Pharmaceutical Industry Research Articles

PFoods: selecting a segment for a sustainable product

Learning outcomes After working on the assignment questions, the learners can achieve the following learning outcomes: understand the buying behavior towards sustainable products in the context of mindful consumption and product characteristics, appraise the market segmentation and positioning strategy of a sustainable business, understand the application of 5C’s framework for a sustainable business and critically evaluate a new sustainable business’s challenges in the emerging business environment. Case overview/synopsis Dr Joe Fenn, founder and director of PFoods, with extensive experience in the pharma industry overseas, observed a decline in the consumption of traditional dairy foods. Alternative plant foods come as a savior to people who are lactose intolerant and offer a host of health benefits with low environmental impact. Riding on the waves of veganism and sustainable foods, he saw an opportunity in India. PFoods developed and launched two products, namely, Just Plants (plant-based milk alternative) and Plotein (plant-based protein alternative), in collaboration with scientists at the Indian Institute of Science, a premier scientific institution in India, and PMEDS (PreEmptive Meds), a US-based nutraceutical Company. PFoods launched and pilot-tested Just Plant, a dairy alternative substitute for milk in select reputed organizations in Bangalore. The upcoming challenges for Fenn would be to select the right segment, educate the market and position the product that would resonate well with the target customers. Complexity academic level The case study suits undergraduate and graduate courses such as marketing management, sustainable marketing and sustainable business. The case study can also be used in entrepreneurship management and entrepreneurial marketing courses to introduce the challenges of a sustainable startup. The case study highlights the marketing challenges faced by the disruptive and growing plant-based foods or alternative dairy industry in emerging markets. Supplementary materials Teaching notes are available for educators only. Subject code CSS 8: Marketing.

The multiple faces of cGAS-STING in antitumor immunity: prospects and challenges

Abstract As a key sensor of double-stranded DNA (dsDNA), cyclic GMP-AMP synthase (cGAS) detects cytosolic dsDNA and initiates the synthesis of 2′3′ cyclic GMP-AMP (cGAMP) that activates the stimulator of interferon genes (STING). This finally promotes the production of type I interferons (IFN-I) that is crucial for bridging innate and adaptive immunity. Recent evidence show that several antitumor therapies, including radiotherapy (RT), chemotherapy, targeted therapies and immunotherapies, activate the cGAS-STING pathway to provoke the antitumor immunity. In the last decade, the development of STING agonists has been a major focus in both basic research and the pharmaceutical industry. However, up to now, none of STING agonists have been approved for clinical use. Considering the broad expression of STING in whole body and the direct lethal effect of STING agonists on immune cells in the draining lymph node (dLN), research on the optimal way to activate STING in tumor microenvironment (TME) appears to be a promising direction. Moreover, besides enhancing IFN-I signaling, the cGAS-STING pathway also plays roles in senescence, autophagy, apoptosis, mitotic arrest, and DNA repair, contributing to tumor development and metastasis. In this review, we summarize the recent advances on cGAS-STING pathway’s response to antitumor therapies and the strategies involving this pathway for tumor treatment.

Redefining the Role of Medical Affairs Professionals as Innovators and Leaders in Industry-Led Medical Education.

Medical affairs professionals are pivotal players at the intersection of medical innovation and practice in the pharmaceutical industry. They are uniquely positioned to translate complex medical knowledge into actionable insights for internal and external stakeholders. Industry-led continuing medical education (CME) programs, guided by these professionals, hold the potential to markedly improve clinicians' application of evidence-based medicine (EBM) in clinical settings, thereby elevating patient care outcomes. However, current CME techniques often overlook the integration of diverse disciplines such as educational theories, cognitive psychology, information mastery, and implementation science, which are important for effective real-time decision-making in patient care. This gap in integrating implementation science is vital, as it is key in ensuring that medical innovations are not just developed but also effectively implemented and efficiently utilized in clinical settings. In this opinion article, we aim to highlight the crucial yet often underrecognized role of medical affairs professionals in shaping robust and practical CME programs within the industry. We explore emerging trends and approaches in medical education and CME based on the principles of adult education. Additionally, we explore how medical affairs professionals can effectively drive the adoption of EBM in clinical practice. This exploration aims to provide insights into enhancing CME programs, with medical affairs professionals at the forefront of innovation and leadership in bridging gaps in clinical practice.

