Contract development and manufacturing organization selection: critical considerations that can make or break your cell and gene therapy development.

BACKGROUND AIMS: With the increase in cell and gene therapy (CGT) clinical trials in recent years has come a subsequent increase in the number of contract development and manufacturing organizations (CDMOs). Successful transition from development and early-phase clinical trials to commercialization of a CGT product often depends on selecting the best-suited CDMO. However, many CGT companies are small biotech companies that lack expertise in the field or do not have experience selecting and transferring a process to a CDMO. METHODS: Given the interest in this topic, a roundtable with CGT developers and CDMO members at the 2023 annual meeting of the International Society of Cell and Gene Therapy Paris discussed these critical aspects of product development, including technical expertise, risk sharing and timing of partnerships. RESULTS AND CONCLUSIONS: Here, we'll analyze the considerations discussed by the panel and elaborate on other factors crucial for CGT development.

Moral justification for the use of 'add-ons' in assisted reproductive technology: experts' views and experiences.

RESEARCH QUESTION: What factors do assisted reproductive terchnology (ART) providers take into account when they make decisions about offering 'add-ons'? DESIGN: A qualitative analysis of interviews with 31 ART professionals, focusing on their views and experiences in relation to add-ons, including the factors that are considered when doctors make decisions about their use. RESULTS: The participants reported that a range of considerations are taken into account when it comes to justifying the use of a particular add-on in a given circumstance, including the likelihood of benefit and harm, patients' perceived psychological needs and preferences, and organizational expectations. Importantly, patient preferences, psychological factors and low risk of harm appear to be stronger motivations than increasing the likelihood of a live birth or the desire to innovate. CONCLUSIONS: These findings suggest that it cannot be taken for granted that add-ons and innovation are closely linked. One possible response to this would be regulatory reform; for example, only allowing 'unproven' add-ons to be used in the context of formal scientific evaluation. Alternatively, it could be made clear that add-ons that are not undergoing formal evaluation have more in common with other therapies lacking a clear evidence base, such as complementary and alternative medicines, than with conventional medical practice. Practices in relation to add-ons may also require a focus on the responsibilities of corporations, and the standards applying to purveyors of consumer goods and services.

Medicine in the marketplace: clinician and patient views on commercial influences on assisted reproductive technology.

RESEARCH QUESTION: What are the views and experiences of patient and expert stakeholders on the positive and negative impacts of commercial influences on the provision of assisted reproductive technology (ART) services, and what are their suggestions for governance reforms? DESIGN: Semi-structured interviews were conducted with 31 ART industry experts from across Australia and New Zealand and 25 patients undergoing ART from metropolitan and regional Australia, between September 2020 and September 2021. Data were analysed using thematic analysis. RESULTS: Expert and patient participants considered that commercial forces influence the provision of ART in a number of positive ways - increasing sustainability, ensuring consistency in standards and providing patients with greater choice. Participants also considered commercial forces to have a number of negative impacts, including increased costs to government and patients; the excessive use of interventions that lack sufficient evidence to be considered part of standard care; inadequately informed consent (particularly with regard to financial information); and threats to patient-provider relationships and patient-centred care. Participants varied in whether they believed that professional self-regulation is sufficient. While recognizing the benefits of commercial investment in healthcare, many considered that regulatory reforms, as well as organizational cultural initiatives, are needed as means to ensure the primacy of patient well-being. CONCLUSIONS: The views expressed in this study should be systematically and critically examined to derive insights into how best to govern ART. These insights may also inform the design and delivery of other types of healthcare that are provided in the private sector.

Challenges and opportunities in commercializing whole-cell bioreporters in environmental application.

Since the initial introduction of whole-cell bioreporters (WCBs) nearly 30 years ago, their high sensitivity, selectivity, and suitability for on-site detection have rendered them highly promising for environmental monitoring, medical diagnosis, food safety, biomanufacturing, and other fields. Especially in the environmental field, the technology provides a fast and efficient way to assess the bioavailability of pollutants in the environment. Despite these advantages, the technology has not been commercialized. This lack of commercialization is confusing, given the broad application prospects of WCBs. Over the years, numerous research papers have focused primarily on enhancing the sensitivity and selectivity of WCBs, with little attention paid to their wider commercial applications. So far, there is no a critical review has been published yet on this topic. Therefore, in this article we critically reviewed the research progress of WCBs over the past three decades, assessing the performance and limitations of current systems to understand the barriers to commercial deployment. By identifying these obstacles, this article provided researchers and industry stakeholders with deeper insights into the challenges hindering market entry and inspire further research toward overcoming these barriers, thereby facilitating the commercialization of WCBs as a promising technology for environmental monitoring.

