PRE- AND POST-MARKETING CONTROL OF DRUG QUALITY AT THE NATIONAL HEALTH LABORATORY, BAMAKO-MALI
Ousmane Dembélé1,2*, Seydou Moussa Coulibaly2, Jacques Dakouo2, Benoît Y Koumaré1,2
1Faculty of Pharmacy of Bamako, University of Sciences, Techniques and Technologies of Bamako, Mali.
2Bamako National Health Laboratory, Mali.
Background and Objectives: In a world marked by the spread of counterfeiting and substandard drugs, often without active ingredients or falsified active ingredients, greater vigilance by pharmaceutical regulatory authorities is necessary. The National Health Laboratory (LNS), in accordance with its mission, takes samples throughout the country in order to ensure their quality control.
Methods: Samples were taken in certain regions and the district of Bamako and analyzed according to the standards of the United State Pharmacopoeia (USP), British Pharmacopoeia (BP) and International Pharmacopoeia (IP)by identification and assay methods. Products that do not meet the required specifications described by these pharmacopoeias are declared non-compliant.
Results: This allowed us to analyze a total of 617 samples with 11 cases of non-compliance for a rate of 2%. The causes of the non-conformities were due to the absence of an active ingredient, an under-dosage of the active ingredient and technical and regulatory defects.
Conclusion: After one year of activity, our results showed that out of a total of 617 drug samples collected and analyzed, 606 were compliant with a rate of 98% against 11 cases of non-compliance or 2% (p≤0,05). The causes of the non-compliance were due to the absence of an active ingredient, an under-dosage of the active ingredient and technical and regulatory defects.
Keywords: non-compliance, quality control, post-marketing, pre-marketing.
INTRODUCTION
In a world marked by several challenges including, among others, the increase in chemo resistance leading to the adoption of therapeutic combinations, the advent of multi-source generic drugs, the spread of counterfeiting and substandard drugs, often without active ingredients or falsified active ingredients, greater vigilance by pharmaceutical regulatory authorities is necessary1. Good quality drugs are essential for effective disease management. Substandard and falsified drugs can cause treatment failure and side effects, increase morbidity and mortality, and contribute to the development of drug resistance. Vulnerable populations and patients with co-morbidities are particularly at risk of being affected by receiving substandard or falsified drugs. Poor quality drugs also increase health care costs for patients and the health system as a whole, wasting resources that could otherwise be used for the benefit of public health.1 Medicines regulation is a complex process that includes various regulatory instruments, such as authorization /registration for marketing. It also implies product documentation, inspection to verify manufacturer’s compliance with the principles of good manufacturing practices (GMP) and approval of product information. It may also include Post-Marketing Surveillance (PMS) activities, such as maintaining product authorization and/or registration through variations or renewals, regular inspections of manufacturers, quality control tests, pharmacovigilance and the implementation of regulatory measures in case a quality problem is found. When a product is made available to the public, it is not possible to predict every conceivable side effect or adverse event that could occur in large and diverse populations1,2.
The quality of drugs can easily deteriorate through improper handling during distribution or storage before they reach patients3. Quality control/quality assurance (QC/QA) of drugs in the distribution system to appropriate specifications is therefore an important prerequisite to ensure optimal results. It is therefore essential to carry out regular monitoring of the quality of medicinal products through sampling missions and pre-marketing controls to guarantee their quality3. Post-market surveillance of drugs therefore plays an important role in uncovering the actual state of products in terms of safety, quality and efficacy that could pose a risk to users. It allows regulatory authorities to take appropriate measures for the withdrawal of falsified and substandard medicines from the market4.
The National Health Laboratory (LNS) in accordance with its mission and as part of the pre- and post-marketing quality control of drugs, periodic samples are taken throughout the territory by LNS agents with the aim of to ensure the monitoring of drugs by their quality control at the laboratory with a view to safeguarding the health of populations.
