Pharmaceutical Projects Research Articles

The Role of Data Science in Enhancing Project Management Practices: A Case Study in the Pharmaceutical Industry

Data science is altering the way in which we manage projects, starting from the planning stage through both execution and tracking phases. In this paper, an examination is made into the productivity and efficiency gains in project management due to the use of data science. It uses previous studies, practical samples and latest advancements to show how decisions based on data can influence the results of a project. Besides, there are two instances looked at concerning pharmaceutical projects. It concentrates on such important aspects of project realization as planning, resource allocation, risk management, requirement analysis, among others.

Enhancing bioavailability of natural extracts for nutritional applications through dry powder inhalers (DPI) spray drying: technological advancements and future directions.

Natural ingredients have many applications in modern medicine and pharmaceutical projects. However, they often have low solubility, poor chemical stability, and low bioavailability in vivo. Spray drying technology can overcome these challenges by enhancing the properties of natural ingredients. Moreover, drug delivery systems can be flexibly designed to optimize the performance of natural ingredients. Among the various drug delivery systems, dry powder inhalation (DPI) has attracted much attention in pharmaceutical research. Therefore, this review will focus on the spray drying of natural ingredients for DPI and discuss their synthesis and application.

Predicting Research and Development Costs for Pharmaceutical Projects: (Cost Reduction and Competitive Advantage Perspective)

Predicting Research and Development Costs for Pharmaceutical Projects: (Cost Reduction and Competitive Advantage Perspective)

Toward Quantitative Models in Safety Assessment: A Case Study to Show Impact of Dose–Response Inference on hERG Inhibition Models

Due to challenges with historical data and the diversity of assay formats, in silico models for safety-related endpoints are often based on discretized data instead of the data on a natural continuous scale. Models for discretized endpoints have limitations in usage and interpretation that can impact compound design. Here, we present a consistent data inference approach, exemplified on two data sets of Ether-à-go-go-Related Gene (hERG) K+ inhibition data, for dose-response and screening experiments that are generally applicable for in vitro assays. hERG inhibition has been associated with severe cardiac effects and is one of the more prominent safety targets assessed in drug development, using a wide array of in vitro and in silico screening methods. In this study, the IC50 for hERG inhibition is estimated from diverse historical proprietary data. The IC50 derived from a two-point proprietary screening data set demonstrated high correlation (R = 0.98, MAE = 0.08) with IC50s derived from six-point dose-response curves. Similar IC50 estimation accuracy was obtained on a public thallium flux assay data set (R = 0.90, MAE = 0.2). The IC50 data were used to develop a robust quantitative model. The model's MAE (0.47) and R2 (0.46) were on par with literature statistics and approached assay reproducibility. Using a continuous model has high value for pharmaceutical projects, as it enables rank ordering of compounds and evaluation of compounds against project-specific inhibition thresholds. This data inference approach can be widely applicable to assays with quantitative readouts and has the potential to impact experimental design and improve model performance, interpretation, and acceptance across many standard safety endpoints.

Discussion on Key Points and Difficulties of Environmental Impact Assessment for Chemical Synthesis Pharmaceutical Projects

Discussion on Key Points and Difficulties of Environmental Impact Assessment for Chemical Synthesis Pharmaceutical Projects

New Measures of Financial Risk, Motivated by Pharmaceutical Research

The paper begins by reviewing the available procedures for measuring value and risk in pharmaceutical research projects. These include Net Present Value (NPV) and its variance, Real Options Valuation (ROV), the Capital Asset Pricing Model (CAPM), Value at Risk (VaR) and Utility. None of these measures focuses specifically on risk as it is perceived by the research manager, except arguably for Utility, which has the serious disadvantage of being by definition a subjective measure. This paper proposes two additional risk measures to go some way towards plugging the gap in what is available. Their advantages are that they: focus on maximum exposure to adverse outcomes, a metric most decision makers have in mind when they wish to evaluate risk; are objective rather than subjective, in contrast to utilities; are easier to specify and more transparent than utilities, since they are in cash terms; are project specific unlike CAPM; satisfy the technical test of coherence, unlike VaR, so it is not possible that diversifying a portfolio could increase the measured risk. The new measures are shown to measure different things from the variance of NPV, which is in some ways similar, and a start is made on exploring what their values are for different patterns of cash flow.

A Supplier Selection Model Emphasizing the Project Risk Management in Drug Production in Pharmaceutical Industry

Risk management is considered to be one of the main phases of project management and one of the eight main areas of the “project management body of knowledge”. The complexities involved in the drug production projects on the one hand, and the need for risk assessment and management in such projects on the other hand, make this issue completely clear. According to the risk mitigation strategies in project management and using the academic professors and experts in the field of drug production and pharmaceutical projects, the present study aimed to provide a checklist for selecting supplier in the drug production projects. This was done using the main eight and 30 secondary indicators related to the top supplier selection and four main and nine secondary indicators related to influencing environmental risks. Finally, after reviewing the statistical results obtained from the questionnaires and utilizing the TOPSIS technique, seven main indicators including “quality, flexibility, delivery, technology, information and communication systems, cost and experience” along with 24 secondary indicators were obtained relating to the top supplier selection. Also, the delivery factors group was identified as the most important group based on the Friedman test results.

