The objective of this study was to evaluate the status of the counterfeit pharmaceuticals in Jordan. Four types of pharmaceuticals Lipitor (Atorvastatin-calcium), Concor (bisoprolol fumarate), Co-Diovan (Valsartan, hydrochlorothiazide) and Plavix (clopidogrel) were subjected to physical and chemical analysis. 173 samples of these four medicines were collected from the three most populated cities in the country, namely Amman, the capital of Jordan, Zarqa and Irbid. A sample of confiscated counterfeited medicines was obtained from the health authorities and tested utilising the HPLC and dissolution testing, in order to validate the reliability of the testing procedures. Samples were then tested using High Performance Liquid Chromatography (HPLC) and dissolution tests in order to assess the quality of these samples. Results of both chemical and physical analyses revealed that all samples were found to fall within the specification limits of United States Pharmacopoeia (USP) and no evidence was found of any counterfeit drug products in the samples examined. Since this study found no indication of a drug counterfeiting problem in Jordan, the researcher has concluded that there seemed to be two contributing factors to this result: first, the very effective legislative campaigns conducted by the health authorities’ in Jordan against counterfeit trade through new public health and pharmacy law which has been launched in 2008. Second, the rigorous tough enforcement measures conducted by health and law enforcement agencies in the country.

Background: In many countries, a significant proportion of medicines traded and consumed are of poor or variable quality. Meanwhile, failures in appropriately framing and responding to the problem have led to a proliferation of public health and governance challenges. Objective: To examine the issues exacerbating the trade and consumption of medicines of poor or variable quality, as well as present locally relevant strategies. Methods: Analytic triangulation was applied to the synthesis of publicly available documents. Results: Where economic and regulatory environments are less structured, supply chain security strategies that fixate on ‘counterfeits’ often fail in limiting the prevalence of poor quality medicines. In addition to a multivariate drug quality classification chart, three quality frameworks are presented for examining appropriate policy strategies in mediating drug quality. Conclusion: These tools can assist stakeholders in determining more locally relevant and context-specific strategies, while interrogating the proposition for greater transparency vis-à-vis drug quality.

Background: In many countries, a significant proportion of medicines traded and consumed are of poor or variable quality. Meanwhile, failures in appropriately framing and responding to the problem have led to a proliferation of public health and governance challenges. Objective: To examine the issues exacerbating the trade and consumption of medicines of poor or variable quality, as well as present locally relevant strategies. Methods: Analytic triangulation was applied to the synthesis of publicly available documents. Results: Where economic and regulatory environments are less structured, supply chain security strategies that fixate on ‘counterfeits’ often fail in limiting the prevalence of poor quality medicines. In addition to a multivariate drug quality classification chart, three quality frameworks are presented for examining appropriate policy strategies in mediating drug quality. Conclusion: These tools can assist stakeholders in determining more locally relevant and context-specific strategies, while interrogating the proposition for greater transparency vis-à-vis drug quality.

Världsmarknaden för läkemedlen beräknades år 2011 till 900 miljarder US$ enligt IMS-health. Marknaden för illegala läkemedel uppskattas vara värd mellan 75-200 miljarder dollar. I Sverige uppskattas den illegala läkemedelsmarknaden till motsvarande ≤0,5 %. Straffet för insmuggling av läkemedel till Sverige är böter eller max 2 års fängelse. Tullverket räknar med att man endast hittar 10 % av det som smugglas in. I andra länder kan straffet variera mellan böter (ekonomisk brottslighet i Afrika) till dödsstraff i Kina. I Utvecklingsländerna uppskattas 10-30 % av alla läkemedel som säljs vara förfalskade, jmf 1 % I-länderna. l. Förekomsten av förfalskade läkemedel har många allvarliga konsekvenser på människor som exempelvis, utebliven effekt, toxiska reaktioner, förgiftningar, som kan i värsta fall leda till döden. Ett annat alvarligt problem är resistensutveckling, ökad spridning av smittsamammasjukdomar som exempel, tuberkulos och/ eller HIV/AIDS. Syftet med detta examensarbete är att besvara frågan: Vilka problem ger den ökande förekomsten av förfalskade läkemedel i samhället. Undersökningen fokuserar på livstidsläkemedel, dvs ett läkemedel en person måste ta resten av sitt liv för behandling av sin kroniska sjukdom. För att komma till rätta med de problem, som förfalskade läkemedel, skapar krävs ett mer utvecklat samarbete mellan olika läkemedelsmyndigheter, läkemedelsföretag, internationella polisorganisationer, tull m.fl. Arbetet med att utveckla förpackningar som är svåra att förfalska bör intensifieras. Straffsatser bör kanske ses över. Det är viktigt att öka medvetandet bland allmänheten om risker med att köpa läkemedel utanför apotek (t ex via nätet).

