Pharmaceutical Regulatory Framework in Ethiopia: A Critical Evaluation of Its Legal Basis and Implementation.

BACKGROUND: Effective and enforceable national regulations describing the manufacture and (re)packaging, export and import, distribution and storage, supply and sale, information and pharmaco-vigilance of medicines are required to consistently ensure optimal patient benefit. Expansion of pharmaceutical industries in many countries with advancement in transport technologies facilitated not only trade of genuine pharmaceutical products but also the circulation of poor quality medicines across the globe. In Ethiopia, even though "The Pharmacists and Druggists Proclamation No 43/1942" was used to regulate both the professions and the facilities where they were practiced, comprehensive regulation of the pharmaceutical market was introduced in 1964 by a regulation called "Pharmacy Regulation No. 288/ 1964". This legislation formed the legal basis for official establishment of drug regulation in the history of Ethiopia, enabling the regulation of the practice of pharmacists, druggists and pharmacy technicians; manufacturing, distribution, and sale of medicines. In June 1999, a new regulation called the "Drug Administration and Control Proclamation No. 176/1999" repealed most parts of the regulation 288/1964. The law established an independent Drug Administration and Control Authority (DACA) with further mandate of setting standards of competence for licensing institutions/facilities. DACA was re-structured as Food, Medicine and Health Care Administration and Control Authority (EFMHACA) of Ethiopia by the "Proclamation No. 661/2009" in 2010 bearing additional responsibilities like regulation of food, health care personnel and settings. The mere existence of this legal framework does not guarantee complete absence of illegal, substandard and falsified products as well as illegal establishments in the pharmaceutical chain. Therefore, the objective of the research is to assess the pharmaceutical regulatory system in Ethiopia and to reveal possible reasons for deficiencies in the pharmaceutical chain. METHODS: An archival review, an in-depth interview of key informants and an institutions-based cross-sectional survey study were conducted during March to April 2013. The comprehensiveness of the pharmaceutical law to protect public health relative to three selected African countries (South Africa, Tanzania and Uganda) and European Union, and implementation was assessed. RESULTS: The study revealed that Ethiopia does have a written national drug policy upon which the Medicines Regulatory Proclamation 661/2009 is based. According to this proclamation, the Ethiopian The Food, Medicines and Healthcare Administration and Control Authority is mandated to execute the regulatory activities as per the council of ministers regulation 189/2010. The legal framework for pharmaceutical regulation of Ethiopia was founded to fulfill all the medicines regulatory functions potentially enabling to combat illegal, substandard and falsified medicines and illegal establishments. Moreover, all the key informants witnessed that the government is commited and proclamation 661/2009 is comprehensive, but they stressed the compelling need of regulatory tools for effective implementation. From the institution-based cross-sectional study, it was revealed that there exist illegal sources formedicine in the pharmaceutical market. The main reasons for their existence were regulatory factors including weak regulatory enforcement (64.5%), lack of informal market control (60.8%), weak port control (50.0%), and poor cooperation between executive bodies (39.6%); and resource constraint (27.8%), which is an institutional factor. CONCLUSIONS: From legislative point of view, the medicines regulatory framework in Ethiopia fulfils all regulatory functions required for effective medicines regulation. However, the existence of the legislation by its own is not a guarantee to prevent the existence of unauthorized/illegal medicine sources since this requires effective implementation of the legislation, which is in fact affected by the governments political commitment, resource and intergovernmental cooperation.

Impurity fingerprints for the identification of counterfeit medicines--a feasibility study.

Most of the counterfeit medicines are manufactured in non good manufacturing practices (GMP) conditions by uncontrolled or street laboratories. Their chemical composition and purity of raw materials may, therefore, change in the course of time. The public health problem of counterfeit drugs is mostly due to this qualitative and quantitative variability in their formulation and impurity profiles. In this study, impurity profiles were treated like fingerprints representing the quality of the samples. A total of 73 samples of counterfeit and imitations of Viagra(®) and 44 samples of counterfeit and imitations of Cialis(®) were analysed on a HPLC-UV system. A clear distinction has been obtained between genuine and illegal tablets by the mean of a discriminant partial least squares analysis of the log transformed chromatograms. Following exploratory analysis of the data, two classification algorithms were applied and compared. In our study, the k-nearest neighbour classifier offered the best performance in terms of correct classification rate obtained with cross-validation and during external validation. For Viagra(®), both cross-validation and external validation sets returned a 100% correct classification rate. For Cialis(®) 92.3% and 100% correct classification rates were obtained from cross-validation and external validation, respectively.

Detection of counterfeit Viagra® by Raman microspectroscopy imaging and multivariate analysis.

During the past years, pharmaceutical counterfeiting was mainly a problem of developing countries with weak enforcement and inspection programs. However, Europe and North America are more and more confronted with the counterfeiting problem. During this study, 26 counterfeits and imitations of Viagra® tablets and 8 genuine tablets of Viagra® were analysed by Raman microspectroscopy imaging. After unfolding the data, three maps are combined per sample and a first PCA is realised on these data. Then, the first principal components of each sample are assembled. The exploratory and classification analysis are performed on that matrix. PCA was applied as exploratory analysis tool on different spectral ranges to detect counterfeit medicines based on the full spectra (200-1800 cm⁻¹), the presence of lactose (830-880 cm⁻¹) and the spatial distribution of sildenafil (1200-1290 cm⁻¹) inside the tablet. After the exploratory analysis, three different classification algorithms were applied on the full spectra dataset: linear discriminant analysis, k-nearest neighbour and soft independent modelling of class analogy. PCA analysis of the 830-880 cm⁻¹ spectral region discriminated genuine samples while the multivariate analysis of the spectral region between 1200 cm⁻¹ and 1290 cm⁻¹ returns no satisfactory results. A good discrimination of genuine samples was obtained with multivariate analysis of the full spectra region (200-1800 cm⁻¹). Application of the k-NN and SIMCA algorithm returned 100% correct classification during both internal and external validation.

Comparison and combination of spectroscopic techniques for the detection of counterfeit medicines.

During this study, Fourier transform infrared spectroscopy (FT-IR), near infrared spectroscopy (NIR) and Raman spectroscopy were applied to 55 samples of counterfeit and imitations of Viagra and 39 samples of counterfeit and imitations of Cialis. The aim of the study was to investigate which of these techniques and associations of them were the best for discriminating genuine from counterfeit and imitation samples. Only the regions between 1800-400 cm(-1) and 7000-4000 cm(-1) were used for FT-IR and NIR spectroscopy respectively. Partial least square analysis has been used to allow the detection of counterfeit and imitation tablets. It is shown that for the Viagra samples, the best results were provided by a combination of FT-IR and NIR spectroscopy. On the other hand, the best results for the Cialis samples were provided by the combination of NIR and Raman spectroscopy (1400-1190 cm(-1)). These techniques not only permitted a clear discrimination between genuine and counterfeit or imitation samples but also the distinction of clusters among illegal samples. This might be interesting for forensic investigations by authorities.