Joint Post Marketing Quality Surveillance of Antibiotics in East African Community: Lessons Learnt

Substandard and falsified (SF) antibiotics compromise treatment outcomes and drive antimicrobial resistance (AMR). To strengthen market surveillance in a region with porous borders and varying regulatory capacity, East African Community (EAC) National Medicines Regulatory Authorities (NRAs) conducted a joint postmarketing quality surveillance of selected antibiotics.

In 2018, NRAs in Kenya, Uganda, Tanzania Mainland, and Zanzibar implemented a risk-based sampling of amoxicillin 250 mg capsules, amoxicillin/clavulanate 500/125 mg tablets, and sulfamethoxazole/trimethoprim (SMX/TMP) 400/80 mg tablets across public, faith based, and private sectors. Sampling covered different supply chain levels, diverse brands and batches. All samples underwent Level 1 screening using visual inspection, disintegration and thin-layer chromatography (TLC). Samples that failed screening, together with 10% of those that passed, were subjected to Level 2 compendial testing at the Word Health Organization (WHO)-prequalified or recognized national quality control laboratories. Product Information Review (PIR) assessed labeling completeness and registration status.

A total of 203 samples were collected: Kenya (58), Uganda (56), Tanzania Mainland (29) and Zanzibar (60). Level 1 screening identified two disintegration failures in Zanzibar and three samples with doubtful TLC results in Kenya. Confirmatory testing showed that the Zanzibar samples failed compendial specifications, while the Kenyan samples complied.  Overall, 62 samples underwent Level 2 testing; among 26 evaluated against full pharmacopeial parameters (identity, content uniformity, assay, dissolution), one SMX/TMP 480 mg sample failed dissolution testing and was withdrawn across the region. Product Information Review (PIR) revealed notable labeling and registration deficiencies in Tanzania Mainland and Zanzibar, including missing registration numbers and incomplete storage information, whereas most samples from Uganda and Kenya complied with PIR requirements.

This EAC joint PMS demonstrated that, most sampled antibiotics met quality standards, with few critical failures promptly addressed, but highlighted persistent labelling and registration gaps requiring regulatory action. Despite limitations related to sample size, uneven participation, and testing heterogeneity, the findings provide useful baseline evidence supporting harmonized, risk-based PMS as an effective approach to strengthening medicines quality assurance and mitigating Antimicrobial Resistance (AMR) in the EAC.

Monitoring the quality of medicinal products beyond market authorization is crucial for quality assurance, ensuring consistency in quality attributes and performance throughout the products' lifecycle and preventing any occurrences that may endanger public health [1]..This is achieved through systematic post-market surveillance schemes, which include testing market samples or samples from entry points of a country by national medicines regulatory authorities (NRAs) [2,3].

The burden of substandard and falsified medicinal products, together with antimicrobial resistance, is a global public health issue that erodes confidence in health systems, health professionals, pharmaceutical manufacturers, and distributors. Poor-quality medical products, including antibiotics, contribute to drug resistance, disability, injury, and death [4]. It is estimated that 4.95 million deaths globally that occurred in 2019 were associated with bacterial antimicrobial resistance (AMR) [5]. Research findings have indicated that AMR is the leading cause of death worldwide, with the highest burdens in low-resource settings such as East Africa [6]. The rise in antibiotic resistance in the East African Community (EAC) is driven by uncontrolled dispensing and use of these products, which are readily available from pharmacies without a doctor’s prescription [7]. Additionally, the continued increase in substandard and falsified antibiotics in the EAC market has posed a threat to the region, leading to treatment failure, an increase in AMR, disability, and deaths [8].

Substandard medical products are those that do not meet quality standards and specifications, often due to poor manufacturing practices or inadequate quality control. Falsified medical products are those that deliberately misrepresent their identity, composition, or source and are mainly created or distributed to deceive consumers for financial gain [9]. Substandard products may result from negligence or human error; although manufactured within legal limits, they may exhibit quality defects. Additionally, medicinal products can deteriorate and become substandard during transportation or storage, or due to environmental factors [10,11]. The extent of the burden caused by substandard and falsified (SF) pharmaceutical products in the East African region remains unknown; however, it is estimated that approximately 10% of globally traded medicines are falsified, with a higher percentage in low-income countries [4,12].

