- Research
- Open access
- Published:
Trends in the availability and prices of quality-assured tuberculosis drugs: a systematic analysis of Global Drug Facility Product Catalogs from 2001 to 2024
Globalization and Health volume 20, Article number: 51 (2024)
Abstract
Background
The Global Drug Facility (GDF) of the Stop TB Partnership was launched in 2001 with the goal of increasing access to quality-assured tuberculosis (TB) drugs and products. We aimed to describe the TB drugs and prices available from the GDF over time and to assess trends.
Methods
We searched the internet, including an internet archive, for past and recent GDF Product Catalogs and extracted the listed TB drugs and prices. We calculated the lowest price for the most common drug formulations assuming drugs with similar active pharmaceutical ingredients (APIs) are substitutes for each other. We assessed time trends in the TB drugs and prices offered by the GDF in univariable regressions over the longest possible period.
Results
We identified 43 different GDF Product Catalogs published between November 2001 and May 2024. These product catalogs included 122 single medicines (31 APIs), 28 fixed-dose combinations (9 API combinations), and 8 patient kits (8 API regimens and other materials). The number of TB drugs listed in the GDF Product Catalog increased from 9 (8 APIs) to 55 (32 APIs). The price decreased for 17, increased for 19, and showed no trend for 12 APIs. The price of 15 (53.6%) of 28 APIs used against drug-resistant TB decreased, including the price of drugs used in new treatment regimens. The decreasing price trend was strongest for linezolid (-16.60 [95% CI: -26.35 to -6.85] percentage points [pp] per year), bedaquiline (-12.61 [95% CI: -18.00 to -7.22] pp per year), cycloserine (-11.20 [95% CI: -17.40 to -4.99] pp per year), pretomanid (-10.47 [95% CI: -15.06 to -5.89] pp per year), and rifapentine (-10.46 [95% CI: -12.86 to -8.06] pp per year). The prices of 16 (61.5%) of 23 APIs for standard drug-susceptible TB treatment increased, including rifampicin (23.70 [95% CI: 18.48 to 28.92] pp per year), isoniazid (20.95 [95% CI: 18.96 to 22.95] pp per year), ethambutol (9.85 [95% CI: 8.83 to 10.88] pp per year), and fixed-dose combinations thereof.
Conclusions
The number of TB drugs available from the GDF has substantially increased during its first 23 years of operation. The prices of most APIs for new TB treatments decreased or remained stable. The prices of most APIs for standard drug-sensitive TB treatment increased.
Introduction
With 1.3Â million deaths in 2022, an estimated incidence of 10.6Â million in 2022, and estimated donor support of $2.46Â billion in 2023, tuberculosis (TB) remains a major global public health concern [1, 2]. Resistance against first-line TB drugs is common and includes mono-resistant, poly-resistant, multidrug-resistant (MDR), and extensively drug-resistant (XDR) TB. Drug-resistant TB usually requires longer treatment with more drugs or newer TB drugs than the treatment of drug-susceptible TB. Drug-related costs are a major contributor to TB treatment costs, constituting, for instance, the largest or second largest cost component in cost-effectiveness analyses of MDR TB treatment in Peru, Estonia, Russia, and the Philippines [3]. In cost analyses of drug-susceptible TB treatment, TB drugs constituted 25% of overall treatment costs in low-income countries [4]. In addition to high drug costs, TB programs face issues of substandard and counterfeit TB drugs. An analysis from pharmacies in 17 low-income and middle-income countries showed that 9.1% of the analyzed rifampicin and isoniazid samples failed to meet basic quality targets [5]. Use of substandard and counterfeit TB drugs may cause adverse drug effects, TB treatment failure, aggravation of antimicrobial resistance, loss of confidence in national TB programs, and elevated costs for people with TB and TB programs [6].
To increase access to low-priced quality-assured TB drugs, the Global Drug Facility (GDF) was founded by the Stop TB Partnership in 2001 [7, 8]. The GDF provides procurement and supply services for TB drugs and diagnostics; it uses competitive bidding to pursue bulk purchases from TB drugs suppliers [7, 9, 10]. To ensure that the TB drugs available from the GDF meet World Health Organization (WHO) quality standards, the GDF established quality assurance standards and control systems [11]. Suppliers to the GDF generally need to provide drugs that are prequalified by the WHO or authorized by a stringent regulatory authority [12]. The GDF also aims at shaping the supply markets for TB products by increasing demand and decreasing risks for suppliers, by encouraging new manufacturers to enter the market, by facilitating innovation, and by lowering transaction costs [10]. The GDF’s market share varies across WHO regions [13] and was globally estimated at 42.9% for second-line tuberculosis drugs and 19.2% for first-line TB drugs in 2012 [14].
GDF products and prices are relevant for numerous national TB programs and are used in cost and cost-effectiveness analyses of TB care [15,16,17,18,19,20,21]. Despite the common use of GDF prices as reference prices, past GDF Product Catalogs, GDF products, or GDF prices have been neither comprehensively assembled nor systematically analyzed in the existing literature. Relatedly, the development of the availability and prices of TB drugs from the GDF over time has not been studied. We aimed to describe TB drugs and prices listed in the GDF Product Catalog from the launch of the GDF in 2001 until May 2024 and to assess time trends in the TB drugs and prices offered by the GDF.
