scholarly journals Cell-Based Therapy Manufacturing in Stirred Suspension Bioreactor: Thoughts for cGMP Compliance

2020 ◽  
Vol 8 ◽  
Author(s):  
Suman C. Nath ◽  
Lane Harper ◽  
Derrick E. Rancourt
Keyword(s):  
Manufacturing Systems ◽  
Cost Effective ◽  
Storage Conditions ◽  
Age Related Macular Degeneration ◽  
Cell Processing ◽  
Cell Based Therapy ◽  
Current Cell ◽  
Cell Manufacturing ◽  
Age Related ◽  
Multi Stage

Cell-based therapy (CBT) is attracting much attention to treat incurable diseases. In recent years, several clinical trials have been conducted using human pluripotent stem cells (hPSCs), and other potential therapeutic cells. Various private- and government-funded organizations are investing in finding permanent cures for diseases that are difficult or expensive to treat over a lifespan, such as age-related macular degeneration, Parkinson’s disease, or diabetes, etc. Clinical-grade cell manufacturing requiring current good manufacturing practices (cGMP) has therefore become an important issue to make safe and effective CBT products. Current cell production practices are adopted from conventional antibody or protein production in the pharmaceutical industry, wherein cells are used as a vector to produce the desired products. With CBT, however, the “cells are the final products” and sensitive to physico- chemical parameters and storage conditions anywhere between isolation and patient administration. In addition, the manufacturing of cellular products involves multi-stage processing, including cell isolation, genetic modification, PSC derivation, expansion, differentiation, purification, characterization, cryopreservation, etc. Posing a high risk of product contamination, these can be time- and cost- prohibitive due to maintenance of cGMP. The growing demand of CBT needs integrated manufacturing systems that can provide a more simple and cost-effective platform. Here, we discuss the current methods and limitations of CBT, based upon experience with biologics production. We review current cell manufacturing integration, automation and provide an overview of some important considerations and best cGMP practices. Finally, we propose how multi-stage cell processing can be integrated into a single bioreactor, in order to develop streamlined cGMP-compliant cell processing systems.

Cell-based therapy for ocular disorders: A promising frontier

2021 ◽  
Vol 16 ◽  
Author(s):  
Milad Ahani-Nahayati ◽  
Vahid Niazi ◽  
Alireza Moradi ◽  
Bahareh Pourjabbar ◽  
Reza Roozafzoon ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wide Spectrum ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Ocular Tissue ◽  
Ocular Diseases ◽  
Cell Based Therapy ◽  
Age Related ◽  
Ocular Disorders

: As the ocular disorders causing long-term blindness or optical abnormalities of the ocular tissue affect the quality of life of patients to a large extent, awareness of their corresponding pathogenesis and the earlier detection and treatment need more consideration. Though current therapeutics result in desirable outcomes, they do not offer an inclusive solution for development of visual impairment to blindness. Accordingly, stem cells, because of their particular competencies, have gained extensive attention for application in regenerative medicine of ocular diseases. In the last decades, a wide spectrum of stem cells surrounding mesenchymal stem/stromal cells (MSC), neural stem cells (NSCs), and embryonic/induced pluripotent stem cells (ESCs/iPSCs) accompanied by Müller glia, ciliary epithelia-derived stem cells, and retinal pigment epithelial (RPE) stem cells have been widely investigated to report their safety and efficacy in preclinical models and also human subjects. In this regard, in the first interventions, RPE cell suspensions were successfully utilized to ameliorate visual defects of the patients suffering from age-related macular degeneration (AMD) after subretinal transplantation. Herein, we will explain the pathogenesis of ocular diseases and highlight the novel discoveries and recent findings in the context of stem cell-based therapies in these disorders, focusing on the in vivo reports published during the last decade.

scholarly journals Perspectives of Stem Cell–Based Therapy for Age-Related Retinal Degenerative Diseases

2017 ◽  
Vol 26 (9) ◽  
pp. 1538-1541 ◽  
Author(s):  
Vladimir Holan ◽  
Barbora Hermankova ◽  
Jan Kossl
Keyword(s):  
Stem Cell ◽  
Treatment Protocol ◽  
The Elderly ◽  
Age Related Macular Degeneration ◽  
Degenerative Diseases ◽  
Cell Type ◽  
Retinal Cells ◽  
Cell Based Therapy ◽  
Age Related ◽  
Retinal Degenerative Diseases

Retinal degenerative diseases, which include age-related macular degeneration, retinitis pigmentosa, diabetic retinopathy, and glaucoma, mostly affect the elderly population and are the most common cause of decreased quality of vision or even blindness. So far, there is no satisfactory treatment protocol to prevent, stop, or cure these disorders. A great hope and promise for patients suffering from retinal diseases is represented by stem cell–based therapy that could replace diseased or missing retinal cells and support regeneration. In this respect, mesenchymal stem cells (MSCs) that can be obtained from the particular patient and used as autologous cells have turned out to be a promising stem cell type for treatment. Here we show that MSCs can differentiate into cells expressing markers of retinal cells, inhibit production of pro-inflammatory cytokines by retinal tissue, and produce a number of growth and neuroprotective factors for retinal regeneration. All of these properties make MSCs a prospective cell type for cell-based therapy of age-related retinal degenerative diseases.

