University of Macau / Institute of Chinese Medical Sciences

Bakgrund: Läkemedelsbranschen är idag en av de mest reglerade branscherna på marknaden. Forskning och utveckling har en stor betydelse för läkemedelsföretagen. För att lansera ett läkemedel krävs det att företagen genomför kliniska prövningar, deras utfall kan mycket väl avgöra företagens framtid. Problemformulering: hur stor inverkan har de olika faserna inom produktutvecklingen på aktiekurserna för företag i läkemedelsbranschen. Syfte: Syftet med uppsatsen är att undersöka hur marknaden reagerar när läkemedel som är under utveckling går in i de tre olika kliniska faserna.Metod: Studien baseras på kvantitativ data där ett bekvämlighetsval gjorts på sju stycken läkemedelsföretag. PR meddelanden där läkemedel i utveckling går in i fas-1, fas-2 och fas-3 kliniska prövningar har valts ut som enskilda händelsen i eventstudien som genomförts. Vi har studerat vad som händer 5 dagar före och 5 dagar efter att händelsen utspelar sig. Därefter har vi mätt marknadens reaktion genom beräkning av den anormala avkastningen. Slutsatser: Studien visar på att aktiemarknaden reagerar positivt på alla de tre kliniska faserna. Marknaden har en förmåga att övervärdera fas-1 studiers betydelse. Det finns tecken på att marknaden har svårt att värdera forskningen och utvecklingens riktiga värde. / Background: The pharmaceutical industry is a heavily regulated market. Costs for research and development are of utmost importance for the industry. To successfully launch a new drug requires clinical trials, and their outcomes could well determine the future of the company’s business. Problem formulation: how much influence do the various stages of product development have on the stock prices for companies in the pharmaceutical industry. Purpose: How does the market react when a drug under development undergoes the three different clinical phases. Method: The study is based on quantitative data. Seven pharmaceutical companies have been selected for this study. PR messages for when drugs in development go into phase-1, phase-2 and phase-3 clinical trials, have been selected as the event in focus for our study. We have studied what occurs five days before and five days after an event takes place. Next we measure the markets reaction by calculating the abnormal return. Conclusion: The study shows that the stock market reacts positively to all three clinical phases. The market has a way to overestimate phase-1 studies importance. There are signs that the market has difficulties evaluating R&Ds real value.

The current trend in the pharmaceutical industry is towards continuous flow processes. Continuous flow reactor technology can produce a cheaper, better quality product at reduced energy and environmental cost through more efficient mass and heat transfer. It also enables a simplified and faster approach to bulk production by scaling out as opposed to scaling up. The research presented here focuses on the configuration and installation of a continuous flow system into the laboratory, and the transfer of a Meerwein-Ponndorf-Verley (MPV) reduction from batch to continuous mode. The Corning® glass continuous flow reactor in our laboratory utilizes specially-designed mixing structures for enhanced mass transfer. Additionally, the glass reactor offers nonreactivity and corrosion resistance over a wide range of temperature and pressure, which conventional steel reactors do not allow. The MPV reduction is a well-known method to prepare primary and secondary alcohols from aldehydes and ketones, respectively. The traditional MPV reduction protocol (Al(OiPr)₃ in isopropanol) was modified to enable the technological transfer from batch to continuous mode. This is the first time MPV reduction reactions were carried out in continuous mode. As a result, the MPV reduction of the model compound, benzaldehyde, was successfully conducted with 60% less catalyst and product yield was improved up to 20% (average of 10%) in continuous flow reactions as compared to current batch technology. These results are being used to develop a technology roadmap for the pharmaceutical industry to implement continuous flow processes in their manufacturing operations.

