Process Analytical Technology Approach on Fluid Bed Granulation and Drying : Identifying Critical Relationships and Constructing the Design Space

Fluid bed granulation is a key pharmaceutical process which improves many of the powder properties for tablet compression. Dry mixing, wetting and drying phases are included in the fluid bed granulation process. Granules of high quality can be obtained by understanding and controlling the critical process parameters by timely measurements. Physical process measurements and particle size data of a fluid bed granulator that are analysed in an integrated manner are included in process analytical technologies (PAT). Recent regulatory guidelines strongly encourage the pharmaceutical industry to apply scientific and risk management approaches to the development of a product and its manufacturing process. The aim of this study was to utilise PAT tools to increase the process understanding of fluid bed granulation and drying. Inlet air humidity levels and granulation liquid feed affect powder moisture during fluid bed granulation. Moisture influences on many process, granule and tablet qualities. The approach in this thesis was to identify sources of variation that are mainly related to moisture. The aim was to determine correlations and relationships, and utilise the PAT and design space concepts for the fluid bed granulation and drying. Monitoring the material behaviour in a fluidised bed has traditionally relied on the observational ability and experience of an operator. There has been a lack of good criteria for characterising material behaviour during spraying and drying phases, even though the entire performance of a process and end product quality are dependent on it. The granules were produced in an instrumented bench-scale Glatt WSG5 fluid bed granulator. The effect of inlet air humidity and granulation liquid feed on the temperature measurements at different locations of a fluid bed granulator system were determined. This revealed dynamic changes in the measurements and enabled finding the most optimal sites for process control. The moisture originating from the granulation liquid and inlet air affected the temperature of the mass and pressure difference over granules. Moreover, the effects of inlet air humidity and granulation liquid feed rate on granule size were evaluated and compensatory techniques used to optimize particle size. Various end-point indication techniques of drying were compared. The ∆T method, which is based on thermodynamic principles, eliminated the effects of humidity variations and resulted in the most precise estimation of the drying end-point. The influence of fluidisation behaviour on drying end-point detection was determined. The feasibility of the ∆T method and thus the similarities of end-point moisture contents were found to be dependent on the variation in fluidisation between manufacturing batches. A novel parameter that describes behaviour of material in a fluid bed was developed. Flow rate of the process air and turbine fan speed were used to calculate this parameter and it was compared to the fluidisation behaviour and the particle size results. The design space process trajectories for smooth fluidisation based on the fluidisation parameters were determined. With this design space it is possible to avoid excessive fluidisation and improper fluidisation and bed collapse. Furthermore, various process phenomena and failure modes were observed with the in-line particle size analyser. Both rapid increase and a decrease in granule size could be monitored in a timely manner. The fluidisation parameter and the pressure difference over filters were also discovered to express particle size when the granules had been formed. The various physical parameters evaluated in this thesis give valuable information of fluid bed process performance and increase the process understanding.

Design and testing of stand-specific bucking instructions for use on modern cut-to-length harvesters

This study addresses three important issues in tree bucking optimization in the context of cut-to-length harvesting. (1) Would the fit between the log demand and log output distributions be better if the price and/or demand matrices controlling the bucking decisions on modern cut-to-length harvesters were adjusted to the unique conditions of each individual stand? (2) In what ways can we generate stand and product specific price and demand matrices? (3) What alternatives do we have to measure the fit between the log demand and log output distributions, and what would be an ideal goodness-of-fit measure? Three iterative search systems were developed for seeking stand-specific price and demand matrix sets: (1) A fuzzy logic control system for calibrating the price matrix of one log product for one stand at a time (the stand-level one-product approach); (2) a genetic algorithm system for adjusting the price matrices of one log product in parallel for several stands (the forest-level one-product approach); and (3) a genetic algorithm system for dividing the overall demand matrix of each of the several log products into stand-specific sub-demands simultaneously for several stands and products (the forest-level multi-product approach). The stem material used for testing the performance of the stand-specific price and demand matrices against that of the reference matrices was comprised of 9 155 Norway spruce (Picea abies (L.) Karst.) sawlog stems gathered by harvesters from 15 mature spruce-dominated stands in southern Finland. The reference price and demand matrices were either direct copies or slightly modified versions of those used by two Finnish sawmilling companies. Two types of stand-specific bucking matrices were compiled for each log product. One was from the harvester-collected stem profiles and the other was from the pre-harvest inventory data. Four goodness-of-fit measures were analyzed for their appropriateness in determining the similarity between the log demand and log output distributions: (1) the apportionment degree (index), (2) the chi-square statistic, (3) Laspeyres quantity index, and (4) the price-weighted apportionment degree. The study confirmed that any improvement in the fit between the log demand and log output distributions can only be realized at the expense of log volumes produced. Stand-level pre-control of price matrices was found to be advantageous, provided the control is done with perfect stem data. Forest-level pre-control of price matrices resulted in no improvement in the cumulative apportionment degree. Cutting stands under the control of stand-specific demand matrices yielded a better total fit between the demand and output matrices at the forest level than was obtained by cutting each stand with non-stand-specific reference matrices. The theoretical and experimental analyses suggest that none of the three alternative goodness-of-fit measures clearly outperforms the traditional apportionment degree measure. Keywords: harvesting, tree bucking optimization, simulation, fuzzy control, genetic algorithms, goodness-of-fit