Fluorine NMR functional screening: from purified enzymes to human intact living cells.

The substrate- or cofactor-based fluorine NMR screening, also known as n-FABS (n fluorine atoms for biochemical screening), represents a powerful method for performing a direct functional assay in the search of inhibitors or enhancers of an enzymatic reaction. Although it suffers from the intrinsic low sensitivity compared to other biophysical techniques usually applied in functional assays, it has some distinctive features that makes it appealing for tackling complex chemical and biological systems. Its strengths are represented by the easy set-up, robustness, flexibility, lack of signal interference and rich information content resulting in the identification of bona fide inhibitors and reliable determination of their inhibitory strength. The versatility of the n-FABS allows its application to either purified enzymes, cell lysates or intact living cells. The principles, along with theoretical, technical and practical aspects, of the methodology are discussed. Furthermore, several applications of the technique to pharmaceutical projects are presented.

It's a Matter of Trust: Joint Inventorship and Traditional Knowledge Owners

This is a paper on joint inventorship for Indigenous Peoples, which subject matter is an intangible asset defined generally as Traditional Knowledge. We present arguments to deal with joint inventorship for such intangible collection of methods, processes and discoveries involving manipulation of plants and chemical knowledge belonging to Traditional Knowledge owners. As prospective patentees, their innovative techniques applied for therapeutical use on humans based on knowledge acquired from local plants should be acknowledged as an economic element in the intellectual property legal frame for a claimed invention. The second argument supports Traditional Knowledge owners as co-patent holders on their intangible subject matter for a just legal system. It is generally accepted that an inventor’s rights are inclusive from the time of conception, when ideas are in development, to regular practice, when the prototype is ready and workable. Joint inventorship is not a novel concept, but it has been used quite often with some good results. For instance, inventions based on business methods have been accepted as subject matter for a patent, which usually involves more than one inventor. However, co-ownership in inventions unveils issues with trust and transparency when one patent holder decides he is entitled to exercise exclusive rights. Having intellectual property protection to orally transmitted knowledge on use of plants with Indigenous therapeutic utility is novel. This paper discusses patent co-ownership based on international jurisprudence, particularly in Burroughs Welcome & Co v Barr Laboratories, which tested the limits of collaboration in independent research teams working in the same invention with non-contractual arrangements in pharmaceutical projects. Most recently an Australian joint patent application by The Chuulangun Aboriginal Corporation of a patent for medicinal use with the University of South Australia has illustrated an entrepreneurial activity in Aboriginal Australia to protect and commercialise medicinal flora associated to Traditional Knowledge. The question is whether intellectual property policies have welcomed such novelty or are stalling them from happening; if so, it is time to welcome trust among the parties involved, especially newcomers as Traditional Knowledge owners.

Ligand-Based Fluorine NMR Screening: Principles and Applications in Drug Discovery Projects.

Ligand-based fluorine NMR screening has gained popularity in drug discovery projects during the past decade and has become a powerful methodology to produce high quality hits. Its high sensitivity to protein binding makes it particularly suitable for fragment screening, allowing detection and binding strength measurement of very weak affinity ligands. The screening can be performed in direct or competition format, and its versatility allows application to complex biological and chemical systems. As the potential of the methodology has now been recognized and successfully demonstrated in several relevant medicinal chemistry projects, it is now an appropriate time to report the learned lessons and point the way to the future. In this Perspective the principles of the methodology along with several applications to pharmaceutical projects are presented.

Significance of time and cost dimensions in pharmaceutical projects and prioritisation of project phases

The success of any project depends upon different dimensions like time, cost, quality and customer satisfaction. Of all these, time and cost have been treated as the most common and major tangible measures from the perspective of both developer and user. Each project phase has a unique set of activities and its successful completion will be influenced by such factors. This paper aims to examine the emphasis attributed to time and cost in handling different phases of pharmaceutical projects. From a survey around four big Indian pharmaceutical companies, useful feedback was collected. After weighing the importance of both time and cost dimensions, analytic hierarchy process (AHP) was used to prioritise different phases of pharmaceutical projects. Results top ranked 'execution' phase followed by 'monitoring and control' phase. The findings are helpful to pharmaceutical project people in successfully completing different phases of projects on the basis of time and cost dimensions.

