Estimated generic prices for novel treatments for drug-resistant tuberculosis.

Background: The estimated worldwide annual incidence of MDR-TB is 480 000, representing 5% of TB incidence, but 20% of mortality. Multiple drugs have recently been developed or repurposed for the treatment of MDR-TB. Currently, treatment for MDR-TB costs thousands of dollars per course. Objectives: To estimate generic prices for novel TB drugs that would be achievable given large-scale competitive manufacture. Methods: Prices for linezolid, moxifloxacin and clofazimine were estimated based on per-kilogram prices of the active pharmaceutical ingredient (API). Other costs were added, including formulation, packaging and a profit margin. The projected costs for sutezolid were estimated to be equivalent to those for linezolid, based on chemical similarity. Generic prices for bedaquiline, delamanid and pretomanid were estimated by assessing routes of synthesis, costs/kg of chemical reagents, routes of synthesis and per-step yields. Costing algorithms reflected variable regulatory requirements and efficiency of scale based on demand, and were validated by testing predictive ability against widely available TB medicines. Results: Estimated generic prices were US$8-$17/month for bedaquiline, $5-$16/month for delamanid, $11-$34/month for pretomanid, $4-$9/month for linezolid, $4-$9/month for sutezolid, $4-$11/month for clofazimine and $4-$8/month for moxifloxacin. The estimated generic prices were 87%-94% lower than the current lowest available prices for bedaquiline, 95%-98% for delamanid and 94%-97% for linezolid. Estimated generic prices were $168-$395 per course for the STREAM trial modified Bangladesh regimens (current costs $734-$1799), $53-$276 for pretomanid-based three-drug regimens and $238-$507 for a delamanid-based four-drug regimen. Conclusions: Competitive large-scale generic manufacture could allow supplies of treatment for 5-10 times more MDR-TB cases within current procurement budgets.

Global health equity in United Kingdom university research: a landscape of current policies and practices.

BACKGROUND: Universities are significant contributors to research and technologies in health; however, the health needs of the world's poor are historically neglected in research. Medical discoveries are frequently licensed exclusively to one producer, allowing a monopoly and inequitable pricing. Similarly, research is often published in ways that make it inaccessible. Universities can adopt policies and practices to overcome neglect and ensure equitable access to research and its products. METHODS: For 25 United Kingdom universities, data on health research funding were extracted from the top five United Kingdom funders' databases and coded as research on neglected diseases (NDs) and/or health in low- and lower-middle-income countries (hLLMIC). Data on intellectual property licensing policies and practices and open-access policies were obtained from publicly available sources and by direct contact with universities. Proportions of research articles published as open-access were extracted from PubMed and PubMed Central. RESULTS: Across United Kingdom universities, the median proportion of 2011-2014 health research funds attributable to ND research was 2.6% and for hLLMIC it was 1.7%. Overall, 79% of all ND funding and 74% of hLLMIC funding were granted to the top four institutions within each category. Seven institutions had policies to ensure that technologies developed from their research are affordable globally. Mostly, universities licensed their inventions to third parties in a way that confers monopoly rights. Fifteen institutions had an institutional open-access publishing policy; three had an institutional open-access publishing fund. The proportion of health-related articles with full-text versions freely available online ranged from 58% to 100% across universities (2012-2013); 23% of articles also had a creative commons CC-BY license. CONCLUSION: There is wide variation in the amount of global health research undertaken by United Kingdom universities, with a large proportion of total research funding awarded to a few institutions. To meet a level of research commitment in line with the global burden of disease, most universities should seek to expand their research activity. Most universities do not license their intellectual property in a way that is likely to encourage access in resource-poor settings, and lack policies to do so. The majority of recent research publications are published open-access, but not as gold standard (CC-BY) open-access.

Estimated Sustainable Cost-Based Prices for Diabetes Medicines.