A Decentralized Session Management Framework for Heterogeneous Ad-Hoc and Fixed Networks

Wireless technologies are continuously evolving. Second generation cellular networks have gained worldwide acceptance. Wireless LANs are commonly deployed in corporations or university campuses, and their diffusion in public hotspots is growing. Third generation cellular systems are yet to affirm everywhere; still, there is an impressive amount of research ongoing for deploying beyond 3G systems. These new wireless technologies combine the characteristics of WLAN based and cellular networks to provide increased bandwidth. The common direction where all the efforts in wireless technologies are headed is towards an IP-based communication. Telephony services have been the killer application for cellular systems; their evolution to packet-switched networks is a natural path. Effective IP telephony signaling protocols, such as the Session Initiation Protocol (SIP) and the H 323 protocol are needed to establish IP-based telephony sessions. However, IP telephony is just one service example of IP-based communication. IP-based multimedia sessions are expected to become popular and offer a wider range of communication capabilities than pure telephony. In order to conjoin the advances of the future wireless technologies with the potential of IP-based multimedia communication, the next step would be to obtain ubiquitous communication capabilities. According to this vision, people must be able to communicate also when no support from an infrastructured network is available, needed or desired. In order to achieve ubiquitous communication, end devices must integrate all the capabilities necessary for IP-based distributed and decentralized communication. Such capabilities are currently missing. For example, it is not possible to utilize native IP telephony signaling protocols in a totally decentralized way. This dissertation presents a solution for deploying the SIP protocol in a decentralized fashion without support of infrastructure servers. The proposed solution is mainly designed to fit the needs of decentralized mobile environments, and can be applied to small scale ad-hoc networks or also bigger networks with hundreds of nodes. A framework allowing discovery of SIP users in ad-hoc networks and the establishment of SIP sessions among them, in a fully distributed and secure way, is described and evaluated. Security support allows ad-hoc users to authenticate the sender of a message, and to verify the integrity of a received message. The distributed session management framework has been extended in order to achieve interoperability with the Internet, and the native Internet applications. With limited extensions to the SIP protocol, we have designed and experimentally validated a SIP gateway allowing SIP signaling between ad-hoc networks with private addressing space and native SIP applications in the Internet. The design is completed by an application level relay that permits instant messaging sessions to be established in heterogeneous environments. The resulting framework constitutes a flexible and effective approach for the pervasive deployment of real time applications.

Communities of wood-inhabiting fungi : Ecological requirements and responses to forest management and fragmentation

Despite much research on forest biodiversity in Fennoscandia, the exact mechanisms of species declines in dead-wood dependent fungi are still poorly understood. In particular, there is only limited information on why certain fungal species have responded negatively to habitat loss and fragmentation, while others have not. Understanding the mechanisms behind species declines would be essential for the design and development of ecologically effective and scientifically informed conservation measures, and management practices that would promote biodiversity in production forests. In this thesis I study the ecology of polypores and their responses to forest management, with a particular focus on why some species have declined more than others. The data considered in the thesis comprise altogether 98,318 dead-wood objects, with 43,085 observations of 174 fungal species. Out of these, 1,964 observations represent 58 red-listed species. The data were collected from 496 sites, including woodland key habitats, clear-cuts with retention trees, mature managed forests, and natural or natural-like forests in southern Finland and Russian Karelia. I show that the most relevant way of measuring resource availability can differ to a great extent between species seemingly sharing the same resources. It is thus critical to measure the availability of resources in a way that takes into account the ecological requirements of the species. The results show that connectivity at the local, landscape and regional scales is important especially for the highly specialized species, many of which are also red-listed. Habitat loss and fragmentation affect not only species diversity but also the relative abundances of the species and, consequently, species interactions and fungal successional pathways. Changes in species distributions and abundances are likely to affect the food chains in which wood-inhabiting fungi are involved, and thus the functioning of the whole forest ecosystem. The findings of my thesis highlight the importance of protecting well-connected, large and high-quality forest areas to maintain forest biodiversity. Small habitat patches distributed across the landscape are likely to contribute only marginally to protection of red-listed species, especially if habitat quality is not substantially higher than in ordinary managed forest, as is the case with woodland key habitats. Key habitats might supplement the forest protection network if they were delineated larger and if harvesting of individual trees was prohibited in them. Taking the landscape perspective into account in the design and development of conservation measures is critical while striving to halt the decline of forest biodiversity in an ecologically effective manner.

