scholarly journals Manufacturing Readiness Assessment for Evaluation of the Microarray Patch Industry: An Exploration of Barriers to Full-Scale Manufacturing

2021 ◽  
Author(s):  
Ben Creelman ◽  
Collrane Frivold ◽  
Sierra Jessup ◽  
Gene Saxon ◽  
Courtney Jarrahian
Keyword(s):  
Scale Up ◽  
Full Scale ◽  
Drying Methods ◽  
Product Lines ◽  
Readiness Assessment ◽  
Contract Manufacturing ◽  
Production Methods ◽  
Manufacturing Organizations ◽  
Manufacturing Readiness

Abstract Microarray patch (MAP) technology is a promising new delivery technology for vaccines and pharmaceuticals. Yet due to several differing and novel production methods, barriers to full-scale manufacturing exist. PATH conducted a manufacturing readiness assessment and follow-up interviews to identify both the current manufacturing readiness of the industry as well as how readiness varies by developer type and MAP type. Follow-up interviews identified barriers the industry faces in reaching full manufacturing readiness, including the perceived regulatory and investment risk of manufacturing MAPs at scale due to quality requirements and control methods, uncertain sterility requirements, lack of standard production methods (especially around dissolvable MAP drying methods), and the lack of available contract manufacturing organizations with MAP manufacturing capabilities. A Regulatory Working Group has been established to identify and address critical quality issues specific to MAP manufacturing with the aim of providing developers insight into what will be expected for MAP product approvals. Standardizing MAP production equipment and automatic, visual quality control could reduce the overall risk to developers and contract manufacturing organizations in pursuing pilot-scale manufacturing capabilities and ultimately lower barriers to the scale-up of full medical MAP product lines.

scholarly journals Manufacturing readiness assessment for evaluation of the microneedle array patch industry: an exploration of barriers to full-scale manufacturing

2021 ◽  
Author(s):  
Ben Creelman ◽  
Collrane Frivold ◽  
Sierra Jessup ◽  
Gene Saxon ◽  
Courtney Jarrahian
Keyword(s):  
Full Scale ◽  
Investment Risk ◽  
Microneedle Array ◽  
Product Lines ◽  
Readiness Assessment ◽  
Contract Manufacturing ◽  
Production Methods ◽  
Manufacturing Organizations ◽  
Manufacturing Readiness

AbstractMicroneedle array patch (MAP) technology is a promising new delivery technology for vaccines and pharmaceuticals, yet due to several differing and novel production methods, barriers to full-scale manufacturing exist. PATH conducted a manufacturing readiness assessment and follow-up interviews to identify both the current manufacturing readiness of the industry as well as how readiness varies by developer type and MAP type. Follow-up interviews identified barriers the industry faces in reaching full manufacturing readiness, including the perceived regulatory and investment risk of manufacturing MAPs at scale due to quality requirements and control methods, uncertain sterility requirements, lack of standard production methods (especially around dissolvable MAP drying methods), and the lack of available contract manufacturing organizations with MAP manufacturing capabilities. A Regulatory Working Group has been established to identify and address critical quality issues specific to MAP manufacturing with the aim of providing developers insight into what will be expected for MAP product approvals. Standardizing MAP production equipment and automatic, visual quality control could reduce the overall investment risk to developers and contract manufacturing organizations in pursuing pilot-scale manufacturing capabilities and ultimately lower barriers to the scale-up of full medical MAP product lines. Graphical abstract

scholarly journals A 17 year experience of attrition from care among HIV infected children in Nnewi South-East Nigeria

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chinyere Ukamaka Onubogu ◽  
Ebelechuku Francesca Ugochukwu
Keyword(s):  
Financial Constraints ◽  
Scale Up ◽  
Linkage To Care ◽  
Late Presentation ◽  
Young Age ◽  
Attrition Rate ◽  
Bivariate Analysis ◽  
Female Ratio ◽  
Art Initiation