<p>This master’s thesis compares the OECD transfer pricing recommendations with the transfer pricing rules of the US. The main focus is the ethical pharmaceutical industry and intangible property, in particular marketing intangibles. The Glaxo case is used to illustrate how the US takes advantage of areas of uncertainty to increase the country’s tax revenue. The US shows little consideration for the OECD’s objectives of having a set of universally applicable transfer pricing rules. The purpose of this master’s thesis is to explain and analyze why the IRS took a new approach on marketing intangibles in the Glaxo case, evaluate the global effect of the Glaxo case, and discuss how similar situations should be dealt with in the future.</p><p>The natural forum to achieve universally harmonized transfer pricing rules is the OECD. When the OECD fails to provide adequate recommendations, the US and other countries take matters into their own hands by constructing rules deviating from the recommendations of the OECD. These rules tend to put the countries’ interests first creating a competitive international transfer pricing community harmful to MNEs. The consequence is a negative effect on global trade and investment.</p><p>In the Glaxo case the US took advantage of the area of uncertainty regarding intangible property and marketing intangibles to serve its own purpose and came up with a new approach on marketing intangibles. This approach has consequences for all MNEs with affiliates in the US and distributors outside the US. The new approach states that the value of a product is attributable to the marketing activities conducted by a US subsidiary rather than to R&D carried out by a UK parent. The new approach may affect distributors outside the US since the value they have can be allocated to a US affiliate conducting marketing and sales activities. The ethical pharmaceutical industry depends on intangible property and R&D is the most important value-driver in this industry. In addition, the characteristics of the ethical pharmaceutical industry are such that ethical pharmaceutical companies are priority targets of the IRS’s audits. If the IRS’s new approach prevails, the negative consequences for the ethical pharmaceutical industry as well as the society as a whole may be severe.</p><p>There are three main conclusions and recommendations in this master’s thesis. First, the Member countries of the OECD have to respect the principle of transfer pricing as neutral concept. Second, tax authorities must take into consideration the sound business reasons of MNEs and understand their need for tax predictability. Finally, it is in the interest of all countries to cooperate and establish a uniform interpretation and application of transfer pricing thereby avoiding double taxation and creating a balance in the international transfer pricing community.</p> / <p>Denna magisteruppsats jämför OECD:s rekommendationer gällande internprissättning med de amerikanska internprissättningsreglerna. I uppsatsen fokuserar författarna på internprissättningsproblematiken gällande immateriella tillgångar i läkemedelbranschen, med särskilt fokus på den typ av immateriella tillgångar som uppstår genom försäljning och marknadsföring (marketing intangibles). USA använder sig av områden där rättsläget är osäkert för att öka sina skatteintäkter. För att illustrera detta beskrivs och analyseras Glaxo-fallet. USA visar på så sätt lite hänsyn till ett av OECD:s viktigaste mål; att skapa en universellt harmoniserad tolkning och tillämpning av internprissättning för att motverka dubbelbeskattning och öka möjligheten för multinationella företag att förutse och planera sin skatt. Syftet med denna magisteruppsats är att förklara och analysera varför den amerikanska skattemyndigheten (IRS) valde en ny inställning till marketing intangibles i Glaxo-fallet, utvärdera den globala effekten av Glaxo-fallet och diskutera hur liknande situationer bör hanteras i framtiden.</p><p>OECD är det mest lämpliga instrumentet för att skapa en internationell konsensus på internprissättningsområdet. Eftersom internprissättning av transaktioner som involverar immateriella tillgångar och särskilt marketing intangibles utgör ett osäkert område med endast lite vägledning från OECD finns det stort utrymme för länder att skapa egna regler och rättspraxis på området. När länder som USA tar saken i egna händer och skapar sina egna regler inom internprissättning tenderar de att sätta sina egna intressen i första rummet. Konsekvensen blir en internationell internprissättningsmiljö där konkurrensen om de multinationella företagens vinster är stor, vilket skadar den internationella handeln och investeringsviljan hos företag. Det är just detta som skett i Glaxo-fallet.</p><p>Resultatet av Glaxo-fallet blev en ny inställning till hanteringen av denna typ av transaktioner, något som USA länge eftersökt för att lösa problemet med en minskande skattebas. Den nya amerikanska inställningen får konsekvenser för alla multinationella företag med företag i intressegemenskap i USA och distributörer utanför USA. USA sänder nu ut en signal att värdet av en produkt inte styrs utav de år av forskning och utveckling som krävdes för att skapa ett patent av det brittiska moderbolaget i Glaxo-fallet. Istället är det de immateriella tillgångar som uppkommer av försäljnings- och marknadsföringsaktiviteter som tillför en produkt det egentliga värdet. I Glaxo-fallet innebar detta att en majoritet av vinsten av försäljningen av läkemedlet Zantac skulle hänföras till det amerikanska dotterbolaget och därmed beskattas i USA. Inställningen innebär att distributörer utanför USA kan komma att påverkas genom att värdet de tillfört genom forskning och utveckling eller andra viktiga funktioner kan bli mindre betydelsefullt än värdet som tillförs av marknadsföring. Läkemedelsbranschen är beroende av immateriella tillgångar för att kunna fungera och forskning och utveckling är den mest betydelsefulla värdeskapande funktionen inom industrin. Företag i läkemedelsbranschen är dessutom mycket benägna att hamna i blickfånget för internprissättningsrevisioner. Om den nya amerikanska inställningen vinner mark är det mycket troligt att konsekvenserna blir allvarliga både för läkemedelsindustrin och för samhället i stort.</p><p>I denna magisteruppsats har författarna antagit tre huvudsakliga slutsatser med rekommendationer. Den första är att OECD:s medlemsländer måste respektera principen om en neutral inställning till internprissättning. Som en andra slutsats kan sägas att skattemyndigheter måste beakta de affärsmässiga skälen till de transaktioner som företas av multinationella företag och förstå multinationella företags behov av förutsebarhet beträffande beskattning. Slutligen ligger ett internationellt samarbete i alla länders intresse och en internationell konsensus gällande tolkning och tillämpning av internprissättning skapar balans och motverkar dubbelbeskattning.</p>

