the global market. International stimulate a new era of competition seven manufacturers, including stakeholders should do their utmost in a market that has traditionally the Chengdu Institute of Biological to promote this potential by creating been dominated by a handful of Products. CNBG reports selling the right legal and policy enabling multinational companies. approximately 800 million vaccine environments, working to resolve doses a year, supplying more than any barriers to market entry, such Chinese manufacturers have been 85% of the vaccines used in China’s as regulatory or patent barriers, supplying their domestic market for national immunisation programme. and accelerating the entrance of these decades. The China Food and Drug products in the international market. Administration (CFDA) reports that Chinese companies have a range of China has 34 vaccine manufacturers; vaccine products at different stages four of these are international joint of development, including products “ We introduced two new vaccines recently...and because there are only two suppliers for each vaccine, there’s no competition and we pay a premium. „ Dr Yogan Pillay, Deputy Director General, Department of Health, South Africa © Aurelie Baumel/MSF 28 Médecins Sans Frontières | The Right Shot 2nd Edition January 2015 Vaccine adaptation vaccine adaptation In resource-poor contexts, conventional vaccine profiles can complicate vaccine delivery. Vaccine adaptations – optimising profiles for resource-limited environments – can extend outreach and improve immunisation coverage. Key vaccine adaptations include vaccines that do not require constant refrigeration, provide full protection with fewer doses, include serotypes most appropriate for local disease burden, or can be administered by community health workers through simplified delivery systems. Progress in vaccine adaptation Few better-adapted vaccines have greater investment in vaccine In 2012, the WHO member states reached clinical development. Many adaptation to bring these adopted the Global Vaccine Action promising adaptations in preclinical products to market.104 Plan (GVAP) as the international development require partnerships framework under the Decade of The largest vaccine purchasers – such with vaccine manufacturers to reach Vaccines for expanding access to as UNICEF Supply Division – have clinical trials. immunisation. The GVAP monitoring the opportunity to shape adapted and evaluation plan includes A 2013 landscape analysis conducted vaccine development by having their indicators for relabelling vaccines by MSF on all EPI vaccine adaptations procurement policies indicate the to allow a controlled temperature in clinical trials found 13 vaccine ‘value’ of adapted vaccine attributes chain [see overleaf] and targets for presentation advances (including in their purchasing decisions. vaccine delivery devices. ten oral rotavirus candidates in the Quantification of adapted vaccine pipeline), one packaging adaptation, benefits, with cost-effectiveness and and 16 delivery-device innovations. systems cost measures, and indication Most of these adaptations have of country preferences for vaccine been developed through product technologies, can encourage further “ We would development partnerships.101 investment in better products.102 like a whole While donor support to vaccine Vaccine adaptation has been new range research has been significant, there gaining prominence on the global of vaccines has been a lack of follow-through immunisation agenda. In 2007, WHO that are to enable these technologies to and PATH created Project Optimize, ultimately reach the places where which defined an ideal vaccine simpler to they are needed most.102 For vaccine supply chain and supported efforts use, are heat- manufacturers, changing the to implement these changes. Along stable, and standard presentation, packaging with partners, Project Optimize and delivery for vaccines incurs re-established the Vaccine Presentation have simpler additional risk. Without clarity on and Packaging Advisory Group schedules, market uptake, developing a business (VPPAG), which has developed a making it case for adapted vaccines remains generic preferred product profile challenging.103 Early policy guidance (gPPP) for vaccines that includes easier for us on antigen-specific procurement can recommendations for formulation, to vaccinate shape adapted vaccine development presentation, labelling and packaging kids. „ at the point when the incorporation for vaccines intended for use in of these optimisations will have the low- and middle-income countries. Dr Greg Elder, MSF Deputy lowest marginal cost. Stronger ‘pull’ The WHO is planning to publish an Director of Operations mechanisms can also incentivise updated generic product profile. Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 29 Controlled temperature chain Keeping vaccines cold remains a major stability studies, with the exception of using 155,000 doses of MenAfriVac in constraint on their delivery [see box: a few antigens where clinical bridging 150 remote villages in Banikoara.106,107 Cold chain challenges, opposite], studies would be required. Following the pilot, 98.7% of supervisors as half of the healthcare facilities and 100% of vaccinators involved Vaccine adaptation Vaccine Implementing vaccination in CTC in the poorest countries have no preferred the CTC approach to electricity supply and only 10% have There are two options for vaccines in traditional campaign immunisation a reliable electricity supply.98 Many CTC: routine immunisation and outreach which requires the cold chain.108 vaccines, however, are fairly heat- activities, such as vaccination campaigns. Vaccination campaigns using stable; labelling and using vaccines Outreach can include outbreak response, CTC could dramatically reduce according to their true temperature mobile immunisation clinics for remote immunisation costs. In a recent stability would result in a controlled areas, and immunisation campaigns. publication, Lydon et al. modelled the temperature chain (CTC) or ‘flexible Outreach activities typically require only costs of implementing a MenAfriVac cold chain’, whereby vaccines can several days of heat stability. In contrast, campaign in CTC and compared it be used outside the traditional strict routine immunisation would require heat 105 with the actual costs in a MenAfriVac cold chain. This approach has stability for at least one month, given the campaign in three regions of Chad considerable benefits, including cost current vaccine delivery systems. savings, preventing vaccine damage in 2011. They found that CTC caused by accidental freezing, and Despite the clear benefits for CTC in implementation at the district level most importantly, making it easier vaccination campaigns, the benefits would have saved more than 20% to reach children living in remote have not yet been fully realised. of the cost of the vaccine doses for places who would otherwise remain Only the Meningitis A vaccine the campaign.109 Considering these unvaccinated. Relabelling a vaccine for (MenAfriVac) has been relabelled were some of Chad’s most densely CTC does not require changes to the and used in a CTC for campaigns. populated and accessible districts, vaccine itself; the relabelling process In 2012, the Ministry of Health in the cost savings of CTC may be even is likely to need only inexpensive Benin implemented the first CTC pilot greater in more remote regions. © Sami Siva 30 Médecins Sans Frontières | The Right Shot 2nd Edition January 2015 Vaccine adaptation Cold chain challenges Vaccination rates are often poor logistical burdens and reducing and received two doses of the tetanus in low-resource environments; costs. A recent CTC campaign with toxoid vaccine. Women in the control one of several reasons is that MenAfriVac in Benin halved the group received vaccine kept in a health facilities lack access to the logistical costs while achieving safe strict cold chain; those in the second physical infrastructure needed and widespread immunisation. group received vaccine kept out of to properly store and manage the cold chain (up to 40°C for up vaccines. Inadequate supply and MSF is also conducting research to 30 days). Participants in both logistics systems prove a barrier to on the potential use of vaccines in groups reached adequate levels of transporting vaccines to the most CTC. In 2013, MSF and Epicentre, protection against tetanus. These remote areas of a country, and the its research arm, together with results strongly suggest that the burdensome cold chain means partners, carried out a two-phase Serum Institute of India’s tetanus that the most low-resource areas, study to determine the stability and toxoid vaccine maintains its efficacy lacking electricity, may not be able continued efficacy of the tetanus under CTC conditions. to properly store vaccines. In the toxoid vaccine produced by the poorest countries, it is estimated that Serum Institute of India under CTC Campaigns with vaccine used in half of the health facilities effectively conditions.111 In the initial phase of CTC can increase immunisation have no electrical supply, while a the study, laboratory tests confirmed coverage and save lives, but the mere 10% have reliable electricity.98 that the vaccine retained its chemical onus rests on manufacturers to and biological properties when kept initiate relicensing of their vaccines For outreach and supplementary at ambient temperatures of up to for CTC flexibilities. Many vaccine immunisation activities (SIAs), the 40°C for up to 30 days. The second companies have existing stability logistical challenges mount. In a phase was a clinical study undertaken data generated during their clinical 2010 measles vaccination campaign in Chad, in the Moïssala district, trials, but have not undertaken the targeting 500,000 people in Chad, to see how effective the vaccine relabelling process with regulatory MSF had to freeze 22,000 ice packs remained in practice, under similar authorities, thus denying countries in just 11 days.110 For a recent conditions. The participants – 2,128 the opportunity to implement measles vaccination campaign women of childbearing age – were simpler and more effective in Guinea, Sophie Dunkley, an each assigned to one of two groups vaccination outreach. MSF epidemiologist, explains the logistical challenges: “At the base, where we hold our stock, we have 17 fridges full of the vaccines. We also have the 17 freezers to make and store the 5,000 ice packs we need. The ice packs go into a big cold box that is taken out to the vaccination sites. But even there, we then have to transfer the vaccines from the big cold box into smaller cold boxes, because at each single stage we have to protect the vaccines so that they remain effective. It’s a nightmare”. For vaccination campaigns, there is an increasing interest in eliminating the need for cold chain for vaccines stable beyond the standard 2 – 8°C range for several days or even weeks. Use of a CTC for vaccination outreach has been effective in © Ikram N‘gadi immunising more people, reducing Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 31 Solutions to foster innovation: building a better vaccine Current vaccine adaptation technologies value products, and quantifying have been underused, even as early-stage the benefits of vaccine adaptation, Vaccine adaptation Vaccine innovation increases. The fundamental particularly additional immunisation “ We have 17 fridges question remains: is the global health coverage and reduced system costs full of the vaccines. community prepared to prioritise better for these technological advances. We also have the vaccines that may be more expensive Another example of an incentivising 17 freezers to to develop and manufacture initially but mechanism is the European will allow savings in the long run and, make and store Commission’s Vaccine Prize, which more importantly, allow more children the icepacks... in 2013 issued a call for innovations to benefit? Key ways to incentivise at each single that can ease cold chain challenges adapted vaccine development are through vaccine formulation, stage we have listed in Table 4. preservation and transportation. to protect the Kristensen and Chen have outlined ways The prize, of 2 million euros, was vaccines so that to advance vaccine technologies better awarded in 2014 to a German they remain suited to resource-poor environments. company that has developed a effective. It’s a Their paper lists actionable points for stabilising technology to protect nightmare. 102 „ all major stakeholders; these include vaccines against elevated temperatures increased specificity in Generic Preferred and accidental freezing.112 This Sophie Dunkely, MSF Epidemiologist, Product Profiles (gPPPs) for desirable European Commission prize fund, measles vaccination campaign, product attributes, funding for early- however, does not include important Guinea, February 2014 stage research on vaccine technologies, access conditions nor adequate capacity to pay premiums for higher intellectual property provisions. Table 4: Benefits and examples of incentive options to develop adapted vaccines Incentive option Benefits Past examples Provides incentives for using inexpensive or Auto-disable (AD) syringe Include off-the-shelf adaptation requirements in the off-the-shelf technology including freeze-stable requirement in UNICEF gPPPs* for new vaccines excipients and stability studies for CTC procurement Country vaccine preference Enable countries using procurement agents – such Provides a pull mechanism that incentivises through UNICEF SD (e.g. as UNICEF Supply Division – to purchase vaccines vaccine manufacturers to incorporate value-adding high demand for the rotavirus according to their product characteristics preferences components into vaccines vaccine two-dose schedule) Foster public-private partnerships with critical access Provides risk-sharing, technical know-how, and provisions and price considerations built into the funding needed to overcome market failures for Meningitis Vaccine Project vaccine target product profile investing in vaccine adaptation * gPPPs: Generic Preferred Product Profiles 32 Médecins Sans Frontières | The Right Shot 2nd Edition January 2015 Conclusion and recommendations Conclusion and recommendations Improved vaccine access has averted deaths and serious illness across the world, but the benefits of immunisation are still not available to all. Selected initiatives have improved affordability and adaptability of vaccines, but the focus of the past decade has been primarily on low-income countries. With financial subsidies and negotiation of lower prices by Gavi, low-income countries have introduced new vaccines at a faster rate than others; this puts into sharper focus the large group of countries and organisations that have yet to benefit from the newest vaccines because of a lack of strategies to ensure affordability for all. With the mounting concern over the sustainability of immunisation programmes in countries losing Gavi support and the growing voice of countries and organisations left out of pricing and procurement mechanisms, there is an urgent need for deliberate steps to improve vaccine affordability worldwide. Affordability and prices - ensuring Increased price transparency: conducted their own vaccine vaccines are affordable for all will vaccine price data are scarce, market analyses, including cost require action, including: with little information to inform of manufacturing, and who purchasing negotiations and policy are actively involved in price makers. There is a need to bolster negotiations, should make this Accurate and publicly existing mechanisms, and invest information publicly available. available information on in additional mechanisms, to share research and development price data. (R&D) and manufacture Monitoring and accountability costs: availability of information Procurement entities such as UNICEF of vaccine prices: standard on the R&D and manufacturing and the Gulf Cooperation Council, indicators to effectively monitor costs of new vaccines, and public among others, should publish all of vaccine prices across purchasing investments made towards those their available price data. Gavi and entities (countries, procurement costs, will enable countries, other global health actors that are agents) are needed with collectively or individually, stewards of public funds should accountability measures in place. champion price transparency, and to negotiate affordable prices. WHO and UNICEF should build commit to continued publication of Governments that contribute on the work started on vaccine prices. Forthcoming procurement public funding to vaccine price indicators in the Decade of bodies should incorporate price development need first to make Vaccines/Global Vaccine Action transparency principles into their that information readily available Plan monitoring, evaluation procurement models from the outset. to the public, and demand that and accountability framework, their investments be recouped Governments, which are the to ensure that indicators are for improving the public’s health primary purchasers of vaccines, continuously improved. Price indicators should also be tracked through affordable prices to should share their information across a broader set of countries. purchasers; and second, to win the via price data mechanisms, such argument with donors and the as the WHO Vaccine Product, Pharmaceutical companies should vaccine industry about ‘the right Price, Procurement (V3P) project. more clearly articulate their pricing price’ for a vaccine, i.e. that is strategies, including components used Donor governments and not value-based but based on in determining prices for purchasers, philanthropic entities like the cost plus reasonable profit. and be held accountable to at least Bill & Melinda Gates Foundation, meet their own standards. Currently Pharmaceutical companies should which contribute funds to norm- tiered pricing often has no clear publicly disclose their investments setting bodies such as WHO rationale or relation to a country’s in vaccine development and and development assistance economic classification level. clarify what costs are attributed mechanisms such as Gavi, to R&D and manufacture, and what should insist on vaccine price Governments and other vaccine is needed to sustain participation transparency. Entities, such as purchasers, such as Gavi / UNICEF, in the market. the Gates Foundation, which have should be held accountable for Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 33 prices negotiated, particularly as those strategies and not create handful of adapted vaccines tailored to public monies are used for the nor endorse policies that will developing country needs is available. purchase. Governments should undermine the capacity of Adaptation - stimulating establish national price regulations, governments to implement them. research and development of including price controls (e.g. adapted vaccines will require reference pricing, controlled mark- action, including: ups, maximum retail prices, etc.) Support for increased competition and entry of lower-cost manufacturers: Identification of adaptation Increased use of effective entry of new manufacturers, preferences by countries: procurement strategies, particularly those with lower country-level practitioners and such as pooled procurement, manufacturing costs, needs to be programme managers know multi-year contracts, accelerated through technology best what adaptations will improve Conclusion and recommendations competitive tenders: a variety transfer, access to licences and their immunisation programme of strategies and policies should key technology know-how. performance; they need to be be pursued to increase the in the driving seat for setting Gavi and other global health actors effective use of procurement priority adaptations. strategies, including investment in supporting immunisation should capacity building and to improve invest in measures to stimulate Countries with challenges facing forecasting so that tools such as competition and broaden the vaccine their immunisation programme pooled procurement and multi-year product base, with a focus on performance should voice their contracts can be used to lower prices. emerging country manufacturers. needs in a global forum and insist that the products specifically Countries should commit to working Donors that support R&D, such supported by donors best meet together to achieve economies of as countries and philanthropic their context needs. scale through pooled procurement entities, should invest funding mechanisms. Exploring unifying in innovative research and Procurement agencies, such characteristics – such as regional development models, and steps as UNICEF, should develop a groupings or other common that increase competition, methodology for surveying vaccine interests – to combine their vaccine particularly among lower-cost adaptation preferences of the volumes will enable more powerful manufacturers with the goal countries they support and prioritise price negotiations. of ensuring that the resulting products that meet their needs. vaccines are manufactured at the WHO, UNICEF and other technical lowest possible cost and reach all agencies should provide support populations in need. Demonstrate utility of to countries wishing to improve adaptations: vaccine adaptations WHO should provide technical, vaccine procurement competencies have been shown to improve policy and political support to and establish pooled procurement immunisation coverage, but more overcome barriers to product mechanisms. WHO regional evidence must be generated to development, and support emerging offices, in particular, should ‘make the case‘ for investment. support countries to come manufacturers including through together and explore pooled regulatory processes to facilitate Donors, such as developed procurement options. prequalification applications. countries and philanthropic entities like the Bill & Melinda Donors, such as developed countries Gates Foundation, should invest Measures to improve vaccine product and philanthropic entities like the funding in modelling vaccine characteristics – or adaptations – to Bill & Melinda Gates Foundation, adaptations to show their efficacy should provide resources for immunisation needs in resource-poor and the need for them. countries to convene and work settings are ongoing but moving at towards establishing effective a slow pace. These innovations are WHO and other technical agencies procurement strategies, including not commonly developed because supporting immunisation programmes pooled procurement. Donors the populations living in resource- in low-resource countries should should allow countries to self- poor settings do not represent a large quantify the contribution of vaccine determine the principles of commercial market. To date, only a adaptations to improving coverage. 