To minimize the circulation of substandard and falsified medical products, countries must establish robust post-marketing surveillance systems that protect the public from their harmful effects. Monitoring the safety, quality, and effectiveness of medicines, vaccines, and medical devices after authorization for use, and providing public safety information, are essential functions of national healthcare systems. These responsibilities fall to national medicines regulatory authorities (NRAs) and healthcare professionals at all levels of the healthcare system [13,14].

Post-marketing surveillance (PMS) involves systematically sampling pharmaceuticals from distribution channels, including hospitals, dispensaries, health centers, wholesalers, retail pharmacies, accredited drug dispensing outlets, and drug stores, according to a prearranged sampling plan [15-17]. The collected samples are screened using minilab test kits, and laboratory confirmatory tests are performed in accordance with the protocol. Results are statistically analyzed to identify potential public health threats and published to enhance public awareness. Legal action is also pursued against importers or distributors found responsible for circulating poor-quality products [18,19].

An effective PMS system requires strong legislation, transparency, accountability, qualified staff, structured PMS programs, facilities for collection, storage, screening, and analysis, and mechanisms for publishing results and pursuing legal action against offenders. Post-marketing surveillance is essential for identifying and reducing the spread of substandard and falsified medicines and for reducing antimicrobial resistance [20,18]. However, no single country can manage this alone due to porous borders; concerted efforts are required to address the rise in substandard and falsified medical products, including antibiotics.

Since 2017, EAC Partner States' National Medicines Regulatory Authorities (NRAs) have collaborated to strengthen PMS and pharmacovigilance systems by sharing information on products recalled for quality defects, developing a regional strategy for post-marketing surveillance, and conducting joint quality surveillance of medical products. This initiative has benefited various stakeholders, including patients, the public, authorities, and the pharmaceutical industry. Joint post-marketing surveillance is a regulatory function carried out by the NRAs of EAC Partner States through the East African Medicines Regulatory Harmonization Program. The program is implemented to varying degrees across eight countries, with some having well-functioning National Medicines Regulatory Authority systems and structures, while others lack basic quality-control infrastructure. Additionally, only three drug quality control laboratories in the EAC have been pre-qualified by the World Health Organization (WHO), located in Kenya, Tanzania (mainland), and Uganda [21,22]. The physical facilities vary among Partner States and require expansion to support the comprehensive range of functions related to the regulation of medical products and health technologies.

This research presents findings from the joint post-marketing surveillance of the quality of selected antibiotics (Amoxicillin Capsules 250 mg; Amoxicillin/Clavulanate Tablets 625 mg; and Sulfamethoxazole/Trimethoprim Tablets 480 mg), conducted in 2018 by four EAC National Medicines Regulatory Authorities (NRAs). The aim was to assess quality and establish baseline data to inform regulatory decisions. Participating NRAs included the Pharmacy and Poisons Board (PPB) of Kenya, the National Drug Authority (NDA) of Uganda, the Tanzania Medicines and Medical Devices Authority (TMDA), and the Zanzibar Food and Drugs Agency (ZFDA) of the United Republic of Tanzania.

Study Objectives

The objectives of the study were to:

1. To assess the quality of antibiotics circulating in the EAC Partner States.
2. To generate baseline data on the quality of selected antibiotics across the EAC Partner States.
3. To generate evidence to inform regulatory actions, respond to patient safety concerns, and protect the public.

The study focused on specific antibiotics from the EAC Partner States’ Essential Medicine List. The selection criteria were as follows:

1. Usage pattern of medicines
2. (Complaints (Public, lack of efficacy)
3. (Intelligence (previous product failure, GMP reports). 

The products selected for this study were Amoxicillin Capsules 250 mg; Amoxicillin/Clavulanate Tablets 625 mg; and Sulfamethoxazole/Trimethoprim Tablets 480 mg. The study protocol was developed and approved by the forum of the Heads of EAC National Medicines Regulatory Authorities [23].

