Number Of Pharmaceutical Companies Research Articles

BACE1 Inhibitors for Alzheimer's Disease: The Past, Present and Any Future?

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder and the most common cause of dementia in the elderly. The complexity of AD has hindered the development of either a cure or a disease-modifying therapy to halt the disease progression. Numerous hypotheses were presented in order to explain the mechanisms underlying the pathogenesis of AD. Introduced in 1992, the "Amyloid Cascade Hypothesis" had a huge impact on the field and inspired the rise of various drug candidates, especially amyloid-beta (Aβ)-directed drugs; including beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors. Adopted by a number of pharmaceutical companies, the development of BACE1 inhibitors has gained momentum in the past decade with promising results from experimental and early clinical-phase studies. Nevertheless, nearly all BACE1 inhibitors failed in later phases of clinical trials, due to safety and/or efficacy issues, and others were discontinued early in favor of second-generation small-molecule candidates. This paper aims to provide a comprehensive review of all BACE1 inhibitors to ever reach clinical trials, and we discuss the challenges and different perspectives on whether BACE1 inhibitors are to be reconsidered or revitalized in the future.

Deep Learning for Medication Recommendation: A Systematic Survey

ABSTRACT Making medication prescriptions in response to the patient's diagnosis is a challenging task. The number of pharmaceutical companies, their inventory of medicines, and the recommended dosage confront a doctor with the well-known problem of information and cognitive overload. To assist a medical practitioner in making informed decisions regarding a medical prescription to a patient, researchers have exploited electronic health records (EHRs) in automatically recommending medication. In recent years, medication recommendation using EHRs has been a salient research direction, which has attracted researchers to apply various deep learning (DL) models to the EHRs of patients in recommending prescriptions. Yet, in the absence of a holistic survey article, it needs a lot of effort and time to study these publications in order to understand the current state of research and identify the best-performing models along with the trends and challenges. To fill this research gap, this survey reports on state-of-the-art DL-based medication recommendation methods. It reviews the classification of DL-based medication recommendation (MR) models, compares their performance, and the unavoidable issues they face. It reports on the most common datasets and metrics used in evaluating MR models. The findings of this study have implications for researchers interested in MR models.

Considerations for Human ADME Strategy and Design Paradigm Shift(s) - An Industry White Paper.

The human absorption, distribution, metabolism, and excretion (hADME) study is the cornerstone of the clinical pharmacology package for small molecule drugs, providing comprehensive information on the rates and routes of disposition and elimination of drug-related material in humans through the use of 14 C-labeled drug. Significant changes have already been made in the design of the hADME study for many companies, but opportunity exists to continue to re-think both the design and timing of the hADME study in light of the potential offered by newer technologies, that enable flexibility in particular to reducing the magnitude of the radioactive dose used. This paper provides considerations on the variety of current strategies that exist across a number of pharmaceutical companies and on some of the ongoing debates around a potential move to the so called "human first/human only" approach, already adopted by at least one company. The paper also provides a framework for continuing the discussion in the application of further shifts in the paradigm.

First-in-class and best-in-class dendrimer nanoplatforms from concept to clinic: Lessons learned moving forward.

Research to develop active dendrimers by themselves or as nanocarriers represents a promising approach to discover new biologically active entities that can be used to tackle unmet medical needs including difficult diseases. These developments are possible due to the exceptional physicochemical properties of dendrimers, including their biocompatibility, as well as their therapeutic activity as nanocarriers and drugs themselves. Despite a large number of academic studies, very few dendrimers have crossed the 'valley of death' between. Only a few number of pharmaceutical companies have succeeded in this way. In fact, only Starpharma (Australia) and Orpheris, Inc. (USA), an Ashvattha Therapeutics subsidiary, can fill all the clinic requirements to have in the market dendrimers based drugs/nancocarriers. After evaluating the main physicochemical properties related to the respective biological activity of dendrimers classified as first-in-class or best-in-class in nanomedicine, this original review analyzes the advantages and disavantages of these two strategies as well the concerns to step in clinical phases. Various solutions are proposed to advance the use of dendrimers in human health.

Bacteriophages as Therapeutic Preparations: What Restricts Their Application in Medicine.

