Abstract
Background
Substandard and falsified (S&F) antimalarial medicines undermine malaria control efforts across sub-Saharan Africa, with an estimated 19% of antimalarials failing to meet quality standards and contributing to 40,000–160,000 preventable deaths annually. ACTs, particularly artemether-lumefantrine (AL), are the cornerstone of malaria treatment, yet their effectiveness is threatened by poor pharmaceutical quality and emerging drug resistance. This study evaluated the pharmaceutical quality of AL circulating in Rwanda's public health supply chain to assess compliance with international pharmacopeial standards.
Methods
A cross-sectional survey was conducted in February 2023 across eight districts representing all five provinces of Rwanda and encompassing both high- and low-malaria transmission settings. A total of 19 samples (3588 AL tablets) were sampled from three supply chain levels: Rwanda Medical Supply (RMS) headquarters and district branches, health centers, and Community Health Workers. Samples underwent comprehensive quality testing at a WHO-recognized laboratory, including visual inspection, tablet weight determination, high-performance liquid chromatography (HPLC) assay for artemether and lumefantrine content (acceptance range: 95.0–105.0%), and dissolution testing using pharmacopeial methods. The study followed Medicine Quality Assessment Reporting Guidelines (MEDQUARG) guidelines for medicine quality surveillance.
Results
All 19 samples (3588 tablets, 100%) met international pharmacopeial quality standards across all testing parameters. Visual inspection revealed no packaging defects, labeling errors, or tablet abnormalities. Tablet weight uniformity complied with specifications for both dispersible tablets (mean: 356.27 mg; range: 355.04–357.65 mg; specification: 339.50–360.50 mg) and regular tablets (mean: 241.63 mg; range: 239.79–242.72 mg). Artemether assay values ranged from 97.3 to 99.4% (mean: 98.7%), while lumefantrine ranged from 97.3 to 104.3% (mean: 99.2%), with all samples meeting the 95.0–105.0% acceptance criteria. Dissolution testing demonstrated 100% compliance for both active pharmaceutical ingredients across all samples.
Conclusions
All AL samples met international quality standards, contrasting with sub-Saharan Africa's 19% failure rate. Rwanda's centralized procurement, regulatory oversight, and WHO-prequalified sourcing demonstrate a replicable model for ensuring antimalarial quality and combating drug resistance.
Keywords: Malaria, Artemether-lumefantrine, Antimalarial drug quality, Substandard medicines, Falsified medicines, Rwanda, Artemisinin-based combination therapy, Pharmaceutical quality assurance, MEDQUARG
Background
Malaria remains a leading cause of morbidity and mortality in Africa, with sub-Saharan Africa accounting for the majority of the world's malaria cases and deaths. Children under five bear a disproportionate burden, making malaria a major public health challenge [1]. Despite the scale-up of vector control, diagnostics, and ACTs, the fight against malaria resistance is increasingly undermined by the circulation of S&F antimalarial medicines, which are widespread throughout the African continent [2–4].
Recent reviews of antimalarial drug quality across Africa have reported alarming trends: approximately 35% of antimalarial samples obtained from 21 African countries failed chemical analysis, highlighting poor quality control in both private and public supply chains [5]. Meanwhile, estimates suggest that 19% of antimalarials circulating in sub-Saharan Africa are substandard or falsified, contributing to 40,000–160,000 avoidable deaths annually, primarily among young children [3, 6]. In several African countries, including Nigeria, Kenya, DR Congo, Uganda, Benin, and Madagascar, non-quality-assured ACTs have been detected at significant levels, threatening both individual patient outcomes and community-level malaria control [5]. More recent post-market surveillance evidence from East Africa further reinforces these concerns. A systematic review of antimalarial drug quality in East Africa found that approximately 19.7% of tested samples failed at least one quality control parameter, with dissolution failure the most frequently recorded deficiency, followed by sub-therapeutic API content [7]. A separate systematic review of antimicrobials across selected East African countries reported a 24% failure rate specifically for antimalarial medicines, with API content being the most commonly examined and failing parameter [8]. A comprehensive five-year national post-market surveillance programme across 15 regions in Tanzania (2019–2023) confirmed that, while sampled products met assay and dissolution specifications, over half failed product information review due to incomplete package labelling, demonstrating that quality gaps persist even in better-regulated systems [9]. In Uganda, where artemisinin partial resistance is now confirmed, 18.9% of AL samples tested were substandard, predominantly due to sub-therapeutic artemether content [10]. Most recently, a 2025 systematic review of ACT quality, clinical efficacy, and regulatory progress across East Africa found that 11.2% of ACT samples were of poor quality, while also documenting the concurrent threats of emerging artemisinin partial resistance and weak regulatory enforcement as compounding risks for malaria control in the region [11].
The problem is compounded by an active market for falsified and degraded artemisinin derivatives, with studies documenting falsified artesunate and amodiaquine-based therapies manufactured with sub-therapeutic active ingredients or unexpected adulterants across at least eight African countries [12, 13]. Such medicines expose malaria parasites to sub-lethal drug concentrations, a major driver of the emergence and spread of antimalarial drug resistance [8]. In addition, Africa is already facing early signals of artemisinin-resistant Plasmodium falciparum, which has profound implications for ACT effectiveness [14].
High rates of S&F antimalarials are fueled by structural weaknesses: inadequate regulatory enforcement, porous distribution networks, widespread informal drug markets, and limited quality assurance capacity [10]. This context underscores the need for standardized, transparent medicine quality surveillance, as prescribed by the World Health Organization (WHO) and MEDQUARG guidelines, which aim to harmonize field surveys and strengthen public health impact [15].
Rwanda provides an important and underexplored context for antimalarial quality surveillance. Malaria remains a significant public health burden in Rwanda, although the country has made substantial progress. Between 2019 and 2023, Rwanda reduced its malaria caseload by approximately 85%, from an estimated 4.9 million cases to approximately 749,000, representing one of the most dramatic reductions in the WHO African Region [1]. Reported malaria incidence declined from 76 to 47 per 1000 population at risk in fiscal year 2022–2023, with the slide positivity rate falling from 22 to 14% over the same period [16]. These gains reflect sustained investment in vector control (insecticide-treated nets and indoor residual spraying), universal access to rapid diagnostic testing, and prompt treatment with ACTs [17]. AL is the nationally recommended first-line treatment for uncomplicated Plasmodium falciparum malaria in Rwanda, consistent with WHO guidelines and prescribed across all levels of the public health system from community health workers to district hospitals [17]. Dihydroartemisinin-piperaquine serves as a second-line therapy, while injectable artesunate is reserved for severe malaria cases.