Methods
Study design
First, we systematically searched for past GDF Product Catalogs and extracted their content. Second, we analyzed the TB drugs and prices listed in the GDF Product Catalogs for trends over the longest possible period. The reporting of information followed the Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER) [22].
Global Drug Facility Product Catalog
The GDF Product Catalog is a list of TB products available from the GDF for TB treatment in adults and children. In recent years, the GDF has separately published a ‘GDF Medicines Catalog’ and a ‘GDF Diagnostics, Medical Devices & Other Health Products Catalog’. Products are listed at their current purchase prices in US Dollar ($) unless noted otherwise. A unique price or a price range is provided in the catalog for most products. For some products, the prices and/or availability are only available upon request from the GDF. Discounts or donations are indicated where available (e.g., the Janssen-USAID Bedaquiline Donation Program [23]). Early GDF Product Catalogs were mostly published as a website. Later product catalogs were published as a PDF brochure on the GDF website. As the GDF Product Catalog was updated, past catalogs were no longer available through the GDF Product Catalog website [24].
Global Drug Facility product codes
The GDF uses product codes to uniquely identify TB drugs and other products. The product code of single medicines represents a combination of the drug abbreviation, dosage in milligram or gram, drug packaging, and the number of drug units per pack. The drug packaging can be either ampoule (A), bottle (BTL), blistered tablets or capsules (B), blistered dispersible tablets (B-DT), loose tablets or capsules in a jar, container, or bottle (L), vial (V), or sachet (S) (e.g., Rbt-150-(L)-100 for a jar with 100 capsules containing 150 mg rifabutin). Product codes of fixed-dose combinations (FDCs) can contain an additional prefix with the number of active ingredients in the drug (e.g., 4-FDC/RHZE-150/75/400/275-(B)-672 for a blister with 672 tablets combining rifampicin 150 mg, isoniazid 75 mg, pyrazinamide 400 mg, and ethambutol 275 mg). The product code of patient kits (PKs) combines a prefix and patient kit identifier (e.g., PK-Cat I & III-A). Drug and patient kit abbreviations used within the product code and patient kit contents are described in the supplementary Tables S1–S3.
Search strategy
We searched the internet archive ‘Wayback Machine’ (https://archive.org/) from inception to May 21, 2024, for five URLs that had been used to reference GDF Product Catalogs in publications or archived versions of the GDF website (https://web.archive.org/web/*/stoptb.org/gdf/drugsupply/drugs.available.html, https://web.archive.org/web/*/stoptb.org/gdf/drugsupply/drugs_available.asp, https://web.archive.org/web/*/stoptb.org/gdf/drugsupply/drugs_diagnostics.asp, https://web.archive.org/web/*/stoptb.org/gdf/drugsupply/product_catalog.asp, https://web.archive.org/web/*/stoptb.org/global-drug-facility-gdf/gdf-product-catalog). We usually screened four archived website copies per year during the period the respective URL was active to identify changes in the GDF Product Catalog. When possible, we screened the first archived copy in the first two quarters of each year and the last archived copy in the last two quarters. We included catalogs in this study that showed product or price updates. To identify GDF Product Catalog updates, we screened archived websites for changes in the displayed publication date, products, and prices and/or for changes in linked PDFs and embedded thumbnails of catalogs. We added GDF Product Catalogs to the internet archive search results that we had either previously downloaded from the GDF website and archived or that we identified through internet searches via Google or on the GDF website. The internet searches included the terms: Global Drug Facility, GDF, product catalogue, product catalog, medicines catalogue, and medicines catalog.
Data extraction
From the GDF Product Catalogs included in the study, we included single medicines, FDCs, and patient kits for adults and children. We excluded TB drugs for special purpose (e.g., GDF India Programme products) and non-pharmaceutical TB products if listed (e.g., syringes, water for injection, diagnostic supplies, or adherence technologies). For the single medicines, FDCs, and patient kits in each GDF Product Catalog, we extracted the product code, active pharmaceutical ingredient(s) (API[s]), drug dose, drug packaging, drug units per pack, and the price per pack. From catalogs published in 2018 or later, we also extracted drug usage information (drug-susceptible TB, drug-resistant TB, and TB preventive treatment that was also called treatment of latent TB infection). When no publication date was listed for a website update, we used the archiving date. When no publication month was listed for a PDF catalog, we extracted the creation date from the PDF-file’s metadata.
Data analysis
First, we summarize the product codes, which describe the API(s), dose, form, and units per pack, for all TB drugs listed in the identified GDF Product Catalogs. We further describe the number of times a drug was listed in the GDF Product Catalog, the number of listing changes, the last price at which a drug was available, the first and last year in which a TB drug was listed, and the years of the lowest and highest drug price. Second, we describe and assess how the number of drug products and APIs available from the GDF changed over time, grouping single medicines, FDCs, and patient kits. Third, we describe and assess how the price of the APIs of the TB drugs listed in the GDF Product Catalog developed over time based on calculating the lowest price-per-dose across TB drugs with the same API(s). We use GDF product codes and drug abbreviations when reporting results.
