bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety Pharmacology: Similarities and Differences between Small Molecules and Novel Biopharmaceuticals
Authors: Bernton Edward W. 
Published: March 2010

AbstractSafety pharmacology studies of small molecule drugs are conducted to investigate unsuspected “off‐target” activities and adverse effects associated with the specific therapeutic class of the drug candidate or preclinical studies. The safety evaluation of new biopharmaceuticals is often made more difficult by the higher percentage of novel drug targets, compared to small molecules. For these products, safety pharmacology tends to be a more focused investigation of highly specific drug‐target interactions, and an in‐depth characterization of pharmacodynamic effects.
Genetic Toxicology Testing of Biopharmaceuticals
Authors: Jacobson‐Kram David , Ghantous Hanan 
Published: March 2010

Abstract
Genotoxic risks of pharmaceuticals are assessed by genetic toxicity assays. The assays rely on cytotoxicity to ensure assay validity. Performance of the assays is influenced by properties of the biopharmaceutical, synthesis techniques, product stability, presence of residual organic chemicals, and pharmacology. This article focuses on genetic toxicity testing of biopharmaceuticals.
General Toxicity Testing and Immunotoxicity Testing for Biopharmaceuticals
Authors: Bussiere Jeanine L. 
Published: March 2010

Abstract
Toxicity testing of biopharmaceuticals is highly dependent on species specificity. If the molecule is pharmacologically active in both rodent and nonrodent species, then the toxicology studies should be conducted in two species. On the other hand, alternative strategies for conducting safety studies such as testing with surrogate molecules, or using transgenic/knockout mice, need to be considered if the molecule is not active in nonhuman primates.
Reproductive/Developmental Toxicity Assessment of Biopharmaceuticals in Nonhuman Primates
Authors: Weinbauer Gerhard F. , Frings Werner , Fuchs Antje , Niehaus Michael , Osterburg Ingrid 
Published: March 2010

AbstractDevelopmental and reproductive toxicity (DART) evaluation of biopharmaceuticals frequently necessitates the use of nonhuman primate models (NHPs) owing to species specificity. NHPs offer several advantages over rodents and rabbits with regard to DART because of similarity to human. This article provides a state‐of‐the‐art account on the feasibility and limitations of using NHPs for DART evaluation in the context of preclinical development of biopharmaceuticals.
Immunogenicity of Therapeutic Proteins and the Assessment of Risk
Authors: Schellekens Huub , Jiskoot Wim 
Published: March 2010

AbstractNearly all therapeutic proteins induce an immune response. The immunogenic response may lead to complications such as skin reactions, anaphylaxis‐like reaction, transfusion reactions, and serum sickness due to immunogenic response to impurities and contaminants. This article focuses on risk analysis and management program for new therapeutic proteins and the factors influencing the probability of an antibody response.
Current Practices in the Preclinical Safety Assessment of Peptides
Authors: Heidel Shawn M. , Page Todd J. 
Published: March 2010

Abstract
There has been an explosion of peptides in drug development and there are currently dozens of marketed therapeutic peptides. The road map for developing peptides is by association to existing biopharmaceutical and/or new chemical entity guidance documents rather than a guidance that is specific for peptides. This article reviews the preclinical development experience across therapeutic peptides, highlighting what has gone before and some considerations for the future.
Strategy Considerations for Developing the Preclinical Safety Testing Programs for Protein Scaffold Therapeutics
Authors: Roberts Stanley A. , Woodnutt Gary , Bradshaw Curt W. 
Published: March 2010

Abstract
This article focuses on key issues pertaining to the design of the preclinical safety assessment program for protein scaffold therapeutics. These new compounds are diverse and include several different protein scaffolds such as monoclonal antibodies, transferrin, and albumin. Small pharmacologically active molecules are attached to the scaffolds so that these therapeutics can have many potential modes of intended pharmacologic action.
Preclinical Safety Evaluation of Immunotoxins
Authors: Brown Jennifer G. , Entwistle Joycelyn , Glover Nick , Macdonald Glen C. 
Published: March 2010

Abstract
Immunotoxins continue to be actively investigated as viable alternatives to conventional therapies for a variety of diseases. An array of different recombinant, antibody formats have improved the overall in vitro and preclinical in vivo efficacy of immunotoxins. This article describes the development of immunotoxins and the preclinical development required for advancing VB4‐845, an anti–EpCAM targeting scFv linked to a truncated form of Pseudomonas exotoxin A(252‐608), into the clinic.
Preclinical Safety Evaluation of Viral Vaccines
Authors: Dempster A. Marguerite , Haworth Richard 
Published: March 2010