Importance: The burden of diabetes is growing worldwide. The costs associated with diabetes put substantial pressure on patients and health budgets, especially in low- and middle-income countries. The prices of diabetes medicines are a key determinant for access, yet little is known about the association between manufacturing costs and current market prices. Objectives: To estimate the cost of manufacturing insulins, sodium-glucose cotransporter 2 inhibitors (SGLT2Is), and glucagonlike peptide 1 agonists (GLP1As), derive sustainable cost-based prices (CBPs), and compare these with current market prices. Design, Setting, and Participants: In this economic evaluation, the cost of manufacturing insulins, SGLT2Is, and GLP1As was modeled. Active pharmaceutical ingredient cost per unit (weighted least-squares regression model using data from a commercial database of trade shipments, data from January 1, 2016, to March 31, 2023) was combined with costs of formulation and other operating expenses, plus a profit margin with an allowance for tax, to estimate CBPs. Cost-based prices were compared with current prices in 13 countries, collected in January 2023 from public databases. Countries were selected to provide representation of different income levels and geographic regions based on the availability of public databases. Main Outcomes and Measures: Estimated CBPs; lowest current market prices (2023 US dollars). Results: In this economic evaluation of manufacturing costs, estimated CBPs for treatment with insulin in a reusable pen device could be as low as $96 (human insulin) or $111 (insulin analogues) per year for a basal-bolus regimen, $61 per year using twice-daily injections of mixed human insulin, and $50 (human insulin) or $72 (insulin analogues) per year for a once-daily basal insulin injection (for type 2 diabetes), including the cost of injection devices and needles. Cost-based prices ranged from $1.30 to $3.45 per month for SGLT2Is (except canagliflozin: $25.00-$46.79) and from $0.75 to $72.49 per month for GLP1As. These CBPs were substantially lower than current prices in the 13 countries surveyed. Conclusions and Relevance: High prices limit access to newer diabetes medicines in many countries. The findings of this study suggest that robust generic and biosimilar competition could reduce prices to more affordable levels and enable expansion of diabetes treatment globally.

Novel approaches to enable equitable access to monoclonal antibodies in low- and middle-income countries.

Monoclonal antibodies (mAbs) are revolutionizing management of non-communicable diseases in high-income countries and are increasingly being advanced for a range of infectious diseases (IDs). However, access to existing mAbs is limited in low- and middle-income countries (LMICs), and investment in developing fit-for-purpose mAbs for IDs that disproportionately affect LMICs has been limited. Underlying these access barriers are systemic challenges, including a lack of commercial incentives to target LMIC markets and complexity in manufacturing and regulatory processes. Novel strategies are needed to overcome systemic access barriers for mAbs. We outline key areas where new approaches could address these barriers, based on a multistakeholder consultation in March 2023. Three disease-market archetypes are identified to guide thinking about business models tailored to different contexts. New business models are needed to incentivize development and manufacturing of ID mAbs and to ensure mAbs are optimized with a target product profile and cost of goods that enable use in diverse LMIC settings. Lessons can be applied from voluntary licensing strategies and product development partnerships that have shown success in catalysing development and affordable supply for a range of infectious diseases. Technology transfer will be key to expand LMIC research and manufacturing capacity and to enable sustainable and diversified supply. Improved market intelligence, demand aggregation mechanisms, and portfolio-based manufacturing models could be used to de-risk commercial investment and establish a sustainable manufacturing ecosystem for affordable mAbs. Novel regulatory approaches and robust technology transfer may reduce data requirements and timelines for biosimilar approvals. Trailblazer products, with coordinated "end-to-end" support from funders, can demonstrate proof of concept for pathways to accessible mAbs across a broader range of LMICs. Research funders; local, regional, global health agencies; and, private sector partners should commit to implementing innovative partnerships and end-to-end strategies that enable equitable access to mAbs for infectious diseases in LMICs.

Trends in cost and consumption of essential medicines for non-communicable diseases in Azerbaijan, Georgia, and Uzbekistan, from 2019 to 2021.