To assess linear time trends, we regressed the number of drugs and the nominal drug prices listed in the GDF Product Catalog on the publication date of the catalog from which data were extracted. The publication month was converted to a fraction of a year. We estimated univariable regression models with Huber-White robust standard errors and assessed trends for the longest observational period of each outcome. We also estimated the same regression models with drug prices adjusted to a January 2024 price level using the gross domestic product deflator for advanced economies from the International Monetary Fund (IMF) World Economic Outlook database [25]. We interpolated linearly between annual deflator values to obtain monthly deflator values (supplementary Fig. S1). For the number of products listed in the GDF Product Catalog, we performed a supplementary regression analysis comparing the fit of models with a linear time trend and a stepwise increase. When a GDF Product Catalog reported a price range, we used the lowest price in the regression analysis. Where drugs with the same API, API combination, or API regimen were listed in a product catalog in different doses, we calculated the price equivalent of the most listed drug for the regression analysis using the lowest price per dose of APIs available from the GDF in different pharmaceutical forms. For instance, different rifampicin (R) formulations like R-150-(B)-800 and R-300-(B)-100 were treated as perfect substitutes of each other.
Discounts listed in the GDF Product Catalog for certain orders (e.g., 20% free goods for each 10 packs of Bdq-100-(L)-188 ordered between 2020 and 2024) were included in the calculation of the lowest price. From April 2015 to March 2019, bedaquiline (Bdq) was available through the Bedaquiline Donation Program between the US Agency for International Development (USAID) and Janssen Therapeutics [23]. The Bdq-100-(L)-188 price of zero listed in the 2016 catalog was excluded from the descriptive statistics and regression analysis. Drug prices that were listed as upon request/contact GDF were also excluded from the analysis. We grouped drugs that differed only in their packaging (i.e., blister/loose and vial/ampoule) and patient kits Cat-II that differed by 4 units of streptomycin and/or 4 units of syringes and needles. We report monetary price changes in US-dollar ($) and percentage point (pp) price changes to allow for trend comparisons across APIs. To estimate changes in pp, prices were normalized such that the first listed price is 100. Occasionally, drug prices were listed in Euro or CHF. These prices were converted to US-Dollar using the IMF annual exchange rate for the respective years [26]. Statistical significance was assumed at P < 0.05. All analyses were performed in Stata 18.5 SE.
Results
Search results
We identified 318 copies of GDF Product Catalog subsites in the internet archive ‘Wayback Machine’. Based on screening 102 archived copies for changes in the listed publication date, products, prices, linked PDF catalog, or thumbnail image of a linked PDF catalog, we included 38 GDF Product Catalogs in the study. An additional 5 GDF Product Catalogs were added to the study from Google searches, GDF website searches, and self-archived PDF catalogs. Product catalogs were published as a website between 2001 and 2011 and as downloadable PDF brochures between 2011 and 2024. A ‘GDF Medicines Catalog’ and a ‘GDF Diagnostics, Medical Devices & Other Health Products Catalog’ were published as PDF brochures since 2016. No GDF Product Catalog updates could be found for the years 2012, 2013, 2015, and 2017. In other years, the number of catalog updates identified ranged from 1 to 6 per year (Fig. 1 and supplementary Table S4).
TB drugs available from the GDF
From 2001 to 2024, 122 single medicines, 28 FDCs, and 8 patient kits were listed in the GDF Product Catalog. Of these 158 drug products, 69 (43.7%) could be used against drug-susceptible TB, 127 (80.4%) against drug-resistant TB, and 21 (13.3%) for TB preventive treatment. The single medicines included 31 different APIs. The FDCs included 9 different API combinations. Patient kits were available for first-time treatment of drug-susceptible TB (Category I & III) and for recurrent TB treatment (Category II). The patient kits included 8 different API regimens and differed further by whether auto-disabling syringes were included or not (e.g., PK-Cat II-A1 versus II-A2).
Products were listed 1–42 times across the 43 GDF Product Catalogs included in the study. The median (IQR) number of products listed in the catalog was 27 (18–48) single medicines, 9 (8–11) FDCs, and 1 (1–7) patient kit. Between 2001 and 2024, we observed 413 changes in 1362 listings of single medicines, 176 changes in 431 listings of FDCs, and 57 changes in 117 listings of patient kits including listings of product prices or availability only upon request from the GDF (Table 1 and supplementary Tables S4, S5).
Trends in the available TB drugs
The number of TB drugs available from the GDF increased from 9 (8 APIs) in 2001 to 55 (32 APIs) in 2024. A peak was reached in 2016, when the GDF Product Catalog listed 70 drugs (38 APIs) and the largest selection of 58 single medicines (29 APIs) of all years. The number of FDCs peaked at 16 (6 APIs) in the years 2007 and 2008. The number of patient kits peaked at 7 between 2006 and 2010. Since 2018, only one patient kit has been listed in the product catalog. On average, the GDF Product Catalog contained 1.8 (95% CI: 1.4 to 2.1) more TB drugs per year. This increase was driven by the inclusion of 2.1 (95% CI: 1.9 to 2.3) additional single medicines per year and offset by reductions in the number of available FDC products (-0.2 [95% CI: -0.3 to -0.07] per year) and patient kits (-0.1 [95% CI: -0.2 to -0.03] per year) (Fig. 2 and supplementary Tables S4, S6).
As several TB drugs contain the same API(s) in different form, similar but less pronounced trends occurred for the number of APIs available from the GDF. The peak number of APIs listed in the GDF Product Catalogs was 29 (58 drugs) in 2016 for single medicines, 7 (7–10 drugs) in 2016 and from the end of 2020 to 2024 for FDCs, and 7 (7 drug regimens) from mid-2006 to 2010 for patient kits. The number of APIs available from the GDF increased on average by 1.1 (95% CI: 0.9 to 1.3) per year, resulting from increases in the APIs available as single medicines (0.1 [95% CI: 0.08 to 0.12] per year) as well as FDCs (0.1 [95% CI: 0.08 to 0.12] per year). The number of API combinations available as FDCs had an increasing trend despite a decreasing time trend in the number of FDC drugs (Fig. 2 and supplementary Tables S4, S6).
