CAR T-cell therapies: The concept of a dynamic supply chain

Novarti’s Kymriah and Kite’s Yescarta, are the first Chimeric Antigen Receptor (CAR) T-cell therapies to receive regulatory approval both in the United States and in Europe. They are suggested as new face in cancer treatment and in particular in B-cell acute lymphoblastic leukaemia (ALL). Their promising results have encouraged numerous research groups and manufacturers to explore the potential of those therapies in the treatment of various cancer types, resulting into 317 clinical trials globally (based on a recent search on ClinicalTrials.gov (2018)). Today, in the UK CAR T cells are only available through clinical trial schemes (approximately 250 patients per trial), thus being produced and delivered at a small scale. However, their recent European Medicines Agency Approval will allow them to become available to a wider patient population (approximately 40,000 eligible patients by 2031 (Figure 1), based on research performed on the UK patient population), requiring, therefore significant scale up/out both in the manufacturing line as well as in the logistics/supply chain model. In this work we focus on the design of a modelling tool to assist the decision making in the design of the supply chain model of CAR T cell therapies. Expanding our previous work (Wang et al., 2018), we demonstrate the design of a Resource Technology Network (RTN) for the identification of the key steps/decisions in the CAR T supply chain model. Based on previous qualitative results (Papathanasiou, 2018), we present a comparison between three supply chain model structures and we introduce the concept of the “dynamic” supply chain model. The latter refers to a versatile supply chain network that is tailored to the varying therapy demand. Based on the demand profiles, the modelling tool decides on: (a) number and location of clinical sites, (b) number and location of manufacturing sites and (c) best means of transport for the therapy. Lastly, the model considers time restrictions related to product shelf life, as well as different business decisions (e.g. in-house versus outsourcing quality control). Please click Additional Files below to see the full abstract

Primary CNS Burkitt Lymphoma: A Case Report of a 55-Year-Old Cerebral Palsy Patient

With primary central nervous system lymphoma (PCNSL) being a rare disease, the subtype of Burkitt lymphoma (BL) presenting as a sole CNS lesion is an even more exceptional diagnosis. A case of coexistent primary CNS Burkitt lymphoma (PCNSBL) with cerebral palsy (CP) is presented. A 55-year-old Caucasian male presented with increasing bilateral lower extremity weakness above his baseline in addition to signs of increased intracranial pressure. Four abnormal enhancing masses were detected on MRI with biopsy results consistent with Burkitt lymphoma. Complete staging workup was completed with no evidence of extra- CNS disease noted on PET/CT, bone marrow biopsy, or cerebral spinal fluid analysis. The patient was treated with intravenous as well as intrathecal chemotherapy and found to be in a complete remission at six months. Recurrence in the CNS was observed four months later with treatment consisting of whole brain radiation as well as intrathecal chemotherapy. Thirty months after diagnosis, the patient remains disease-free. To our knowledge, this is the first case of PCNSBL in the setting of CP. A review of literature regarding treatment options in this controversial setting is provided

Primary CNS Burkitt Lymphoma: A Case Report of a 55- Year-Old Cerebral Palsy Patient

With primary central nervous system lymphoma (PCNSL) being a rare disease, the subtype of Burkitt lymphoma (BL) presenting as a sole CNS lesion is an even more exceptional diagnosis. A case of coexistent primary CNS Burkitt lymphoma (PCNSBL) with cerebral palsy (CP) is presented. A 55-year-old Caucasian male presented with increasing bilateral lower extremity weakness above his baseline in addition to signs of increased intracranial pressure. Four abnormal enhancing masses were detected on MRI with biopsy results consistent with Burkitt lymphoma. Complete staging workup was completed with no evidence of extra-CNS disease noted on PET/CT, bone marrow biopsy, or cerebral spinal fluid analysis. The patient was treated with intravenous as well as intrathecal chemotherapy and found to be in a complete remission at six months. Recurrence in the CNS was observed four months later with treatment consisting of whole brain radiation as well as intrathecal chemotherapy. Thirty months after diagnosis, the patient remains disease-free. To our knowledge, this is the first case of PCNSBL in the setting of CP. A review of literature regarding treatment options in this controversial setting is provided

Adult Sporadic Burkitt’s Lymphoma Presenting with Rapid Development of Peritoneal Lymphomatosis

Sporadic Burkitt’s Lymphoma (BL) is a highly aggressive form of non-Hodgkin’s lymphoma which requires prompt diagnosis and treatment. Though usual presentation involves abdominal lymphadenopathy with possible solid organ involvement, sporadic BL can rarely present with peritoneal lymphomatosis. We present a unique case with rapid evolution of BL presenting as peritoneal and omental lymphomatosis with hepatic lesions and pelvic and pericardial adenopathy

Root cause analysis of medication errors at a multi-specialty hospital in Western India