Can we eliminate the primate pet trade in the United States?

International laws and conventions have gone a long way in reducing the number of wild primates entering the United States of America (US) for the pet trade. However, breeding primates for sale to private owners in the United States continues, and individual states present a bewildering array of laws and regulations on the holding of primates as pets. As primatologists we can act to decrease the demand for primate pets by (1) speaking out on the inappropriate use of primates in mass media and especially in social media; (2) not posing in photographs in close proximity to primates; (3) continuing to educate about why primates do not make good pets; and (4) contributing to the science that underlies state and federal legislation with the goal of eliminating captive breeding of primates for the pet trade. We encourage primatologists and others in related fields to be cognizant of the persistent commercialization of primates and be willing to take action to deter it.

Addressing the consequences of the corporatization of reproductive medicine.

In Australia and the UK, commercialization and corporatization of assisted reproductive technologies have created a marketplace of clinics, products, and services. While this has arguably increased choice for patients, 'choice', shaped by commercial imperatives may not mean better-quality care. At present, regulation of clinics (including clinic-corporations) and clinicians focuses on the doctor-patient dyad and the clinic-consumer dyad. Scant attention has been paid to the conflicts between the clinic-corporation's duty to its shareholders and investors, the medical profession's duty to the corporations within which they practice, and the obligations of both clinicians and corporations to patients and to health systems. Frameworks of regulation based in corporate governance and business ethics, such as stakeholder models and 'corporate social responsibility', have well-recognized limits and may not translate well into healthcare settings. This means that existing governance frameworks may not meet the needs of patients or health systems. We argue for the development of novel regulatory approaches that more explicitly characterize the obligations that both corporations and clinicians in corporate environments have to patients and to society, and that promote fulfilment of these obligations. We consider mechanisms for application in the multi-jurisdictional setting of Australia, and the single jurisdictional settings of the UK.

Harnessing the action mechanisms of microbial endophytes for enhancing plant performance and stress tolerance: current understanding and future perspectives.

Microbial endophytes are microorganisms that reside within plant tissues without causing any harm to their hosts. These microorganisms have been found to confer a range of benefits to plants, including increased growth and stress tolerance. In this review, we summarize the recent advances in our understanding of the mechanisms by which microbial endophytes confer abiotic and biotic stress tolerance to their host plants. Specifically, we focus on the roles of endophytes in enhancing nutrient uptake, modulating plant hormones, producing secondary metabolites, and activating plant defence responses. We also discuss the challenges associated with developing microbial endophyte-based products for commercial use, including product refinement, toxicology analysis, and prototype formulation. Despite these challenges, there is growing interest in the potential applications of microbial endophytes in agriculture and environmental remediation. With further research and development, microbial endophyte-based products have the potential to play a significant role in sustainable agriculture and environmental management.

Application of essential oils as natural biopesticides; recent advances.

There is an urgent need for the development of sustainable and eco-friendly pesticide formulations since common synthetic pesticides result in many adverse effects on human health and the environment. Essential oils (EOs) are a mixture of volatile oils produced as a secondary metabolite in medicinal plants, and show activities against pests, insects, and pathogenic fungi. Their chemical composition is affected by several factors such as plant species or cultivar, geographical origin, environmental conditions, agricultural practices, and extraction method. The growing number of studies related to the herbicidal, insecticidal, acaricidal, nematicidal, and antimicrobial effects of EOs demonstrate their effectiveness and suitability as sustainable and environment-friendly biopesticides. EOs can biodegrade into nontoxic compounds; at the same time, their harmful and detrimental effects on non-target organisms are low. However, few biopesticide formulations based on EOs have been turned into commercial practice upto day. Several challenges including the reduced stability and efficiency of EOs under environmental conditions need to be addressed before EOs are widely applied as commercial biopesticides. This work is an overview of the current research on the application of EOs as biopesticides. Findings of recent studies focusing on the challenges related to the use of EOs as biopesticides are also discussed.

Wafer-scale striped network transistors based on purified semiconducting carbon nanotubes for commercialization.

