Objective : To assess the quality of oxytocin and misoprostol products available in Côte d’Ivoire and Senegal. Methods : Samples of oxytocin injections and misoprostol tablets were collected from three different levels of the supply chain in Côte d’Ivoire and Senegal from August to December 2021. The sampling process was done by personnel from the National Medicines Regulatory Authorities, employing a methodology and sampling plan aligned with WHO guidelines for conducting surveys on the quality of medicines. These samples were then transported under controlled conditions to qualified laboratories for quality assessment, where they underwent testing according to the specifications outlined in the 10th Edition of the International Pharmacopeia. Findings : A total of 196 samples of oxytocin and misoprostol were collected from 130 health facilities across the two countries. Analyses revealed that 30% of the oxytocin and 23% of the misoprostol samples did not meet the quality criteria at all levels of the supply chain in both countries. Furthermore, although oxytocin samples were stored in refrigerators, the absence of proper temperature monitoring equipment was a common finding. Conclusion : A substantial proportion of oxytocin and misoprostol products available in Côte d’Ivoire and Senegal were found to be substandard. Investing in quality-assured medicines is crucial for delivering safe and effective healthcare, reducing overall healthcare costs, and securing the long-term success of universal health coverage in low-income countries.
Introduction Postpartum haemorrhage (PPH) is defined as blood loss of at least 500 ml within 24 hours after birth and it affects about 5% of all women giving birth around the world. [1, 2] PPH is the leading cause of maternal mortality worldwide, being responsible for nearly a quarter of all maternal deaths. [3] However, the majority of these deaths could be avoided through timely and appropriate administration of prophylactic uterotonics during labour and delivery.[4] Improving care of women during childbirth to prevent PPH is a necessary step toward the achievement of the Sustainable Development Goals by 2030 [5]. WHO recommends the use of oxytocin injection as an effective uterotonic for the prevention of PPH during the third stage of labour for all births.[4] Importantly, oxytocin is included in the WHO Essential Medicines List and in the UN Commission on Life-Saving Commodities (UNCoLSC).[6] Proper storage conditions for oxytocin are crucial as it is temperature sensitive and should be stored between 2-8°C to maintain its effectiveness.[7-9] In many low- and middle-income country (LMIC) settings, maintaining the required storage conditions for medicines, including oxytocin, can be a challenge.
Deviations from the recommended storage temperature can impact the stability of oxytocin, leading to degradation and potentially compromising its efficacy.[10] Misoprostol is an affordable generic medicine, suggested as an alternative to oxytocin and listed in the WHO Essential Medicines List.[11] However, it’s essential to note that misoprostol is sensitive to humidity and can degrade rapidly if not stored properly.[12] Ensuring that essential medicines like oxytocin and misoprostol are stored correctly in health facilities is crucial to maintain their effectiveness. The presence of substandard oxytocin and misoprostol in LMICs poses a significant challenge to maternal healthcare. While studies have highlighted this problem in Anglophone countries, there is a lack of data from Francophone African countries.
[13] Addressing the quality and availability of these essential medicines is crucial for improving maternal health outcomes. In 2019, West African Economic and Monetary Union countries (WAEMU) took steps to enhance the quality of oxytocin by convening to address this issue in the region. The group formulated and ratified the “Dakar Roadmap,” which outlined essential activities to be executed at the national level to enhance the availability of high-quality oxytocin. This collaborative effort aligned with the guidelines established by WHO, UNICEF, and UNFPA on the proper management of oxytocin within the cold chain.[7] This regional initiative meant a significant stride towards ensuring the accessibility and reliability of oxytocin in the region.
Given the crucial role that assured quality and affordable uterotonics play in addressing maternal health disparities worldwide, and in response to the concerns raised by certain West African countries, WHO in collaboration with the National Medicines Regulatory Authorities from Côte d’Ivoire and Senegal conducted a post-marketing surveillance study. This study aimed to evaluate the quality of oxytocin and misoprostol products within these markets, underscoring the commitment to ensuring safe and reliable maternal healthcare interventions in the region.
Methods Sampling framework The post-marketing surveillance (PMS) survey, was coordinated by WHO in partnership with the national regulatory authorities and quality control laboratories of Senegal and Côte d’Ivoire. Both countries, are among the world’s 49 poorest countries as identified by the “Every Woman Every Child (EWEC)” movement.[14] The study protocol, developed by WHO and approved by the National Medicines Regulatory Authorities (NMRAs) in the participating countries, involved a sampling plan based on the Medicines Risk Assessment tool (MedRS) from the United States Pharmacopoeia (USP). The sampling strategy targeted facilities at three levels of the supply chain: level-1 (points of entry to the market, warehouses of importers, central medical stores); level-2 (wholesalers and/or distributors); and level-3 (authorized dispensers such as pharmacies, hospitals, health center depots, health posts, district hospitals, clinics, maternity and treatment center); and followed a 20%:20%:60% ratio (level-1:level-2:level-3) in both public and private health sectors.[15, 16] The highest risk was assigned at the levels where medicines were dispensed directly to the patients with limited or poor management oversight.
All regions were targeted considering similarity of conditions throughout the country. In Côte d’Ivoire, 13 out of 31 regions and in Senegal 7 out of 14 regions were selected for sampling the medicines. Ethical approval for the survey was obtained from the relevant committees and Ministries of Health in Côte d’Ivoire and Senegal. Informed consent was not required as the study solely focused on sample collection and storage information. Sample collection For this study, a sample was defined as an item collected from each medicine’s form, including details such as the name, dosage of active pharmaceutical ingredient (API), dosage form, strength, batch/lot number, and manufacturer, all from the same collection site.
For oxytocin, each sample comprised 10 units from the same manufacturer and batch, while for misoprostol, a minimum of 60 tablets from the same manufacturer and batch constituted a sample. Sample collectors were equipped with logistical support and ensured temperature-controlled storage during sample handling and transportation. They were also responsible for assessing and reporting on the storage conditions of the samples at the health facilities during collection. Prior to sampling, each country team was required to identify all registered oxytocin and misoprostol brands approved by their national regulatory authorities. The goal was for each country to collect a total of 100 samples (50 oxytocin and 50 misoprostol), all obtained in their original packaging.
Laboratory analysis The oxytocin samples were tested by the Monash Institute of Pharmaceutical Sciences (MIPS) laboratory in Australia, while the samples of misoprostol were tested by the National Laboratory of the Ugandan National Drug Authority (NDA), from both countries. Testing was conducted according to the guidelines specified in the International Pharmacopoeia (Ph. Int) 10th Edition (2020).[17] The Ph. Int monograph for oxytocin injection specifies requirements for description, labeling, packaging, identification, assay, pH, particulate matter, and related substances. The Ph. Int monograph for misoprostol tablets outlines specifications for various parameters including description, labeling, packaging, storage, identification, assay, uniformity of content, and dissolution. Any test result that fell outside the acceptance criteria set by the Ph.
Int monographs was considered a failed test, leading to the classification of the sample as substandard. In cases where tests for dissolution and uniformity of content failed at level-1, they were deemed inconclusive if there were insufficient sample units available to carry out the subsequent testing levels as outlined in the Ph. Int monograph for misoprostol tablets.
Results Between August and December 2021, a total of 196 samples of oxytocin injection and misoprostol tablets were collected from 130 health facilities across Côte d’Ivoire and Senegal. Côte d’Ivoire collected 100 samples (52 oxytocin and 48 misoprostol) from 62 facilities, while Senegal collected 96 samples (62 oxytocin and 34 misoprostol) from 68 facilities. Detailed information about the samples of oxytocin and misoprostol collected in both countries can be found in Tables S1 and S2 and in Figures S1 and S2 respectively. Tables 1 and 2 present the products sampled in Côte d’Ivoire and Senegal based on the source of manufacture. Figures 1 and 2 display the distribution of oxytocin and misoprostol samples according to the level of supply in both the public and private sectors in Côte d’Ivoire and Senegal.
Notably, the majority of samples (71%) were collected from Level-3 facilities in both countries. Although oxytocin ampules in both countries were stored in refrigerators at all facilities, the sampling teams reported inadequate temperature monitoring equipment and absence of alert systems linked to the refrigerators at the time of sampling. The sampling teams were instructed to verify the registration status of all collected samples with the NMRAs. Table 3 provides information on the registration status at national level and WHO prequalification status of all samples included in this survey. Figure 1 : Distribution of samples per level of supply and health sector Figure 2 : Distribution of oxytocin and misoprostol collectected per health sector Figure S1 : Proportion of oxytocin and misoprostol brands collected in Cotes d’lvoire Figure S2 : Proportion of oxytocin and misoprostol brands collected in Senegal Table 1: Samples of oxytocin and misoprostol from Côte d’Ivoire as per source of manufacture INN Name Manufacturer Batch No.