34 Médecins Sans Frontières | The Right Shot 2nd Edition January 2015 Conclusion and recommendations Setting a clear vaccine to incentivise development of the countries it supports. With its adaptation agenda: establish better adapted products. substantial resources, Gavi should design preferential procurement consensus-based, early-stage target Donors, such as developed countries, strategies – such as more shares product profiles (TPPs) that include developing countries with a strong or premiums to better products – key vaccine adaptations to guide interest in using adapted vaccines, that incentivise adapted product researchers, product developers, and philanthropic entities like the Bill development. and manufacturers. & Melinda Gates Foundation, should help to design innovative models WHO, as a body that sets global for vaccine technologies and invest Clarify and streamline the health norms, should convene funding to realise their development. regulatory process: while the relevant stakeholders to set In supporting immunisation maintaining high quality-assurance a clear agenda of priority vaccine programmes, all governments that standards, the regulatory pathway adaptations to guide donor contribute funding should insist that for innovative and adapted investments and the work of their funding be strategically used to vaccines and delivery devices researchers, product developers incentivise adapted products. Any should be clarified. and manufacturers. Implementing adaptations that emerge from WHO and other regulatory countries should be a leading such investments should not lead bodies, such as national and constituent in this forum. to unaffordable prices or the regional entities, should clarify creation of additional barriers, and, where possible, streamline, especially intellectual property Funding for innovative regulatory requirements for barriers, that would prevent technologies and incentivising vaccine adaptations and delivery increased use of such vaccines. strategies: innovation needs to be technologies. Guidance on criteria fostered through direct investments Gavi should become more involved for seeking WHO prequalification (push funding), prizes or other funding in upstream product development, with adaptation attributes, such as mechanisms. Resources available investing funds in product extended thermostability, should for immunisation programmes must adaptations and innovative models be communicated clearly to be used to their utmost potential that deliver better vaccines for product developers. © Erwin Vantland Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 35 Yann Libessart/MSF © Yann Product Cards Summary and introduction Product Cards: Summary and introduction The nine following product cards a clear overview of these vaccines network; does not include wholesale presented here and summarised overleaf in one place, intends to support or retail margins, but may include bring together for the first time key decision making at country level and taxes and transportation fees. information on important monovalent to broaden the discussion on price • Retail price (Retail): and combined vaccines. Each vaccine comparison and price opacity. product card itemises disease price as paid by the population, burden, WHO recommendations, Vaccine prices: a note on inclusive of taxes, transportation administration schedule(s), product terminology used in the fees, and margins; sometimes characteristics, product pipeline, access product cards referred to as ‘private sector’ price. challenges, pricing and affordability. For the purpose of our analysis, All prices except the ‘government Where possible, historical price vaccine price data have been price’ are official prices available information is analysed. subdivided into four main price types: outside of government immunisation The lack of price transparency and programmes. In some countries, • Government price (Gvt): product availability is a barrier to health insurance will cover the cost of price paid by the government for improving and scaling up access the vaccine purchased in the private national immunisation programmes. to vaccines, and there has been no market, representing a cost to public single source of information providing • Hospital price (Hosp./Hospitals): health insurance schemes. In other details on both product characteristics price paid in hospitals and public countries, where the vaccine is not 23 and prices. While other initiatives institutions. reimbursed by health insurance, the (e.g. the Vaccine Product, Price, ‘retail price’ is a direct burden on a and Procurement (V3P) project) are • Manufacturer price (Manuf.): family’s budget. evolving, we have created this unique price of the vaccine before it enters compendium which, by providing the wholesale and retail distribution DISCLAIMER / METHODOLOGY Except where stated otherwise, Description of development from 2013 or 2014). For more details the vaccines presented are WHO pipelines does not intend to be on the pricing methodology, please prequalified (WHO PQ). exhaustive, but summarises publicly refer to Annex A. available information on products Prices presented are based on the in Phases II and III of clinical trials. lowest publicly published prices available on the UNICEF Supply Between-country price comparison is Division website, except where based on the latest price data available otherwise noted. at the time of the analysis (usually Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 37 Presentations Industrialised manufacturers Lowest price available Pipeline outlook ( IFPMA* ) and emerging per dose, 2014 Vaccine (products in Phase II or III manufacturers ( DCVMN** ) of (UNICEF prices, Single- Multiple- ‡ 113 † clinical trials) WHO prequalified vaccines dose dose US$) Human Industrialised: 2 (GSK, Merck) papillomavirus Yes Yes 4.50 – 4.60 (HPV) Emerging: 0 (GSK 2-dose) Industrialised: 4 (Bilthoven Biologicals BV, GSK, Sanofi Pasteur, Inactivated Statens Serum Institute) Yes Yes 0.75 – 2.80 poliovirus (IPV) Emerging: 1 (Serum Institute ( Some combination of India/Bilthoven Biologicals) vaccines in development ) Industrialised: 1 (Sanofi Pasteur) Measles Emerging: 3 (Bio Farma, GPO- Yes Yes 0.22 – 0.45 Merieux, Serum Institute of India) Product Cards: Summary and introduction Industrialised: 0 Measles-rubella Yes Yes 0.55 (MR) Emerging: 1 (Serum Institute of India) Industrialised: 3 (GSK, Merck, Sanofi Measles-mumps- Pasteur) Yes Yes 1.02 – 3.25 rubella (MMR) Emerging: 1 (Serum Institute of India) Industrialised: 2 (Sanofi Pasteur, Novartis) 0.53 – 0.58 Meningococcal Yes Yes Emerging: 2 (Bio-Manguinhos, (2013, MenA only) (Several tetravalent Serum Institute of India) vaccines not WHO PQ or in development) Industrialised: 2 (Berna Biotech [Crucell], GSK) Pentavalent Yes Yes 1.19 – 2.95 (1 – 3 new manufacturers (DTP-HepB-Hib) Emerging: 4 (Biological E, LG Life Sciences, Panacea Biotec, Serum within next 3 years; Institute of India) hexavalent products in development) Pneumococcal Industrialised: 2 (GSK, Pfizer) Yes Yes 3.30 – 7.00 conjugate (PCV) Emerging: 0 (GSK 2-dose) (Not expected before 2017) Industrialised: 1 (Crucell) Oral cholera (OCV) Yes No 1.85 – 4.75 Emerging: 1 (Shanta Biotech) Industrialised: 2 (GSK, Merck) Rotavirus (RV) Yes No 2.50 – 5.00 Emerging: 0 Industrialised: 2 (BB-NCIPD, Sanofi Pasteur) Tetanus toxoid (TT) Emerging: 4 (Bio Farma, Biological Yes Yes 0.05 – 0.09 E, Serum Institute of India, Shantha Biotechnics) * IFPMA: International Federation of Pharmaceutical Manufacturers and Associations. ** DCVMN: Developing Countries Vaccine Manufacturers Network. † Lowest and highest price offered to UNICEF, across all presentations and conditions. The lowest price is usually accessible only to countries eligible for support from Gavi, the Vaccine Alliance. ‡ Based on public information about vaccine development pipelines; number of products in Phase II or III of clinical trials: : >3; : 2 or 3; : 0 or 1. 38 Médecins Sans Frontières | The Right Shot 2nd Edition January 2015 MSF/Vivian Cox © MSF/Vivian Human Papillomavirus Vaccines (HPV) WHO recommendations & general information Cervical cancer is estimated to cause years prior to onset of sexual As of February 2014, 66 countries 266,000 to 275,000 deaths globally activity. WHO also recommended had introduced HPV vaccines per year114–116 and is projected to taking into consideration national in their national immunisation be responsible for 474,000 deaths public health priorities, programmatic programmes and pilot programmes per year by 2030. More than 95% feasibility and cost-effectiveness were underway in an additional of those deaths will be in low- and before inclusion of HPV vaccines in 40 countries.117 121 middle-income countries, in many a country’s immunisation schedule. In late 2013, the bivalent HPV of which cervical cancer is the A combined analysis of two Phase vaccine received European leading cause of cancer-related II trials of the quadrivalent (types Commission approval125 for a uman Papillomavirus Vaccines ( H PV) H uman Papillomavirus Vaccines deaths among women and a 6, 11, 16, 18) HPV vaccine found reduced two-dose schedule (at leading cause of death overall.117–119 that the vaccine was 99% effective 0 and 6 months) for girls aged in preventing HPV infection Human papillomavirus (HPV) 9–14 years.115,126,127 In 2014 the (assessed by absence of cervical is sexually transmitted and is quadrivalent product received intraepithelial neoplasia grade the primary cause of cervical European Commission approval128,129 ≥2 or adenocarcinoma in situ) cancer.114,120 Persistent infection by for a two-dose schedule ( at 0 and when administered before virus oncogenic HPV is a prerequisite for 6 months ) for girls aged 9–13 years. exposure.121 The quadrivalent developing cervical cancer, and at vaccine offers added value by In April 2014, on the basis of least 13 viral genotypes are known protecting against genital warts, as research indicating that alternative to be carcinogenic.121 Viral type 16 90% of these are caused by infection dosing schedules could be as is the dominant oncogenic type with HPV types 6 and 11. There is effective as existing schedules,130 in all regions and, with viral type evidence for significant vaccine- the WHO Strategic Advisory Group 18, accounts for about 70% of all induced cross-protection with of Experts recommended switching cervical cancers worldwide.121 other cancer-causing serotypes.122 to a two-dose schedule for girls In 2009, WHO recommended The quadrivalent vaccine has been provided that vaccination was started inclusion of HPV vaccines in national shown to substantially reduce before 15 years of age.115,128,129,131,132 immunisation programmes for disease incidence of genital warts in administration to girls aged 9–13 countries with high coverage rates.123 Doses in primary series Vaccine124 Age at 1st dose Booster (interval between doses) Quadrivalent HPV 2 doses for girls <15 years (minimum 6 months between 1st and 2nd dose) 9 – 13 years If the interval between the two doses is <6 months, Not recommended Bivalent HPV then a 3rd dose should be given at least 6 months after the 1st dose Quadrivalent or bivalent HPV: Applicable for girls 3 doses (minimum 1–2 months between 1st and 2nd Not recommended delayed start* ≥15 years dose; minimum 4 months between 2nd and 3rd dose) * This schedule is also recommended for immunocompromised individuals. 40 Médecins Sans Frontières | The Right Shot 2nd Edition January 2015 H uman Papillomavirus Vaccines ( H PV) Products & manufacturers Lowest WHO PQ Form and Vaccine vial monitor (VVM) type Product Manufacturer known price date presentation and cold chain volume (per dose) (UNICEF, US$) VVM 30 Single dose Box, 1 vial: 57.7 cm3 Cervarix Box, 10 vials: 11.5 cm3 Bivalent HPV Liquid, 1- dose GSK July 2009 and 2 - dose 4.60 Box, 100 vials: 4.8 cm3 (types 16 and 18) vials* vaccine Two doses Box, 1 vial: 28.8 cm3 Box , 10 vials: 5.7 cm3 Box, 100 vials: 9.7 cm3 Gardasil/Silgard VVM 30 Quadrivalent HPV Liquid, 1- dose Merck May 2009 4.50 (types 6, 11, 16 vial Box, 1 vial: 75 cm3 and 18) vaccine Box, 10 vials: 15 cm3 Pipeline products Challenges Merck has the nine-valent Lack of routine health services for target population is adolescent vaccine V503 in Phase III of adolescent girls in many countries and teenage girls, who need to development.133,134 V503 targets poses a challenge to vaccine be vaccinated before the onset nine HPV subtypes (6, 11, 16, delivery for the target 9 –13 age of sexual activity.114,141,142 18, 31, 33, 45, 52 and 58) and is group,115 and this is particularly the Merck, together with WHO and the being developed in collaboration case in middle- and low-income Program for Appropriate Technology with CSL (Australia). countries with regard to HPV in Health (PATH), is exploring the vaccination.120 As HPV vaccine is Xiamen Innovax has a recombinant stability of Gardasil in the controlled likely to be provided outside of bivalent vaccine targeting HPV 16 temperature chain (CTC).127 Pending clinics, more user-friendly products and 18 in Phase III.135,136 regulatory reviews and processes, such as needle-free formulations – Gardasil could carry CTC labelling Other companies, including ISA for example, vaccine patches – may by early 2015 indicating that it is Pharmaceuticals, Genexine and prove helpful.140 Transgene, have vaccines that use a stable at temperatures up to 42°C 143 mono-therapy approach to target Sociocultural attitudes and beliefs in for four days. This is especially HPV 16 in Phase II.137–139 different countries and communities important because HPV vaccines are can have a negative impact on likely to be delivered at schools and vaccine acceptance among parents, other locations outside traditional especially when the specific vaccine cold chain-supported environments. * Two-dose preservative-free liquid is a novel presentation for UN-supported Expanded Programme on Immunization (EPI) programmes and requires specific training and management for its roll-out and administration. Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 41 Prices and affordability The HPV vaccine market is a duopoly, the two suppliers being Merck and GSK. Together with the pneumococcal conjugate vaccines (PCV) and rotavirus vaccines, HPV vaccines are among the newest and most expensive vaccines, presenting affordability challenges that hinder access. In 2013, Gavi entered into their respective vaccines to Gavi vaccine since it was first approved agreements to purchase the HPV ‘at cost’.58 in 2006.59,61,144 Taking into account vaccines from Merck and GSK at the 111 million doses of Gardasil the reduced price of US$4.50 and Ongoing research shows that sold worldwide as of May 2013145, US$4.60 per dose, respectively. the manufacturing cost of the at a manufacturing cost of US$4.50 a HPV manufacturers announced vaccine could be much lower. As dose, the company made more than that at these prices they did not of May 2013, Merck had already US$8 billion in profit (excluding the intend to make a profit, explicitly earned more than US$8.6 billion cost of research and development) on uman Papillomavirus Vaccines ( H PV) H uman Papillomavirus Vaccines stating that they were selling in revenues from sales of its HPV HPV vaccine sales over seven years. HPV vaccine in South Africa: Addressing high price challenges Sub-Saharan Africa has the highest Department of Health is on a par MICs. Increasingly, the world’s cervical cancer prevalence (24%)146 with the lowest prices currently paid unvaccinated children are located in and mortality rate in the world. In by some middle-income countries middle-income and non-Gavi eligible South Africa, cervical cancer is the or regional bodies, including the countries; without a policy change at second most common cancer among PAHO Revolving Fund. While this Gavi, these children will continue to women (prevalence of 21%).147 was a significant achievement for be unprotected.150 Additionally, HIV-positive patients South Africa, the cost per dose of the are more likely to be infected with vaccine is still approximately three MSF participation in South multiple HPV types (16, 18, 35, 45) times greater than the price paid by Africa’s HPV campaign and have an increased risk of more Gavi. Moreover, if the vaccine is to An HPV campaign was conducted aggressive, pre-cancerous lesions at be offered to a broader age range in the Western Cape from 10 March a younger age.148 Therefore, in May of girls in the future, or eligibility is to 11 April 2014. MSF partnered 2013, the South African Minister to expand to include male students, with the Department of Health in of Health, Dr Aaron Motsoaledi, the current cost is not sustainable. Khayelitsha sub-district to implement announced South Africa’s intention Countries like South Africa – middle- the campaign, including providing to provide the HPV vaccine for free income countries with relatively small clinical training for health workers, to all girls in grade 4 at public schools markets and not benefiting from support for data collection and and over the age of nine years, pooled procurement mechanisms – advocacy activities to promote covering around 520,000 girls with struggle with escalating costs. If South vaccination. MSF also produced a two-dose schedule.149 Africa paid less for the vaccine itself, educational radio sessions and articles the country could instead use funds for local newspapers on the HPV South Africa does not qualify for Gavi to further strengthen the vaccination vaccine and prevention of sexually subsidies, but negotiated a price of programme’s operational capacity transmitted infections, cervical 157 rand (approximately US$13) and broaden age or gender eligibility. cancer, and sexual violence. Results per dose of Cervarix, GSK’s HPV of the campaign in Khayelitsha vaccine. Adding HPV vaccine to the South Africa contributes funds showed that 2,121 girls in 35 South African immunisation schedule to Gavi, but fails to benefit from schools received the vaccine, out of increased the cost of fully vaccinating Gavi’s market-shaping role. The a reported 2,425 grade 4 girls; the a girl in South Africa by about 18%, South African government should vaccine coverage was thus 87%, from more than 1,115 rand to more demand access to Gavi’s lower with 436 (21%) of girls vaccinated than 1,363 rand per girl.* The price negotiated prices and use its voice by the MSF vaccination team during per dose negotiated by the National to champion access issues for other a ‘mop-up’ campaign. * Cost projections based on prices provided in May 2014 by the National Department of Health to MSF. These prices are not inclusive of VAT or delivery charges. Vaccines include two doses of rotavirus, four doses of DTaP-IPV-Hib, three doses of HBV, three doses of PCV, two doses of measles and two doses of Td, to which the price of the HPV is added. Prices were not provided for the two doses of OPV or single dose of BCG that are also included in the South African EPI. 42 Médecins Sans Frontières | The Right Shot 2nd Edition January 2015 H uman Papillomavirus Vaccines ( H PV) Price evolution: UNICEF and PAHO (See Annex A for more information on prices used in this section) At US$13.08 –13.79 a dose, the announced in 2013, PAHO started vaccines purchased by Gavi at lower Pan American Health Organization negotiations with manufacturers prices (e.g. for PCV and rotavirus (PAHO) pays more than three times to try to lower the price for its vaccines), the countries of the PAHO the price offered through UNICEF to member states, on the basis of the region adopted a resolution in 2013 Gavi-eligible countries [Graph 6]. most favoured nation (MFN) clause to announce the review of past included in all its contracts with exceptions made to its MFN clause,96 In 2014, there has been no price suppliers. The clause stipulates that in an effort to safeguard its access to published by the PAHO Revolving prices offered by manufacturers the lowest prices. Negotiations on Fund at the time of publication. to PAHO should be the lowest HPV vaccines were ongoing at the After prices for the HPV vaccines available global price. After having time of publication. sold to Gavi / UNICEF were granted several waivers for previous Graph 6: Price evolution of Human Papillomavirus Vaccines (HPV) for PAHO and Gavi/UNICEF 15 14.25 13.79 14.00 13.48 13.08 10 US$ PER DOSE 4.60 4.60 5 4.50 4.50 0 2011 2012 2013 2014 2015* Gavi/UNICEF, GSK (bivalent, 2-dose vial) PAHO, Merck (quadrivalent) Gavi/UNICEF, Merck (quadrivalent) PAHO, GSK (bivalent, 1-dose vial) Sources: PAHO Revolving Fund, UNICEF Supply Division * Forecasted data. Prices remain the same for Merck’s vaccine between 2015 and 2017. Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 43 Prices in countries The high price of HPV vaccine has school-based HPV vaccination the gross national income (GNI) per been a barrier to its introduction in programme in 2014 with a two- capita of the countries where it is several countries that do not benefit dose schedule (at around US$13 sold. The company appears to be from the support of Gavi. Several per dose, one-fifth of the price using tiered pricing as a strategy studies show that for the vaccine in the private sector).149 to expand access in these markets. to be cost-effective the price per MSF remains highly concerned that In Brazil, HPV vaccine is supplied dose should be drastically reduced. tiered pricing results in unaffordable through a partnership between In a study done in Thailand, HPV vaccine prices. Merck’s Gardasil, Merck and Instituto Butantan, vaccination as a single intervention when compared with GSK's via an investment of 1.1 million was deemed cost-effective when the Cervarix in different countries, Brazilian reals (US$462 million*) to cost per vaccinated girl was US$10 is more expensive and shows ≤ purchase 36 million doses over five (approximately US$2 per dose).151 less correlation between price years (15 million doses should be and country GNI. The Flemish uman Papillomavirus Vaccines ( H PV) H uman Papillomavirus Vaccines In another study, from Latin distributed the first year, starting region of Belgium, as a result of America, the vaccine was again in March 2014).154 2014 is the first a special offer by Sanofi Pasteur deemed cost-effective in 26 of the year in which Instituto Butantan MSD (selling Gardasil in Europe) 33 countries studied when priced has distributed batches of HPV 152 through a public tender in 2010, at US$10 per vaccinated girl. vaccine; after five years of supply secured the HPV vaccine for its Looking at prices of HPV vaccine in by Merck, it will produce its own school immunisation campaign middle-income countries [Graphs version. As seen in Graph 7, and at the price of EUR20 / US$26.56) 7 and 8, opposite], the price per thanks to a technology transfer per dose, making it one of the dose in 2013–2014 is at least 6.5 agreement, Brazil pays one of the world’s lowest registered prices times higher than the cost-effective lowest global prices for HPV (about for the vaccine. Some of the price calculated in these studies. 