ISO 13567 - The Proposed International Standard for Structuring Layers in Computer Aided Building Design

Layering is a widely used method for structuring data in CAD-models. During the last few years national standardisation organisations, professional associations, user groups for particular CAD-systems, individual companies etc. have issued numerous standards and guidelines for the naming and structuring of layers in building design. In order to increase the integration of CAD data in the industry as a whole ISO recently decided to define an international standard for layer usage. The resulting standard proposal, ISO 13567, is a rather complex framework standard which strives to be more of a union than the least common denominator of the capabilities of existing guidelines. A number of principles have been followed in the design of the proposal. The first one is the separation of the conceptual organisation of information (semantics) from the way this information is coded (syntax). The second one is orthogonality - the fact that many ways of classifying information are independent of each other and can be applied in combinations. The third overriding principle is the reuse of existing national or international standards whenever appropriate. The fourth principle allows users to apply well-defined subsets of the overall superset of possible layernames. This article describes the semantic organisation of the standard proposal as well as its default syntax. Important information categories deal with the party responsible for the information, the type of building element shown, whether a layer contains the direct graphical description of a building part or additional information needed in an output drawing etc. Non-mandatory information categories facilitate the structuring of information in rebuilding projects, use of layers for spatial grouping in large multi-storey projects, and storing multiple representations intended for different drawing scales in the same model. Pilot testing of ISO 13567 is currently being carried out in a number of countries which have been involved in the definition of the standard. In the article two implementations, which have been carried out independently in Sweden and Finland, are described. The article concludes with a discussion of the benefits and possible drawbacks of the standard. Incremental development within the industry, (where ”best practice” can become ”common practice” via a standard such as ISO 13567), is contrasted with the more idealistic scenario of building product models. The relationship between CAD-layering, document management product modelling and building element classification is also discussed.

From Creative Ideas to New Emerging Ventures: Entrepreneurial Processes among Finnish Design Entrepreneurs

This study focuses on self-employed industrial designers and how they emerge new venture ideas. More specifically, this study strives to determine what design entrepreneurs do when they create new venture ideas, how venture ideas are nurtured into being, and how the processes are organized to bring such ideas to the market in the given industrial context. In contemporary times when the concern for the creative class is peaking, the research and business communities need more insight of the kind that this study provides, namely how professionals may contribute to their entrepreneurial processes and other agents’ business processes. On the one hand, the interviews underlying this study suggest that design entrepreneurs may act as reactive service providers who are appointed by producers or marketing parties to generate product-related ideas on their behalf. On the other hand, the interviews suggest that proactive behaviour that aims on generating own venture ideas, may force design entrepreneurs to take considerable responsibility in organizing their entrepreneurial processes. Another option is that they strive to bring venture ideas to the market in collaboration, or by passing these to other agents’ product development processes. Design entrepreneurs’ venture ideas typically emerge from design related starting points and observations. Product developers are mainly engaged with creating their own ideas, whereas service providers refer mainly to the development of other agents’ venture ideas. In contrast with design entrepreneurs, external actors commonly emphasize customer demand as their primary source for new venture ideas, as well as development of these in close interaction with available means of production and marketing. Consequently, design entrepreneurs need to address market demand since without sales their venture ideas may as well be classified as art. In case, they want to experiment with creative ideas, then there should be another source of income to support this typically uncertain and extensive process. Currently, it appears like a lot of good venture ideas and resources are being wasted, when venture ideas do not suite available production or business procedures. Sufficient communication between design entrepreneurs and other agents would assist all parties in developing production efficient and distributable venture ideas. Overall, the findings suggest that design entrepreneurs are often involved simultaneously in several processes that aim at emerging new product related ventures. Consequently, design entrepreneurship is conceptualized in this study as a dual process. This implies that design entrepreneurs can simultaneously be in charge of their entrepreneurial processes, as they operate as resources in other agents’ business processes. The interconnection between activities and agents suggests that these kinds of processes tend to be both complex and multifaceted to their nature.

Offering Development in the Restaurant Sector. A Comparison Between Customer Perceptions and Management Beliefs

The present study concentrates on a small – but important – area of marketing: offering development within the service sector, more exactly the restaurant sector. The empirical part of the study has been carried out in the Helsinki metropolitan area using six successful restaurants. First, a conceptual offering development model is developed based on how the management perceives the offering development processes. Second, customer perceptions of offerings and management beliefs about how the customers perceive the offerings are analysed. Finally, an extended offering development model is created based on the management perceptions (the first model) as well as on observed gaps between customer perceptions of offerings and management beliefs about the customer perceptions. The study reveals that customer perceptions and management beliefs are rather similar but also that some differences exist. These differences are taken into account in the extended offering development model (the second model). The empirical data was collected through interviews and surveys. All together 393 customers and 14 managers participated in the study. The study suggests that successful offering development has to be closely connected with the general strategy of the company. A shared vision within the company in combination with a systematic strategic offering development process create a sound basis for the practical development work. The main contribution of the study is the extended offering development model forming a framework for further studies within the area.