Despite this well-established treatment policy framework, concerns about medicine quality cannot be assumed away. Reports of substandard or falsified antimalarials within Rwanda’s public supply chain have historically been rare, owing in part to centralized procurement through Rwanda Medical Supply (RMS), which sources exclusively from WHO-prequalified manufacturers. However, a multi-country survey that included Rwanda, conducted as part of the ACT Consortium drug quality programme and reporting results from six malaria-endemic countries, detected substandard ACTs in all sampled countries, including substandard artemisinin-based combination samples in Rwanda’s private sector [18]. This underscores that even well-regulated national systems are not entirely insulated from quality risks, particularly at the market periphery. The rationale for selecting AL as the focus of this quality surveillance study is therefore threefold: its status as Rwanda’s first-line antimalarial, its widespread procurement and distribution across all supply chain levels, and its critical role in a context where artemisinin partial resistance is now an emerging concern in Rwanda and the broader East African region [14, 19].
Building on this rationale, the present study evaluates the pharmaceutical quality of AL circulating in Rwanda’s public health supply chain, assessing assay content, dissolution performance, and physical characteristics across multiple districts and supply chain levels, to contribute robust national evidence and inform malaria control policy in Rwanda and the wider East African region.
Methods
Study design and setting
This cross-sectional study evaluated the pharmaceutical quality of AL circulating in Rwanda's public health supply chain and was conducted within the policy framework of the Rwanda Extended Malaria Strategic Plan 2020–2024, which mandates routine quality surveillance of antimalarial medicines to preserve therapeutic efficacy [17].
Sample collection was performed in February 2023 across eight Rwandan districts representing all five provinces, selected to provide adequate geographic coverage and to include both high- and low-malaria-transmission settings. High-transmission districts included Nyagatare, Kirehe, Gisagara, Rusizi, Gicumbi, and Gasabo; low-transmission districts included Rubavu and Ruhango, as classified by the Rwanda National Malaria Strategic Plan 2020–2024 [17]. The sampling frame encompassed the RMS headquarters and district branches, public health centers, and Community Health Workers (CHWs), reflecting major access pathways through which AL reaches patients in Rwanda.
Rwanda’s antimalarial supply chain is governed by a centralized procurement and distribution model overseen by two principal institutions: Rwanda Medical Supply (RMS) and the Rwanda Food and Drug Authority (Rwanda FDA). RMS is the designated national procurement agency responsible for quantifying, procuring, storing, and distributing all essential medicines in the public health system, including AL. Procurement is conducted exclusively from manufacturers holding WHO Prequalification status, a prerequisite that provides assurance of manufacturing quality and compliance with Good Manufacturing Practice (GMP) standards [20]. Once procured, AL products are imported by air or sea freight under temperature-controlled or ambient conditions as specified in the manufacturer’s product dossier and shipped directly to the RMS central warehouse in Kigali. From the central warehouse, products are distributed to RMS district-level branches, which in turn supply public health centers and community health workers according to periodic resupply schedules coordinated by the Rwanda Biomedical Center (RBC)/Malaria and Other Parasitic Disease Division (MOPDD). Throughout this chain, cold chain management is not required for AL, which is stored at controlled room temperature (not exceeding 30 °C); however, RMS facilities maintain environmental monitoring systems to detect temperature excursions. Rwanda FDA enforces regulatory oversight through mandatory product registration, batch release requirements, and post-market surveillance regulations [21, 22]. Products are only authorized for distribution after Rwanda FDA confirms registration status and batch documentation, providing a further safeguard against the entry of unregistered or falsified products. To minimize risks of product diversion or adulteration, the supply chain operates within a closed public-sector system with no significant parallel informal market for antimalarials. Inventory management systems at each supply chain node track batch numbers, quantities, and expiry dates, facilitating traceability and enabling prompt recall if quality issues are identified post-distribution [23].
All samples were subsequently submitted to the designated laboratories for quality testing as part of the national initiative to assess antimalarial quality across the supply chain. Laboratory testing of samples took place between 3 August and 4 September 2023 at Société Générale de Surveillance (SGS) Laboratories India Pvt. Ltd. (Navi Mumbai, India), which is a facility accredited to ISO/IEC 17025:2017 by the National Accreditation Board for Testing and Calibration Laboratories (NABL) and received WHO Prequalification of Medicines Programme (WHO-PQT) approval in May 2023, confirming its technical competence to provide testing services to all countries serviced by the WHO [24, 25].
Sample size, sampling strategy, and sample collection
The sampling strategy followed a census approach, where, during site visits, field teams from United States Agency for International Development (USAID), Global Health Supply Chain—Procurement and Supply Management (GHSC-PSM), Rwanda Biomedical Center/Malaria and Other Parasitic Disease Division (RBC/MOPDD), and Rwanda Food and Drugs Authority (Rwanda FDA) identified all AL products available at each facility on the day of inspection. These products were all included in the study. No formal sample size calculation was performed, as the study aimed to characterize the quality of available products across the supply chain rather than to estimate the population prevalence of substandard medicines. The resulting 19 samples represent the complete universe of accessible products across the sampled sites.
To ensure sample integrity, each sample consisted of a full market unit, either a sealed blister pack or a complete box, to ensure accuracy in downstream analyses and to comply with WHO recommendations for sampling and handling of antimalarial medicines [26].
In addition, Rwanda FDA participated actively in sample collection, indicating that AL products are registered and authorized for distribution in Rwanda [23]. Moreover, storage conditions at each site were assessed during collection, with all samples having remained at least one month onsite and stored according to manufacturer-recommended conditions, ensuring that quality was preserved throughout the supply chain.
To document sample characteristics systematically, all samples were documented for product identity, dosage form, packaging characteristics, batch number, expiry date, and observable storage conditions. Similarly, sample handling adhered to WHO good pharmaceutical sampling practices, which emphasize the use of moisture-proof containers, avoidance of direct sunlight, and maintenance of adequate ventilation and temperature control to prevent drug degradation [26]. These precautions are particularly important in African settings, where high environmental temperatures and humidity have been implicated in degrading the quality of antimalarial formulations [18].
Visual inspection of packaging and tablets
Visual inspection followed standardized WHO quality screening procedures, examining labeling accuracy, packaging integrity, blister seal quality, and tablet physical appearance. This step is an essential first-line method widely used in African antimalarial quality assessments, where visual anomalies often serve as initial indicators of falsified or degraded medicines [7]. The inspection further assessed tablet color, shape, friability, and overall consistency relative to expected characteristics documented in the manufacturer's Certificate of Analysis (CoAs).
