Prevalence and predictors of residual antibiotics in children's blood in community settings in Tanzania.

OBJECTIVE: Children account for a significant proportion of antibiotic consumption in low- and middle-income countries, with overuse occurring in formal and informal health sectors. This study assessed the prevalence and predictors of residual antibiotics in the blood of children in Mbeya and Morogoro regions of Tanzania. METHODS: The cross-sectional community-based survey used two-stage cluster sampling to include children aged under 15 years. For each child, information on recent illness, healthcare-seeking behavior, and use of antibiotics, as well as a dried blood spot sample, were collected. The samples underwent tandem mass spectrometry analysis to quantify the concentrations of 15 common antibiotics. Associations between survey variables and presence of residual antibiotics were assessed using mixed-effects logistic regression. RESULTS: In total, 1742 children were surveyed, and 1699 analyzed. The overall prevalence of residual antibiotics in the blood samples was 17.4% (296/1699), the highest among children under the age of five years. The most frequently detected antibiotics were trimethoprim (144/1699; 8.5%), sulfamethoxazole (102/1699; 6.0%), metronidazole (61/1699; 3.6%) and amoxicillin (43/1699; 2.5%). The strongest predictors of residual antibiotics in the blood were observed presence of antibiotics at home (aOR=2.9; 95% CI: 2.0-4.1) and reported consumption of antibiotics in the last two weeks (aOR=2.5; 95% CI: 1.6-3.9). However, half (145/296) of the children who had residual antibiotics in their blood, some with multiple antibiotics, had no reported history of illness or antibiotic consumption in the last two weeks, and antibiotics were not found at home. DISCUSSION: This study demonstrated a high prevalence of antibiotic exposure among children in Tanzanian communities, albeit likely underestimated, especially for compounds with short half-lives. A significant proportion of antibiotic exposure was unexplained and may have been due to unreported self-medication or environmental pathways. Incorporating biomonitoring into surveillance strategies can help better understand exposure patterns and design antibiotic stewardship interventions.

Quality equivalence and in-vitro antibiotic activity test of different brands of amoxicillin/clavulanic acid tablets in Mwanza, Tanzania: A cross sectional study.

Background: Each film coated tablet of amoxicillin/clavulanic acid contains 500 mg of amoxicillin as an active pharmaceutical ingredient and 125 mg of clavulanic acid. Different brands have the same active ingredients but different excipients, which may cause differences in efficacy. With the emergence of generic antibiotics post-patent expiration, the antibiotic activity of generics is in question in comparison to the innovator. This study aims at determining the pharmaceutical quality and in-vitro antimicrobial activity of different brands of amoxicillin/clavulanate. Method: ology: The study was a cross-sectional laboratory-based experimental study conducted at the TMDA (Tanzania Medicines and Medical Devices Authority) Lake Zone laboratory and the CUHAS Microbiology Laboratory from in May 2021. The study samples were four brands of amoxicillin/clavulanate and sixty archived isolates, thirty of which were E. coli and the remaining thirty K. pneumoniae. Determination of minimum inhibitory concentrations, assay and dissolution test results were used to make conclusions for the study. Results: All tablets samples complied with the British pharmacopeia (BP) specifications, however sixty archived isolates which were tested in this study showed resistance towards the standard AMC disc (68 %). The innovator brand (AC1) showed significant mean difference from 2 out of 3 generics (p-values <0.05) while the first generic brand (AC2) showed significant superiority among the generics. Conclusion: Thus, the four samples that were used all complied with the specifications according to BP on dissolution and assay tests but there was an overall resistance towards amoxicillin/clavulanate, and this was moreover seen by generic brands in comparison to the innovator which proved to be of superior activity.

Trends of measles in Tanzania: A 5-year review of case-based surveillance data, 2018-2022.

