The influence of marketing factors and substance characteristics on pharmaceutical sales in a state-controlled prescriptions pharmaceuticals market

The present dissertation investigates the influence of brand as well as substance-related marketing attributes on prescription pharmaceutical sales within a state-controlled market. For this purpose, a systematic literature review was conducted in the first instance, during which knowledge about the most relevant research within this field was gathered. Consequently, over 538 publications were reviewed and indicated as being potentially relevant, leading to an eventual count of 98 core publications. However, most of these studies had been conducted in the mainly unrestricted US market. These findings were then summarised and statistically evaluated. In a second step, based on the literature review, a qualitative study, containing focus and Delphi groups, was then performed. The participants in these studies were involved in pharmaceutical marketing within a state-controlled prescriptions pharmaceuticals market. Consequently, the findings were slightly different to those derived by the systematic literature review. Based on this second step, seven hypotheses were proposed. In the third step, these hypotheses were tested, using collected data and a secondary market dataset provided by a market research institute. A statistical analysis was then performed, applying descriptive as well as multiple regression analytical methods. The evaluation of the results resulted in a conceptual model of physician targeting, leading to several theoretical, methodological and managerial implications.

Drivers of peak sales for pharmaceutical brands

Peak sales are an important metric in the pharmaceutical industry. Specifically, managers are focused on the height-of-peak-sales and the time required achieving peak sales. We analyze how order of entry and quality affect the level of peak sales and the time-to-peak-sales of pharmaceutical brands. We develop a growth model that includes these two variables as well as control variables for own and competitive marketing activities. We find that early entrants achieve peak sales later, and they have higher peak-sales levels. High-quality brands achieve peak sales earlier, and their peak-sales levels are higher. In addition, quality has a moderating effect on the order of entry effect on time-to-peak-sales. Our results indicate that late entrants have longer expected time-to-peak-sales when they introduce a brand with high quality.

Modeling the effects of pharmaceutical marketing

Successful innovation of prescription drugs requires a substantial amount of marketing support. There is, however, much concern about the effects of marketing expenditures on the demand of pharmaceutical products (Manchanda et al., Market Lett 16(3/4):293–308, 2005). For example, excessive marketing could stimulate demand for products in the absence of a fundamental need. It also has been suggested that increased marketing expenditures may reduce the price elasticity of demand and allow firms to charge higher prices (Windmeijer et al., Health Econ 15(1):5–18, 2005). In this paper, we present the outcomes of an empirical study in which we determine the effects of pharmaceutical marketing expenditures using a number of frequently used “standardized” models. We determine which models perform best in terms of predictive validity and adequate descriptions of reality. We demonstrate, among others, that the effects of promotional efforts are brand specific and that most standardized models do not provide adequate descriptions of reality. We find that marketing expenditures have no or moderate effects on demand for pharmaceutical products in The Netherlands.

Pharmaceutical process optimisation of bulk lyophilisates:implications of powder handling