Submitted by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2016-09-22T19:12:48Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Willian Ricardo da Rosa de Almeida.pdf: 1728935 bytes, checksum: add5d55f493e0f08fd42042f07a7a9b7 (MD5) / Approved for entry into archive by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2016-09-22T19:15:44Z (GMT) No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Willian Ricardo da Rosa de Almeida.pdf: 1728935 bytes, checksum: add5d55f493e0f08fd42042f07a7a9b7 (MD5) / Made available in DSpace on 2016-09-22T19:15:44Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Willian Ricardo da Rosa de Almeida.pdf: 1728935 bytes, checksum: add5d55f493e0f08fd42042f07a7a9b7 (MD5) Previous issue date: 2016 / A sildenafila é um fármaco utilizado como tratamento de primeira escolha para a disfunção erétil, sendo disponível comercialmente na forma farmacêutica de comprimidos. Atualmente, a sildenafila está entre os medicamentos mais vendidos no mercado mundial. Por esta razão, também está entre os medicamentos que mais são contrabandeados e/ou falsificados. O desenvolvimento de métodos analíticos para avaliar a qualidade de produtos farmacêuticos bem como aqueles voltados para análise de amostras forenses são de extrema importância e constituem-se como ferramentas para a disponibilização de medicamentos com qualidade garantida. Desta forma, o presente trabalho teve por objetivo desenvolver e validar um método analítico indicativo de estabilidade por UFLC para a quantificação de sildenafila em comprimidos, bem como avaliar a cinética de degradação fotolítica e a segurança biológica dos fotoprodutos de degradação obtidos. Ainda, amostras suspeitas de falsificação de comprimidos de sildenafila (cedidas pela Superintendência Regional da Polícia Federal do Rio Grande do Sul) foram avaliadas em relação aos critérios de qualidade estabelecidos em compêndios internacionais através dos testes de: (a) resistência mecânica, (b) desintegração, (c) dissolução, (d) teor, (e) perfil químico por espectrometria no infravermelho médio e (f) perfil físico (diâmetro, peso e altura). Os resultados foram avaliados utilizando ferramentas de controle estatístico de processo e análise multivariada. No desenvolvimento do método por UFLC, as seguintes condições foram estabelecidas: fase móvel acetonitrila:trietilamina pH 4,0 (60:40, v:v), fluxo 0,7 ml min-1, coluna C18 (100mm x 4,6mm x 5μm), temperatura 50°C e detecção em 290 nm. O método foi validado segundo a normativa do ICH e mostrou-se específico, linear, preciso, exato e robusto. A segurança biológica foi determinada pelos ensaios de: (a) de Azul de Tripan, (b) Teste de Micronúcleos e (c) Ensaio Cometa. O fármaco e seus produtos de fotodegradação apresentaram citotoxicidade, no entanto não foram observados mutagenicidade e genotoxicidade. Na avaliação dos comprimidos suspeitos de falsificação não foram encontrados desvios de qualidade e a análise multivariada (por Análise Hierárquica de Agrupamentos) se mostrou adequada para classificação das amostras quanto ao perfil físico. / Sildenafil is the first choice pharmaceutical product for erectile dysfunction treatment and commercially available in tablets dosage form. Nowadays, Sildenafil is among the largest selling pharmaceutical products in the worldwide marketing. For this reason, is also among the most falsified and/or smuggled in the world. The development of analytical techniques that aim to evaluate pharmaceutical products’ quality, as well as those that aim forensic samples, are extremely valuable, once they are resources for quality guaranteed pharmaceutical products availability. Thus, our present study aimed to develop and validate a stability-indicative analytical method by UFLC, in order to quantify Sildenafil in tablets. Photolytic degradation’s kinetics and biological safety of Sildenafil’s photoproducts were evaluated. Additionally, Sildenafil tablets that were suspect of falsification (conceded by Regional Superintendence of Federal Police), were evaluated according to quality criteria previously established by international compendiums, being them: (a) mechanical resistance, (b) disintegration, (c) dissolution, (d) assay, (e) chemical profile by infrared spectroscopy, and (f) physical profile. The results were evaluated by control-process statistical and multivariate analysis. The following conditions were established for UFLC method: acetonitrile:triethylamine (60:40, v:v) as mobile phase, flux at 0.7mL.min-1, C18 column (100mm x 4,6mm x 5μm), 50°C, pH 4.0 and 290 nm. Proposed method was validated following ICH’s guidance, and showed specificity, linearity, precision, accuracy, and robustness. Biological safety was determined by the following assays: (a) Trypan Blue, (b) Micronucleus, and (c) Comet assay. The intact molecule, as well as its photoproducts showed cytotoxicity even no mutagenicity or genotoxicity was detected. Finally, tablets (suspected of falsification) had no quality deviation and multivariate analysis (Hierarchical Component Analysis) applied in physical profile showed adequate for sample’s classification.