Average tablet weight determination
Tablet weight testing was conducted according to the WHO International Pharmacopoeia (Ph.Int.) requirements, which specify that AL dispersible tablets should average 350 mg ± 3%, whereas regular tablets should average 240 mg ± 3%. The average weight of 20 tablets should be within ± 5% of the nominal weight (240 mg for the standard Ajanta Pharma formulation), with no individual tablet deviating by more than ± 10% [27]. Weight uniformity is a critical parameter in assessing manufacturing quality, as variations may correlate with inconsistent Active pharmaceutical Ingredient (API) content or poor formulation control [27].
Assay of active pharmaceutical ingredients
Quantification of artemether and lumefantrine content was conducted using validated HPLC methods aligned with WHO and international pharmacopeial standards [27]. Pharmacopeial requirements specify an acceptable API content of 90–110% of the labeled claim, although SGS Laboratories applied a narrower acceptance range of 95.0–105.0% based on its certification protocols [27]. HPLC is considered the gold standard for antimalarial assay testing and is routinely employed in WHO prequalification evaluations and African antimalarial quality research [10].
Specifically, the HPLC method follows the WHO International Pharmacopoeia (Ph.Int.) monograph for artemether and lumefantrine tablets, which employs a gradient ion-pair chromatographic procedure: a reverse-phase C18 column is used with a gradient mobile phase comprising acetonitrile and an ion-pair reagent solution (containing 1-heptanesulphonic acid sodium salt), with UV detection at 210 nm for artemether and 380 nm for lumefantrine [17]. These dual detection wavelengths reflect the distinct UV absorption maxima of the two analytes and are consistent with the original International Pharmacopoeia monograph, which was harmonised with the United States Pharmacopoeia (USP) method for AL capsules [17, 28]. Reference standards were certified pharmacopeial-grade working standards procured from WHO-approved sources and used to construct calibration curves with a minimum of five concentration levels spanning 80–120% of the nominal concentration; linearity was accepted when the coefficient of determination (R2) was ≥ 0.999. The method was validated in accordance with ICH Q2(R1) guidelines for specificity, linearity, accuracy, precision, and robustness prior to use in sample analysis, with accuracy assessed as percentage recovery in the range of 98.0–102.0% across three concentration levels. System suitability was verified at the beginning of each analytical run, with acceptance criteria including a plate count of ≥ 2,000 theoretical plates, tailing factor ≤ 2.0, and relative standard deviation (RSD) ≤ 2.0% for replicate injections of the reference standard [28].
Dissolution testing
Dissolution testing was carried out using pharmacopeial methods for both APIs, with artemether analyzed by HPLC and lumefantrine assessed using UV spectrophotometry [27, 29].
This reference method, specified in the WHO International Pharmacopoeia (Ph.Int.), 11th edition [17], was developed to address historically recognized analytical challenges in dissolution testing of AL formulations, including the poor aqueous solubility of lumefantrine, a Biopharmaceutics Classification System (BCS) Class IV compound, which necessitates surfactant-containing dissolution media to adequately simulate gastrointestinal conditions. Dissolution methodology for AL historically lacked pharmacopeial harmonization, with laboratories using diverse media and apparatus that limited inter-laboratory comparability [17]; the WHO Ph.Int. monograph now represents the current international consensus method and formed the basis for testing in this study.
At SGS, this Ph.Int. method was implemented under the laboratory’s validated in-house procedure (SGS MOA No. EDC-000370/EDC-000376; STP/W/18–19/0136, Version 17). For artemether, dissolution was measured by HPLC at two timepoints: the acceptance criterion at 1 h was not less than 45.0% (Q) of the labelled amount of artemether dissolved, and the acceptance criterion at 3 h was not less than 65.0% (Q) of the labelled amount dissolved [17]. These two-timepoint criteria were applied consistently across all samples as confirmed by the SGS Certificates of Analysis. Each determination was performed in six replicates (Rep 1-Rep 6), with individual results reported per replicate. For lumefantrine, dissolution was measured by UV–Visible Spectrophotometry at 45 min. For conventional AL 20/120 mg tablets (6 × 4 blister), the acceptance criterion was not less than 60.0% (Q) of the labelled amount dissolved. For dispersible AL 20/120 mg tablets (6 × 1 and 6 × 2 blister formats), the acceptance criterion was not less than 65.0% (Q) dissolved at 45 min, reflecting the higher specification applicable to that formulation type. Six replicates were tested per batch for lumefantrine in the same manner. All testing referenced SGS’s internal Standard Test Procedure (STP/W/18–19/0136) and Finished Product Specification (FPS/W/18–19/0136), both Version 17, as documented on each Certificate of Analysis.
This aspect is of particular importance because slow or insufficient dissolution leads to sub-therapeutic plasma concentrations, a known driver of antimalarial drug resistance [18].
Data management and analysis
Laboratory results from individual CoAs were extracted into a structured dataset, transferred to STATA Version 14.0 for analysis, and analyzed at the level of the individual sample. Each sample was categorized by district, supply chain level, dosage form, and its performance across all quality testing parameters. Data were analyzed using descriptive statistics and presented as means with ranges, frequencies, and proportions.
Results
Study population and sampling framework
A total of 19 samples with 3588 AL tablets were sampled across eight districts: Nyagatare, Kirehe, Gicumbi, Ruhango, Gisagara, Rubavu, Rusizi, and Gasabo.
Characteristics of collected samples
Of the 19 samples, 16 (84.2%) were collected from high-transmission districts and 3 (15.8%) from low-transmission districts. Two dosage forms were represented: dispersible tablets (13 samples; 58.2% of total tablets, n = 2088) and regular tablets (6 samples; 41.8% of total tablets, n = 1500). Pack size distribution across samples was as follows: 6 × 4 (7 samples, 36.8%), 6 × 2 (7 samples, 36.8%), 6 × 1 (4 samples, 21.1%), and 6 × 3 (1 sample, 5.3%). By supply chain level, RMS HQ contributed 4 samples (21.1%), RMS district branches 7 samples (36.8%), health centers 4 samples (21.1%), and community health workers 4 samples (21.1%) (Table 1).
Table 1.