Leaching Approach for β-Glucosidase Extraction from Fermented Rice Husk in Solid State Cultivation by Aspergillus protuberus.

Environmental problems are caused by the disposal of agrowastes in developing countries. It is imperative to convert such wastes into useful products, which require enzymes such as β-glucosidase. β-Glucosidase has variety of applications in biotechnology including food, textile, detergents, pulp and paper, pharmaceutical and biofuel industries. β-Glucosidase production was performed using the locally isolated Aspergillus protuberus using best growth circumstances on rice husk in solid-state fermentation (SSF). Leaching of β-glucosidase from fermented rice husk with number of solvents to evaluate their extraction efficacy. Among the different solvents examined, acetate buffer (0.02M, pH 5.0) proved to be the best solvent. The subsequent parameters were optimized with acetate buffer. Two washes with acetate buffer each by shaking (30min) in a ratio of 1g of rice husk: 5ml of acetate buffer together attained maximum recovery of β-glucosidase with 41.95 U/g of rice husk.

The cost-effectiveness of iruplinalkib versus alectinib in anaplastic lymphoma kinase-positive crizotinib-resistant advanced non-small-cell lung cancer patients in China

BackgroundIruplinalkib is a second-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) with efficacy in patients with ALK-positive crizotinib-resistant advanced non-small cell lung cancer (NSCLC), which is independently developed by a Chinese pharmaceutical company. This study examined the cost-effectiveness of iruplinalkib versus alectinib in the Chinese healthcare setting.MethodsA partitioned survival model was developed to project the economic and health outcomes. Efficacy was derived using unanchored matching-adjusted indirect comparison (MAIC). Cost and utility values were obtained from the literature and experts’ opinions. Deterministic and probabilistic sensitivity analyses (PSA) were carried out to evaluate the model’s robustness.ResultsTreatment with iruplinalkib versus alectinib resulted in a gain of 0.843 quality-adjusted life years (QALYs) with incremental costs of $20,493.27, resulting in an incremental cost-effectiveness ratio (ICER) of $24,313.95/QALY. Parameters related to relative efficacy and drug costs were the main drivers of the model outcomes. From the PSA, iruplinalkib had a 90% probability of being cost-effective at a willingness-to-pay threshold of $37,863.56/QALY.ConclusionCompared to alectinib, iruplinalkib is a cost-effective therapy for patients with ALK-positive crizotinib-resistant advanced NSCLC.

Polyphenolic Composition and Antimicrobial, Antioxidant, Anti-Inflammatory, and Antihyperglycemic Activity of Different Extracts of Teucrium montanum from Ozren Mountain

Teucrium montanum has widespread use in folk medicine on the Balkan peninsula. In order to scientifically justify this use, the composition and biological activity of aqueous, ethanol, and acetone extract were investigated in this study. Moreover, acetone and ethanol extracts were obtained from the plant material previously exhausted by water extraction. A total of 27 compounds were detected in extracts by UHPLC-DAD-MS/MS analysis, with all of them present in acetone and ethanol extracts. Consequentially, the acetone and ethanol extracts showed higher contents of total phenols of 23% and 18%, respectively, compared to the water extract. The results indicated high biological potential in the investigated extracts. Among all extracts, the aqueous extract showed slightly higher antimicrobial potential, especially against Gram-positive strains, probably due to the release of components soluble in water from the dry unexhausted plant material. On the other hand, the acetone and ethanol extracts had significantly higher antioxidative (by 20%), anti-inflammatory activity (up to 3 and 4 times higher, respectively), and α-glucosidase inhibitory potential (3 times higher) than the aqueous extract. The results of this investigation reveal the great potential of the use of T. montanum in various branches of food, cosmetics, and the pharmaceutical industry. An important part of this research is a confirmation that, once exhausted by water extraction, for example by hydrodistillation, T. montanum plant material can be reused for obtaining valuable products with a wide range of biological activities.