No. of Samples per batch Pack Size Expiry date Oxytocin Injection 5 IU Oxytocin (5 IU) Rotexmedica Gmbh. Artzeimittel Werk Bunsenstrasse 4-22946 Trittau, Germany 00871 1 10 x 1ml Oct-23 Oxytocin (5 IU) North China Pharma Co -NCPC No 217-1 East Heping Road Shijiazhuang Zhuang China 190522 1 10 x 1ml May-22 200217 3 Feb-23 200222 1 Feb-23 200223 4 Feb-23 200310 3 Mar-23 210208 11 Feb-24 Oxytocin (5 IU) Medisol S.A.S Rue Jacques Monod, Lyon, France ME011X5 1 10 x 1ml May-23 Oxytocin (5 IU) Ciron Drugs Pharma, Ltd. 119/2 Dist Polghor – 401506, India 1EB02241 1 10 x 1ml May-23 1EB04265 1 Jun-23 Oxytocin (5 IU) Troikaa Pharma Ltd.
Thol,Gujarat, India 043147 3 3 x 1ml Sep-22 043148 3 Jun-23 043150 4 Jul-23 043152 2 Aug-23 043153 5 Aug-23 Oxytocin (5 IU) Sterile-Gene Life Sciences Ltd. No.45, Mangalam Village Villanur, India JR00001A 1 10 x 1ml Nov-22 JR00001B 3 Nov-22 Research Article Oxytocin (10 IU) Bharat Parenterals Ltd. Haripura,TA.Savili,Dist. Vadodara-391520, Gujarat, India 00001 2 10 x 1ml May-22 00002 1 May-22 00004 1 May-22 Total Samples 52 Misoprostol Tablets 200mg Misoprostol Quimica Y Farmaceutica -Spain P003 2 B/3 May-23 Misoprostol ACME Formulation Ltd. Ropar Road, Nanalagarh Dist.Solan, Pradesh -India MCL2107074 1 B/4 Jun-23 Misoprostol NAARI Pharma Plot 14-16, 55-57, Sector-5, IIE, Pantnagar, Rurdapur -263153, Dist, Udham S. Nagar, Uttarakhand – India NR00605B 1 B/4 Nov-22 NR00628D 5 Dec-22 NR00665B 1 Jan-23 NR00666C 3 Feb-23 NR00711A 11 Mar-23 Misoprostol ACME Formulation Ltd.
Ropar Road, Nanalagarh Dist. Solan, Himachal Pradesh, India ACE2006041 7 B/3 May-22 ACE2006042 8 May-22 ACE2103038 1 Feb-23 ACE2103039 1 Feb-23 Misoprostol ACME Formulation Ltd. Ropar Road, Nanalagarh Dist. Solan, Himachal Pradesh, India ACG2002002 1 B/4 Jan-22 Misoprostol China Resources Zizhu Pharma -N 27, Chaoyang Dist. Beijing 100024, China 45200501 6 B/3 May-22 Total Samples 48 Table 2: Samples of oxytocin and misoprostol from Senegal as per source of manufacture INN Name Manufacturer Batch N° # Samples per batch Pack Size Expiry date Oxytocin Injection (5 IU) Oxytocin (5 IU) Troikka Pharmaceuticals Ltd, Thol - 382 728, Gugarat, India 043139 2 3 x 1ml Jun-2022 043140 4 Jun-2022 043142 1 July-2022 043146 9 Sep-2022 043147 6 Sep-2022 Oxytocin (5 IU) Steril-Gene Life Sciences NO: 45, Mangalam Main Road Mangalam Villianur - Puducherry - 605 110, India JR0001A 1 10 x 1ml Nov-2022 JR0001B 1 Nov-2022 Oxytocin (5 IU) XIER Kangtai Pharmaceuticals Anhui Hongye Pharmaceuticals Ltd.
Fengyang Rd, Bengbu , Anhui Province , China S230Q01 1 10 x 1ml Jul-2022 S230Q02 1 Feb-2023 S230Q03 34 Jul-2023 S230Q04 2 Jul-2024 Total Samples 62 Misoprostol Tablets 200 mg Misoprostol United Biotech (P) Ltd., Bagbania, Baddi-Nalagarh Dist. Solan (HP)- 174 101, India MBTC1A1 22 B/4 Feb-23 Misoprostol ACME Formulation Ltd.., Ropar Road, Nalagarh Dist. Solan, Himachal,PRADESH- 174101, India MCL2008069 5 B/4 Jul-2022 MCL2105058 1 Apr-2023 MCL2002019 2 Jan-2022 Misoprostol ACME Formulation Ltd.., Ropar Road, Nalagarh Dist. Solan, Himachal,PRADESH- 174101, India MIS2010005 4 B/4 Sep-2022 Total Samples 34 Table 3: Registration and WHO prequalification status of oxytocin and misoprostol collected from Côte d’Ivoire and Senegal. INN name Manufacturer Registration WHO Prequalification Côte d’Ivoire Oxytocin Rotexmedica GmbH, Germany Not registered Not prequalified Oxytocin NCPC International - China Not registered Not prequalified Oxytocin CIRON Drugs & Pharma, India Not registered Not prequalified Oxytocin Troikaa Pharmaceuticals, India Registered Not prequalified Oxytocin Medisol S.A.S - France Not registered Not prequalified Oxytocin Steril-Gene Life Sciences, India Registered Not prequalified Oxytocin Bharat parenterals ltd., India Not registered Not prequalified Misoprostol Quimica Y Farmaceutica, Spain Registered Not prequalified Misoprostol China Res.
Zizhu Pharma, Not registered RH048 Nov., 2016 Misoprostol ACME Formulation, India MA expired RH056 Apr., 2016 Misoprostol ACME Formulation, India Not registered RH056 Apr., 2016 Misoprostol ACME Formulation, India Not registered RH056 Apr., 2016 Misoprostol NAARI Pharmaceuticals, India Registered Not prequalified Senegal Oxytocin Xier Kangtai pharmaceutical Registered (Special import authorization) Not prequalified Oxytocin Troikaa pharmaceuticals, Registered Not prequalified Oxytocin Steril-gene life sciences, Registered Not prequalified Misoprostol United biotech Registered (Special import authorization) Not prequalified Misoprostol ACME Formulation (Misoclear) Registered WHO-PQ: ref: RH056 (04/2016) Misoprostol ACME Formulation (Misodia) Registered WHO-PQ: ref: RH056 04/2016 Research Article Table S1. Misoprostol and oxytocin samples collected from Côte d’Ivoire Sample code Region Sampling site Type of facility Sector Level of Supply Product Name Sample (200 mg tablets) Manufacturer Batch number Expiry date Nbr.
of units collected RCI/MSP/C1-03- 22/11/2021 Abidjan UBIPHARM-CI ZI, Abidjan Central warehouse Private 1 MISOFAR Misoprostol Industria Quimica & Farmaceutica VIR, Spain P003 May-23 56 RCI/MSP/C1-04- 22/11/2021 Abidjan UBIPHARM-CI ZI, Abidjan Central warehouse Private 1 MISO-FEM Misoprostol Naari Pharma Ltd. India NR00711A March-23 56 RCI/MSP/C1-05- 22/11/2021 Abidjan COPHARMED -ABIDJAN Central warehouse Private 1 MISOFAR Misoprostol Industria Quimica & Farmaceutica VIR, Spain P003 may-23 56 RCI/MSP/C1-06- 22/11/2021 Abidjan COPHARMED -ABIDJAN Central warehouse Private 1 MISOCLEAR Misoprostol ACME FORMULATION PVT LTD - INDIA MCL2107074 Jun-23 56 RCI/MSP/C1-07- 22/11/2021 Abidjan COPHARMED -ABIDJAN Central warehouse Private 1 MISO-FEM Misoprostol Naari Pharma Ltd. India NR00665B Jan-23 56 RCI/MSP/C1-08- 22/11/2021 Abidjan DPCI ABIDJAN Central warehouse Private 1 MISO-FEM Misoprostol Naari Pharma Ltd.