Distribution of artemether-lumefantrine samples by transmission setting, dosage form, pack size, and tablet weight uniformity across Rwanda's public health supply chain (N = 19)
| Unique ID | Supply chain level | Transmission | Dosage form | Pack size | Average Weight in mg (339.50—360.50 mg) * | Number of tablets n (%) |
|---|---|---|---|---|---|---|
| S01 | Community | High | Dispersible tablet | 6 × 1 (6 tablets) | 355.8 | 120 (3.34%) |
| S02 | Community | High | Dispersible tablet | 6 × 2 (12 tablets) | 356.69 | 120 (3.34%) |
| S03 | Community | High | Dispersible tablet | 6 × 2 (12 tablets) | 356.11 | 120 (3.34%) |
| S04 | Community | High | Regular tablet | 6 × 4 (24 tablets) | 242.18 | 216 (6.02%) |
| S05 | RMS District branches | High | Dispersible tablet | 6 × 2 (12 tablets) | 355.29 | 168 (4.68%) |
| S06 | RMS District branches | Low | Regular tablet | 6 × 4 (24 tablets) | 242.72 | 312 (8.70%) |
| S07 | RMS District branches | Low | Regular tablet | 6 × 3 (18 tablets) | 241.54 | 126 (3.51%) |
| S08 | RMS District branches | High | Dispersible tablet | 6 × 1 (6 tablets) | 356.02 | 192 (5.35%) |
| S09 | RMS District branches | High | Dispersible tablet | 6 × 1 (6 tablets) | 357.65 | 96 (2.68%) |
| S10 | RMS District branches | High | Dispersible tablet | 6 × 2 (12 tablets) | 356.04 | 144 (4.01%) |
| S11 | RMS District branches | High | Dispersible tablet | 6 × 1 (6 tablets) | 357.09 | 126 (3.51%) |
| S12 | Health center | High | Dispersible tablet | 6 × 2 (12 tablets) | 355.9 | 192 (5.35%) |
| S13 | Health center | High | Regular tablet | 6 × 4 (24 tablets) | 241.24 | 72 (2.01%) |
| S14 | Health center | Low | Dispersible tablet | 6 × 2 (12 tablets) | 356.54 | 144 (4.01%) |
| S15 | Health center | High | Dispersible tablet | 6 × 1 (6 tablets) | 357.51 | 126 (3.51%) |
| S16 | RMS HQ | High | Dispersible tablet | 6 × 2 (12 tablets) | 355.88 | 360 (10.03%) |
| S17 | RMS HQ | High | Regular tablet | 6 × 4 (24 tablets) | 239.79 | 720 (20.07%) |
| S18 | RMS HQ | High | Regular tablet | 6 × 3 (18 tablets) | 242.31 | 54 (1.51%) |
| S19 | RMS HQ | High | Dispersible tablet | 6 × 1 (6 tablets) | 355.04 | 180 (5.02%) |
*Specification shown applies to dispersible tablets. The regular tablets were assessed against a Ph.Int. criterion of 228–252 mg
All samples were manufactured by Ajanta Pharma Limited (India), a WHO-prequalified supplier [20], reflecting the homogeneity of Rwanda's public supply chain at the time of sampling. They were tested within their stated expiry periods, with lot expiry dates ranging from December 2023 to May 2024, confirming that observed quality outcomes were not attributable to post-expiry degradation.
Visual and physical quality attributes
The visual and physical quality assessment of the 19 artemether–lumefantrine samples demonstrated full compliance across all evaluated parameters. All samples passed packaging integrity, labelling accuracy, and blister-seal quality checks. Likewise, tablet colour, shape, and surface characteristics were consistently compliant, with no visible defects detected. Overall, each sample achieved a “Pass” outcome (Table 2).
Table 2.
Visual and physical quality assessment of Artemether–Lumefantrine samples across Rwanda’s public health supply chain (N = 19)
| Unique ID |
Packaging integrity |
Labelling accuracy |
Blister seal quality |
Tablet colour |
Tablet shape |
Tablet surface |
Overall result |
|---|---|---|---|---|---|---|---|
| S01 | Pass | Pass | Pass | Compliant | Compliant | Compliant | Pass |
| S02 | Pass | Pass | Pass | Compliant | Compliant | Compliant | Pass |
| S03 | Pass | Pass | Pass | Compliant | Compliant | Compliant | Pass |
| S04 | Pass | Pass | Pass | Compliant | Compliant | Compliant | Pass |
| S05 | Pass | Pass | Pass | Compliant | Compliant | Compliant | Pass |
| S06 | Pass | Pass | Pass | Compliant | Compliant | Compliant | Pass |
| S07 | Pass | Pass | Pass | Compliant | Compliant | Compliant | Pass |
| S08 | Pass | Pass | Pass | Compliant | Compliant | Compliant | Pass |
| S09 | Pass | Pass | Pass | Compliant | Compliant | Compliant | Pass |
| S10 | Pass | Pass | Pass | Compliant | Compliant | Compliant | Pass |
| S11 | Pass | Pass | Pass | Compliant | Compliant | Compliant | Pass |
| S12 | Pass | Pass | Pass | Compliant | Compliant | Compliant | Pass |
| S13 | Pass | Pass | Pass | Compliant | Compliant | Compliant | Pass |
| S14 | Pass | Pass | Pass | Compliant | Compliant | Compliant | Pass |
| S15 | Pass | Pass | Pass | Compliant | Compliant | Compliant | Pass |
| S16 | Pass | Pass | Pass | Compliant | Compliant | Compliant | Pass |
| S17 | Pass | Pass | Pass | Compliant | Compliant | Compliant | Pass |
| S18 | Pass | Pass | Pass | Compliant | Compliant | Compliant | Pass |
| S19 | Pass | Pass | Pass | Compliant | Compliant | Compliant | Pass |
| TOTAL/SPEC | 19/19 Pass | 19/19 Pass | 19/19 Pass | 19/19 Pass | 19/19 Pass | 19/19 Pass | 19/19 Pass |
For dispersible AL tablets, all reported average tablet weights were within the stated specification of 339.50–360.50 mg, totaling 19/19 compliant site-level entries. The mean average weight across sites was 356.27 mg, ranging from 355.04 to 357.65 mg. For regular tablets, all weights complied with the Ph.Int. specification of 240 mg ± 5% (228–252 mg); the mean tablet weight was 241.63 mg, ranging from 239.79 to 242.72 mg (Table 1).
Assay of active ingredients
Assay values for Artemether ranged from 97.3 to 99.4% of label claim, with a mean of 98.7%, while Lumefantrine results ranged from 97.3% to 104.3%, with a mean of 99.2%. All reported assay values complied with the stated specification limits of 95.0–105.0%. Notably, no out-of-specification results were identified for either API (Table 3).
Table 3.