Specifying a stepwise change for the periods 2001–2006, 2007–2013, and 2014–2024 rather than a continuous time trend in the regression model explained more variation in the data. The average number of TB drugs listed in the GDF Product Catalog was, for instance, estimated at 17.3 (95% CI: 14.8 to 19.8) in the period 2001–2006, 43.8 (95% CI: 41.9 to 45.7) in the period 2007–2013, and 56.8 (95% CI: 54.5 to 59.1) in the period 2014–2024 (Wald-test P < 0.001) (supplementary Table S6).
TB drug prices of the GDF
Drug product prices ranged from $0.66 to $1700 per pack of single medicines, from $1.33 to $99 per pack of FDCs, and from $11.56 to $98.90 per patient kit. The median (IQR) of the lowest prices from 2001 to 2024 was $13.38 (6.82–33) for single medicines, $21.96 (11.77–31.78) for FDCs, and $31.52 (21.50–54.21) for patient kits. The drug bedaquiline (Bdq) was listed at no purchasing cost in the 2016 product catalog due to a donation program available at the time. Prices including the bedaquiline donation price of zero were provided for 1651 (86.4%) of 1910 product listings. Price changes occurred in 646 (33.8%) of 1910 product listings. No prices were ever listed for 17 (9.8%) of 173 products in the GDF Product Catalog (Table 1 and supplementary Table S5).
Trends in TB drug prices
Single medicines
We estimated significant price trends for 22 (71.0%) of the 31 APIs in the single medicines of the GDF Product Catalog. There was no unique price trend across single medicines. The price of 16 APIs decreased on average over time. The price of 6 APIs increased. The price of 9 APIs showed no trend. The five largest nominal price decreases were on average all larger than 10 pp per year (95% CI-bounds ranging from -26.35 to -4.99) and occurred for linezolid (Lzd), bedaquiline (Bdq), cycloserine (Cs), pretomanid (Pa), and rifapentine (Rpt). Average price increases were between 1.97 (95% CI: 1.58 to 2.36) to 45.15 (95% CI: 39.99 to 50.31) pp per year. The APIs with an increasing price trend were streptomycin (S), rifampicin (R), isoniazid (H), PAS sodium (PAS-[Na]), ethambutol (E), and pyrazinamide (Z). In monetary terms, the price trends of single medicines correspond to price decreases between -$0.08 (95% CI: -0.11 to -0.05) for Pyr(B6)-100-(L)-250 and -$50.43 (95% CI: -72.00 to -28.87) for Bdq-100-(L)-188 per year. Increasing price trend estimates were between $0.17 (95% CI: 0.13 to 0.20) for Z-400-(B)-672 and $1.76 (95% CI: 1.11 to 2.42) for PAS-(Na)-4-(S)-25 per year (Table 2, Fig. 3 and supplementary Fig. S2 blue plots).
Fixed-dose combinations
FDC tablets combined between 2 and 4 APIs, mostly consisting of rifampicin (R), isoniazid (H), pyrazinamide (Z), and/or ethambutol (E). FDCs of isoniazid, pyridoxine hydrochloride, sulfamethoxazole, and trimethoprim (HPST) and of rifapentine and isoniazid (3-HP) for TB preventive treatment became available in 2018 and 2020, respectively. We estimated price trends for 8 (88.9%) of the 9 API combinations used in FDCs. Only the price of 3-HP-300/300-(B)-36 had a decreasing trend (-10.49 [95% CI: -17.35 to -3.62] pp per year). Prices increased on average between 3.22 (95% CI: 1.31 to 5.14) and 37.94 (95% CI: 32.87 to 43.01) pp per year for HPST and most FDCs of EH, RH, RHZ, RHE. In monetary terms, the price of 3-HP-300/300-(B)-36 decreased on average by -$1.57 (95% CI: -2.60 to -0.54) per year. In monetary terms, the increasing price trends were between $0.06 (95% CI: 0.03 to 0.10) for HPST-Q-TIB-(L)-30 and $1.81 (95% CI: 0.23 to 3.39) for RH-150/150-(B)-672 per year and product (Table 2, Fig. 4 and supplementary Fig. S3 blue plots).
Patient kits
The price increased for 6 (75.0%) of 8 patient kits (PK-Cat I & III-A/B and PK-Cat II-A/B), showed no trend for 1 patient kit (PK-Cat I & III-C), and could not be estimated for another patient kit that was only listed once (PK-Cat II-C). The average price increase over the listing period ranged from 4.61 (95% CI: 1.98 to 7.24) pp per year for PK-Cat I & III-B to 11.09 (95% CI: 7.78 to 14.39) pp per year for PK-Cat II-A1. For PK-Cat I & III-A, which was available longest and the only patient kit in the 2024 GDF Product Catalog, the price increased on average by $0.83 (95% CI: 0.72 to 0.95) per year. This was the lowest significant price trend for patient kits. The steepest price trend was an additional $5.39 (95% CI: 4.01 to 6.77) per year for PK-Cat II-B1 (Table 2, Fig. 5 and supplementary Fig. S4 blue plots).