Abstract Background A large number of HIV-infected children continue to die despite reported scale-up of paediatric HIV services. Aim The trend in attrition among children enrolled in an anti-retroviral therapy (ART) programme was evaluated. Methods This was a retrospective review of children enrolled into NAUTH ART programme between 2003 and 2019. Results 1114 children < 15 years at enrolment were studied. The male: female ratio was 1:1 while median age at enrolment was 4.3 years. About two-thirds had WHO stage 3 or 4 disease at enrolment. The rate of loss to follow-up (LTFU) and death were 41.0 and 8.4%, respectively, with overall attrition incidence of 108/1000PY. Despite the downward trend, spikes occurred among those enrolled in 2008 to 2011 and in 2017. The trend in 6-, 12-, 24- and 36-months attrition varied similarly with overall rates being 20.4, 27.7, 34.3 and 37.3%, respectively. Among those on ART, > 50% of attrition was recorded within 6 months of care. Advanced WHO stage, young age, non-initiation on ART or period of enrolment (P <  0.001), and caregiver (p = 0.026) were associated with attrition in bivariate analysis. Apart from caregiver category, these factors remained significant in multivariate analysis. Most LTFU could not be reached on phone. Among those contacted, common reasons for being lost to follow-up were financial constraints, caregiver loss, claim to divine healing, family disharmony/child custody issues and relocation of family/child. Conclusion/recommendation Attrition rate was high and was mostly due to LTFU. Predictors of attrition were late presentation, young age, delay in ART initiation and financial constraints. Efforts should be intensified at early diagnosis, linkage to care and implementation of “test and treat” strategy. Innovative child centered approaches should be adopted to enable the HIV-infected children remain in care despite challenges which can truncate treatment.

scholarly journals Complete biosynthesis of a sulfated chondroitin in Escherichia coli

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Abinaya Badri ◽  
Asher Williams ◽  
Adeola Awofiranye ◽  
Payel Datta ◽  
Ke Xia ◽  
...  
Keyword(s):  
Chondroitin Sulfate ◽  
Scale Up ◽  
Production Methods ◽  
E Coli ◽  
Microbial Cell Factories ◽  
Cell Factories ◽  
Microbial Product ◽  
Dry Cell Weight ◽  
One Step ◽  
Dry Cell

AbstractSulfated glycosaminoglycans (GAGs) are a class of important biologics that are currently manufactured by extraction from animal tissues. Although such methods are unsustainable and prone to contamination, animal-free production methods have not emerged as competitive alternatives due to complexities in scale-up, requirement for multiple stages and cost of co-factors and purification. Here, we demonstrate the development of single microbial cell factories capable of complete, one-step biosynthesis of chondroitin sulfate (CS), a type of GAG. We engineer E. coli to produce all three required components for CS production–chondroitin, sulfate donor and sulfotransferase. In this way, we achieve intracellular CS production of ~27 μg/g dry-cell-weight with about 96% of the disaccharides sulfated. We further explore four different factors that can affect the sulfation levels of this microbial product. Overall, this is a demonstration of simple, one-step microbial production of a sulfated GAG and marks an important step in the animal-free production of these molecules.

Follow-up of a full-scale network assembly

1984 ◽  
Vol 6 (2) ◽  
pp. 102-113 ◽  
Author(s):  
David W. Trimble ◽  
Jodie Kliman ◽  
Albert Villapiano ◽  
William Beckett
Keyword(s):  
Full Scale ◽  
Scale Network

Benchmarking of Truss Spar Vortex Induced Motions Derived From CFD With Experiments

2005 ◽  
Author(s):  
John Halkyard ◽  
Senu Sirnivas ◽  
Samuel Holmes ◽  
Yiannis Constantinides ◽  
Owen H. Oakley ◽  
...  
Keyword(s):  
Scale Up ◽  
Vertical Cylinder ◽  
Reynolds Numbers ◽  
Full Scale ◽  
Scale Model ◽  
Current Direction ◽  
Test Results ◽  
Helical Strakes ◽  
Truss Spar ◽  
Scale Data

Floating spar platforms are widely used in the Gulf of Mexico for oil production. The spar is a bluff, vertical cylinder which is subject to Vortex Induced Motions (VIM) when current velocities exceed a few knots. All spars to date have been constructed with helical strakes to mitigate VIM in order to reduce the loads on the risers and moorings. Model tests have indicated that the effectiveness of these strakes is influenced greatly by details of their design, by appurtenances placed on the outside of the hull and by current direction. At this time there is limited full scale data to validate the model test results and little understanding of the mechanisms at work in strake performance. The authors have been investigating the use of CFD as a means for predicting full scale VIM performance and for facilitating the design of spars for reduced VIM. This paper reports on the results of a study to benchmark the CFD results for a truss spar with a set of model experiments carried out in a towing tank. The focus is on the effect of current direction, reduced velocity and strake pitch on the VIM response. The tests were carried out on a 1:40 scale model of an actual truss spar design, and all computations were carried out at model scale. Future study will consider the effect of external appurtenances on the hull and scale-up to full scale Reynolds’ numbers on the results.

