There is a large gap between contemporary evidence-based remedies for pain control and what is offered to Ukrainian patients with pain. Having thousands of people needlessly suffer from avoidable pain forces a consideration of 1) what prevents from their access to pain relief, 2) are their human rights being violated and 3) how can the situation be improved. In order to identify the obstacles to adequate pain management in Ukraine I collected evidence using two methods. First, I designed a questionnaire for the Ukrainian doctors, received approval from the University of Ottawa Ethics Board, distributed the questionnaire among potential responders and then organized the obtained results. Second, I did an extensive literature review to provide evidence from the patients. Then I analysed the provisions of Ukrainian domestic and international legislation as well as the available case law to find out if the human rights of Ukrainian patients and doctors are being violated by denial of adequate pain relief. According to my findings, the barriers to pain control in Ukraine are multidimensional and interdependent. They cause violations of human rights, which are not being effectively defended through the courts of Ukraine. These findings call for a more constructive approach to the development of the Ukrainian health law and policy, which I offer in this thesis.

Magister Pharmaceuticae - MPharm / Medicines have to be regulated in an effort to monitor their quality, safety, and efficacy. The process of medicines registration is lengthy, costly, and document-heavy. Many countries have limited expertise and resources at national medicines regulatory authorities (NMRAs) and some countries have adopted unified approaches to medicines registration legislation. Harmonised guidelines and initiatives have been adopted in South Africa and the Southern African Development Community (SADC). However, there are no studies that have identified the effects of these initiatives and guidelines on major stakeholders such as the pharmaceutical industry and regulators.

In Canada, less than half of the drugs that the World Health Organization classifies as Essential Medicines for the treatment of Neglected Diseases like Chagas disease, drug-resistant tuberculosis, echinococcosis, leishmaniasis, leprosy, malaria and sleeping sickness are formally available, even as collectively hundreds of patients require access to them each year. Essential Medicines, according to the WHO, are those “intended to be available within the context of functioning health systems at all times in adequate amounts, in the appropriate dosage forms, with assured quality, and at a price the individual and the community can afford”. Nevertheless, many of these Essential Medicines, like the conditions they treat, are neglected by pharmaceutical companies and governments alike in low-burden, high-income countries like Canada. The result is a reversal of the usual access to medicines narrative around novel, patented medicines unavailable in low-income countries; these are old, off-patent Essential Medicines, many of which have become widely available in low and middle-income countries yet increasingly difficult to access in many high-income countries. Their absence from countries like Canada is not due to their lack of medical utility – many of them are recognized domestically as the standard of care – but their lack of commercial value. Unfortunately, Canada’s regulatory system is premised upon keeping unsafe, ineffective or poor-quality drugs out, not bringing Essential Medicines in. As a result, these drugs must be accessed through ill-fitting mechanisms like Canada’s Special Access Programme (SAP). Other high-income countries face similar access challenges, though they may manifest in different ways; in the United States for instance, drugs that have disappeared from the Canadian market or simply never been introduced in the first place have instead had de facto monopolies unscrupulously exploited. In turn, as the COVID-19 pandemic has served to underscore, access to these Essential Medicines for Neglected Diseases is an issue that cannot be solved solely at the domestic level. Essential Medicines that threaten to disappear before the diseases they treat do also serve to highlight broader issues of domestic and international concern, from drug shortages to antimicrobial resistance. This thesis provides an in-depth exploration of the problem, and offers guidance on what Canada in particular can do about improving access to medicines, especially those for Neglected Diseases that have been largely absent from the Canadian pharmaceutical agenda.

In recent years health care personnel have seen changes to their roles and responsibilities. A number of reports both from within the occupation and from government have recommended changes in the roles of community pharmacists so that they become more active in the provision of health care. The new roles and services suggested have become known as "extended roles" and include health promotion, treatment of minor ailments, provision of advice on prescribed medicines to the public and to other health care personnel. The aim of this study was to investigate the factors affecting the extended roles of the community pharmacist. The investigation initially took an exploratory approach and used unstructured interviews with pharmacists to ascertain influences on every day practice which could have implications on implementation of extended roles. The findings from the initial qualitative stage were incorporated into a national survey of community pharmacists. A number of interrelated factors were found to be important including work practices, financial considerations, people's expectations, relationships with GPs and pharmacists' own definitions of their roles. These findings are explained in terms of the progressive division of labour in the market for the provision of health care. Recommendations are made for extending the role of the community pharmacist