Sampling Strategy

A risk-based sampling strategy combined random and purposive sampling across multiple levels of the pharmaceutical supply and distribution chain in the public, faith-based, and private sectors. The sampling strategy was in accordance with the approved joint EAC post-marketing surveillance protocol. Random and purposive sampling was used to maximize the likelihood of detecting substandard and falsified antibiotics while reflecting real-world regulatory practice. Selected antibiotics- amoxicillin capsules 250mg, amoxicillin/clavulanate tablets 500/125mg, and sulfamethoxazole/trimethoprim tablets 400/80 mg, were prioritized based on high utilization, prior complaints through pharmacovigilance centers, known market intelligence, and public health relevance. Samples were collected across multiple levels of the pharmaceutical supply chain, including importers, wholesalers, central medical stores, retail outlets, public, private, and faith-based hospitals.

The sampling approach was designed to support regulatory signal detection rather than statistical prevalence estimation, consistent with WHO-recommended risk-based post-marketing surveillance methodologies. Diversification criteria, including brand variety, batch variability, storage conditions, and border area risk, were applied to enhance the likelihood of identifying quality defects.

Site Selection

Site selection was based on risk management priorities and the availability of medicines in each Partner State. EAC Partner States developed a site selection plan in line with the country-specific protocols. Each Partner State collected samples from two regions, one of which was the NRA headquarters location. Each Partner State also sampled selected antibiotics at five sites, as indicated below:

Region Facility Type

Region 1: This is the region where the NRA was located, and samples of selected antibiotics were collected from Central Medical Stores, Wholesalers, Retailers, Public Hospitals, and Private Hospitals.

Region 2: This region lies outside the NRA, and samples were collected from wholesalers, retailers, public and private hospitals, and faith-based organizations.

Sampling Plan

Each country was to collect approximately 20 samples of each selected study product from both the public and private sectors, according to study protocol.

Sample Definition

For this study, a sample was defined as a medicine with a specific active pharmaceutical ingredient (API), dosage form, strength, and lot number from a specified level in the distribution chain. Samples with the same attributes, including the same lot number, were collected only if they were from a different level in the distribution chain, such as wholesaler versus retailer. A sample consisted of multiple units (i.e., the same product name, manufacturer, dosage form, packaging material, and strength) representing the same batch and collected at the same location or outlet at a given time. 

Criteria for Diversification of Sampling

To diversify the samples collected at each site, the following characteristics were applied:

Different brands of the same API; different batch or lot numbers; different sectors (private, public, informal); different sources or outlets (same product or duplicate lots from different sources or outlets); suspicious medicines; high-risk areas (border areas, etc.); improperly stored medicines at the sampling site (exposed to sunlight, humid or wet conditions, etc.); and different packaging of the same product (i.e., blister vs. bulk). For bulk-packed products, the entire container was collected if it contained more than 100 units.

Sample Collection Process

Only unopened, original packages were collected; the number of units per sample varied by pack size. If fewer tablets or capsules were available for the batch than requested (i.e., fewer than 100 units), the sample was not collected, and another batch was selected.

Only dosage forms and strengths specified in the National Medicines List were selected for sampling and collected. If more strengths or pack sizes of a medicine were recommended in the survey and available for the product in the region, it was sufficient to collect one of them. In principle, the lowest strengths and the largest pack sizes were collected.

Samples from different brands were collected rather than multiple batches from a single brand. If more brands than the required number were available for sampling, priority was given to the most commonly used brands or those that had received complaints.

Sampling was documented using the agreed-upon sample collection form. When required information was unavailable, it was marked “NA” in the appropriate field on the form, and any abnormalities were also noted. To prevent confusion, each sample was assigned a unique code in accordance with the Standard Operating Procedure (SOP) on Sampling.

During sample collection, the storage conditions at the site were evaluated and described in the sample collection form. Each Partner State had a focal person responsible for briefing inspectors to ensure they were familiar with the sampling plan and detailed instructions for sample collection and that those instructions were followed. Each collected sample was placed in a sealable container, and the corresponding sample collection form was attached.

Sample Transportation and Handling

Collected samples were packed, transported, and stored to prevent deterioration, contamination, or adulteration. Samples were stored in their original sealed containers, following each product's storage instructions. A list of all samples in a given sample collection carton-including product names, manufacturers, batch numbers, and exact quantities-was prepared. If more than one parcel or box was used, a packing list was prepared for each parcel or box to detail its contents.