BACKGROUND: Access to medicines is a global priority. Azerbaijan, Georgia, and Uzbekistan have different approaches to pricing policies for pharmaceuticals. The aim of this study was to analyze recent trends in the consumption and prices of non-communicable disease (NCD) medicines in Azerbaijan, Georgia, and Uzbekistan, in the outpatient setting. METHODS: We included medicines for asthma and COPD, cancer, cardiovascular disease, diabetes, epilepsy, and mental disorders. Sales data for pharmaceutical products in community pharmacies were extracted from a commercial database. Changes in consumption and prices were analyzed across all included NCD medicines, by disease category and pharmacological group. RESULTS: Consumption of NCD medicines was highest in Georgia, at twice the levels in Azerbaijan, and four times levels in Uzbekistan. Average prices of NCD medicines, weighted by consumption, increased by 26% in Georgia, but decreased by 3% in Azerbaijan and by 0.1% in Uzbekistan. Prices increased for all disease groups in Georgia (from +13% for epilepsy medicines to +86% for cancer), varied by group in Uzbekistan (from -22% for epilepsy medicines to +47% for cancer), while changes in Azerbaijan were smaller in magnitude (from -4% for medicines for cardiovascular disease to +11% for cancer). Cancer medicines had markedly higher prices in Uzbekistan, and asthma and COPD medicines had markedly higher prices in Azerbaijan and Uzbekistan. CONCLUSIONS: Georgia showed the highest outpatient consumption of NCD medicines, suggesting the broadest access to treatment. However, Georgia also saw marked price increases, greater than in the other countries. In Georgia, where there was no price regulation, widespread price increases and increases in consumption both contribute to increasing pharmaceutical expenditures. In Azerbaijan and Uzbekistan, increases in outpatient pharmaceutical expenditures were primarily driven by increases in consumption, rather than increases in price. Comparing trends in consumption and pricing can identify gaps in access and inform future policy approaches.

Correction: Global health research and education at medical faculties in Germany.

[This corrects the article DOI: 10.1371/journal.pone.0231302.].

Public investments in the development of GeneXpert molecular diagnostic technology.

BACKGROUND: The GeneXpert diagnostic platform from the US based company Cepheid is an automated molecular diagnostic device that performs sample preparation and pathogen detection within a single cartridge-based assay. GeneXpert devices can enable diagnosis at the district level without the need for fully equipped clinical laboratories, are simple to use, and offer rapid results. Due to these characteristics, the platform is now widely used in low- and middle-income countries for diagnosis of diseases such as TB and HIV. Assays for SARS-CoV-2 are also being rolled out. We aimed to quantify public sector investments in the development of the GeneXpert platform and Cepheid's suite of cartridge-based assays. METHODS: Public funding data were collected from the proprietor company's financial filings, grant databases, review of historical literature concerning key laboratories and researchers, and contacting key public sector entities involved in the technology's development. The value of research and development (R&D) tax credits was estimated based on financial filings. RESULTS: Total public investments in the development of the GeneXpert technology were estimated to be $252 million, including >$11 million in funding for work in public laboratories leading to the first commercial product, $56 million in grants from the National Institutes of Health, $73 million from other U.S. government departments, $67 million in R&D tax credits, $38 million in funding from non-profit and philanthropic organizations, and $9.6 million in small business 'springboard' grants. CONCLUSION: The public sector has invested over $250 million in the development of both the underlying technologies and the GeneXpert diagnostic platform and assays, and has made additional investments in rolling out the technology in countries with high burdens of TB. The key role played by the public sector in R&D and roll-out stands in contrast to the lack of public sector ability to secure affordable pricing and maintenance agreements.

Reimbursement models to tackle market failures for antimicrobials: Approaches taken in France, Germany, Sweden, the United Kingdom, and the United States.