30 reals per dose, or US$12.83*). special conditions for this price However, restrictive terms in the The recently announced two-dose (about 105,000 doses per year technology transfer agreement schedule for HPV142 will help lower for five years, to vaccinate 35,000 could limit the opportunity for Brazil costs by one-third, even though girls in their first year of secondary to benefit from real competition if prices will have to be further school)156 are known. Based upon emerging manufacturers enter the reduced to improve access in most the known prices on offer for global market with cheaper products middle-income countries. The Gardasil, Merck is not using tiered during the contract period. change in schedule is expected to pricing as a corporate strategy reduce the Gavi budget for HPV GSK has implemented a tiered to expand access but rather as a vaccines by approximately US$100 pricing strategy for Cervarix, strategic tool to set prices that allow million over the next strategic based on the price data [Graph 7, the company to capture market period.153 South Africa started its opposite], that is closely related to share and maximise its revenues. * The exchange rate quoted (1 Brazilian real = US$0.42) is the monthly average exchange rate from OANDA current in January 2014, when the contract was published.155 44 Médecins Sans Frontières | The Right Shot 2nd Edition January 2015 H uman Papillomavirus Vaccines ( H PV) Graph 7: Prices for GSK Human Papillomavirus Vaccine (HPV) in several countries, by income group and price type, 2013/2014* 200 180 160 148.49 140 128.75 119.51 120 103.85 100 91.77 94.33 78.43 80 77.48 73.10 61.85 US$ PER DOSE 60 51.14 55.19 45.45 48.75 40 32.24 20 12.87 13.08 4.60 0 USA USA PAHO France France Tunisia Belgium Belgium Belgium Lebanon Morocco Morocco Czech Rep. Czech Rep. South Africa South Africa South Africa Gavi/UNICEF Gvt Hosp. Manuf. Retail International organisation LMIC UMIC HIC Sources: PAHO Revolving Fund, UNICEF Supply Division, country price analysis * Annex A, Section C Graph 8: Prices for Merck Human Papillomavirus Vaccine (HPV) in several countries, by income group and price type, 2013/2014* 200 187.77 180 180.38 163.92 160 157.26 141.38 140 132.79 132.90 121.03 120 113.49 100 94.23 80 62.33 US$ PER DOSE 57.27 60 51.14 40 26.56 20 12.83 13.79 4.50 0 USA USA PAHO France France Brazil** Belgium Belgium Lebanon Morocco Morocco Czech Rep. Czech Rep. South Africa South Africa Gavi/UNICEF Gvt Hosp. Manuf. Retail Belgium-Flanders*** International organisation LMIC UMIC HIC **Via Fundacao Butantan and technology transfer agreement with Merck. January 2014 monthly exchange rate from Oanda. ***Special price obtained by the Flemish region through public tender. Sources: PAHO Revolving Fund, UNICEF Supply Division, country price analysis * Annex A, Section C Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 45 © Emily Gerardo Inactivated Poliovirus Vaccines (IPV) I nactivated Poliovirus Vaccines ( I PV) WHO recommendations & general information Poliomyelitis (polio) is an acute endemic countries are Afghanistan, 2-strains from OPV (making it 159,160 viral infection consisting of three Nigeria and Pakistan. For bivalent). IPV is less effective than distinct serotypes (1, 2 and 3). the year 2014, as of 30 April, OPV in inducing mucosal immunity there had been 68 reported polio Before the introduction of among previously unvaccinated cases worldwide, with Pakistan the Expanded Programme on children, but administering both accounting for 54 of them.161 Immunization (EPI) in 1974,157,158 formulations in immunisation campaigns has resulted in uniformly the disease was the leading cause The WHO recommends that all high antibody titres against all three of disability among children. children worldwide should be fully poliovirus types.157,158 vaccinated against polio and that WHO member states resolved at countries using only the oral polio the 1988 World Health Assembly Recent research shows that vaccine (OPV) should include at to eradicate polio by the year fractional doses of IPV can be least one dose of inactivated polio 2000. At the time global polio administered intradermally vaccine (IPV).157 incidence was estimated to be with specialised adapters to around 350,000 cases per year.157 IPV was first used in the 1950s. auto-disposable syringes or Sustained immunisation activities Current formulations of IPV jet injectors. Use of fractional reduced polio incidence by >99% are highly immunogenic, with doses allows a lower dose to between 1988 and 2012,157 and 94 –100% seroconversion rates for be given without reduction in there were 223 and 403 reported all three polio serotypes.157 The immunogenicity and can provide cases of polio in 2012 and 2013 addition of the functionally trivalent overall cost savings.162,163 Research respectively.157 In 2013, India, and IPV has been recommended to also underlines the potential with it the entire WHO South-East mitigate against potential re- for combining fractional IPV Asia region, was declared polio emergence of polio serotype 2, doses with hexavalent vaccine free. The only remaining polio- following the withdrawal of type formulations.164 Recommended Doses in primary series Age at 1st dose Booster schedules (interval between doses) OPV: 1st dose at 6 weeks 3 doses OPV + 1 dose IPV OPV: birth dose (4 weeks between doses 1, 2 and 3) No booster (OPV plus IPV)* IPV: dose at 14 weeks 1 – 2 doses IPV+ ≥2 OPV IPV: 14 weeks IPV: 2 months IPV: 2nd dose at 3 – 4 months (Sequential IPV OPV)** No booster OPV: after last IPV OPV: 2nd dose 4 – 8 weeks after 1st dose dose If primary series is begun 4 weeks between 1st and 2nd doses, and between 2nd at <2 months, booster 3 doses IPV (IPV only)† 2 months and 3rd doses recommended at ≥6 months (becomes a 4 - dose schedule). * WHO no longer recommends OPV-only schedules. The OPV plus IPV schedule is applicable to polio-endemic countries and those with high risk of importation.124 ** Applicable to countries with 90 – 95% immunisation coverage, low importation risk and where vaccine-acquired polio is a significant concern.124 † Applicable to countries with sustained high immunisation coverage and lowest risk of wild poliovirus importation and transmission.124 Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 47 Products & manufacturers Lowest WHO PQ Form and Vaccine vial monitor (VVM) type Product Manufacturer known price date presentation and cold chain volume (per dose) (UNICEF, US$) VVM 7 Inactivated polio Bilthoven Liquid; Dec 2010 2.80 vaccine (IPV) Biologicals BV* 1- dose vial Akylux tray of 360 vials = 15.7 cm3 Serum Institute Inactivated polio Liquid; of India/Bilthoven N/A 2.00165 N/A vaccine (IPV) 5 - dose vial** Biologicals VVM 7 VVM 14 (1-dose vial) (2 - dose vial) nactivated Poliovirus Vaccines ( I PV) I nactivated Poliovirus Vaccines Poliorix Liquid; Inactivated polio GSK Aug 2012 1- dose and N/A vaccine 2- dose vials ‡ Carton, 1, 10 or 100 vials (1- and 2-dose vials) Imovax Polio No VVM Liquid; Inactivated polio Sanofi Pasteur Dec 2005 1.04† 10-dose vial ‡ vaccine 10 vials of 10 doses = 2.46 cm3 VVM 7 IPV Vaccine SSI Statens Serum Liquid; Carton, 1 vial = 101.4 cm3 Inactivated polio Dec 2010 N/A Institut 1-dose vial vaccine Carton, 10 vials = 26.8 cm3 Carton, 50 vials = 12.9 cm3 Pipeline products Challenges DTP-HepB-IPV-Hib (PR5I): On 5 May 2014, WHO declared maintenance of the recommended paediatric hexavalent vaccine the international spread of polio measures for a period of 12 in Phase III of development to date in 2014 to be a Public months with no evidence of from Sanofi Pasteur.173 Health Emergency of International transmission.161,177,178 Concern and an “extraordinary DTP-HepB-IPV-Hib (V419): There are significant supply event” posing a ”public health paediatric hexavalent vaccine bottlenecks relating to IPV. With risk to other states for which a in Phase III from Merck.134 five-dose and new versions of the coordinated international response 10-dose vials only made available DPT-IPV (TAK-361S): tetravalent is essential”.161,177,178 WHO from mid- to late 2014, current vaccine in Phase II from Takeda identified Pakistan, Cameroon availability of one- and two-dose and Japan Polio Research and Syria as states posing the vials will be heavily constrained.169 Institute.174 greatest risk of wild poliovirus exportation, and a further seven To expedite supply of IPV, UNICEF Sabin IPV (sIPV) products countries (including Afghanistan recommends that countries provide from Panacea, Takeda and and Nigeria) as infected with timely information on preferred Intravacc (Netherlands Vaccine wild poliovirus but not currently vial size, acceptable alternatives, Institute) in varying phases exporting. WHO recommendations and national licensing requirements of development.175,176 include vaccination of all country and their anticipated timetable residents, visitors and travellers and for introduction.167,169,179 * Acquired by Serum Institute of India in July 2012. ** 5-dose vial presentation from Serum Institute of India/Bilthoven was put forward for the UNICEF bid tender although not WHO prequalified.166 It is anticipated to be prequalified and available for procurement by the end of 2014.167–169 † Price listed is the Gavi price, converted from euros to US dollars.170 Currently UNICEF procures Imovax Polio from Sanofi Pasteur for non-Gavi countries at three different price tiers that are based on adjusted Gross National Income per capita (see ‘Prices and affordability’ section, opposite).171 This arrangement does not cover all middle-income countries, prices for which are country- and supplier specific.169 ‡ All multidose opened vials must be discarded not more than six hours after opening (WHO multidose open-vial policy).172 48 Médecins Sans Frontières | The Right Shot 2nd Edition January 2015 I nactivated Poliovirus Vaccines ( I PV) Prices and affordability The Global Polio Eradication Initiative The Global Polio Eradication since 2012 WHO has declared immunisation schedules as a key Initiative (GPEI) was created in 1988, ending polio a “programmatic element of eradication and post- following a resolution passed at the emergency for global public eradication activities,180 reducing World Health Assembly. GPEI is a health”, as a result of which the the risk of re-emerging type-2 public–private partnership with the Polio Eradication and Endgame polio while also accelerating wild goal to eradicate polio worldwide. Strategic Plan 2013–2018 was poliovirus eradication.1,2,6,7,180 In Thus far more than US$8.2 billion developed.157 The plan includes the 2013, Gavi decided to support has been spent on polio eradication. phasing-out of OPV and progressive the introduction of IPV in routine Efforts intensified after 2008 and introduction of IPV into routine immunisation programmes.179 Price evolution: UNICEF and PAHO (See Annex A for more information on prices used in this section) Before 2010, there was only one the same year at US$2.90 and then lowest tier. According to the UNICEF WHO prequalified IPV product at US$2.80 in 2014, a 30% price website, tiers were determined on (Sanofi Pasteur’s Imovax Polio). drop [Graph 9, overleaf]. the basis of “GNI per capita, and by In 2010, Statens Serum Institute, considering each country’s overall In February 2014, price GSK and Bilthoven obtained level of development by adjusting announcements were made WHO prequalification status the GNI per capita to account for following UNICEF’s IPV tender. for their IPV vaccines. In July inequities in wealth distribution Sanofi Pasteur and Serum Institute 2012, Serum Institute of India within each country”.11 purchased Bilthoven Biologicals, of India/Bilthoven Biologicals and in 2013, the newly created responded to the tender and offered Sanofi’s announcement to sell Intravacc (the Dutch Institute for their IPV vaccines at a reduced price. IPV to UNICEF at a lower price was Translational Vaccinology) and Sanofi Pasteur offered different prices supported by the Bill & Melinda Bilthoven Biologicals started their based on groups of countries, while Gates Foundation and is heralded collaboration to improve the IPV Serum Institute of India offered one as critical in light of the Global Polio production process, with the aim of price for all countries. Endgame Strategy.171 But despite a more affordable vaccine.175,183 However, the price announcement efforts to reduce prices, the lowest PAHO has benefited from the entry raised some concerns as it was price for IPV remains more than of these new manufacturers into the first time that a manufacturer seven times as expensive as the the market. In 2013, the price responded to a UNICEF tender with lowest price for OPV: in 2014, the of IPV was reduced as a result of a clear tiered-pricing offer. Sanofi’s lowest price to UNICEF for OPV Bilthoven’s participation in the price offer classified countries in four is US$0.12 per dose (Bio Farma, Revolving Fund. PAHO purchased tiers: three groups of countries that 20-dose presentation), while IPV is IPV at US$4.14 from GSK in 2013, pay three distinct prices, and the priced at US$1 (Sanofi Pasteur, Gavi but purchased the Bilthoven vaccine Gavi-supported group comprising the countries only, 10-dose presentation). Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 49 Graph 9: Price evolution of Inactivated Poliovirus (IPV) vaccines for PAHO, UNICEF and Gavi 7.00 5.98 6.00 5.50 5.00 4.50 4.10 4.00 3.30 3.40 3.30 3.19 3.00 2.80 US$ PER DOSE 2.56 2.00 1.98 nactivated Poliovirus Vaccines ( I PV) I nactivated Poliovirus Vaccines 1.90 1.00 1.00 0 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015* PAHO, 1-dose UNICEF, Tier 2 countries, UNICEF, Tier 1 countries, UNICEF, Tier 3 countries, Sanofi Pasteur, 10-dose** Sanofi Pasteur, 10-dose** Sanofi Pasteur, 10-dose** UNICEF, Bilthoven Biologicals/Serum UNICEF, Gavi countries, UNICEF, Bilthoven Biologicals, 1-dose Institute of India, 5-dose Sanofi, 10-dose*** Sources: PAHO Revolving Fund, UNICEF Supply Division * Forecasted data. Prices remain the same between 2015 and 2018. ** Special terms apply except for a single-dose liquid presentation. MSF requested details from UNICEF on these special terms but the information was not provided. *** Sanofi Pasteur and the Gates Foundation have designed a price mechanism with additional financial contributions to attain the Gavi IPV price. MSF requested details on these subsidies but the information was not provided. Notes and methodology: • For PAHO, a weighted average price is used for 2006–2012, an average of the two available actual prices (from GSK and Bilthoven Biologicals) is used for 2013 and the actual price from Bilthoven Biologicals (sole supplier) is used in 2014. • The rise in price for PAHO from 2006 to 2013 occurred because, prior to 2013, only one country had introduced IPV in its routine immunisation programme. • Tiers for Sanofi Pasteur’s vaccine are:11 • Tier 1 countries: Cape Verde, Egypt, Morocco, Palestine, Philippines, Samoa, Swaziland, Vanuatu (GNI/capita: • Tier 2 countries: Albania, Algeria, Fiji, Iran, Macedonia, Maldives, Namibia, Serbia, Thailand, Tonga, Tunisia, Turkmenistan (GNI/capita: US$4,000–6,000). • Tier 3 countries: Botswana, Gabon, Lebanon, Mauritius, Seychelles, Tuvalu (GNI/capita: >US$6,000). 50 Médecins Sans Frontières | The Right Shot 2nd Edition January 2015 I nactivated Poliovirus Vaccines ( I PV) Prices in countries There are few data points from Pasteur’s tiered prices being aligned relationship between the price countries on IPV as several with country GNI per capita for of the vaccine and the country’s countries have introduced IPV countries who procure through wealth is much less obvious, even through pentavalent or hexavalent UNICEF, the end result continues when keeping in mind that there combination vaccines that contain to be high and unaffordable prices are different price categories IPV. Therefore, prices of standalone for many countries. Comparing the represented in the graph. IPV listed here might be higher in PAHO price to the UNICEF price, Prices of combination vaccines countries that have also introduced the PAHO price appears pegged to such as hexavalent DTaP-HepB-Hib- one of these combination vaccines the UNICEF price gradation despite UNICEF and PAHO procuring two IPV vaccine or the DTaP-Hib-IPV (e.g. South Africa). different products. Regarding vaccine have been explored in the The graph below [Graph 10] prices of IPV in countries that do pentavalent vaccines product card demonstrates that despite Sanofi not procure through UNICEF, the [see page 65]. Graph 10: Prices for Inactivated Poliovirus (IPV) vaccines by GNI/capita in several countries, 2013/2014* 14 60 12.46 12 50 9.98 10 40 8 7.74 6.90 30 6 US$ PER DOSE 4.05 20 4 GNI PER CAPITA 2.80 3.19 2.56 1.98 10 2 1.00 0 0 Gavi/ UNICEF, UNICEF, PAHO UNICEF, France India Tunisia South USA UNICEF*** Tier 1** Tier 2** Tier 3** Africa UNICEF, PAHO and Gavi Countries Gvt Hosp. Manuf. Retail GNI per capita (2012) Sources: PAHO Revolving Fund, UNICEF Supply Division, country price analysis (see Annex A for more information). * Annex A, Section C ** Special terms apply except for a single-dose liquid presentation. MSF requested details from UNICEF on these special terms but was not given information. *** Sanofi Pasteur and the Gates Foundation have designed a price mechanism with additional financial contributions to attain the Gavi IPV price. MSF requested details on these subsidies but was not given information. Notes and methodology: • All prices are for Sanofi Pasteur products (Ipol in the US, Imovax Polio in other countries), across presentations, except the PAHO price, which is for Bilthoven Biologicals vaccine. • For the Sanofi Pasteur vaccine purchased through UNICEF, GNI per capita thresholds are: Tier 1: up to US$4,000; Tier 2: US$4,000 – 6,000; Tier 3: over US$6,000.184 • PAHO GNI per capita estimated at US$7,500.184 Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 51 © Ikram N‘gadi Measles-containing Vaccines (Measles, MR, MMR) Measles-containing Vaccines (Measles, MR, MMR) WHO recommendations & general information Measles-containing vaccines include administered at 11–12 months coverage for routine measles and combination vaccines for measles of age, provides a seroconversion rubella vaccination at >80%. All and rubella (MR) and for measles, rate of 99%. Of children who fail mumps vaccine strains (except the mumps and rubella (MMR) and to respond to the first dose, 97% Rubini strain) confer short-term monovalent measles vaccines. (median value) develop immunity protective efficacy rates above 90% after the second dose.187 Mumps with administration of one dose.188 Measles is a highly infectious infection affects primarily the Rubella is an acute, contagious and viral disease. Vaccination against salivary glands and is most common generally mild viral disease, usually measles has been recommended as among children aged between affecting susceptible children and part of the Expanded Programme five and nine years. The disease is young adults. Rubella infections on Immunization (EPI) since the generally self limiting but serious occurring before conception or programme’s inception in 1974. complications can occur; these in early pregnancy are of greatest Before that, 90% of individuals were include meningitis, encephalitis, concern because rubella can be infected with measles before the age 188 deafness and orchitis. teratogenic, potentially leading of ten years.185 There were 122,000 to miscarriage, fetal death, or measles deaths in 2012, most of Mumps incidence has declined congenital malformations as part of which were among children aged dramatically since the 1960s, congenital rubella syndrome (CRS). under five years.185 Surveillance data when vaccines against it were first CRS can cause ophthalmic, auditory, show that there were 177,510 total introduced. Currently, global mumps cardiac and brain anomalies190 and reported measles cases globally for incidence is 100–1,000 cases per worldwide an estimated 110,000 2013, and 45,566 for the first five 100,000 population, with epidemic children are born every year months of 2014.186 peaks every two to five years.189 with CRS.191 Large scale rubella The WHO recommends measles The WHO recommends routine vaccinations over the past decade vaccination for all susceptible mumps vaccination in countries have substantially reduced rubella infants, young children and adults where reduction of mumps is a and CRS in many countries but (in the absence of contraindications) public health priority, provided more needs to be done to reach as part of national immunisation the country has a well-established the measles and rubella elimination programmes globally.187 The childhood vaccination programme targets set out in the Global Measles first dose of measles vaccine, if and the capacity to maintain and Rubella Strategic Plan.191–193 Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 53 The WHO recommends that of rubella infection from childhood Giving the second dose at 15–18 190 all countries yet to introduce to fertile age groups. All licensed months ensures early protection rubella vaccines (including those combined rubella vaccines (as of the individual and slows that are a component of MMR) part of MMR) should immediately accumulation of susceptible young induce seroconversion at a rate consider adding them to national children, thereby reducing the risk of 95% or higher after a single 124,185 immunisation programmes. of an outbreak. dose, with vaccine efficacy of WHO also recommends reviewing 90–100%.190 The choice of age for rubella national-level epidemiological vaccination depends entirely on factors, CRS burden and specific Nine months is the preferred age when the first dose of measles population profiles when for the first dose for countries with vaccine is given. Vaccination determining the immunisation ongoing measles transmission and in pregnant women should be strategy for targeting rubella. high risk of measles mortality. avoided because of the theoretical To keep CRS in check and work In countries with low rates of risk of congenital rubella.124,190 towards rubella control and measles infection among infants, elimination, vaccination coverage 12 months is the preferred age Mumps vaccination is recommended needs to be sustained at or above for the first dose to achieve a as part of the combined measles, Measles-containing Vaccines (Measles, MR, MMR) (Measles, MR, MMR) Measles-containing Vaccines 80% in an attempt to avoid shifting seroconversion rate of >90%. mumps and rubella vaccine.124,188 Doses in primary series Vaccine Age at 1st dose Booster (interval between doses) Measles 9 or 12 months (not <6 months)* 2 doses (minimum 4 weeks) No booster 2 doses (2nd dose at least 1 month before Mumps 12 – 18 months with measles-containing vaccine No booster school entry) Rubella 9 or 12 months with measles-containing vaccine 1 dose No booster 54 Médecins Sans Frontières | The Right Shot 2nd Edition January 2015 Measles-containing Vaccines (Measles, MR, MMR) Products & manufacturers Lowest known WHO PQ Form and Vaccine vial monitor (VVM) type Product Manufacturer price date presentation* and cold chain volume (per dose) (UNICEF, US$) VVM 14 Apr 1997 Lyophilised, 10- or Measles (10 - dose) 0.219 Carton, 50 vials (active) + carton, 50 ampoules Bio Farma 20 - dose vials + water of diluent = 26.11 cm3 (1- dose vials), 13.1 cm3 vaccine Sep 2006 (10 doses) diluent (2 - dose vials), 5.22 cm3 (5 - dose vials), 2.611 cm3 (20 - dose) (10-dose vials) Lyophilised, 10 - dose VVM Type 14 Measles GPO –Merieux Sep 2010 vial + water (5 ml) N/A vaccine Box, 10x10 - dose vials + box, 10 vials of 5 ml diluent diluent = 2.13 cm3 Rouvax Lyophilised, 10 - dose VVM 14 Measles Sanofi Pasteur May 2002 vial + water for 0.450 Box, 10x10 - dose vials + box, 10 vials of 5 ml vaccine injection (5 ml) diluent diluent = 2.46 cm3 0.252 VVM 14 Measles Lyophilised, 1-, 2-, (10 doses) Serum Institute Carton, 50 vials (active) + carton, 50 ampoules vaccine (live, Feb 1993 5- and 10 - dose vials + of India 0.770 of diluent = 26.11 cm3 (1- dose vials), 13.1 cm3 attenuated) ampoule water diluent (1 dose; (2 - dose vials), 5.22 cm3 (5 - dose vials), 2.611 