scholarly journals Minimum manufacturing costs, national prices and estimated global availability of new repurposed therapies for COVID-19.

2021 ◽  
Author(s):  
Junzheng Wang ◽  
Jacob Levi ◽  
Leah Ellis ◽  
Andrew Hill
Keyword(s):  
Export Price ◽  
Production Costs ◽  
Equitable Access ◽  
Successful Management ◽  
Access To Treatment ◽  
Drug Candidates ◽  
Pharmaceutical Ingredients ◽  
Current Availability ◽  
Selection Of ◽  
List Prices

Background Currently, only dexamethasone, tocilizumab and sarilumab have conclusively been shown to reduce mortality of COVID-19. No drug for prevention or treatment in earlier stages of COVID-19 are yet found; although several new candidates including ivermectin, dutasteride, baricitinib, budesonide and colchicine are being studied with some early promising results. Safe and effective treatments will need to be both affordable and widely available globally. Objectives This analysis will estimate and compare potential generic production costs of a selection of COVID-19 drug candidates with international list prices. Methods Costs of production for new and potential COVID-19 drugs (dexamethasone, ivermectin, dutasteride, budesonide, baricitinib, tocilizumab, sarilumab and colchicine) were estimated using active pharmaceutical ingredients (API) data extracted from global shipping records. This was compared with national pricing data from low, medium, and high-income countries. Annual API export volumes from India were used to estimate the current availability of each drug. Results Repurposed therapies can be generically manufactured at very low per-course costs: ranging from $2.58 for IV dexamethasone (or $0.19 orally) to $0.12 for ivermectin. No export price data was available for baricitinib, tocilizumab or sarilumab. When compared against international list prices, we found wide variations between countries. Drug API availability was generally good, with colchicine being the most available with sufficient annual API exported for 59.8 million treatment courses. Conclusions Successful management of COVID-19 will require equitable access to treatment for all populations, not just those able to pay high prices. Analysed drugs are widely available and affordable, whilst IV treatment courses are more expensive.

scholarly journals Minimum manufacturing costs, national prices and estimated global availability of new repurposed therapies for COVID-19

2021 ◽  
Author(s):  
Junzheng Wang ◽  
Jacob Levi ◽  
Leah Ellis ◽  
Andrew Hill
Keyword(s):  
Export Price ◽  
Equitable Access ◽  
Access To Treatment ◽  
Drug Candidates ◽  
Pharmaceutical Ingredients ◽  
Current Availability ◽  
Repurposed Drugs ◽  
Inhaled Budesonide ◽  
Selection Of ◽  
List Prices

Abstract Background Currently, only dexamethasone, tocilizumab and sarilumab have conclusively been shown to reduce mortality of COVID-19. Safe and effective treatments will need to be both affordable and widely available globally to be used alongside vaccination programmes. This analysis will estimate and compare potential generic minimum costs of a selection of approved COVID-19 drug candidates with available international list prices. Methods We searched for repurposed drugs that have been approved by at least one of the WHO, FDA or NICE, or at least given emergency use authorisation or recommended for off-label prescription. Drug prices were searched for, for dexamethasone, budesonide, baricitinib, tocilizumab, casirivimab and imdevimab, and sarilumab using active pharmaceutical ingredients (API) data extracted from global shipping records. This was compared with national pricing data from a range of low, medium, and high-income countries. Annual API export volumes from India were used to estimate the current availability of each drug. Results Repurposed therapies can be generically manufactured for some treatments at very low per-course costs, ranging from $2.58 for IV dexamethasone (or $0.19 orally) and $4.34 for inhaled budesonide. No export price data was available for baricitinib, tocilizumab, casirivimab and imdevimab or sarilumab, but courses of these treatments are priced highly, ranging from $6.67 for baricitinib to $875.5 for sarilumab. When comparing international list prices, we found wide variations between countries. Conclusions Successful management of COVID-19 will require equitable access to treatment for all populations, not just those able to pay high prices. Dexamethasone and budesonide are widely available and affordable, whilst monoclonal antibodies and IV treatment courses are more expensive.

scholarly journals 407. Minimum Manufacturing Costs, National Prices and Estimated Global Availability of New Repurposed Therapies for COVID-19

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S305-S305
Author(s):  
Junzheng Wang ◽  
Jacob Levi ◽  
Leah Ellis ◽  
Andrew Hill
Keyword(s):  
Export Price ◽  
Production Costs ◽  
Access To Treatment ◽  
Pharmaceutical Ingredients ◽  
Current Availability ◽  
Recent Developments ◽  
Repurposed Drugs ◽  
Exposure Prophylaxis ◽  
The Cost ◽  
List Prices