OBJECTIVES: Tanzania observed a gradual increase in the number of measles cases since 2019 with a large outbreak recorded during 2022. This study describes the trend of measles in Tanzania over a 5-year period from 2018-2022. METHODS: This was a descriptive study conducted using routine measles case-based surveillance system including 195 councils of the United Republic of Tanzania. RESULTS: Between 2018 and 2022 there were 12,253 measles cases reported. Out of 10,691 (87.25%) samples tested by enzyme-linked immunosorbent assay, 903 (8.4%) were measles immunoglobulin M positive. The highest number of laboratory-confirmed measles cases was in 2022 (64.8%), followed by 2020 (13.8%), and 2019 (13.5%). Out of 1279 unvaccinated cases, 213 (16.7%) were laboratory-confirmed measles cases compared to 77/723 (10.6%) who were partially vaccinated and 71/1121 (6.3%) who were fully vaccinated (P < 0.001). Children aged between 1-4 years constituted the most confirmed measles cases after laboratory testing, followed by those aged 5-9 years. There was a notable increase in the number of laboratory-confirmed measles cases in children <1 year and 10-14 years during 2022 compared to previous years. The vaccination coverage of the first dose of measles-containing vaccine (MCV1) was maintained >90% since 2013 while MCV2 increased gradually reaching 88% in 2022. CONCLUSIONS: Accumulation of susceptible children to measles due to suboptimal measles vaccination coverage over the years has resulted in an increase in the number of laboratory-confirmed measles cases in Tanzania with more cases recorded during the COVID-19 pandemic. Strengthening surveillance, routine immunization, and targeted strategies are key to achieving the immunity levels required to interrupt measles outbreaks.

Improved knowledge on substandard and falsified (SF) medical products through a dedicated course for pharmacy students at three universities in sub-Saharan Africa.

BACKGROUND: Too few pharmacists receive formal training on substandard and falsified (SF) medical products. Strengthening knowledge across pharmacists is considered a moral and ethical duty of academia, that is, to build the health systems' capacities to combat this global health threat these poor-quality products represent. This study therefore aimed to evaluate whether a dedicated educational course for undergraduate pharmacy students can improve their knowledge on these products. METHODS: A survey was conducted at three sub-Saharan universities. Knowledge was assessed through scores on a 20-point questionnaire with questions related to the course content. Scores were compared before and after the course, and a linear mixed-effects model analysis was used to analyse score differences. Students were furthermore asked for feedback and self-assessment. In addition, teachers were interviewed on the context of the course introduction. These data were analysed descriptively. RESULTS: Among 335 out of 355 students who completed the survey (n=41/53 in Cameroon, n=244/252 in Senegal and n=50/50 in Tanzania), knowledge of SF medical products was enhanced, with increase in all countries, overall, by 3.5 (95% CI 3.1 to 3.9) score points. Students improved in all offered modules in each country. Students confirmed their improvement through self-assessment.The course was well received among students and teachers. Barriers included time constraints and access to practical means (equipment availability, room allocation, internet accessibility and affordability). These barriers can be overcome by key enablers such as the support from university leadership and early involvement of the university in the course design. CONCLUSIONS: The course improved students' knowledge on SF medical products. These findings encourage further full implementation of this course in existing curricula beyond the pilot and can inform possible future scale-up. This has a potential for reinforcing the capacity of health systems to protect communities from SF medicines, by empowering all pharmacist across the health systems to intervene.

Effectiveness of a structured stimulated spontaneous safety monitoring of medicines reporting program in strengthening pharmacovigilance system in Tanzania.

Under-reporting of adverse drug events (ADEs) is a challenge facing developing countries including Tanzania. Given the high magnitude of under-reporting, it was necessary to develop and assess the effectiveness of a 'structured stimulated spontaneous safety monitoring' (SSSSM) reporting program of ADEs which aimed at strengthening pharmacovigilance system in Tanzania. A quasi-experimental design and data mining technique were used to assess the effect of intervention after the introduction of program in seven tertiary hospitals. ADEs reports were collected from a single group and compared for 18 months before (July 2017 to December, 2018) and after the program (January 2019 to June 2020). Out of 16,557 ADEs reports, 98.6% (16,332) were reported after intervention and 0.1% (23) death related to adverse drug reactions (ADRs) were reported. Reports increased from 20 to 11,637 after intervention in Dar es salaam, 49 to 316 in Kilimanjaro and 17 to 77 in Mbeya. The population-based reporting ratio per 1,000,000 inhabitants increased from 2 reports per million inhabitants in 2018 to 85 reports in 2019. The SSSSM program can increase the reporting rate of ADEs and was useful in detecting signals from all types of medicines. This was first effective developed spontaneous program to monitor medicine safety in Tanzania.