Drug utilization by the population as an indicator of health protection culture in the region

   The relevance of the research is determined by the total dependence of the level of health of the population on the availability of medicines. The problem of consumer culture is among the problems of drug circulation, because the health of the nation directly depends on it. The state-economic program for providing the population with necessary products from the pharmaceutical industry is also related to the issues of health maintenance culture.   The purpose of the research is to determine the population’s attitude towards the consumption of medicines as an indicator of health conservation.   The study is based on the use of a questionnaire survey method. The main questions were the peculiarities of the respondents’ attitude towards taking medications, the question of medical prescription of drugs, the importance of drug prices for the population, the influence of advertising on drug consumption, etc. According to the survey results, it has been proven that the quality of life of the vast majority of people directly depends on the use of drugs. The culture of the population regarding the consumption of drugs is quite high, as evidenced by the information about studying theinstructions before taking the drug by the majority of respondents, a reasonable attitude towards advertising drugs in the media, and an optimal level of trust in the quality of pharmacy products. An important issue in the culture of health conservation remains the provision of people with chronic diseases with drugs for daily use, which should not be completely dependent on imports from other countries, as well as a pricing policy that allows patients to purchase the necessary medicine. Maintaining a high level of culture of drug consumption should be ensured by the state, which implements a reasonable social policy and effective control over meeting people's needs for resources to maintain the health of the nation.

First Report of Paramyrothecium breviseta Causing Target Spot on Amorphophallus muelleri in Yunnan, China.