INTRODUCTION: The pipeline of new antibacterials remains limited. Reasons include low research investments, limited commercial prospects, and scientific challenges. To complement existing initiatives such as research grants, governments are exploring policy options for providing new market incentives to drug developers. MATERIALS AND METHODS: Reimbursement interventions for antibacterials in France, Germany, Sweden, US, and UK were reviewed and analysed by the authors. RESULTS: In France, Germany, and the US, implemented interventions centre on providing exceptions in cost-containment mechanisms to allow higher prices for certain antibacterials. In the US, also, certain antibacterials are granted additional years of protection from generic competition (exclusivity) and faster regulatory review. The UK is piloting a model that will negotiate contracts with manufacturers to pay a fixed annual fee for ongoing supply of as many units as needed. Sweden is piloting a model that will offer manufacturers of selected antibacterials contracts that would guarantee a minimum annual revenue. A similar model of guaranteed minimal annual revenues is under consideration in the US (PASTEUR Act). CONCLUSIONS: The UK and Sweden are piloting entirely novel procurement and reimbursement models. Existing interventions in the US, France, and Germany represent important, but relatively minor interventions. More countries should explore the use of novel models and international coordination will be important for 'pull' incentives to be effective. If adopted, the PASTEUR legislation in the US would constitute a significant 'pull' incentive.

Potential approaches for the pricing of cancer medicines across Europe to enhance the sustainability of healthcare systems and the implications.

Introduction: There are growing concerns among European health authorities regarding increasing prices for new cancer medicines, prices not necessarily linked to health gain and the implications for the sustainability of their healthcare systems.Areas covered: Narrative discussion principally among payers and their advisers regarding potential approaches to the pricing of new cancer medicines.Expert opinion: A number of potential pricing approaches are discussed including minimum effectiveness levels for new cancer medicines, managed entry agreements, multicriteria decision analyses (MCDAs), differential/tiered pricing, fair pricing models, amortization models as well as de-linkage models. We are likely to see a growth in alternative pricing deliberations in view of ongoing challenges. These include the considerable number of new oncology medicines in development including new gene therapies, new oncology medicines being launched with uncertainty regarding their value, and continued high prices coupled with the extent of confidential discounts for reimbursement. However, balanced against the need for new cancer medicines. This will lead to greater scrutiny over the prices of patent oncology medicines as more standard medicines lose their patent, calls for greater transparency as well as new models including amortization models. We will be monitoring these developments.

Public investments in the clinical development of bedaquiline.

INTRODUCTION: In 2012, bedaquiline became the first new treatment from a novel class to be approved for tuberculosis in nearly five decades and is now a core component of the standard of care for multidrug-resistant tuberculosis. In addition to the originator pharmaceutical company, Janssen, a range of governmental and non-profit entities have contributed to the development of bedaquiline. MATERIALS AND METHODS: We identified various avenues of public investments in the development of bedaquiline: direct funding of clinical trials and a donation programme, tax credits and deductions, and revenues resulting from the priority review voucher (PRV) awarded to the originator. Data on investments were gathered through contact with study leads and/or funders; for non-responses, published average costs were substituted. The originator company's expenses were estimated by similar methods. Tax credits and deductions were calculated based on estimated originator trial costs and donation expenses. The value of the PRV was estimated by application of a published model. RESULTS: Public contributions through clinical trials funding were estimated at US$109-252 million, tax credits at US$22-36 million, tax deductions at US$8-27 million, administration of a donation programme at US$5 million, PRV revenues at US$300-400 million. Total public investments were US$455-747 million and originator investments were US$90-240 million (if capitalized and risk-adjusted, US$647-1,201 million and US$292-772 million, respectively). CONCLUSIONS: Estimating the investments in the development of a medicine can inform discussions regarding fair pricing and future drug development. We estimated that total public investments exceeded the originator's by a factor of 1.6-5.1.

Price of a hepatitis C cure: Cost of production and current prices for direct-acting antivirals in 50 countries.

