Exploring Pharmaceutical Mass Customization

The core purpose of therapeutic pharmaceutical products is to induce responses to various diseases in patients and thereby bring societal value; however, unmet medical needs currently prevail. Conventional treatment of these products predominantly embraces a one-size-fits-all design and is manufactured in a mass-production context. A mass-production context is driven by economies of scale, however, a one-size-fits-all product design challenges the satisfaction of individual patient needs. Pharmaceutical product customization thus aims to satisfy individuals’ treatment needs and thereby improve their therapeutic outcome; however, this implies a high product variety and low-volume production environment which challenges the cost-effective production with current mass-production platforms.To address this challenge of achieving the cost-effective production of customized pharmaceutical products, this thesis explores a unified approach to cost-effective design, manufacturing and supply of customized pharmaceutical products. For this purpose, the mass customization principles of product modularization, process flexibility and postponement are adopted and adapted in a pharmaceutical production context.This thesis proposes methodologies to design and model customized pharmaceutical products and production systems in a unified manner. Furthermore, customized product designs are proposed using product modularization as a design strategy and reconfigured pharmaceutical supply chain (SC) archetypes using postponement as a strategy for the cost-effective design, manufacturing and supply. The findings suggest that an increased degree of modularization in the pharmaceutical product increases the patient benefit and thus improves therapeutic patient outcomes. In addition, current mass production platforms do not display the process flexibility required for the cost-effective production of customized pharmaceutical products. Moreover, with an increased degree of postponement, opportunities for reduced production costs in the SC emerge. Finally, the cost-effective customization of pharmaceutical products requires an integrated approach of product modularization and postponement. While modeling the production system, this thesis, however, considers an SC from the manufacturer to the pharmacy and patient assessing contemporary cost-effectiveness. Future research directions should investigate societal consequences from a wider, spatial and temporal, health care system perspective

Integrated Product and Production Platforms for Pharmaceutical Products: Design Thinking for the Development of Personalized Medicines

Treatments, when customized according to individual patient attributes, are in recent yearsreferred to as personalized medicines. Personalized medicines aim at improving the therapeutic outcome of the patient. However, current pharmaceutical production is dominatedby mass production in a batch manner, i.e. producing large volumes of identical products.Uncertainties prevail regarding the ability of current production to respond to the productcustomization need in an economically and technically realizable manner. However,without customized treatment reaching the patient the benefit of personalized medicinescannot be achieved. Hence, a mass customization-paradigm, i.e. economic feasibilitywhen designing, producing and delivering customized pharmaceutical products, is desired.Pharmaceutical product customization has been discussed from a product and productionperspective. These discussions mainly focus either on product or production design.Additionally, the economic feasibility of suggested approaches is not fully explored.Mass customization requires joint consideration of product and production system design.Hence, the aim of this thesis is to explore integrated pharmaceutical product and productionsystem design facilitating a shift toward mass customization-paradigm.Methodologies to design the integrated product and production systems of pharmaceuticalproducts supporting customization are proposed. Set-based concurrent engineering(SBCE) principles are adapted due to the ability of efficient product development.Platform-based design is adapted due to a successful approach to mass customization inmanufacturing industry. Additionally, an integrated design approach to product value assessment is proposed to emphasize the customized pharmaceutical product value.The methodology application is illustrated for oral dosage forms for the purpose of demonstrating refined approaches to integrated design of these. Knowledge regarding oral dosage forms as enablers for personalized medicines is generated.Results show that the adaption of SBCE principles enables efficient consequence analysisof pharmaceutical product designs for production system designs and is accomplished byacquiring a set-based approach to simultaneous assessment of the performance of variousdesigns. Platform-based design enables flexible pharmaceutical product and productionsystem design, thus supporting mass customization. Finally, oral dosage forms embracingmodularized designs provide substantial product design flexibility but affects manufacturingcomplexity and hence, the discussion of product and production system design cannotbe separated

Pharmaceutical product modularization as a mass customization strategy to increase patient benefit cost-efficiently

Customized pharmaceutical products aim to comply with the individual needs of a patient to enhance the treatment outcome. The current pharmaceutical production paradigm is, however, dominated by mass production, where the pharmaceutical products embrace a one-size-fits-all design with a low possibility of treatment optimization to patient needs. This production paradigm is not designed or intended for customized pharmaceutical products and operating this production context for customized pharmaceutical products is argued to be cost-inefficient. To address this challenge of inefficient production of customized pharmaceutical products, this study proposes an approach to modular pharmaceutical product design. As a mass customization strategy, product modularization enables serving customers with customized products cost-efficiently. The proposed modular pharmaceutical products integrate three product design requirements originating from patient needs: a scalable dose strength, a flexible target release profile, and a scalable treatment size. An approach to assess the value of these product designs is presented, by means of proposing three benefit metrics complying with respective design requirements and a cost metric assessing the cost of producing these modular pharmaceutical product designs. Results suggest that pharmaceutical product modularization can, by keeping the number of produced components low, substantially increase the external product variety and, hence, enhance the treatment outcome of patients. Fur-thermore, results indicate that the achieved benefit for the patient through product modularization increases beyond additional costs arising during production. However, a careful modularization must be performed to optimize the tradeoff between the increased benefit and cost