Background: Medication use is a complex process in a medical setting, it starts with physician prescribing, followed by nurse transcribing, pharmacist dispensing, medication administration, and patient monitoring. There is a definite role of clinical pharmacists in reduction of Medication errors by examining and evaluating its causes and communicate the results to physicians and caregivers. The aim of the present study was study of medication errors for the safety & the health benefit of the patient visiting multi specialty hospital. Methods: The Observational study was carried out at in-patient appointments at multi specialty hospital during the period of June 2012 to April 2013 at Baroda. Results: Total of 300 patients were observed out of which medication error has occurred in 117 (39%) cases considering 62% were males & 38% female patients. Out of 117 cases 28% of transcription errors, 62% of prescription errors, 11% of dispensing errors & 16 % Administration errors. 51% of medication errors were occurring in the age group of 40-60. Root cause analysis showed that prescription error was due to Illegible handwriting, No dosage form prescribed, the Wrong Brand name prescribed; transcription error due to Wrong drug is transcribed; administrative error due to Wrong dose is administered, Drug administered through wrong route, Wrong drug is administered while dispensing error due to Urgent dispensation not done within 10 to 15 minutes, Wrong dose dispensed.Conclusion: Most common medication errors were Prescription error & Transcription error which accounts for almost 77% of the total error, which is according to Pareto 80:20 Principle

The greenhouse gas emissions performance of cellulosic ethanol supply chains in Europe

<p>Abstract</p> <p>Background</p> <p>Calculating the greenhouse gas savings that may be attributed to biofuels is problematic because production systems are inherently complex and methods used to quantify savings are subjective. Differing approaches and interpretations have fuelled a debate about the environmental merit of biofuels, and consequently about the level of policy support that can be justified. This paper estimates and compares emissions from plausible supply chains for lignocellulosic ethanol production, exemplified using data specific to the UK and Sweden. The common elements that give rise to the greatest greenhouse gas emissions are identified and the sensitivity of total emissions to variations in these elements is estimated. The implications of including consequential impacts including indirect land-use change, and the effects of selecting alternative allocation methods on the interpretation of results are discussed.</p> <p>Results</p> <p>We find that the most important factors affecting supply chain emissions are the emissions embodied in biomass production, the use of electricity in the conversion process and potentially consequential impacts: indirect land-use change and fertiliser replacement. The large quantity of electricity consumed during enzyme manufacture suggests that enzymatic conversion processes may give rise to greater greenhouse gas emissions than the dilute acid conversion process, even though the dilute acid process has a somewhat lower ethanol yield.</p> <p>Conclusion</p> <p>The lignocellulosic ethanol supply chains considered here all lead to greenhouse gas savings relative to gasoline An important caveat to this is that if lignocellulosic ethanol production uses feedstocks that lead to indirect land-use change, or other significant consequential impacts, the benefit may be greatly reduced.</p> <p>Co-locating ethanol, electricity generation and enzyme production in a single facility may improve performance, particularly if this allows the number of energy intensive steps in enzyme production to be reduced, or if other process synergies are available. If biofuels policy in the EU remains contingent on favourable environmental performance then the multi-scale nature of bioenergy supply chains presents a genuine challenge. Lignocellulosic ethanol holds promise for emission reductions, but maximising greenhouse gas savings will not only require efficient supply chain design but also a better understanding of the spatial and temporal factors which affect overall performance.</p

The commercial performance of cellulosic ethanol supply-chains in Europe

<p>Abstract</p> <p>Background</p> <p>The production of fuel-grade ethanol from lignocellulosic biomass resources has the potential to increase biofuel production capacity whilst minimising the negative environmental impacts. These benefits will only be realised if lignocellulosic ethanol production can compete on price with conventional fossil fuels and if it can be produced commercially at scale. This paper focuses on lignocellulosic ethanol production in Europe. The hypothesis is that the eventual cost of production will be determined not only by the performance of the conversion process but by the performance of the entire supply-chain from feedstock production to consumption. To test this, a model for supply-chain cost comparison is developed, the components of representative ethanol supply-chains are described, the factors that are most important in determining the cost and profitability of ethanol production are identified, and a detailed sensitivity analysis is conducted.</p> <p>Results</p> <p>The most important cost determinants are the cost of feedstocks, primarily determined by location and existing markets, and the value obtained for ethanol, primarily determined by the oil price and policy incentives. Both of these factors are highly uncertain. The best performing chains (ethanol produced from softwood and sold as a low percentage blend with gasoline) could ultimately be cost competitive with gasoline without requiring subsidy, but production from straw would generally be less competitive.</p> <p>Conclusion</p> <p>Supply-chain design will play a critical role in determining commercial viability. The importance of feedstock supply highlights the need for location-specific assessments of feedstock availability and price. Similarly, the role of subsidies and policy incentives in creating and sustaining the ethanol market highlights the importance of political engagement and the need to include political risks in investment appraisal. For the supply-chains described here, and with the cost and market parameters selected, selling ethanol as a low percentage blend with gasoline will maximise ethanol revenues and minimise the need for subsidies. It follows, therefore, that the market for low percentage blends should be saturated before markets for high percentage blends.</p

Advanced technologies in the modern era for augmented patient health care and drug delivery

The objective of the work is to recognize the recent advancements in the modern health care and drug delivery systems. The article describes few recent developments in technology like artificial intelligence, personalized medicines, customized medicines, 3D printing, bioelectronic devices and tele pharmacy, which have the potential to augment health care and drug delivery in coming times. Personalized medication ensures precise health care as per the individual genetic makeup of the patients. The 3D printing technology enables to deliver tailor made solutions to fulfil individual patient requirements. Bioelectronic medicines and devices are new technology where the patient wears a device and its electrical signal cures certain ailments. Tele pharmacy ensures that the technological advances of telecommunications are also passed on to the patient health care sector. Moreover, it can be said that all these modern developments ensure that the quality of life improves and there comes a better control on the health care costs. Keywords: artificial intelligence, personalized medicines, customized medicines, 3D printing, bioelectronic devices and tele pharmac