Adjustment for price level changes
Adjusting GDF Product Catalog prices for gross domestic product deflation in advanced economies caused more pronounced price decreases and less pronounced price increases. Adjusting the price of single medicines resulted in estimating additional decreasing price trends for Dlm-50-(B)-672 and Imp/Cls-500/500-(V)-10. In addition, the deflated price of Z-400-(B)-672 ceased to have an increasing trend. Deflation adjustment of FDC prices eliminated the increasing price trend for HPST-Q-TIB-(L)-30. The significance of the price trends of patient kits was not affected by the price adjustment for deflation (Table 2, Fig. 3–5 and supplementary Fig. S2–S4 light blue plots).
Discussion
Summary of findings
This study described the availability and prices of single medicines, FDCs, and patient kits from the GDF, a major global supplier of TB drugs, and assessed time trends. The number of single medicines available from the GDF substantially increased between 2001 and 2024. Despite a decreasing number of FDCs and patient kits, more API combinations became available from the GDF as FDCs for TB preventive treatment were added to the product catalog. The lowest price of 16 APIs available as single medicines, 1 FDC, and no patient kit decreased over the period for which we had price information. An increasing price trend was estimated for 6 APIs available as single medicines, 7 API combinations available as FDCs, and 6 API regimens available as patient kits. Price adjustment resulted in estimating a decreasing price trend for 19 instead of 17 APIs and estimating an increasing price trend for 17 instead of 19 APIs. Price increases concentrated on the APIs of single medicines and FDCs used in the standard 6-month drug-susceptible TB treatment. The prices of several APIs used in new regimens against drug-resistant TB showed a decreasing trend. Price trends were mixed for APIs of single medicines and FDCs used in TB preventive treatment.
Drug supply and prices by the Global Drug Facility
Availability of and access to quality-assured medicines are key components of TB control [2, 27]. The promotion of FDC tablets as a replacement for single medicines in TB control programs and their addition to national essential medicines lists were among the early priorities of the GDF [28]. In line with evolving needs and opportunities [29,30,31], the GDF Product Catalog expanded over time by listing several new drug products, including drugs in different dosage, packaging, and form. To purchase quality-assured TB drugs at competitive prices, the GDF pools demand and uses tendering among pre-qualified manufactures [7, 13]. In the past, prices for first-line and second-line TB drugs procured through the GDF were lower compared to the private market [14] or international tenders [7] and decreased in a short-term comparison for selected second-line TB drugs [32]. Our analysis showed that the GDF offered several APIs at prices that remained stable or decreased over the past two decades.
Prices of drugs for BPaL and BPaLM regimens
The APIs with a decreasing price trend in our analysis include bedaquiline, linezolid, moxifloxacin, and pretomanid. All of them are used for drug-resistant TB treatment in some of the newest drug regimens. A short oral regimen of bedaquiline, pretomanid, and linezolid (BPaL) regimen was assessed in the Nix-TB study and included in the WHO guidelines for the treatment of drug-resistant TB in 2020 [33, 34]. The subsequent ZeNix trial found a BPaL regimen with a reduced linezolid (Lzd) dose of 600 mg instead of 1200 mg daily favorable [35]. The recently published TB-PRACTECAL trial favored a BPaLM (BPaL plus moxifloxacin) regimen over the local standard of care and also showed the high efficacy of the BPaL regimen with a reduced linezolid dose [36, 37]. The BPaLM and, alternatively, the BPaL regimen with a reduced dose of linezolid were included in WHO’s most recent 2022 guideline update [38, 39]. Given the positive treatment outcomes and substantially shortened treatment times, TB programs may increasingly need stable access to quality-assured bedaquiline, pretomanid, linezolid, and moxifloxacin.
The prices of bedaquiline, pretomanid, and linezolid decreased on average by 10.5 to 16.6 pp per year in our analysis. After the Janssen-USAID Bedaquiline Donation Program ended in early 2019 [23], the price of a pack 188 tablets bedaquiline (Bdq) 10 mg increased to $400 in the GDF Product Catalog. This price fell to $340 (plus a 20% free goods for each 10 packs ordered) in 2020. The price fell further to $244.40 (plus a 50% free goods for each 2 packs ordered) in 2023 and has been directly listed as $122.20 since the October 2023 GDF Product Catalog update. Twenty-six tablets pretomanid (Pa) 200 mg were mostly available for a price of $52 from 2019 to 2022. Their price decreased to $34.29 in the end of 2022 and to $33.95 since 2023. The price of dose equivalent of 100 tablets linezolid (Lzd) 600 mg had the strongest decreasing trend in the study. Their price decreased from $69.00 in 2014, after a jump to $137.90 in 2016, to $17.03 since the end of 2022. The price of 100 tablets moxifloxacin (Mfx) 400 mg decreased from $168 in 2011, to $64.51 in 2014, to a price between $15 and $16.90 since 2019. Considering the large cost contributions of pretomanid and bedaquiline to the price of BPaL and BPaLM regimens [15, 20], falling prices for these drugs contribute to substantial cost savings in TB treatment with BPaL and BPaLM regimens.