Lyophilisation or freeze drying is the preferred dehydrating method for pharmaceuticals liable to thermal degradation. Most biologics are unstable in aqueous solution and may use freeze drying to prolong their shelf life. Lyophilisation is however expensive and has seen lots of work aimed at reducing cost. This thesis is motivated by the potential cost savings foreseen with the adoption of a cost efficient bulk drying approach for large and small molecules. Initial studies identified ideal formulations that adapted well to bulk drying and further powder handling requirements downstream in production. Low cost techniques were used to disrupt large dried cakes into powder while the effects of carrier agent concentration were investigated for powder flowability using standard pharmacopoeia methods. This revealed superiority of crystalline mannitol over amorphous sucrose matrices and established that the cohesive and very poor flow nature of freeze dried powders were potential barriers to success. Studies from powder characterisation showed increased powder densification was mainly responsible for significant improvements in flow behaviour and an initial bulking agent concentration of 10-15 %w/v was recommended. Further optimisation studies evaluated the effects of freezing rates and thermal treatment on powder flow behaviour. Slow cooling (0.2 °C/min) with a -25°C annealing hold (2hrs) provided adequate mechanical strength and densification at 0.5-1 M mannitol concentrations. Stable bulk powders require powder transfer into either final vials or intermediate storage closures. The targeted dosing of powder formulations using volumetric and gravimetric powder dispensing systems where evaluated using Immunoglobulin G (IgG), Lactate Dehydrogenase (LDH) and Beta Galactosidase models. Final protein content uniformity in dosed vials was assessed using activity and protein recovery assays to draw conclusions from deviations and pharmacopeia acceptance values. A correlation between very poor flowability (p<0.05), solute concentration, dosing time and accuracy was revealed. LDH and IgG lyophilised in 0.5 M and 1 M mannitol passed Pharmacopeia acceptance values criteria with 0.1-4 while formulations with micro collapse showed the best dose accuracy (0.32-0.4% deviation). Bulk mannitol content above 0.5 M provided no additional benefits to dosing accuracy or content uniformity of dosed units. This study identified considerations which included the type of protein, annealing, cake disruption process, physical form of the phases present, humidity control and recommended gravimetric transfer as optimal for dispensing powder. Dosing lyophilised powders from bulk was demonstrated as practical, time efficient, economical and met regulatory requirements in cases. Finally the use of a new non-destructive technique, X-ray microcomputer tomography (MCT), was explored for cake and particle characterisation. Studies demonstrated good correlation with traditional gas porosimetry (R2 = 0.93) and morphology studies using microscopy. Flow characterisation from sample sizes of less than 1 mL was demonstrated using three dimensional X-ray quantitative image analyses. A platinum-mannitol dispersion model used revealed a relationship between freezing rate, ice nucleation sites and variations in homogeneity within the top to bottom segments of a formulation.

Freezing process optimisation of pharmaceutical formulations for freeze drying

The body of work presented in this thesis are in three main parts: [1] the effect of ultrasound on freezing events of ionic systems, [2] the importance of formulation osmolality in freeze drying, and [3] a novel system for increasing primary freeze drying rate. Chapter 4 briefly presents the work on method optimisation, which is still very much in its infancy. Aspects of freezing such as nucleation and ice crystal growth are strongly related with ice crystal morphology; however, the ice nucleation process typically occurs in a random, non-deterministic and spontaneous manner. In view of this, ultrasound, an emerging application in pharmaceutical sciences, has been applied to aid in the acceleration of nucleation and shorten the freezing process. The research presented in this thesis aimed to study the effect of sonication on nucleation events in ionic solutions, and more importantly how sonication impacts on the freezing process. This work confirmed that nucleation does occur in a random manner. It also showed that ultrasonication aids acceleration of the ice nucleation process and increases the freezing rate of a solution. Cryopreservation of animal sperm is an important aspect of breeding in animal science especially for endangered species. In order for sperm cryopreservation to be successful, cryoprotectants as well as semen extenders are used. One of the factors allowing semen preservation media to be optimum is the osmolality of the semen extenders used. Although preservation of animal sperm has no relation with freeze drying of pharmaceuticals, it was used in this thesis to make a case for considering the osmolality of a formulation (prepared for freeze drying) as a factor for conferring protein protection against the stresses of freeze drying. The osmolalities of some common solutes (mostly sugars) used in freeze drying were determined (molal concentration from 0.1m to 1.2m). Preliminary investigation on the osmolality and osmotic coefficients of common solutes were carried out. It was observed that the osmotic coefficient trend for the sugars analysed could be grouped based on the types of sugar they are. The trends observed show the need for further studies to be carried out with osmolality and to determine how it may be of importance to protein or API protection during freeze drying processes. Primary drying is usually the longest part of the freeze drying process, and primary drying times lasting days or even weeks are not uncommon; however, longer primary drying times lead to longer freeze drying cycles, and consequently increased production costs. Much work has been done previously by others using different processes (such as annealing) in order to improve primary drying times; however, these do not come without drawbacks. A novel system involving the formation of a frozen vial system which results in the creation of a void between the formulation and the inside wall of a vial has been devised to increase the primary freeze drying rate of formulations without product damage. Although the work is not nearly complete, it has been shown that it is possible to improve and increase the primary drying rate of formulations without making any modifications to existing formulations, changing storage vials, or increasing the surface area of freeze dryer shelves.