OBJECTIVES: Seven years after the introduction of direct-acting antivirals (DAAs) for the treatment of hepatitis C, high prices remain a barrier for treatment programs worldwide. This study seeks to describe current prices for originator DAAs in 50 countries and evaluate the relationship between prices and GDP per capita. METHODS: Data on prices of sofosbuvir, daclatasvir, sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, and glecaprevir/pibrentasvir were collected from national databases for 50 countries. Cost-based generic prices were estimated using an established algorithm, which accounts for costs of the active pharmaceutical ingredient (API), excipients, conversion costs of API to finished pharmaceutical product, taxes assuming manufacture in India, and a 10% profit margin. Correlation between current market prices and GDP per capita was assessed by Spearman rank-order correlation. RESULTS: Median originator prices per standard course were US$40,502 for sofosbuvir, US$26,928 for daclatasvir, US$46,812 for sofosbuvir/ledipasvir, US$34,381 for sofosbuvir/velpatasvir, and US$30,710 for glecaprevir/pibrentasvir (G/P). The estimated cost-based generic prices for a 12-week course were US$28 for sofosbuvir, US$31 for ledipasvir, US$58 for velpatasvir, US$4 for daclatasvir. For fixed-dose combinations, estimated cost-based prices were US$58 for sofosbuvir/ledipasvir, US$85 for sofosbuvir/velpatasvir, and US$31 for sofosbuvir/daclatasvir (API cost data were insufficient to calculate an estimate for G/P). Cumulative originator sales of WHO-recommended DAAs reached US$82 billion by the end of 2019. Across the 50 countries, there was no correlation between GDP per capita and DAA price, nor between estimated viraemic population and DAA price. Sub-analyses within World Bank income groups found a significant negative correlation between price and GDP per capita for all DAAs within the high-income countries group. CONCLUSIONS: Prices of DAAs vary widely across countries. The lack of correlation between DAA price and GDP per capita and viraemic population suggests that prices for DAAs are not adjusted based on country income level or potential patient population. Among high-income countries, DAA prices fall as income levels rise, possibly due to greater negotiating power of wealthier countries. DAA prices in most countries remain many times higher than estimated cost-based generic prices.

Global health research and education at medical faculties in Germany.

BACKGROUND: Universities undertake the majority of publicly funded research in Germany and hence bear a responsibility to contribute to global health efforts. So far, involvement and impact of German medical faculties in global health are unknown. Our aim was to systematically asses and evaluate German medical faculties' contribution to global health related research and education, as well as their policies and practices concerning open access publishing and equitable licensing. METHODS: We assessed the involvement in global health of all 36 publicly funded medical faculties in Germany during 2010-2014 in three areas: innovation, access and education, using the following indicators: research funding and publications focused on global health or poverty-related and neglected diseases; open access publishing and policies promoting access to medical innovations worldwide; provision of global health education. Data were gathered from public databases, university websites and questionnaires sent to individual universities for validation and triangulation. RESULTS: There was a high level of variability between institutions and indicators. The proportion of research funding for poverty-related and neglected diseases research ranged between 0.0-1.1%. The top five institutions received nearly 85% of the total poverty-related and neglected diseases research funding. 20 of 36 universities had an institutional open access publishing policy, 19 had an open access publishing fund, 16 had neither. Only one university reported having used an equitable licensing policy. 22 of 36 faculties provided some global health education, but only one of them included global health in their core undergraduate medical curriculum as a compulsory course with more than just single lectures. CONCLUSION: Obtained data indicate that global health and poverty-related and neglected diseases research at German medical faculties is highly concentrated in a few institutions, open-access publishing and equitable licensing policies are mostly absent, and only little global health education exists. Universities and government should address global health strategically in both research and education at medical faculties to reflect the country's economic and political weight and human resource potential.

Tenofovir alafenamide vs. tenofovir disoproxil fumarate: an updated meta-analysis of 14 894 patients across 14 trials.