Active pharmaceutical ingredient assay results for artemether and lumefantrine by transmission setting and pack size (N = 19)
| Unique ID | Supply chain level | Transmission | Number of tablets n (%) | Pack size | Artemether Assay (95.0—105.0%) | Lumefantrine assay (95.0—105.0%) |
|---|---|---|---|---|---|---|
| S01 | Community | High | 120 (3.34%) | 6 × 1 (6 tablets) | 98 | 103 |
| S02 | Community | High | 120 (3.34%) | 6 × 2 (12 tablets) | 99.2 | 98.1 |
| S03 | Community | High | 120 (3.34%) | 6 × 2 (12 tablets) | 99.3 | 98.7 |
| S04 | Community | High | 216 (6.02%) | 6 × 4 (24 tablets) | 98.9 | 98.7 |
| S05 | RMS District branches | High | 168 (4.68%) | 6 × 2 (12 tablets) | 99 | 97.9 |
| S06 | RMS District branches | Low | 312 (8.70%) | 6 × 4 (24 tablets) | 98.9 | 98.7 |
| S07 | RMS District branches | Low | 126 (3.51%) | 6 × 3 (18 tablets) | 98.9 | 98.7 |
| S08 | RMS District branches | High | 192 (5.35%) | 6 × 1 (6 tablets) | 98.6 | 99.9 |
| S09 | RMS District branches | High | 96 (2.68%) | 6 × 1 (6 tablets) | 97.3 | 99.1 |
| S10 | RMS District branches | High | 144 (4.01%) | 6 × 2 (12 tablets) | 98.9 | 98 |
| S11 | RMS District branches | High | 126 (3.51%) | 6 × 1 (6 tablets) | 97.5 | 97.9 |
| S12 | Health center | High | 192 (5.35%) | 6 × 2 (12 tablets) | 99.4 | 97.3 |
| S13 | Health center | High | 72 (2.01%) | 6 × 4 (24 tablets) | 98.9 | 98.7 |
| S14 | Health center | Low | 144 (4.01%) | 6 × 2 (12 tablets) | 98.9 | 100.2 |
| S15 | Health center | High | 126 (3.51%) | 6 × 1 (6 tablets) | 98.1 | 99.4 |
| S16 | RMS HQ | High | 360 (10.03%) | 6 × 2 (12 tablets) | 99.2 | 98.5 |
| S17 | RMS HQ | High | 720 (20.07%) | 6 × 4 (24 tablets) | 98.9 | 98.7 |
| S18 | RMS HQ | High | 54 (1.51%) | 6 × 3 (18 tablets) | 98.9 | 98.7 |
| S19 | RMS HQ | High | 180 (5.02%) | 6 × 1 (6 tablets) | 98 | 104.3 |
| 3588 (100%) |
Dissolution performance
Dissolution outcomes demonstrated complete compliance, with mean artemether dissolution at 1 h ranged from 73.5% to 81.2% (specification: ≥ 45%), reaching 88.7–93.0% at 3 h (specification: ≥ 65%). Mean lumefantrine dissolution at 45 min ranged from 83.2 to 91.5% (specification: ≥ 60%). All 19 samples passed all dissolution criteria. No failed dissolution results were recorded as per the pharmacopeia limits stipulated in the WHO, international pharmacopeial standards, and the SGS Laboratories acceptance limit (Table 4).
Table 4.
Dissolution test results for artemether and lumefantrine by transmission setting and dosage form (N = 19)
| Unique ID | Transmission | Dosage form | Number of samples tested n (%) | Mean% (SD) Dissolution—Artemether—1 h (≥ 45%) | Mean% (SD) Dissolution—Artemether—3 h (≥ 65%) | Mean% (SD) Dissolution—Lumefantrine—45 min (≥ 60%) |
|---|---|---|---|---|---|---|
| S01 | High | Dispersible tablet | 120 (3.34%) | 80.2 (1.17) | 91.5 (1.22) | 89.7 (1.51) |
| S02 | High | Dispersible tablet | 120 (3.34%) | 80.5 (1.05) | 91.8 (1.17) | 88.3 (1.21) |
| S03 | High | Dispersible tablet | 120 (3.34%) | 80.8 (1.17) | 91.7 (0.82) | 88.7 (1.97) |
| S04 | High | Regular tablet | 216 (6.02%) | 77.1 (1.15) | 88.7 (1.71) | 83.4 (0.20) |
| S05 | High | Dispersible tablet | 168 (4.68%) | 81.0 (1.55) | 92.8 (0.75) | 89.8 (1.17) |
| S06 | Low | Regular tablet | 312 (8.70%) | 76.0 (1.22) | 89.2 (1.57) | 83.5 (0.05) |
| S07 | Low | Regular tablet | 126 (3.51%) | 76.9 (0.65) | 90.7 (0.95) | 83.2 (0.68) |
| S08 | High | Dispersible tablet | 192 (5.35%) | 73.8 (0.41) | 90.5 (0.84) | 90.2 (1.94) |
| S09 | High | Dispersible tablet | 96 (2.68%) | 81.0 (0.63) | 93.0 (0.89) | 91.0 (1.41) |
| S10 | High | Dispersible tablet | 144 (4.01%) | 74.5 (0.55) | 89.7 (1.21) | 90.0 (1.55) |
| S11 | High | Dispersible tablet | 126 (3.51%) | 75.5 (0.84) | 89.2 (1.17) | 90.7 (1.86) |
| S12 | High | Dispersible tablet | 192 (5.35%) | 73.5 (0.55) | 90.2 (0.98) | 88.8 (0.75) |
| S13 | High | Regular tablet | 72 (2.01%) | 76.0 (1.46) | 88.7 (1.15) | 83.6 (0.10) |
| S14 | Low | Dispersible tablet | 144 (4.01%) | 81.2 (0.75) | 92.7 (0.82) | 91.5 (1.52) |
| S15 | High | Dispersible tablet | 126 (3.51%) | 79.5 (1.05) | 91.3 (0.82) | 90.2 (2.14) |
| S16 | High | Dispersible tablet | 360 (10.03%) | 77.0 (0.98) | 91.0 (1.03) | 89.0 (2.17) |
| S17 | High | Regular tablet | 720 (20.07%) | 74.0 (0.84) | 92.6 (0.61) | 85.8 (0.17) |
| S18 | High | Regular tablet | 54 (1.51%) | 76.5 (0.67) | 90.3 (1.27) | 83.5 (0.61) |
| S19 | High | Dispersible tablet | 180 (5.02%) | 76.0 (0.52) | 91.0 (0.52) | 87.0 (0.00) |
| Total Number | 3588 (100%) | 3588 (100%) | 3588 (100%) | 3588 (100%) |
Discussion
This cross-sectional study evaluated the pharmaceutical quality of AL across Rwanda's public health supply chain, analyzing 19 samples with 3,588 tablets collected from eight districts representing all five provinces. The findings demonstrate exceptional quality assurance outcomes: 100% of tested samples met international pharmacopeial standards for visual inspection, tablet weight uniformity, active pharmaceutical ingredient (API) content, and dissolution performance [25, 27]. These results contrast sharply with documented quality failures across much of sub-Saharan Africa and offer important insights into the factors that enable successful antimalarial quality control in resource-limited settings.