The increasing prevalence of bacterial pathogens with multiple antibiotic resistance requires development of new approaches to control infections. Phage therapy is one of the most promising approaches. In recent years, research organizations and a number of pharmaceutical companies have intensified investigations aimed at developing bacteriophage-based therapeutics. In the United States and European countries, special centers have been established that experimentally apply phage therapy to treat patients who do not respond to antibiotic therapy. This review describes the features of bacteriophages as therapeutic tools, critically discusses the results of clinical trials of bacteriophage preparations, and assesses the prospects for using phage therapy to treat certain types of infectious diseases.

Revisiting biomolecular NMR spectroscopy for promoting small-molecule drug discovery.

Recently, there has been increasing interest in new modalities such as therapeutic antibodies and gene therapy at a number of pharmaceutical companies. Moreover, in small-molecule drug discovery at such companies, efforts have focused on hard-to-drug targets such as inhibiting protein-protein interactions. Biomolecular NMR spectroscopy has been used in drug discovery in a variety of ways, such as for the reliable detection of binding and providing three-dimensional structural information for structure-based drug design. The advantages of using NMR spectroscopy have been known for decades (Jahnke in J Biomol NMR 39:87-90, (2007); Gossert and Jahnke in Prog Nucl Magn Reson Spectrosc 97:82-125, (2016)). For tackling hard-to-drug targets and increasing the success in discovering drug molecules, in-depth analysis of drug-target protein interactions performed by biophysical methods will be more and more essential. Here, we review the advantages of NMR spectroscopy as a key technology of biophysical methods and also discuss issues such as using cutting-edge NMR spectrometers and increasing the demand of utilizing conformational dynamics information for promoting small-molecule drug discovery.

Sustainability Reporting Pattern in Pharmaceutical Sector : A Study of Top 10 Economies across the Globe

Sustainability reporting is now a mainstream activity of global corporations and is an important issue of the decade. Transparency and accountability for stakeholders are the most demanding issues in pharmaceutical sectors. Companies or Industries can’t survive without sustainable growth. Since most of the stakeholders are aware of recent problems such as community health, climate change, education and development, business sustainability, etc., the demand for disclosures in these areas have also been remarkably increased. Global companies have started business sustainability for economic and non-economic activities of the venture, along with the accountability of external and internal stakeholders towards the goal of sustainable development. This paper examines the sustainability reporting practices of the top 10 economy's pharmaceutical companies across the globe. For this purpose, sustainability reports based on GRI and Non- GRI guidelines for 5 years (2012 to 2016) of the top 10 economy's pharmaceutical companies were collected from the GRI-Database. The number of pharmaceutical companies along with a country name that published sustainability reports has been classified into four categories such as companies with GRI reports are published for 5 years, less than 5 years, Non-GRI reports and mixed reports (GRI &Non-GRI) and a total number of reports published in the given time periods. The results revealed that the sustainability disclosures in Pharmaceutical sectors are dominated by both the 1st and 2nd largest economies across the globe USA, China, and Brazil, and the worst sustainability disclosures are Canada, Italy, Germany, and India. It means pharmaceutical companies in the USA, China, and Brazil are more conscious about sustainability reporting as compare to the rest of the countries of the top 10 economies in the world.

Antibiotic combination therapy against resistant bacterial infections: synergy, rejuvenation and resistance reduction

ABSTRACTIntroduction: Anti-Microbial Resistance (AMR) is a pandemic which threatens modern medicine. There is a lack of effective drug treatment due to the slow pace, high cost and low achievable sales prices of new antibiotic monotherapies. New hope comes in the shape of antibiotic combination therapy, which although used by mother nature, is under-explored and could provide the solution to AMR.Areas covered: We performed a search of Pubmed and Medline using the keywords ‘combination therapy’, ‘antimicrobial resistance’ for articles between 1930 and 2019, as supplemented with other relevant references to our knowledge. We have reviewed the theoretical considerations for combination development and examine the existing and future clinical indications of combination therapies. We have discussed the potential of antibiotic combinations to provide therapeutic synergy, rejuvenating the effectiveness of old antibiotics to which the bacteria had developed resistance previously. We have examined the current thinking and evidence on resistance reduction using combination therapies, with a review on toxicity and drug-drug antagonism.Expert opinion: Antibiotic combination therapy, exploiting synergies, old-drug rejuvenation and resistance reduction could provide the solution to AMR. The number of pharmaceutical companies in this area is likely to expand, bringing promising combinations to the bedside, to save millions of lives worldwide.

