Reconfiguring global pharmaceutical value networks through targeted technology interventions

Targeting a series of advanced manufacturing technology (AMT) ‘interventions’ provides the potential for significant step changes across the pharmaceutical value chain, from early stage ‘system discovery’ and clinical trials, through to novel service supply models. This research explores future value network configurations which, when aligned with disruptive shifts in technology (process and digital), may enable alternative routes to medicines production and the delivery of additional value to ‘end-users’, i.e. patients and health care providers. We draw on a categorisation of AMTs that may enable a shift from the traditional ‘batch’ and centralised manufacturing paradigm of ‘make-to-stock’, towards more re-distributed ‘continuous’ manufacturing and ‘make-to-order’ models. Despite reported benefits in the academic literature (e.g. reduced footprints, improved quality, enhanced flexibility and inventory savings), current adoption rates of continuous technologies in this sector remain low (c. 5%). This paper presents new data sources, in our study of AMT adoption in a global pharmaceutical context – assessing the barriers to implementation, and the pathways to delivering future continuous manufacturing scenarios. Our findings capture the high level of disparity in viewpoints, highlighting the uncertainties and transformational challenges ahead – in terms of opportunity areas, technological readiness and a future vision for the sector, as a whole

Emerging product-process archetypes in oncology: informing the sustainable provision of next-generation medicines

The emergence of more targeted molecular therapies has contributed to accelerated growth within the oncology market. Projected to become the leading therapeutic area by 2017, forecast spends are expected to be in the range of $74-84 billion. Coupled with its many specificities around pricing, insurance implications, and ethics, we argue that the oncology segment may best inform future pharmaceutical value network design characteristics - in supporting the sustainable manufacture and supply of next-generation medicines. Through exploration of future state scenarios and opportunities areas, driven by the adoption of emerging process and digital technologies, a base framework is extended to enable a systematic assessment of a series of candidates representative of the wider oncology market. These include niche, low volume drugs on-patent with high QALYs (quality-adjusted life years), through to higher volume generics with a history of supply shortages. A series of emerging product-process ‘archetypes’ in oncology are proposed – classified as ‘New Niche’, ‘Old Niche’ and ‘Established Generics’ – with associated models for reconfiguration, based on the clustering of potential supply benefits. A key application of this systems approach is the potential of informing economies of drug ‘repurposing’, through its extension from commercial to drug discovery, development and clinical trial contexts, and in matching emerging process capabilities to future adaptive supply requirements – for the sustainable provision of next-generation medicines

Convergent innovation in emerging healthcare technology ecosystems: Addressing complexity and integration

Precision Medicine and Digital Health are emerging areas in healthcare, and they are underpinned by convergent or cross-industry innovation. However, convergence results in greater uncertainty and complexity in terms of technologies, value networks, and organization. There has been limited empirical research on emerging and convergent ecosystems, especially in addressing the issue of integration. This research identifies how organizations innovate in emerging and convergent ecosystems, specifically, how they address the challenge of integration. We base our research on empirical analyses using a series of longitudinal case studies employing a combination of case interviews, field observations, and documents. Our findings identify a need to embrace the complexity by adopting a variety of approaches that balance “credibility-seeking” and “advantage-seeking” behaviours, to navigate, negotiate, and nurture both the innovation and ecosystem, in addition to a combination of “analysis” and “synthesis” actions to manage aspects of integration. We contribute to the convergent innovation agenda and provide practical approaches for innovators in this domain.innovation and ecosystem, with a combination of ‘analysis’ and ‘synthesis’ actions to manage aspects of integration. We contribute to the convergent innovation agenda and provide practical approaches for innovators in this domain

Inkjet printing for pharmaceutics - A review of research and manufacturing.

Global regulatory, manufacturing and consumer trends are driving a need for change in current pharmaceutical sector business models, with a specific focus on the inherently expensive research costs, high-risk capital-intensive scale-up and the traditional centralised batch manufacturing paradigm. New technologies, such as inkjet printing, are being explored to radically transform pharmaceutical production processing and the end-to-end supply chain. This review provides a brief summary of inkjet printing technologies and their current applications in manufacturing before examining the business context driving the exploration of inkjet printing in the pharmaceutical sector. We then examine the trends reported in the literature for pharmaceutical printing, followed by the scientific considerations and challenges facing the adoption of this technology. We demonstrate that research activities are highly diverse, targeting a broad range of pharmaceutical types and printing systems. To mitigate this complexity we show that by categorising findings in terms of targeted business models and Active Pharmaceutical Ingredient (API) chemistry we have a more coherent approach to comparing research findings and can drive efficient translation of a chosen drug to inkjet manufacturing.This project was supported by (i) the UK Engineering and Physical Sciences Research Council and industrial partners in the Programme Grant number EP/H018913/1 ‘Innovation in Industrial Inkjet Technology’, (ii) EPSRC Centre for Innovative Manufacturing in Continuous Manufacturing and Crystallisation (EP/1033459/1) and (iii) Department of Business, Innovation and Skill’s (BIS) Advanced Manufacturing Supply Chain Initiative (AMSCI) funded Project ‘Remedies’ (TS/L006529/1).This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.ijpharm.2015.03.01