Amorphophallus muelleri is an Araceae plant with perennial tuber, widely used in food, pharmaceutical and chemical industry due to its richness in glucomannan. In April 2022, an outbreak of a target spot on A. muelleri plantlets was observed in a nursery in Ruili, Yunnan, China. The leafstalks of the diseased plantlets in the nursery turned brown and decayed (Fig.1 A-B), then gradually some water-soaked spots on the true leaves developed along the veins (Fig.1 A). Subquencely, the spots on the true leaves turned dark green to white-grayish in the center, which formed light to dark brown concentric rings with a target-like appearance surrounded by a yellow halo (Fig.1 C). When the temperature was 20-34℃ and the relatively humidity was 25-80%, dark-green to black sporodochia with white hypha appeared on the lower and upper leaf surfaces. Finally, 5-8% of the plants surveyed on 800 m2 of one-year-old plantlets in the nursery showed the symptoms and some plants with infected leafstalks would be death. Similar symptoms were also observed on about 10% of the transplanted plants surveyed on 12000 m2 (1.2 ha) of two-year-old plantlets in the field. Five diseased leaves from five distinct plantlets in the nursery were collected for pathogen isolation. Leaf pieces(5 x 5 mm) were cut from the edge of necrotic lesions, and surface-sterilized with 2.5% sodium hypochlorite for 1 min, 75% ethanol for 30 s, then rinsed 5 times by sterilized distilled water, finally put the leaf pieces on sterilized filter paper for 3-5 minutes to dry them and transferred onto potato dextrose agar (PDA) in petri dishes at 25℃ for three days. Five pure cultures identical to colony and conidial characteristics were isolated from five individual plants. The representative pure culture (M1) was grayish-white and circular colonies were 7.50 cm in diamter after 15 days at 25℃, with dark green concentric rings of sporodochia, the dorsal view of the colonies were yellowish. Conidia were aseptate, smooth, cylindrical, 5.00-6.25 (5.71) x 1.25-1.67 (1.63) µm (n = 20) rounded at both ends. A spore suspension (1 x 106 spores/ml) was prepared by harvesting spores from 15-day-old cultures grown in the dark at 25℃, then a thirty-ml of spore suspension was sprayed on the healthy leaves of 10 two-year-old plantlets. Thirty-ml of sterile water was sprayed on the healthy leaves of another 10 seedlings and used as the control. All seedlings were placed in a nursery at 20 to 34℃ and a relative humidity of 25 to 80%. Similar symptoms (Fig.1 D-F) to those observed in the nursery and field developed on all the 10 seedlings inoculated with M1 after two days, but not on the control leaves. The pathogenicity tests were repeated for three times. Fungal cultures reisolated from the infected leaves were identical to the original colonies and conidia, completing Koch's postulates. The internal transcribed spacer (ITS, primers ITS1 and ITS4) region of ribosomal DNA (OQ553785), calmodulin (cmdA, primers CAL-228F and CAL2Rd)(OQ559103), RNA polymerase II second largest subunit (rpb2, primers RPB2-5F2 and RPB2-7cR) (OQ559104) and β-tubulin (tub2, primers Bt2a and Bt2b) (OQ559105) of M1 had 100%, 98.52%, 98.98% and 98.98% identity with the sequences of Paramyrothecium breviseta CBS544.75 (KU846289 for ITS, KU846262 for cmdA, KU846351 for rpb2, and KU846406 for tub2), respectively. In the phylogenic tree based on ITS, cmdA, rpb2 and tub2 gene sequences, the pure culture M1 clustered with P. breviseta CBS544.75, SDBR-CMU387, DRL4 and DRL3, which has been reported as the pathogen of leaf spot of Coffea arabica in China, C. canephora in China and Thailand (Wu et al. 2021; Withee et al. 2022). Molecular and morphological observations showed the pure culture M1 were P. breviseta (Withee et al. 2022), in addition the disease was named as target spot dueing to the typical target symptom on the leaves. To our knowledge, this is the first report of P. breviseta on A. muelleri from Yunnan, China, as well as worldwide. This disease can caused serious economic losses of A. muelleri dueing to that it can result 5-8% death of the plants in the nursery.

Comparative Evaluation of Secondary Metabolite Chemodiversity of Citrus Genebank Collection in Greece: Can the Peel be More than Waste?

Citrus fruits are among the most economically important crops in the world. In the global market, the Citrus peel is often considered a byproduct but substitutes an important phenotypic characteristic of the fruit and a valuable source of essential oils, flavonoids, carotenoids, and phenolic acids with variable concentrations. The Mediterranean basin is a particularly dense area of autochthonous genotypes of Citrus that are known for being a source of healthy foods, which can be repertoires of valuable genes for molecular breeding with the focus on plant resistance and quality improvement. The scope of this study was to characterize and compare the main phenotypic parameters (i.e., peel thickness, fruit volume, and area) and levels of bioactive compounds in the peel of fruits from the local germplasm of Citrus in Greece, to assess their chemodiversity regarding their polyphenolic, volatile, and carotenoid profiles. A targeted liquid chromatographic approach revealed hesperidin, tangeretin, narirutin, eriocitrin, and quercetin glycosides as the major polyphenolic compounds identified in orange, lemon, and mandarin peels. The content of tangeretin and narirutin followed the tendency mandarin > orange > lemon. Eriocitrin was a predominant metabolite of lemon peel, following its identification in lower amounts in mandarin and at least in the orange peel. For these citrus-specific metabolites, high intra- but also interspecies chemodiversity was monitored. Significant diversity was found in the essential oil content, which varied between 1.2 and 3% in orange, 0.2 and 1.4% in mandarin, and 0.9 and 1.9% in lemon peel. Limonene was the predominant compound in all Citrus species peel essential oils, ranging between 88 and 93% among the orange, 64 and 93% in mandarin, and 55 and 63% in lemon cultivars. Carotenoid analysis revealed different compositions among the Citrus species and accessions studied, with β-cryptoxanthin being the most predominant metabolite. This large-scale metabolic investigation will enhance the knowledge of Citrus peel secondary metabolite chemodiversity supported by the ample availability of Citrus genetic resources to further expand their exploitation in future breeding programs and potential applications in the global functional food and pharmaceutical industries.