There are many differentiated product industries in which firms offer multiple products in the same market. In making strategic decisions regarding entry, quality and quantity to be supplied for their multiple products firms must consider the competition with rivals as well as cannibalization of their own products that are close substitutes. In this setting, understanding the relationship between the behavior of consumer demand and firms decisions' regarding product characteristics and strategic variables like advertising are fundamental issues in industrial organization. This dissertation empirically explores these fundamental issues in the pharmaceutical and airline industries. The first paper of my dissertation estimates consumer demand for different anti-cholesterol drugs using panel data on a nationally representative sample of individuals who were diagnosed with cholesterol problems in the period 1996-2002. The data provides detailed information on individuals' medical conditions, medical and drug insurance coverage, drug purchases (if any), and other demographic and medical information. Individuals choose whether to purchase an anti-cholesterol rug and, if so, which drug to buy. The model permits flexible substitution patterns among drug choices and persistence in those choices by incorporating both observed and unobserved consumer heterogeneity. The estimates suggest that lower income patients without prescription drug insurance are very price sensitive: they are less likely to use drugs and, if they do use them, they tend to purchase the less expensive drugs. I find that roughly 500 thousand individuals without drug insurance who are currently not purchasing anti-cholesterol drugs would do so in the counterfactual world in which they are given the standard co-payment plan. The second paper also looks at consumer demands for anti-cholesterol drugs. While the first paper focused on the differentiated products, this paper explores the market expansion effects of direct-to-consumer advertising (DTCA). The study combines the individual data used in the first paper with monthly expenditure data on DTCA for the period 1996-2002. The dynamic demand model estimated in this paper explores the heterogeneous effects of DTCA. Overall, I find a positive effect from DTCA with short term elasticity of 0.107. Through persistence in consumer demand this effect lasts over multiple time periods. I find that individuals not taking a cholesterol drug respond more to advertising than those on the drug. In addition, I find that less educated individuals, those that may be unaware of their health condition, and those without health insurance are most responsive to DTCA. Finally, the third paper studies the effect of product ownership and quality on entry in the airline industry. Specifically, this paper empirically examines the decision of an airline to offer high quality nonstop service between cities given that the airline may or may not be offering lower quality one-stop service. I find that airlines that offer one-stop service through a hub are less likely to enter that same market with nonstop service than those that do not. In addition, the quality of the one-stop service is another determinant of entry. Airlines are more likely to enter a market with nonstop service if their own or their rival's one-stop service in the market are of lower quality. / text

M. Tech. Business Administration / This study focuses on innovator biopharmaceutical companies (also known as biomedical companies) and aims to explore the reasons why such companies invest into South Africa. Biomedical FDI (foreign direct investment) is the type of FDI (foreign direct investment) that takes place in research, both basic and clinical research and development. It also aims to provide useful information and insights about biomedical investments into South Africa, as there is a dearth of publications in this area.

Thesis (MTech. degree in Pharmaceutical Sciences)--Tshwane University of Technology, 2009. / Quality control procedures are vital in the pharmaceutical industry to guarantee the authenticity and quality of products. A major challenge in quality assurance of herbal material is the vast variation of active constituents in plants from the same species. As a result of this variation, the selection of only a few compounds as criteria for quality control is inadequate. Pelargonium (P.) sidoides is indigenous to South Africa and highly valued by traditional healers as a remedy to treat coughs, upper respiratory tract irritations and gastrointestinal conditions. An ethanolic extract of P. sidoides is used in the proprietary herbal tincture known as Umckaloabo®. The composition and concentration of polyphenols are parameters which determine the quality of this herbal medicine because it provides several therapeutic benefits in the non-specific medicinal treatment of infectious diseases. Despite the commercial development of P. sidoides very few studies have been conducted to document the full phytochemical range of variation for natural populations and no study has been published on the development of a fast accurate quality control method for the validation of raw material.