Abstract Background Currently, only dexamethasone, tocilizumab and sarilumab have conclusively been shown to reduce mortality of COVID-19. No drug for prevention or treatment in earlier stages of COVID-19 are yet found, with previously promising drugs such as hydroxychloroquine and remdesivir have been shown to be ineffective. Several new candidates are now being studied in clinical trials. Safe and effective treatments will need to be both affordable and widely available. We therefore revised our original 2020 analysis to reflect recent developments. In this update we analysed the cost of production, current national list prices, and API availability for oral and IV dexamethasone, ivermectin, colchicine, dutasteride, budesonide, baricitinib and monoclonal antibodies tocilizumab and sarilumab. Methods Costs of production for new and potential COVID-19 drugs (dexamethasone, ivermectin, dutasteride, budesonide, baricitinib, tocilizumab, sarilumab and colchicine) were estimated using an established and published methodology based on costs of active pharmaceutical ingredients (API), extracted from the global shipping records database Panjiva. This was compared with national pricing data from low, medium, and high-income countries. Annual API export volumes from India were used to estimate the current availability of each drug. Results Repurposed therapies can be generically manufactured at very low per-course costs: ranging from &2.58 for IV dexamethasone (or &0.19 orally) to &0.12 for ivermectin. No export price data was available for baricitinib, tocilizumab or sarilumab. When compared against international list prices, we found wide variations between countries. Drug API availability was generally good, with colchicine being the most available with sufficient annual API exported for 59.8 million treatment courses. A summary is shown in Table 1. Table 1. Summary of list prices, estimated production costs, and current availability of potential COVID-19 drugs selected for analysis. OD = Once daily, BD = twice per day, EUA = Emergency Use Authorisation (only to be given with remdesivir) *In most recent 12-month period. Conclusion Successful management of COVID-19 will require equitable access to treatment for all, not just those able to pay. Repurposed drugs can be manufactured at very low costs if shown to be clinically effective, and offers an affordable, widely available option for patients at all stages of the disease from pre-exposure prophylaxis to asymptotic and mild infections, through to critical care until vaccination coverage is expanded. Disclosures All Authors: No reported disclosures

scholarly journals Membrane Distillation for the Production of Pharmaceutical-Grade Water—Investigation into the Application of AGMD and VMD

2021 ◽  
Vol 18 (11) ◽  
pp. 6058
Author(s):  
Cornelius Nellessen ◽  
Thomas Klein ◽  
Hans-Jürgen Rapp ◽  
Frank Rögener
Keyword(s):  
Energy Demand ◽  
Tap Water ◽  
Membrane Distillation ◽  
Pharmaceutical Products ◽  
Optimum Process ◽  
The European Union ◽  
Pharmaceutical Ingredients ◽  
Multi Stage ◽  
One Step ◽  
Selection Of

The production of pharmaceutical ingredients, intermediates and final products strongly depends on the utilization of water. Water is also required for the purification and preparation of reagents. Each specific application determines the respective water quality. In the European Union, the European Pharmacopeia (Ph. Eur.) contains the official standards that assure quality control of pharmaceutical products during their life cycle. According to this, the production of water for pharmaceutical use is mainly based on multi-stage distillation and membrane processes, especially, reverse osmosis. Membrane distillation (MD) could be an alternative process to these classical methods. It offers advantages in terms of energy demand and a compact apparatus design. In the following study, the preparation of pharmaceutical-grade water from tap water in a one-step process using MD is presented. Special emphasis is placed on the performance of two different module designs and on the selection of optimum process parameters.

scholarly journals A Dual-Sensor-Based Screening System for In Vitro Selection of TDP1 Inhibitors

Sensors ◽  
2021 ◽  
Vol 21 (14) ◽  
pp. 4832
Author(s):  
Ann-Katrine Jakobsen ◽  
Josephine Geertsen Keller ◽  
María Gonzalez ◽  
Endika Martin-Encinas ◽  
Francisco Palacios ◽  
...  
Keyword(s):  
Dna Damage ◽  
In Vitro Selection ◽  
Main Function ◽  
Screening System ◽  
Drug Candidates ◽  
Topoisomerase 1 ◽  
High Throughput Drug Screening ◽  
Dual Sensor ◽  
Selection Of

DNA sensors can be used as robust tools for high-throughput drug screening of small molecules with the potential to inhibit specific enzymes. As enzymes work in complex biological pathways, it is important to screen for both desired and undesired inhibitory effects. We here report a screening system utilizing specific sensors for tyrosyl-DNA phosphodiesterase 1 (TDP1) and topoisomerase 1 (TOP1) activity to screen in vitro for drugs inhibiting TDP1 without affecting TOP1. As the main function of TDP1 is repair of TOP1 cleavage-induced DNA damage, inhibition of TOP1 cleavage could thus reduce the biological effect of the TDP1 drugs. We identified three new drug candidates of the 1,5-naphthyridine and 1,2,3,4-tetrahydroquinolinylphosphine sulfide families. All three TDP1 inhibitors had no effect on TOP1 activity and acted synergistically with the TOP1 poison SN-38 to increase the amount of TOP1 cleavage-induced DNA damage. Further, they promoted cell death even with low dose SN-38, thereby establishing two new classes of TDP1 inhibitors with clinical potential. Thus, we here report a dual-sensor screening approach for in vitro selection of TDP1 drugs and three new TDP1 drug candidates that act synergistically with TOP1 poisons.