BACKGROUND: Both tenofovir disoproxil fumarate (TDF)/emtricitabine and tenofovir alafenamide (TAF)/emtricitabine demonstrate excellent efficacy and safety overall, but concerns remain over specific changes in markers of bone and renal function. Lower plasma tenofovir concentrations are seen with TAF and in unboosted regimens. We assess TAF vs. TDF safety with and without booster coformulation. METHODS: A previous systematic review was updated with recent clinical trials. TAF vs. TDF efficacy and safety were compared in boosted and unboosted subgroups. Efficacy was measured by viral suppression. Key safety endpoints included all adverse events, serious adverse events, Grades 3-4 adverse events and adverse event discontinuation. Further specific renal and bone markers were also assessed. RESULTS: A total of 14 clinical trials comparing TDF and TAF regimens were identified. A significant difference (P = 0.0004) in efficacy was shown in the boosted subgroup in favour of TAF, but no difference was seen in the unboosted subgroup. There were no significant differences between TAF and TDF for any of the key safety endpoints analysed. No differences were seen for the bone markers analysed. No difference was found for renal tubular events. There was a difference in risk for discontinuation due to renal adverse events when boosted (P = 0.03), but none when unboosted. CONCLUSION: Across all main safety endpoints, no differences between TAF and TDF are seen. Boosted TDF regimens were associated with lesser comparative efficacy than boosted TAF and a higher risk of renal event discontinuation. However, modern antiretroviral regimens are more commonly unboosted. This study finds no difference in efficacy or safety in unboosted TAF vs. TDF.

Estimation of cost-based prices for injectable medicines in the WHO Essential Medicines List.

OBJECTIVES: Challenges remain in ensuring universal access to affordable essential medicines. We previously estimated the expected generic prices based on cost of production for medicines in solid oral formulations (ie, capsules or tablets) on the WHO Model List of Essential Medicines (EML). The objectives of this analysis were to estimate cost-based prices for injectable medicines on the EML and to compare these to lowest current prices in England, South Africa, and India. DESIGN: Data on the cost of active pharmaceutical ingredients (APIs) exported from India were extracted from an online database of customs declarations (www.infodriveindia.com). A formula was designed to use API price data to estimate a cost-based price, by adding the costs of converting API to a finished pharmaceutical product, including the cost of formulation in vials or ampoules, transportation and an average profit margin. RESULTS: For injectable formulations on the WHO EML, medicines had prices above the estimated cost-based price in 77% of comparisons in England (median ratio 2.54), and 62% in South Africa (median ratio 1.48), while 85% of medicines in India had prices below estimated cost-based price (median ratio 0.30). 19% of injectable medicines in England, 9% in South Africa, and 5% in India had prices more than 10 times the estimated cost-based price. Medicines that appeared in the top 20 by ratio of lowest current price to estimated cost-based price for more than one country included numerous oncology medicines-irinotecan, leuprorelin, ifosfamide, daunorubicin, filgrastim and mesna-as well as valproic acid and ciclosporin. CONCLUSIONS: Estimating manufacturing costs can identify cases in which profit margins for medicines may be set significantly higher than average.

Quantifying changes in global health inequality: the Gini and Slope Inequality Indices applied to the Global Burden of Disease data, 1990-2017.

BACKGROUND: The major shifts in the global burden of disease over the past decades are well documented, but how these shifts have affected global inequalities in health remains an underexplored topic. We applied comprehensive inequality measures to data from the Global Burden of Disease (GBD) study. METHODS: Between-country relative inequality was measured by the population-weighted Gini Index, between-country absolute inequality was calculated using the population-weighted Slope Inequality Index (SII). Both were applied to country-level GBD data on age-standardised disability-adjusted life years. FINDINGS: Absolute global health inequality measured by the SII fell notably between 1990 (0.68) and 2017 (0.42), mainly driven by a decrease of disease burden due to communicable, maternal, neonatal and nutritional diseases (CMNN). By contrast, relative inequality remained essentially unchanged from 0.21 to 0.19 (1990-2017), with a peak of 0.23 (2000-2008). The main driver for the increase of relative inequality 1990-2008 was the HIV epidemic in Sub-Saharan Africa. Relative inequality increased 1990-2017 within each of the three main cause groups: CMNNs; non-communicable diseases (NCDs); and injuries. CONCLUSIONS: Despite considerable reductions in disease burden in 1990-2017 and absolute health inequality between countries, absolute and relative international health inequality remain high. The limited reduction of relative inequality has been largely due to shifts in disease burden from CMNNs and injuries to NCDs. If progress in the reduction of health inequalities is to be sustained beyond the global epidemiological transition, the fight against CMNNs and injuries must be joined by increased efforts for NCDs.