Emerging Antimicrobial Drug Resistance in Africa and Latin America: Search for Reasons.

Medicine quality and methods for its assessment play a major role in the effectiveness of therapies and the treatment of many infectious diseases. However, poor-quality and/or falsified products are circulating in huge amounts in many low- and middle-income countries and are one of the major reasons why more and more resistant bacteria emerge. The development of resistance is additionally triggered by a plethora of antibiotic medicines which is easily available through pharmacies and unofficial sources. The uncontrolled overuse of these products is a huge problem not only in single countries but worldwide. In this review, we aim to demonstrate the factors which are involved in an emerging resistance development and how strong regulatory authorities, routine quality control by means of proficiency testing, and post-marketing surveillance as well as training personnel and patients can be combined to curb the problem.

Quality of selected anti-retroviral medicines: Tanzania Mainland market as a case study.

BACKGROUND: Antiretroviral drugs (ARVs) have significantly reduced morbidity, mortality and improved the quality of life of people living with HIV infection. Poor quality ARVs may result in harmful consequences such as adverse drug reactions, treatment failure and development of drug resistant strains and sometimes death, which in turn may undermine the healthcare delivery system. To ensure optimal treatment outcomes, medicines quality control must be undertaken regularly. This study was aimed at evaluating the quality of ARVs circulating on the Tanzania Mainland market. METHODS: This was a survey study. ARVs samples were collected in 20 regions of Tanzania Mainland, between 2012 and 2018. All sampled ARVs were subjected to screening testing using the Global Pharma Health Fund® Mini-Lab kits. Sampled ARV's that failed screening test or yielded doubtful results and 10 % (10 %) of all that complied with the screening test requirements were selected for full quality control testing. Quality control testing was conducted at the Tanzania Medicines and Medical Devices Authority (TMDA) laboratory a World Health Organisation prequalified. Samples collected from the medicine distribution outlets were also, subjected to product information review. RESULTS: A total of 2,630 samples were collected, of which 83.7 % (2200/2630) were from port of entry (POEs). All sampled ARVs were screened and conformed to the specifications, except of the fixed dose combination (FDC) lopinavir/ritonavir 0.27 % (7/2630) and lamivudine/zidovudine/nevirapine 0.27 % (7/2630) that failed the disintegration test. Out of the 100 samples selected for full quality control testing, 3 % of them failed to comply with the specifications, of which FDC stavudine/lamivudine/nevirapine failed disintegration and assay tests 2 % (2/100) and 1 % (1/100), respectively. Samples failing the assay test had low content of stavudine (86.6 %) versus specification limits (90 -110 %). Out of the 430 samples which were subjected to product information review, 25.6 % (110/430) failed to comply with the TMDA packaging and labelling requirements. CONCLUSIONS: The quality of majority of ARVs circulating on the Tanzania Mainland market was good, even so, significant deficiencies on labelling and packaging were observed. These results call for continuous monitoring of quality of medicines circulating on the Tanzania Mainland market.

Harmonization of medical products regulation: a key factor for improving regulatory capacity in the East African Community.