Significance of time and cost dimensions in pharmaceutical projects and prioritisation of project phases

The success of any project depends upon different dimensions like time, cost, quality and customer satisfaction. Of all these, time and cost have been treated as the most common and major tangible measures from the perspective of both developer and user. Each project phase has a unique set of activities and its successful completion will be influenced by such factors. This paper aims to examine the emphasis attributed to time and cost in handling different phases of pharmaceutical projects. From a survey around four big Indian pharmaceutical companies, useful feedback was collected. After weighing the importance of both time and cost dimensions, analytic hierarchy process (AHP) was used to prioritise different phases of pharmaceutical projects. Results top ranked 'execution' phase followed by 'monitoring and control' phase. The findings are helpful to pharmaceutical project people in successfully completing different phases of projects on the basis of time and cost dimensions.

АНАЛІЗ ІННОВАЦІЙНОГО ПОТЕНЦІАЛУ ФАРМАЦЕВТИЧНОГО РИНКУ

The article substantiates the urgency of the problem of managing the development of innovative potential of the enterprise, caused by the practical need to solve this problem. Insufficient theoretical elaboration of issues of innovation potential development management in the context of the pharmaceutical sector, especially in the domestic literature, and, as a consequence, insufficient elaboration of this issue in practice have been identified. Theoretical and methodological principles of managing the development of innovative potential of the enterprise are considered. Namely, the economic essence of innovation potential is determined. The review and analysis of theoretical aspects of management of innovative potential of enterprises is carried out. The current state of the innovation potential management system in the pharmaceutical market is considered. The innovative potential of the pharmaceutical market of Ukraine is researched and analyzed. Ways to improve the innovation potential management system are proposed. It is substantiated that based on the level of innovation of domestic pharmaceutical products and the identified problems of the pharmaceutical market of Ukraine, a relatively high level of wages in the field of pharmaceuticals is not an effective catalyst for scientific and research activities. Public targeted funding for pharmaceutical research projects should be strengthened, especially for those groups of diseases whose prevalence requires priority control. It is proved that the state should coordinate joint research activities between relevant business structures, research institutions, medical institutions, as well as higher education institutions that train specialists with appropriate qualifications. The scientific novelty of the obtained results is the development of scientific and practical principles for the implementation of recommendations for improving the components of managing the innovative potential of the pharmaceutical market.

Structure-Based Design and Synthesis of a New Phenylboronic-Modified Affinity Medium for Metalloprotease Purification.

Metalloproteases are emerging as useful agents in the treatment of many diseases including arthritis, cancer, cardiovascular diseases, and fibrosis. Studies that could shed light on the metalloprotease pharmaceutical applications require the pure enzyme. Here, we reported the structure-based design and synthesis of the affinity medium for the efficient purification of metalloprotease using the 4-aminophenylboronic acid (4-APBA) as affinity ligand, which was coupled with Sepharose 6B via cyanuric chloride as spacer. The molecular docking analysis showed that the boron atom was interacting with the hydroxyl group of Ser176 residue, whereas the hydroxyl group of the boronic moiety is oriented toward Leu175 and His177 residues. In addition to the covalent bond between the boron atom and hydroxyl group of Ser176, the spacer between boronic acid derivatives and medium beads contributes to the formation of an enzyme-medium complex. With this synthesized medium, we developed and optimized a one-step purification procedure and applied it for the affinity purification of metalloproteases from three commercial enzyme products. The native metalloproteases were purified to high homogeneity with more than 95% purity. The novel purification method developed in this work provides new opportunities for scientific, industrial and pharmaceutical projects.

Analysis of cost escalations in pharmaceutical projects

Purpose– The purpose of this paper is to examine different possible issues that can contribute to cost escalations in pharmaceutical capital projects and identify remedial measures to control them.Design/methodology/approach– The study is supported by a detailed survey performed around some big pharmaceutical companies of Indian sub-continent. Various issues that lead to cost escalations of projects have been identified. Both exploratory and confirmatory factor analyzes have been applied to the feedback data.Findings– The study derived and validated four prominent factors leading to cost escalations. The paper discusses these factors along with the remedies identified to control project cost. Convergent and discriminant validity have been well established for the model.Research limitations/implications– The data needful for the study were collected from only four big pharmaceutical companies established in Southern India. Through frequent and elaborate interactions with senior project managers of those companies, it became possible to get a consolidated list of reasons that contribute to cost escalations in pharmaceutical projects. The list and the feedback data may be more exhaustive if some more companies would have been surveyed. Future research is committed to cover some more notable pharmaceutical companies both nationally and internationally and enhance the sample size. This would add more strength to the analysis and derive more consistent and validated results.Practical implications– This study provides necessary support to the project people to analyze different issues that stand as hurdles for project success and enable them to look for remedies to resolve them. The results would help the project managers to enhance their awareness in controlling the project costs. The study stands as a stepping stone and a roadmap to embed further research in this direction.Originality/value– Since several significant issues impact the progress of the projects, this work focussed on analyzing cost-related issues in projects; since there is meager research work done in the area of pharmaceutical project management, as an attempt to fill the research gap, this work carried out detailed analysis of different issues leading to cost escalations in pharmaceutical capital projects; factor analysis, including exploratory and confirmatory, has been applied to the data collected and several important factors derived and the measurement model well validated; the research work was done in close interaction with the project people working in four big Indian pharmaceutical companies and useful information was collected; in addition to generation of important factors from the factor analysis, the study was further extended to collect various remedies to mitigate the issues that lead to cost escalations; the research work has enough strength to act as a role model to motivate researchers and project people to further their research on other issues and also refine the present work.