Intelligence at Six Years in Relation to Neonatal Bilirubin Level: Follow-up of The National Institute of Child Health and Human Development Clinical Trial of Phototherapy

PEDIATRICS ◽  
1991 ◽  
Vol 87 (6) ◽  
pp. 797-805
Author(s):  
Peter C. Scheidt ◽  
Barry I. Graubard ◽  
Howard J. Hoffman ◽  
Dolores A. Bryla ◽  
Karin B. Nelson ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Birth Weight ◽  
Child Health ◽  
Human Development ◽  
Bilirubin Level ◽  
Controlled Trial ◽  
Full Scale ◽  
The Central Nervous System ◽  
Bilirubin Toxicity

Results of the National Institute of Child Health and Human Development Randomized Controlled Trial of Phototherapy were examined for the relationship of neonatal bilirubin level to neurological and developmental outcome at 6-year follow-up. This analysis focused on 224 control children with birth weight of less than 2000 g. Bilirubin levels were maintained below previously specified levels by the use of exchange transfusion only (24%). Rates of cerebral palsy were not significantly higher for children with elevated maximum bilirubin level than for those whose level remained low. No association was evident between maximum bilirubin level and IQ (Full Scale, Verbal, or Performance) by simple correlation analysis (r = -.087, P = .2 for Full Scale) or by multiple linear regression adjusting for factors that covary with IQ (β = -.15, P = .58). IQ was not associated with mean bilirubin level, time and duration of exposure to bilirubin, or measures of bilirubin-albumin binding. Thus, over the range of bilirubin levels permitted in this clinical trial, there was no evidence of bilirubin toxicity to the central nervous system. Measures used to control the level of bilirubin in low birth weight neonates appear to prevent effectively the risk of bilirubin-induced neurotoxicity.

Model-based evaluation of a new upgrading concept for N-removal

2002 ◽  
Vol 45 (6) ◽  
pp. 169-176 ◽  
Author(s):  
S. Salem ◽  
D. Berends ◽  
J.J. Heijnen ◽  
M.C.M. van Loosdrecht
Keyword(s):  
Mathematical Modelling ◽  
Scale Up ◽  
Treatment Plant ◽  
Ammonia Concentration ◽  
Pilot Scale ◽  
Full Scale ◽  
Model Based ◽  
N Removal ◽  
Quantitative Basis ◽  
Treatment Concepts

Mathematical modelling is considered a time and cost-saving tool for evaluation of new wastewater treatment concepts. Modelling can help to bridge the gap between lab and full-scale application. Bio-augmentation can be used to obtain nitrification in activated sludge systems with a limited aerobic sludge retention time. In the present study the potential for augmenting the endogenous nitrifying population is evaluated. Implementing a nitrification reactor in the sludge return line fed with sludge liquor with a high ammonia concentration leads to augmentation of the native nitrifying population. Since the behaviour of nitrifiers is relatively well known, a choice was made to evaluate this new concept mainly based on mathematical modelling. As an example an existing treatment plant (wwtp Walcheren, The Netherlands) that needed to be upgraded was used. A mathematical model, based on the TUDP model and implemented in AQUASIM was developed and used to evaluate the potential of this bioaugmentation in the return sludge line. A comparison was made between bio-augmentation and extending the existing aeration basins and anoxic tanks. The results of both modified systems were compared to give a quantitative basis for evaluation of benefits gained from such a system. If the plant is upgraded by conventional extension it needs an increase in volume of about 225%; using a bioaugmentation in the return sludge line the total volume of the tanks needs to be expanded by only 75% (including the side stream tanks). Based on the modelling results a decision was made to implement the bioaugmentation concept at full scale without further pilot scale testing, thereby strongly decreasing the scale-up period for this process.

scholarly journals Strengthened capacity of India´s bedaquiline Conditional Access Programme for introducing new drugs and regimens