Methodology for Language Analysis and Generation in Closed Domains: Pharmaceutical Leaflet

The best results in the application of computer science systems to automatic translation are obtained in word processing when texts pertain to specific thematic areas, with structures well defined and a concise and limited lexicon. In this article we present a plan of systematic work for the analysis and generation of language applied to the field of pharmaceutical leaflet, a type of document characterized by format rigidity and precision in the use of lexicon. We propose a solution based in the use of one interlingua as language pivot between source and target languages; we are considering Spanish and Arab languages in this case of application.

Functionalised particles using dry powder coating in pharmaceutical drug delivery:promises and challenges

Introduction: Production of functionalised particles using dry powder coating is a one-step, environmentally friendly process that paves the way for the development of particles with targeted properties and diverse functionalities. Areas covered: Applying the first principles in physical science for powders, fine guest particles can be homogeneously dispersed over the surface of larger host particles to develop functionalised particles. Multiple functionalities can be modified including: flowability, dispersibility, fluidisation, homogeneity, content uniformity and dissolution profile. The current publication seeks to understand the fundamental underpinning principles and science governing dry coating process, evaluate key technologies developed to produce functionalised particles along with outlining their advantages, limitations and applications and discusses in detail the resultant functionalities and their applications. Expert opinion: Dry particle coating is a promising solvent-free manufacturing technology to produce particles with targeted functionalities. Progress within this area requires the development of continuous processing devices that can overcome challenges encountered with current technologies such as heat generation and particle attrition. Growth within this field requires extensive research to further understand the impact of process design and material properties on resultant functionalities.

Characterization of Grewia gum, a potential pharmaceutical excipient

Grewia gum was extracted from the inner stem bark of Grewia mollis and characterized by several techniques such as gas chromatography (GC), gel permeation chromatography (GPC), scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and thermogravimetric analysis of the extracted sample. Spectroscopic techniques such as x-ray photoelectron spectroscopy (XPS), fourier-transformed infrared (FT-IR), solid-state nuclear magnetic resonance (NMR), and 1H and 13C NMR techniques were also used to characterize the gum. The results showed that grewia gum is a typically amorphous polysaccharide gum containing glucose, rhamnose, galactose, arabinose and xylose as neutral sugars. It has an average molecular weight of 5925 kDa expressed as the pullulan equivalent. The gum slowly hydrated in water, dispersing and swelling to form a highly viscous dispersion exhibiting pseudoplastic flow behaviour. The polysaccharide gum is thermally stable and may have application as stabilizer or suspending agent in foods, cosmetics and in pharmaceuticals. It may have application as a binder or sustained-release polymer matrix in tablets or granulations. © IPEC-Americas Inc.

A társadalmi felelősségvállalás tendenciái a gyógyszeriparban = Corporate Social Responsibility in the Pharmaceutical Industry

A gyógyszeripar egyszerre tartozik a leginkább csodált és a legtöbbet kritizált iparágak közé. Az iparág produktumai életeket menthetnek, emberek millióinak könnyítik meg az életét, és a gyógyszereknek köszönhetően számos korábbi gyilkos kór vált ismeretlenné a fejlett országokban. Mindezek mellett azonban az iparágat számos kritika is éri: túl magas árakkal dolgozik, etikátlan promóciós praktikákkal él, magára hagyja a világ szegényeit, kétes etikai hátterű klinikai kísérleteket végez, és állami intézményekkel köt háttéralkukat. A CSR koncepciójának intenzív jelenléte az iparágban többek között a fenti ellentmondásokra adott válaszként is értelmezhető (erre utalnak a későbbiekben bemutatandó kvalitatív kutatás eredményei is). Az alábbi tanulmányban arra teszek kísérletet, hogy feltárjam, a magyar gyógyszeripar szereplői hogyan látják társadalmi felelősségüket, milyen programokat valósítanak meg CSR kezdeményezéseik során. Milyen kihívások várnak a gyógyszeripari cégek vezetőire, és milyen dilemmákkal szembesülnek társadalmi felelősségvállalásuk kapcsán? Mennyiben találhatók meg a nemzetközi kutatások által feltárt nézőpontok a hazai cégek CSR interpretációiban, illetve vannak-e a magyar gyógyszeriparnak sajátosságai ebben a tekintetben? / === / The pharmaceutical industry is among the most admired and most criticized of all. The pharmaceutical products can save lives, they make the lives of millions of people lot easier, and many legendary diseases were eradicated from the world thanks to the innovations of the industry. However, the industry receives many criticisms in the same time: the big pharma is often accused of working with high prices, applying immoral marketing practices, abandoning the poor, having a no money-no cure attitude, doing ethically questionable clinical trials, etc. This contradiction can be one reason why pharmaceutical industry is among the most CSR-oriented sectors. In this paper I investigate what the CSR initiatives and activities of the pharmaceutical companies look like in Hungary. How do the managers of these firms react to the challenges of the industry? What is their perception about the contradictions described in the previous paragraph? Are there Hungarian peculiarities regarding CSR principles and actions? During research I also wanted to identify patterns of CSR activities of the Hungarian pharmaceutical firms in order to create clusters that group companies with similar characteristics.