Prices of drugs for drug-susceptible TB regimens
We found increasing price trends for all four APIs of the single medicines used in standard 6-month drug-susceptible TB treatment, namely for rifampicin (R), isoniazid (H), pyrazinamide (Z), and ethambutol (E). We also observed increasing price trends in the FDCs used in the intensive phase and continuation phase of standard drug-susceptible TB treatment. The price of the dose equivalent of 672 tablets RHZE in a 150 mg/75 mg/400 mg/275 mg ratio used during the intensive treatment phase increased from $20.50 in 2002 to $40.06 in 2018 and to $62.90 since the end of 2022. The price of the dose equivalent of 672 FDC tablets RH in a 150 mg/75 mg ratio used during the continuation phase increased from $7.19 in 2002 to $31.78 since the end of 2022. Although drug-susceptible TB drug regimen cost less than drug-resistant TB drug regimens [15], increasing prices for drugs used in drug-susceptible TB treatment could increase funding needs in TB care as drug-susceptible TB is more common than drug-resistant TB. The estimated 2022 global incidence of drug-resistant TB was 5.2 (95% uncertainty interval: 4.7 to 5.7) per 100,000 as compared to a total TB incidence of 133 (95% uncertainty interval: 124 to 143) per 100,000 [40].
The TBTC Study 31/A5349 showed that a 4-month regimen of rifapentine, moxifloxacin, isoniazid, and pyrazinamide was non-inferior to the standard 6-month drug regimen [41]. Since 2022, this new regimen has been included in the WHO recommendations for drug-susceptible TB treatment [39]. Contrary to the increasing price trends for most APIs used in the standard 6-month regimen against drug-susceptible TB, key APIs for the newer 4-month regimen have become available at lower prices from the GDF. A pack of 24 tablets rifapentine (Rpt)Â 150Â mg was first listed in the GDF Product Catalog in 2016 with a price of $24 and has been available from the GDF at a price between $3.31 and $5.25 since 2020. Price reductions for rifapentine and moxifloxacin contribute to decreasing the costs of the 4-month drug-susceptible TB regimen.
Prices of drugs for TB preventive treatment
For TB preventive treatment, WHO guidelines recommend a monotherapy of daily isoniazid for 6 or 9 months, a combination of weekly rifapentine and isoniazid for 3 months, a combination of daily isoniazid and rifampicin for 3 months, or a monotherapy of daily rifampicin for 4 months [42, 43]. Based on the BRIEF TB/A5279 Study [44], the 2020 WHO guideline update further recommended 1 month of daily rifapentine and isoniazid for TB preventive treatment [42]. In 2022, 1–3-month drug regimens were provided to 0.6 million out of 3.8 million people receiving TB preventive treatment, compared to 0.19 million out of 2.9 million people in 2021 [2]. The dose equivalent of 672 tablets isoniazid (H) 300 mg had an increasing trend from $2.45 in 2002 to a price between $11.48 and $13.52 since 2011. We also found trends for increasing prices for the dose-equivalent of 100 tablets of rifampicin (R) 300 mg, which could be obtained for $7.30 in 2016 and $19.33 since the end of 2022. Further, the prices of three different FDC tablets containing isoniazid and rifampicin and the price a FDC of isoniazid, pyridoxine hydrochloride, sulfamethoxazole, and trimethoprim (HPST), which is used for TB preventive treatment in adults living with HIV, increased. In turn, we found decreasing price trends for rifapentine and the FDC of isoniazid and rifapentine (HP). The price of 36 tablets 3-HP in a 300/300 ratio cost $15 in 2020 and $9.99 since the second half of 2023. As a result of these drug price trends, the prices of newer and older regimens are converging. This may contribute to the adoption of new rifapentine-based drug regimens in favor of other options for TB preventive treatment, which aligns with WHO’s recommendation to expand 1–3-month rifapentine/rifampicin-based drug regimens [2].
Implication of trends in drug prices for TB programs
With $5.8Â billion in 2022, funding for TB care in low- and middle-income countries reached 44% of its $13Â billion target [2]. Considering this funding gap and the large contribution of TB drug prices to TB program costs [3, 4], drug price variations may have a profound impact on the number of people with TB that can receive treatment and on the TB drug regimens offered by TB programs. Decreasing prices for key drugs of new and shorter drug regimens for MDR-TB and drug-susceptible TB, such as bedaquiline, pretomanid, linezolid, moxifloxacin, and rifapentine, may facilitate the rollout of newer and shorter drug regimens. Increasing prices of drugs used in the 6-month drug-susceptible TB treatment may increase the funding needs of TB programs. In turn, a decreasing rifapentine price might facilitate the adoption of a rifapentine-based 4-month drug-susceptible TB regimen. To the extent that the presented findings are indicative of robust trends, this study can help TB programs optimize their choice of drug regimens considering treatment effectiveness, drug costs, and drug price trends.
Strengths and limitations
This study is based on a comprehensive internet search through which past and recent GDF Product Catalogs were identified. Study limitations include, first, that the availability and prices of drug products were assessed based on product catalog entries, not GDF confirmed availability or actual purchases. Second, identified GDF Product Catalogs remain an incomplete subset of GDF drug products and prices. Third, drug prices that were only available through contacting the GDF were excluded from analysis. Fourth, price trends were assessed based on the lowest price per dose of an API. Reducing 158 TB drugs listed in GDF Product Catalogs to 48 APIs, API combinations, and API regimens facilitated the price comparison of drug products over time and provided a benchmark for the lowest price of an API. However, focusing on the lowest GDF prices of APIs assumed that drugs with the same API(s) can be arbitrarily multiplied or divided and substituted irrespective of their pharmaceutical form and packaging. This lowest price benchmark may not reflect the prices at which TB programs purchase a range of drugs with the same API(s) from the GDF. Fifth, we assessed a uniform linear trend over the longest period for which data was available even if some data plots suggested a low model fit.