BACKGROUND: Limited capacity to regulate medical products is associated with circulation of products which do not meet standards of quality, safety and efficacy with negative public health and economic outcomes. This study focused on assessing the effect of the East African Community (EAC) medicines regulatory harmonization initiative on the capacity of national medicines regulatory agencies, with a focus on registration and inspection systems. METHODS: An exploratory mixed-method design using both qualitative and quantitative data to access data from six national medicines regulatory authorities (NMRAs) and the EAC Secretariat. Data was collected using a combination of semi-structured interviews, questionnaires, and checklists for the period 2010/11-2015/16 with 2010/11 data serving as baseline. Heads of NMRAs, regulatory and monitoring and evaluation experts, and the EAC Secretariat Project Officer were enrolled in the study. A set of 14 indicators grouped into 6 categories were used to assess NMRAs performance. RESULTS: Policy and legal frameworks provide a foundation for effective regulation. Collaboration, harmonization, joint dossier reviews and inspections of manufacturing sites, reliance and cooperation are key factors for building trust and capacity among NMRAs. Five out of six of the EAC Partner States have comprehensive medicines laws with autonomous NMRAs. All the NMRAs have functional registration and good manufacturing practice inspection systems supported by regional harmonised guidelines for registration, inspection, quality management and information management systems with four NMRAs attaining ISO 9001:2015 certification. CONCLUSIONS: The EAC regulatory harmonization initiative has contributed to improved capacity to regulate medical products. The indicators generated from this research can be replicated for evaluation of similar initiatives across and beyond the African continent and contribute to public health policy.

A retrospective cross-sectional study to determine chirality status of registered medicines in Tanzania.

Medicines with a stereogenic center (asymmetric carbon) are mainly present as racemates with a mixture of equal amounts of enantiomers. One enantiomer may be active while the other inactive, alternatively one may produce side-effects and even toxicity. However, there is lack of information on the chirality status (either racemates, single active enantiomer or achiral) of medicines circulated on the market particularly in African countries. We established the chirality status of registered medicines in Tanzania by conducting a retrospective cross-sectional study. Registration data for the past 15 years from 2003 to 2018 were extracted from TMDA-IMIS database to Microsoft excel for review and analysis. A total of 3,573 human medicines had valid registration. Out of which 2,150 (60%) were chiral and 1,423 (40%) achiral. Out of the chiral medicines, 1,591 (74%) and 559 (26%) were racemates and single active enantiomers, respectively. The proportion of racemates within chiral medicines was considerably higher than single enantiomer medicines. The use of racemates may cause harm to the public and may contribute to antimicrobial resistance due to potential existence of inactive and toxic enantiomers. In order to protect public health, regulatory bodies need to strengthen control of chiral medicines by conducting analysis of enantiomeric impurity.

Coming together to improve access to medicines: The genesis of the East African Community's Medicines Regulatory Harmonization initiative.

Hiiti Sillo and colleagues reveal how the East African Community's Medicines Regulatory Harmonization initiative improves access to important medicines in Africa.

National medicines regulatory authorities financial sustainability in the East African Community.