India NR00666C Feb-23 56 RCI/MSP/C1-09- 23/11/2021 SUD COMOE PHARMACIE BIANOUAN Private pharmacy Private 3 MISO-FEM Misoprostol Naari Pharma Ltd. India NR00711A March-23 56 RCI/MSP/C1-13- 24/11/2021 SUD COMOE PHARMACIE SANWI Private pharmacy Private 3 MISO-FEM Misoprostol Naari Pharma Ltd. India NR00628D déc-22 56 RCI/MSP/C1-16- 24/11/2021 SUD COMOE HOPITAL GENERAL DE MAFERE Hospital Public 3 MISOPROSTOL Misoprostol CHINA RESOURCES ZIZHU PHARMACEUTICAL Co LTD, CHINA 45200501 May-22 30 RCI/MSP/C1-18- 25/11/2021 Abidjan TEDIS PHARMA Abidjan Central warehouse Private 1 MISO-FEM Misoprostol Naari Pharma Ltd. India NR00711A March-23 56 RCI/MSP/C1-20- 25/11/2021 Abidjan HOPITAL GENERAL D’ADJAME Hospital Public 3 ACE MISO Misoprostol ACME FORMULATION PVT LTD - INDIA ACE2006041 May-2 57 RCI/MSP/C1-21- 26/11/2021 Abidjan NPSP-CI, BP V5 Abijan Central warehouse Public 1 ACE MISO Misoprostol ACME FORMULATION PVT LTD - INDIA ACE2103039 Feb-23 80 RCI/MSP/C1-22- 26/11/2021 Abidjan NPSP-CI, BP V5 Abidjan Central purchasing Public 1 ACE MISO Misoprostol ACME FORMULATION PVT LTD - INDIA ACE2103038 Feb-23 80 RCI/MSP/C1-25- 26/11/2021 Abidjan PHARMACI AGBAN, 06 BP 1279 Abidjan Pharmacy Private 3 MISO-FEM Misoprostol NAARI PHARMA PRIVATE LIMITED, - INDIA NR00711A March-23 56 RCI/MSP/C2-04- 29/11/2021 INDENIE- DJUANBLIN DISTRICT SANTITAIRE D’AGNIBILEKROU Regional Warehouse Public 2 Misoprostol Misoprostol CHINA RESOURCES ZIZHU PHARMACEUTICAL Co LTD, CHINA 45200501 May-22 57 RCI/MSP/C2-06- 29/11/2021 INDENIE- DJUANBLIN HOPITAL GENERAL D’AGNIBILEKROU Hospital Public 3 ACE MISO Misoprostol ACME FORMULATION PVT LTD - INDIA ACE2006041 May-22 54 RCI/MSP/C2-07- 29/11/2021 INDENIE- DJUANBLIN PHARMACIE K BOILOT AGNIBILEKROU Pharmacy Private 3 MISO-FEM Misoprostol NAARI PHARMA PRIVATE LIMITED, - INDIA NR00711A March-23 32 RCI/MSP/C2-12- 30/11/2021 INDENIE- DJUANBLIN PHARMACIE MARCHE D’ABENGOUROU Pharmacy Private 3 MISO-FEM Misoprostol NAARI PHARMA PRIVATE LIMITED, - INDIA NR0066C Feb-23 40 Research Article RCI/MSP/C2-15- 01/12/2021 INDENIE- DJUANBLIN DISTRICT SANTITAIRE D’ABENGOUROU Regional Warehouse Public 2 Misoprostol Misoprostol CHINA RESOURCES ZIZHU PHARMACEUTICAL Co LTD, CHINA 45200501 May-22 54 RCI/MSP/C2-17- 01/12/2021 INDENIE- DJUANBLIN CHR ABENGOUROU Hospital Public 3 ACE MISO Misoprostol ACME FORMULATION PVT LTD - INDIA ACE2006041 May-22 54 RCI/MSP/C2-20- 02/12/2021 IFFOU HOPITAL GENERAL DE DAOUKRO Hospital Public 3 MISO PROSTOL Misoprostol CHINA RESOURCES ZIZHU PHARMACEUTICAL Co LTD, CHINA 45200501 May-22 54 RCI/MSP/C2-22- 02/12/2021 IFFOU PHARMACIE DE L’AMITIE Pharmacy Private 3 MISO-FEM Misoprostol NAARI PHARMA PRIVATE LIMITED, - INDIA NR00711A March-23 32 RCI/MSP/C2-24- 03/12/2021 INDENIE- DJUANBLIN HOPITAL GENERAL D’ADZOPE Hospital Public 3 ACE MISO Misoprostol ACME FORMULATION PVT LTD - INDIA ACE2006041 May-22 54 RCI/MSP/C3-01- 29/11/2021 LÔH-DJIBOUA CHR DIVO Hospital Public 3 ACE MISO Misoprostol ACME FORMULATION PVT LTD - INDIA ACE2006041 May-22 54 RCI/MSP/C3-04- 29/11/2021 LÔH-DJIBOUA PHARMACIE DU MARCHE Pharmacy Private 3 MISO-FEM Misoprostol NAARI PHARMA PRIVATE LIMITED, - INDIA NR00711A March-23 32 RCI/MSP/C3-05- 29/11/2021 LÔH-DJIBOUA HOPITAL GENERAL DE LAKOTA Hospital Public 3 ACE MISO Misoprostol ACME FORMULATION PVT LTD - INDIA ACE2006041 May-22 54 RCI/MSP/C3-07- 29/11/2021 LÔH-DJIBOUA PHARMACIE DE LAKOTA Pharmacy Private 3 AVERTISO Misoprostol ACME FORMULATION PVT LTD - INDIA ACG2002002 Jan-22 32 RCI/MSP/C3-10- 29/11/2021 GÔH DISTRICT SANITAIRE GAGNOA 1 Regional Warehouse Public 2 ACE MISO Misoprostol ACME FORMULATION PVT LTD - INDIA ACE2006041 May-22 54 RCI/MSP/C3-12- 30/11/2021 GÔH UBIPHARM CI, Gagnoa Regional Warehouse Private 2 MISO-FEM Misoprostol NAARI PHARMA PRIVATE LIMITED, - INDIA NR00628D déc-22 56 RCI/MSP/C3-13- 30/11/2021 GÔH COPHARMED GAGNOA Regional Warehouse Private 2 MISO-FEM Misoprostol NAARI PHARMA PRIVATE LIMITED, - INDIA NR00666C Feb-23 56 RCI/MSP/C3-14- 01/12/2021 DISTRICT AUTONOME CHR YAMOUSSOKRO Hospital Public 3 MISOPROSTOL Misoprostol CHINA RESOURCES ZIZHU PHARMACEUTICAL Co LTD, CHINA 45200501 May-22 54 RCI/MSP/C3-16- 02/12/2021 DISTRICT AUTONOME PHARMACIE DE YAMOUSSOKRO Pharmacy Private 3 MISO-FEM Misoprostol NAARI PHARMA PRIVATE LIMITED, - INDIA NR00628D déc-22 56 RCI/MSP/C3-19- 02/12/2021 GBÊKÊ DISTRICT SANITAIRE BOUAKE SUD Regional Warehouse Public 2 ACE MISO Misoprostol ACME FORMULATION PVT LTD - INDIA ACE2006042 May-22 54 RCI/MSP/C3-20- 02/12/2021 GBÊKÊ PHARMACIE EL NISSI Pharmacy Private 3 MISO-FEM Misoprostol NAARI PHARMA PRIVATE LIMITED, - INDIA NR00711A March-23 56 RCI/MSP/C3-23- 03/12/2021 GBÊKÊ DPCI BOUAKE Regional Warehouse Private 2 MISO-FEM Misoprostol NAARI PHARMA PRIVATE LIMITED, - INDIA NR00628D déc-22 56 RCI/MSP/C3-24- 03/12/2021 GBÊKÊ TEDIS PHARMA BOUAKE Regional Warehouse Private 2 MISO-FEM Misoprostol NAARI PHARMA PRIVATE LIMITED, - INDIA NR00628D déc-22 56 RCI/MSP/C4- 001-23/11/2021 PORO HOPITAL REGIONAL DE KORHOGO Hospital Public 3 ACE MISO Misoprostol ACME FORMULATION PVT LTD - INDIA ACE2006042 May-22 30 Research Article RCI/MSP/C4- 004-23/11/2021 PORO DISTRICT SANITAIRE DE KORHOGO Regional Warehouse Public 2 MISOPROSTOL Misoprostol CHINA RESOURCES ZIZHU PHARMACEUTICAL Co LTD, CHINA 45200501 May-22 30 RCI/MSP/C4- 005-23/11/2021 PORO PHARMACIE PALAIS DE JUSTICE, KORHOGO Pharmacy Private 3 MISO-FEM Misoprostol NAARI PHARMA PRIVATE LIMITED, - INDIA NR00605B nov-22 40 RCI/MSP/C4- 006-24/11/2021 TCHOLOGO HOPITAL GENERAL DE OUANGOLO Hospital Public 3 ACE MISO Misoprostol ACME FORMULATION PVT LTD - INDIA ACE2006042 May-22 30 RCI/MSP/C4- 008-23/11/2021 TCHOLOGO PHARMACIE MODERNE DE OUANGOLO Pharmacy Private 3 MISO-FEM Misoprostol NAARI PHARMA PRIVATE LIMITED, - INDIA NR00711A March-23 40 RCI/MSP/C4- 011-25/11/2021 BAGOUE CSUS-PM DE BOUNDIALI