Distinctiveness of the Integration of Digital Economic Systems into the Activities of Specialized Retail Chains

Relevance. The basis of the digital economy is the digitalization process, which realizes the possibility of using innovative technologies delegated to optimize management systems in various fields of activity. In turn, digital technologies are modifying the usual format of a number of industries, which directly affects the restructuring of business models of organizations.The purpose of the study is to identify industries of specialized retail chains that claim the need to introduce digital technologies and determine the impact of the digital economy on their activities.Objectives: to study the process of formation of digitalization in the economy; determine the specifics of the influence of the digital economy in the activities of specialized retail chains; to specify the distinctiveness of the use of digital technologies in retail trade; demonstrate the need for the introduction of digital technologies in the leading direction of specialized trade. Methodology. In this study, methods of comparative analysis, synthesis, generalization, graphical techniques for processing information, as well as statistical data presented in the public domain on the official Internet portal of the analytical agency TAdviser were used.Results. The authors found that the process of forming digitalization in the economy involves transforming the stages of economic activity through the introduction of digital technologies into them. A procedure has been established for the influence of the digital economy on the activities of specialized retail chains at the exchange stage. The specifics of introducing digital technologies in retail trade have been studied. It has been established that the pharmaceutical industry is a priority area of specialized trade, claiming the need for digital transformation. Its transformation will involve reengineering processes such as sales, dispensing and pharmaceutical consulting. The distinctiveness of the digital economy is determined through the introduction of trends caused by digital transformation in the activities of pharmacy retail.Conclusions. The authors substantiate the relevance of studying the distinctiveness of the digital economy in the activities of specialized retail chains; Specific examples of the implementation of digital technologies within specialized retail are considered, influencing the change in the economic structure through the formation of more efficient economic processes provided by digital infrastructures.Key words: business models, retail, specialized retail chains, pharmaceutical activities, digital technologies, digital transformation, digital economy, economic activity.

Microbiological acceptance criteria, specifications of herbal drugs and herbal drug preparations in various pharmacopoeias: a global scenario.

A pharmacopoeia is a compendium of guidelines and criteria for drug quality. It was established by a national or regional entity and has legal significance. This applies to administration of drugs in a particular nation or region. In this study, the differences and similarities of microbiological acceptance criteria, specifications for microbial enumeration of herbal drugs and herbal drug preparations in 14 national and international pharmacopeias were investigated. It was found that 12 pharmacopeias have given separate microbial limits for total aerobic microbial count (TAMC) and total yeast and mold count (TYMC), and a list of specified microorganisms for which acceptance criteria are defined. However, similarities were noticed in Ph.Eur, Ph. Helv and, BP. Salmonella, and Escherichia coli are the most common pathogens specified for herbal preparations in which boiling water is added prior to use and for internal use in all Pharmacopoeias because they serve as indicators of potential contamination. From this study, it can be concluded that the differences in microbial limit tests and their acceptance criteria as specified in the various pharmacopoeias need to be harmonized. It will become a more convenient option for global drug manufacturers to import/export herbal drugs, and this would also eliminate the burden of performing various analytical methods and comply with different microbial acceptance criteria set by various pharmacopoeias. The comparative data obtained from this study will be used to develop strategies for revisions of pharmacopoeias in a harmonized manner with respect to microbiological acceptance criteria, specifications for microbial enumeration of herbal drugs and herbal drug preparations.

Conflicts of Interest Among Cardiology Clinical Practice Guideline Authors in Japan.