Antimicrobial growth promoters (AGPs) are substances that are added to feed in sub-therapeutic levels in intensive animal production to improve weight gain and conversion of feed (FCR) into body mass. AGPs have been used widely as growth promoters in broiler and pig production under high-density growth conditions. Despite the observed efficacy, the use of AGPs has been criticized due to its possible role in the development of antibiotic resistance in human pathogens. Directive 183/2003 of the European Parliament, issued in 2003, banned of the use of all antibiotic agents as growth promoters in the European Union from 2006. The new context caused an increase in the search for alternative growth promoters. The aim of this study was to produce a commercially viable prophylactic antibacterial phytogenic product from Ginkgo biloba and Hypericum perforatum with a low potential to develop resistance, as an alternative to AGPs in poultry production. The first objective of this study based on earlier results of the Phytomedicine Programme, was to evaluate the activity and potentize extracts from Ginkgo biloba and Hypericum perforatum for optimal activity against relevant bacterial pathogens. Extracts of ethyl acetate (EA), hexane, dichloromethane (DCM) and acetone (in order of activity) from a direct extraction procedure of powdered G. biloba leaves were active against Enterococcus faecalis, Staphylococcus aureus and Clostridium perfringens. The EA, hexane and DCM extracts were 2 to 3 times more active than the acetone extract (average total activity 1728 ml/g dry extract for the 3 pathogens). The DCM-, EA-, acetone- and hexane extracts (in order of activity) from the direct extraction procedure from H. perforatum were only active against C. perfringens with the first three extracts having a total activity of between 1026 and 1333 ml/g dry material and the hexane extract a total activity of 333 ml/g dry material. The spectrum of activity of G. biloba corresponds to that of Zn-bacitracin, which is commonly used an antibiotic growth promoter in the poultry industry. The second objective in this study was to combine extracts or fractions of extracts of G. biloba and H. perforatum to optimise activity against selected bacterial pathogens. A synergistic effect could be observed when combining a ratio of 1:5 of G. biloba: H. perforatum (hexane extracts) or 1:15 (acetone extracts) against E. faecalis while only an indifferent (neutral) effect was observed against C. perfringens. After elucidation of the quantitative and qualitative aspects involved in the antimicrobial activity, the major antibacterial compound from G. biloba was isolated and characterized as ginkgolic acid (C17:1). It was also determined whether activity against E. faecalis and C. perfringens in an extract or fraction of and extract of G. biloba can be attributed only to ginkgolic acid or whether synergism or other interactions also play a role in the antibacterial activity. It was shown that synergistic interactions are at play between constituents in the hexane and EA fraction, with the last mentioned fraction not containing any ginkgolic acid. These results support the use of the whole extract as opposed to isolated compounds as antimicrobial agents against pathogenic organisms. Two important pharmacodynamic parameters were investigated i.e. resistance development to a hexane extract and the isolated ginkgolic acid from G. biloba against E. faecalis and secondly the time-kill dynamics of this hexane extract over 24 h against E. faecalis. The bactericidal nature of the hexane extract from G. biloba as well the absence of decreased susceptibility to this extract (and the isolated ginkgolic acid) in the resistance studies against E. faecalis indicate that this extract has potential to be exploited as a alternative to AGPs in the poultry industry. The final objective was to determine the effect of extracts of G. biloba alone or in combination with H. perforatum extracts on the performance of broiler chickens over a 35 day period. The effect of these extracts on C. perfringens in the intestine of broilers was also investigated. No significant differences were found with relation to any of the production parameters studied (FCR, live weight or % survival) although a trend towards more favourable European Performance Efficiency Factor index values were observed for treatments containing G. biloba (5% improvement) or a combination of G. biloba and H. perforatum (2.1% improvement) compared to the untreated control. Similarly, Zn-Bacitracin resulted in a 5.5% improvement compared to the untreated control. There was a general trend (not statistically significant, P=0.05) towards a reduction in C. perfringens scores in the feed supplemented with G. biloba- in combination with H. perforatum extract which can probably be ascribed to the direct antimicrobial effect. The rate of colonization was however too low to cause infection probably due to lack of virulence of the C. perfringens challenge and the absence of predisposing factors due to the hygienic growth conditions used. It is necessary for an effective disease model to be developed in order for the efficacy of any new treatment method to be properly evaluated. Such a model will require a much higher incidence of disease and reproducibility than was achieved in this project. The safety of using extracts of G. biloba with ginkgolic acid as the prime antibacterial compound was considered. The active dose was at least 42 times lower than safe dosage recommended in the literature. The combination of extracts of G. biloba and H. perforatum holds promise as a potential growth promoter in poultry production. Better results may be achieved if potentized extracts are used and compared with Zn-Bacitracin and a negative control under industrial growth conditions where the birds are stressed and natural infections would take place. Copyright / Thesis (PhD)--University of Pretoria, 2009. / Paraclinical Sciences / unrestricted