After minilab screening by participating NRAs, products that failed the screening test, along with 10% of all passing products, were shipped by DHL to the Uganda National Quality Control Laboratory for compendial testing.

Receipt and Testing of Samples by a Testing Laboratory

Upon receipt of the samples by laboratory personnel, each sample was inspected to ensure that the labeling matched the information on the sample collection form. An electronic database was also created. Samples were stored in accordance with their respective labeling requirements. Quality control testing was conducted in accordance with the approved procedure, per the SOP for testing medicine samples. Analytical Test Reports were generated and handled as required. For noncompliant results, the out-of-specification procedure was followed, and appropriate investigations were undertaken.

Records of testing for each sample, along with accompanying documents and retention samples, were kept in accordance with the laboratory's approved procedures.

Sample Analysis

Once samples were collected, they were tested on-site using minilab screening. Those that failed, along with 10% of the passing products, were sent for compendial analysis.

The minilab screening tests were conducted at the country level, while the compendial tests were performed centrally at the Uganda NDA Laboratory. However, not all Partner States submitted their samples to NDA for compendial analysis; Kenya conducted its compendial tests at the National Quality Control Laboratory in Kenya. Confirmatory testing was performed in a logical sequence rather than conducting the full compendial testing all at once.

Reporting Data

Each Partner State collected samples using a harmonized sample collection form. The results of Level I screening (e.g., minilab) were then reported in a standardized format.

Sample Collected and Sample Collection Sites

Kenya: A total of 58 samples were collected from retail and wholesale pharmacies, healthcare facilities, and the central medical store. The Kisumu region accounted for the largest share of samples, while the central stores had the fewest. Most samples (77.6%) were collected from the private sector, while the public sector contributed 22.4%.

Tanzania (Mainland): A total of 29 medicine samples were collected in the Dar Es Salaam region, comprising: Amoxicillin Capsules 250 mg (10), a fixed-dose combination of Sulphamethoxazole/Trimethoprim Tablets 480 mg (10), and Amoxicillin/Clavulanate Tablets (9). Table 1 below summarizes the number of samples collected in each district of the Dar Es Salaam region where the NRA was located during sample collection. Samples were collected from various levels of the medicine distribution channels, including the Medical Store Department (MSD), private and public hospitals, and pharmacies. Most samples were collected from private wholesale pharmacies (41.4%). Hospital pharmacies accounted for 31% of the samples, retail pharmacies for 17.2%, and MSD for 10.3%. Of the 29 samples, 10% were manufactured domestically and 90% were imported from Austria, China, Egypt, Kenya, India, the United Kingdom, and the United Arab Emirates (U.A.E).

Tanzania (Zanzibar): A total of sixty (60) samples were collected, including Amoxicillin capsules 250 mg, Amoxicillin/Clavulanic acid tablets 625 mg, and Cotrimoxazole tablets 480 mg.

Uganda: Of the 56 samples collected from the Ugandan market and sent for analysis at the National Drug Quality Control Laboratory (NDQCL), 19 (34%) contained Amoxicillin, 18 (32%) contained Amoxicillin/Clavulanate Potassium, and 19 (34%) were formulated with Sulfamethoxazole/ Trimethoprim. 19 (34%) of the samples were collected from the public sector, including public hospitals and healthcare centers, while 37 (66%), the majority, were collected from the private sector, including wholesale and retail pharmacies.

Table 1: Number of Samples Collected from the Public and Private Sectors of Kenya, Uganda, and Tanzania.

Product Information Review (Registration Status, Labeling Requirements)

Kenya: All the sampled products were registered by the Pharmacy and Poisons Board (PPB), Kenya.

The sampled products were well labeled with their indications and uses, the source of the product, and the recommended storage temperature.

Tanzania (Mainland): All 29 samples were reviewed for their Product Information Review (PIR) information on the label and in the associated package insert against the approved labeling and package insert requirements.

A review of the package inserts showed that most lacked a registration number. This was observed in 89% (8) of the Amoxicillin/Clavulanic Acid samples, 70% (7) of the Sulfamethoxazole/ Trimethoprim samples, and 60% (6) of the Amoxicillin samples.