Clinical practice guidelines (CPGs) offer disease management recommendations based on scientific evidence. However, financial conflicts of interest between CPG developers and the pharmaceutical industry could bias these recommendations, potentially affecting patient care. Proper management of these conflicts of interest is particularly crucial for maintaining the integrity of CPGs. The study aimed to evaluate the extent of financial relationships between the pharmaceutical industry and authors of CPGs for cardiovascular diseases in Japan. The study analyzed personal payments from the pharmaceutical industry to authors of cardiovascular disease CPGs published by the Japanese Circulation Society from January 2015 to December 2022. Payment data, including speaking, consultancy, and writing fees from 2016 to 2020, were extracted from a publicly available database containing personal payments disclosed by all major pharmaceutical companies. A total of 929 unique authors from 37 eligible Japanese Circulation Society CPGs were identified. Notably, 94.4% of these authors received personal payments from pharmaceutical companies, totaling >US $70.8 million. The mean±SD payment per author was US $76 314±138 663) and the median payment per author was US $20 792 (interquartile range: US $4262-US $76 998) over the 5-year period. Chairs of CPGs received significantly higher payments than other authors. More than 80% of authors in each CPG received personal payments. The study elucidated that there were considerable financial relationships between pharmaceutical companies and cardiology CPG authors in Japan. This finding deviates from international conflict of interest management policies, suggesting the need for more stringent conflict of interest management strategies by the Japanese Circulation Society to ensure the development of trustworthy and evidence-based CPGs.

Decarbonizing Process Heat Supply in the Austrian Pharmaceutical Industry

In the pharmaceutical industry, energy efficiency has played a minor role compared to other energy-intensive industries. However, there is a growing recognition of the need to address environmental concerns. With ambitious climate targets and the increasing demand for significant reductions in CO2 emissions, the pharmaceutical industry is now embracing the opportunity to enhance its sustainability practices. Mainly fossil fuels are used to provide process steam at moderate temperature levels at about 160-180°C and to a lesser extent to provide hot water or for on-site power production in CHPs. In this paper, the main processes with demands for process heat, such as media supply, cleaning, or air conditioning, are presented and possibilities for increasing efficiency, for switching to alternative heat supply and for using alternative process technologies are evaluated with respect to economics, but also regarding hurdles for implementation such as requirements for revalidation of production processes and possible necessity of re-approval of products. The present study highlights the potentials for decarbonization of the Austrian pharmaceutical industry using a generic but representative production site applying various measures that either reduce heating and cooling requirements or alter the temperature requirements for heat supply. It is shown that, at least for the example case, full decarbonization is technically feasibly without an increase in energy costs if efficiency measures are progressively used on demand level.

Barriers and Facilitators of Using R for Decision Analytic Modeling in Health Technology Assessment: Focus Group Results.

Decision models for health technology assessment (HTA) are largely submitted to HTA agencies using commercial software, which has known limitations. The use of the open-source programming language R has been suggested because of its efficiency, transparency, reproducibility, and ability to consider complex analyses. However, its use in HTA remains limited. This qualitative study aimed to explore the main reasons for this slow uptake of R in HTA and identify tangible facilitators. We undertook two semi-structured focus group discussions with 24 key stakeholders from government agencies, consultancy, pharmaceutical companies, and academia. Two 1.5-hour discussions reflected on barriers identified in a previous study and highlighted additional barriers. Discussions were recorded and semi-transcribed, and data were organized and summarized into key themes. Human resources constraints were identified as a key barrier, including a lack of training, prioritization and collaboration, and resistance to change. Another key barrier was the lack of acceptance, or clear guidance, around submissions in R by HTA agencies. Participants also highlighted a lack of communication around accepted packages and decision model structures, and between HTA agencies on standard decision modeling structures. There is a need for standardization, which can facilitate decision model sharing, coding homogeneity, and improved country adaptations. The creation of training materials and tailored workshops was identified as a key short-term facilitator. Increased communication and engagement of stakeholders could also facilitate the use of R by identifying needs and opportunities, encouraging HTA agencies to address structural barriers, and increasing incentives to use R.