Kereslet-előrejelzés sporadikus keresletű termékekre: Egy gyógyszer-nagykereskedelmi vállalat esettanulmánya (Forecasting of Sporadic Products - A Case Study of a Pharmaceutical Wholesaler Company)

A vállalatok jelentős része szembesül azzal, hogy termékei jelentős része iránt viszonylag kevés alkalommal jelentkezik kereslet. Ebből következik, hogy az ilyen termékekre a klasszikus előrejelzési módszerek, mint pl. a mozgó átlag számítása, vagy az exponenciális simítás nem alkalmazható. Azon termékeket, amelyek iránt viszonylag ritkán jelenik meg kereslet, sporadikus keresletű termékeknek nevezzük. A megkülönböztetés a sporadikus és nem sporadikus termékek között sokszor csak hüvelykujj szabály alapján állapítható meg, de erre vonatkozóan a szakirodalomban találunk iránymutatást. A nemzetközi szakirodalomban már megjelentek olyan új kereslet-előrejelzési módszerek, melyeket kimondottan az ilyen, sporadikus kereslettel rendelkező termékek estében javasoltak. Cikkünk célja, hogy ezeket a szakirodalmi ajánlásokat egy konkrét hazai vállalat valós adatain esettanulmány jelleggel tesztelje. A nemzetközi szakirodalomban is ritkán publikálnak tudományos dolgozatokat, amelyek ezt a témakört valós alkalmazási környezetben tárgyalják; ismereteink szerint magyar nyelven erről tudományos dolgozat pedig még nem született. Elméleti bevezetőnk után egy gyógyszer-nagykereskedelmi vállalatnál valós adatait használva vizsgáljuk a kérdéskört. Sor kerül a vállalat termékportfóliójának a kereslet-előrejelzés szempontjából történő tipizálására, majd sporadikus keresletű termékek keresletének előrejelzésére és ennek során a szakirodalomban az alkalmazandó módszerekre vonatkozó ajánlások vizsgálatára. _____ Significant numbers of companies have the problem that demand for their products are sporadic in nature. Demand of such products is not continual in time; its demand is diffused, is random with large proportion of zero values in the analyzed time series. The sporadic character of a demand pattern actually means that available information on the demand of previous selling periods is leaky resulting in lower quality of data available. In these cases traditional forecasting techniques do not result in reliable forecast. Special forecasting algorithms have been developed during the last decade dealing with this problem. The paper introduces these techniques and offers suggestions for application. It also presents the case study of a Hungarian pharmaceutical wholesaler company. Based on real data we develop a topology of the company's product portfolio, carry out forecasts using different techniques including those developed for products with sporadic demand and also analyze the quality of these forecasts.

Determinants of pharmaceutical innovation diffusion: social contagion and prescribing characteristics

This article studies the determinants of pharmaceutical innovation diffusion among specialists. To this end, it investigates the influences of six categories of factors—social embeddedness, socio-demography, scientific orientation, prescribing patterns, practice characteristics, and patient panel composition—on the use of new drugs for the treatment of type 2 diabetes mellitus in Hungary. Here, in line with international trends, 11 brands were introduced between April 2008 and April 2010, outperforming all other therapeutic classes. The Cox proportional hazards model identifies three determinants—social contagion (in the social embeddedness category) and prescribing portfolio and insulin prescribing ratio (in the prescribing pattern category). First, social contagion has a positive effect among geographically close colleagues—the higher the adoption ratio, the higher the likelihood of early adoption—but no influence among former classmates and scientific collaborators. Second, the wider the prescribing portfolio, the earlier the new drug uptake. Third, the lower the insulin prescribing ratio, the earlier the new drug uptake—physicians’ therapeutic convictions and patients’ socioeconomic statuses act as underlying influencers. However, this finding does not extend to opinion-leading physicians such as scientific leaders and hospital department and outpatient center managers. This article concludes by arguing that healthcare policy strategists and pharmaceutical companies may rely exclusively on practice location and prescription data to perfect interventions and optimize budgets.