Other deficiencies identified in the inserts included inappropriate storage instructions, the absence of a physical description of the product, a list of excipients, and a publication date. Notably, these deficiencies were more prevalent in the inserts of samples of Amoxicillin Capsules and Sulfamethoxazole/Trimethoprim tablets than in those of Amoxicillin/Clavulanic Acid tablets.

Likewise, 55% (5) of the Amoxicillin/Clavulanic Acid samples lacked a registration number on the primary pack label. This issue was not observed on the labels of the Sulfamethoxazole/trimethoprim samples. Additionally, the primary pack label included inappropriate storage instructions, an incomplete physical address for the manufacturer, and omitted the product's storage conditions.

Furthermore, 30% (3) of Sulfamethoxazole/ trimethoprim tablets, 22% (2) of Amoxicillin/ clavulanic acid tablets, and 10% (1) of Amoxicillin capsules lacked a registration number on the secondary pack label. Additionally, the label listed inappropriate storage conditions, such as “store below 25ºC,” and omitted the product's manufacturing date.

Tanzania (Zanzibar): The results indicated that two samples of Sulfamethoxazole/trimethoprim 400/80mg tablets were not registered in Zanzibar or on the Tanzanian mainland. Samples of domestically manufactured Sulfamethoxazole/Trimethoprim 400/80mg tablets lacked registration numbers on both the primary and secondary packaging.

Additionally, two samples of Amoxicillin Capsules 250 mg, manufactured in Oman and China, were not registered in Zanzibar or on the Tanzanian mainland. One domestically manufactured sample of Amoxicillin had no registration number on its primary or secondary packaging.

Three samples of Amoxicillin/Clavulanic Acid 500/125 mg, manufactured by companies based in Germany, India, and the U.A.E., were not registered in Zanzibar or on the Tanzanian mainland. In summary, 7 samples were not registered in Zanzibar or Tanzania mainland, and three (3) samples manufactured on the Tanzania mainland have no registration number on their primary or secondary packaging.

Uganda: The manufacturing facilities that produced the collected samples from the central and eastern regions were found to be registered with the National Drug Authority, as published on the NDA website (www.nda.or.ug).

The samples were assessed to ensure they met the labeling requirements outlined in the guidelines for submitting documentation for the marketing authorization of a pharmaceutical product for human use. The labels and patient information leaflet were evaluated for the batch number, manufacturing date, expiration date, the manufacturer's physical address, amount of API, list of excipients, and storage conditions. All samples collected met the product information requirements. 

Basic Level 1 Screening Test Results (Minilab)

Kenya: All selected samples underwent minilab screening at two sites in Kisumu and Mombasa. Of the 58 samples, 94.8% (n = 55) passed the screening, while 3 samples (5.2%), originating from China, India, and Kenya, were deemed doubtful due to differences in RF and Thin Layer Chromatography (TLC) spot intensity.

Tanzania (Mainland): All 29 samples were subjected to quality screening using Global Pharma Health Fund (GPHF) Mini-Lab kit methods. Visual inspections, disintegration tests, and Thin Layer Chromatography (TLC) identification tests were performed. The screening results indicated that all samples of Amoxicillin capsules (10), Amoxicillin/clavulanic acid (9), and Sulfamethoxazole/ trimethoprim (10) passed the tests.

Tanzania (Zanzibar): All collected samples (100%) passed physical inspection and Thin Layer Chromatography (TLC). However, only 58 samples (96.6%) passed the disintegration test, while 2 samples (3.3%) failed to disintegrate within the specified time. These samples were sent to the Uganda Quality Control Laboratory for the Compendial Test, where they also failed the disintegration test, as indicated in Table 4c.

Uganda: Three basic tests were performed using the Minilab kit, namely Visual Inspection, Tablet/Capsule Disintegration, and Identification by Thin-Layer Chromatography (TLC), for all collected samples, i.e., Amoxicillin (250 mg), Amoxicillin/Clavulanic Acid (500/125 mg) Tablets, and Sulfamethoxazole/Pyrimethamine (400/80) Tablets. All samples comply with the specifications.

Level 2 Compendial Test Results

Kenya: Nine samples underwent compendial analysis in the quality control laboratory. This included three samples of questionable quality, representing 10% of the total samples collected. Tests performed included identification, uniformity of weight, dissolution, and assay. All samples met the compendial test parameters, as summarized in Table 2 below:

Table 2: Summary of Results of Compendial Test Analysis (Kenya).