Additional aspects to consider are that different drugs were available at different times and for different periods such that trend comparisons can have different reference periods. Inflation adjustment was based on the GDP deflator for advanced economics. While this might be a reasonable approximation for TB programs supported by donors, the purchasing power changes for specific countries could differ. Further, we analyzed prices at which TB programs could purchase TB drugs from the GDF, but these prices exclude additional import costs TB programs incur to provide drugs at the point of care [45]. Finally, we estimated trends in GDF prices without assessing underlying causes. How drug patents, production costs, new treatment guidelines, advocacy work, or the GDF as a major purchaser affect drug prices therefore remained unexplored in this study.
Conclusions
TB programs benefit from a stable supply of low-priced quality-assured drugs and often procure through the GDF. We compiled GDF Product Catalogs since the GDF was launched in 2001 and assessed over 20 years of TB drug availability and price data. In line with growing pharmaceutical needs and opportunities in TB treatment, the number of single medicines listed in GDF Product Catalogs increased substantially over time. There was no unique price trend across the APIs available from the GDF in various drug forms. We found price increases for drugs used in standard 6-month drug-susceptible TB treatment and price reductions for drugs that are part of new drug-susceptible TB, drug-resistant TB, and TB preventive treatments, namely bedaquiline, pretomanid, linezolid, moxifloxacin, and rifapentine.
Data availability
The data and code that support the findings of this study are openly available in heiDATA at https://doi.org/10.11588/data/PIKWU6.
References
Institute for Health Metrics and Evaluation. Health focus areas of development assistance for health. 2024 [cited 2024 May 21]; https://ihmeuw.org/6f9x
World Health Organization. Global Tuberculosis Report 2023. Geneva: World Health Organization; 2023.
Fitzpatrick C, Floyd K. A systematic review of the cost and cost effectiveness of treatment for multidrug-resistant tuberculosis. PharmacoEconomics. 2012;30(1):63–80.
Laurence YV, Griffiths UK, Vassall A. Costs to health services and the patient of treating tuberculosis: a systematic literature review. PharmacoEconomics. 2015;33(9):939–55.
Bate R, et al. Substandard and falsified anti-tuberculosis drugs: a preliminary field analysis. Int J Tuberc Lung Dis. 2013;17(3):308–11.
World Health Organization. A study on the public health and socioeconomic impact of substandard and falsified medical products. Geneva: World Health Organization; 2017.
Kumaresan J, et al. The global TB drug facility: innovative global procurement. Int J Tuberculosis Lung Disease. 2004;8(1):130–8.
Parmaksiz K, van de Bovenkamp H, Bal R. Does structural form matter? A comparative analysis of pooled procurement mechanisms for health commodities. Global Health. 2023;19(1):90.
Global Drug Facility. Increasing global access to quality-assured TB treatments and diagnostics. 2023 [cited 2024 May 21]; https://www.stoptb.org/facilitate-access-to-tb-drugs-diagnostics/global-drug-facility-gdf.
Global Drug Facility. Market & partner coordination. 2023 [cited 2024 May 21]; https://www.stoptb.org/global-drug-facility-gdf/market-partner-coordination.
Hauk C, et al. Quality assurance in anti-tuberculosis drug procurement by the Stop TB Partnership—Global Drug Facility: procedures, costs, time requirements, and comparison of assay and dissolution results by manufacturers and by external analysis. PLoS ONE. 2020;15(12):e0243428.
Global Drug Facility. GDF Quality Assurance (QA) Policy for TB products. Geneva: Global Drug Facility; 2022.
Arinaminpathy N, et al. The Global Drug Facility and its role in the market for tuberculosis drugs. Lancet. 2013;382(9901):1373–9.
Arinaminpathy N, et al. The Global Drug Facility as an intervention in the market for tuberculosis drugs. Bull World Health Organ. 2015;93(4):237–A248.
Kohler S, et al. The contribution of drug import to the cost of tuberculosis treatment: a cost analysis of longer, shorter, and short drug regimens for Karakalpakstan, Uzbekistan. PLOS Global Public Health. 2022;2(8):e0000567.
Kohler S et al. Costs and import costs of past, present, and future TB drug regimens: a case study for Karakalpakstan, Uzbekistan. J Public Health. 2023;45(2):481–7
Kohler S, et al. Programme costs of longer and shorter tuberculosis drug regimens and drug import: a modelling study for Karakalpakstan, Uzbekistan. ERJ Open Res. 2022;8(1):00622–2021.
Médecins Sans Frontières Access Campaign. DR-TB drugs under the microscope 2022; 8th edition; Pricing and patent landscape of medicines for adults and children. Geneva: Médecins Sans Frontières Access Campaign; 2022.
Gunther G, et al. Availability and costs of medicines for the treatment of tuberculosis in Europe. Clin Microbiol Infect. 2023;29(1):77–84.
Mulder C et al. Budgetary impact of using BPaL for treating extensively drug-resistant tuberculosis. BMJ Glob Health, 2022. 7(1):e007182.
Stop TB Partnership. The global plan to end TB 2023–2030. Geneva: Stop TB Partnership; 2022.