Cell line access to revolutionize the biosimilars market.

Biologic drugs are notoriously expensive. Biosimilars, though priced lower, are also costly. Analysis of the cost of production of biologics suggests that the cost of manufacture is in many cases less than 10% of the price in high-income countries, and less than a third of the price of biosimilars in India. This in turn implies that the relatively high prices of biosimilars are largely due to the need to undertake laborious reverse-engineering and phase 3 trials to demonstrate clinical similarity. In this article, it is proposed that originators could be required to submit cell line stocks to regulators and disclose details of manufacturing processes. These would be shared with prospective non-originator manufacturers to greatly reduce the investments needed to bring a non-originator biologic to market. This system would allow far greater price reductions for biologics after the expiry of monopoly rights (e.g. patents), while maintaining the monopoly rights used to incentivize drug development.

Production costs and potential prices for biosimilars of human insulin and insulin analogues.

INTRODUCTION: High prices for insulin pose a barrier to treatment for people living with diabetes, with an estimated 50% of 100 million patients needing insulin lacking reliable access. As insulin analogues replace regular human insulin (RHI) globally, their relative prices will become increasingly important. Three originator companies control 96% of the global insulin market, and few biosimilar insulins are available. We estimated the price reductions that could be achieved if numerous biosimilar manufacturers entered the insulin market. METHODS: Data on the price of active pharmaceutical ingredient (API) exported from India were retrieved from an online customs database. Manufacturers of insulins were contacted for price quotes. Where market API prices could not be identified, prices were estimated based on comparison of similarity, in terms of manufacturing process, with APIs for which prices were available. Potential biosimilar prices were estimated by adding costs of excipients, formulation, transport, development and regulatory costs, and a profit margin. RESULTS: The manufacturing processes for RHI and insulin analogues are similar. API prices were US$24 750/kg for RHI, US$68 757/kg for insulin glargine and an estimated US$100 000/kg for other analogues. Estimated biosimilar prices were US$48-71 per patient per year for RHI, US$49-72 for neutral protamine Hagedorn (NPH) insulin and US$78-133 for analogues (except detemir: US$283-365). CONCLUSION: Treatment with biosimilar RHI and insulin NPH could cost ≤US$72 per year and with insulin analogues ≤US$133 per year. Estimated biosimilar prices were markedly lower than the current prices for insulin analogues. Widespread availability at estimated prices may allow substantial savings globally.

Estimated costs of production and potential prices for the WHO Essential Medicines List.

INTRODUCTION: There are persistent gaps in access to affordable medicines. The WHO Model List of Essential Medicines (EML) includes medicines considered necessary for functional health systems. METHODS: A generic price estimation formula was developed by reviewing published analyses of cost of production for medicines and assuming manufacture in India, which included costs of formulation, packaging, taxation and a 10% profit margin. Data on per-kilogram prices of active pharmaceutical ingredient exported from India were retrieved from an online database. Estimated prices were compared with the lowest globally available prices for HIV/AIDS, tuberculosis (TB) and malaria medicines, and current prices in the UK, South Africa and India. RESULTS: The estimation formula had good predictive accuracy for HIV/AIDS, TB and malaria medicines. Estimated generic prices ranged from US$0.01 to US$1.45 per unit, with most in the lower end of this range. Lowest available prices were greater than estimated generic prices for 214/277 (77%) comparable items in the UK, 142/212 (67%) in South Africa and 118/298 (40%) in India. Lowest available prices were more than three times above estimated generic price for 47% of cases compared in the UK and 22% in South Africa. CONCLUSION: A wide range of medicines in the EML can be profitably manufactured at very low cost. Most EML medicines are sold in the UK and South Africa at prices significantly higher than those estimated from production costs. Generic price estimation and international price comparisons could empower government price negotiations and support cost-effectiveness calculations.