The LUX-ZEPLIN (LZ) Experiment

We describe the design and assembly of the LUX-ZEPLIN experiment, a direct detection search for cosmic WIMP dark matter particles. The centerpiece of the experiment is a large liquid xenon time projection chamber sensitive to low energy nuclear recoils. Rejection of backgrounds is enhanced by a Xe skin veto detector and by a liquid scintillator Outer Detector loaded with gadolinium for efficient neutron capture and tagging. LZ is located in the Davis Cavern at the 4850' level of the Sanford Underground Research Facility in Lead, South Dakota, USA. We describe the major subsystems of the experiment and its key design features and requirements

Framework for strategic wind farm site prioritisation based on modelled wolf reproduction habitat in Croatia

In order to meet carbon reduction targets, many nations are greatly expanding their wind power capacity. However, wind farm infrastructure potentially harms wildlife, and we must therefore find ways to balance clean energy demands with the need to protect wildlife. Wide-ranging carnivores live at low density and are particularly susceptible to disturbance from infrastructure development, so are a particular concern in this respect. We focused on Croatia, which holds an important population of wolves and is currently planning to construct many new wind farms. Specifically, we sought to identify an optimal subset of planned wind farms that would meet energy targets while minimising potential impact on wolves. A suitability model for wolf breeding habitat was carried out using Maxent, based on six environmental variables and 31 reproduction site locations collected between 1997 and 2015. Wind farms were prioritised using Marxan to find the optimal trade-off between energy capacity and overlap with critical wolf reproduction habitat. The habitat suitability model predictions were consistent with the current knowledge: probability of wolf breeding site presence increased with distance to settlements, distance to farmland and distance to roads and decreased with distance to forest. Spatial optimisation showed that it would be possible to meet current energy targets with only 31% of currently proposed wind farms, selected in a way that reduces the potential ecological cost (overall predicted wolf breeding site presence within wind farm sites) by 91%. This is a highly efficient outcome, demonstrating the value of this approach for prioritising infrastructure development based on its potential impact on wide-ranging wildlife species

The LUX-ZEPLIN (LZ) experiment

We describe the design and assembly of the LUX-ZEPLIN experiment, a direct detection search for cosmic WIMP dark matter particles. The centerpiece of the experiment is a large liquid xenon time projection chamber sensitive to low energy nuclear recoils. Rejection of backgrounds is enhanced by a Xe skin veto detector and by a liquid scintillator Outer Detector loaded with gadolinium for efficient neutron capture and tagging. LZ is located in the Davis Cavern at the 4850’ level of the Sanford Underground Research Facility in Lead, South Dakota, USA. We describe the major subsystems of the experiment and its key design features and requirements

The LUX-ZEPLIN (LZ) radioactivity and cleanliness control programs

LUX-ZEPLIN (LZ) is a second-generation direct dark matter experiment with spin-independent WIMP-nucleon scattering sensitivity above 1.4×10−48cm2 for a WIMP mass of 40GeV/c2 and a 1000days exposure. LZ achieves this sensitivity through a combination of a large 5.6t fiducial volume, active inner and outer veto systems, and radio-pure construction using materials with inherently low radioactivity content. The LZ collaboration performed an extensive radioassay campaign over a period of six years to inform material selection for construction and provide an input to the experimental background model against which any possible signal excess may be evaluated. The campaign and its results are described in this paper. We present assays of dust and radon daughters depositing on the surface of components as well as cleanliness controls necessary to maintain background expectations through detector construction and assembly. Finally, examples from the campaign to highlight fixed contaminant radioassays for the LZ photomultiplier tubes, quality control and quality assurance procedures through fabrication, radon emanation measurements of major sub-systems, and bespoke detector systems to assay scintillator are presented