Novel therapeutic approach targeting mucosal APRIL in IgA nephropathy

Immunoglobulin A nephropathy (IgAN) is a form of glomerulonephritis. Also known as Berger's disease, it is the most common type of primary glomerulonephritis worldwide and is characterised by IgA deposits in the glomerulus. IgA nephropathy expert Prof. Yusuke Suzuki, who is based at Jutendo University Faculty of Medicine in Japan, explains that studies suggest that a number of factors, including aberrently-glycosylated IgA1, or its immune complex with glycan-specific IgG and IgA may play key roles in the pathogenesis of the condition. 'A proliferation-inducing ligand (APRIL) is one of protein froms the tumour necrosis factor (TNF) ligand superfamily. Research suggests a key role for this ligand in the long-term survival of plasma cells in the bone marrow and lymphoid tissues including mucosae and it is being explored as a potential target for the development of therapeutic options for autoimmune diseases and B cell malignancies. 'Recent studies into the pathological role of APRIL in IgAN, including our own recent findings, have led us to consider a new therapeutic approach,' he outlines. 'Our data using human samples from patients with IgAN and targeting APRIL in animal models has provided proof of concept (POC) of the beneficial effects of neutralising APRIL in IgAN.' Based on this work, clinical trials of new drugs that target APRIL have so far demonstrated exciting possibilities as one of the most promising new treatments for IgAN. A number of pharmaceutical companies are currently working on this and other, related drugs to treat the condition.

Market analysis of dietary supplements that affect the respiratory function

The purpose of work is the analysis of the range of dietary supplements of the modern pharmaceutical market of Ukraine on the basis of medicinal plant raw materials that affect the respiratory system. Materials and methods. The materials of the study included: regulatory documents, sources of scientific literature, online pharmacies sites, price lists of weekly publication the “Apteka” (“Pharmacy”), directory the “Compendium-2019”. The system-analytical, mathematical-statistical and comparative methods of analysis have been used in the work, the site of the Swiss Energy Pharma GmbH. Results. The analysis of the range of dietary supplements that affect the respiratory system has been made. The relationship between OTC drugs and dietary supplements in the modern pharmaceutical market of Ukraine has been studied. It has been found that the proportion of dietary supplements in the study group is 42 %. The corporate and the range structures have been analysed. The results have been showed that the vast majority of the goods in this group come from India and Ukraine (28.12 % for each). Ukraine ranks first in the range – 34.65 %. The study of the dosage form indicated the heterogeneity of the products of this group. Thus, dietary supplements that affect the respiratory system are available in the form of 9 dosage forms, the vast majority of which are lollipops, which is 50 %. The study of the corporate structure made it possible to distinguish the leader among foreign pharmaceutical companies, the company was in the top three Swiss Energy Pharma GmbH. Thus, the development of new dietary supplements of this action and further introduction to the modern pharmaceutical market of Ukraine is topical. Conclusion. Dietary supplements affecting the respiratory system are represented by a large number of pharmaceutical companies, the leaders are Ukraine and India, and Ukraine by assortment. The vast majority belongs to lollipops (50 %) among the dosage forms in the range of dietary supplements of the ENT group. In the corporate structure of the national market, foreign manufacturers occupy leading positions, namely Ansa herbs & foods Pvt. Ltd (17.8 %), Herbion Pakistan Pvt. Ltd. (15.1 %) and Swiss Energy Pharma GmbH (12.3 %).

Institutional barriers and enablers to implementing and complying with internationally accepted quality standards in the local pharmaceutical industry of Pakistan: a qualitative study.