MATERIALS AND METHODS
The material consisted of all the drugs analyzed from January 2020 to December 2020 at the LNS. In this study, data was collected using analytical certificates of drugs subject to quality control. The following information was collected: origin, place of collection, galenic form, therapeutic class, analytical methods, analytical equipment, and analytical results. Various analytical methods and tests are important for the development and manufacture of pharmaceutical formulations but also for their quality control. The evaluation was carried out according to the standards of the United State Pharmacopoeia (USP), the British Pharmacopoeia (BP) and the International Pharmacopoeia (IP) by test methods (Friability, Disaggregation, Dissolution, pH, Average Volume, Coefficient of Variation of Weight, Loss on Desiccation), identifications (Thin Layer Chromato-graphy, Minilab®, FTIR, RAMAN and assays (High Performance Liquid Chromatography, UV-Visible Spectrophotometry, Titrimetry)5-8.
Figure 1: Global situation of samples according to their quality.
RESULTS AND DISCUSSION
Out of a total of 617 drug samples taken and analyzed, 606 comply with the required specifications, therefore compliants, a rate of 98% against 11 cases of non-compliance with 2%.These data are similar to those of Konaté et al., who found 6.9% of non-compliance9.
Galenic forms
In this study, the most represented dosage form was the compressed form with 41.3% followed by the injectable form 36.1% which is similar to that of Konaté et al., who found 57.05%. We found that the syrup form represented the greatest number of non-compliance, i.e. 54.54% of the total number of non-compliant products, followed by the syrup/suspension form with 36.36%9 (Table 1).
Pharmacological classes
In this study, the predominant pharmacological class was antimalarials 24%, followed by antibiotics 19.4%. These results are contrary to those of Konaté et al., who found 34.84% for antibiotics followed by 16.89% for antimalarials. Total 45.45% of the total number of non-compliance products were found. This is different from that of the same study which found a high rate of non-compliance in antiseptics with 48.59%9 (Table 2).
Quality and manufacturer's country
These results showed that the samples analyzed came mainly from India with 57.4% followed by China 16%. These results confirm those of Sidibé et al., who found 45% and 17% respectively for India and China10.
It was also found that 13.1% of our samples were of unknown origin, these were mainly products of the Central Purchasing of Medicines (PPM) (Table 3).
Distribution/sampling circuit
In order to control the quality of our drugs by touching the entire distribution chain, samples were taken at all levels of the distribution circuit. Samples were taken in large part from the Pharmacy Popular of Mali (PPM) 67.1% which is the local purchasing center, followed by samples taken during LNS post-marketing surveillance missions with 11.3%, unlike those of Harira et al., who found that 59.4% came from Hospitals/Health centers11(Table 4).
Assay methods
In this study among the assay methods, the HPLC technique was the most used, followed by UV-Visible spectroscopy and titrimetry with 38%, 36% and 26% respectively (Figure 2).
Test and identification methods
In this study of the test methods, the uniformity of dosage units (UDU), pH and volume were the most used test methods. The colored test was the most widely used identification technique followed by TLC and FTIR (Figure 3).
Statistical analysis
After entering the data into an Excel file (database), it was exported to SPSS version 20 software for statistical analysis.
CONCLUSION
The proliferation of sources of supply and illicit sale of drugs as well as the inadequate conditions of their storage and the non-observance of good manufacturing practices can cause, with acuteness, problems at the level of the quality of the drugs available on the market. The LNS National Health Laboratory, in accordance with its mission and as part of the pre- and post-marketing quality control of drugs, takes periodic samples throughout the country for their quality control at the Laboratory. After one year of activity, our results showed that out of a total of 617 drug samples collected and analyzed, 606 were compliant, a rate of 98% against 11 cases of non-compliance or 2%. The causes of the non-conformities were due to the absence of an active ingredient, an under-dosage of the active ingredient and technical-regulatory defects and mainly affected antimalarials 24%, followed by antibiotics 19.4%. The results of these analyzes were transmitted to the socio-health authorities who proceeded with the withdrawals of these poor quality drugs thus safeguarding the health of the populations and advice was given in order to maintain the quality of the drugs at the points of sale and storage.Emphasis was also placed on the need to respect the master plan for the supply and distribution of Medicines which guarantees the safety of products up to the patient.
CONFLICT OF INTEREST
No conflict of interest associated with this work.
AUTHOR'S CONTRIBUTION
The contribution of all authors was essential for the success of this work.
ACKNOWLEDGMENTS
The authors thank the Management of the National Health Laboratory for making the Laboratory database available.
REFERENCES