Tanzania (Mainland): Three samples were sent to the National Drug Authority Laboratory in Kampala, Uganda, for confirmatory testing, which included identification, weight uniformity, dissolution, and assay. All samples met the compendial test parameters as indicated in Table 4a, 4b, 4c and 4d.

Compendial Test Results (United Republic of Tanzania (Mainland and Zanzibar), Burundi and Uganda)

For confirmatory tests, an average of two samples of each of the three selected antibiotics was analyzed. The United Republic of Tanzania (Zanzibar) submitted three (3) samples each of cotrimoxazole (Sulfamethoxazole + trimethoprim) and Amoxicillin/Clavulanic acid for confirmatory analysis. The summary of the samples collected by the National Drug Authority of Uganda's quality control laboratory is presented in Table 3 below:

Table 3: Samples Received and Tested from the Four (4) EAC National Medicines Regulatory Authorities (NRA).

Prescribed methods from the United States Pharmacopeia (USP) were used for samples of Amoxicillin/Clavulanic Acid Tablets and Sulfamethoxazole/Trimethoprim Tablets. For samples of Amoxicillin 250 mg, only uniformity of dosage unit, identification, and assay results were reported. The official USP dissolution method had limitations, as many of the sampled Amoxicillin Capsules 250 mg were labeled as BP (British Pharmacopoeia) rather than USP. The BP doesn’t list a dissolution test for amoxicillin as one of the required confirmatory tests. Hence, for samples labeled as BP products, the dissolution test was not performed. Dissolution test was performed to Amoxicillin Capsules 500mg based on USP 2018 and results are summarized in Table 4b.

Uniformity of Dosage Units: The uniformity of dosage units was assessed using the USP 2018 weight variation test procedure. The procedure was applied to each unit of each sample by using the mean weight and assay value for each sample. Then, the API content in each dosage unit and acceptance values were calculated (23).

Identification: High-Performance Liquid Chromatography (HPLC) was used to confirm the chemical structure of Amoxicillin. A sample solution was prepared by dissolving 200 mg of anhydrous amoxicillin in a 200-ml volumetric flask and diluting to volume with buffer. The mixture was sonicated to ensure complete dissolution. The solution was injected into the HPLC system, and amoxicillin was detected by UV at wavelengths around 230-272 nm. Identification was confirmed by matching the retention time of the principal peak in the sample with that of a standard.

Assay: Assay was conducted based on the USP monograph, 2018 (23), as indicated below:

Buffer: Dissolved 6.8 g/L of monobasic potassium phosphate in water, then adjusted with 45% potassium hydroxide Test Solution (TS) to a pH of 5±0.1

Mobile Phase: Acetonitrile and buffer were used (1:24)

Standard Solution: 1.2 mg/mL of USP Amoxicillin RS was dissolved in Buffer for 6 hours

Sample Solution: The amoxicillin content was removed from the capsules, and 200 mg of anhydrous amoxicillin was placed in a 200-mL volumetric flask. Buffer was added to volume, and the solution was sonicated to ensure complete dissolution. The solution was used after 6 hours.

Chromatographic System

Model: Liquid Chromatography

Detector: UV 230 nm

Column: 4-mmx25-cm; 10-µL

System Suitability

Sample: Standard Solution

Suitability Requirements

Tailing Factor: NMT 2.5

Relative Standard Deviation: NMT 2.0%

Analysis

Samples: Standard Solution and Sample Solution

The percentage of the labeled amount of amoxicillin (C16H19N3O5S) in the portion of the capsules sampled.

Results were calculated using the following formula:

Result=(ru/rs) x (Cs/Cu) x P x F x 100

Where ru = peak response from the Sample solution; rs = peak response from the Standard solution; Cs = concentration of USP Amoxicillin RS in the Standard solution (mg/mL); Cu = nominal concentration of amoxicillin in the Sample solution (mg/mL); P = potency of amoxicillin in USP Amoxicillin RS (µg/mg); F = conversion factor, 0.001mg/ µg

Acceptance Criteria: 90.0% - 120.0%

Tables 4a and 4b present a summary of the results for the test parameters applied to the Amoxicillin Capsules 250 mg and Amoxicillin Capsules 500 mg, respectively.