Complying with good manufacturing practices (GMP) and ensuring a quality system is integral to production and supply of quality medicines and achieving universal health coverage. This study focus on the local production of medicines in Pakistan, a lower middle-income country that has observed considerable growth in the number of pharmaceutical companies over the past two decades. Against this background, we investigated: (1) How is quality assurance (QA) and GMP compliance understood and acted upon by local pharmaceutical manufacturers?; (2) What are the institutional barriers and enablers for QA and GMP compliance in the local pharmaceutical sector from the perspective of key stakeholders?; and (3) What are the institutional barriers and enablers for strengthening local regulatory capacity to improve QA in the industry in the long term? We used a qualitative study design involving 22 interviews of the drug regulatory bodies (n = 9), academia (n = 3) and local manufacturers (n = 10), identifying key themes in data by thematic analysis. Document analysis was used to collect additional information and supplement the interview data. We identified that manufacturing facilities operated under different GMP standards and interpretations, pointing towards an absence of harmonization in quality standards across the industry. Views diverged about the status of GMP compliance, with interviewees from academia presenting a more critical view compared with regulators who promoted a more positive story. Among the barriers explaining why companies struggled with quality standards, the lack of a mindset promoting quality and safety among profit-oriented manufacturers was prominent. At the federal level, DRAP’s establishment represented an institutional improvement aiming to promote QA through inspections and guidance. While some positive measures to promote quality have been observed, the need for DRAP to strengthen its technical and regulatory capacity, enhance its engagement in international collaboration and learning, and improve transparency and accountability were highlighted. Overall, since the challenges in Pakistan are shared with other low- and middle-income countries with local production, there is a need to commit to international collaborative mechanisms, such as those lead by WHO, on this issue.

Organisational climate and team performance: the mediating role of psychological empowerment at Jordanian pharmaceutical companies

Nowadays, pharmaceutical companies are considered one of the main pillars of the economic development of any country. The number of pharmaceutical companies has increased rapidly in the last decade in Jordan and many have adopted new managerial practices to improve their efficiency by boosting employees' performance. Accordingly, this paper built a conceptual framework that links organisational climate to team performance through psychological empowerment. To do so, 466 questionnaires were distributed to employees and their managers at four pharmaceutical companies; 424 responses were received, from 364 employees and 60 managers. Structural equation modelling (SEM) was employed to test the hypothesis, determine the validity of the model and measure the structural evaluation. Furthermore, a Sobel test was conducted to assess the capacity of psychological empowerment to influence the relationship between organisational climate and team performance. The major findings are that: 1) organisational climate has a significant positive relationship with psychological empowerment; 2) psychological empowerment has a positive relationship with team performance; 3) the significant positive relationship between organisational climate and team performance is mediated through psychological empowerment.

Organisational climate and team performance: the mediating role of psychological empowerment at Jordanian pharmaceutical companies

Nowadays, pharmaceutical companies are considered one of the main pillars of the economic development of any country. The number of pharmaceutical companies has increased rapidly in the last decade in Jordan and many have adopted new managerial practices to improve their efficiency by boosting employees' performance. Accordingly, this paper built a conceptual framework that links organisational climate to team performance through psychological empowerment. To do so, 466 questionnaires were distributed to employees and their managers at four pharmaceutical companies; 424 responses were received, from 364 employees and 60 managers. Structural equation modelling (SEM) was employed to test the hypothesis, determine the validity of the model and measure the structural evaluation. Furthermore, a Sobel test was conducted to assess the capacity of psychological empowerment to influence the relationship between organisational climate and team performance. The major findings are that: 1) organisational climate has a significant positive relationship with psychological empowerment; 2) psychological empowerment has a positive relationship with team performance; 3) the significant positive relationship between organisational climate and team performance is mediated through psychological empowerment.

Proving the Preclusion of Data Manipulation Using Parallel Data Acquisition in Chromatography

Traceability has an enormous value for companies, but especially for those working in the regulated environment. It plays a special role in the field of pharmacy with respect to manufacturing, controlling and distributing batches of drugs. Through the guidance of Good Manufacturing Practice (GMP) traceability should be ensured. An increasing number of pharmaceutical companies are member of one of the global pharmacopoeias (United States Pharmacopeia, European Pharmacopeia and Japanese Pharmacopeia). The specifications of these pharmacopoeias describe the best practice in documentation, control, qualification and risk management. But however, the pharmacopoeias are written very generally and do not distinguish between the vendors of the analytical instruments. Here, we analyze how chromatographic analyses and data acquisition rely on a specific vendor of the device and the chromatography data system (CDS), the controlling software. We present a way to compare the data acquisition of different CDSs communicating with HPLC instruments. A newly developed software called Data Collector allows the acquisition of data from a HPLC detector parallel to the controlling CDS in the same run. Two HPLC systems and two different CDSs using a well defined sample standard have been tested. The direct comparison of the acquired data precludes unexpected data manipulations of both tested CDSs and shows that there are primarily deviations between the CDSs due to time variations only which depend on the sampling rate. All in all the Data Collector can be used for the traceability of data acquisition.