Hospital Public 3 ACE MISO Misoprostol ACME FORMULATION PVT LTD - INDIA ACE2006042 May-22 39 RCI/MSP/C4- 012-25/11/2021 BAGOUE HOPITAL GENERAL DE BOUNDIALI Hospital Public 3 ACE MISO Misoprostol ACME FORMULATION PVT LTD - INDIA ACE2006042 May-22 39 RCI/MSP/C4- 014-25/11/2021 BAGOUE PHARMACIE FATIMA; BOUNDIALI Pharmacy Private 3 MISO-FEM Misoprostol NAARI PHARMA PRIVATE LIMITED, - INDIA NR00711A March-23 40 RCI/MSP/C4- 015-26/11/2021 KABADOUGOU HOPITAL GENERAL DE MADINANI Hospital Public 3 ACE MISO Misoprostol ACME FORMULATION PVT LTD - INDIA ACE2006042 May-22 39 RCI/MSP/C4- 018-27/11/2021 KABADOUGOU CHR D’ODIENNE Hospital Public 3 ACE MISO Misoprostol ACME FORMULATION PVT LTD - INDIA ACE2006042 May-22 39 RCI/MSP/C4- 021-27/11/2021 KABADOUGOU DISTRICT SANITAIRE D’ODIENNE Medicines depot Public 2 ACE MISO Misoprostol ACME FORMULATION PVT LTD - INDIA ACE2006042 May-22 30 RCI/MSP/C4- 023-27/11/2021 KABADOUGOU GRANDE PHARMACIE DU DENGUELE Pharmacy Private 3 MISO-FEM Misoprostol NAARI PHARMA PRIVATE LIMITED, - INDIA NR00711A March-23 32 RCI/OCY/C1- 01/22/11/2021 Abidjan UBIPHARM- CI ZI, Abidjan Central warehouse Private 1 OXYTROY Oxytocin TROIKAA PHARMACEUTICALS LTD, India 043152 Aug-23 24 amp RCI/OCY/C1- 02/22/11/2021 Abidjan UBIPHARM- CI ZI, Abidjan Central warehouse Private 1 OXYTROY Oxytocin TROIKAA PHARMACEUTICALS LTD, India 043153 Aug-23 24 amp RCI/OCY/C1- 10/23/11/2021 SUD COMOE Pharmacie de BIANOUAN Pharmacy Private 3 OCYTOCINE INJECTION Oxytocin NCPC International Corp.
China 200222 Feb-23 20 amp RCI/OCY/C1- 11/24/11/2021 SUD COMOE DISTRICT SANITAIRE ABOISSO Medicines depot Public 2 OCYTOCINE INJECTION Oxytocin NCPC International Corp. China 200310 March-23 20 amp RCI/OCY/C1- 12/24/11/2021 SUD COMOE CHR ABOISSO Hospital Public 3 OCYTOCINE INJECTION Oxytocin NCPC International Corp. China 200217 Feb-23 20 amp RCI/OCY/C1- 14/24/11/2021 SUD COMOE Pharmacie du SANWI Pharmacy Private 3 OXYTROY Oxytocin TROIKAA PHARMACEUTICALS LTD, India 043153 Aug-23 24 amp RCI/OCY/C1- 15/24/11/2021 SUD COMOE HOPITAL GENERAL MAFERE Hospital Public 3 OCYTOCINE INJECTION Oxytocin NCPC International Corp. China 200217 Feb-23 20 amp RCI/OCY/C1- 1724/11/2021 SUD COMOE Pharmacie AKA EBA Private Pharmacy Private 3 OXYTOCIN 5 Oxytocin ROTEXMEDICA Werk,Bunsenstrasse 4-22946 Trittau 00871 oct-23 20 amp RCI/OCY/C1- 19/25/11/2021 Abidjan TEDIS PHARMA, Central Warehouse Private 1 OXYTROY Oxytocin TROIKAA PHARMACEUTICALS LTD, India 043150 Jul-23 24 amp RCI/OCY/C1- 23/26/11/2021 Abidjan NPSP-CI, BP V5 Abidjan Central Warehouse Public 1 OXYTOCINE INJECTABLE BP Oxytocin CIRON DRUGS &PHARMACEUTICALS PVT.LTD India 1EB02241 may-23 20 amp RCI/OCY/C1- 24/26/11/2021 Abidjan NPSP-CI, BP V5 Abidjan Central Warehouse Public 1 OXYTOCINE INJECTABLE BP Oxytocin CIRON DRUGS &PHARMACEUTICALS PVT.LTD India 1EB04265 Jun-23 20 amp RCI/OCY/C1- 26/26/11/2021 Abidjan Pharmacie d’AGBAN Pharmacy Private 3 OXYTROY Oxytocin TROIKAA PHARMACEUTICALS LTD, India 043147 sept-22 24 amp RCI/OCY/C2- 01/29/11/2020 Gontougou Pharmacie des Brons Pharmacy Private 3 OXYTROY Oxytocin TROIKAA PHARMACEUTICALS LTD, India 043150 Jul-23 24 amp RCI/OCY/C2- 02/29/11/2021 Gontougou CENTRE DE SANTE RURAL DE SIASSO Hospital Public 3 OXYTOCIN INJECTION BP Oxytocin NCPC International Corp.
China 210208 Feb-24 20 amp RCI/OCY/C2- 03/29//1/2021 INDENIE- DJUANBLIN DISTRICT SANITAIRE D’AGNIBILEKRO Regional Werehouse Public 2 OCYTOCINE INJECTION Oxytocin NCPC International Corp. China 210208 Feb-24 20 amp RCI/OCY/C2- 05/29/11/2021 INDENIE- DJUANBLIN HOPITAL GENERAL AGNIBILEKRO Hospital Public 3 OXYTOCIN INJECTION BP Oxytocin BHARAT PARENTERALS LTD India 00001 May-22 20 amp RCI/OCY/C2- 08/29/11/2021 INDENIE- DJUANBLIN Pharmacie MAIRIE- NORD Pharmacy Private 3 PHARMA CINON Oxytocin STERIL-GENE LIFE SCIENCES(P) LTD India JR00001A Nov-22 20 amp RCI/OCY/C2- 09/30/11/221 INDENIE- DJUANBLIN CENTRE DE SANTE URBAIN DE NIABLE Hospital Public 3 OCYTOCINE INJECTION Oxytocin NCPC International Corp. China 210208 Feb-24 20 amp RCI/OCY/C2- 10/30/11/2021 INDENIE- DJUANBLIN CENTRE DE SANTE URBAIN D’EBILASSOKRO Hospital Public 3 OXYTOCIN INJECTION BP Oxytocin BHARAT PARENTERALS LTD India 00001 May-22 20 amp RCI/OCY/C2- 11/30/11/2021 INDENIE- DJUANBLIN Pharmacie d’EBILASSOKRO Pharmacy Private 3 OXYTROY Oxytocin TROIKAA PHARMACEUTICALS LTD, India 043150 Jul-23 15 amp RCI/OCY/C2- 13/30/11/2021 INDENIE- DJUANBLIN Pharmacie du MARCHE Pharmacy Private 3 OXYTROY Oxytocin TROIKAA PHARMACEUTICALS LTD, India 043153 Aug-23 24 amp RCI/OCY/C2- 14/01/12/2021 INDENIE- DJUANBLIN DISTRICT SANITAIRE d’ABENGOUROU Regional Warehouse Public 2 OCYTOCINE INJECTION Oxytocin NCPC International Corp.
China 210208 Feb-24 20 amp RCI/OCY/C2- 16/01/12/2021 INDENIE- DJUANBLIN CENTRE HOSPITALIER REGIONAL d’ABENGOUROU Hospital Public 3 OCYTOCINE INJECTION Oxytocin NCPC International Corp. China 200223 Feb-23 20 amp RCI/OCY/C2- 18/01/12/2021 IFFOU FORMATION SANITAIRE DE PEPRESSOU Hospital Public 3 OXYTOCIN INJECTION BP Oxytocin BHARAT PARENTERALS LTD Inde 00004 May-22 20 amp RCI/OCY/C2- 19/02/12/2021 IFFOU HOPITAL GENERAL DE DAOUKRO Hospital Public 3 OCYTOCINE INJECTION Oxytocin NCPC International Corp. China 210208 Feb-24 20 amp RCI/OCY/C2- 21/02/12/2021 IFFOU Pharmacie de DAOUKRO Pharmacy Private 3 OXYTROY Oxytocin TROIKAA PHARMACEUTICALS LTD, India 043147 sept-22 24 amp RCI/OCY/C2- 23/03/12/2021 INDENIE- DJUANBLIN HOPITAL GENERAL D’ADZOPE Hospital Public 3 OXYTOCIN INJECTION BP Oxytocin BHARAT PARENTERALS LTD India 00002 May-22 20 amp RCI/OCY/C2- 25/03/12/2021 INDENIE- DJUANBLIN Pharmacie EUREKA Pharmacy Private 3 OXYTROY Oxytocin TROIKAA PHARMACEUTICALS LTD, India 043153 Aug-23 24 amp RCI/OCY/C3- 02/29/11/2021 LÔH-DJIBOUA CENTRE HOSPITALIER REGIONAL DIVO Hospital Public 3 OCYTOCINE INJECTION Oxytocin NCPC International Corp.