Remote Monitoring and Data Collection for Decentralized Clinical Trials

Less than 5% of patients with cancer enroll in a clinical trial, partly due to financial and logistic burdens, especially among underserved populations. The COVID-19 pandemic marked a substantial shift in the adoption of decentralized trial operations by pharmaceutical companies. To assess the current global state of adoption of decentralized trial technologies, understand factors that may be driving or preventing adoption, and highlight aspirations and direction for industry to enable more patient-centric trials. The Bloomberg New Economy International Cancer Coalition, composed of patient advocacy, industry, government regulator, and academic medical center representatives, developed a survey directed to global biopharmaceutical companies of the coalition from October 1 through December 31, 2022, with a focus on registrational clinical trials. The data for this survey study were analyzed between January 1 and 31, 2023. Adoption of decentralized clinical trial technologies. The survey measured (1) outcomes of different remote monitoring and data collection technologies on patient centricity, (2) adoption of these technologies in oncology and all therapeutic areas, and (3) barriers and facilitators to adoption using descriptive statistics. All 8 invited coalition companies completed the survey, representing 33% of the oncology market by revenues in 2021. Across nearly all technologies, adoption in oncology trials lags that of all trials. In the current state, electronic diaries and electronic clinical outcome assessments are the most used technology, with a mean (SD) of 56% (19%) and 51% (29%) adoption for all trials and oncology trials, respectively, whereas visits within local physician networks is the least adopted at a mean (SD) of 12% (18%) and 7% (9%), respectively. Looking forward, the difference between the current and aspired adoption rate in 5 years for oncology is large, with respondents expecting a 40% or greater absolute adoption increase in 8 of the 11 technologies surveyed. Furthermore, digitally enabled recruitment, local imaging capabilities, and local physician networks were identified as technologies that could be most effective for improving patient centricity in the long term. These findings may help to galvanize momentum toward greater adoption of enabling technologies to support a new paradigm of trials that are more accessible, less burdensome, and more inclusive.

Recovery Animals in Toxicology Studies: An Innovation and Quality Consortium Perspective on Best Practices With Case Study Examples.

The inclusion of recovery animals in nonclinical safety studies that support clinical trials is undertaken with a wide diversity of approaches even while operating under harmonized regulatory guidance. While empirical evaluation of reversibility may enhance the overall nonclinical risk assessment, there are often overlooked opportunities to reduce recovery animal use by leveraging robust scientific and regulatory information. In the past, there were several attempts to benchmark recovery practices; however, recommendations have not been consistently applied across the pharmaceutical industry. A working group (WG) sponsored by the 3Rs Translational and Predictive Sciences Leadership Group of the IQ Consortium conducted a survey of current industry practice related to the evaluation of reversibility/recovery in repeat dose toxicity studies. Discussion among the WG representatives included member company strategies and case studies that highlight challenges and opportunities for continuous refinements in the use of recovery animals. The case studies presented in this paper demonstrate increasing alignment with the Society of Toxicologic Pathology recommendations (2013) towards (1) excluding recovery phase cohorts by default (include only when scientifically justified), (2) minimizing the number of recovery groups (e.g., control and one dose level), and (3) excluding controls in the recovery cohort by leveraging external and/or dosing phase data. Recovery group exclusion and decisions regarding the timing of reversibility evaluation may be driven by indication, modality, and/or other scientific or strategic factors using a weight of evidence approach. The results and recommendations discussed present opportunities to further decrease animal use without impacting the quality of human risk assessment.

Pushing Boundaries: What's Next in Metal-Free C-H Functionalization for Sulfenylation?