AbstractFor nearly a century vaccines have proved to be one of the most important and effective medical treatments. Vaccines continue to prevent millions of deaths worldwide and protect children from a variety of serious diseases such as diphtheria, pertussis, measles, tetanus, and rubella. This article focuses on the preclinical safety evaluation strategy for vaccine approaches to the prophylaxis and treatment of viral diseases.
Preclinical Safety Evaluation of Biopharmaceuticals
Authors: Serabian Mercedes A. , Huang Ying 
Published: March 2010

AbstractPreclinical studies for any experimental pharmaceutical agent, including gene therapy products, are conducted to provide better scientific insight into the potential pharmacologic and toxiologic effects that may result from the administration of the agent in humans. These studies are critical for helping to define the risk‐benefit ratio of the experimental agent of interest in the desired clinical population prior to initiation of a clinical trial and throughout the development program for the pharmaceutical agent. This article provides a perspective of the preclinical assessment of gene therapy products intended for clinical use in therapeutic indications.
Tissue Engineered Products: Preclinical Development of Neo‐Organs
Authors: Bertram Timothy A. , Jayo Manuel 
Published: March 2010

Abstract
Tissue engineering draws on specialized expertise from two traditional disciplines: engineering and the life sciences. The combination of these disciplines forms a foundation upon which the commercial development of neo‐organs is possible. This article discusses development challenges and available solution strategies for bringing these transformational technologies to patients in need.
GLP
Requirements and Current Practices
Authors: Scharton‐Kersten Tanya 
Published: March 2010

Abstract
It is expected by the US FDA that all preclinical safety studies supporting the safety of research or marketing application will be performed in a manner consistent with GLP provisions and that sponsors justify any non‐conformance. Application of GLP principles to testing of biopharmaceuticals, including cell therapies and infectious agent vaccines and therapies, can be difficult. This article focuses on the U.S. and global GLP regulations.
Adaptive Research
Authors: Rosenberg Michael 
Published: March 2010

Abstract
Adaptive research denotes an approach to clinical trials that incorporates what is learned during the course of a study or development program into how it is completed, without compromising validity or integrity. The goal of adaptive research is to make better and accurate decisions to allocate all study resources more efficiently, reduce costs and timelines, and better achieve informational goals. This article describes different types of adaptive techniques.
Process of Data Management
Authors: Trocky Nina , Brandt Cynthia 
Published: March 2010

Abstract
The process of data management is composed of various discrete and interrelated activities that are linked in an individual and building in a successive fashion. The data management study plan (DMSP) can provide the framework for how and where the processes and procedures are defined and outlined for individual protocols or studies. This article discusses quality plan, data management team structure, case report form (CRF) design and guidelines, and data acquisition and handling guidelines.
Designing and Conducting PhaseIIIStudies
Authors: Saba Nabil , Kauh John , Shin Dong M. 
Published: March 2010

AbstractPhase III studies are defined as randomized controlled studies enrolling large numbers of patients with the purpose of rendering a definitive assessment of how effective the studied intervention is, compared with the existing standard of care. The randomized clinical trial is characterized by two or more therapeutic treatment groups. This article focuses on design and conduct of phase III studies.
Regulatory Approval
Authors: Henry Fred , Shih Weichung J. 
Published: March 2010

Abstract
Clinical trial conduct is governed by national laws that are supplemented by international, regional, and national guidance documents. Fast‐track approval programs emphasize the critical nature of close, early communication between the FDA and sponsors. This article describes activities necessary to achieve and maintain regulatory clearance for the conduct of clinical trials and some general strategies for the cooperative design of clinical programs to support marketing approval.
New Paradigm for Analyzing Adverse Drug Events
Authors: Szarfman Ana , Levine Jonathan G. , Tonning Joseph M. 
Published: March 2010

AbstractA new paradigm for computer‐assisted analysis of adverse drug events is sorely needed. Critics of the current paradigm emphasize the need for more transparency in the data review process, claiming that there is the potential for suppressing negative results or for hiding safety issues in both interventional and observational studies. It is essential to transition from quasi‐computerized methods, in which the different elements of the analytical process are treated as discrete, paper report tasks, to a comprehensive informatics approach, in which the entire data collection and analysis is considered as a single reusable, extensible, auditable, and reproducible system.
Gynecology Randomized Control Trials
Authors: Khan Khalid S. , Selman Tara , Daniels Jane 
Published: March 2010

AbstractRandomized control trials (RCTs) are widely accepted as a gold standard for scientific evaluation of all treatments. Benign gynecological conditions such as chronic pelvic pain, heavy menstrual bleeding, and subfertility can be treated with suboptimal therapies when there is not a commitment to the development of new drugs and a thorough evaluation of the relative merits of existing ones. This article focuses on the issues regarding the design and analysis of RCTs that are pertinent to benign gynecology.
Pharmacological Treatment Options for Nonexudative and Exudative Age‐Related Macular Degeneration
Authors: Oliver Alejandro , Ciulla Thomas A. , Harris Alon 
Published: March 2010