cm3 2003 price) (10 - dose vials) Measles VVM 14 Lyophilised, 1-, 2-, and rubella Serum Institute Jul 2000 5- and 10 - dose vials + N/A Carton, 50 vials + 50 ampoules = 25.11 cm3 vaccine (live, of India ampoule water diluent (1- dose vials), 13.1 cm3 (2 - dose vials), 5.22 cm3 attenuated) (5 - dose vials), 2.611 cm3 (10 - dose vials) VVM 7 Priorix Mar 2001 Lyophilised, 1- and Vaccine vial = Measles, (1- dose) 2 - dose vials + ampoule 3.250 9.6 cm3 + diluent ampoule = 25.6 cm3 GSK mumps and Dec 2011 water for injection (2 dose) rubella vaccine (2 - dose) diluent Carton, 100 vials of vaccine and 100 ampoules diluent = 4.8 cm3 (vaccine vial) + 12.8 cm3 (diluent ampoule) M-M-R II Measles, Merck Sharp & VVM 7 Jan 2009 Lyophilised, 1-dose vial N/A mumps and Dohme rubella vaccine Carton, 10 vials = 15 cm3 3.100 No VVM (1 dose); VVM 14 (10 dose) Trimovax Lyophilised, 1-dose (1 dose, Merieux 10 vials of 1 dose vaccine + 10 of 0.5 ml water vial + 1-dose ampoule 2012) Measles, Sanofi Pasteur Apr 2002 in ampoules = 12.66 cm3 (diluent); and 10-dose mumps and 1.890 vial + 5 ml vial diluent rubella vaccine (10 doses, 10 vials of 10 dose vaccine + 10 of 5 ml water 2014) diluent = 2.46 cm3 2.150 Measles, (1 dose) VVM Type 14 mumps Lyophilised, 1-, 2-, 5- Serum Institute 1.040 and rubella Aug 2003 and 10 - dose vials of India (5 doses) vaccine (live, (+ ampoule diluent Carton, 50 vials + carton, 50 ampoules diluent = 26.11 cm3 (1- dose vials), 13.1 cm3 (2-dose vials), attenuated) 1.025 5.22 cm3 (5 - dose vials), 2.611 cm3 (10 - dose vials) (10 doses) * All reconstituted multidose vials must be discarded no more than six hours after opening (WHO multi-dose open-vial policy).172 Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 55 Pipeline products of conclusive independent evidence with highly mobile populations disproving the alleged causal link and countries facing complex A live, attenuated MMR vaccine between MMR and autism, among humanitarian emergency situations, from GSK is in Phase III of other safety concerns, claimed by where measles case fatality rates development.194 anti-vaccine advocates.197,198 can be as high as 25%.193 Bio-Manguinhos, in association The Global Measles and Rubella Alternative vaccine delivery with the Bill & Melinda Gates Strategic Plan lists several methods, such as by the nasal route, Foundation, is developing an are in development after research MR vaccine.195,196 challenges to the elimination of these diseases. These include indicating they can provide a viable establishing and guaranteeing pathway for delivery, with improved 199 Challenges sustained and predictable financing vaccine seroconversion rates. Outbreaks of both mumps for immunisation efforts; improving The measles monovalent vaccine and measles have surged in data and reporting of vaccination supply is fragile because a single developed countries in recent coverage; and addressing concerns manufacturer (Serum Institute of years. This is largely because public on the capacities of health systems. India) produces 80% of the supply misconceptions about vaccine safety The plan also calls for working and is also the sole manufacturer Measles-containing Vaccines (Measles, MR, MMR) (Measles, MR, MMR) Measles-containing Vaccines are causing parents to choose not to with governments to reach areas of the only WHO prequalified vaccinate their children,193 in spite of high population density, areas MR vaccine.200 © Seb Geo 56 Médecins Sans Frontières | The Right Shot 2nd Edition January 2015 Measles-containing Vaccines (Measles, MR, MMR) Prices and affordability Price evolution: UNICEF and PAHO (See Annex A for more information on prices used in this section) Measles vaccine MR vaccine MMR vaccine The price of the measles vaccine Recent recommendations by WHO MMR vaccines are more expensive is relatively low, but has followed (2011)190 to include rubella in than MR or measles vaccines. For an upward trend in the past routine immunisation have increased instance, the lowest price per dose decade [Graph 11]. This likely demand for MR and MMR vaccines. offered to UNICEF for the MMR reflects reduced demand for vaccine (10-dose presentation However, the number of the monovalent product, as by Serum Institute of India at manufacturers of the MR vaccine countries progressively switch to US$1.025) is almost twice that has always been limited to two, combination vaccines such as MR of the MR vaccine offered in the and following Crucell’s exit and MMR (for instance, PAHO same presentation by the same from the market in 2012, Serum ceased orders for measles vaccines manufacturer (at US$0.55) Institute of India was left as the sole in 2006), and a decreasing number [Graph 13, overleaf]. manufacturer of a WHO prequalified of manufacturers. MR vaccine.113 There are large price differences The number of different products between the products containing Increasing demand from UNICEF procured by UNICEF has declined different strains of mumps. For and a diminishing number of from seven in 2002 to only three, instance, the PAHO price in 2014 for manufacturers have driven up two of which are produced by the single-dose MMR Jeryl Lynn strain prices of the MR vaccine emerging manufacturers. Mono- vaccine (manufactured by GSK and [Graph 12, overleaf]. dose measles vaccines were Merck) was about 2.4 times more purchased by UNICEF for the last In 2013, Gavi announced expensive than the single-dose MMR time in 2003; since then the much its support of large-scale catch Urabe strain vaccine (manufactured less expensive multi-dose vial up campaigns with the MR by Sanofi Pasteur), and five times presentation has been preferred. vaccine, provided that countries more expensive than the lowest- self-finance the introduction of priced presentation of the MMR the vaccine into their routine Zagreb strain vaccine (manufactured immunisation programmes.201 by Serum Institute of India). Sources: Graph 11: Price evolution of measles vaccines PAHO Revolving Fund, for PAHO and UNICEF UNICEF Supply Division 1.00 0.97 0.88 Notes: 0.90 0.80 0.73 • Products omitted from graph 0.77 because of data discontinuity. 0.68 A 10-dose presentation was sold 0.60 to UNICEF by Tanabe Seiyaku 0.50 from 2002 to 2003; and Eisai Co from 2001 to 2003. 0.40 US$ PER DOSE 0.28 • Sanofi Pasteur product was 0.19 sold under Aventis Pasteur 0.20 0.14 0.23 Canada from 2001 to 2003. 0.19 0.16 0.10 0.11 0.12 • Novartis supplied measles vaccines 0.00 to UNICEF in 2005 but has not 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015* 2016* agreed to the publication of prices. PAHO, 1-dose UNICEF, Serum Institute of India, 10-dose UNICEF, Sanofi Pasteur, 10-dose UNICEF, Aventis Pasteurs Canada, 1-dose PAHO, 10-dose UNICEF, Statens Serum Institute, 10-dose UNICEF, Bio Farma, 10-dose UNICEF, Serum Institute of India, 1-dose *Forecasted data Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 57 Graph 12: Price evolution of Measles-Rubella (MR) vaccines for PAHO and UNICEF 2.00 1.80 1.80 1.65 1.60 1.35 1.40 1.20 1.10 1.00 0.80 US$ PER DOSE 0.60 0.55 0.61 0.60 0.48 0.48 0.50 0.40 0.20 0.00 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015* 2016* PAHO, 1-dose PAHO, 10-dose UNICEF, Crucell, 10-dose UNICEF, Serum Institute of India, 10-dose *Forecasted data Measles-containing Vaccines (Measles, MR, MMR) (Measles, MR, MMR) Measles-containing Vaccines Sources: PAHO Revolving Fund, UNICEF Supply Division Note: Products omitted from graph because of data discontinuity: PAHO purchased a two-dose presentation of the vaccine from 2003–2005. Graph 13: Price evolution of Measles-Mumps-Rubella (MMR) vaccines for PAHO and UNICEF 6.00 5.75 5.00 5.00 4.00 3.60 3.50 3.25 3.25 3.00 2.70 2.70 2.50 2.37 2.05 US$ PER DOSE 2.00 2.00 1.60 1.50 1.55 1.99 1.16 0.92 1.03 1.13 1.00 0.90 0.89 0.85 0.99 0.69 0 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015* 2016* PAHO, Jeryl Lynn strain, 1-dose PAHO, Urabe strain, 10-dose UNICEF, GSK, Jeryl Lynn strain, 1-dose PAHO, Urabe strain, 1-dose PAHO, Zagreb strain, 10-dose UNICEF, Sanofi Pasteur, Urabe strain, 10-dose PAHO, Zagreb strain, 1-dose UNICEF, Serum Institute of India, UNICEF, Serum Institute of India, PAHO, Zagreb strain, 5-dose Zagreb strain, 1-dose Zagreb strain, 10-dose *Forecasted data Sources: PAHO Revolving Fund, UNICEF Supply Division Notes: • Products omitted from graph because of data discontinuity: UNICEF purchased a 10-dose MMR Jeryl Lynn strain from GSK in 2002, and a Sanofi Pasteur Urabe-strain MMR vaccine in 2010 and 2012. Serum Institute of India also offers a two-dose MMR vaccine since 2010, priced similarly to its 10-dose presentation. • Novartis has supplied MMR to UNICEF but has not agreed to the publication of prices. 58 Médecins Sans Frontières | The Right Shot 2nd Edition January 2015 Measles-containing Vaccines (Measles, MR, MMR) Prices in countries: focus on MMR Vaccines made with the Jeryl Lynn of the measles vaccine from the Combined measles, mumps, rubella mumps strain are more expensive; government is US$0.59, while a dose and varicella (MMRV) vaccines countries opting for a measles or MR of MMR through the private sector are not yet WHO prequalified, vaccine instead of an MMR product will cost US$13.51 [Graph 14]. but countries might decide to use will unfortunately lose a disease- MMRV instead of MMR. In the The price of the MMR vaccine in the control opportunity to vaccinate countries we analysed, only the against mumps.197 retail market in the US (MMRII, by USA and South Africa had pricing Merck, at US$56.14) is extremely data available for MMRV. The In countries where only measles is high compared to that in other vaccine is markedly more expensive included in the Expanded Programme countries; it is double the price paid than MMR, retailing in the private on Immunization (EPI), MMR is in Belgium, the next high-income sector at US$36.42 per dose in available only through the private country included in our analysis South Africa (Priorix Tetra, by sector, often at very high prices. In (for Priorix, by GSK, at US$29.27), GSK) and at US$157.64 in the South Africa, for instance, the price and triple the price paid in France. USA (ProQuad, by Merck). Graph 14: Prices for MMR vaccines in several countries, by manufacturer and price type, 2013/2014* 60 56.14 Government price Retail price 50 40 29.27 30 19.91 17.55 18.26 US$ PER DOSE 20 13.47 13.51 13.78 10 3.25 3.60 5.00 0.99 1.03 1.07 1.13 1.75 1.89 0 USA USA MSF PAHO PAHO PAHO France UNICEF UNICEF UNICEF Belgium Lebanon Morocco Morocco Thailand** Philippines South Africa **Thailand purchases its vaccine Serum Institute of India Sanofi Pasteur GSK Merck Other from GPO Merieux (not WHO PQ) Sources: PAHO Revolving Fund, UNICEF Supply Division, MSF Supply, country price analysis. * Annex A, Section C Notes: • Prices for UNICEF, MSF, PAHO, Thailand and the Philippines are for multidose vials; those for the other countries are for single-dose vials. • MSF price is Incoterm Carriage Paid To (named destination) (see Annex C). • When a country or organisation purchases several presentations of a same vaccine, only the lowest price is presented in the graph. Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 59 © Aurelie Baumel/MSF Meningococcal Vaccines Meningococcal Vaccines WHO recommendations & general information Meningococcal meningitis is a (December to June), during which vaccination is recommended life-threatening form of bacterial time disease rates can reach 1,000 for high-risk groups such as 202–204 children, young adults living meningitis, and the Neisseria cases per 100,000. in closed communities, and for meningitidis bacterium causes one In 2010, there were an immunosuppressed individuals of the most virulent and severe estimated 422,851 deaths (e.g those with asplenia or forms of the disease. Six serogroups 205 from meningitis. The WHO advanced HIV).202 – A, B, C, X, W135 and Y – are recommends that countries responsible for almost all outbreaks with high (more than ten cases Delivery strategy (routine of meningitis, with most outbreaks per 100,000 population) or immunisation, supplementary caused by serogroup A.202–204 intermediate (two to ten cases immunisation activities or private services) and the choice of An area stretching from Senegal per 100,000) endemic rates, as which specific vaccine* to use is to Ethiopia in sub-Saharan Africa, well as countries with frequent dependent on the country-specific known as the African meningitis epidemics, should introduce epidemiological profile, locally belt, experiences the largest meningococcal vaccination prevalent serogroups, and overall and most frequent outbreaks. programmes.202 In countries socioeconomic capability.202 Meningococcal disease incidence with low endemicity (fewer peaks annually in the dry season than two cases per 100,000), Doses in primary series Vaccine Age at 1st dose Booster (interval between doses) Need for booster yet MenA Conjugate 1– 29 years 1 dose to be established ≥12 months (including teenagers 1 dose No booster and adults) MenC Conjugate Booster 1 year 2 – 11 months 2 doses (2 months) after 2nd dose st Quadrivalent 2 doses (1 dose at 9 months with 3 -month 9 – 23 months st nd No booster Conjugate interval between 1 and 2 doses) Vaccine ACYW-135 ≥2 years 1 dose No booster * Polysaccharide vaccines can be used for children aged more than two years in outbreak settings or when there are conjugate vaccine supply constraints. Conjugate vaccines are preferred for their superior immunogenicity and potential to induce herd immunity. They are recommended for all children and adolescents aged nine months to 18 years, with other groups included on the basis of surveillance data.202 Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 61 Products & manufacturers Lowest known WHO PQ Form and Vaccine vial monitor (VVM) type Product Manufacturer price date presentation and cold chain volume (per dose) (UNICEF, US$) Meningococcal Vaccines VVM 30* MenAfriVac Lyophilised, 10 - dose Meningococcal A Serum Institute of India Jun 2010 vial + 10 - dose 0.52 – 0.58 Carton, 50 vials (active) + 50 ampoules conjugate vaccine ampoule (diluent) (diluent) = 2.6 cm3 VVM 14 Lyophilised, 10 - dose Polysaccharide 0.80 meningococcal Bio-Manguinhos Dec 2007 vial + buffered saline (2012) A+C vaccine solution diluents** 10 vials = 2.96 cm3 Lyophilised, 10 - dose No VVM Polysaccharide vial + specific meningococcal Sanofi Pasteur Jul 1997 1.22 10 vials of 10 doses (vaccine) + 10 vials meningococcal A+C vaccine 5 ml (diluents) in separate box = 2.46 diluents in vial (5 ml)** cm3 VVM 7 Menactra Meningococcal Sanofi Pasteur Mar 2014 Liquid, 1- dose vial N/A Carton, 5 vials = 20.50 cm3 ACYW -135 conjugate vaccine Carton, 1 vial = 54.88 cm3 Menomune VVM 30 Meningococcal 2 - vial set: lyophilised ACYW-135 Sanofi Pasteur May 2013 10 - dose vial + diluent 4.00 Carton, 1 vial active + 1 vial diluent = † polysaccharide vial 11.13 cm3 vaccine Menveo VVM: N/A 1- dose lyophilised Meningococcal Novartis †† + conjugate N/A ACYW -135 component** Box, 10 doses conjugate vaccine * Stable under controlled temperature chain settings, i.e. at up to 40°C for four days, after which unopened vials should be discarded if not used.206 ** All reconstituted multidose vials must be discarded no more than six hours after opening (WHO multidose open-vial policy).172 † As it is preservative free, opened vials can be kept for subsequent use (up to a maximum of 28 days) within stipulations of the WHO Policy Statement on use of opened multidose vials in subsequent immunisation sessions.172 †† At time of research and publication, the link on the WHO PQ page did not work (www.who.int/immunisation_standards/vaccine_quality/PQ_vaccine_list_en/en/). 62 Médecins Sans Frontières | The Right Shot 2nd Edition January 2015 Meningococcal Vaccines Pipeline and other products GSK previously produced in emergency settings, but GSK Serum Institute of India has a a meningococcal ACW-135 ceased its production in 2012.208 meningitis ACYW-135 quadrivalent polysaccharide vaccine in a 50-dose vaccine in development and GSK also produces a meningococcal presentation for outbreak response Novartis has a meningitis ABCW- C and Y conjugate vaccine with Hib for only. This particular presentation 135 Y product in Phase II.212,213 was procured by UNICEF at the USA and a European Commission- US$1.25 per dose in 2012,207 after approved meningococcal ACYW-135 Pfizer has a meningococcal B approval by the International conjugate vaccine (Nimenrix), but (bivalent rLP2086) product Coordinating Group (ICG) for use neither is WHO prequalified.194,209–211 in Phase III.214,215 Challenges Inadequate global surveillance data public health response to recent push to evaluate other vaccines make it difficult to predict more localised epidemics and seasonal for use in CTC. Encouraging accurately the global burden of hyperendemicity observed between manufacturers to develop CTC disease specifically attributable to 2006 and 2010.216 vaccines and to relabel vaccines for meningococcal meningitis.202 CTC use is a continuous challenge.110 MenAfriVac has paved the way as Absence of a licensed vaccine for the first vaccine approved by WHO serogroup X will hinder countries’ for use in a controlled temperature abilities to provide an adequate chain (CTC) and has prompted a Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 63 Prices and affordability The Meningitis Vaccine Project The Meningitis Vaccine Project (MVP) and Research of the US Food and countries such as Chad and Nigeria, was established in 2001 by the Drug Administration (FDA), with the number of cases in the Program for Appropriate Technology Serum Institute of India began Meningitis Belt at their lowest for a Meningococcal Vaccines in Health (PATH) and WHO, with development of a meningococcal decade.220 The low cost of the vaccine funding (US$70 million) from the conjugate A vaccine, called makes the project sustainable, as Bill & Melinda Gates Foundation. MenAfriVac, in 2003. MenAfriVac countries can finance and purchase The aim of the MVP was to develop was WHO prequalified in June 2010. vaccines themselves.221 meningococcal conjugate vaccines Serum Institute of India is the sole In 2012, MenAfriVac was approved for appropriate for Africa. Serum Institute supplier of the vaccine, selling it at use in a controlled temperature chain of India joined the partnership, US$0.528 a dose in 2013.11 The (CTC) for up to 40°C for up to four received technology transfers, and total project cost was just US$60 days. Other broader benefits of using committed to develop a vaccine million, excluding the cost of the a CTC include increased acceptance priced at US$0.50 a dose or less.217 manufacturing plant.218 In 2013, among healthcare workers because A major aim of the MVP was to the Bill & Melinda Gates Foundation of reduced logistical burdens, and develop a vaccine that could provide awarded the project an extension cost savings of up to 50% of the an effective and affordable solution grant of US$17 million over 2.5 years vaccine price.108 Modelling studies to combat epidemic meningitis while ‘to support clinical research related show that making individual vaccines also addressing cold chain-related to the use of the newly developed more thermostable not only increases logistical challenges.217 vaccine in infants’.219 their availability, but also the availability With the cooperation of Synco Bio More than 100 million people have of other vaccines they are administered Partners in the Netherlands, and been vaccinated and MenAfriVac with, in addition to alleviating supply the Center for Biologics Evaluation has successfully halted outbreaks in chain bottlenecks and lowering costs.222 Price evolution: UNICEF and PAHO (See Annex A for more information on prices used in this section) The development of MenAfriVac at a low price, allowing UNICEF to most expensive vaccine purchased is one of the best examples of a purchase MenAfriVac at US$0.53 by the Revolving Fund. vaccine research and development per dose in 2013. Both meningitis A vaccine for process that set affordability and The price for conjugate meningitis UNICEF and meningitis C vaccine adaptability targets from the C vaccines for the PAHO Revolving for PAHO have increased in price outset. The MVP has been an Fund has never decreased below in 2013, by 23% for UNICEF (from extremely successful initiative US$14 per dose, and has even US$0.43 to US$0.53) and 39% for that succeeded in producing a increased in recent years to reach PAHO (from US$14 to US$19.50). conjugate meningococcal vaccine US$19.50 per dose, making it the Prices in countries MSF purchases the meningitis Prices for meningitis C vaccines A few countries also provided prices A vaccine via the International in our analysis were only found for the tetravalent meningitis ACYW- Coordinating Group (ICG) in high-income countries and 135 vaccine, which is priced higher. mechanism at US$0.53 per dose Hungary for the private sector. For instance, meningitis ACYW-135 (Incoterm CPT). Other than Outside of PAHO, retail prices vaccines are available in Lebanon the MVP price for the meningitis per dose of meningitis C vaccines at the retail price of US$85.67– A vaccine, the price of other range from US$29.11 in Hungary 87.27 per dose (for Menveo by conjugate meningococcal for Menjugate by Novartis to Novartis and Menactra by Sanofi vaccines is very high. US$50.62 in the Czech Republic Pasteur, respectively). for the same product. 64 Médecins Sans Frontières | The Right Shot 2nd Edition January 2015 Yann Libessart/MSF © Yann Pentavalent Vaccines (DTP-HepB-Hib) WHO recommendations & general information The pentavalent vaccine combines Programme on Immunization Perinatal infections account for diphtheria, tetanus, whole- (EPI) that was started in 1974. 