The Quest for Well-being in Growth Industries: Contexts, Research Design and Methodological Development

This Working Paper reports the background to the first stage of the ongoing research project, The Quest for Well-being in Growth Industries: A Collaborative Study in Finland and Scotland, conducted under the auspices of the Academy of Finland research programme The Future of Work and Well-being (2008-2011). This collaborative project provides national and transnational data, analysis and outputs. The study is being conducted in the Department of Management and Organisation, Hanken School of Economics, Finland, in collaboration with Glasgow Caledonian University, University of East London, Heriot-Watt University and Reading University, UK. The project examines policies and practices towards the enhancement of work-related well-being in growth industries, and contradictory pressures and tensions posed in this situation. The overall aim is to evaluate the development, implementation and use of work-related well-being policies in four selected growth industries. These sectors – electronics, care, finance and accounting, and tourism – have been selected on the basis of European Union and national forecasts, and demographic and socio-economic trends in employment. In this working paper we outline the background to the research study, the initial research plan, and how the survey of employers has been constructed. The working paper concludes with a brief discussion of general ongoing research issues arising in the project.

Stock Option Compensation in Finland: An Analysis of Economic Determinants, Contracting Frequency, and Design

This paper addresses several questions in the compensation literature by examining stock option compensation practices of Finnish firms. First, the results indicate that principal-agent theory succeeds quite well in predicting the use of stock options. Proxies for monitoring costs, growth opportunities, ownership structure, and risk are found to determine the use of incentives consistent with theory. Furthermore, the paper examines whether determinants of stock options targeted to top management differ from determinants of broad-based stock option plans. Some evidence is found that factors driving these two types of incentives differ. Second, the results reveal that systematic risk significantly increases the likelihood that firms adopt stock option plans, whereas total firm risk and unsystematic risk do not seem to affect this decision. Third, the results show that growth opportunities are related to time-dimensional contracting frequency, consistent with the argument that incentive levels deviate more rapidly from optimum in firms with high growth opportunities. Finally, the results suggest that vesting schedules are decreasing in financial leverage, and that contract maturity is decreasing in firm focus. In addition, both vesting schedules and contract maturity tend to be longer in firms involving state ownership.

Inventory Routing - A Strategic Management Accounting Perspective

This dissertation develops a strategic management accounting perspective of inventory routing. The thesis studies the drivers of cost efficiency gains by identifying the role of the underlying cost structure, demand, information sharing, forecasting accuracy, service levels, vehicle fleet, planning horizon and other strategic factors as well as the interaction effects among these factors with respect to performance outcomes. The task is to enhance the knowledge of the strategic situations that favor the implementation of inventory routing systems, understanding cause-and-effect relationships, linkages and gaining a holistic view of the value proposition of inventory routing. The thesis applies an exploratory case study design, which is based on normative quantitative empirical research using optimization, simulation and factor analysis. Data and results are drawn from a real world application to cash supply chains. The first research paper shows that performance gains require a common cost component and cannot be explained by simple linear or affine cost structures. Inventory management and distribution decisions become separable in the absence of a set-dependent cost structure, and neither economies of scope nor coordination problems are present in this case. The second research paper analyzes whether information sharing improves the overall forecasting accuracy. Analysis suggests that the potential for information sharing is limited to coordination of replenishments and that central information do not yield more accurate forecasts based on joint forecasting. The third research paper develops a novel formulation of the stochastic inventory routing model that accounts for minimal service levels and forecasting accuracy. The developed model allows studying the interaction of minimal service levels and forecasting accuracy with the underlying cost structure in inventory routing. Interestingly, results show that the factors minimal service level and forecasting accuracy are not statistically significant, and subsequently not relevant for the strategic decision problem to introduce inventory routing, or in other words, to effectively internalize inventory management and distribution decisions at the supplier. Consequently the main contribution of this thesis is the result that cost benefits of inventory routing are derived from the joint decision model that accounts for the underlying set-dependent cost structure rather than the level of information sharing. This result suggests that the value of information sharing of demand and inventory data is likely to be overstated in prior literature. In other words, cost benefits of inventory routing are primarily determined by the cost structure (i.e. level of fixed costs and transportation costs) rather than the level of information sharing, joint forecasting, forecasting accuracy or service levels.