However, the complete compliance observed in this study stands in stark contrast to the broader African experience with antimalarial quality. For example, systematic reviews have documented that approximately 35% of antimalarial samples from 21 African countries fail chemical analysis [5], with an estimated 19% of antimalarials circulating in sub-Saharan Africa classified as substandard or falsified [4].
In addition, multi-country surveys across severely malarious regions have reported failure rates ranging from 20% to over 60% in some settings, with quality deficiencies detected across both private and public supply chains [5, 7]. Similarly, in East Africa specifically, studies in Kenya, Uganda, and Tanzania have identified significant proportions of non-quality-assured ACTs, including samples with sub-therapeutic API content and inadequate dissolution profiles [18].
Against this backdrop, Rwanda's success appears attributable to several structural factors. First, the country operates a centralized public procurement and distribution system through Rwanda Medical Supply (RMS), which sources antimalarials exclusively from WHO-prequalified manufacturers and implements rigorous quality control protocols at multiple supply chain nodes [17]. This centralized approach stands in contrast to contexts with fragmented supply chains and widespread informal markets, where multiple entry points increase the risk of S&F medicines infiltrating the system [2, 10]. Moreover, Rwanda's national regulatory framework, overseen by the Rwanda FDA, enforces mandatory post-market surveillance and maintains strict import controls [17, 21, 22]. Additionally, the absence of a significant private antimalarial market in Rwanda eliminates a major pathway through which poor-quality medicines typically enter African health systems [18].
In regard to the API content, the assay results for both artemether (mean: 98.7%, range: 97.3–99.4%) and lumefantrine (mean: 99.2%, range: 97.3–104.3%) demonstrate tight quality control during manufacturing and suggest minimal degradation during storage and distribution. All samples met the acceptance range of 95.0–105.0% specified by SGS Laboratories, which is more stringent than the WHO International Pharmacopoeia requirement of 90–110% [27]. Notably, this finding is particularly significant given that sub-therapeutic API levels are a primary driver of antimalarial treatment failure and contribute to the selection pressure that facilitates drug resistance [5, 14].
By contrast, studies from other African settings have documented substantial API variability in circulating ACTs [12]. For instance, surveys in Nigeria and the Democratic Republic of Congo found that 15–30% of AL samples contained artemether or lumefantrine levels below pharmacopeial limits, with some samples containing as little as 50–70% of labeled API content [13, 30]. Consequently, such deficiencies expose malaria parasites to sub-lethal drug concentrations, a mechanism implicated in the emergence of artemisinin-resistant Plasmodium falciparum strains now confirmed in Uganda, Rwanda, and other parts of East Africa [14, 19].
Likewise, the complete dissolution compliance observed in this study is equally important. Dissolution testing measures the rate and extent to which tablets release active ingredients in simulated gastrointestinal conditions, directly predicting bioavailability and therapeutic efficacy [27]. Poor dissolution performance has been documented even in samples with adequate API content, reflecting formulation defects, manufacturing errors, or storage-induced degradation [5, 18]. Indeed, studies from Kenya and Tanzania have reported dissolution failure rates of 10–25% among AL samples, highlighting this as a critical but often overlooked dimension of antimalarial quality [30].
Additionally, the compliance of all samples with tablet weight specifications (dispersible tablets: 339.50–360.50 mg; regular tablets: approximately 240 mg indicates consistent manufacturing practices and appropriate storage conditions. Weight uniformity is a fundamental quality indicator because deviations often correlate with API content variability, poor mixing during formulation, or compression defects [27, 30]. African antimalarial quality surveys have identified tablet weight failures in 5–15% of samples, particularly from unregulated sources or products exposed to high temperatures and humidity during storage [13, 18].
Similarly, visual inspection revealed no packaging defects, labeling errors, or tablet abnormalities across the 19 samples examined. This finding suggests minimal risk of falsified products within Rwanda's public supply chain and contrasts with reports from other African countries where counterfeit AL products with altered packaging, missing batch numbers, or suspicious physical characteristics have been detected [12, 18].
Taken together, the exceptional quality of AL circulating in Rwanda's public system has direct implications for malaria treatment outcomes and the preservation of ACT effectiveness. High-quality antimalarials ensure optimal therapeutic efficacy, reducing the risk of treatment failure, recrudescence, and onward transmission [1]. Conversely, exposure to substandard or falsified antimalarials is estimated to cause 40,000–160,000 avoidable malaria deaths annually in sub-Saharan Africa, primarily among children under five [4, 5].
Furthermore, the quality of medicine plays a crucial role in preventing antimalarial drug resistance. Sub-therapeutic drug exposure, whether from inadequate dosing or poor-quality formulations, creates selective pressure that allows parasites with reduced drug susceptibility to survive and proliferate [5, 19]. The emergence of artemisinin partial resistance mutations (Plasmodium falciparum kelch13 variants) in East Africa, including Rwanda, underscores the urgency of maintaining high-quality ACT deployment [14, 19]. Ensuring that every dose of AL delivers the intended API content and achieves adequate dissolution is a critical component of resistance containment strategies.
This study's primary strength is its comprehensive geographic and supply chain coverage, encompassing central procurement, district distribution, health centers, and community health workers across both high- and low-transmission settings. The use of WHO-recognized laboratory facilities and adherence to international pharmacopeial testing standards enhance the reliability and comparability of results [25]. Furthermore, alignment with MEDQUARG guidelines ensures methodological rigor and transparency [15].
Nevertheless, several limitations warrant consideration. First, sampling was conducted exclusively within the public supply chain; private pharmacies and cross-border markets were not included. While Rwanda's private antimalarial market is limited, these channels may introduce quality risks not captured in this study [18]. In addition, a further limitation concerns manufacturer representation. All 19 samples originated exclusively from Ajanta Pharma Limited, reflecting Rwanda's centralized procurement policy of sourcing AL from a single WHO-prequalified supplier [17, 20]. While this confirms the quality of the specific product circulating within the public supply chain, it limits generalizability beyond a single manufacturer's performance. Second, the cross-sectional design provides a snapshot of quality at a single time point and cannot assess temporal trends or the impact of seasonal variations in storage conditions. Finally, samples were not subjected to advanced analytical techniques such as impurity profiling, which can detect chemical adulterants or degradation products not identified by standard assay and dissolution testing [31].
Despite these limitations, Rwanda's success in ensuring AL quality offers a model for other African countries confronting S&F antimalarial challenges. Key elements of this approach include centralized procurement from WHO-prequalified manufacturers, rigorous regulatory oversight, post-market surveillance integrated into routine supply chain operations, elimination of unregulated antimalarial markets, and investment in quality assurance capacity at national and district levels [17, 21].