Table 4a: Results Obtained for Samples Containing Amoxicillin (250mg) at Level 2.

Table 4b: Results Obtained for Samples Containing Amoxicillin (500mg) at Level 2.

Table 4c presents the results obtained for the test parameters conducted on all products containing Sulfamethoxazole/Trimethoprim sampled from the four countries. Compendial tests were performed based on the USP, 2018.

Table 4c: Results Obtained for Samples Containing Sulfamethoxazole/Trimethoprim (400/80mg).

The results obtained from the full monograph analysis of samples containing Amoxicillin/Clavulanic Acid (500/125 mg) at Level 2 are presented in Table 4d below:

Table 4d: Results Obtained for Samples Containing Amoxicillin /Clavulanic Acid (500/125mg).

This multicountry baseline PMS demonstrates both the feasibility and added value of joint surveillance in a region with heterogeneous regulatory capacity. By pooling expertise, harmonizing sampling, and centralizing confirmatory testing, EAC NRAs identified an SF-related performance failure (poor dissolution of an SMX/TMP product) that led to a regional recall and removal from markets-an outcome unlikely to occur as quickly through isolated, country-only efforts [24].

The overall quality signal for the three antibiotics was encouraging: nearly all screened samples passed TLC identification and disintegration tests, and 96% of products subjected to full compendial testing were compliant. However, significant PIR deficiencies-particularly missing registration numbers and incomplete storage instructions on primary and secondary packs and PILs in Tanzania Mainland and Zanzibar-pose risks of misuse, improper storage, and limited traceability. These findings underscore the need to enforce labeling standards aligned with the EAC Medicines Evaluation and Registration guidelines, under which PIL content and legibility are mandatory and should mirror the Summary of Product Characteristics (SmPC) [25]. The PIL is the primary reference for the end user (patient), and when it lacks essential details, such as proper storage conditions, a list of excipients, or a physical description of the product, it can create confusion for both healthcare professionals and patients [26]. Unclear information in a patient information leaflet can negatively affect a patient’s medication adherence, which, in turn, may contribute to the development of antimicrobial resistance [27].

Since 2017, the EAC-MRH initiative has strengthened cross-border information sharing, shortened market authorization timelines [28], and laid the groundwork for joint PMS activities. Our data provide practical evidence that harmonized PMS can surface actionable issues (e.g., a failing batch, unregistered products in Zanzibar) and enable rapid risk management across borders. Such collaborative surveillance aligns with EAC’s intent to improve public health protection while enabling the legitimate trade of quality-assured medical products.

SF antibiotics, through under- or overdosing and poor dissolution, can cause resistant organisms and contribute to treatment failure. Although our study did not measure clinical AMR outcomes, the identification and removal of a noncompliant SMX/TMP product is a concrete policy lever to reduce inappropriate exposure to subtherapeutic dosing, thereby mitigating one pathway to resistance. Routine, risk-based PMS that prioritizes antibiotics with known market complaints and high utilization is, therefore a pragmatic component of national AMR action plans [29,30].

This was a pragmatic regulatory study rather than a formal inferential analysis. The sample size (203), unbalanced participation (no field sampling from Rwanda and South Sudan), and variable submission of confirmatory samples to NDA Uganda limit generalizability. Differences in pharmacopoeia designation (USP vs BP) constrained dissolution testing for some amoxicillin 250 mg capsules. The study period (2018) also predates recent EAC access changes and post COVID market dynamics, which may affect current risk profiles and supply chains. These limitations highlight the need for larger, periodic, risk-based surveys with standardized compendial testing and region-wide participation to yield more representative estimates and trend data.

Recommendations

Strengthen and Institutionalize Joint PMS: Implement routine, EAC-wide joint post-marketing surveillance using harmonized, risk-based sampling frameworks with minimum sample targets per country to improve comparability and trend monitoring. 

Enforce Product Information and Registration Compliance: Prioritize regulatory enforcement actions to address missing registration numbers, incomplete labeling, and deficient patient information leaflets, particularly at market entry and during post-approval inspections.

Standardize Confirmatory Testing: Ensure consistent submission of screening failures and a predefined proportion of compliant samples for compendial testing at designated laboratories, with harmonized pharmacopoeial standards and testing protocols.