INTRODUCTION: Adequate and sustainable funding of national medicine regulatory agencies (NMRAs) is key for assurance of quality, safety and efficacy of medical products circulating in a market. The study aimed to determine factors affecting NMRAs funding in five East African Community (EAC) countries namely: Burundi, Kenya, Rwanda, Tanzania (Mainland and Zanzibar) and Uganda. METHODOLOGY: An exploratory, mixed method design using both qualitative and quantitative data, was employed. Data from six NMRAs was collected through a combination of semi-structured interviews, questionnaires, and checklists for the period 2011/12-2014/15 while 2010/11 data served as baseline. Interviews were conducted with heads of NMRAs and monitoring and evaluation experts of the respective agencies. NMRA's financing was assessed using six indicators namely, funding policy, financial autonomy, the total annual budget, actual funding per annum, funds received from various sources, and the NMRA expenditure. RESULTS: The average total annual budget for all the EAC countries during the study period 2011-2015 ranged from USD 824,328.67 to USD 10,724,536.50. The low budget in Zanzibar may be attributed to population and pharmaceutical market size. Uganda's attainment of 98.75% (USD 10,656,704) revenue from industry fees is a result of deliberate government policy change from 100% reliance on donor funding over a period of 10 years (1995-2015). On average, the proportion of revenue against budget per annum is 54.8% (USD 458,970.11), 98.7% (USD 10,302,295.25) and 100% (USD 7,375,802.08) for Zanzibar Food & Drugs Agency (ZFDA), Uganda National Drug Authority (NDA) and Tanzania Medicines and Medical Devices Authority (TMDA) respectively. Governments, industry fees and donors are the major sources of funding across all NMRAs in the EAC region, with TMDA and Uganda NDA relying more on industry fees by 73.20% (USD 4,664,777.59) and 98.25% (USD 8,077,238.20) respectively. While Burundi relies solely on government funding, ZFDA, on the other hand, received on average 50.40% (USD 252,557.22) from government and 40.60% (USD 165,303.34) from industry fees and the remaining 9% from donors and other sources. An overall contribution of funds received from donors by each NMRA was the least among other sources of financing. Observation of expenditure patterns indicated operational costs to be the major expense in the majority of the NMRAs, followed by salaries and infrastructure development. The Kenya NMRA has the highest degree of average expenditure across all three categories, with the least average expenditures being marked by Burundi NMRA. The operational costs on average increased considerably in all the NMRAs during the study period. CONCLUSION: Evidence from the EAC suggests that government and industry fees are the main sources of funding while donor contributions vary from country to country. Government policy, legal framework, and fees structure are the key enablers of NMRAs funding sustainability.

Pharmaceuticals imports in Tanzania: Overview of private sector market size, share, growth and projected trends to 2021.

BACKGROUND: To assess the extent to which foreign pharmaceutical imports vary from year to year and identifying leading generic and branded formulations, key countries and key importers of pharmaceuticals in private sector supply chain. METHODOLOGY: A systematic analysis of data for pharmaceutical imports from the Ministry of Health.Data from 2013 to 2016 fiscal years and relevant documents were accessed from the Tanzania Food and Drugs Authority (TFDA). Data cleaning was carried out to remove duplicate entries and to exclude pharmaceutical imports for individual uses, promotion purpose, donations, raw material, medical devices, government institutions and veterinary products. RESULTS: A total of 397 different suppliers imported pharmaceutical in Tanzania mainland from 2013 to 2016 fiscal years. In the 2013-2014 fiscal year, the private sector suppliers imported pharmaceutical worth 216 U.S million dollars. India ranked as the first country for exporting highest value of pharmaceutical into the country. It displays a 54% cumulative market share of total imports from 2013-2016, followed by Egypt (11.7%), Switzerland and the USA hold 4.1% of cumulative market share. By 2020-2021 fiscal years, we forecast for imported pharmaceuticals to reach a total value of 906 U.S million dollars for the private sector supply chain. All analysis in this study and the forecasted figures are limited to private sector pharmaceutical supply chain only and does not include data for government pharmaceutical supply chain. CONCLUSIONS: Our result shows that the vast majority of pharmaceutical imports in the private sector supply chain are dominated by imports from India. India is competing with other countries such as Egypt, Switzerland, USA and South Africa among the top importing countries. There was almost an equal distribution of pharmaceutical for both communicable and non-communicable diseases. Data presented shows a growing trend for the market segment for medicines required for the management of non-communicable diseases. Generally, the private sector pharmaceutical market is keeping on rising at a rapid pace. By the year 2021, the growth is forecasted to increase by 28% compared to the current market value. The projected growth rate could be good news for foreign pharmaceutical companies seeking new sources of growth in international pharmaceutical trading. It is also good news to the poor patients if the availability of drugs previously unavailable in the country is significantly increased.

Formulation development of chewable albendazole tablets with improved dissolution rate.