Highly purified and solution-processed semiconducting carbon nanotubes (s-CNTs) have developed rapidly over the past several decades and are near-commercially available materials that can replace silicon due to its large-area substrate deposition and room-temperature processing compatibility. However, the more s-CNTs are purified, the better their electrical performance, but considerable effort and long centrifugation time are required, which can limit commercialization due to high manufacturing costs. In this work, we therefore fabricated 'striped' CNT network transistor across industry-standard 8 inch wafers. The stripe-structured channel is effective in lowering the manufacturing cost because it can maintain good device performance without requiring high-purity s-CNTs. We evaluated the electrical performances and their uniformity by demonstrating striped CNT network transistors fabricating from various s-CNT solutions (e.g. 99%, 95%, and 90%) in 8 inch wafers. From our results, we concluded that by optimizing the CNT network configurations, CNTs can be sufficiently utilized for commercialization technology even at low semiconducting purity. Our approach can serve as a critical foundation for future low-cost commercial CNT electronics.

Epitomizing biohydrogen production from microbes: Critical challenges vs opportunities.

Hydrogen is a clean and green biofuel choice for the future because it is carbon-free, non-toxic, and has high energy conversion efficiency. In exploiting hydrogen as the main energy, guidelines for implementing the hydrogen economy and roadmaps for the developments of hydrogen technology have been released by several countries. Besides, this review also unveils various hydrogen storage methods and applications of hydrogen in transportation industry. Biohydrogen productions from microbes, namely, fermentative bacteria, photosynthetic bacteria, cyanobacteria, and green microalgae, via biological metabolisms have received significant interests off late due to its sustainability and environmentally friendly potentials. Accordingly, the review is as well outlining the biohydrogen production processes by various microbes. Furthermore, several factors such as light intensity, pH, temperature and addition of supplementary nutrients to enhance the microbial biohydrogen production are highlighted at their respective optimum conditions. Despite the advantages, the amounts of biohydrogen being produced by microbes are still insufficient to be a competitive energy source in the market. In addition, several major obstacles have also directly hampered the commercialization effors of biohydrogen. Thus, this review uncovers the constraints of biohydrogen production from microbes such as microalgae and offers solutions associated with recent strategies to overcome the setbacks via genetic engineering, pretreatments of biomass, and introduction of nanoparticles as well as oxygen scavengers. The opportunities of exploiting microalgae as a suastainable source of biohydrogen production and the plausibility to produce biohydrogen from biowastes are accentuated. Lastly, this review addresses the future perspectives of biological methods to ensure the sustainability and economy viability of biohydrogen production.

Optimistic contributions of plant growth-promoting bacteria for sustainable agriculture and climate stress alleviation.

Global climate change is the major cause of abiotic and biotic stresses that have adverse effects on agricultural productivity to an irreversible level, thus threatening to limit gains in production and imperil sustainable agriculture. These climate change-induced abiotic stresses, especially saline, drought, extreme temperature, and so on affect plant morphological, physiological, biochemical, and metabolic characteristics through various pathways and mechanisms, ultimately hindering plant growth, development, and productivity. However, overuse and other inappropriate uses of agrochemicals are not conducive to the protection of natural resources and the environment, thus hampering sustainable agricultural development. With the vigorous development of modern agriculture, the application of plant growth-promoting bacteria (PGPB) can better ensure sustainable agriculture, due to their ability to improve soil properties and confer stress tolerance in plants. This review deciphered the underlying mechanisms of PGPB involved in enhancing plant stress tolerance and performance under various abiotic and biotic stresses. Moreover, the recent advancements in PGPB inoculation techniques, the commercialization of PGPB-based technology and the current applications of PGPB in sustainable agriculture were extensively discussed. Finally, an outlook on the future directions of microbe-aided agriculture was pointed out. Providing insights into plant-PGPB interactions under biotic and abiotic stresses and offering evidence and strategies for PGPB better commercialization and implementation can inspire the development of innovative solutions exploiting PGPB under climatological conditions.

Antitrust as a Guardrail for Socially Responsible Neurotechnology Design.

The neurotechnology sector is likely to develop under pressure towards commercialized, nonmedical products and may also undergo market consolidation. This possibility raises ethical, social, and policy concerns about the future responsibility of neurotechnology innovators and companies for high-consequence design decisions. Present-day internet technology firms furnish an instructive example of the problems that arise when providers of communicative technologies become too big for accountability. As a guardrail against the emergence of similar problems, concerned neurotechnologists may wish to draw inspiration from antitrust law and direct efforts, where appropriate, against undue consolidation in the commercial neurotechnology market.

Challenges encountered by natural repellents: Since obtaining until the final product.