Dietary Approaches to Prevent Age Related Macular Degeneration:A Review

2016 ◽  
Vol 53 (2) ◽  
pp. 241
Author(s):  
Kapur Punam ◽  
Pathak Ashok ◽  
Suri Manjula
Keyword(s):  
Fatty Acids ◽  
Dietary Pattern ◽  
Cost Effective ◽  
Nutritional Supplementation ◽  
Age Related Macular Degeneration ◽  
Dietary Carbohydrates ◽  
Omega 3 ◽  
Age Related ◽  
Disease Study

Age Related Macular Degeneration (ARMD) is the leading cause of irreversible blindness in older adults which has no cure and limited therapeutic options. ARMD may become an increasing concern in the developing countries like India as a result of socio-economic and dietary changes that accompany the economic development1. Diet is potentially one of the most cost effective strategies to prevent the development of end stage condition of ARMD. This review describes the current literature on the role of quality of diet and nutritional supplementation in prevention of advanced ARMD. Various researchers have explored the association between diet, nutrient intake and advanced ARMD. In the Age Related Eye Disease Study (AREDS), use of a daily antioxidant supplementation reduced the rate of progression from intermediate to advanced ARMD by 25% over a period of 5 years and resulted in a 19% reduction in the risk of moderate visual loss<sup>2</sup>. A high dietary fat intake was reported to be associated with a higher incidence of late ARMD whereas higher intakes of fish or n-3 fatty acids were associated with lower incidence of ARMD<sup>3</sup>. Chiu et al. reported that quality of dietary carbohydrates influences the risk of ARMD<sup>4</sup>. But at present, research shows insufficient evidence to recommend dietary modifications and nutritional supplementation in ARMD. Therefore to summarize, the temporal relationship of the diet to advanced ARMD, is a function of the quality of diet. Observational studies suggest that increased dietary intake of omega-3 fatty acids, macular carotenoids, antioxidants and oriental dietary pattern reduces the risk of ARMD whereas, poor dietary carbohydrates quality (as defined by dietary glycemic index) and western dietary pattern may increase the risk of ARMD.

scholarly journals A new method for pharmaceutical compounding and storage of anti-VEGF biologics for intravitreal use in silicone oil-free prefilled plastic syringes

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Heidrun Elisabeth Lode ◽  
Torleif Tollefsrud Gjølberg ◽  
Stian Foss ◽  
Magne Sand Sivertsen ◽  
Jørgen Brustugun ◽  
...  
Keyword(s):  
Silicone Oil ◽  
Drug Stability ◽  
Vitreous Body ◽  
Cost Effective ◽  
Age Related Macular Degeneration ◽  
Intravitreal Injections ◽  
Term Therapy ◽  
Anti Vegf ◽  
Age Related ◽  
And Storage

AbstractIntravitreal injections of antibody-based biologics targeting vascular endothelial growth factor (VEGF) are highly effective and have markedly decreased the risk of visual impairment associated with prevalent retinal diseases, such as neovascular age-related macular degeneration and diabetes macular oedema. The diseases are chronic in their nature, and most patients need long-term therapy to suppress disease activity. We previously reported a compounding method for repackaging and storage of aflibercept (Eylea), a commonly used anti-VEGF biologic, in silicone oil-coated plastic syringes without compromising drug stability or activity. In addition to improving safety and time spent per patient, compounding of anti-VEGF biologics enables single-dose vials to be split into multiple syringes, thereby considerably reducing waste and drug expenses. However, symptomatic silicone oil droplets may deposit in the eye’s vitreous body after repetitive injections. To fully avoid this complication, we here report on a novel pharmaceutical compounding method using silicone oil-free syringes and a 33 G × 9 mm Low Dead Space Needle hub injection needle. We evaluate the method for three anti-VEGF biologics commonly used in ophthalmology: aflibercept, ranibizumab (Lucentis) and bevacizumab (Avastin). Our results show that compounding and storage for one week does not compromise the functional activity of the biologics and allows for safe and cost-effective compounding of anti-VEGF biologics for intravitreal injections in prefilled silicone oil-free syringes.