Stevens GA, Alkema L, Black RE, Boerma JT, Collins GS, Ezzati M, et al. Guidelines for accurate and transparent health estimates reporting: the gather statement. Lancet. 2016;388(10062):e19-e23. https://doi.org/10.1016/S0140-6736(16)30388-9
Rutta E, Kambili C, Mukadi Y. The Bedaquiline Donation Program: progress and lessons learned after 4 years of implementation. Int J Tuberc Lung Dis. 2020;24(10):1039–45.
Stop TB Partnership. Global Drug Facility (GDF): GDF Product Catalog. 2022 [cited 2024 May 21]; https://www.stoptb.org/global-drug-facility-gdf/gdf-product-catalog.
International Monetary Fund. World economic outlook database: October 2023. 2023 [cited 2024 May 21]; https://www.imf.org/en/Publications/WEO/weo-database/2023/October/download-entire-database.
International Monetary Fund. Official exchange rate (LCU per US$, period average) - Euro area. 2023 [cited 2024 January 20]; https://data.worldbank.org/indicator/PA.NUS.FCRF?locations=XC-CH.
Dartois VA, Rubin EJ. Anti-tuberculosis treatment strategies and drug development: challenges and priorities. Nat Rev Microbiol. 2022;20(11):685–701.
WHO Communicable Diseases Cluster. Fixed-dose combination tablets for the treatment of tuberculosis: report of an informal meeting held in Geneva Tuesday, 27 April 1999. Geneva: World Health Organization; 1999.
Dye C, et al. Evolution of tuberculosis control and prospects for reducing tuberculosis incidence, prevalence, and deaths globally. JAMA. 2005;293(22):2767–75.
Matteelli A, et al. Programmatic management of tuberculosis preventive therapy: past, present, future. Int J Infect Dis. 2023;130(Suppl 1):S43–6.
World Health Organization. Improving TB drug management: accelerating DOTS expansion. Geneva: World Health Organization; 2002.
Lunte K, Cordier-Lassalle T, Keravec J. Reducing the price of treatment for multidrug-resistant tuberculosis through the Global Drug Facility. Bull World Health Organ. 2015;93(4):279–82.
World Health Organization. WHO operational handbook on tuberculosis. Module 4: Treatment. Drug-resistant tuberculosis treatment. Geneva: World Health Organization; 2020.
Conradie F, et al. Treatment of highly drug-resistant pulmonary tuberculosis. N Engl J Med. 2020;382(10):893–902.
Conradie F, et al. Bedaquiline–pretomanid–linezolid regimens for drug-resistant tuberculosis. N Engl J Med. 2022;387(9):810–23.
Nyang’wa B-T, et al. A 24-week, all-oral regimen for rifampin-resistant tuberculosis. N Engl J Med. 2022;387(25):2331–43.
Nyang'wa B-T, et al. Short oral regimens for pulmonary rifampicin-resistant tuberculosis(TB-PRACTECAL): an open-label, randomised, controlled, phase 2B-3, multi-arm, multicentre, non-inferiority trial. Lancet Respir Med. 2024;12(2):117–28.
World Health Organization. WHO operational handbook on tuberculosis. Module 4: Treatment. Drug-resistant tuberculosis treatment. 2022 update. Geneva: World Health Organization; 2022.
World Health Organization. WHO consolidated guidelines on tuberculosis. Module 4: Treatment. Drug-resistant tuberculosis treatment. 2022 update. Geneva: World Health Organization; 2022.
World Health Organization. Tuberculosis profile: Global. Estimates of TB burden, 2022. [cited 2024 May 21]; https://worldhealthorg.shinyapps.io/tb_profiles/.
Dorman SE, et al. Four-month rifapentine regimens with or without moxifloxacin for tuberculosis. N Engl J Med. 2021;384(18):1705–18.
World Health Organization. WHO consolidated guidelines on tuberculosis. Module 1: Prevention. Tuberculosis preventive treatment. Geneva: World Health Organization; 2020.
World Health Organization. Latent tuberculosis infection: updated and consolidated guidelines for programmatic management. Geneva: World Health Organization; 2018.
Swindells S, et al. One month of rifapentine plus isoniazid to prevent HIV-related tuberculosis. N Engl J Med. 2019;380(11):1001–11.
Kohler S, Sitali N, Paul N. A framework for assessing import costs of medical supplies and results for a tuberculosis program in Karakalpakstan, Uzbekistan. Health Data Science; 2021.
Acknowledgements
We acknowledge financial support from the Open Access Publication Fund of Charité – Universitätsmedizin Berlin.
Funding
Not applicable.
Open Access funding enabled and organized by Projekt DEAL.
Author information
Authors and Affiliations
Contributions
SK conceived the study and analyzed the data. SK and NP interpreted data and wrote the manuscript. All authors provided critical feedback and approved the manuscript.
Corresponding author
Ethics declarations
Ethics approval and consent to participate
Ethics approval and consent to participate were not sought as this study used secondary data.
Consent for publication
Consent for publication was not sought as this study used no personal data.
Competing interests
The authors declare that they have no competing interests.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
About this article
Cite this article
Kohler, S., Achar, J., Mulder, C. et al. Trends in the availability and prices of quality-assured tuberculosis drugs: a systematic analysis of Global Drug Facility Product Catalogs from 2001 to 2024. Global Health 20, 51 (2024). https://doi.org/10.1186/s12992-024-01047-7
Received:
Accepted:
Published:
DOI: https://doi.org/10.1186/s12992-024-01047-7