Vector-borne diseases, particularly the arboviruses dengue, Zika, chikungunya, and yellow fever caused by the Aedes aegypti mosquito, have been driving the use of repellents worldwide. The most representative synthetic repellent, DEET stands out as the market's oldest and most efficient repellent. It is considered a reference standard but presents considerable toxicity, not recommended for children up to 6 months old and pregnant women. For this reason, alternatives have been sought, and natural repellents derived mainly from essential oils have been studied, highlighting the essential oils of lemon (Corymbia citriodora), citronella (Cympobogon sp.), Andiroba (Carapa guianensis). However, the development and commercialization of products containing natural repellents are significantly lower when compared to DEET and other synthetic repellents. In order to understand the reasons, aspects related to safety, mechanism of action, efficacy as well development and complexity of the products were evaluated. It is concluded that, as for safety, there is lacking information in the literature regarding the effects on non-target organisms and robust toxicity data. The mechanism of action is based on theories, with less information on the exact mode of action, molecular targets, and interaction with the olfactory and taste receptors of insects. Despite being a current trend to search for actives from natural sources highly present in essential oils, however they reduced action time because due to rapid evaporation after application to the skin, thus requiring repellent vehicles. The development and complexity related to these products bring challenging aspects, beginning on the plant cultivation and extraction processes to produce essential oils with a more homogeneous chemical composition towards the formulation stabilization processes due to fast evaporation and short action time, with the use of pharmaceutical technology such as encapsulation techniques.

Variation in North American bumble bee nest success and colony sizes under captive rearing conditions.

Of the 265 known bumble bee (Bombus) species, knowledge of colony lifecycle is derived from relatively few species. As interest in Bombus commercialization and conservation grows, it is becoming increasingly important to understand colony growth dynamics across a variety of species since variation exists in nest success, colony growth, and reproductive output. In this study, we reported successful nest initiation and establishment rates of colonies and generated a timeline of colony development for 15 western North American Bombus species, which were captively reared from wild-caught gynes from 2009 to 2019. Additionally, we assessed variation in colony size among 5 western North American Bombus species from 2015 to 2018. Nest initiation and establishment rates varied greatly among species, ranging from 5-76.1% and 0-54.6%, respectively. Bombus griseocollis had the highest rates of nest success across the 11-yr period, followed by B. occidentalis, B. vosnesenskii, and B. huntii. Furthermore, days to nest initiation and days to nest establishment varied among species, ranging from 8.4 to 27.7 days and 32.7 to 47 days. Colony size also differed significantly among species with B. huntii and B. vosnesenskii producing more worker/drone cells than B. griseocollis, B. occidentalis, and B. vancouverensis. Additionally, gyne production differed significantly among species with B. huntii colonies producing more gynes than B. vosnesenskii. Results from this study increase knowledge of systematic nesting biology for numerous western North American Bombus species under captive rearing conditions, which can further improve rearing techniques available to conservationists and researchers.

[Medical Institution's Multiple Role in the Collaborative Innovation Transformation Mode of "Industry-University-Research-Medicine" on Domestic Surgical Robots].

In recent years, with the rapid development of Chinese domestic surgical robot technology and the expansion of the application market, the "industry-university-research-medicine" collaborative innovation transformation mode has gradually developed and formed. Medical institutions play an important role in multi-party cooperation with enterprises, universities, and research institutes, as well as in product planning, technology research and development, achievement transformation, and personnel training. On the basis of reviewing the current situation of the development of the "industry-university-research-medicine" collaborative innovation transformation mode of domestic surgical robots, this study explores the multiple roles played by medical institutions in this mode and challenges, further putting forward corresponding recommendations.

Ligand conjugated lipid-based nanocarriers for cancer theranostics.

Cancer is one of the major health-related issues affecting the population worldwide and subsequently accounts for the second-largest death. Genetic and epigenetic modifications in oncogenes or tumor suppressor genes affect the regulatory systems that lead to the initiation and progression of cancer. Conventional methods, including chemotherapy/radiotherapy/appropriate combinational therapy and surgery, are being widely used for theranostics of cancer patients. Surgery is useful in treating localized tumors, but it is ineffective in treating metastatic tumors, which spread to other organs and result in a high recurrence rate and death. Also, the therapeutic application of free drugs is related to substantial issues such as poor absorption, solubility, bioavailability, high degradation rate, short shelf-life, and low therapeutic index. Therefore, these issues can be sorted out using nano lipid-based carriers (NLBCs) as promising drug delivery carriers. Still, at most, they fail to achieve site-targeted drug delivery and detection. This can be achieved by selecting a specific ligand/antibody for its cognate receptor molecule expressed on the surface of the cancer cells. In this review, we have mainly discussed the various types of ligands used to decorate NLBCs. A list of the ligands used to design nanocarriers to target malignant cells has been extensively undertaken. The approved ligand-decorated lipid-based nanomedicines with their clinical status have been explained in tabulated form to provide a wider scope to the readers regarding ligand-coupled NLBCs.