The synthesis of thioether derivatives has been explored widely due to the potential application of these derivatives in medicinal chemistry, pharmaceutical industry and material chemistry. Within this context, there has been an increasing demand for the environmentally benign construction of C-S bonds via C-H functionalization under metal-free conditions. In the present article, we highlight recent developments in metal-free sulfenylation that have occurred in the past three years. The synthesis of organosulfur compounds via a metal-free approach using a variety of sulfur sources, including thiophenols, disulfides, sulfonyl hydrazides, sulfonyl chlorides, elemental sulfur and sulfinates, is discussed. Non-conventional strategies, which refer to the development of thioether derivatives under visible light and electrochemically mediated conditions, are also discussed. The key advantages of the reviewed methodologies include broad substrate scope and high reaction yields under environmentally benign conditions. This comprehensive review will provide chemists with a synthetic tool that will facilitate further development in this field.

Efficient Tandem Cu-Catalyzed Click Synthesis of Multi-Sugar-Modified Oligonucleotides.

Nucleic acids in the form of siRNA, antisense oligonucleotides or mRNA are currently explored as new promising modalities in the pharmaceutical industry. Particularly, the success of mRNA-vaccines against SARS-CoV-2, along with the successful development of the first sugar-modified siRNA therapeutics has inspired the field. The development of nucleic acid therapeutics requires efficient chemistry to link oligonucleotides to chemical structures that can improve stability, boost cellular uptake, or enable specific targeting. For the siRNA therapeutics currently in use, modification of the 3'-end of the oligonucleotides with triple-N-acetylgalactosamine (GalNAc)3 was shown to be of significance. This modification is currently achieved via a cumbersome multi-step synthesis and subsequent loading onto the solid support material. Here, we report the development of a bifunctional click-reactive linker that allows the modification of oligonucleotides in a tandem click reaction with multiple sugars, regardless of the position within the oligonucleotide, with remarkable efficiency and in a one-pot reaction.

Non-Microbiological Mycobacterial Detection Techniques for Quality Control of Biological Products: A Comprehensive Review

Mycobacteria can be one of the main contaminants of biological products, and their presence can have serious consequences on patients’ health. For this reason, the European Pharmacopoeia mandates the specific testing of biological products for mycobacteria, a critical regulatory requirement aimed at ensuring the safety of these products before they are released to the market. The current pharmacopeial reference, i.e., microbial culture method, cannot ensure an exhaustive detection of mycobacteria due to their growth characteristics. Additionally, the method is time consuming and requires a continuous supply of culture media, posing logistical challenges. Thus, to overcome these issues, pharmaceutical industries need to consider alternative non-microbiological techniques to detect these fastidious, slow-growing contaminating agents. This review provides an overview of alternative methods, which could be applied within a quality control environment for biological products and underlines their advantages and limitations. Nucleic acid amplification techniques or direct measurement of mycobacteria stand out as the most suitable alternatives for mycobacterial testing in biological products.

Immunoassays and Mass Spectrometry for Determination of Protein Concentrations in Genetically Modified Crops.

Quantifying protein levels in genetically modified (GM) crops is crucial in every phase of development, deregulation, and seed production. Immunoassays, particularly enzyme-linked immunosorbent assay, have been the primary protein quantitation techniques for decades within the industry due to their efficiency, adaptability, and credibility. Newer immunoassay technologies like Meso Scale Discovery and Luminex offer enhanced sensitivity and multiplexing capabilities. While mass spectrometry (MS) has been widely used for small molecules and protein detection in the pharmaceutical and agricultural industries (e.g., biomarkers, endogenous allergens), its use in quantifying protein levels in GM crops has been limited. However, as trait portfolios for GM crop have expanded, MS has been increasingly adopted due to its comparable sensitivity, increased specificity, and multiplexing capabilities. This review contrasts the benefits and limitations of immunoassays and MS technologies for protein measurement in GM crops, considering factors such as cost, convenience, and specific analytical needs. Ultimately, both techniques are suitable for assessing protein concentrations in GM crops, with MS offering complementary capabilities to immunoassays. This comparison aims to provide insights into selecting between these techniques based on the user's end point needs.