BACKGROUND: Albendazole is an orally administered broad-spectrum anthelmintic. Currently it is mostly used in the treatment of soil transmitted helminthes, hydatidosis and neurocysticercosis caused Taenia solium.Aim of the study. To develop and optimize a formulation of chewable albendazole tablet with improved dissolution rate. METHODOLOGY: This study was specifically focused on formulation development which passes compatibility studies and optimization of the developed formulation. The formulations were evaluated on assay, dissolution, friability, hardness, weight variation, disintegration and similarity in comparison with the reference product on the market. Analysis was required to be undertaken by High performance thin layer chromatography (HPTLC) analytical methods. Design of Expert version 7 software was used for selection or making scientific decisions in selecting the best composition of the best formulation. RESULTS: Five formulations out of ten (F-6, F-7, F-8, F-9 and F10) had all parameters in acceptable range. On optimization, one formulation with independent variables, Sodium Laury Sulphate (SLS) 1.911%, polyvinyl pyrrolidone (PVP-K30) 3.128%, and Sodium Cross carmellose (CCM) 4.95% was selected out of ten predictions made with Design expert version 7.0. It was found that assay of the best formulation is 99.23% which was within the in-house assay specification 95-105%. Dissolution single point in 30 min was found to be 91.5% disintegration between 2-5 min and friability 0.45%.The optimized formulation was tested and found to be within the acceptable limits. The formulation was comparable to the reference product on the market with similarity factor (f2) 62 and difference factor (f1) of 6 at pH1.2. CONCLUSION: A new generic albendazole tablet with improved dissolution rate was formulated, developed and optimized by using a wet granulation method.

Economic cost of substandard and falsified human medicines and cosmetics with banned ingredients in Tanzania from 2005 to 2015: a retrospective review of data from the regulatory authority.

OBJECTIVE: To estimate the economic cost of substandard and falsified human medicines and cosmetics with banned ingredients in Tanzania from 2005 to 2015. DESIGN: A retrospective review of data. SETTING: Tanzania Food and Drugs Authority and premises dealing with importations and distributions of pharmaceuticals. ELIGIBILITY CRITERIA: Confiscation reports of substandard human medicines, falsified human medicines and cosmetics with banned ingredients. PRIMARY AND SECONDARY OUTCOME MEASURES: Quantities and costs of pharmaceutical products, costs of transportation, storage, court cases and disposal of products. RESULTS: The economic cost of substandard and falsified human medicines and cosmetics with banned ingredients was estimated at US$16.2 million, that is, value of substandard medicines US$13.7 million (84.4%), falsified medicines US$0.1 million (1%), cosmetics with banned ingredients US$1.3 million (8%) and other/operational costs US$1.1 million (6.6%). Some of the identified substandard and falsified human medicines include commonly used antibiotics such as phenoxymethylpenicillin, amoxicillin, cloxacillin and co-trimoxazole; antimalarials such quinine, sulfadoxine-pyrimethamine, sulfamethoxypyrazine-pyrimethamine and artemether-lumefantrine; antiretroviral drugs; antipyretics and vitamins among others. CONCLUSION: The economic cost of substandard and falsified human medicines and cosmetics with banned ingredients represent a relatively large loss of scarce resources for a poor country like Tanzania. We believe that the observed increase in the quantities and the economic cost of these products over time could partly be due to the improvement in the regulatory capacity in terms of human resources, infrastructure and frequency of inspections.

Conformity of package inserts information to regulatory requirements among selected branded and generic medicinal products circulating on the East African market.