21% of the overall global HepB cell pertussis, hepatitis B and HepB vaccines were first WHO disease burden,239 the highest Haemophilus influenzae type b prequalified in 1987, followed proportion of deaths from which (DTwP-HepB-Hib) vaccines to by Hib vaccines in 1998.12 DTP occur in Asia and Africa. At prevent all five diseases. Annually vaccines were first used in 1948,229 present only 18 out of 56 Gavi- across the world, diphtheria and then integrated with HepB eligible countries offer the WHO- accounts for an average of 2,500 and Hib to form a pentavalent recommended HepB birth dose,240 deaths,223 pertussis for 89,000 vaccine. The first pentavalent and even among them coverage is ib) (DTP- H epB- ib) Pentavalent Vaccines deaths224 and tetanus for 72,600 vaccine was introduced in the poor. However, with support, there deaths among children aged under late 1990s.12 Vaccine efficacy is evidence to suggest that coverage 225 five years. for the components of the rates can reach ≥90%. This was exemplified by the partnership Hepatitis B (HepB) alone accounts pentavalent vaccine is 85 – 95% 228,230,231 232 between Gavi and the Chinese for between 500,000 and 700,000 for Hib, 95% for HepB, government, whereby provision deaths per year,226 with most cases 95.5% for diphtheria,233 61– 89% of a HepB birth dose free of charge occurring in developing countries. for pertussis,234 and 80 –100% for to the public (through co-financing Most cases of liver cancer across tetanus.235 Studies evaluating the between Gavi and the government the world (60–80%) are also combined efficacy of the diphtheria- of China) catalysed a dramatic attributable to infection with tetanus-whole-cell-pertussis (DTwP) scale-up in coverage rates from the HepB virus.226 vaccine found efficacy ranged from around 40% in poorer counties to 46% to 92%.234 Haemophilus influenzae type b >90% in most parts of the country, (Hib) accounts for 200,000 annual More than 170 countries with <1% of children overall being 241,242 deaths, with a disease incidence of worldwide,236 including all 73 infected with HepB. two to three million cases; the most 237 Gavi-eligible countries, have The WHO recommends that all serious cases occur in children aged introduced the pentavalent infants receive their first dose of six to 12 months.227,228 vaccine, including India, which monovalent HepB vaccine124,229 Historically, the trivalent independently is forecast to within 24 hours of birth; such diphtheria-tetanus-pertussis account for 20% of the global administration is 90% effective (DTP) vaccine was considered demand for pentavalent vaccine in halting vertical disease the cornerstone of the Expanded (28,000,000 doses) in 2014.238 transmission.243 Doses in primary series Vaccine Age at 1st dose Booster (interval between doses) • DTP booster at 1– 6 years (preferably in 2nd year of life) 3 doses (4 weeks between 1st and 2nd doses; and 2nd DTwP-HepB-Hib 6 weeks and 3rd dose) • Hib booster only where high disease burden exists, at 15 – 18 months 66 Médecins Sans Frontières | The Right Shot 2nd Edition January 2015 Pentavalent Vaccines (DTP- H epB- ib) Products & manufacturers Lowest known WHO PQ Form and Vaccine vial monitor (VVM) type Product Manufacturer price date presentation and cold chain volume (per dose) (UNICEF, US$) VVM 14 Quinavaxem 3 Berna Biotech 2 ml vial = 10.28 cm DTwP-HepB-Hib Sep 2006 Liquid, 1-dose vial 2.40 – 2.60 (Crucell) vaccine 3 ml vial (Green Cross)* = 12.85 cm3 3 ml vial (Berna) = 13.14 cm3 VVM 14 Box, 24 vials of 1-dose DTwP-HepB and 24 vials 3 Liquid (DTP-HepB) of 1-dose Hib = 29.36 cm DTwP-HepB-Hib + lyophilised (Hib), 1.80 Biological E Aug 2011 Box, 15 vials of 10-dose DTwP-HepB and 15 vials vaccine 1- and 10-dose (10-dose vial) of 10-dose Hib = 7.8 cm3 vials Additional 1- dose mono carton packaging presentation with one set of 2 vials DTwP-HepB- Hib = 34.7 cm3 1.19 VVM 7 (10-dose vial) Box, 24 vials of 10 - dose = 2.9 cm3 DTwP-HepB-Hib Fully liquid, 1- and Biological E May 2012 2.35 vaccine 10-dose vials (1-dose vial) Box, 48 vials of 1- dose =14.6 cm3 VVM 14 Euforva/Hib Inj Liquid (DTP-HepB) Box, 1 vial Hib +1 vial DTwP-HepB = 41.33 cm3 1.96 LG Life Sciences Aug 2012 + lyophilised (Hib), (2-dose vials) DTwP-HepB-Hib (2 - dose vial) 1- and 2 - dose vials vaccine Box, 5 vials DTwP-HepB + 5 vials Hib = 14.15 cm3 (2 - dose vials) Tritanrix VVM 14 Liquid (DTP-HepB) HB+Hib 2.95 GSK May 2006 + lyophilised (Hib), (2 dose) DTwP-HepB-Hib 1- and 2-dose vials Packaging: N/A vaccine 2.96 VVM 14 Easyfive – TT Fully liquid, (1 dose) Carton, 800 vials = 18.05 cm3 (1- dose vials) DTwP-HepB-Hib Panacea Biotec Oct 2013 1- and 10-dose vials 1.94 vaccine Carton, 24x25 = 600 vials = 4.30 cm3 (10 dose) (10 - dose vials) DTwP-HepB-Hib Serum Institute Fully liquid, VVM 14 Sep 2010 N/A vaccine of India 2- dose vial Carton, 24x25 = 600 vials = 4.30 cm3 * Green Cross is a contracted manufacturer of Berna Biotech, responsible for filling the WHO prequalified Quinavaxem in vials of 3 ml occupying a cold chain volume of 12.85 3cm Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 67 VVM 14 Liquid, 1- and 2-dose ampoule Carton, 4x50 = 200 vials Hib + 4x50 = 200 DTwP-HepB-Hib Serum Institute 2.25 May 2010 (DTPw-HepB) + ampoules DTwP-HepB = 39.2 cm3 (1- dose vial) vaccine of India (2011 price) lyophilised 1- and 2- dose vials (Hib) Carton, 4x50 = 200 vials of Hib + 4x50 = 200 ampoules of DTwP-HepB =19.6 cm3 (2 - dose vial) 2.70 VVM 14 (1 dose) Carton, 50 vials = 26.1 cm3 (1- dose vials) DTwP-HepB-Hib Serum Institute Fully liquid, 1- and Sep 2010 1.95 – 2.10 vaccine of India 10-dose vials (10 dose) Carton, 50 vials = 2.6 cm3 (10 - dose vials) ib) (DTP- H epB- ib) Pentavalent Vaccines Notes: • Shantha Biotechnics, a subsidiary of Sanofi Pasteur, previously had a WHO prequalified fully liquid, pentavalent vaccine – Shan5. Absent from the prequalified list for the past four years, having been withdrawn because of quality concerns, it is in the process of regaining WHO prequalification.244,245 • Except for Serum Institute of India’s DTwP-HepB-Hib 10-dose vial, which can be kept for up to 28 days for future immunisation sessions, all multidose reconstituted vials must be discarded no more than six hours after opening (WHO’s multidose open-vial policy).172 Pipeline products Gavi anticipates the entry of one to Several companies are developing and Sanofi Pasteur have a product four new manufacturers within the hexavalent vaccines; building on nearing the end of Phase III.164,249 next three years.246 One of these is the the success of pentavalent products, In 2013, Biological E and GSK also Indonesian manufacturer Bio Farma; these new vaccines will additionally announced that they were jointly the prequalification process for their include the inactivated polio vaccine developing a whole-cell pertussis PentaBio vaccine is ongoing, with (IPV). Merck and Sanofi Pasteur fully liquid hexavalent vaccine.250 WHO evaluation expected to take have a collaborative product in place in late 2014.247 Phase III134,164,248 clinical trials Challenges Some countries continue to use vaccines to a thermostable who are subject to Indian national vaccines containing acellular variant could result in improved regulatory authorities. The WHO pertussis (aP). However, recent availability of other EPI vaccines lists six critical control functions that guidelines from WHO’s Strategic by up to 93% and improved all national regulatory authorities Advisory Group of Experts (SAGE) availability of pentavalent vaccines must exercise in a competent and underline the need for countries by up to 97%.222 independent manner in order using whole-cell pertussis (wP) to guarantee vaccine quality. to continue doing so; wP provides As countries have moved to Dependence on a single national a higher initial efficacy and pentavalent vaccine, demand authority is therefore considered slower waning of immunity, for standalone DTP has declined potentially risky in the event of any and has a greater impact on significantly. In 2012, demand for adverse changes to even one of the disease transmission compared DTP through UNICEF represented control functions.252 to aP vaccines.251 17% of DTP-containing vaccine orders. In 2013, there was only Any decrease in the number of Adapting existing vaccines to more manufacturers producing pentavalent one supplier (Bio Farma) for DTP thermostable variants, which could vaccines could adversely constrain vaccines through UNICEF.238 be used in a controlled temperature vaccine supply. Gavi forecasts that, chain, could result in major cost More than 70% of Gavi and to meet demand, at least four critical savings. Modeling studies have UNICEF’s pentavalent vaccine suppliers must remain in the market shown that changing pentavalent supply is from Indian manufacturers for the next ten years.246 68 Médecins Sans Frontières | The Right Shot 2nd Edition January 2015 Pentavalent Vaccines (DTP- H epB- ib) Prices and affordability Price evolution: UNICEF and PAHO (See Annex A for more information on prices used in this section) The pentavalent vaccine market is compared to the previous lowest US$1.19 per dose in 2013 (Biological the best example of a competitive existing price of US$3.50 per dose E, 10-dose presentation). market in which entry by emerging (GSK, two-dose presentation). Prices of all presentations have manufacturers has greatly contributed The introduction of vaccines in 10- decreased, an indication of strong to lowering prices [see Graph 2, dose vials in 2011 and 2012 and the competition in this market and a page 1]. The price of pentavalent decision of emerging manufacturers sustained demand over time for vaccines started to decline in 2008 to decrease their prices99 further significant volumes. However, [Graph 15] with the entrance lowered the price: the lowest price UNICEF prices seem to have of Shantha Biotech, offering its available decreased by 56%, from stabilised, which means that the US$2.90 single-dose vaccine to US$2.70 per dose in 2010 (Shantha price for this vaccine might have UNICEF at a 17% reduced priced Biotech, single-dose presentation) to reached its floor. Graph 15: Price evolution of pentavalent vaccines for PAHO and Gavi/UNICEF 4.00 3.65 3.63 3.50 3.50 3.50 3.10 2.95 2.95 3.00 2.90 2.80 2.80 2.64 2.70 2.50 2.35 2.40 2.25 2.20 US$ PER DOSE 2.25 2.25 1.95 1.95 1.94 2.00 1.97 1.95 1.75 1.94 1.94 1.85 1.70 1.50 1.34 1.19 1.00 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015* 2016* Gavi/UNICEF, Berna Biotech (Crucell), 1-dose Gavi/UNICEF, Biological E., 1-dose Gavi/UNICEF, Panacea Biotech, 1-dose Gavi/UNICEF, Serum Institute of India, 1-dose Gavi/UNICEF, GSK, 2-dose Gavi/UNICEF, Biological E., 10-dose** Gavi/UNICEF, Panacea Biotech, 10-dose** Gavi/UNICEF, Serum Institute of India, 10-dose Gavi/UNICEF, Shantha Biotech, 1-dose Gavi/UNICEF, LG Life Sciences, 2-dose Gavi/UNICEF, Serum Institute of India, 2-dose PAHO, 1-dose PAHO, 10-dose Sources: PAHO Revolving Fund, UNICEF Supply Division * Forecasted data ** Special terms apply that are not publicly available Notes: • All single-dose and 10-dose vaccines are liquid; all two-dose vaccines are lyophilised. • Biological E also offered a 10-dose lyophilised vaccine in 2012, not represented on this graph. Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 69 Prices in countries Pentavalent and other vaccine (Serum Institute of India) The hexavalent vaccine is considered combination vaccines costs US$8.60 and IPV (Sanofi a good combination vaccine to Pasteur) costs US$6.90 [ see IPV increase coverage of Hib and For certain countries, the Product Card, page 46], while a HepB in developing countries pentavalent vaccine remains DTaP-Hib-IPV (by Sanofi Pasteur) while integrating IPV in EPI. unaffordable. For example, Egypt costs US$35.54, which is more But the higher cost of hexavalent only introduced pentavalent vaccine than twice the price of the two vaccines is likely to result in slow to its EPI in 2014, after entering into other vaccines combined. Countries uptake in low- and middle-income a ten-year agreement to procure countries, particularly until there introducing different combination 80 million doses of Biological E’s is a broader manufacturer base vaccines might also scatter the product through the UNICEF Supply to help lower costs. Currently, 253,254 demand across products, negatively Division for US$200 million. the cost of a hexavalent vaccine impacting prices. ib) (DTP- H epB- ib) Pentavalent Vaccines Among the countries we analysed, remains higher than IPV and pentavalent together.164,255 few had pentavalent vaccines in Looking at current prices [Graph 16], DTaP-Hib-IPV vaccines are available their drug lists, as several other Hexavalent vaccines are also not at similar prices across all the presentations are available, such as perfectly suited to respond to the hexavalent (DTaP-HepB-Hib- countries we analysed (with the needs of developing countries. IPV) vaccine or the DTaP-Hib-IPV exception of the US, where the Acellular pertussis is much more vaccine (e.g. South Africa). The price vaccine retails at more than twice expensive to manufacture than of these presentations is usually the price available in any other whole cell, while manufacturers much higher than prices for DTwP- country), which may show that will have to overcome several HepB-Hib pentavalent vaccines, manufacturers are not targeting technical difficulties before a and there are no WHO prequalified developing countries and have not whole-cell pertussis hexavalent products yet.113 For example, in the developed strategies to expand vaccine is available on the global Indian private sector, a pentavalent affordability and access. market [see page 68].164,255 Graph 16: Prices for DTaP-Hib-IPV and Hexavalent Notes: (DTaP-HepB-Hib-IPV) vaccines in several countries, • All prices are for 2014, except for by price type and manufacturers, 2013/2014* the DTaP-Hib-IPV in India that is from 2008. 90 80 80.43 DTaP-Hib-IPV vaccines Hexavalent vaccines 70 64.82 60 52.43 53.17 54.69 50 41.23 40 35.10 35.46 35.54 36.13 36.61 34.94 30 27.96 28.18 27.27 US$ PER DOSE 20 11.50 12.94 10 0 USA USA India PAHO France France Tunisia Tunisia Belgium Lebanon Lebanon Morocco Morocco Morocco Morocco South Africa South Africa Gvt Hosp. Retail Hosp. Retail Sanofi Pasteur GSK Other/na Sources: PAHO Revolving Fund, UNICEF Supply Division, country price analysis. * Annex A, Section C 70 Médecins Sans Frontières | The Right Shot 2nd Edition January 2015 Pentavalent Vaccines (DTP- H epB- ib) HEPATITIS B Now the HepB market has matured, than 15 times higher than the middle-income country government Early recombinant vaccines against and the entry of several emerging price included in our analysis manufacturers has enabled a drop HepB by GSK and Merck were first (US$0.37 per dose, South Africa) in price that allows international sold in high-income markets for for a WHO prequalified vaccine. US$40 a dose. Progress toward organisations and governments to access the vaccine at a rather low Outside of government purchases, lower-cost vaccines was hindered by price (US$0.16–0.37 per dose for affordable prices are only available originator company patents. In the WHO prequalified vaccines in our from emerging manufacturers. The case of recombinant HepB vaccines, analysis – see Graph 17). HepB vaccine in hospitals in Tunisia, originators held dozens of process for instance, is a LG Life Sciences patents on development technology, In the retail market, the vaccine is Ltd product, and is available delaying the efforts of lower-cost much more expensive. The lowest at a price almost comparable producers to create similar, lower- retail price included in our analysis to government prices in other cost vaccines.256 ($6.20 per dose, Lebanon) is more countries (US$0.63 per dose). Graph 17: Prices for pediatric Hepatitis B vaccines Notes: in several countries, by income group and price • Manufacturer names given in type, 2013/2014* parentheses (Crucell, GSK, Merck, LG=LG Life Science; Sanofi=Sanofi 25 23.20 21.37 Pasteur); where none is specified, 20 the manufacturer is unknown/ 16.71 undisclosed. 15 13.17 13.84 11.00 11.08 • Paediatric presentation of the HepB 10 9.42 vaccine only. US$ PER DOSE 6.20 • Only the lowest price available to 5 1.26 PAHO and UNICEF is presented in 0.16 0.16 0.25 0.31 0.37 0.63 0 the graph. MSF • The Philippines procures through PAHO Thailand** USA (GSK) USA (GSK) UNICEF. Philippines Tunisia (LG) South Africa USA (Merck) USA (Merck) France (GSK) France (Sanofi) Hungary (GSK) Lebanon (GSK) Morocco (GSK) UNICEF (Crucell) Gvt Hosp. Retail • Prices for UNICEF, MSF and the Philippines are for multidose vials; two-dose vial for Thailand; single- International organisation LMIC UMIC HIC **Thailand purchases its Hep B vaccine from GPO Merieux (not WHO prequalified). dose vials for the other countries. • MSF price is with Incoterm CPT (see Annex C). Sources: PAHO Revolving Fund, UNICEF Supply Division, MSF Supply, country price analysis • For the USA, this is the price * Annex A, Section C as reported by manufacturers. Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 71 © Aurelie Baumel/MSF Pneumococcal Conjugate Vaccines (PCV) Pneumococcal Conjugate Vaccines (PCV) WHO recommendations & general information Every year, 2.58 million episodes (PCV) for inclusion in national In 2012, 88 countries had immunisation programmes.260 of severe pneumonia caused by introduced PCV into their routine Streptococcus pneumoniae occur PCV is considered safe for immunisation schedules, including globally in children aged under administration in all target groups, 23 countries with Gavi support. five years, accounting for 18% of including immunocompromised As of October 2013 that number all episodes of severe pneumonia individuals. Vaccine efficacy against increased to 32 Gavi-eligible and 33% of all pneumonia-related invasive pneumococcal disease deaths.257 Most of this burden is countries, with a further 19 caused by serotypes contained in disproportionately borne by low- approved for introduction with PCV vaccine was found to be 71% and middle-income countries.257,258 Gavi support beyond 2013.262,263 when following the schedule in Children with HIV are eight times Option 2 (see table below).124,260 If the primary series is interrupted, more likely to develop invasive WHO’s recommendation was resume without repeating the pneumococcal disease than are 261 updated in 2012 to include previous dose. their HIV-negative peers.259 and focus on the available In 2007, WHO recommended 10-valent and 13-valent pneumococcal conjugate vaccine conjugate vaccines.260 Recommended Doses in primary series Age at 1st dose Booster schedules124 (interval between doses) No booster with 3 - dose schedule except for HIV+ and preterm 3 doses with DTP (4 weeks between Option 1 6 weeks (minimum) neonates in their 2nd year if doses 1, 2 and 3) 3 primary doses were completed within the 1st year Option 2 6 weeks (minimum) 2 doses before 6 months (8 weeks) Booster dose at 9 – 15 months If <1 year: 2- or 3 - dose schedule Booster at 9 –15 months if 8-week interval between doses for both following 2 - dose schedule. Delayed start If aged 1– 2 years or 2 – 5 years + high groups Second booster if HIV+ or preterm risk: 2 doses neonate Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 73 Products & manufacturers Lowest WHO PQ Form and Vaccine vial monitor (VVM) type Product Manufacturer known price date presentation and cold chain volume (per dose) (UNICEF, US$) Prevnar 7 VVM 30 Wyeth-Pfizer Dec 2009 Liquid, single-dose vial* N/A PCV7* vaccine Box, 5 vials = 21 cm3 VVM 30 Prevnar 13 Liquid, single-dose Wyeth-Pfizer Aug 2010 3.30264 Box, 50 vials = 12 cm3 PCV13 vaccine vial** Box, 25 vials = 15.7 cm3 VVM 30 Single-dose 3 Pneumococcal Conjugate Vaccines (PCV) (PCV) Pneumococcal Conjugate Vaccines Carton, single 1- dose vial = 58 cm vial: Liquid, available Synflorix GSK Oct 2009 in 1- or 2-dose 3.40–3.50264 PCV10 vaccine † 2- dose vial: preservative-free vial Carton, single 2- dose vial = 4.8 cm3 Mar 2010 Pipeline products Challenges No new PCV vaccines are expected data from Phase II. The second is a Supply of the WHO prequalified to achieve WHO prequalification PCV10 vaccine focused on serotypes products has been constrained in or meet the Gavi Advance Market prevalent in developing countries, developing countries, particularly Commitment Target Product Profile under development by Serum as scale-up of introductions in 213,266,267 263,270 (TPP) before 2018.263 Institute of India. Gavi-eligible countries continues. PATH has two products in the Merck has a pneumoconjugate For the two-dose presentation pipeline. One is a protein plus vaccine candidate provisionally of GSK’s preservative-free PCV10 134,268 vaccine, specific pre-introduction conjugate vaccine developed in named V114 in Phase II. measures are required, including partnership with GSK, the Medical Sanofi Pasteur is reportedly training. Post-introduction Research Council Unit in The Gambia collaborating with Korean company evaluations are also required.258,265 and the London School of Hygiene SK Chemicals to develop, produce & Tropical Medicine, about to enter and market a pneumococcal Phase III trials after evaluation of conjugate vaccine soon.269 * Being replaced by PCV13 or PCV10. ** Also available in prefilled syringe but not WHO prequalified. † Two-dose presentation requires specific training and management.265 74 Médecins Sans Frontières | The Right Shot 2nd Edition January 2015 Pneumococcal Conjugate Vaccines (PCV) Prices and affordability The PCV vaccine market is a duopoly of manufacturers Pfizer and GSK. Together with the HPV and rotavirus vaccines, PCV vaccines are some of the newest and most expensive vaccines, and present affordability challenges that prevent access. Price evolution: UNICEF and PAHO (See Annex A for more information on prices used in this section) PCV vaccine is significantly more Prices of PCV for PAHO have expensive than the traditional declined, but remain high, at vaccines. According to volumes and US$14.12 and US$15.68 for PCV10 prices published on the UNICEF and PCV13, respectively [Graph 18, Supply Division (SD) website,86 overleaf], at more than four times purchases of PCV accounted in the Gavi tail price [see box below] value for 39.2% of all UNICEF SD offered to UNICEF. vaccine purchases but only for 3% in terms of volume. The pneumococcal Advance Market Commitment (AMC) for Gavi The pneumococcal Advance Market All Gavi-graduated and representing 73% of the 200 Commitment (AMC) is a mechanism graduating countries that have million doses per year targeted to incentivise companies to scale- not yet introduced a PCV vaccine by the AMC.263 up manufacturing capacity to meet are eligible to apply to introduce the needs of Gavi-eligible countries. the vaccine under the AMC, In 2013, Pfizer reduced its tail The AMC sets a maximum price of which means that these countries price to US$3.40 per dose, with a US$3.50 (‘tail price’) per dose for can purchase the vaccine at the subsequent decrease to US$3.30 Gavi and Gavi-eligible countries tail price, but have to finance per dose starting in 2014. Special through the UNICEF supply channel it themselves. Some other conditions of the Pfizer price only. Manufacturers commit to not conditions apply.271 decrease include that the AMC exceed this price for ten years, and donor funding for Pfizer contracts in exchange they receive a part As of July 2013, 73% of the Gavi will be fully disbursed by 2015 at of the committed AMC subsidy AMC subsidy had been awarded the latest, and that Gavi provides (US$1.5 billion) in proportion to their to Pfizer and GSK (corresponding a financial guarantee for the tail contribution to the target demand to US$1,095 million). price component of a total of (target demand at 200 million doses 80% of the doses contracted in per year). Critiques of the AMC have As of 2016, the annual supply 2013–2015.272 GSK also reduced been discussed earlier in this report. of PCV to Gavi/UNICEF is its tail price to US$3.40 per dose projected to be 146 million doses, for the 2014–2024 contract. Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 75 Graph 18: Price evolution of Pneumococcal Notes and methodology: Conjugate Vaccines (PCV) for PAHO and Gavi/UNICEF • All presentations are single-dose 25 except PCV10 for UNICEF, which is a two-dose vial. 21.75 20 • See UNICEF SD web page11 on PCV 20 for full information on tenders and 16.34 15.84 agreements for these prices. 