scholarly journals Efektywność produkcji FAME na podstawie wymagań normy ISO 14045:2012

Nafta-Gaz ◽  
2021 ◽  
Vol 77 (3) ◽  
pp. 208-214
Author(s):  
Michał Pajda ◽  
◽  
Wojciech Mazela ◽  
Keyword(s):  
Natural Environment ◽  
New Technologies ◽  
Negative Impact ◽  
New Technology ◽  
Methyl Esters ◽  
Production Costs ◽  
Raw Material ◽  
Energy Materials ◽  
The Impact ◽  
Selection Of

The aim of the work was to present the issue of eco-efficiency, based on the PN-EN ISO 14045:2012 standard in relation to the production of fatty acid methyl esters (FAME). The ecoefficiency analysis takes into account economic and environmental aspects in the improvement of products and processes / technologies. Eco-efficiency considers the product and technology throughout the life cycle, from the construction phase, through use to decommissioning. The impact on the natural environment is assessed on the basis of: consumption of energy, materials, dust and gas emissions, waste and sewage. Total costs include: production costs, raw material costs, costs during the use phase including maintenance, repair and operating costs, product disposal or recycling. The eco-efficiency analysis is helpful in making decisions regarding the selection of a new product or designing a new technology, and enables the selection of the variant that is the most economical and has the least possible impact on the natural environment. These issues are particularly important in the case of biofuels. The rapid growth of their production and the European Union’s policy, which aims to increase the share of energy from renewable sources, cause concerns of many experts regarding the threats related to the production of biofuels, both for the environment and food security. In particular, efforts are made to minimize the amount of waste and residues by implementing the idea of a circular economy. This approach promotes the development of new technologies that are more environmentally friendly. Due to the regulations set out in the RED and RED II Directives, there is a chance that the biofuels will have a less negative impact on the environment. This results from the obligation to certify compliance with the sustainability criteria, which is carried out by voluntary systems recognized by the European Commission, such as the KZR INiG System.

scholarly journals Kleiber ratios and growth curves of African Black and Red Neck ostrich breeds and their crossbreeds

2021 ◽  
Vol 42 (6supl2) ◽  
pp. 4059-4072
Author(s):  
Marcos Paulo Gonçalves de Rezende ◽  
◽  
Paulo Luiz Souza Carneiro ◽  
Riccardo Moretti ◽  
Johnny Iglesias Mendes Araujo ◽  
...  
Keyword(s):  
Feed Efficiency ◽  
Growth Curves ◽  
Production Costs ◽  
Adult Weight ◽  
Kleiber Ratio ◽  
Final Weight ◽  
African Black ◽  
One Year ◽  
Lower Production ◽  
Selection Of

The selection of animals with lower production costs can be achieved by using feed efficiency and growth curve information. Kleiber ratio (KR) is an alternative option for discriminating against the animals that have the greatest weight gain about their final weight. Alternative feed efficiency and growth curves for ostriches of the African Black (AB) and Red Neck (RN) breeds and their crossbreeds (CB) were investigated using KR and Gompertz equation. Univariate and multivariate analyses were used. The highest adult weight was identified in the RN and CB. AB was more precocious than the RN and CB individuals. Only AB animals reached 75% of their mature weight at one year of age. At 180 days, AB showed better KR. AB was different from the others, mainly for KR at 90 days and 180 days. Considering multivariate analysis, AB animals were different from the others, regardless of sex, mainly for KR at 90 days and KR at 180 days. Other subgroups separated the animals by sex. In a market preferring animals of minor structure (smaller cuts) and greater precocity, it would be suitable to opt for AB. When animals with greater body structure (larger cuts) are desired, males RN and CR is the best option, however, it will be slaughtered with greater age and lower value for KR (may generate a bigger production cost ). It is possible to obtain animals with precocity and high KR, being well represented by the AB breed.

scholarly journals Screening Strategies and Methods for Better Off-Target Liability Prediction and Identification of Small-Molecule Pharmaceuticals