RATIONALE AND AIM: The double checking of medicines in health care is a contestable procedure. It occupies an obvious position in health care practice and is understood to be an effective defence against medication error but the process is variable and the outcomes have not been exposed to testing. This paper presents an appraisal of the process using data from part of a larger study on the contributory factors in medication errors and their reporting. METHODS: Previous research studies are reviewed; data are analysed from a review of 991 drug error reports and a subsequent series of 40 in-depth interviews with health professionals in an acute hospital in northern England. RESULTS: The incident reports showed that errors occurred despite double checking but that action taken did not appear to investigate the checking process. Most interview participants (34) talked extensively about double checking but believed the process to be inconsistent. Four key categories were apparent: deference to authority, reduction of responsibility, automatic processing and lack of time. Solutions to the problems were also offered, which are discussed with several recommendations. CONCLUSIONS: Double checking medicines should be a selective and systematic procedure informed by key principles and encompassing certain behaviours. Psychological research may be instructive in reducing checking errors but the aviation industry may also have a part to play in increasing error wisdom and reducing risk.

Magister Pharmaceuticae - MPharm / Medicines (CMs) are widely available to the South African public. However, CMs have not yet been evaluated by the Medicines Control Council (MCC). The MCC has published new guidelines for the regulation of CMs, with which CM companies are required to comply. OBJECTIVE: Determine to what degree Western Herbal CM labelling complies with the MCC’s requirements. METHODS: Thirteen CM products containing recognised Western Herbal ingredients were selected from pharmacies in the northern suburbs of Johannesburg. Labelling information on the immediate and outer container labels, as well as the package inserts, was investigated. The relevant corresponding European Medicines Agency (EMA) monographs and MCC guidelines were used to assess compliance. RESULTS: None of the products complied with the product dosage section of the monographs. Furthermore, the products contained indications that were not present in the monographs. The products did not fully meet the MCC’s mandatory minimum labelling requirements, and they did not demonstrate total compliance with all of the MCC’s requirements for product labels and package inserts.

Abstract A recent World Health Organisation study conducted in 26 countries found substantial disagreement in the prescribing information available in those countries, as well as significant disparity between brands within the same country. This appears to be a common experience in other countries. This may mislead prescribers, patients and those comparing drug-use patterns across countries, and have serious safety implications. This study was carried out to investigate the variability of prescribing information currently available within South Africa, comparing generic and originator brands. It also investigated the extent of variability between the Standardised Package Insert (SPI) mandated by the Medicines Control Council, versus internationally approved prescribing information for given drug substances. Five drug substances were selected that are widely used in South Africa. The package inserts of the originator product were compared in terms of the indications, dosage, cautions, side-effects and drug interactions versus five generic brands of each drug substance registered in South Africa, using a comprehensive method adapted from the WHO study. The SPI was also compared against the South African originator brand package insert and those approved in four international MCC Reference Countries (ie. USA, EU, Canada & Australia) for each drug substance. Substantial disagreement was found between the originator and generic products for each drug substance, which may be due, in part, to the absence of a mandatory periodic updating requirement for package inserts in the post-registration phase in South Africa. This may result in divergence between materials from companies that voluntarily submit safety updates over the life of the product, and those that do not. There was also substantial disagreement between the SPI and the originator and international reference country materials. The reason is less simple to explain. The SPI project is in its early stages, and requires validation to ensure that the texts are in fact, entirely in line with latest best clinical practice and with the reference countries with which MCC aligns itself. These findings are comparable with those found in international WHO study. Regulatory authorities have key responsibility in ensuring that prescribing information is current and consistent across originator, generic and international materials. It is recommended that the MCC implement a mandatory updating requirement for all registered medicines with specified timelines. Secondly, a validation step should be introduced in the MCC SPI project to ensure consistency with international materials. Additional recommendations are made to improve the quality and practicality of prescribing information to ensure that it remains relevant in the South African and regional context. vThese findings are comparable with those found in international WHO study. Regulatory authorities have key responsibility in ensuring that prescribing information is current and consistent across originator, generic and international materials. It is recommended that the MCC implement a mandatory updating requirement for all registered medicines with specified timelines. Secondly, a validation step should be introduced in the MCC SPI project to ensure consistency with international materials. Additional recommendations are made to improve the quality and practicality of prescribing information to ensure that it remains relevant in the South African and regional context.

no / New antimalarial drugs are urgently needed to combat emerging multidrug resistant strains of malaria parasites. This Highlight focuses on plant-derived natural products that are of interest as potential leads towards new antimalarial drugs including synthetic analogues of natural compounds, with the exception of artemisinin derivatives, which are not included due to limited space. Since effective antimalarial treatment is often unavailable or unaffordable to many of those who need it, there is increasing interest in the development of locally produced herbal medicines; recent progress in this area will also be reviewed in this Highlight.

Mestrado em Controlo de Qualidade / MSc in Quality Control