Essays on Competition in the Pharmaceutical Industry

Chapter 1: Patents and Entry Competition in the Pharmaceutical Industry: The Role of Marketing Exclusivity Effective patent length for innovation drugs is severely curtailed because of extensive efficacy and safety tests required for FDA approval, raising concern over adequacy of incentives for new drug development. The Hatch-Waxman Act extends patent length for new drugs by five years, but also promotes generic entry by simplifying approval procedures and granting 180-day marketing exclusivity to a first generic entrant before the patent expires. In this paper we present a dynamic model to examine the effect of marketing exclusivity. We find that marketing exclusivity may be redundant and its removal may increase generic firms' profits and social welfare. Chapter 2: Why Authorized Generics?: Theoretical and Empirical Investigations Facing generic competition, the brand-name companies some-times launch generic versions themselves called authorized generics. This practice is puzzling. If it is cannibalization, it cannot be profitable. If it is divisionalization, it should be practiced always instead of sometimes. I explain this phenomenon in terms of switching costs in a model in which the incumbent first develops a customer base to ready itself against generic competition later. I show that only sufficiently low switching costs or large market size justifies launch of AGs. I then use prescription drug data to test those results and find support. Chapter 3: The Merger Paradox and R&D Oligopoly theory says that merger is unprofitable, unless a majority of firms in industry merge. Here, we introduce R&D opportunities to resolve this so-called merger paradox. We have three results. First, when there is one R&D firm, that firm can profitably merge with any number of non-R&D firms. Second, with multiple R&D firms and multiple non-R&D firms, all R&D firms can profitably merge. Third, with two R&D firms and two non-R&D firms, each R&D firms prefer to merge with a non-R&D firm. With three or more than non-R&D firms, however, the R&D firms prefer to merge with each other.

Telescoped approach to aryl hydroxymethylation in the synthesis of a key pharmaceutical intermediate

An efficient synthetic approach leading to introduction of the hydroxymethyl group to an aryl moiety via combination of the Bouveault formylation and hydride reduction has been optimized using a rational, mechanistic-based approach. This approach enabled telescoping of the two steps into a single efficient process, readily amenable to scaleup.

Development of Advanced Capillary Electrophoresis Techniques with UV and Mass Spectrometry Detection for Forensic, Pharmaceutical and Environmental Applications

Capillary electrophoresis (CE) is a modern analytical technique, which is electrokinetic separation generated by high voltage and taken place inside the small capillaries. In this dissertation, several advanced capillary electrophoresis methods are presented using different approaches of CE and UV and mass spectrometry are utilized as the detection methods. Capillary electrochromatography (CEC), as one of the CE modes, is a recent developed technique which is a hybrid of capillary electrophoresis and high performance liquid chromatography (HPLC). Capillary electrochromatography exhibits advantages of both techniques. In Chapter 2, monolithic capillary column are fabricated using in situ photoinitiation polymerization method. The column was then applied for the separation of six antidepressant compounds. Meanwhile, a simple chiral separation method is developed and presented in Chapter 3. Beta cycodextrin was utilized to achieve the goal of chiral separation. Not only twelve cathinone analytes were separated, but also isomers of several analytes were enantiomerically separated. To better understand the molecular information on the analytes, the TOF-MS system was coupled with the CE. A sheath liquid and a partial filling technique (PFT) were employed to reduce the contamination of MS ionization source. Accurate molecular information was obtained. It is necessary to propose, develop, and optimize new techniques that are suitable for trace-level analysis of samples in forensic, pharmaceutical, and environmental applications. Capillary electrophoresis (CE) was selected for this task, as it requires lower amounts of samples, it simplifies sample preparation, and it has the flexibility to perform separations of neutral and charged molecules as well as enantiomers. Overall, the study demonstrates the versatility of capillary electrophoresis methods in forensic, pharmaceutical, and environmental applications.