Biomanufacturing readiness levels [BRL]-A shared vocabulary for biopharmaceutical technology development and commercialization.

The Manufacturing Readiness Levels (MRLs) developed by the Department of Defense are well-established tools for describing the maturity of new technologies resulting from government-sponsored Research and Development programs, from the concept phase to commercial deployment. While MRLs are generally applicable to a wide range of industries and technologies, there is significant value in offering an industry-specific view on how the basic principles may be applied to biomanufacturing. This paper describes Biomanufacturing Readiness Levels (BRLs) developed by the National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL), a public/private partnership that is part of the Manufacturing USA network. NIIMBL brings together private, federal, nonprofit, and academic stakeholders to accelerate the deployment of innovative technologies for biopharmaceutical production and to educate and train a world-leading biomanufacturing workforce. We anticipate that these BRLs will lay the groundwork for a shared vocabulary for assessment of technology maturity and readiness for commercial biomanufacturing that effectively meets the needs of this critical, specialized, and highly regulated industry.

The current use and evolving landscape of nutraceuticals.

The nutraceutical market is currently a high-impact multi-billion-dollar industry, and it is anticipated to grow rapidly over the next decade. Nutraceuticals comprise diverse food-derived product categories that have become widespread due to increased consumer awareness of potential health benefits and the need for improved wellness. This targeted review is designed to identify the current global trends, market opportunities, and regulations that drive the nutraceutical industry. Safety and efficacy concerns are also explored with a view to highlighting areas that necessitate further research and oversight. Key drivers of the nutraceutical market include aging populations, consumer awareness, consumer lifestyle, increasing cost of healthcare, and marketing channels. Although some nutraceuticals hold promising preventive and therapeutic opportunities, there is a lack of a universal definition and regulatory framework among countries. Moreover, there is a lack of adequate evidence for their efficacy, safety, and effectiveness, which was even further highlighted during the ongoing coronavirus pandemic. Future prospective epidemiological studies can delineate the health impact of nutraceuticals and help set the scientific basis and rationale foundation for clinical trials, reducing the time and cost of trials themselves. Together, an understanding of the key drivers of the nutraceutical market alongside a consistent and well-defined regulatory framework will provide further opportunities for growth, expansion, and segmentation of nutraceuticals applications.

Prospective pathways of green graphene-based lab-on-chip devices: the pursuit toward sustainability.

At present, analytical lab-on-chip devices find their usage in different facets of chemical analysis, biological analysis, point of care analysis, biosensors, etc. In addition, graphene has already established itself as an essential component of advanced lab-on-chip devices. Graphene-based lab-on-chip devices have achieved appreciable admiration because of their peerless performance in comparison to others. However, to accomplish a sustainable future, a device must undergo "green screening" to check its environmental compatibility. Thus, extensive research is carried out globally to make the graphene-based lab-on-chip green, though it is yet to be achieved. Nevertheless, as a ray of hope, there are few existing strategies that can be stitched together for feasible fabrication of environment-friendly green graphene-based analytical lab-on-chip, and those prospective pathways are reviewed in this paper.

Captive Rearing Success and Critical Thermal Maxima of Bombus griseocollis (Hymenoptera: Apidae): A Candidate for Commercialization?

Commercialized bumble bees (Bombus) are primary pollinators of several crops within open field and greenhouse settings. However, the common eastern bumble bee (Bombus impatiens Cresson, 1863) is the only species widely available for purchase in North America. As an eastern species, concerns have been expressed over their transportation outside of their native range. Therefore, there is a need to identify regionally appropriate candidates for commercial crop pollination services, especially in the western U.S.A. In this study, we evaluated the commercialization potential of brown-belted bumble bees (Bombus griseocollis De Geer, 1773), a broadly distributed species throughout the U.S.A., by assessing nest initiation and establishment rates of colonies produced from wild-caught gynes, creating a timeline of colony development, and identifying lab-reared workers' critical thermal maxima (CTMax) and lethal temperature (ecological death). From 2019 to 2021, 70.6% of the wild-caught B. griseocollis gynes produced brood in a laboratory setting. Of these successfully initiated nests, 74.8% successfully established a nest (produced a worker), providing guidance for future rearing efforts. Additionally, lab-reared workers produced from wild-caught B. griseocollis gynes had an average CTMax of 43.5°C and an average lethal temperature of 46.4°C, suggesting B. griseocollis can withstand temperatures well above those commonly found in open field and greenhouse settings. Overall, B. griseocollis should continue to be evaluated for commercial purposes throughout the U.S.A.