Finally, the findings of this study also underscore the importance of standardized, transparent medicine quality surveillance as prescribed by MEDQUARG guidelines [15]. Harmonized field surveys, consistent sampling methodologies, and transparent reporting enable cross-country comparisons, identify regional quality hotspots, and inform evidence-based policy responses. Expanding such surveillance to include private sector outlets and neighboring countries would provide a more comprehensive picture of antimalarial quality risks in the East African region.
Looking ahead, future studies should expand sampling to include private pharmacies to assess quality risks beyond the public supply chain. Longitudinal surveillance is needed to monitor temporal trends and evaluate the impact of policy interventions on antimalarial quality. Advanced analytical methods, including impurity profiling and isotopic analysis, should be used to detect chemical adulterants and trace the origin of suspected products. Finally, linking medicine quality data with malaria treatment outcomes and drug resistance surveillance would clarify the public health impact of quality assurance interventions.
Conclusion
All 19 samples of AL from Rwanda's public supply chain met international quality standards, contrasting sharply with sub-Saharan Africa's 19% substandard/falsified antimalarial prevalence. Rwanda's success derives from centralized procurement, rigorous regulatory oversight, and WHO-prequalified sourcing. Maintaining pharmaceutical quality is critical for treatment efficacy and preventing drug resistance, particularly given emerging artemisinin resistance in East Africa. Future surveillance should expand to private markets while sustaining current quality assurance systems.
Acknowledgements
The authors wish to express their sincere gratitude to the Rwanda Food and Drug Authority (Rwanda FDA) and the Rwanda Biomedical Center/Malaria and Other Parasitic Disease Division (RBC/MOPDD) for their active participation in sample collection across the eight study districts and for providing regulatory oversight and product registration confirmation that ensured the legitimacy of all sampled products within Rwanda's supply chain. The authors also acknowledge the district health teams, health center staff, and community health workers across Nyagatare, Kirehe, Gisagara, Rusizi, Gicumbi, Gasabo, Rubavu, and Ruhango districts who facilitated access to sampled facilities and provided storage condition information during field visits.
Abbreviations
- ACTs
Artemisinin-based combination therapies
- AL
Artemether Lumefantrine
- S&F
Substandard and falsified
- API
Active pharmaceutical Ingredient
- MEDQUARG
Medicine Quality Assessment Reporting Guidelines
- RBC/MOPPD
Rwanda Biomedical Center/ Malaria and Other Parasitic Disease Division
- Rwanda FDA
Rwanda Food and Drugs Authority
- CoAs
Certificate of Analysis
- HPLC
High-Performance Liquid Chromatography
- WHO
World Health Organization
- USAID
United States Agency for International Development
Author contributions
Conceptualization: R.R., L.N., L.M., M.D., and N.R; methodology: R.R., M.D., A.U., L.M., and C.C.; investigation and interpretation: R.R., A.U., L.N., E.L.N., M.D., L.M., and C.C.; writing-original draft: R.R., N.R., E.L.N., L.M., and C.C.; writing—review & editing: R.R., L.M., A.U., and C.C.; supervision: L.M., N.R., and M.D.; funding acquisition: L.M. and M.D.
Funding
Sample collection was conducted as part of a joint field activity by the Rwanda FDA, Rwanda Biomedical Center/MOPDD, and the USAID GHSC-PSM program. Laboratory testing was funded by the President’s Malaria Initiative (PMI), which is supporting the National Malaria control program and the Rwanda Food and Drug Authority (Rwanda FDA) to conduct the quality control of antimalarial medicines sampled across the different supply chain levels. Additional external funding was received for the analysis and writing of this manuscript from the FD-TACT Project, an open-label, randomized, controlled, non-inferiority trial to compare the efficacy, safety and tolerability of a fixed dose Triple Artemisinin-based Combination Therapy (TACT) artemether-lumefantrine-amodiaquine versus first-line Artemisinin-based Combination Therapies (ACTs) for the treatment of uncomplicated Plasmodium falciparum malaria), which is a Clinical Trial with a Trial Registration Number ClinicalTrials.gov ID NCT05951595.
Data availability
The dataset supporting the conclusions of this article is available in Zenodo repository, on https://doi.org/10.5281/zenodo.19367496
Declarations
Ethics approval and consent to participate
This study involved testing commercially available pharmaceutical products obtained through routine supply chain activities. No human subjects, biological samples, or personal data were involved; therefore, ethical approval was not required under Rwandan national research ethics regulations or international guidelines.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Mehul Dhorda and Leon Mutesa have contributed equally to this work.
Contributor Information
Robert Rutayisire, Email: robertrutayisire@gmail.com.
Leon Mutesa, Email: lmutesa@gmail.com.