Analysis and control of issues that delay pharmaceutical projects

Every project will have certain objectives and service levels to be achieved. The success of a project depends on several dimensions like time, cost/budget, quality, etc. and managing a project involves completing the project within time, within budget and with quality to satisfy the users. Because of the significance of health, pharmaceutical companies realized the importance of project management methods and techniques to make available the life saving drugs in time to the needy patients and hospitals. In literature, there is meager information about pharmaceutical project management oriented towards analysis of issues and factors that contribute to the failure or success of projects. This study attempts to analyse different issues that contribute to time delays in pharmaceutical product-based projects, group them under a finite set of prominent factors and identify remedial measures to control those delays. The feedback of project people of some big pharmaceutical firms of Indian sub-continent was collected for this purpose. Exploratory factor analysis (EFA) has been used to reduce the reasons for time delays to a limited number of prominent factors and the EFA model has been further examined by confirmatory factor analysis (CFA) for its validation. Remedial measures under each factor of time delays have been gathered and a framework designed to mitigate the time delays in pharmaceutical projects. The derived factors that delay the pharmaceutical projects include resource, monitoring & control, scheduling and planning problems. Important remedial measures like blended resource approach, estimation and forecast of shortage of labour and skills, regular quality training, etc. have been recommended.

ChemInform Abstract: Practical Aspects and Mechanism of Asymmetric Hydrogenation with Chiral Half‐Sandwich Complexes

AbstractReview: 91 refs.

Economic Aspects of Small and Large Molecule Pharmaceutical Technologies

There are differences between small and large molecule pharmaceutical technologies from a scientific perspective. However, there do not appear to be measurable differences with respect to the economic characteristics of small and large molecule pharmaceutical projects. The economic characteristics underlying developing, manufacturing, and marketing products based on small and large molecule technologies appear to be similar. The growing importance of large molecule technologies in addressing unmet medical needs will create a need for additional research on identifying material economic differences that may require changes in public policies.

Localized Heuristic Inverse Quantitative Structure Activity Relationship with Bulk Descriptors Using Numerical Gradients

State-of-the-art quantitative structure-activity relationship (QSAR) models are often based on nonlinear machine learning algorithms, which are difficult to interpret. From a pharmaceutical perspective, QSARs are used to enhance the chemical design process. Ultimately, they should not only provide a prediction but also contribute to a mechanistic understanding and guide modifications to the chemical structure, promoting compounds with desirable biological activity profiles. Global ranking of descriptor importance and inverse QSAR have been used for these purposes. This paper introduces localized heuristic inverse QSAR, which provides an assessment of the relative ability of the descriptors to influence the biological response in an area localized around the predicted compound. The method is based on numerical gradients with parameters optimized using data sets sampled from analytical functions. The heuristic character of the method reduces the computational requirements and makes it applicable not only to fragment based methods but also to QSARs based on bulk descriptors. The application of the method is illustrated on congeneric QSAR data sets, and it is shown that the predicted influential descriptors can be used to guide structural modifications that affect the biological response in the desired direction. The method is implemented into the AZOrange Open Source QSAR package. The current implementation of localized heuristic inverse QSAR is a step toward a generally applicable method for elucidating the structure activity relationship specifically for a congeneric region of chemical space when using QSARs based on bulk properties. Consequently, this method could contribute to accelerating the chemical design process in pharmaceutical projects, as well as provide information that could enhance the mechanistic understanding for individual scaffolds.

Practical aspects and mechanism of asymmetric hydrogenation with chiral half-sandwich complexes.

This review is oriented toward the asymmetric transfer hydrogenation (ATH) of imines regarding mostly fundamental, yet important topics from the practical point of view. Development of analytical methods for the monitoring of ATH (i.e., kinetics and stereoselectivity) belongs to those topics, as well as studies on the influence of reaction conditions and structural variations on the reaction performance. The second part is devoted to the reaction mechanism with the emphasis on imine ATH and catalyst behaviour under acidic conditions. The review also addresses the asymmetric hydrogenation (AH) of ketones and imines using molecular hydrogen and the application of ATH in pharmaceutical projects. The contributions of our group to each area are included.