Lessons learned from the application of enhanced Function-Means modelling

Although well researched and praised in academic publications, function modelling (FM) does not\ua0have gained much traction in industrial application. To investigate into possible reasons for this,\ua0this publication researches literature of nine different projects where enhanced function-means modelling has been applied. The projects are analysed for their purpose of FM-use, applied\ua0benefits and discovered challenges of the FM approach. From this, the main challenges for FM\ua0application are the abstraction level of the modelling language as well as the lack of an interface to\ua0CAD modelling

Applying Function-Means Tree Modelling to Personalized Medicines

Recent breakthroughs in diagnostics, genotyping and so forth, has created opportunities to satisfy the individual therapeutic needs of each patient, i.e. treatment can be tailored according to the patient’s biological attributes as well as according to behavioural and environmental factors. Medicines, when tailored to the individual needs are often referred to as personalized medicines. So far, pharmaceutical production platforms are dominated by mass production in a batch manner with limited possibilities to fully satisfy the emerging customization needs of pharmaceutical products. To face the challenge of customization in an economically feasible manner, re-engineering of the product and production concept is inevitable. The aim of the present work is to introduce a novel approach to customize treatments by structural parameterization of the medicinal product concept. The primary adaption is here evaluated for solid oral dosage forms (SODFs), e.g. tablets. The tablet concept is re-designed to embrace a modular architecture. A platform approach, more specifically the Configurable Component (CC) method (Claesson, 2006), is used for efficient configuration of product families. To support the design work, computer-aided design tools are used. The Configurable Component modeller (CCM) (Claesson, op. cit.) is used for the function-means tree modelling of the tablet concept and from this product variants are automatically generated. The properties of the generated product families are then evaluated with regards to following criteria; product variety and manufacturing complexity to identify critical trade-offs

Adapting discrete goods supply chains to support mass customisation of pharmaceutical products

Emerging research within the field of personalised medicines has aimed to enhance patient treatment through the use of pharmaceutical products that are customized to the individual needs and preferences of the patient. The currently dominant production platforms of pharmaceutical products, however, regard a mass production paradigm and are thus unfeasible for the production and provision of personalised medicines. The production platforms are not designed or are intended for a customisation context. Operating such a context with the current supply chain entails challenges such as increasing costs, time to patient and efforts in quality assurance activities. To address these challenges, this paper presents four reconfigured pharmaceutical supply chain designs. A qualitative operational performance assessment elicits the strengths and weaknesses of the respective supply chain design operating in a customisation context. The results suggest that a later point of variegation, i.e., the point in the supply chain where the final customisation is achieved, can relieve the operational effort of the stakeholders in the supply chain while providing the benefits of personalised medicines, i.e., an enhanced treatment outcome of the patient. A trade-off remains, however, between the supply chain’s decreased operational effort and degree of necessary reconfigurations, such as introducing new functions to stakeholder operation, reallocating activities to other stakeholders or educating stakeholders

Water transport and absorption in pharmaceutical tablets – a numerical study

The quality of a coated pharmaceutical tablet can be strongly affected by the interactions of water droplets with the porous substrate during processes such as coating process. Three different mechanisms co-exist in the coating process: water spreading, absorption and evaporation. Disentangling the fundamental understanding of these phenomena can therefore be crucial for achieving a higher quality of the products (e.g. a longer shelf-life of the tablets) and for controlling the efficiency of the process. This paper aims to investigate the spreading and absorption mechanisms after droplet impingement on a tablet using a Lattice-Boltzmann methodology. Our numerical results (droplet height and spreading, penetration depth and absorbed volume) are in a good agreement with experimental data and numerical simulations available in the literature. In particular, the spreading phase is characterised by the capillary spreading time scale, as confirmed by previous studies. In contrast to previous studies, we find that the absorption process begins at times shorter than the capillary spreading time but with a different power-law in the absorbed volume. We explain this behaviour through a modified Washburn law that takes into account three-dimensional effects. Our data can be used as a benchmark to test novel mathematical models

Integrated product and manufacturing system platforms supporting the design of personalized medicines

Pharmaceutical product customization, a prerequisite for\ua0personalized medicines, is currently a widely researched topic. Patient characteristics can be mapped and translated into parameters for designing patients’ individual treatment, i.e., the dosage form. However, current pharmaceutical manufacturing is dominated by mass production and lacks the capability and flexibility required to produce customized products. Mass customization is a proven successful approach in, for example, the manufacturing industry and thus has been discussed as an enabler for pharmaceutical product customization but has never been fully explored in a pharmaceutical context. Inspired by mass customization approaches in the manufacturing industry, this study proposes a novel methodology to develop integrated product and manufacturing system platforms for pharmaceutical products supporting a mass customization paradigm. The proposed methodology establishes sets of product and manufacturing system platform variants and suggests an approach to feasible platform design selection. The applicability of the proposed methodology is illustrated for diabetes treatment as a selected case example. Integrated platform designs are developed for the conventional treatment of a fully integral tablet design and for a design enabling product customization with a modularized tablet design. The manufacturing platforms are still embracing a mass production design in the methodology illustration and should elicit knowledge on the utility of the current production design in a mass customization context. The performance and utility of the respective platform are assessed in terms of production cost and patient benefit. The results suggest a substantial increase in patient benefit afforded by the modularized tablet design, however the production cost is increased. This trade-off between the production cost and patient benefit thus calls for novel manufacturing system concepts to achieve the feasible manufacturing of customized pharmaceutical products