scholarly journals A longitudinal study to assess the frequency and cost of antivascular endothelial therapy, and inequalities in access, in England between 2005 and 2015

BMJ Open ◽  
2017 ◽  
Vol 7 (10) ◽  
pp. e018289 ◽  
Author(s):  
William Hollingworth ◽  
Tim Jones ◽  
Barnaby C Reeves ◽  
Tunde Peto
Keyword(s):  
Longitudinal Study ◽  
Diabetic Macular Oedema ◽  
Cost Effective ◽  
Age Related Macular Degeneration ◽  
Geographical Variations ◽  
Anti Vegf ◽  
Age Related ◽  
Eye Disorders ◽  
Effective Care ◽  
Endothelial Growth Factor

ObjectivesHigh-cost antivascular endothelial growth factor (anti-VEGF) medicines for eye disorders challenge ophthalmologists and policymakers to provide fair access for patients while minimising costs. We describe the growth in the use and costs of these medicines and measure inequalities in access.DesignLongitudinal study using Hospital Episode Statistics (2005/2006 to 2014/2015) and hospital prescribing cost reports (2008/2009 to 2015/2016). We used Poisson regression to estimate standardised rates and explore temporal and geographical variations.SettingNational Health Service (NHS) care in England.PopulationPatients receiving anti-VEGF injections for age-related macular degeneration, diabetic macular oedema and other eye disorders.InterventionsHigher-cost drugs (ranibizumab or aflibercept) recommended by the National Institute for Health and Care Excellence or lower-cost drug (bevacizumab) not licensed for eye disorders.Main outcome measuresNational procedure rates and variation between and within clinical commissioning groups (CCGs). Cost of ranibizumab and aflibercept prescribing.ResultsInjection procedures increased by 215% between 2010/2011 and 2014/2015. In 2014/2015 there were 388 031 procedures (714 per 100 000). There is no evidence that the dramatic growth in rates is slowing down. Since 2010/2011 the estimated cost of ranibizumab and aflibercept increased by 247% to £447 million in 2015/2016, equivalent to the entire annual budget of a CCG. There are large inequalities in access; in 2014/2015 procedure rates in a ‘high use’ CCG were 9.08 times higher than in a ‘low use’ CCG. In the South-West of England there was twofold variation in injections per patient per year (range 2.9 to 5.9).ConclusionsThe high and rising cost of anti-VEGF therapy affects the ability of the NHS to provide care for other patients. Current regulations encourage the increasing use of ranibizumab and aflibercept rather than bevacizumab, which evidence suggests is more cost-effective. NHS patients in England do not have equal access to the most cost-effective care.

scholarly journals Bevacizumab vs. Ranibizumab in Preserving or Improving Vision in Patients with Wet, Age-Related Macular Degeneration: A cost-effectiveness Review

2012 ◽  
Vol 4 ◽  
pp. CMT.S7439
Author(s):  
Chukwuemeka C. Nwanze ◽  
Abumere Akinwale ◽  
Ron A. Adelman
Keyword(s):  
Cost Effectiveness ◽  
Adverse Events ◽  
Macular Degeneration ◽  
Treatment Protocol ◽  
Cost Effective ◽  
Treatment Costs ◽  
Age Related Macular Degeneration ◽  
Insurance Company ◽  
Age Related ◽  
The Cost

Objective To evaluate the cost-effectiveness of monthly and as-needed dosing protocols using ranibizumab or bevacizumab for the treatment of neovascular age-related macular degeneration (AMD), when the treatment costs of severe ocular and systemic adverse events are considered. Methods A Markov model was developed to assess the cost effectiveness of each of the following protocols: monthly ranibizumab, monthly bevacizumab, as-needed ranibizumab and as-needed bevacizumab. Direct costs and utilities were assessed from the perspective of a third-party payer or an insurance company. Cost effectiveness was evaluated in 2011 US dollars per quality-adjusted life year (QALY). Results Considering the treatment costs of severe medical and ocular adverse events, the cost effectiveness of each protocol is as follows: monthly ranibizumab $63,333/QALY, ranibizumab as needed $18,571/QALY, bevacizumab monthly $2,676/QALY and bevacizumab as needed $3,333/QALY Sensitivity analysis of the treatment costs of medical and ocular adverse events demonstrated minimal impact on relative cost-effectiveness. Conclusion At current prices, monthly bevacizumab is the most cost-effective anti-VEGF AMD treatment protocol. Ranibizumab is as cost effective as bevacizumab at a maximum price of $158 per dose.

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