Target High-Risk Manufacturers and Products: Link PMS findings to manufacturer oversight, including risk-based GMP inspections, corrective and preventive actions, and follow -up monitoring of implicated products or batches

Ensure Data Sharing and Regulatory Coordination: Strengthen regional information-sharing mechanisms for PMS outcomes, recalls, and noncompliance to enable timely, coordinated regulatory responses across EAC Partner States.

Among 203 antibiotic samples from four EAC NRAs, the vast majority met screening and compendial specifications; however, one SMX/TMP 480 mg product failed dissolution and was withdrawn from all EAC markets, and PIR deficiencies-especially missing registration numbers and incomplete storage guidance—were common in parts of the region. These findings validate the value of joint PMS for rapidly detecting and addressing quality risks while revealing regulatory gaps in labeling and market authorization that warrant enforcement. Future EAC PMS should be fully harmonized, adequately powered, and consistently submitted for confirmatory testing to generate representative, trendable evidence that informs enforcement, manufacturer oversight, and regional AMR strategies.

Limitations of The Study

This study had several methodological and operational limitations that should be considered when interpreting the findings, this includes:

1. Sampling strategy was primarily risk-based and purposive, rather than probabilistic. While appropriate for regulatory signal detection, this approach limits the ability to estimate the rue prevalence of substandard or falsified antibiotics or to generalize findings to the entire EAC pharmaceutical market.
2. Uneven participation across EAC Partner States introduced variability in the scope and depth of surveillance. Limited resources constrained field sampling in some countries, and not all NRAs submitted samples for Level 2 compendial testing, reducing cross-country comparability and potentially underestimating quality failures.
3. Heterogeneity in compendial testing posed analytical constraints. Difference in pharmacopoeia designation (United States Pharmacopoeia versus British Pharmacopoeia) limited the application of dissolution testing for some Amoxicillin 250 mg capsules samples, resulting in incomplete assessment of certain quality attributes across products.
4. The analysis was descriptive and compliance based, without inferential statistical modeling or formal hypothesis testing. As a pragmatic regulatory exercise, the study focused on identifying quality signals rather than establishing casual relationships or assessing associations with clinical or antimicrobial resistance outcomes.
5. The surveillance was conducted in 2018, before major changes in global pharmaceutical supply chains, regulatory reforms, and market dynamics following the COVID-19 pandemic. The results may not fully reflect current market risks or present prevalence of substandard and falsified antibiotics in the region.

Despite these limitations, the study provides valuable baseline evidence on the feasibility and utility of joint, risk-based post-marketing surveillance in the EAC and highlights priority areas for methodological strengthening in future surveys.

Survey of Antibiotics in East African Community

Financial and technical support for surveying antibiotics in the East African Community was provided by Physikalisch-Technische Bundesanstalt (PTB), Germany. Additionally, PTB supplied Minilab test kits to the NRAs of Zanzibar, Burundi, and Rwanda for basic screening tests.

Funding for Preparing the Manuscript for Publication

This research publication did not receive any financial support. 

Authorship Contribution Statement

Jane Mashingia: Conceptualization, formal analysis, data curation, methodology, writing the original draft, and reviewing the manuscript

Nasser Lubowa: Validation of data, writing-review and editing

Nimubona Israel: Validation of data, writing-review and editing

Mwadini A. Mwadini: Validation of data, writing-review and editing

Seth Kisenge: Validation of data, writing-review and editing

Vivian Rakuomi: Validation of data, writing-review and editing

Maper Dut Ador: Validation of data, writing-review and editing

Eliangiringa Kaale: Supervision, validation, writing review, and editing

Vicky Manyanga: Supervision, validation, writing review and editing

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Data Availability

Data will be available on request.

Acknowledgements

Authors express appreciation to the Director General of the EAC National Medicines Regulatory Authorities (NRAs) and the Heads of Post-Market Surveillance Departments for promoting collaboration and strengthening the regulatory system to combat substandard and falsified medical products. Special thanks to the Physikalisch-Technische Bundesanstalt (PTB) for its technical and financial resources to the EAC-MRH program for procurement of minilab test kits and support for the baseline study of antibiotic quality in the region.