China 210208 Feb-24 20 amp RCI/OCY/C3- 03/29/11/2021 LÔH-DJIBOUA Pharmacie du MARCHE Pharmacy Private 3 OXYTROY Oxytocin TROIKAA PHARMACEUTICALS LTD, India 043152 Aug-23 24 amp RCI/OCY/C3- 06/29/11/2021 LÔH-DJIBOUA HOPITAL GENERAL DE LAKOTA Hospital Public 3 OCYTOCINE INJECTION Oxytocin NCPC International Corp. China 210208 Feb-24 20 amp RCI/OCY/C3- 08/29/11/2021 LÔH-DJIBOUA Pharmacie de LAKOTA Pharmacy Private 3 OXYTROY Oxytocin TROIKAA PHARMACEUTICALS LTD, India 043148 Jun-23 24 amp RCI/OCY/C3- 09/29/11/2021 GÔH DISTRICT SANITAIRE DE GAGNOA 1 Regional Warehouse Public 2 OCYTOCINE INJECTION Oxytocin NCPC International Corp. China 200217 Feb-23 20 amp RCI/OCY/C3- 11/30/11/2021 GÔH UBIPHARM CI, Gagnon Regional Warehouse Private 2 OXYTROY Oxytocin TROIKAA PHARMACEUTICALS LTD, India 043148 Jun-23 24 amp RCI/OCY/C3- 15/01/12/2021 DISTRICT AUTONOME YAMOUSSOKRO CENTRE HOSPITALIER REGIONAL de YAMOUSSOKRO Hospital Public 3 OCYTOCINE INJECTION Oxytocin NCPC International Corp.
China 200223 Feb-23 20 amp RCI/OCY/C3- 17/02/12/2021 DISTRICT AUTONOME YAMOUSSOKRO Pharmacie de YAMOUSSOKRO Pharmacy Private 3 PHARMA CINON Oxytocin STERIL-GENE LIFE SCIENCES(P) LTD India JR00001B nov-22 24 amp RCI/OCY/C3- 18/02/12/2021 GBÊKÊ DISTRICT SANITAIRE BOUAKE SUD Regional Warehouse Public 2 OCYTOCINE INJECTION Oxytocin NCPC International Corp.China 210208 Feb-24 20 amp RCI/OCY/C3- 21/02/12/2021 GBÊKÊ Pharmacie EL NISSI Pharmacy Private 3 OXYTROY Oxytocin TROIKAA PHARMACEUTICALS LTD, Inde 043153 Aug-23 24 amp RCI/OCY/C3-23- 03/12/2021 GBÊKÊ TEDIS Pharma ,Bouake Regional Warehouse Private 2 PHARMA CINON Oxytocin STERIL-GENE LIFE SCIENCES(P) LTD India JR0001B nov-22 24 amp RCI/OCY/C4- 02/23/11/2021 PORO HOPITAL REGIONAL de KORHOGO Hospital Public 3 OCYTOCINE INJECTION Oxytocin NCPC International Corp. China 210208 Feb-24 30 amp RCI/OCY/C4- 03/23/11/2021 PORO DISTRICT SANITAIRE de KORHOGO Regional Warehouse Public 2 OCYTOCINE INJECTION Oxytocin NCPC International Corp.
China 200223 Feb-23 30 amp RCI/OCY/C4- 07/24/11/2021 TCHOLOGO DISTRICT SANITAIRE de OUANGOLO Regional Warehouse Public 2 OCYTOCINE INJECTION Oxytocin NCPC International Corp. China 210208 Feb-24 30 amp RCI/OCY/C4- 09/23/11/2021 TCHOLOGO Pharmacie MODERNE Pharmacy Private 3 PHARMA CINON Oxytocin STERIL-GENE LIFE SCIENCES(P) LTD India JR0001B Nov-22 21 amp RCI/OCY/C4- 10/23/11/2021 TCHOLOGO Pharmacie MODERNE Pharmacy Private 3 OCYTOCINE MEDISOL Oxytocin MEDISOL S.A.S 11 rue Jacques Monod 69007 Lyon ME011X5 may-23 25 amp RCI/OCY/C4- 13/25/11/2021 BAGOUE HOPITAL GENERAL de BOUNDIALI Hospital Public 3 OCYTOCINE INJECTION Oxytocin NCPC International Corp. China 210208 Feb-24 25 amp RCI/OCY/C4- 16/26/11/2021 KABADOUGOU HOPITAL GENERAL de MADINANI Hospital Public 3 OCYTOCINE INJECTION Oxytocin NCPC International Corp. China 200310 March-23 30 amp RCI/OCY/C4- 17/26/11/2021 KABADOUGOU HOPITAL GENERAL de MADINANI Hospital Public 3 OCYTOCINE INJECTION Oxytocin NCPC International Corp.
China 190522 May-22 30 amp RCI/OCY/C4- 19/27/11/2021 KABADOUGOU CENTRE HOSPITALIER REGIONAL Hospital Public 3 OCYTOCINE INJECTION Oxytocin NCPC International Corp. China 200223 Feb-23 30 amp RCI/OCY/C4- 20/27/11/2021 KABADOUGOU CENTRE de SANTE URBAIN-PMI Hospital Public 3 OCYTOCINE INJECTION Oxytocin NCPC International Corp. China 200310 March-23 2.5 amp RCI/OCY/C4- 22/27/11/2021 KABADOUGOU Grande Pharmacie du DENGUELE Pharmacy Private 3 OXYTROY Oxytocin TROIKAA PHARMACEUTICALS LTD, India 043148 Jun-23 21 amp RCI/OCY/C4- 24/27/11/2021 KABADOUGOU Grande Pharmacie du DENGUELE Pharmacy Private 3 OXYTROY Oxytocin TROIKAA PHARMACEUTICALS LTD, India 043150 Jul-23 21 amp RCI/OCY/C4- 25/27/11/2021 KABADOUGOU Grande Pharmacie du DENGUELE Pharmacy Private 3 OXYTROY Oxytocin TROIKAA PHARMACEUTICALS LTD, India 043147 sept-22 21 amp Table S2: Samples of oxytocin and misoprostol collected from Senegal Sample Code Sample site Type of facility Sector Level of Supply Product name Manufacturer Batch number Expiry date Number of units collected SN/DAK/ OCT/01/30- 08-21 Laborex Senegal central Private 1 Oxytocin STERIL-GENE LIFE SCIENCES (P) Ltd JR0001A 11/2022 10 SN/DAK/ OCT/02/30- 08-21 Laborex Senegal Central Private 1 Oxytocin STERIL-GENE LIFE SCIENCES (P) Ltd JR0001B 11/2022 15 SN/DAK/ OCT/22/30- 08-2021 PNA central central Public 1 Oxytocin XIER KANGTAI PHARMACEUTICAL CO., LTD S230Q04 07/2024 10 SN/DAK/ OCT/23/30- 08-2021 PNA central central Public 1 Oxytocin XIER KANGTAI PHARMACEUTICAL CO., LTD S230Q04 07/2024 10 SN/DAK/ OCT/24/30/- 08-2021 Ubipharm Belair central Private 1 Oxtroy TROIKAA PHARMACEUTICALS LTD 043147 09/22 12 SN/DAK/ OCT/25/30/- 08-2021 UBIPHARM BEL AIR central Private 1 Oxtroy TROIKAA PHARMACEUTICALS LTD 043147 09/22 12 SN/KAF/ OCT/01/27- 08-21 District de Kaffrine District sanitaire Public 2 Oxytocin XIER KANGTAI PHARMACEUTICAL CO., LTD S230Q03 07/2023 10 SN/KAF/ OCT/02/27- 08-21 Poste de santé URBAIN 1 Poste de santé Public 3 Oxytocin XIER KANGTAI PHARMACEUTICAL CO., LTD S230Q03 07/2023 10 SN/KAF/ OCT/03/27- 08-21 Pharmacie La Kongheuloise Pharmacy Private 3 Oxtroy TROIKAA PHARMACEUTICALS LTD 043146 09/22 12 SN/KAF/ OCT/04/27- 08-21 EPS Kaffrine Hospital Public 3 Oxytocin XIER KANGTAI PHARMACEUTICAL CO., LTD S230Q03 07/2023 10 SN/KAF/ OCT/05/30- 08-21 Pharmacie Régionale DE KAFFRINE Wholesaler regional Private 2 Oxytocin XIER KANGTAI PHARMACEUTICAL CO., LTD S230Q03 07/2023 10 Research Article SN/KAF/ OCT/06/30- 08-21 Poste de santé DIAMAGUEUNE Poste de santé Public 3 Oxytocin XIER KANGTAI PHARMACEUTICAL CO., LTD S230Q03 07/2023 10 SN/KAF/ OCT/07/30- 08-21 Pharmacie Ndeye Fary SY Pharmacy Private 3 Oxtroy TROIKAA PHARMACEUTICALS LTD 043146 09/22 12 SN/KAF/ OCT/08/30- 08-21 Pharmacie NDOUCOUMANE Pharmacy Private 3 Oxtroy TROIKAA PHARMACEUTICALS LTD 