14.85 15.68 15 • For UNICEF, where agreements 14.24 14.12 14.12 include a range of prices during 10 a calendar year period or for US$ PER DOSE different countries or groups 7.00 7.00 of countries, the lowest price 5 in the range was kept. 3.50 3.40 3.40 3.40 3.50 3.40 3.30 3.30 0 Pneumococcal Conjugate Vaccines (PCV) (PCV) Pneumococcal Conjugate Vaccines 2009 2010 2011 2012 2013 2014 2015* Gavi/UNICEF, PCV (with AMC subsidy) PAHO, GSK (PCV10) Gavi/UNICEF, Pfizer (PCV13) PAHO, Pfizer (PCV13) Gavi/UNICEF, GSK (PCV10, 2-dose vial) *Forecasted data Sources: PAHO Revolving Fund, UNICEF Supply Division. Prices in countries The high price of PCV has hindered is ready to manufacture PCV on many middle-income countries to access in middle-income countries. its own.274 The price per dose* opt for the introduction of Synflorix While many Gavi-eligible countries was EUR11.50 / US$16.03 in the over that of Prevnar 13. have already introduced the vaccine, first years, then decreasing to Companies claim that they use many middle-income countries EUR5.00 / US$6.97.170,275 However, differential pricing strategies like have not [see Graph 3, page 14]. the terms of the technology transfer tiered pricing to maximise access, Cost effectiveness and especially arrangements are not publicly in effect maximising their revenues the price of the vaccine have been available and could limit the in middle-and low-income cited by several countries as major opportunity for Brazil to benefit from countries. In practice, prices in barriers to introduction.41 A study by real competition when emerging middle-income countries are Nakamura et al. in 2011 estimated manufacturers enter the market extremely high and sometimes that the vaccine could be cost with cheaper products. The comparable to prices in high- effective in most low- to middle- strategy could therefore not be income countries. Graphs 19 and income countries at US$10 per dose advantageous for Brazil in the 20, opposite, show that despite or lower.273 But in 2014 Brazil was long term, for instance when claims of differential pricing, the the only country outside of Gavi- Serum Institute of India enters the price of Pfizer’s PCV13 remains eligible countries to have access to market with a PCV candidate in high in many countries, and Graph the vaccine at this price. 2016/2017 at the expected lower 5 on page 26 of this report shows price of US$2 per dose.84 Brazil is an example of a country that the price countries pay for using technology transfer As Pfizer’s PCV vaccine, Prevnar 13 PCV13 is not entirely dependent agreements to produce PCV (PCV13), has an advantage over on their wealth – despite relative domestically. The country entered GSK’s Synflorix (PCV10) because of wealth often being used by a partnership with GSK in 2009 its additional serotypes (PCV10 vs companies as a proxy to set prices to vaccinate 13 million children PCV13), GSK remains competitive by for different markets. (39 million doses) per year for at setting the price below that of Pfizer. least eight years, until the country The price difference is grounds for * Using OANDA average 2009 exchange rate euros to US dollars at 1.3937. 76 Médecins Sans Frontières | The Right Shot 2nd Edition January 2015 Pneumococcal Conjugate Vaccines (PCV) Graph 19: Prices for GSK's Pneumococcal Conjugate Vaccine (PCV10) in several countries, by income group and price type, 2013/2014* 160 140 120 100 93.54 80 62.85 63.37 60 51.27 50.36 53.35 54.34 US$ PER DOSE 41.57 45.05 40 34.38 20 14.09 14.12 16.17 3.40 6.97 0 India PAHO Tunisia Brazil** Belgium Lebanon Morocco Morocco Czech Rep. Czech Rep. South Africa South Africa South Africa (2-dose vial) Gavi/UNICEF Philippines*** Gvt Hosp. Manuf. Retail International organisation LMIC UMIC HIC **Via tech transfer agreement ***Via UNICEF SD Sources: PAHO Revolving Fund, UNICEF Supply Division, country price analysis. *Annex A, Section C Graph 20: Prices for Pfizer's Pneumococcal Conjugate Vaccine (PCV13) in several countries, by income group and price type, 2013/2014* 160 140 135.80 120 112.44 98.99 100 94.54 96.36 81.35 80 72.08 75.32 63.74 67.26 65.38 58.43 61.49 60 49.42 US$ PER DOSE 40 20 15.68 3.30 0 USA USA India PAHO France France Tunisia Hungry Hungry Belgium Lebanon Morocco Morocco Czech Rep. Czech Rep. Gavi/UNICEF Gvt Hosp. Manuf. Retail International organisation LMIC UMIC HIC Sources: PAHO Revolving Fund, UNICEF Supply Division, country price analysis. * Annex A, Section C Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 77 Andrea Bruce/Noor Images Oral Cholera Vaccines (OCV) O ral Cholera Vaccines ( O CV) WHO recommendations & general information Cholera is an acute diarrhoeal vaccination, but this efficacy drops preschool and school-age children, disease, caused primarily by to 47% at the end of two years. HIV-infected individuals, pregnant the O1 and O139 toxigenic For children aged over five years, mothers and the elderly are to 44,276 serogroups of the Vibrio cholerae Dukoral has a protective efficacy at be prioritised. Pre-emptive or bacterium. The spread of cholera one and two years post-vaccination reactive vaccination, or both, can is exacerbated by poor sanitation of 78% and 63%, respectively. be considered depending on local and a lack of clean drinking After two doses, Shanchol vaccine infrastructure and an evaluation of the water; the disease most seriously (Shantha Biotechnics) offers a current and historical epidemiological affects young children living in protective efficacy of 66% across all situation for epidemic settings, but disease-endemic settings.276 WHO ages, and 50% overall, three to five not to the exclusion of appropriate conservatively estimates there to years after vaccination.276 oral rehydration therapy and be 2.8 million (uncertainty range: measures to improve water quality WHO emphasises that cholera 1.2–4.3 million) cases of cholera and sanitation.276,278 control should be a priority in globally per year resulting in disease-endemic regions and specific There has been increasing 91,000 deaths (uncertainty range: geographic areas susceptible to evidence of the effectiveness of 28,000–142,000). Morbidity and outbreaks. WHO recommends providing oral cholera vaccines mortality estimates are probably immunisation with existing vaccines, in epidemic settings [see box, under-reported because of a lack of in conjunction with other preventive page 81],279,280 and the creation consistent global surveillance.277 and control strategies, through of a global oral cholera vaccine Dukoral vaccine (Crucell) provides periodic mass vaccination campaigns stockpile in 2012 [see box, page effective protection (100%) against or the incorporation of cholera 81] 281 will in the future allow for cholera for children aged two to vaccination into routine immunisation a robust and early response to five years for up to six months after efforts. High-risk populations, potential epidemic outbreaks. Doses in primary series Vaccine Age at 1st dose Booster (interval between doses) At 2 – 5 years of age: 3 doses (minimum 7 days and maximum 6 weeks between 1st and 2nd dose nd rd At 2 – 5 years of age: every 6 months Dukoral 2 years* and 2 and 3 doses**) At ≥ 6 years of age: every 2 years At ≥ 6 years: 2 doses (14 days between 1st and 2nd doses) Shanchol 1 year 2 doses (14 days between 1st and 2nd doses) After 2 years (and mORC-Vax) * Dukoral is not licensed for children aged under two years. ** Restart primary series if interval between first and second dose or second and third dose is more than six weeks or if interval between primary series and booster is more than six months. Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 79 Products & manufacturers Lowest WHO PQ Form and Vaccine vial monitor (VVM) type Product Manufacturer known price date presentation and cold chain volume (per dose) (UNICEF, US$) Dukoral No VVM Inactivated, 1- dose carton = 271 cm3 monovalent-O1, Liquid, 1-dose vial + 278,8,282 3 CV) ( O CV) O ral Cholera Vaccines whole-cell oral Crucell Oct 2001 4.75 2 - dose carton = 136 cm buffer sachet cholera vaccine 3 with toxin B 20 - dose carton = 44 cm cholera subunit 170 - dose carton = 24.4 cm3 Shanchol VVM 14 Inactivated Shantha bivalent-O1/ Sep 2011 Liquid, 1-dose vial 1.85283 Biotechnics O139 oral cholera Carton, 35 vials = 16.8 cm3 vaccine Pipeline products Paxvax has a single-dose, oral, whole-cell cholera vaccine, undergoing licensing in Korea; live, attenuated cholera vaccine designed to be administered in the vaccine is expected to be WHO (PVXV0200) in Phase III of clinical a two-dose regimen. This product prequalified in 2015.286 trials that is expected to be has been redeveloped into a bivalent Cuba’s Finlay Instituto is developing approved shortly by the US FDA. (O1/O139), whole-cell vaccine a live and an inactivated oral cholera The vaccine is anticipated to be (mORCVAX) and has been licensed vaccine said to be in the “advanced used in epidemic outbreak settings for use in Vietnam since 2009. WHO stage” (probably Phase III) of and for individuals travelling to prequalification is expected to take clinical trials.287,288 cholera-endemic regions.284 place by 2015.285 Vietnam-based VABiotech produces Korean manufacturer Eubiologics a reformulated, buffer-free, killed has an oral cholera vaccine Challenges Manufacturing capacity is limited, Questions remain regarding Biotechnic’s parent company) and but manufacturers have announced prioritisation and usage of the independent scientists.293 Relabelling that they could scale up production cholera vaccine stockpile when Shancol for use under controlled if there is a committed demand. faced with multiple simultaneous temperature chain (CTC) settings Shanchol’s manufacturer, for epidemics or emergency situations has progressed with Indian drug example, has indicated the combined with seasonal peaks in regulatory authorities and could immediate availability of up to incidence in endemic countries.290,291 be a precursor for future WHO 600,000 doses and the capacity prequalification for use in CTC. There are as yet no guidelines for to scale up production to two to the use of cholera vaccine among four million doses in 2013 and children aged under one year.291 to ten to twenty million doses in 2014 if merited by the demand,289 Shanchol is stable for at least 5 days but managing irregular demand is at up to 40°C, according to research thought to pose a challenge.290 by both Sanofi Pasteur292 (Shantha 80 Médecins Sans Frontières | The Right Shot 2nd Edition January 2015 O ral Cholera Vaccines ( O CV) The growing evidence that Oral Cholera Vaccine should be used to control cholera outbreaks In Haiti, after the onset of the Haiti’s routine immunisation schedule as an additional tool to control the cholera epidemic in October 2010, while conducting Supplemental epidemic in the country. Researchers a decision was made not to use Immunisation Activities (SIA) in camps found that the two doses of OCV oral cholera vaccine (OCV), in part and rural areas.289 In 2012, Partners provided 86% protective effectiveness because not enough doses of the in Health sponsored one pilot project against cholera.279,280 vaccine were available. In early 2011, and provided 45,000 doses of OCV in it was decided to consider cholera the Artibonite region of the country A study of the outbreak response vaccination if sufficient volumes could and reached very high coverage, campaign shows that cholera be made. At the same time, both showing that the vaccine could be immunisation was well accepted and manufacturers announced that they used in the midst of an epidemic.295 reached high coverage, validating the could scale up production capacity, benefits of cholera immunisation as provided that firm orders and In 2012, the Ministry of Health in “an additional tool in the outbreak commitments were made.294 In 2012, Guinea and MSF organised Guinea’s response strategies”.279 the PAHO Technical Advisory Group first mass vaccination campaign, recommended introduction of OCV in with two doses of OCV (Shanchol) The Oral Cholera Vaccine Stockpile The use of oral cholera vaccine MSF, UNICEF and WHO),296 and 20 million doses per year for the (OCV) in low-income countries was has received financial commitments period 2014–2018, for use in first mentioned in a World Heath from the Bill & Melinda Gates epidemic and endemic settings. Assembly resolution in 2011.281 Foundation, the European Union and The total contribution from Gavi 281 Following several rounds of technical other donors. The OCV stockpile is estimated at US$115 million 290,297 consultations, a global OCV stockpile was planned to initially comprise over the five-year period. two million doses per year, stored was created in 2013, with the aim The stockpile was used for the first and maintained by participating time in February 2014 in South Sudan, that it would serve as an additional manufacturers.281 Between July 2013 where MSF and MedAir delivered tool to control cholera epidemics and and June 2014, the stockpile made its 132,925 doses of the vaccine for use outbreaks, especially in low-income first two million doses available.296 in internally displaced populations.298 countries. The stockpile is managed by the International Coordinating In November 2013, the Gavi Board Group (ICG), composed of four decided to support the stockpile by decision-making partners (IFRC, gradually increasing its capacity to Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 81 Prices and affordability Price evolution: UNICEF and PAHO (See Annex A for more information on prices used in this section) Several cost-effectiveness studies As shown in the table on compared to Dukoral; in particular, have been conducted on the use page 80, Shanchol’s form and it does not need to be reconstituted of OCV in endemic situations and presentation offer operational with a glass of water and presents CV) ( O CV) O ral Cholera Vaccines in refugee settings, but there is a and programmatic advantages a lower cold chain volume. lack of information relative to the synergistic impact of immunisation when coupled with traditional cholera interventions (e.g. sanitation and education).276 The most recent cost-effectiveness study showed that immunisation was cost effective at US$1 per dose of the vaccine (with an additional cost of delivering the vaccine of US$0.50 in low-income countries and US$1 in middle- income countries), under specific conditions and taking into account the benefits of vaccination herd immunity.299 This study shows that cost effectiveness is reachable, but with a low-priced vaccine. Dukoral was the only WHO prequalified OCV available prior to 2011 and it was quite expensive not only because of the manufacturer’s monopoly, but also because of low and unpredictable demand. A background paper prepared by UNICEF for the 2009 WHO SAGE showed that the cost of immunisation mainly comprised the high cost of the vaccine. For instance, in a refugee setting in Sudan in 2004 the cost of protection against cholera was US$7.10 per fully immunised person, 90% of which was the vaccine price (US$6.40 for two doses).300 The momentum for increased use of OCV has followed the entrance in 2011 of a new product – Shanchol by Shanta Biotech – offered at a much lower price than the pre-existing Dukoral vaccine. Shanchol costs about US$1.85 per dose, which is about one-third the price per dose of Dukoral (US$4.75).278–283 If demand Emily Gerardo for Shanchol increases, the price © could potentially decrease further. 82 Médecins Sans Frontières | The Right Shot 2nd Edition January 2015 Ton Koene © Ton Rotavirus Vaccines (RV) WHO recommendations & general information 302,309 Diarrhoea accounts for 11% of of strains in Africa and Asia. vaccinated; however, There is mounting evidence for recent studies indicate that the all deaths in children aged under significant cross-protection among relative risk of intussusception five years.301 It is transmitted Rotavirus Vaccines (RV) Rotavirus Vaccines predominant strains of rotavirus for the GSK monovalent vaccine directly via the faecal-oral route for both the monovalent and exceeds 8.1 while the Merck or indirectly through infected pentavalent vaccines.303,304 pentavalent vaccine has a fomites.302 Rotavirus is one of non-significant relative risk of the most common aetiological Rotavirus vaccination can reduce 1.1.310 In a modelling exercise organisms and is responsible severe rotavirus infections by on non-restricted vaccination for 40% of diarrhoea-related 74%305, although lower vaccine age (up to three years), an hospitalisations, according to efficacy against severe rotavirus additional 47,200 lives in low- sentinel site observations.302 Nearly diarrhoea has been seen in some and middle-income countries low-income countries in Africa every child will be infected by could be saved compared to the (Malawi 49.4%).306 rotavirus before the age of three to restricted schedule. However, an five years. The WHO estimates that The WHO recommends rotavirus additional 294 children would 453,000 rotavirus gastroenteritis vaccination in all national die of intussusception caused by (RVGE)-associated deaths occur immunisation programmes.302 older age at administration.311 annually in children aged under As of July 2014, rotavirus vaccination Continuous monitoring and 302 five years. had been implemented in public evaluation of the risk of health programmes in 67 countries, intussusception is required, As a result of genetic reassortment including 39 Gavi-supported including in countries newly within the genome, rotavirus has countries.307,308 introducing the vaccine. at least 12 different G-type viral particle antigens and 15 P-type The WHO estimates the incidence viral particle antigens.302 The most of rotavirus vaccine-induced common strain is G1P[8], but there intussusception to be one to is more diversity in the distribution two cases per 100,000 infants Doses in primary series Vaccine124 Age at 1st dose Booster (interval between doses) 2 doses, administered concurrently with DTP1 Rotavirus 1 6 weeks Not recommended and DTP2 (4 weeks between doses) 3 doses, administered concurrently with DTP1, Rotavirus 5 6 weeks Not recommended DTP2 and DTP3 (4 weeks between doses) RV1 or RV5: Not applicable if 2 doses for RV1 or 3 doses for RV5 Not recommended delayed start aged >24 months (4 weeks between doses) 84 Médecins Sans Frontières | The Right Shot 2nd Edition January 2015 Rotavirus Vaccines (RV) Products & manufacturers Lowest WHO PQ Form and Vaccine vial monitor (VVM) type Product Manufacturer known price date presentation and cold chain volume (per dose) (UNICEF, US$) VVM 14 Box, 1 dose (applicator) = 143 cm3 Box, 10 doses (applicator) = 85.3 cm3 Rotarix Monovalent: liquid, Box, 1 dose (plastic tube) = 115.3 cm3 Monovalent GSK Mar 2009 single-dose vial, 2.50 rotavirus vaccine tube or applicator Box, 10 doses (plastic tube) = 43.3 cm3 Box, 50 doses (plastic tube) = 17.1 cm3 Box, 1 dose (vial) = 256 cm3 Box, 10 doses (vial) = 156 cm3 No VVM technology has been validated for use with RotaTeq RotaTeq Pentavalent: liquid, Pentavalent Merck Oct 2008 3.50 Box, 10 doses = 75.3 cm3 single-dose tube rotavirus vaccine Box, 25 doses = 46.3 cm3 Pipeline products Lanzhuo Institute Biological Bharat Biotech received commercial (conducted by the Murdoch Products (China) has two oral lamb licensing in January 2014316 for Children’s Research Institute) for rotavirus vaccines: (LLR)312 which Rotavac (116E), an oral, single-dose neonatal rotavirus vaccine.317,318 was approved in China 2000313 and multidose presentation with International Medical Foundation and Ovine LD9 + human G2, G3, G4 a 3-dose regimen.316 Cold chain has redeveloped Rotashield to in Phase III.314 storage includes 36 months at –20oC be administered as a two-dose to – 25oC and six months at 2– 8oC.316 The Center for Research & regimen, with one dose soon Production of Vaccines & Biologicals Phase I studies supported after birth and the second by (Polyvac, Vietnam) obtained progression to the currently two months of age. Phase IIb trials licensing for oral, single-dose underway Phase II safety and were completed in Ghana.319–321 rotavirus vaccine (three-dose immunogenicity studies of the RV3- regimen) in April 2012.315 BB rotavirus vaccine programme Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 85 Prices and affordability The rotavirus vaccine market is a duopoly between Merck and GSK. Together with the PCV and HPV vaccines, rotavirus vaccines are some of the newest and most expensive vaccines, presenting affordability challenges that prevent access. Rotarix by GSK has the advantage of following a two-dose schedule while three doses are necessary Rotavirus Vaccines (RV) Rotavirus Vaccines to complete the schedule for RotaTeq by Merck. Therefore, even when the price per dose of Rotarix is higher than of RotaTeq, the price per immunisation course for Rotarix may still be lower. Price evolution: UNICEF and PAHO (See Annex A for more information on prices used in this section) The Gavi/UNICEF agreement with For PAHO, prices for rotavirus manufacturers for rotavirus vaccines vaccines have remained high, is recent (2012) and prices have not decreasing only by 6% and 13% changed much since. for the Merck and GSK products, respectively, between 2008 and 2014. Graph 21: Price evolution of rotavirus vaccines (RV) for PAHO and Gavi/UNICEF 9.00 7.90 8.00 7.50 7.50 7.50 6.88 7.00 6.50 6.50 6.00 5.50 5.15 5.25 5.25 5.15 5.00 US$ PER DOSE 5.00 4.00 3.50 3.50 3.00 2.50 2.50 2.00 2008 2009 2010 2011 2012 2013 2014 2015* 2016* Gavi/UNICEF, GSK (2-dose schedule) Gavi/UNICEF, Merck (3-dose schedule) PAHO, GSK (2-dose schedule) PAHO, Merck (3-dose schedule) *Forecasted data Sources: PAHO Revolving Fund, UNICEF Supply Division. Notes and methodology: • For UNICEF, the price offered by GSK is only available to the 73 countries eligible for Gavi support in 2009, provided the procurement is done through UNICEF. The price for Merck‘s vaccine “consists of 1) a number of doses to be procured at US$5 for a single country in 2013–2015, with doses free of charge to be made available in 2015 – 2016 based on achieving the required number of doses to be procured, and 2) contracted quantities for other countries at US$3.50”.11 • When prices were expressed in euros (rotavirus vaccine from GSK), prices were converted into US dollars using the 2013 average annual exchange rate as provided by OANDA (euros to US dollars: 1.3279).170 86 Médecins Sans Frontières | The Right Shot 2nd Edition January 2015 Rotavirus Vaccines (RV) Prices in countries Prices for rotavirus vaccines remain Competition from emerging-country in a three-dose schedule,85 making high, limiting their introduction suppliers is expected to increase the full schedule 40% cheaper than in middle-income countries. For between 2015 and 2020 and should the lowest price currently available instance in Lebanon, the retail make rotavirus vaccine available to UNICEF per schedule (US$3 vs price* of Rotarix (GSK) is 30 times at a lower price. Bharat Biotech US$5). In countries like India, the the price for UNICEF and more announced it will sell its Rotavac price per schedule could even be than 2.7 times the retail price for vaccine for US$1 per dose for use reduced 12- to 17-fold. South Africa [Graph 22]. The retail price of RotaTeq (Merck) in Lebanon is also on par with the price of the Graph 22: Prices for GSK's rotavirus vaccine vaccine in Belgium [Graph 23], in several countries, by income group and despite the five-fold difference price type, 2013/2014* 120 in GNI/capita between these two 106.57 countries. Variation of GNI/capita 100 92.15 94.67 is normally the basis on which 80 75.66 76.34 companies say they set tiered prices. 