BACKGROUND: Availability of correct and adequate information about medicines is an important aspect in ensuring rational use of medicines and hence facilitating safety and expected efficacy of medicines during therapy. Package inserts have proven to be a good source of information to the prescribers and patients whereby they have been useful in highlighting important information pertaining proper use and handling of the medicines. The present study was aimed at establishing the extent to which package inserts of medicines circulating on the markets of the East African Community (EAC) Partner States conform to medicines information requirements as established in the harmonized guidelines as well as national guidelines. METHODS: A total of 99 package inserts from six (6) types of medicines namely Albendazole, Artemether/Lumefantrine (ALu), Ciprofloxacin, Paracetamol, Amoxicillin and Metronidazole were purposefully collected from three EAC Partner States: Kenya, Tanzania and Uganda. The medicines were selected based on their indications as first line treatments, high rates of utilization within the medicines supply system and their positions in treatment of diseases of public importance across EAC Partner States. The inserts were evaluated on the availability of information regarding fifteen (15) parameters as extracted from the EAC harmonized guidelines for registration of medicines. Moreover, comparisons were made between the percentage conformity of the branded versus generic products, markets from which the samples were collected, origin of the manufacturer and type of medicine. RESULTS: Majority (93.9-100%) of the medicines' package inserts highly conformed to the inclusion of the information regarding the description and composition of the medications, indications, dosage and methods of administration, warnings and precautions, contraindications and storage conditions. However, the information on handling and disposal, container package description, excipients used, clinical pharmacology of the medicines, and directions regarding overdose ranked the least in conformance with conformity ranging from 13.1-52.5%. The parameter with the lowest observed percentage conformity among the branded products scored 50% as compared to 10.8% among the generic products. Moreover, there was no significant difference (P<0.05) in the percentage conformity of the package inserts collected from each of the three Partner States as compared to the average from studied medicines. A generally good conformity was observed among medicines manufactured by European based manufacturers as compared to those based in Asia and EAC Partner States. In addition, PIs of Albendazole, Ciprofloxacin, Amoxicillin and Artemether/Lumefantrine did show overall high conformity across most of the product information requirements. CONCLUSION: Our study revealed the existence of a significant number of medicinal products circulating on the markets of EAC Partner States without necessary compliance with all product information requirements. We therefore recommend that NMRAs ensure thorough pre-market assessment of product information as well as strengthening their post marketing surveillance to ensure that medicines circulating on the market comply to medicines information requirements at all times. Emphasis should also be given to manufacturers on the importance of inclusion of appropriate and adequate product information for the safety of patients, including advocating for inclusion of patient-friendly and easy to understand medicines information.

Medicines Regulation in Africa: Current State and Opportunities.

Sound regulatory systems are critical for protecting public health against use of medical products which do not meet international standards of quality, safety and efficacy. This review provides a summary of the current status of National Medicines Regulatory Authorities (NMRAs) in Africa, and various initiatives that have been established to improve their performance. All countries in Africa (except Sahrawi Republic), have NMRAs but their organizational set-up and functionality is variable. Some are located within Ministries of Health and others are semi-autonomous. There is progressive improvement in regulatory capacity, particularly in quality control and post-marketing surveillance, pharmacovigilance and clinical trials oversight. The African Vaccines Regulatory Forum, African Medicines Regulatory Harmonization Initiative, Network of Official Medicines Control Laboratories and WHO Prequalification Scheme have helped countries strengthen their regulatory capacities. The potential establishment of the African Medicines Agency (AMA) in 2018 is an opportunity to improve NMRAs' capacity in Africa.

Formulation development and optimization of Lamivudine 300 mg and Tenofovir Disoproxil Fumarate (TDF) 300 mg FDC tablets by D-optimal mixture design.

The usage of fixed dose combination (FDC) tablets of Lamivudine and Tenofovir Disoproxil Fumarate (TDF) is increasing due to increased incidences of HIV/Hepatitis B and HIV/TB co-infections. This is likely to increase the financial crisis due to limited resources for funding procurement of ready-made products from the pharmaceuticals manufacturing leading countries. Therefore, production of local oral tablets containing Lamivudine and TDF FDC is inevitable. Lamivudine 300 mg/TDF 300 mg tablets were developed and optimized by D-optimal mixture design and produced by direct compression technique. Twenty trial formulations with independent variables, including PVP-CL 1-12.00%, PVP-K30 1-10.00%, starch-1500 2.5-12.5% and Avicel-PH102 2-19.25% were prepared by direct compression technique. The formulations were assessed on assay, dissolution, friability, weight variation and disintegration time. It was found that assay ranged from 98.13-101.95% for Lamivudine, 98.25-102.84 for TDF, both were within the in-house assay specification of 95 to 105%. Dissolution at single point was above 80% for Lamivudine 93.96-100.55% and 95.85-103.15% for TDF, disintegration time was between 1.92-66.33 min and friability 0.06-12.56%. Out of twenty formulation trials, eight formulations had all parameters in proven acceptable range. On optimization, one formulation with independent variables, PVP-CL 5.67%, PVP-K30 1.00%, Starch-1500 5.76% was selected. The optimized formulation was comparable to the reference product on the market with similarity factor (f2) and difference factor (f1) within the acceptable range for both Lamivudine and TDF.