Submitted in partial fulfilment of the requirements for the degree of Masters in Business Administration (MBA), Business Studies Unit, Durban University of Technology, 2008 / The pharmaceutical industry is in the midst of a fundamental transformation. Time and cost constraints are forcing marketers to search for new ways to maintain and grow brand awareness. The amount of time that doctors allow for representatives to market their products is becoming less and less and as a result products are not getting the exposure they used to. Organisations that find innovative ways to maintain exposure of their products may gain a competitive advantage over those organisations that rely on traditional marketing methods. The prolific increase in the use of the internet may provide pharmaceutical organisations with a complementary channel to market their products. The objective of this study is to determine the levels of internet technology adoption among general practitioners. The Technology Acceptance Model (TAM) is one of the most influential research models in studies of the determinants of information systems/ information technology (IS/IT) acceptance. In TAM, perceived usefulness and perceived ease of use are hypothesised and empirically supported as fundamental determinants of user acceptance of a given IS/IT. Using TAM, this study sets out to determine general practitioners’ intention to use the internet as a source of pharmaceutical information. The literature review provides an extensive evaluation on the development of TAM and its application in different technologies. Based on these findings, the researcher developed this study to investigate internet technology acceptance in the pharmaceutical industry. Use is made of the descriptive survey method and data is retrieved from a sample of 105 general practitioners in Kwazulu-Natal. The observation is made via the benefit of a questionnaire. The process of sampling is that of convenient sampling. The analysis is quantitative and makes use of statistical analysis appropriate for the data. Analysis of the survey results produces useful insights into the factors influencing internet technology adoption by general practitioners. When analysing the independent variables, respondents were not in strong agreement about the perceived usefulness nor the perceived ease of use of internet technology as a source of pharmaceutical information. However, positive results from the relationships between the independent (perceived usefulness and perceived ease of use) and dependent variables (attitude and intention to use) provide valuable data with which organisations may develop internet-based marketing strategies. Based on the survey findings, recommendations using the Beynon-Davies (2004) Internet Adoption Model are suggested.

Aktuell gibt es unterschiedliche Trends in der pharmazeutischen Industrie. Die Herstellung von API´s wird zunehmend bei den Herstellern der finalen Produkte vorgenommen. BIG Pharma integriert die API Herstellung in House. Die Batchproduktion geht tendenziell zu immer kleinen Volumen mit speziellen Anwendungsbereichen. Produkte mit größerem Volumen werden vom Batchvolumen in eine kontinuierliche Produktion überführt und speziell auch auf diese neue Herstellungstechnologie entwickelt. Die Anforderungen für diese unterschiedlichen Applikationen sind völlig unterschiedlich.

Research Doctorate - Doctor of Philosophy (PhD) / In January 2005 Australia implemented the Australia-United States Free Trade Agreement (AUSFTA). The AUSFTA was a historic document because it laid out a closer trading association between Australia and its close ally, the United States (US). The Agreement was generally welcomed in both countries but it contained provisions that were controversial, perhaps none more so than those covering pharmaceuticals. In Australia there was deep concern over the effects of these provisions on the Pharmaceutical Benefits Scheme (PBS). A Senate Committee investigating the likely impact of the AUSFTA was apprehensive that the provisions would result in the PBS paying higher prices for some medicines. The many outcomes from the research reported in this thesis are preliminary but amongst them, three stood out. First, the AUSFTA instituted a number of small but significant changes to Australian pharmaceutical policies and processes. Some changes, around transparency and listing times, were positive while others, such as sponsor hearings before the PBAC, will probably have limited negative impact. Second, there is now a need to consider the AUSFTA commitments when Australian health policy is reassessed in the future, which will now make Australia’s regulatory processes more complex. Third, it is argued that the AUSFTA may have had input into major reforms of the Australian PBS. These reforms delivered on an outcome that had been sought by the US: a weakening of reference pricing as used by the Australian PBS. The benefit from the change to reference pricing for Australia is unclear, but the PBS is now more vulnerable to higher prices for new medicines in the future.