60 * Because the vaccine was not in the 40 36.36 US$ PER DOSE 31.81 23.52 27.53 national schedule in Lebanon as of 21.04 19.93 20 31 6.06 2014, the retail price corresponds 2.50 6.50 to the price at which individuals can 0 US US India PAHO purchase the vaccine in the country. Tunisia Belgium Belgium Lebanon Morocco Morocco South Africa South Africa South Africa Rotavirus vaccination is considered Gavi/UNICEF Gvt Hosp. Manuf. Retail by several studies to be a very cost- effective intervention in developing International organisation LMIC UMIC HIC countries, but most of the studies use vaccine prices much lower than Sources: PAHO Revolving Fund, UNICEF Supply Division, country price analysis. the actual cost per dose paid by * Annex A, Section C middle-income countries.322,323 Even if price is not the only element for a country to consider when Graph 23: Prices for Merck's rotavirus vaccine in deciding to introduce the vaccine, several countries, by income group and price type, ‘vaccine price has a significant 2013/2014* influence on the cost-effectiveness 120 of vaccination’,324 and only a 100 decrease in current prices could 80 75.20 lower barriers to the introduction 68.69 63.96 61.87 55.90 of rotavirus vaccination in several 60 52.74 middle-income countries. US$ PER DOSE 40 29.45 19.48 Even in high-income countries, 20 15.46 16.75 3.50 5.15 the high price of rotavirus vaccine 0 has been cited as a barrier to its US US PAHO Belgium Belgium Belgium Lebanon introduction (together with safety Morocco Morocco South Africa South Africa concerns). As a result, most Western Gavi/UNICEF** Gvt Hosp. Manuf. Retail European countries, including the UK, France and Germany,325–326 International organisation LMIC UMIC HIC have delayed introduction of the **The price for Rotavirus vaccine, pentavalent, consists of a.) a number of doses to be procured at US$5 for a single country in 2013–2015, vaccine. For instance, the UK with doses free of charge to be made available in 2015–2016 based on achieving the required number of doses to be procured, and announced the introduction of b.) contracted quantities for other countries at US$3.50. the vaccine in its immunisation program in late 2012,326 and Sources: PAHO Revolving Fund, UNICEF Supply Division, country price analysis. France only in early 2014.327,328 * Annex A, Section C Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 87 © Emily Gerardo/MSF Tetanus Toxoid Vaccines (TT) Tetanus Toxoid Vaccines (TT) WHO recommendations & general information Tetanus is a bacterial disease and Neonatal Tetanus Elimination this is under the assumption that they have completed the caused by the Clostridium tetani Initiative, page 91]. childhood vaccination series. bacterium. Infection can result In countries where the elimination Pregnant women with unknown in case-fatality rates as high as target has not been reached, the immunisation history are to 100%. Disease in humans results WHO recommends using the receive two doses, the first as from production of the potent ‘high-risk approach’, whereby all early as possible, and the second a neurotoxin tetanospasmin, which women of childbearing age are minimum of four weeks later.329,332 manifests in symptoms such as targeted through use of concerted muscle stiffness and spasms.329 campaigns and supplementary It is recommended that districts Most tetanus cases occur in immunisation activities.329 with limited access to routine developing countries among vaccination services and areas Vaccines against tetanus are newborns or in mothers after where the elimination target (fewer available as: single tetanus toxoid unhygienic births or poor postnatal than one case per 1,000 live births) (TT); combined with diphtheria has not been achieved adopt the hygiene. The WHO estimates that and pertussis vaccines (DTwP, ’high-risk approach’. Implementing in 2010, 58,000 newborns died as DTaP); alone with diphtheria (DT, this approach covers all women of a result of neonatal tetanus, and in dT; ‘D’ and ‘d’ vaccines contain, child-bearing age with three doses 2011, 72,600 children under the age respectively, a higher and lower of TT over a 12-month period, with of five died from tetanus.225,329–331 dose of diphtheria toxin); as a an attempt to complete five doses component of the pentavalent Since 1999, the WHO has declared overall if possible.329,332 vaccine (DTwP-HepB-Hib).329 the goal of eliminating maternal and neonatal tetanus globally In countries with a high prevalence and achieving and sustaining of maternal and neonatal tetanus high coverage of three doses of (MNT), all pregnant women are to be DTP to prevent tetanus in all age immunised with at least one dose of groups [see box, The Maternal a TT-containing vaccine (usually dT); Doses in primary series Vaccine Age at 1st dose Booster (interval between doses) 1st DTP booster at 1– 6 years of age If aged 4 – 7 years, 1st booster administered as DT <1 year (doses to DTP, 3 doses (4 weeks minimum between 1st and 2nd be given at 6, 10, 2nd at 12 – 15 years (TT) primary course dose and between 2nd and 3rd dose) 14 weeks) 3rd booster (6th dose of tetanus vaccine overall) for women at time of first pregnancy (TT) Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 89 Products & manufacturers Lowest WHO PQ Form and Vaccine vial monitor (VVM) type Product 113 Manufacturer known price date presentation and cold chain volume (per dose) (UNICEF, US$) 333 VVM 14 Teatox TT Liquid, Tetanus toxoid BB-NCIPD May 2006 N/A 10-vial carton, 10 - dose vials = 4.12 cm3 10- and 20- dose vials* vaccine 10 vial carton, 20 - dose vials = 2.05 cm3 Tetanus Toxoid Vaccines (TT) (TT) Vaccines Toxoid Tetanus VVM 30 TT vaccine Liquid, 10-dose: 0.095 Bio Farma Mar 1999 10 - vial box, 10 - dose vials = 2.10 cm3 Tetanus toxoid 10- and 20- dose vials* (2013) 10 - vial box, 20 - dose vials = 0.75 cm3 Tetanus toxoid VVM 30 vaccine Bio Farma Oct 2003 Liquid, 1- dose Uniject N/A (1 dose Uniject) Secondary packaging of 100 = 12 cm3 Dec 2009 VVM 30 (20-dose vial) Tetanus Liquid, 10-dose: 0.070 48 - vial box, 1- dose vials = 14.70 cm3 toxoid vaccine Biological E Jul 2012 1-, 10-* and 20-dose: 0.050 30 - vial box, 10 - dose vials = 3.90 cm3 (adsorbed) (1- and 20-*dose vials 10-dose vials) 20 - vial carton, 20-dose vials = 2.90 cm3 Tetavax No VVM Liquid; Tetanus toxoid Sanofi Pasteur Jul 1997 N/A 10- and 20-dose vials* vaccine 10 vials of 10 doses = 2.46 cm3 VVM 30 Liquid, 1-dose ampoule 50-ampoule carton, Tetanus toxoid 10 - dose: 0.077 Serum Institute 1- dose ampoules = 15.71 cm3 vaccine Apr 1995 Liquid, 10- and of India 20 - dose: 0.053 (adsorbed) 20- dose vials* 50-vial carton, 10 - dose vials = 2.61 cm3 25-vial carton, 20 - dose vials = 2.43 cm3 VVM 14 Shan TT Shantha Liquid, 10- and Tetanus toxoid Aug 2007 10 - dose: 0.080 30-vial carton, 10-dose vials = 4.36 cm3 Biotechnics 20-dose vials* vaccine 30-vial carton, 20-dose vials = 2.57 cm3 Pipeline products Challenges The Chinese manufacturer Walvax Lack of adequate health Major funding gaps continue has a TT vaccine in Phase III infrastructure in countries with to exist for continuation of key clinical trials.334 high MNT prevalence continues immunisation activities targeting to be a challenge to improving MNT, including strengthening of routine immunisation and existing immunisation programmes, supplementary immunisation routine immunisation structures activities that address MNT.332,335,336 and supplementary immunisation activities.332,337 * Opened multidose vials can be kept for use in subsequent immunisation sessions for up to a maximum of 28 days, provided certain conditions are met (WHO policy on use of opened multidose vials).172 90 Médecins Sans Frontières | The Right Shot 2nd Edition January 2015 Tetanus Toxoid Vaccines (TT) The Maternal and Neonatal Tetanus Elimination Initiative The first call to eliminate neonatal Strategies to achieve MNTE focus on Finance Facility for Immunization tetanus was made at the World promoting clean delivery practices, (IFFIm) since 2007 and allocated Health Assembly in 1989; ten years routine immunisation of pregnant to 32 countries.337 The association later this was bolstered by the women, TT-SIAs in high risk areas, Kiwanis also partnered with UNICEF call to eliminate maternal tetanus and surveillance.331 It is estimated that in 2010 through The Eliminate (elimination is considered achieved the cost of immunising women with Project and has raised US$51 million when there is fewer than one three doses of TT through TT-SIAs is to date (with a goal of reaching case per 1,000 live births in every around US$1.80335 per woman. As of US$110 million before 2015).335 district of a country). However, December 2013, 34 countries (out of both calls missed their initial target the 59 identified countries that had As more countries approach of eliminating neonatal tetanus by not eliminated MNT in 1999) had elimination, the current 2012–2015 1995 and maternal tetanus by 2005, achieved MNT elimination, leaving strategic plan aims to achieve and and progress towards elimination 25 countries where the disease is yet maintain elimination. The estimated has been slow. The Maternal and to be eliminated.331,330 The MNTE cost to achieve elimination, mainly Neonatal Tetanus Elimination (MNTE) initiative is supported by the public through TT-SIAS, between 2012 and initiative was re-launched in 1999, and private sectors, with stakeholders 2015, is US$227 million. One of the and the current goal is to achieve including governments, civil societies, biggest challenges of the initiative global elimination by 2015.329,332 the Bill & Melinda Gates Foundation, is the availability of funds.332 Funds Cumulatively, 54 countries initiated Gavi, PATH, UNICEF, USAID, WHO, are especially hard to secure, as or expanded TT Supplementary and others. Funding from Gavi has the initiative is competing against Immunisation Activities (TT-SIAs) reached US$61.4 million, through other global health priorities such as between 1999 and 2012.330 funds received from the International measles and polio eradication.336 Ton Koene © Ton Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 91 Prices and affordability Price evolution: UNICEF and PAHO (See Annex A for more information on prices used in this section) As seen in Graph 24 below, the price to UNICEF has increased by 127% A large supplier base and fierce of TT vaccines supplied to UNICEF between 2001 and 2014 (the competition on price can drive is relatively low: between US$0.05– lowest prices being US$0.22/dose originator manufacturers out of 0.093 per dose in 2014. for a vaccine by CSL Limited in a the market. Crucell decided to leave Tetanus Toxoid Vaccines (TT) (TT) Vaccines Toxoid Tetanus However, despite the large 20-dose vial in 2001 and US$0.50/ the TT market after it could not manufacturer base and a generally dose for a vaccine by Biological E compete with lower price offers low price, the lowest price available in a ten-dose vial in 2014). to UNICEF from other suppliers. Graph 24: Price evolution of Tetanus Toxoid (TT) vaccines for PAHO and UNICEF 0.11 0.11 0.10 0.10 0.10 0.09 0.08 0.08 0.08 0.08 0.08 0.07 0.07 0.07 0.06 0.06 0.06 0.06 US$ PER DOSE 0.05 0.05 0.05 0.05 0.04 0.04 0.04 0.03 0.03 0.03 0.03 0.03 0.02 0.02 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015* UNICEF, Bio Farma, 10-dose UNICEF, Serum Institute of India, 10-dose UNICEF, CSL Limited, 20-dose UNICEF, Biological E., 10-dose UNICEF, Shantha Biotech, 10-dose UNICEF, Intervax, 20-dose UNICEF, Crucell, 10-dose UNICEF, Biological E., 20-dose UNICEF, Serum Institute of India, 20-dose UNICEF, Intervax, 10-dose *Forecasted data Sources: PAHO Revolving Fund, UNICEF Supply Division. Notes: • For UNICEF, where agreements include a range of prices during a calendar year period or for different countries or groups of countries, the lowest price of the range was kept. • Not represented on the graph: Intervax offered 10-dose and 20-dose presentations to UNICEF at US$0.037–0.043 per dose and US$0.024–0.027 (respectively) in 2001–2003; Sanofi Pasteur offered 10-dose and 20-dose presentations to UNICEF at US$0.08 per dose in 2003. • Novartis has supplied TT to UNICEF but has not agreed to the publication of prices. 92 Médecins Sans Frontières | The Right Shot 2nd Edition January 2015 Tetanus Toxoid Vaccines (TT) Prices in countries From Graph 25 below, it appears from emerging manufacturers. For effective (at US$0.04 per dose of that the price of TT vaccines is low instance, in hospitals in Tunisia, a TT the vaccine, representing 11% for international organisations, but vaccine by Serum Institute of India is of the total cost of immunisation, goes up to US$7.74 in the private available for US$1.98 per dose. at US$0.40 per dose administered).338 sector (Czech Republic). One study from Pakistan in 2004 The vaccine is available for close Outside of government purchases, showed that SIAs to prevent to this price through international low prices seem to be available neonatal tetanus were cost- organisations such as UNICEF. Graph 25: Prices for Tetanus Toxoid (TT) vaccines in several countries, by income group and price type, 2013/2014* 9.00 8.00 7.74 7.00 6.34 6.00 5.54 5.00 3.87 4.00 3.74 3.00 US$ PER DOSE 1.98 2.00 1.00 0.55 0.05 0.05 0.06 0.07 0.14 0 PAHO France Tunisia UNICEF UNICEF Hungary Philippines Czech Rep. Czech Rep. South Africa South Africa (1 -dose per vial ) (1 -dose per vial ) (1 -dose per vial ) (1 -dose per vial ) MSF (multidose) (20-doses per vial) (20 -doses per vial ) (10 -doses per vial ) (10 -doses per vial ) (10 -doses per vial ) (10 -doses per vial ) Gvt Hosp. Retail Biological E. Serum Institue of India Novartis Sanofi Pasteur Other/na Sources: PAHO Revolving Fund, UNICEF Supply Division, country price analysis. * Annex A, Section C Notes: • Numbers in parentheses are number of doses per vial, when known. • MSF price is with CPT Incoterm (see Annex C). • The Philippines procures through UNICEF. • Only the lowest price available to PAHO, UNICEF and MSF is presented in the graph. Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 93 ANNEXES Annex A: Sources and methodology for price analysis 1. INTERNATIONAL ORGANISATIONS UNICEF PAHO MSF Sources: UNICEF Supply Division;86,11 Sources: PAHO Revolving Fund Source: MSF Supply. WHO recommendations for routine website;67 PAHO Archives and Extract date: 28 May 2014. immunisation: summary tables;124 Immunization Newletters;339 WHO WHO list of prequalified vaccines.113 list of prequalified vaccines.113 Definitions and comments: Extract date: 11 March 2014. Extract date: 11 March 2014. • Raw quotations from each manufacturer. Incoterms vary Definitions and comments: Definitions and comments: by vaccine and manufacturer. • Data show the awarded price per • Data show the price per dose per • Data collected focused on dose per product per supplier per antigen per calendar year, based on paediatric vaccines. calendar year, based on multiyear annual contracts. Prices are weighed Annex A: Sources and methodology for price analysis supply agreements. average price (WAP), except if a • When prices were expressed in manufacturer’s name is mentioned. euros, prices were converted into • Data show most prices with CPT US dollars using the 2013 average (‘Carriage paid to’) Incoterms for • Assumptions about the manufacturer annual exchange rate as provided by 2001–2003; FCA (‘Free carrier’) were sometimes made based OANDA170 (euros to US dollars: 1.3279). Incoterms* for 2004–2006 onwards. on the WHO prequalified vaccines list and the country of origin, • In the analysis, MSF is included in the • Where agreements include a range of when available. ‘international organisation’ category. prices during a calendar year period or for different countries or groups • PAHO does not specify the Incoterm of countries, the lowest price of the used in its vaccine procurement. Prices range was used. are assumed to be CPT (‘Carriage paid to’), FOB (‘Free on board’) or FCA • Data collected focused on (‘Free carrier’) Incoterms. paediatric vaccines. • Graphs do not include manufacturers who refused to provide their prices to UNICEF (e.g. Novartis). Manufacturers that supplied a vaccine for only one year are also usually not represented. • When prices were expressed in euros, prices were converted into US dollars using the 2013 average annual exchange rate as provided by ONDA170 (euros to US dollars: 1.3279). * Incoterms: Please see Annex C 94 Médecins Sans Frontières | The Right Shot 2nd Edition January 2015 Annex A: Sources and methodology for price analysis 2. COUNTRIES A. Disclaimer differences that exist between Where there was uncertainty about countries and the absence of easily the reliability and accuracy of the While constructing the price database accessible and comparable vaccine data provided, it was not included for the publication, we aimed to be price data. The lack of descriptive in the analysis (e.g. errors on as precise and up-to-date as possible information enabling a precise names of products, sometimes no and took all reasonable precautions to contextualisation of the data clear identification of product or verify the accuracy and reliability of the prevents this analysis from being manufacturer, unrealistic product data used in the analysis. MSF is not used as a stand-alone comparative presentations, etc.) held responsible for data and content tool for international vaccine pricing. coming from and available on third- There was usually no mention of party websites. Incoterms associated with vaccine B. Data description prices. In this analysis, except if As much as possible, the data otherwise mentioned, all prices are presented in a comparable Methodology are assumed to be Incoterm DDP way. However, because of the Sources used: country national (Delivered Duty Paid) . complexity of vaccine pricing and registries, Ministry of Health the lack of transparency regarding Difficulties encountered in data websites, literature search, vaccine price components, not gathering that may have influenced press search and personal every price point is comparable. the analysis include: communication. Comparisons are subject to specific • websites that were difficult situations and factors that can Data collected focused on to navigate, often providing affect prices and that are particular paediatric vaccines and WHO information only in the local to each country. See below for prequalified products. language; country-specific information, The selection of countries included sources and definitions. • pricing lists that were in the database is mainly based on sometimes hard to read, The mention of specific data availability. with no consistency regarding products does not mean that Collection and formatting of names of antigens, products MSF endorses or recommends prices from local registries was or manufacturers; specific company products. done between April and May 2014; • a lack of descriptive information; All price data are provided in 320 price points were collected a lack of price components US dollars (US$). Exchange rate from 13 countries. information (e.g. taxes, logistics volatility may be responsible for Searches in national medicine price fees, exchange rate, wholesale price differences. To mitigate registries were conducted using and retail margins, etc.) exchange rate volatility, the rate ATC codes (Anatomical Therapeutic and little to no information used for all price points is the Chemical (ATC) Classification regarding procurement systems average exchange rate over a System for the classification of and Incoterms used; one-year period (average of 2013: drugs), product names, antigen 1 January to 31 December 2013) • price targets sometimes names, manufacturer’s names, as provided by OANDA,170 except ambiguous (price to the depending on information if otherwise mentioned. public, to hospitals, to specific provided in each database. programmes, etc.) The intended goal of this analysis Searches were conducted in local is to show the purchase price languages when needed. Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 95 Price categories - Hospital price (Hosp/ All prices except the ‘government Hospitals): price paid in Prices of vaccines can be price’ are official prices available hospitals and public institutions. comprised of different components, outside of government depending on what is incorporated - Manufacturer price immunisation programmes. in the price, as described in the (Manuf.): price of the vaccine In some countries, health insurance illustration below. before it enters the wholesale will cover the cost of the vaccine and retail distribution network. For the purpose of our analysis, price purchased in the private market, Does not include wholesale or data have been subdivided into four representing a burden for public retail margins, but may include main price types: health insurance schemes. In other taxes and transportation fees. countries, where the vaccine is not - Government price (Gvt): - Retail price (Retail): price as reimbursed by health insurance, price paid by the government paid by the population, inclusive the ‘retail price’ is a direct burden for national immunisation of taxes, transportation fees, and to personal budgets. programs. margins. Sometimes referred to as ‘private sector’ price. * Annex A: Sources and methodology for price analysis The components of vaccine price Ex-works price1 COMMENTS . 1. Initial price of the vaccine, + Cost of transportation, insurance, tariffs and duties, at the manufacturer’s 2 and inspection charges. Sometimes also includes production site. local importer margin. 2. Seller or buyer bears the Government costs, depending on the Incoterms used in contracts. Manufacturer price4 3 3. DDP (Delivered Duty Paid) price (DDP) price is when the goods are + Wholesale margin and other logistics fees. placed at the disposal of the Price to programmes buyer. In our country analysis we assumed that “manufacturer prices” were Wholesale price using DDP incoterm. 5 4. Government tenders do not + Retail margin / pharmacist margin + VAT and other logistics fees and other logistics fees. include any additional mark ups or taxes. Sometimes “government price” is the 6 ex-works price and does not Net retail price Hospital price include other costs. + VAT 5. Pharmacist margins are usually regulated by law. Gross retail price Price to end user 6. Prices accessible in hospitals, excluding cost of administration. * This is an example of components of vaccine prices, but components and order of the components could change from one country to another. 