043146 09/22 12 SN/KAF/ OCT/09/30- 08-21 Pharmacie Khadimar Rassoul Pharmacy Private 3 Oxtroy TROIKAA PHARMACEUTICALS LTD 043147 09/22 12 SN/KAO/ OCT/01/23- 08-21 SODIPHARM KAOLACK Wholesaler regional Private 2 Oxtroy TROIKAA PHARMACEUTICALS LTD 043147 09/22 12 SN/KAO/ OCT/02/23- 08-21 UBIPHARM KAOLACK Wholesaler regional Private 2 Oxtroy TROIKAA PHARMACEUTICALS LTD 043147 09/22 12 SN/KAO/ OCT/03/23- 08-21 UBIPHARM KAOLACK Wholesaler regional Private 2 Oxtroy TROIKAA PHARMACEUTICALS LTD 043146 09/22 12 SN/KAO/ OCT/04/23- 08-21 Pharmacie Kaolackoise Pharmacy Private 3 Oxtroy TROIKAA PHARMACEUTICALS LTD 043139 06/22 12 SN/KAO/ OCT/05/24- 08-21 Pharmacie Village Artisanal Pharmacy Private 3 Oxtroy TROIKAA PHARMACEUTICALS LTD 043146 09/22 12 SN/KAO/ OCT/06/25- 08-21 Poste de santé Keur SOCE Poste de santé Public 3 Oxtroy XIER KANGTAI PHARMACEUTICAL CO., LTD S230Q03 07/2023 10, inc.
1 broken SN/KAO/ OCT/07/25- 08-21 District de Kaolack District sanitaire Public 2 Oxytocin XIER KANGTAI PHARMACEUTICAL CO., LTD S230Q01 (S230Q03 on box) 07/2023 10 SN/KAO/ OCT/08/25- 08-21 Poste de santé Keur BAKA Poste de santé Public 3 Oxytocin XIER KANGTAI PHARMACEUTICAL CO., LTD S230Q01 07/2022 10 SN/KAO/ OCT/09/25- 08-21 Pharmacie Hopital Régional de Kaolack Hospital Public 3 Oxytocin XIER KANGTAI PHARMACEUTICAL CO., LTD S230Q01 (S230Q03 on box) 07/2023 10 SN/KAO/ OCT/10/26- 08-21 Poste de santé DIALEGNE Poste de santé Public 3 Oxytocin XIER KANGTAI PHARMACEUTICAL CO., LTD S230Q03 07/2023 10 SN/KAO/ OCT/11/26- 08-21 Pharmacie Boulevard de la Medina Officine Private 3 Oxytocin TROIKAA PHARMACEUTICALS LTD 431400 (043140 on box) 06/22 12 SN/KED/ OCT/11/25- 08-2021 Centre de santé Kédougou Centre de Santé Public 3 Oxytocin XIER KANGTAI PHARMACEUTICAL CO., LTD S230Q03 07/2023 10 SN/KED/ OCT/12/25- 08-2021 District de Kédougou District sanitaire Public 2 Oxytocin XIER KANGTAI PHARMACEUTICAL CO., LTD S230Q03 07/2023 10 Research Article SN/KED/ OCT/13/25- 08-2021 Poste de santé de MAKO Poste de santé Public 3 Oxytocin XIER KANGTAI PHARMACEUTICAL CO., LTD S230Q03 07/2023 10 SN/KED/ OCT/14/25- 08-2021 PHARMACIE YA SALAM Officine Private 3 Oxtroy TROIKAA PHARMACEUTICALS LTD 043140 06/22 12 SN/KED/ OCT/15/25- 08-2021 PHARMACIE AL MAKHTOUM Officine Private 3 Oxtroy TROIKAA PHARMACEUTICALS LTD 043139 06/22 12 SN/KED/ OCT/16/25- 08-2021 PHARMACIE KENYA Officine Private 3 Oxytocin TROIKAA PHARMACEUTICALS LTD 043146 09/22 12 SN/KED/ OCT/17/25- 08-2021 POSTE DE SANTE DE TOMBORONKOTO Poste de santé Public 3 Oxytocin XIER KANGTAI PHARMACEUTICAL CO., LTD S230Q03 07/23 10 SN/KED/ OCT/18/26- 08-2021 POSTE DE SANTE DE BEMBOU Poste de santé Public 3 Oxytocin XIER KANGTAI PHARMACEUTICAL CO., LTD S230Q03 07/23 10 SN/KED/ OCT/19/26- 08-2021 CENTRE DE SANTE DE SARAYA Centre de Santé Public 3 Oxytocin XIER KANGTAI PHARMACEUTICAL CO., LTD S230Q03 07/23 10 SN/LOU/ OCT/01/23- 08-21 Hospital Amadou Sakhir Louga Hospital public 3 Oxytocin XIER KANGTAI PHARMACEUTICAL CO., LTD S230Q03 07/23 30 SN/LOU/ OCT/02/23- 08-21 PRA LOUGA Wholesaler regional public 2 Oxytocin XIER KANGTAI PHARMACEUTICAL CO., LTD S230Q03 07/23 10 SN/LOU/ OCT/04/24- 08-21 Pharmacie EL HADJI OMAR TALL Officine Private 3 Oxtroy TROIKAA PHARMACEUTICALS LTD 043146 09/22 9 SN/LOU/ OCT/05/24- 08-21 Pharmacie BOROM DAROU Officine Private 3 Oxtroy TROIKAA PHARMACEUTICALS LTD 043142 07/22 12 SN/LOU/ OCT/06/24- 08-21 Poste de Santé FASS TOURE Poste de santé Public 3 Oxytocin XIER KANGTAI PHARMACEUTICAL CO., LTD S230Q02 (S230Q03 on box) 07/2023 10 SN/LOU/ OCT/07/24- 08-21 Poste de Santé DAROU MARNANE Poste de santé Public 3 Oxytocin XIER KANGTAI PHARMACEUTICAL CO., LTD S230Q03 07/2023 10 SN/LOU/ OCT/08/24- 08-21 POSTE DE SANTE MARIEME FAYE SALL Poste de santé Public 3 Oxytocin XIER KANGTAI PHARMACEUTICAL CO., LTD S230Q03 07/2023 10 SN/LOU/ OCT/09/24- 08-21 District SANITAIRE DE DAROU MOUSTY District sanitaire Public 2 Oxytocin XIER KANGTAI PHARMACEUTICAL CO., LTD S230Q03 07/2023 10 SN/SAI/ OCT/01/25- 08-21 PRA SAINT-LOUIS Wholesaler regional Public 2 Oxytocin XIER KANGTAI PHARMACEUTICAL CO., LTD S230Q03 07/2023 10 SN/SAI/ OCT/02/25- 08-21 HOPITAL REGIONAL DE SAINT-LOUIS Hospital Public 3 Oxytocin XIER KANGTAI PHARMACEUTICAL CO., LTD S230Q03 07/2023 10 Research Article SN/SAI/ OCT/03/25- 08-21 Pharmacie ROKHAYA GAYE Officine Private 3 OXYTROY TROIKAA PHARMACEUTICALS LTD 043146 09/22 12 SN/SAI/ OCT/05/26- 08-21 District Sanitaire de RICHARD-TOLL District sanitaire Public 2 Oxytocin XIER KANGTAI PHARMACEUTICAL CO., LTD S230Q03 07/2023 10 SN/SAI/ OCT/06/26- 08-21 Poste de santé THIABAKH Poste de santé Public 3 Oxytocin XIER KANGTAI PHARMACEUTICAL CO., LTD S230Q02 02/2023 10 SN/SAI/ OCT/07/26- 08-21 Poste de santé TAOWEY Poste de santé Public 3 Oxytocin XIER KANGTAI PHARMACEUTICAL CO., LTD S230Q03 07/23 10 SN/TAM/ OCT/20/26- 08-2021 Not reported in country sampling report Not reported in country sampling report Not reported in country sampling report Not reported in country sampling report Oxytocin XIER KANGTAI PHARMACEUTICAL CO., LTD S230Q03 07/23 10 SN/TAM/ OCT/01/23- 08-2021 EPS TAMBA EPS Public 3 Oxytocin XIER KANGTAI PHARMACEUTICAL CO., LTD S230Q03 07/23 10 SN/TAM/ OCT/02/23- 08-2021 PHARMACIE NAMOUSSA Pharmacy Private 3 Oxtroy TROIKAA PHARMACEUTICALS LTD 043140 06/22 12 SN/TAM/ OCT/03/23- 08-2021 POSTE SANTE SINTHIOU MALHEM Poste de santé Public 3 Oxytocin XIER KANGTAI PHARMACEUTICAL CO., LTD S230Q03 07/23 10 SN/TAM/ OCT/04/23- 08-2021 POSTE SANTE DEPOT TAMBACOUDA Poste de santé Public 3 Oxytocin XIER KANGTAI PHARMACEUTICAL CO., LTD S230Q03 07/23 10 SN/TAM/ OCT/05/23- 08-2021 POSTE SANTE GOUREL DIADE Poste de santé Public 3 Oxytocin XIER KANGTAI PHARMACEUTICAL CO., LTD S230Q03 07/23 6 SN/TAM/ OCT/06/23- 08-2021 PRA TAMBA Wholesaler regional Public 2 Oxytocin