2018 ◽  
Vol 24 (1) ◽  
pp. 1-24 ◽  
Author(s):  
Terry R. Van Vleet ◽  
Michael J. Liguori ◽  
James J. Lynch ◽  
Mohan Rao ◽  
Scott Warder
Keyword(s):  
Data Sets ◽  
Multiple Sources ◽  
Drug Candidates ◽  
Critical Gap ◽  
Screening Strategies ◽  
Feasible Option ◽  
Stage Development ◽  
Integrated Screening ◽  
Expensive Process ◽  
Selection Of

Pharmaceutical discovery and development is a long and expensive process that, unfortunately, still results in a low success rate, with drug safety continuing to be a major impedance. Improved safety screening strategies and methods are needed to more effectively fill this critical gap. Recent advances in informatics are now making it possible to manage bigger data sets and integrate multiple sources of screening data in a manner that can potentially improve the selection of higher-quality drug candidates. Integrated screening paradigms have become the norm in Pharma, both in discovery screening and in the identification of off-target toxicity mechanisms during later-stage development. Furthermore, advances in computational methods are making in silico screens more relevant and suggest that they may represent a feasible option for augmenting the current screening paradigm. This paper outlines several fundamental methods of the current drug screening processes across Pharma and emerging techniques/technologies that promise to improve molecule selection. In addition, the authors discuss integrated screening strategies and provide examples of advanced screening paradigms.

Activity-Based Costing System for a Small Manufacturing Company

2011 ◽  
pp. 1-19 ◽  
Author(s):  
Arkadiusz Januszewski
Keyword(s):  
Integrated Circuits ◽  
Production Costs ◽  
Cost Calculation ◽  
Activity Based Costing ◽  
False Information ◽  
Direct Production ◽  
Costing System ◽  
The Right ◽  
The Cost ◽  
Selection Of

The selection of the right cost calculation method is of critical importance when it comes to determining the real product profitability (as well as clients and other calculation objects). Traditional cost calculation methods often provide false information. The literature offers many examples of big companies that have given up traditional methods and applied a new method: activity-based costing (ABC). They discovered that many products that are manufactured generate losses and not profits. Managers, based on incorrect calculations, mistakenly believed in the profitability of each product. Turney (1991) reports on an example of an American manufacturer of over 4,000 different integrated circuits. The cost calculation with the allocation of direct production costs as machinery-hour markup demonstrated a profit margin of over 26% for each product. Implementing ABC showed that the production of more than half of the products was not profitable, and having factored in additional sales and management costs (which accounted for about 40% of the total costs), it was as much as over 75%.

scholarly journals Continuous one-flow multi-step synthesis of active pharmaceutical ingredients

2020 ◽  
Vol 5 (7) ◽  
pp. 1186-1197 ◽  
Author(s):  
Victor R. L. J. Bloemendal ◽  
Mathilde A. C. H. Janssen ◽  
Jan C. M. van Hest ◽  
Floris P. J. T. Rutjes
Keyword(s):  
Continuous Flow ◽  
Active Pharmaceutical Ingredients ◽  
Pharmaceutical Ingredients ◽  
Flow Processes ◽  
Selection Of

This review highlights a selection of multistep continuous flow (one-flow) processes leading to the synthesis of active pharmaceutical ingredients (APIs).

Computational Design of Copper Ligands with Controlled Metal Chelating, Pharmacokinetics, and Redox Properties for Alzheimer’s Disease

2020 ◽  
pp. 1-15
Author(s):  
Diego Chaparro ◽  
Areli Flores-Gaspar ◽  
Jorge Alí-Torres
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Density Functional ◽  
Computational Design ◽  
Redox Properties ◽  
Drug Candidates ◽  
Metal Chelating ◽  
Structure Search ◽  
Copper Ligands ◽  
Selection Of

Background: Redox active metal cations, such as Cu2 +, have been related to induce amyloid plaques formation and oxidative stress, which are two of the key events in the development of Alzheimer’s disease (AD) and others metal promoted neurodegenerative diseases. In these oxidative events, standard reduction potential (SRP) is an important property especially relevant in the reactive oxygen species formation. Objective: The SRP is not usually considered for the selection of drug candidates in anti-AD treatments. In this work, we present a computational protocol for the selection of multifunctional ligands with suitable metal chelating, pharmacokinetics, and redox properties. Methods: The filtering process is based on quantum chemical calculations and the use of in silico tools. Calculations of SRP were performed by using the M06-2X density functional and the isodesmic approach. Then, a virtual screening technique (VS) was used for similar structure search. Results: Protocol application allowed the assessment of chelating, drug likeness, and redox properties of copper ligands. Those molecules showing the best features were selected as molecular scaffolds for a VS procedure in order to obtain related compounds. After applying this process, we present a list of candidates with suitable properties to prevent the redox reactions mediated by copper(II) ion. Conclusion: The protocol incorporates SRP in the filtering stage and can be effectively used to obtain a set of potential drug candidates for AD treatments.

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