Malaria is still an epidemic in many parts of the world-about 220 million people are still infected with malaria worldwide and about 700 thousand people die from this disease per year. Most of the drugs used to treat malaria work well if they are used as required and they contain the right amounts of the active ingredient; however, it is estimated that more than 10% of drugs traded worldwide are counterfeits including 38% to 53% of antimalarial tablets produced in China and India. Due to the lack of data covering the extent of counterfeit antimalarial drugs in Ghana, the purpose of this quantitative study was to determine the percentage of counterfeit antimalarial drugs sold in Ghana by assessing the amounts of the 2 most common antimalarial drugs, artemether (ATMT) and lumefantrine (LMFT) in drugs sold in Ghana retail outlets. These drugs were purchased from retail outlets in Ghana and analyses at the Mayo Clinic Pharmacology core lab (Rochester, MN). The quality of the drugs were characterized by comparing the actual amount of ATMT & LMFT in each tablet to the expected amount. Using explanatory theory along with dose response-response occupancy theory, the researcher addressed quantitative solutions to questions related to the percentage and distribution of counterfeit ATMT and LMFT tablets. The results revealed that overall 20% of the drugs are counterfeit; this is not dependent on the location or kind of outlet but rather depends on whether the tablets were imported or locally manufactured and whether the tablets had a pedigree scratch panel. This study provides a better understanding of how much antimalarial medication is counterfeit in Ghana, which will aid interventions to minimize the adverse effects of counterfeit antimalarial medication in Ghana

Herewith are presented the results of an investigation the statistical power of USP compendial release tests and recommended alternatives. <br>The U.S. drug supply chain, formerly protected by a closed distribution network, is now threatened by the legal and illegal importation of drug products. Whereas quality can never be inspected into final products, compendial release standards may represent the only valid assessment that products of dubious origin would receive. Reliable tests for content uniformity and dissolution are required to protect the safety of the supply chain. A study was designed to test the hypothesis that existing compendial tests for content uniformity and dissolution would protect the supply chain against substandard and counterfeit drugs if basic field tests failed. <br>Compendial tests for content uniformity and dissolution were evaluated for statistical power using simulation studies. The results revealed that the revised content uniformity test, based on tolerance analysis, was subject to an unacceptable level of consumers' risk. The Bergum method proved to be an excellent secondary standard for product assessment and is recommended as an alternative to the USP method. Simulations with the USP dissolution test revealed significant weaknesses and inconsistencies in the test structure. Theoretical models and power assessments confirmed that the coverage specification of the dissolution test was an unacceptably high 50% coverage with 50% confidence. <br>A Bayesian D-optimal design program was used to investigate alternative methods to improve the coverage capability of the USP dissolution test. The result of this program was the identification of two alternatives to the existing USP procedure. The first alternative is based on the addition of attribute coverage tests to stages 2 and 3 of the USP test, whereas the second alternative is based on the concept of tolerance analysis. <br>Validation studies confirmed that both alternatives significantly improved the statistical power of the USP dissolution test without increasing the sample size or modifying the current three-stage procedure. The attribute test is non-parametric and behaves similarly to the existing USP with improved coverage, whereas the continuous alternative is more sensitive and is consistent with the recent revisions to the content uniformity test. / Mylan School of Pharmacy and the Graduate School of Pharmaceutical Sciences / Pharmaceutics / PhD / Dissertation