XIER KANGTAI PHARMACEUTICAL CO., LTD S230Q03 07/23 10 SN/TAM/ OCT/07/24- 08-2021 CENTRE DE SANTE TAMBACOUNDA Centre de Santé Public 3 Oxytocin XIER KANGTAI PHARMACEUTICAL CO., LTD S230Q03 07/23 10 SN/TAM/ OCT/08/24- 08-2021 District Tambacouda District sanitaire Public 2 Oxytocin XIER KANGTAI PHARMACEUTICAL CO., LTD S230Q03 07/23 10 SN/TAM/ OCT/09/24- 08-2021 POSTE DE SANTE DE PONT Poste de santé Public 3 Oxytocin XIER KANGTAI PHARMACEUTICAL CO., LTD S230Q03 07/23 10 SN/TAM/ OCT/10/24- 08-2021 DUOPHARM TAMBA Wholesaler regional Private 2 Oxtroy TROIKAA PHARMACEUTICALS LTD 043146 09/22 12 Research Article SN/TAM/ OCT/21/27- 08-2021 Not reported in country sampling report Not reported in country sampling report Not reported in country sampling report Not reported in country sampling report Oxtroy TROIKAA PHARMACEUTICALS LTD 043147 09/22 12 Results of oxytocin and misoprostol products sampled in Côte d’Ivoire The quality control results revealed that all 52 oxytocin samples met the monograph specifications for description, identity, pH, and particulate matter.
However, 9.6% of the samples tested failed the assay test, and 48% failed the related substances test. This amounts to a 54% failure rate (Table 4). Notably, 92% of the oxytocin samples that failed were not registered with the local NMRA. The National Laboratory (Laboratoire National de Santé Publique, LNSP) in Côte d’Ivoire conducted identity, pH, and assay tests on the same oxytocin samples tested by MIPS. Their findings indicated that all samples met the requirements for identity and pH tests. However, 33% of the samples failed the assay test according to the Ph. Int monograph. The assay test failure rate reported by LNSP was higher than the MIPS results (Table 5).
LNSP did not conduct any out-of-specification investigations for the assay tests on the oxytocin samples, and related substances tests were not performed by LNSP. The quality control of 47 tested misoprostol samples met the Ph. Int monograph specifications for description, packaging, labeling, identification, and assay tests. One sample was excluded from the analysis due to its expiration. While 95.8% of the samples passed the tests, 2 samples (4.2%) yielded inconclusive results. One sample failed the level-1 uniformity of content test, and the other failed the stage-1 dissolution test. However, due to insufficient units for further testing, both results were deemed inconclusive as per Ph. Int guidelines (Table 6). Substandard oxytocin and misoprostol samples were identified at both level-2 and level-3 of the supply chain in Côte d’Ivoire, mainly within public health facilities (Table 7).
Table 4 : Summary of test results of oxytocin samples from Côte d’Ivoire Commercial name Manufacturer No. batch tested Assay Related substances (RS) Total samples Pass Fail Pass Fail Fail Pharmacinon Sterile-Gene Life Sciences Pharma (SGLS), India 4 1 3 4 0 3 Oxtroy Troikka Formulation 17 17 0 16 1 1 Oxytocin Medisol SAS, France 1 1 0 1 0 0 Oxytocin Ciron Pharma, India 2 2 0 2 0 0 Oxytocin North China Pharmaceutical Co (NCPC), China 23 21 2 0 23 23 Oxytocin Bharat Parenterals 4 4 0 3 1 1 Oxytocin Rotexomedica 1 1 0 1 0 0 TOTAL 52 47 5 27 25 28 Research Article Table 5: Comparison of assay test failures between LNSP and MIPS laboratory from oxytocin samples in Côte d’Ivoire Oxytocin Samples Manufacturer LNSP Lab – Assay test results MIPS Lab – Assay test results RCI/OCY/C1-10 NCPC 74.3 89.8 RCI/OCY/C1-11 NCPC 87.9 96.4* RCI/OCY/C1-12 NCPC 88.8 95.9* RCI/OCY/C2-02 NCPC 82.5 108.7* RCI/OCY/C2-08 SGLS Pharma 85.8 89.5 RCI/OCY/C2-09 NCPC 87.6 102.5* RCI/OCY/C2-19 NCPC 87.3 101.0* RCI/OCY/C3-06 NCPC 88.4 108.2* RCI/OCY/C3-09 NCPC 88.1 97.6* RCI/OCY/C3-15 NCPC 88.2 101.3* RCI/OCY/C3-17 SGLS Pharma 88.4 88.3 RCI/OCY/C3-18 NCPC 87.1 101.5* RCI/OCY/C4-07 NCPC 89.0 101.3* RCI/OCY/C4-09 SGLS Pharma 87.3 88.5 RCI/OCY/C4-13 NCPC 88.8 101.8* RCI/OCY/C4-17 NCPC 68.5 81.7 RCI/OCY/C4-19 NCPC 88.2 100.2* Total oxytocin samples that failed the assay test 17 5 Table 6: Failed misoprostol samples from Côte d’Ivoire Region Supply Level INN Name Manufacturer Batch No.
Failed Test Tchologou Level-2 Misoprostol ACME Formul. ACE2006042 UoC at L1 Kabadougou Level-2 Misoprostol ACME Formul. ACE2006042 Diss at S1 47 samples tested out of 48 misoprostol samples collected 2 failed * Table 7: Quality test results per levels of the supply chain in Côte d’Ivoire OXYTOCIN INJECTION MISOPROSTOL TABLETS No. samples tested No. samples that pass the test (%) No. samples that fail the test (%) No. samples tested No. samples that pass the test (%) No. samples that fail the test (%) LEVEL 1 5 5 (100%) 0 (0%) 9 9 (100%) 0 (0%) LEVEL 2 9 2 (22.2%) 7 (77.8%) 10 9 (90%) 1 (10%) LEVEL 3 38 17 (44.7%) 21 (55.3%) 29 28 (96.6%) 1 (3.4%) Results of oxytocin and misoprostol products sampled in Senegal The quality control results revealed that 62 samples of oxytocin met the Ph.
Int specifications for description, particulate matter, identity, pH, and related substances tests. However, 5% of the samples failed the assay test (Table 8). Among the three non-compliant samples, two were from public level-3 and one from private level-1 facilities. The quality control of 33 misoprostol samples met the specifications outlined in the Ph. Int monograph for description, storage, identification, and assay. One sample was excluded from the analysis due to its expiration. Only one sample failed the uniformity of content test. However, due to insufficient tablets to complete the subsequent test stage, the results were reported as inconclusive. Additionally, 41.4% samples failed at the first dissolution stage, but the lack of sufficient units prevented continuation to stage 2, resulting in inconclusive results (Table 9).