2020 ◽  
Vol 24 (10) ◽  
pp. 1067-1072
Author(s):  
K. S. Sachdeva ◽  
N. Arora ◽  
R. Solanki ◽  
R. Singla ◽  
R. Sarin ◽  
...  
Keyword(s):  
Scale Up ◽  
New Drugs ◽  
Serious Adverse Events ◽  
Conditional Access ◽  
Conversion Rates ◽  
Drug Safety Monitoring ◽  
Access Programme ◽  
Pre Treatment ◽  
Culture Conversion

BACKGROUND: Addressing TB in India is critical to meeting global targets. With the scale-up of diagnostic networks and the availability of new TB drugs, India had the opportunity to improve the detection and treatment outcomes in drug-resistant TB (DR-TB).OBJECTIVE: To document how the introduction of new drugs and regimens is helping India improve the care of DR-TB patients.DESIGN: In 2016, India´s National TB Programme (NTP) introduced bedaquiline (BDQ) under a Conditional Access Programme (BDQ-CAP) at six sites after providing extensive training and strengthening laboratory testing, pre-treatment evaluation, active drug safety monitoring and management (aDSM) and follow-up systems.RESULTS: An interim analysis reflected earlier and better culture conversion rates: 83% of the 620 patients converted within a median time of 60 days. However, 248 serious adverse events were reported, including 73 deaths (12%) and 100 cardiotoxicity events (16.3%). Encouraged by the evidence of safety and efficacy of BDQ, the NTP took steps to systematically expand its access to cover the entire population by 2018.CONCLUSION: The cautious yet focused approach used to introduce BDQ under BDQ-CAP paved the way for the rapid introduction of delamanid, as well as the shorter treatment regimen and the all-oral regimen for DR-TB.

Nonsyndromic craniosynostosis in Vietnam: initial surgical outcomes of subspecialty mentorship

2021 ◽  
pp. 1-8
Author(s):  
Dang Do Thanh Can ◽  
Jacob R. Lepard ◽  
Nguyen Minh Anh ◽  
Pham Anh Tuan ◽  
Tran Diep Tuan ◽  
...  
Keyword(s):  
Scale Up ◽  
Unmet Need ◽  
Case Series ◽  
Surgical Care ◽  
Cranial Vault ◽  
Female Ratio ◽  
Estimated Blood Loss ◽  
Common Diagnosis ◽  
Cranial Vault Remodeling

OBJECTIVE There is a global deficit of pediatric neurosurgical care, and the epidemiology and overall surgical care for craniosynostosis is not well characterized at the global level. This study serves to highlight the details and early surgical results of a neurosurgical educational partnership and subsequent local scale-up in craniosynostosis correction. METHODS A prospective case series was performed with inclusion of all patients undergoing correction of craniosynostosis by extensive cranial vault remodeling at Children’s Hospital 2, Ho Chi Minh City, Vietnam, between January 1, 2015, and December 31, 2019. RESULTS A total of 76 patients were included in the study. The group was predominantly male, with a male-to-female ratio of 3.3:1. Sagittal synostosis was the most common diagnosis (50%, 38/76), followed by unilateral coronal (11.8%, 9/76), bicoronal (11.8%, 9/76), and metopic (7.9%, 6/76). The most common corrective technique was anterior cranial vault remodeling (30/76, 39.4%) followed by frontoorbital advancement (34.2%, 26/76). The overall mean operative time was 205.8 ± 38.6 minutes, and the estimated blood loss was 176 ± 89.4 mL. Eleven procedures were complicated by intraoperative durotomy (14.5%, 11/76) without any damage of dural venous sinuses or brain tissue. Postoperatively, 4 procedures were complicated by wound infection (5.3%, 4/76), all of which required operative wound debridement. There were no neurological complications or postoperative deaths. One patient required repeat reconstruction due to delayed intracranial hypertension. There was no loss to follow-up. All patients were followed at outpatient clinic, and the mean follow-up period was 32.3 ± 18.8 months postoperatively. CONCLUSIONS Surgical care for pediatric craniosynostosis can be taught and sustained in the setting of collegial educational partnerships with early capability for high surgical volume and safe outcomes. In the setting of the significant deficit in worldwide pediatric neurosurgical care, this study provides an example of the feasibility of such relationships in addressing this unmet need.

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