96 Médecins Sans Frontières | The Right Shot 2nd Edition January 2015 Annex A: Sources and methodology for price analysis COUNTRY SPECIFICATIONS The 13 countries included in this analysis are classified as follows: Exchange rate PCV3 DTP3 Country, GNI per capita Country Birth cohort, to US$, average coverage in coverage in currency (US$ 2012) classification in thousands year 2013 2013 (%) 2013 (%) India, INR 0.0172 1,580 LMIC N/A 76 25,595.2 Philippines, PHP 0.0235 2,500 LMIC N/A 94 2,403.9 Morocco, MAD 0.1178 2,960 LMIC 82 99 749.9 Tunisia, TND 0.6135 4,150 UMIC N/A 98 189.5 Thailand, THB 0.0325 5,210 UMIC N/A 99 686.7 South Africa, ZAR 0.1038 7,610 UMIC 87 90 1,098.8 Lebanon, LBP 0.0007 9,190 UMIC N/A 98 63.8 Brazil, BRL 0.4643 11,630 UMIC 93 95 2,994.6 Hungary, HUF 0.0045 12,380 UMIC 92 99 98.1 Czech Republic, CZK 0.0511 18,120 HIC N/A 99 118.3 France, EUR 1.3279 41,750 HIC 89 99 791.9 Belgium, EUR 1.3279 44,660 HIC 93 99 129.3 United States, USD 1.0000 52,340 HIC 92 94 4,229.9 WHO WHO World Sources OANDA170 World Bank45 World Bank97 immunisation immunisation Population coverage31 coverage31 Prospects340 N/A: Not Applicable. Note on income groups: economies are divided according to 2012 GNI per capita, calculated using the World Bank Atlas method.45,97 The groups are: low-income country (LIC), US$1,035 or less lower-middle-income country (LMIC), US$1,036–4,085 upper-middle-income country (UMIC), US$4,086–12,615 high-income country (HIC), US$12,616 or more Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 97 C. Individual country sources and definitions Belgium Extract date: 5 May 2014. Products and Foods for Special Medicinal Purposes (‘List’). Sources: Price categories: • INAMI, http://www.inami.fgov.be/ • Government price: price obtained • The List, published on the first day care/fr/hospitals/specific-information/ through agreements with companies. of the calendar month, includes a full forfaitarisation/index.htm. list of medicinal products (MPs) and Additional information: 156 341 foods for special medicinal purposes • Other sources: Le Soir, VaxInfo.org. • Brazil uses technology transfer (FSMPs) covered by the public health agreements that allow the country Last update: 1 April 2014. insurance scheme; these products to access vaccines (e.g. HPV vaccine are reimbursed by decision of the Extract date: 5 May 2014. and PCV) at lower prices; such Institute, including the maximum partnerships could limit the longer- Price categories: or announced ex-factory prices, the term opportunity for Brazil to • Manufacturer price: price exclusive of benefit from real competition when amount and terms of reimbursement, transportation fees, margins and taxes. emerging manufacturers enter the including the maximum possible reimbursement for the end consumer. • Hospital price: price paid in hospitals. market with cheaper products. • Retail price: as purchased at the Czech Republic France pharmacy, includes wholesale margin, pharmacist’s margin, Source: SUKL, State Institute for Drug Source: AMELI ‘Base de données des transportation fees and VAT. Control, http://www.sukl.eu/sukl/ médicaments et informations tarifaires’: Annex A: Sources and methodology for price analysis list-of-reimbursed-medicinal-products- http://www.codage.ext.cnamts.fr/ Additional information: valid-as-of-1-4-2014. codif/bdm_it/index_presentation. • The special price of the Gardasil php?p_site=. HPV vaccine at EUR20 per dose in Last update: 1 April 2014. Flanders was obtained through a Last update: 29 April 2014. Extract date: 25 April 2014. public tender. The two manufacturers Extract date: 5 May 2014. of HPV vaccine participated and Price categories: the Flemish region gave the entire • Manufacturer price: net Price categories: market to the company with the best manufacturer’s price (ex-factory), • Manufacturer price: price exclusive of offer (525,000 doses: 105,000 doses excludes any wholesale and retail transportation fees, margins and taxes. per year for five years). In Belgium, margins and excludes 15% VAT. there is no public tender at the • Retail price: as purchased at the • Retail price: gross retail price, national level for drugs or vaccines. pharmacy, includes wholesale final price to consumer. Includes margin, pharmacist’s margin, manufacturer price plus the Brazil transportation fees and VAT. maximum profit margin under the Sources: Ministry of Health’s price regulation Additional information: • Portal da Transparencia, Federal and VAT. • Only reimbursed vaccines are Government: http://www. Additional information: included in the list. portaldatransparencia.gov.br/ • Acting in compliance with Section convenios/DetalhaConvenio.asp?Cod • Data are updated every week. 39n(1) of Act No. 48/1997 Coll., on Convenio=677932&TipoConsulta=0. Public Health Insurance, as amended • Other sources: Agencia Brasil,154 (‘Act’), the State Institute for Drug The Financial Times,275 Control publishes the List of Prices FirstWord-Pharma.274 and Reimbursements for Medicinal 98 Médecins Sans Frontières | The Right Shot 2nd Edition January 2015 Annex A: Sources and methodology for price analysis Hungary • Retail price: price as listed on the Additional information: website, inclusive of the pharmacist’s Source: National Health Insurance • Most of the vaccines in the margin (between 19.35% and 23.08%). Fund Administration (OEP): Philippines are procured through UNICEF SD, thus prices for most http://www.oep.hu/portal/page?_ Additional information: vaccines are very similar to prices pageid=35,56067708&_dad=portal&_ • Drugs Public Price List according to published by UNICEF. schema=PORTAL. the resolution 51/1 and based on the Last update: 14 January 2014. exchange rate number 14/2/9990 South Africa issued on 10 April 2014. Extract date: 24 April 2014. Sources: Price categories: Morocco • South African Medicine Price Registry: http://www.mpr.gov.za/. • Manufacturer price: excludes wholesale Source: Agence Nationale de margin, retail margin and taxes. l’Assurance Maladie (ANAM) - guide • Communication with the South • Retail price: includes wholesale and des médicaments remboursables: African Department of Health. retail margins and taxes (5% taxes). http://www.assurancemaladie.ma/ Last update: 12 March 2014. anam.php?id_espace=6&id_srub=19. Extract date: 4 April 2014. India Extract date: 21 April 2014. Price categories: Sources: Price categories: • Government price: exclusive of VAT • Communication with a private practice. • Hospital price: this is the price and transportation costs. • R. Lodha and A. Bhargava 2010.342 accessible to hospitals. Defined on the ANAM website as the ‘Prix en • Manufacturer price: excludes logistics Price categories: Etablissement de soins’. fees and VAT. • Retail price: official maximum retail price (MRP) inclusive of all taxes, as • Retail price: this is the price • Retail price: SEP (single exit price), indicated on the vaccine box. accessible to the public when which is the maximum anyone should purchased in pharmacies. Defined be charged for a product, including Additional information: on the ANAM website as the ‘Prix logistics fees, VAT, etc. • Price data are from 2008 and 2014. Officine (Pharmacie)’. Additional information: Additional information: Lebanon • Note that prices in the Medicine • All vaccines in this list are Price Registry are provided by Source: Lebanon Drugs Public Price reimbursed, except HPV and product and by ml (price per List: http://www.moph.gov.lb/Drugs/ rotavirus vaccines. All reimbursed dose needs to be calculated). Pages/Drugs.aspx. vaccines are reimbursed at 100%. • In South Africa, EPI vaccines are Last update: 1 April 2014. purchased through BioVac, and The Philippines Extract date: 18 April 2014. contracts sometimes include Source: Communication with techology transfer arrangements to Price categories: a country EPI contact. BioVac so that South Africa can build • Manufacturer price: the pharmacist’s up its national manufacturing capacity. margin has been subtracted from Date: 10 March 2014. the retail price to obtain the price • The exchange rate South African without the margin. This price Price categories: rand/US$ rate is volatile; therefore is an estimate, representing the • Government price: price of vaccines part of price differences with other manufacturer price, with taxes and purchased by the EPI department of countries might be attributed to transportation fees. the Ministry of Health. the fluctuating exchange rate. Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 99 Thailand United States Source: Thailand National Health Source: Centers for Disease Control Security Office (NHSO). and Prevention (CDC) website: http:// www.cdc.gov/vaccines/programs/vfc/ Date: 1 May 2014. awardees/vaccine-management/price- Price categories: list/index.html. • Government price: excludes Last update: 1 April 2014. overhead cost under the Government Pharmaceutical Organisation’s Vendor Extract date: 4 April 2014. Managed Inventory (VMI) System Price categories: (5% for vaccines). • Government price: for vaccines Additional information: included in the CDC Vaccines for • For vaccines, the NHSO supply only Children Program (VFC) list of two of the vaccines we analysed. The paediatric vaccines. Price includes Department of Disease Control (DDC) Federal Excise Tax and transportation is the chief supplier of vaccines to the fees. This would correspond to the public sector. Incoterm Delivery Duty Paid (DDP), named place of destination. • The price listed here is the lowest price available for that product. • Manufacturer price: private sector prices are those reported by vaccine Annex A: Sources and methodology for price analysis manufacturers annually to CDC. Tunisia Additional information: Source: Pharmacie Centrale de Tunisie: http://www.phct.com.tn/ • The CDC Vaccine Price Lists provide index.php?option=com_searchproduct vaccine contract prices for CDC &view=searchproduct&Itemid=48&lan contracts that are established for the g=en&ctg=M. purchase of vaccines by immunisation programmes that receive CDC Last update: 19 March 2014. immunisation grant funds (i.e., state Extract date: 24 April 2014. health departments, certain large city immunisation projects, and certain Price categories: current and former US territories). • Hospital price: this is the price Prices quoted include Federal Excise accessible to hospitals; it does not Tax and transportation fees. Private include taxes. providers and private citizens cannot directly purchase vaccines through CDC contracts. 100 Médecins Sans Frontières | The Right Shot 2nd Edition January 2015 Annex B: Company contacts Annex b: Company contacts Bio farma GlaxoSmithKline (GSK) Pfizer Mr Supaporn S., Ms Jin Montesano, Ms Lindsey M. Dietschi, Export Sales Manager Vice President, Global Public Affairs Director, International Public Affairs and Communications, GSK Vaccines 19 Soi Udomsuk37, Sukumvit 103 Road, 235 East 42nd St, New York, Bangjak, Prakanong, Bangkok 10260, Rue de l’Institut 89, 1330 Rixensart, New York 10017, USA Thailand Belgium Tel: +1 212 733 2149 Tel: +6623618110 Email: [email protected] Email: [email protected] Email: [email protected] Merck Sanofi Pasteur Biological E Dr Joan Benson, Dr Michael Watson, Ms Mahima Datla, Executive Director, Strategic Partnerships VP Global Immunisation Policy Managing Director & Stakeholder Engagement, Lead Cervical 2 avenue du Pont Pasteur - Cancer Initiative Divya Bijlwan, 69367 - Lyon cedex 07 Associate Vice President Strategic One Merck Drive, PO Box 100, Email: [email protected] Operations and Planning Whitehouse Station, New Jersey 08889-0100, USA 18/1&3, Azamabad, Hyderabad - Tel: +1 215 652 1815 500 020, Andhra Pradesh, India Serum Institute Email: [email protected] of India Ltd (SII) Email: [email protected]; [email protected] Dr Suresh Jadhav, 212/2, Hadapsar, Off Soli Poonawalla Panacea Road, Pune, India Mr Rishi Prakash, Crucell Tel: +91 20 2660 2378 General Manager - Business Development Dr Olga Popova, Email: [email protected] Head of Government Affairs & Global B1 Ext. A-27, Mohan Co-op Industrial Vaccine Policy Company Estate, Mathura Road, New Delhi, India Tel: +91 41578000 PO Box 2048, 2301 CA Leiden, Email: [email protected] The Netherlands Tel: +39 342 394751 Email: [email protected] Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 101 Annex c: Incoterms Incoterms (International Commercial • FCA Free Carrier: ‘Free Carrier’ goods already so delivered. The risk of Terms), “provide rules and guidance means that the seller delivers the loss of or damage to the goods passes to importers, exporters, lawyers, goods to the carrier or another person when the goods are on board the transporters, insurers and students of nominated by the buyer at the seller’s vessel, and the buyer bears all costs Annex C: I ncoterms international trade.”343 premises or another named place. from that moment onwards. The parties are well advised to specify Incoterms are an important part of • DDP Delivered Duty Paid: as clearly as possible the point of trade. They define when responsibility ‘Delivered Duty Paid’ means that the handover within the named place of for goods is transferred from the seller seller delivers the goods when the delivery, as the risk passes to the buyer to the buyer, and what part of the goods are placed at the disposal of at that point. transportation, logistics and insurance the buyer, cleared for import on the costs is the responsibility of each of the • CPT Carriage Paid To: ‘Carriage arriving means of transport ready parties. They will influence the price paid Paid To’ means that the seller for unloading at the named place of for vaccines, as for any other goods. delivers the goods to the carrier or destination. The seller bears all the another person nominated by the costs and risks involved in bringing seller at an agreed place (if any such the goods to the place of destination Incoterms mentioned in this report are:* place is agreed between parties) and and has an obligation to clear the that the seller must contract for and • EXW Ex Works: ‘Ex Works’ means goods not only for export but also pay the costs of carriage necessary that the seller delivers when it places for import, to pay any duty for both to bring the goods to the named the goods at the disposal of the buyer export and import and to carry out place of destination. at the seller’s premises or at another all customs formalities. named place (i.e., works, factory, • FOB Free On Board (for transport warehouse, etc.). The seller does by sea and inland waterway): not need to load the goods on any ‘Free On Board’ means that the seller * Definitions reproduced from collecting vehicle, nor does it need delivers the goods on board the vessel ‘The Incoterms Rules’, International to clear the goods for export, where nominated by the buyer at the named Chamber of Commerce website,343 such clearance is applicable. port of shipment or procures the where more information is available. Annex C - Incoterms Point of destination, Point of origin Onboard buyer’s warehouse EXW E I FCA E I FOB E I CPT E I DDP E I E = Export clearance Seller covers payment and risks Sources: International Chamber of Commerce343, Yusen Logistics344, I = Import clearance Buyer covers payment and risks WCL Incoterms Quick Reference Chart 102 Médecins Sans Frontières | The Right Shot 2nd Edition January 2015 Annex D: Abbreviations Annex D: abbreviations AMC Advance Market Commitment ARV Antiretroviral drug BCG Bacillus Calmette-Guérin vaccine (against tuberculosis) CDC United States Centers for Disease Control and Prevention CTC Controlled Temperature Chain DCVM Developing Country Vaccine Manufacturers DCVMN Developing Countries Vaccine Manufacturers Network DFID Department for International Development (UK) DOV Decade of Vaccines Collaboration DTP Diphtheria, Tetanus and Pertussis vaccine DTwP Diphtheria, Tetanus and whole-cell Pertussis vaccine EPI Expanded Programme on Immunization FDA Food and Drug Administration (US) Gavi The Gavi Alliance (formerly Global Alliance for Vaccines and Immunizations) GNI Gross National Income GPRM Global Price Reporting Mechanism GSK GlaxoSmithKline GVAP Global Vaccine Action Plan Hep B Hepatitis B Hib Haemophilus influenzae type b HIC High-income country HIV Human Immunodeficiency Virus HPV Human Papillomavirus Vaccine IFPMA International Federation of Pharmaceutical Manufacturers & Associations IPV Inactivated Polio Vaccine LMIC Lower-middle-income country LPC Lowest price clauses MIC Middle-income country M&E Monitoring & Evaluation MFN clause Most Favoured Nations Provision/Clause MR Measles-rubella vaccines MMR Combined Measles, Mumps and Rubella vaccine MMRV Combined Measles, Mumps, Rubella and Varicella vaccine MSF Médecins Sans Frontières OANDA Online foreign exchange broker OCV Oral Cholera Vaccine OPV Oral Polio Vaccine Pentavalent Combined diphtheria, tetanus, whole-cell pertussis, hepatitis B and Haemophilus influenzae type b (DTwP-HepB-Hib) vaccine PAHO Pan American Health Organization PATH Program for Appropriate Technology in Health PCV Pneumococcal Conjugate Vaccine Polio Poliomyelitis PVP Pooled Vaccine Procurement initiative PQ Prequalification or Prequalified (WHO) Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 103 QSS WHO Quality, Safety and Standards R&D Research and Development SAGE Strategic Advisory Group of Experts SIA Supplemental Immunisation Activities SII Serum Institute of India Ltd TPP Target Product Profile Annex D: Abbreviations Td Tetanus-diphtheria vaccine TT Tetanus Toxoid UMIC Upper-middle-income country UNICEF United Nations Children’s Fund (UNICEF SD: Supply Division) V3P Vaccine Product, Price and Procurement Project VVM Vaccine Vial Monitor WHA World Health Assembly WHO World Health Organization WHO PQ WHO Prequalification of Medicines Programme 104 Médecins Sans Frontières | The Right Shot 2nd Edition January 2015 Annex E : Summary of W HO position papers – recommendations for routine immunisation Annex E: Summary of WHO Position Papers – recommendations for routine immunisation Last update: 30 May 2014 For more information, go to: http://www.who.int/immunization/policy/Immunization_routine_table1.pdf?ua=1 Antigen Children Adolescents Adults Considerations BCG 1 dose Exceptions HIV+ • Birth dose • Premature and low birth 3 doses (for high-risk groups if not weight Hepatitis B 3 – 4 doses previously immunised) • Co-administration and combination vaccine • Definition high-risk • OPV birth dose 3 – 4 doses (at least one dose of • Type of vaccine Poliomyelitis IPV) with DTP • Transmission and importation risk criteria 3 doses Booster (Td) in • Delayed/Interrupted DTP Booster (DTP) Booster (Td) early adulthood or schedule 1 – 6 years of age pregnancy • Combination vaccine Option 1 3 doses, with DTP • Single dose if ≥12 months of age • Not recommended for Haemophilus children >5 yrs old influenzae 2 or 3 doses, with booster at least type b Option 2 • Delayed/Interrupted 6 months after last dose schedule • Co-administration and combination vaccine Option 1 3 doses with DTP • Vaccine options • Start before 6 months of age Pneumococcal 2 doses before 6 months of age, (conjugate) Option 2 plus booster dose at 9–15 months • Co-administration of age • HIV+ and preterm neonates booster • Vaccine options Rotarix: 2 doses with DTP Rotavirus • Not recommended RotaTeq: 3 doses with DTP if >24 months old • Combination vaccine Measles 2 doses • HIV+ early vaccination • Pregnancy • Achieve and sustain 1 dose (adolescent girls and/or women 80% coverage Rubella 1 dose of child-bearing age if not previously • Co-administration and vaccinated) combination vaccine • Pregnancy • Target 9 –13-year-old girls • Pregnancy HPV 2 doses (girls) • Older age groups (≥15 years) • HIV+ and immunocompromised Bringing down barriers to affordable and adapted vaccines | www.msfaccess.org/rightshot2 105 Annex f: Notes and methodology for the graph on the price of vaccines to immunise a child Graph 1 (from page 7 of this report) 50 45.59** 45 HPV & IPV, +41% 41.09*** 40 MR & rotavirus, +14% 32.66 35 PCV, +221% 28.59 32.22 30 25 US$ x68 Hib (penta), +767% 20 15 HepB, +127% 11.43 10 5 0.67 1.28 0 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 ** Includes 3 doses of HPV vaccine. *** Includes 2 doses of HPV vaccine. Notes: • Baseline cost in 2001 based on the • Most prices are with CPT Incoterms* considered the ‘reference price’, following schedule: 1 BCG + 2 measles from 2001 to 2003; FCA Incoterms* we used this price in the analysis. + 3 DTP + 3 OPV. Cost in 2014 based from 2004 to 2006 onwards. • For the rotavirus vaccines, we used on the following schedule: 1 BCG + 2 • Only specific countries can access the cheapest full course option, MR + 3 Penta + 3 OPV + 1 IPV + 3 PCV these low prices (mostly Gavi-eligible Rotarix (GSK), which has a schedule + 2 Rota + 3 HPV. countries). Prices are based on multi- of two doses (versus three doses for • Indicator used: lowest available UNICEF year supply agreements. Merck’s RotaTeq). Annex F: Notes and methodology for the graph on price of vaccines to immunise a child price per antigen per year since • The analysis does not include vaccines • For the MR/MMR vaccine, the 2001 (across UNICEF’s suppliers and recommended for specific regions price has been calculated using the across presentations) to complete all (e.g. yellow fever). It includes only cheapest option, which is to use primary series in routine immunisation doses in primary series, not booster the MR vaccine. Also, WHO only as recommended by WHO. The dose recommendations. recommends vaccination against percentage presented in the graph is mumps in specific settings. the difference from the previous year. • The analysis includes HPV as it is a primary series vaccine, even though • Exchange rate: when prices were • The graph does not represent the full WHO recommendations are for expressed in euros, prices were cost of immunisation, only the cost adolescents girls only. converted into US dollars using the of vaccines. Many elements, such 2013 average annual exchange rate as human resources, transportation, • For PCV, the price per dose is as provided by OANDA (euros to US cold chain, infrastructure, wastage, composed of a tail price (US$3.50) and dollars 2013 annual average exchange other immunisation supplies, waste subsidies (US$3.50) achieved through rate: 1.3279). management, etc., would need to be the Advance Market Commitment added to have a full picture. (AMC). As US$7 dollars is often 106 Médecins Sans Frontières | The Right Shot 2nd Edition January 2015 Annex F: Notes and methodology for the graph on price of vaccines to immunise a child Timeline: WHO recommendations and Gavi decisions on vaccines funding • 2001: used as the baseline year, as immunisation before 2006. The finance the vaccines for their routine it is the year the GAVI Alliance (the pentavalent price is used as of 2006. immunisation programme. Global Alliance for Vaccines and • 2010: first Gavi-eligible country • 2013: Gavi supports the introduction Immunisation, now known simply receives pneumococcal conjugate of HPV in Gavi-eligible countries; as Gavi) was created. The baseline vaccine under the Advance Market 21 countries were approved in 2013 vaccine routine immunisation includes Commitment (WHO recommended one BCG, three DTP, three OPV and and 2014 to receive Gavi support to vaccination with PCV in 2007). two measles vaccines. introduce the HPV vaccine. • 2011: first Gavi-eligible country • 2004: WHO reiterates 1992 • 2014: At the end of 2013 SAGE recommendation for universal in Africa receives rotavirus vaccine (WHO Strategic Advisory Group of vaccination against hepatitis B. (WHO recommended vaccination Experts on Immunisation) published with rotavirus vaccine in 2009). WHO guidelines on the introduction of IPV • 2006: WHO recommends universal recommends universal immunisation in routine immunisation. As part of vaccination against Haemophilus with rubella vaccine, especially using the polio end-game strategy, Gavi influenzae type b. DTP and HepB rubella-containing vaccines such as vaccine prices are used until 2006, supports the introduction of IPV in MR or MMR vaccines. even though the pentavalent Gavi countries, but also includes vaccine already existed, on the • 2013: Gavi offers support to access several policy exceptions in order to basis that countries were ramping the measles-rubella vaccine by broaden the number of countries that up pentavalent introduction and providing support for measles and can apply for its support. Prices from that Hib was not added to the rubella catch-up campaigns under the UNICEF tenders are published in WHO recommendations for routine the condition that countries self- February 2014. 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