Flow Chemistry, Continuous Processing, and Continuous Manufacturing: A Pharmaceutical Perspective

Flow chemistry has become a vibrant area for research over the past decade. This perspective is intended to capture insights on how these advances have and will continue to impact the development and commercialization of active pharmaceutical ingredients. A series of chemistry examples from a number of pharmaceutical companies will highlight the influence of flow chemistry on this industry.

Making melanoma therapy personal: an interview with Dr Keiran Smalley for Melanoma Management.

Dr Smalley earned his PhD in Pharmacology from the University of Cambridge, UK, in 2001. He worked as a post-doctoral fellow in the Oncology Department of University College London, the Institute of Cancer Research, Fulham Road and the Wistar Institute, PA, USA. Currently, Dr Smalley is a Professor in the Departments of Tumor Biology and Cutaneous Oncology at the Moffitt Cancer Center, FL, USA. He is also currently the Donald A Adam Endowed Chair in Melanoma Research and is the Director of the Melanoma and Skin Cancers Center of Excellence. The lab of Dr Smalley focuses upon the development of targeted therapy strategies for melanoma and is currently funded by the NCI, the pharmaceutical industry and a number of philanthropic sources. Dr Smalley's work is highly translational in nature and work from his lab has led to the initiation of a number of clinical trials. To date, Dr Smalley has published over 120 papers in top peer-reviewed journals including Cancer Research, Cancer Discovery, Cancer Cell, New England Journal of Medicine, the Proceedings of the National Academy of Sciences, the Lancet, Gastroenterology and Clinical Cancer Research. He currently sits on the editorial boards of Clinical Cancer Research, Biochemical Pharmacology, Drugs, Melanoma Research and the American Journal of Clinical Dermatology and is the Associate Editor of Pharmacological Research. Dr Smalley is a charter member of the Basic Mechanisms of Cancer Therapeutics Study Section for the NCI/NIH and has served on many other peer review panels for the Department of Defense, the state of Texas and numerous melanoma research foundations. He has also fulfilled advisory roles with the University of Pennsylvania, the University of Pittsburgh and a number of pharmaceutical companies. Dr Smalley has been a visiting professor at the University of Sao Paulo, Brazil in 2011 and in 2014 received a Science Without Borders Scholarship from the Brazilian Government.

Pay-for-Delay Agreements in the EU Pharmaceutical Industry

This article analyses the compatibility of pay-for-delay agreements with Article 101 of the Treaty on the Functioning of the European Union, in light of the recent judgment of the General Court in H. Lundbeck A/S and Lundbeck Ltd v European Commission. These commercial agreements, also known as reverse payment settlements, are characterised by a value transfer from the originator to generic companies, which results in a delay in generic market entry. The European Commission first examined pay-for-delay agreements in the Pharmaceutical Sector Inquiry in 2009, instituting an annual patent settlements monitoring exercise and initiating proceedings against a number of pharmaceutical companies, imposing fines totalling over €580 million. In September 2016, the General Court confirmed the decision of the Commission against Lundbeck, holding that the generic undertakings involved in the pay-for-delay agreements were potential competitors of the originator company and that the agreements constituted restrictions of competition by object. The seminal decision of the court adds strength to the arguments used by the Commission in its pay-for-delay investigations, providing an apparently coherent legal framework for the assessment of these agreements. However, significant uncertainty remains in relation to the application of key concepts of competition law in the pay-for-delay context.

Vehicle Systems and Excipients Used in Minipig Drug Development Studies.