A significant proportion, 83%, of the failed samples were from the same manufacturer. Overall, the majority of failed misoprostol samples were found in the public sector. Although substandard products were present at all levels of the public sector supply chain, it was predominantly level-3 in the private sector where these were found (Table 9). Overall, substandard oxytocin and misoprostol samples were identified at level-1 and level-2, and at levels 1-3 respectively (Table 10). In Senegal, the oxytocin and misoprostol samples collected were not tested by the local national laboratory. Table 8: Failed oxytocin samples from Senegal Commercial name Manufacturer No. batch tested Assay Related Substances (RS) Total Samples Pass Fail Pass Fail Failed Pharmacinon Steril-gene life Sci.
India 2 1 1 2 0 1 Oxtroy Troikka Formulation, 22 22 0 22 0 1 Oxytocin XIER Kangtai Pharma 38 36 2 38 0 2 TOTAL 62 59 3 62 0 3 (4.8%) Table 9 : Failed misoprostol samples in Senegal Region Supply Level INN Name Manufacturer Batch No. Failed Test Louga Level-3 Misoprostol United Biotech, MBTC1A1 Diss at S1 Louga Level-3 Misoprostol ACME Formul. MCL2008069 Diss at S1 Louga Level-3 Misoprostol United Biotech, MBTC1A1 Diss at S1 St Louis Level-2 Misoprostol United Biotech MBTC1A1 Diss at S1 St Louis Level-3 Misoprostol United Biotech, MBTC1A1 Diss at S1 Tambacounda Level-3 Misoprostol United Biotech, MBTC1A1 Diss at S1 Tambacounda Level-3 Misoprostol ACME Formul.
MCL2010005 Diss at S1 Dakar Level-1 Misoprostol United Biotech, MBTC1A1 Diss at S1 Dakar Level-1 Misoprostol United Biotech MBTC1A1 Diss at S1 Kafferine Level-3 Misoprostol United Biotech MBTC1A1 Diss at S1 Kafferine Level-3 Misoprostol United Biotech, MBTC1A1 Diss at S1 Kafferine Level-2 Misoprostol United Biotech, MBTC1A1 Diss at S1 Dakar Level-3 Misprostol ACME Formul. MCL2008069 UoC at L1 Research Article Table 10 : Quality test results per levels of the supply chain in Senegal Oxytocin Injection Misoprostol Tablets Tested Pass Failed (%) Tested Pass Failed Level 1 4 3 1 (1.6%) 3 1 2 (6%) Level 2 15 15 0 (0%) 9 7 2 (6%) Level 3 43 41 2 (3.2%) 21 8 13 (39%) Total 62 59 3 (4.8) 33 16 17 (51%) Research Article
Discussion This post-marketing surveillance study revealed that 30% of oxytocin samples (54% in Côte d’Ivoire; 5% in Senegal) and 23% of misoprostol samples (4.2% in Côte d’Ivoire; 41.4% in Senegal) were deemed substandard across all levels of the supply chain in both public and private sectors. Of significant concern are the findings on substandard oxytocin samples passing the assay test but failing the related substances test as it suggests that impurities in the finished product formulations might be responsible for the non-compliance, rather than degradation of the active pharmaceutical ingredient. This indicates that storage conditions alone might not be the sole cause for the substandard quality of these products. Notably, 44% of the identified substandard oxytocin in Côte d’Ivoire originated from a single manufacturer.
In Côte d’Ivoire, only 4.2% of misoprostol samples were substandard, while in Senegal, 41.4% of misoprostol samples were found to be substandard at the first dissolution test. Given that the majority of these substandard samples from Senegal originated from the same manufacturer and batch, and were collected from various levels of the supply chain with dissolution values below 85%, it is reasonable to deduce that samples from this batch are likely to fail further stages of the dissolution test. This study represents the first assessment of oxytocin and misoprostol quality in West Africa, showing results consistent with similar surveys conducted in Anglophone African countries[13, 18-22]. The study’s limitations included difficulties in obtaining sufficient units per sample, compounded by the packaging of two misoprostol tablets per pack, which impeded the collection of adequate number of units from the same batch.
Determining the optimal number of units for testing remains a challenge necessitating a balance between cost considerations, the risk of potential medicine shortages, and technical demands of testing requirements. It is to be noted that the substandard batches of both misoprostol and oxytocin were withdrawn from the market following investigations by national agencies post-analysis. The study also evaluated the registration status of the collected products. In Senegal, all the sampled brands were registered by the NMRA; however, in Côte d’Ivoire, only 4 out of the 13 identified brands were registered by the NMRA. This implies a potential prevalence of substandard products in the market, posing a considerable risk to the community.
These findings align with other studies conducted LMICs assessing the quality of oxytocin and misoprostol, revealing instances of unregistered or unlicensed medicines.[13, 18-20, 23] Typically, unregistered medicines are commonly discovered in private and informal sectors during such surveys. However, this study identified unregistered medicines in level-2 and level-3 of public health facilities in all regions evaluated, except in Abidjan in Côte d’Ivoire. Furthermore, while most misoprostol products were sourced from WHO prequalified manufacturers, none of the oxytocin samples were sourced from WHO prequalified manufacturers.[24] This study aimed to enhance the capabilities of the national laboratories in both countries. The LNSP in Côte d’Ivoire conducted all the tests except for related substances due to capacity constraints.
Interestingly, all the samples that failed the testing at the MIPS laboratory also failed at the LNSP laboratory. However, the LNSP identified more failed samples compared to the MIPS lab. This variance in results between the MIPS and LNSP laboratories could be attributed to factors such as varying levels of experience in testing these specific medicines, differences in the quality management systems, and the qualifications of personnel, among other reasons. Lastly, the discovery of similar brands of oxytocin and misoprostol in both Côte d’Ivoire and Senegal underscores the necessity for West African countries to conduct crossborder surveys on the quality of essential medicines. Moreover, some of the oxytocin and misoprostol brands examined in this study were also identified in Rwanda, the Democratic Republic of Congo (DRC), Ghana, and Malawi.
[18, 20-22] Sharing information on substandard and falsified medicines among NMRAs, particularly through the WHO Global Surveillance and Monitoring System (GSMS), can significantly aid in identifying reliable suppliers of uterotonic drugs. The study results were shared with the authorities in Côte d’Ivoire and Senegal. Subsequently, the NMRAs swiftly initiated investigations to identify the underlying causes of substandard products’ presence in the market and recalled the substandard product batches from circulation. This underscores the effectiveness and significance of PMS surveys in strengthening health systems. By compiling data based on evidence and conducting comprehensive analyses, informed decisions were taken to protect public health. To combat the proliferation of falsified and substandard uterotonic medicines, strengthening regulatory systems within these countries is essential.
Moreover, it is recommended that a comprehensive and risk-based postmarketing surveillance of oxytocin and misoprostol in the market should be regularly conducted as part of the overall management of these medications and as a mechanism to bolster the national supply chain.
Conclusion A substantial proportion of oxytocin and misoprostol products available in Côte d’Ivoire and Senegal were found to be substandard. Investing in quality-assured medicines is crucial for delivering safe and effective healthcare, reducing overall healthcare costs, and securing the long-term success of universal health coverage in low-income countries. Acknowledgements The World Health Organization would like to express its gratitude to Dr. Attie Yves Landry, Dr. Guei-Kore Valéry, Suy Bi Bohou, Namakolo Sacre Pascal from AIRP Cote d’Ivoire, and Professor Yerim Mbagnick DIOP, Dr. Oumy Ndiaye Ndao, along with the entire staff from ARP Senegal for their invaluable contributions throughout the course of the study. Our thanks also extend to Eve Ouedraogo and the WHO country offices in Côte d’Ivoire and Senegal for their assistance in coordinating the activities of the study team.
Author contributions All the authors listed on the paper meet the authorship criteria. MW and RK were the initiators of the study and were responsible for conceiving the study and drafting the study protocol. MW, RK, CR, FGM, and ASS were instrumental in organizing the local teams and conducting training on the study procedures. SD, DF, KAT, SOS, FF, and CSC executed the study and made sure that the local authorities concurred with the results of the study. AS contributed to evaluating the study results reports and was responsible for preparing the initial draft of the manuscript. All authors have given their approval for the final manuscript version. Funding This research has been supported by funding from the UNDP/UNFPA/UNICEF/WHO/World Bank Special Program of Research, Development and Research Training in Human Reproduction (HRP), a cosponsored program executed by WHO as well as from MSD, through MSD for Mothers, the company’s global initiative to help create a world where no woman has to die while giving life.
MSD for Mothers is an initiative of Merck & Co., Inc., Rahway, NJ, U.S.A Conflict of interest None of the authors has any conflict of interest to declare.
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