Future supply chains enabled by continuous processing - opportunities and challenges : May 20–21, 2014 continuous manufacturing symposium

This paper examines the opportunities and challenges facing the pharmaceutical industry in moving to a primarily “continuous processing”-based supply chain. The current predominantly “large batch” and centralized manufacturing system designed for the “blockbuster” drug has driven a slow-paced, inventory heavy operating model that is increasingly regarded as inflexible and unsustainable. Indeed, new markets and the rapidly evolving technology landscape will drive more product variety, shorter product life-cycles, and smaller drug volumes, which will exacerbate an already unsustainable economic model. Future supply chains will be required to enhance affordability and availability for patients and healthcare providers alike despite the increased product complexity. In this more challenging supply scenario, we examine the potential for a more pull driven, near real-time demand-based supply chain, utilizing continuous processing where appropriate as a key element of a more “flow-through” operating model. In this discussion paper on future supply chain models underpinned by developments in the continuous manufacture of pharmaceuticals, we have set out; •The significant opportunities to moving to a supply chain flow-through operating model, with substantial opportunities in inventory reduction, lead-time to patient, and radically different product assurance/stability regimes. •Scenarios for decentralized production models producing a greater variety of products with enhanced volume flexibility. •Production, supply, and value chain footprints that are radically different from today's monolithic and centralized batch manufacturing operations. •Clinical trial and drug product development cost savings that support more rapid scale-up and market entry models with early involvement of SC designers within New Product Development. •The major supply chain and industrial transformational challenges that need to be addressed. The paper recognizes that although current batch operational performance in pharma is far from optimal and not necessarily an appropriate end-state benchmark for batch technology, the adoption of continuous supply chain operating models underpinned by continuous production processing, as full or hybrid solutions in selected product supply chains, can support industry transformations to deliver right-first-time quality at substantially lower inventory profiles

Future Supply Chains Enabled by Continuous Processing-Opportunities Challenges May 20-21 2014 Continuous Manufacturing Symposium.

This paper examines the opportunities and challenges facing the pharmaceutical industry in moving to a primarily "continuous processing"-based supply chain. The current predominantly "large batch" and centralized manufacturing system designed for the "blockbuster" drug has driven a slow-paced, inventory heavy operating model that is increasingly regarded as inflexible and unsustainable. Indeed, new markets and the rapidly evolving technology landscape will drive more product variety, shorter product life-cycles, and smaller drug volumes, which will exacerbate an already unsustainable economic model. Future supply chains will be required to enhance affordability and availability for patients and healthcare providers alike despite the increased product complexity. In this more challenging supply scenario, we examine the potential for a more pull driven, near real-time demand-based supply chain, utilizing continuous processing where appropriate as a key element of a more "flow-through" operating model. In this discussion paper on future supply chain models underpinned by developments in the continuous manufacture of pharmaceuticals, we have set out; The paper recognizes that although current batch operational performance in pharma is far from optimal and not necessarily an appropriate end-state benchmark for batch technology, the adoption of continuous supply chain operating models underpinned by continuous production processing, as full or hybrid solutions in selected product supply chains, can support industry transformations to deliver right-first-time quality at substantially lower inventory profiles. © 2015 The Authors. Journal of Pharmaceutical Sciences published by Wiley Periodicals, Inc. and the American Pharmacists Association.The authors would like to acknowledge the following for valuable comments and inputs during the preparation of this white paper; Professor Lee Cronin (Glasgow University, UK), Patricia Hurter (Vertex), Mark Buswell (GSK), and Chris Price (GSK). We would also like to acknowledge the support and funding from the UK's Engineering and Physical Sciences Research Council's (EPSRC) Centre for Innovative Manufacturing in Continuous Manufacturing and Crystallisation (CMAC), and the UK's Department of Business Innovation and Skill's (BIS) Advanced Manufacturing Supply Chain Initiative (AMSCI) funded Project Remedies.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/jps.2434

Salvage laryngectomy and laryngopharyngectomy: Multicenter review of outcomes associated with a reconstructive approach

Background Surgeons have developed various reconstructive techniques to minimize the rate of pharyngocutaneous fistula and optimize functional outcome after salvage laryngectomy or laryngopharyngectomy. Methods Multicenter retrospective review at 33 institutions of 486 patients with a history of squamous cell carcinoma (SCC) of the larynx or hypopharynx previously treated with primary chemoradiotherapy (CRT) who required salvage surgery. Outcomes evaluated were overall fistula rate, fistula requiring reoperation, and 12‐month speech and swallowing function. Results Primary closure of the hypopharynx was associated with a statistically higher overall fistula rate and fistula requiring reoperation compared to reconstruction with vascularized tissue augmentation. Vascularized tissue augmentation with muscle led to worse 12‐month “understandability of speech” and “nutritional mode” scores compared to vascularized tissue augmentation without muscle. Conclusion Vascularized tissue augmentation reduces the overall fistula rate and fistula requiring reoperation but vascularized tissue augmentation with muscle may impair speech and swallowing outcomes

Global mortality from firearms, 1990-2016

Importance: Understanding global variation in firearm mortality rates could guide prevention policies and interventions. Objective: To estimate mortality due to firearm injury deaths from 1990 to 2016 in 195 countries and territories. Design, Setting, and Participants: This study used deidentified aggregated data including 13 812 location-years of vital registration data to generate estimates of levels and rates of death by age-sex-year-location. The proportion of suicides in which a firearm was the lethal means was combined with an estimate of per capita gun ownership in a revised proxy measure used to evaluate the relationship between availability or access to firearms and firearm injury deaths. Exposures: Firearm ownership and access. Main Outcomes and Measures: Cause-specific deaths by age, sex, location, and year. Results: Worldwide, it was estimated that 251 000 (95% uncertainty interval [UI], 195 000-276 000) people died from firearm injuries in 2016, with 6 countries (Brazil, United States, Mexico, Colombia, Venezuela, and Guatemala) accounting for 50.5% (95% UI, 42.2%-54.8%) of those deaths. In 1990, there were an estimated 209 000 (95% UI, 172 000 to 235 000) deaths from firearm injuries. Globally, the majority of firearm injury deaths in 2016 were homicides (64.0% [95% UI, 54.2%-68.0%]; absolute value, 161 000 deaths [95% UI, 107 000-182 000]); additionally, 27% were firearm suicide deaths (67 500 [95% UI, 55 400-84 100]) and 9% were unintentional firearm deaths (23 000 [95% UI, 18 200-24 800]). From 1990 to 2016, there was no significant decrease in the estimated global age-standardized firearm homicide rate (-0.2% [95% UI, -0.8% to 0.2%]). Firearm suicide rates decreased globally at an annualized rate of 1.6% (95% UI, 1.1-2.0), but in 124 of 195 countries and territories included in this study, these levels were either constant or significant increases were estimated. There was an annualized decrease of 0.9% (95% UI, 0.5%-1.3%) in the global rate of age-standardized firearm deaths from 1990 to 2016. Aggregate firearm injury deaths in 2016 were highest among persons aged 20 to 24 years (for men, an estimated 34 700 deaths [95% UI, 24 900-39 700] and for women, an estimated 3580 deaths [95% UI, 2810-4210]). Estimates of the number of firearms by country were associated with higher rates of firearm suicide (P < .001; R2 = 0.21) and homicide (P < .001; R2 = 0.35). Conclusions and Relevance: This study estimated between 195 000 and 276 000 firearm injury deaths globally in 2016, the majority of which were firearm homicides. Despite an overall decrease in rates of firearm injury death since 1990, there was variation among countries and across demographic subgroups