Minipigs have been used for dermal drug development studies for decades, and they are currently more frequently considered as the second nonrodent species for pivotal nonclinical studies, in lieu of the dog or nonhuman primate, for compounds delivered via standard systemic routes of administration. Little is known about the tolerability of different excipients in minipigs; sharing knowledge of excipient tolerability and compositions previously used in nonclinical studies may avoid testing of inadequate formulations, thereby contributing to reduced animal usage. This article reviews vehicles employed in the Göttingen(®)minipig based on the combined experience from a number of pharmaceutical companies and contract research organizations. The review includes vehicles tolerated for single or multiple dosing by the Göttingen minipig, some of which are not appropriate for administration to other common nonrodent species (e.g., dogs). By presenting these data for dermal, oral, subcutaneous, and intravenous routes of administration, studies to qualify these vehicles in minipigs can be minimized or avoided. Additionally, investigators may more frequently consider using the minipig in place of higher species if the tolerability of a vehicle in the minipig is known.

Uzara – A quality control perspective of Xysmalobium undulatum

Context: Xysmalobium undulatum (L.) Aiton f var. (Asclepiadaceae), commonly known as uzara, is an ethnomedicinally important plant from southern Africa used to treat a variety of ailments. In addition to local use in African Traditional Medicine (ATM), formulations containing uzara have been successfully marketed by a number of pharmaceutical companies. Despite its commercialization, published adequate quality control (QC) protocols are lacking.Objective: The study was conducted to develop QC protocols for uzara based on chromatographic and spectroscopic techniques.Materials and methods: High performance thin layer chromatography (HPTLC) and liquid chromatography coupled to mass spectrometry (LC-MS) were used to develop phytochemical fingerprints of ethanolic root extracts of 47 uzara samples collected from eight distinct localities in South Africa. Mid-infrared (MIR) spectroscopy was also explored as a suitable alternative technique for rapid and economic quantification of uzarin.Results: Adequate chromatographic profiles were obtained using both HPTLC and LC-MS analyses. The chromatographic patterns showed qualitative similarities among plants collected from different locations. The levels of uzarin, the major constituent of uzara, were highly variable between locations, ranging from 17.8 to 139.9 mg/g (dry weight). A good coefficient of determination (R2 = 0.939) and low root mean square error of prediction (RMSEP = 7.9 mg/g) confirmed the accuracy of using MIR-PLS calibration models for the quantification of uzarin.Discussion and conclusion: Both HPTLC and LC-MS can be used as tools in developing quality control procedures for uzara. MIR in combination with chemometrics provides a fast alternative method for the quantification of uzarin.

Cost analysis of long established and newer oral antiepileptic drugs available in The Indian Market

Background: Large number of pharmaceutical companies manufactures antiepileptic drugs in India. The price variations among the marketed drugs are wide. Aims: The present study was aimed to find the cost of different oral antiepileptic drugs available in Indian market as monotherapy, combination therapy and number of manufacturing companies for each, to evaluate difference in cost of different brands of same dosage of same active drug by calculating percentage variation of cost. Methods and Materials: Cost of a drug being manufactured by different companies, in the same strength and dosage forms was obtained from “Indian Drug Review” Vol. XXI, Issue No.4, 2014 and “Current Index of Medical Specialties” July-October 2014. The difference in the maximum and minimum price of the same drug manufactured by different pharmaceutical companies and percentage variation in price was calculated. Results: The percentage price variation noted of long-established drugs was – Phenytoin (50mg): 140%, Carbamazepine (100mg): 1033%, Phenobarbital (30mg) : 730%, Valproic acid (300mg) : 420%. Newer drugs –Levetiracetam (250mg): 75%, Lamotrigine (25mg): 66%, Topiramate (50mg): 108%, Zonisamide (100mg): 19%. Combination drugs – Phenobarbital + Phenytoin (30+100) mg: 354.55%. Conclusion: The percentage price variation of different brands of the same commonly used long-established oral antiepileptic drug manufactured in India is very wide. The formulation or brand of Antiepileptic drugs (AED’s) should preferably not be changed since variations in bioavailability or different pharmacokinetic profiles may increase the potential for reduced effect or excessive side effects. Hence, manufacturing companies should aim to decrease the price variation while maintaining the therapeutic efficacy.