The Quality of Selected Essential Medicines Sold in Accredited Drug Dispensing Outlets and Pharmacies in Tanzania.

INTRODUCTION: The purpose of this study was to investigate the quality of a select group of medicines sold in accredited drug dispensing outlets (ADDOs) and pharmacies in different regions of Tanzania as part of an in-depth cross-sectional assessment of community access to medicines and community use of medicines. METHODS: We collected 242 samples of amoxicillin trihydrate, artemether-lumefantrine (ALu), co-trimoxazole, ergometrine maleate, paracetamol, and quinine from selected ADDOs and pharmacies in Mbeya, Morogoro, Singida, and Tanga regions. The analysis included physical examination and testing with validated analytical techniques. Assays for eight of nine products were conducted using high-performance thin-layer chromatography (HPTLC). For ALu tablets, we used a two-tiered approach, where tier 1 was a semi-quantitative Global Pharma Health Fund-Minilab® method and tier 2 was high-performance liquid chromatography (HPLC) as described in The International Pharmacopoeia's monograph for artemether-lumefantrine. RESULTS AND DISCUSSION: The physical examination of samples revealed no defects in the solid and oral liquid dosage forms, but unusual discoloration in an injectable solution, ergometrine maleate. For ALu, the results showed that of 38 samples, 31 (81.6%) passed tier 1 testing and 7 (18.4%) gave inconclusive drug content results. The inconclusive ALu samples were submitted for tier 2 testing and all met the quality standards. The pass rate using the HPTLC and TLC/HPLC assays was 93.8%; the failures were the ergometrine maleate samples purchased from both ADDOs and pharmacies. The disintegration testing of the solid dosage forms was conducted in accordance with US Pharmacopeia monographs. Only two samples of paracetamol, 1.2% of the solid dosage forms, failed to comply to standards. The study revealed a high overall rate of 92.6% of samples that met the quality standards. Although the overall failure rate was 7.4%, it is important to note that this was largely limited to one product and likely due to poor distribution and storage rather than poor manufacturing practices. CONCLUSIONS: Over 90% of the medicines sold in ADDOs and pharmacies met quality standards. Policy makers need to reconsider ergometrine maleate's place on the list of medicines that ADDOs are allowed to dispense, by either substituting a more temperature-stable therapeutically equivalent product or requiring those sites to have refrigerators, which is not a feasible option for rural Tanzania.

Development of a simple, rapid, and robust liquid chromatographic method for the simultaneous determination of sulfalene, sulfadoxine, and pyrimethamine in tablets.

A simple, cost effective, accurate, and precise RP-HPLC method was developed for the simultaneous determination of sulfalene and sulfadoxine in fixed dose dual combinations with pyrimethamine together with their related substances. Proprietary products containing these combinations are often being prescribed in malaria endemic countries. Quantification of the active compounds and impurity profiling was achieved using two standard C18 columns with a mobile phase being composed of 60% (v/v) of a 0.05M KH2PO4 buffer solution (pH=2.6) and 40% (v/v) of methanol, applying an isocratic elution mode and a detection wavelength of 215nm. The method allows a quick quantitative determination of sulfadoxine and sulfalene and the separation of the respective impurities within a total runtime of approximately 15min and was validated with respect to specificity, linearity, precision, accuracy, limits of detection and quantification, robustness, and stability of the standard and sample solutions. The method is simpler than the corresponding method described in the International Pharmacopoeia and the United States Pharmacopoeia in terms of being easy to apply, being less time consuming, and utilizing reagents and chemicals which are cost efficient.