The use of technology in business process is gaining much attention, and many businesses today rely on technology as an important part of an efficient and effective way of meeting customers’ satisfaction. This study deals with the adoption of a proper and electronic means of tracking counterfeit drugs in the supply chain (distribution network) through the use of RFID technology. The case of the Ghanaian pharmaceutical group KAMA is considered. The main objective consists in finding out how the adoption of RFID technology would help tracking counterfeit drugs in the supply chain of this company and which benefits this could generate. Three research questions are stated and a qualitative approach is adopted. Field observation, a series of interviews with management and field workers of Kama as well as a questionnaire allowed collecting the data. The analysis of the data showed that RFID technology should be adopted by Kama to replace the present costly and relatively inefficient way of tracking counterfeit drugs. The motivation of workers to be trained on RFID as well as the company readiness to train employees represent major factors for adoption and implementation of RFID to track counterfeit drugs and hence contribute to increase the profit margin and improve Kama’s image on the market. Recommendations are finally made on the methodology to be adopted by Kama to implement and use RFID technology to track counterfeit drugs. / <p>Validerat; 20111202 (anonymous)</p>

This Thesis examines the benefits and usefulness of a National Drug Policy (NDP) for the developing of the Health Care System in Kuwait. The NDP is one of the most important structures of the Health System which can lead to improved health services by establishing guidelines, proposals and directives to organize, structure and regulate health legislation; it is of help to ensure the availability of quality, safety and efficacy in using medicines and it can reduce the irrational use of medicines. The NDP is a frame work between the government, schools and universities, media, health professionals, pharmaceutical industries and companies and public. It is cooperation between the public and private sectors to achieve the goal of access to good quality medicines for all. However there are many key factors which need to be examined before the National Drug Policy is introduced and these are considered the baseline for establishing a good policy, and includes; selection of essential drugs, affordability of drugs, drug financing, supply management, drug regulation, rational use of drugs, drugs registration, purchasing of drugs, health research and human resource development. During this research study from 2012 – 2015 several visits to the public and private health areas, were undertaken. At this time there were discussions with 121 health professionals and data was collected and this indicated that in Kuwait there are no such policies. This is despite the availability of financial means, specialized human resources and the existence of the ministerial decisions and regulations governing the health sector in both public and private, whether hospitals, health centers, pharmacies and health departments. In addition it is suggested that the process of a good NDP should be built around 3 main components which includes: 1.Development, 2. Implementation and 3. Monitoring and Evaluation. Therefore the establishing of a NDP without implementation and monitoring is not enough and does not achieve the desired results. The aim of this Thesis is to establish a NDP in the State of Kuwait. This policy is necessary for the State of Kuwait to ensure development an improvement of the Health Care System and ensure better health for population.

Ambient mass spectrometry (MS) is a new and growing sub-field in MS which has opened new research avenues, particularly for applications relating to the analysis of solid samples. Results on the implementation and application of ambient MS techniques including: desorption electrospray ionization (DESI) and direct analysis in real time (DART) indicated that these techniques could serve as complementary tools for the rapid qualitative screening of pharmaceuticals, allowing up to two orders of magnitude improvement in throughput compared to traditional methods such as liquid chromatography MS. The selectivity of DESI could be enhanced by performing the experiment in the reactive mode. In this mode, complexation reactions between reagents added to the spray solvent and analytes on the sample surface resulted in analyte stabilization, inhibiting fragmentation. They also resulted in a concomitant enhancement in the analyte surface activity, facilitating their evaporation from secondary droplets culminating in an improvement in sensitivity. Also for drug tablets analysis, the analyte signal dependency on DESI geometrical set-up variables could be mitigated following the careful and controlled addition of an isotopically labeled internal standard (IS) to the sample or by spraying samples with a pair of reagents with different affinities for the analyte. Either of these approaches resulted in an analyte-to-IS signal ratio (in the former) or an analyte complex ratio (in the later), which was largely independent of DESI experimental variables allowing quantitative analysis using this technique. DESI MS was also observed to be a very powerful tool for determining the 2-D distribution of various pharmaceutically important compounds on tablet and tissue surfaces. The ability to map the distribution of molecules of interest by DESI MS has very great implications in drug tablet quality control and in determining the role of chemical signals presented on tissue surfaces. DESI was observed to be limited to ionizing molecules of medium to high polarities without much limitation in terms of mass range, whereas DART was better suited for the analysis of molecules within a broader range of polarities, but within a more limited mass range (up to 800 Da approximately). These limitations were circumvented by implementing a novel multimode ambient ion source, desorption electrospray/metastable-induced ionization (DEMI), which combines various aspects of DESI and DART. Initial experiments with the DEMI ion source demonstrated its ability to enable the simultaneous analysis of molecules within a broader range of polarities and masses than DESI and DART alone.