References
- 1.WHO. World Malaria Report 2023 https://www.who.int/teams/global-malaria-programme/reports/world-malaria-report-2023
- 2.Carlos Chaccour, Harparkash Kaur, Jose Luis Del Pozo. Falsified antimalarials: a minireview. Medicine - Expert Review of Anti-infective Therapy. https://www.tandfonline.com/doi/10.1586/14787210.2015.1015990?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed. [DOI] [PubMed]
- 3.WHO. A study on the public health and socioeconomic impact of substandard and falsified medical products 2017 https://www.who.int/publications/i/item/9789241513432
- 4.Almuzaini T, Choonara I, Sammons H. Substandard and counterfeit medicines: a systematic review of the literature. BMJ Open. 2013;3:e002923. 10.1136/bmjopen-2013-002923. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Tabernero P, Fernández FM, Green M, Guerin PJ, Newton PN. Mind the gaps - the epidemiology of poor-quality anti-malarials in the malarious world - analysis of the WorldWide Antimalarial Resistance Network database. Malar J. 2014;13:139. 10.1186/1475-2875-13-139. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Renschler JP, Walters KM, Newton PN, Laxminarayan R. Estimated under-five deaths associated with poor-quality antimalarials in Sub-Saharan Africa. Am J Trop Med Hyg. 2015;92:119–26. 10.4269/ajtmh.14-0725. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Girma M, Umeta B, Hasen G, Suleman S. Quality of Antimalarial Drugs in East Africa: A Systematic Review. Infect Drug Resist Informa UK Limited. 2022;15:6085–92. 10.2147/idr.s373059. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Tegegne AA, Feissa AB, Godena GH, Tefera Y, Hassen HK, Ozalp Y, et al 2024 Substandard and falsified antimicrobials in selected east African countries: A systematic review. Inocencio Da Luz R, editor. PLOS ONE. 19 e0295956 10.1371/journal.pone.0295956 [DOI] [PMC free article] [PubMed]
- 9.Mlugu EM, Mhagama J, Matiko D, Agustine S, Nandonde M, Masunga E, et al. A comprehensive assessment of quality of antimalarial medicines in mainland Tanzania: insights from five years of postmarket surveillance. Am J Trop Med Hyg. 2024;111:1215–22. 10.4269/ajtmh.24-0145. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Ocan M, Nakalembe L, Otike C, Omali D, Buzibye A, Nsobya S. Pharmacopeial quality of artemether–lumefantrine anti-malarial agents in Uganda. Malar J. 2023;22:165. 10.1186/s12936-023-04600-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Mekasha YT, Tegegne AA, Mashe T, Girma M, Hasen G, Belew S. Artemisinin‐based combination therapies in East Africa: a systematic review of quality, clinical efficacy, and regulatory progress towards sustainable malaria control. Trop Med Int Health. 2026;31:254–73. 10.1111/tmi.70072. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Newton PN, Fernández FM, Plançon A, Mildenhall DC, Green MD, Ziyong L, et al 2008 A Collaborative Epidemiological Investigation into the Criminal Fake Artesunate Trade in South East Asia. Reidenberg M, editor. PLoS Med. 5 e32 10.1371/journal.pmed.0050032 [DOI] [PMC free article] [PubMed]
- 13.Bate R, Coticelli P, Tren R, Attaran A. Antimalarial drug quality in the most severely malarious parts of Africa – a six country study. PLoS ONE. 2008;3:e2132. 10.1371/journal.pone.0002132. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Balikagala B, Fukuda N, Ikeda M, Katuro OT, Tachibana S-I, Yamauchi M, et al. Evidence of artemisinin-resistant malaria in Africa. N Engl J Med. 2021;385:1163–71. 10.1056/NEJMoa2101746. [DOI] [PubMed] [Google Scholar]
- 15.Newton PN, Lee SJ, Goodman C, Fernández FM, Yeung S, Phanouvong S, et al. Guidelines for field surveys of the quality of medicines: a proposal. PLoS Med. 2009;6:e1000052. 10.1371/journal.pmed.1000052. (Public Library of Science (PLoS)). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Kubahoniyesu T, Muhorakeye G, Kampire A, Kanyabwisha F. Malaria incidence and death rates among under-five children (2014- 2024) and pregnant women (2018-2023) in Rwanda. Rwanda Public Health Bull. 2014;6:16–21. 10.4314/rphb.v6i3.3. [DOI] [Google Scholar]
- 17.MoH-RBC. Rwanda Malaria Strategic Plan 2020–2024 2020. https://rbc.gov.rw/fileadmin/user_upload/strategy/Rwanda_Malaria_Strategic_Plan_2020-2024.pdf
- 18.Kaur H, Clarke S, Lalani M, Phanouvong S, Guérin P, McLoughlin A, et al. Fake anti-malarials: start with the facts. Malar J. 2016;15:86. 10.1186/s12936-016-1096-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Uwimana A, Legrand E, Stokes BH, Ndikumana JLM, Warsame M, Umulisa N, et al. Emergence and clonal expansion of in vitro artemisinin-resistant Plasmodium falciparum kelch13 R561H mutant parasites in Rwanda. Nat Med Nature Research. 2020;26:1602–8. 10.1038/S41591-020-1005-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.WHO. Prequalification of Medical Products. Ajanta Pharma Limited. Z/103/A, Dahej SEZ-II, Bharuch Gujarat 392130 India. 2023. https://extranet.who.int/prequal/content/ajanta-pharma-limited
- 21.Rwanda FDA. Medicine Safety Bulletin, Ver03. Kigali: Rwanda Food and Drugs Authority; 2024 https://rwandafda.gov.rw/wp-content/uploads/2024/10/MEDICINE-SAFETY-BULLETIN-vers3.pdf. Accessed 31 Mar 2026
- 22.Rwanda FDA. Vigilance Regulations. Kigali: Rwanda Food and Drugs Authority; 2020 https://rwandafda.gov.rw/wp-content/uploads/2024/02/Regulation%20Governing%20Pharmacovigilance%20in%20Rwanda%20new%20version_final-Rev1.pdf. Accessed 31 Mar 2026
- 23.Registered Pharmaceutical Products. Rwanda FDA; 2023. https://rwandafda.gov.rw/register/monitoring_preview_register
- 24.SGS. SGS receives WHO-PQT approval for its Navi Mumbai laboratory, bolstering support to the global pharma industry. Mumbai; 2023. https://www.prnewswire.com/in/news-releases/sgs-receives-who-pqt-approval-for-its-navi-mumbai-laboratory-bolstering-support-to-the-global-pharma-industry-301838156.html
- 25.SGS India Private Limited-Multi Laboratory. Certificate of Accredtation, ISO/IEC 17025:2017. “‘General Requirements for the Competence of Testing & Calibration Laboratories.’” 2021.
- 26.WHO. WHO guidelines for sampling of pharmaceutical products and related materials. Annex 4. Geneva: World Health Organization; 2005 https://cdn.who.int/media/docs/default-source/medicines/norms-and-standards/guidelines/inspections/trs929-annex4-guidelinessamplingpharmproducts.pdf. Accessed 31 Mar 2026
- 27.WHO. World Health Organization. The International Pharmacopoeia (11th ed.) 2022. https://www.who.int/teams/health-product-and-policy-standards/standards-and-specifications/norms-and-standards-for-pharmaceuticals/pharmacopoeias/international-pharmacopoeia
- 28.Amin NC, Fabre H, Blanchin M-D, Montels J, Aké M. Determination of artemether and lumefantrine in anti-malarial fixed-dose combination tablets by microemulsion electrokinetic chromatography with short-end injection procedure. Malar J. 2013;12:202. 10.1186/1475-2875-12-202. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.International Organization for Standardization. ISO/IEC 17025:2017 General requirements for the competence of testing and calibration laboratories ISO; 2017. https://www.iso.org/standard/66912.html
- 30.Hajjou M, Krech L, Lane-Barlow C, Roth L, Pribluda VS, Phanouvong S, et al. Monitoring the quality of medicines: results from Africa, Asia, and South America. Am J Trop Med Hyg. 2015;92:68–74. 10.4269/ajtmh.14-0535. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Green MD, Nettey H, Rojas OV, Pamanivong C, Khounsaknalath L, Ortiz MG, et al. Use of refractometry and colorimetry as field methods to rapidly assess antimalarial drug quality. J Pharm Biomed Anal. 2007;43:105–10. 10.1016/j.jpba.2006.06.047. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The dataset supporting the conclusions of this article is available in Zenodo repository, on https://doi.org/10.5281/zenodo.19367496