AbstractAge‐related macular degeneration (AMD) is the leading cause of vision loss in the developed world. Any patient who exhibits signs and symptoms consistent with exudative AMD undergoes a thorough dilated fundus exam, stereo color fundus photography, and rapid sequence fluorescein angiography (RSFA). The treatment options for ARM and nonexudative AMD are limited; therefore, prevention of disease progression is viewed as critical.
Bridging Studies in Pharmaceutical Safety Assessment
Authors: Ruckle Jon 
Published: March 2010

AbstractWith globalization making an impact on the pharmaceutical industry, there is an increasing urgency for international regulatory approval and marketing of pharmaceutical compounds in the globalization. Bridging studies are performed to facilitate approval of a medication in a new region after it has already been studied or approved in another region. This article discusses some important issues regarding bridging studies, such as dose selection, product labeling, safety, tolerability, and monitoring of the medication in a new region.
Methods of Randomization
Authors: McPherson Gladys , Campbell Marion 
Published: March 2010

AbstractRandomization is increasingly being used to eliminate the problem of predictability and at the same time to maintain balance across combinations of factors in a clinical trial. The most important factors when choosing a randomization method are the size of the trial, practicality of the method, maintaining the blind, and reducing predictability. This article focuses on the different classes of randomization procedure and factors that influence the trials.
Biomarkers
Authors: Bleavins Michael R. , Carini Claudio , Jurima‐Romet Malle , Rahbari Ramin 
Published: March 2010

AbstractBiomarkers are valuable tools for drug development that provide accurate information regarding drug performance and/or disease progression. Proper incorporation of biomarkers in drug development strategy enables the concept of “fail fast, fail early,” allowing early identification of the extremely high proportion of compounds that fail during drug development. This article discusses all the issues related to the use of biomarkers in diagnosis, prognosis, drug discovery and development.
Blinding and Placebo
Authors: Bauhofer Artur 
Published: March 2010

AbstractBlinding refers to keeping persons, such as participants, investigators, and data assessors, unaware of the allocated treatment or therapy, so that they are not influenced psychologically or physically by that knowledge. Placebos are used to make patients’ and observers’ attitudes to the trial as similar as possible in treatment and control groups and to perform an efficient double‐blinded trial. This article describes important features of placebo and blinding trials for the assessment of outcomes with high expectation influence.
Modeling and Simulation in Clinical Drug Development
Authors: Nedelman Jerry , Bretz Frank , Fisch Roland , Georgieva Anna , Hsu Chyi‐Hung , Kahn Joseph , Kawai Ryosei , Lowe Phil , Maca Jeff , Pinheiro José , Rossini Anthony , Schmidli Heinz , Steimer Jean‐Louis , Yu Jing 
Published: March 2010

AbstractThis chapter describes modeling and simulation (M&S) applied to clinical drug development within a pharmaceutical company. M&S is a tool that shows us how a drug works and helps us design and interpret clinical trials. M&S also serves as a framework for what we learn in the precise language of mathematics.
Inference Following Sequential Clinical Trials
Authors: Liu Aiyi , Yu Kai F. 
Published: March 2010

Abstract

Group sequential testing procedures are increasingly being used to monitor
clinical trials, especially phase III studies comparing the efficacy of two or more treatment agents. In a group sequential clinical trial a set of stopping boundaries are usually specified for a test statistic at a few time points, either in terms of real calendar time or statistical information. This article focuses on several popular approaches to construct point and interval estimation and
P
values with respect to the primary endpoint following the termination of a sequential phase III trial and methods for inference concerning a secondary endpoint.
Proof‐of‐Principle/Proof‐of‐Concept Trials in Drug Development
Authors: Al‐Shurbaji Ayman 
Published: March 2010

AbstractThe importance of early Proof‐of‐Principle/Proof‐of‐Concept (PoP/PoC) trial becomes apparent in the context of high attrition rate in drug development. A positive PoP/PoC significantly improves the chance of finding a partner or successfully licensing out the compound. This article focuses on the biomarkers, pharmacogenomics, proteomics, metabonomics, medical imaging, pharmacological models, and nonpharmacological models in PoP/PoC trials.
Biomarkers: Facing the Challenges at the Crossroads of Research and Health Care
Authors: Downing Gregory J. 
Published: March 2010

Abstract
In recent years, across many segments of the biomedical research enterprise and the health care delivery sectors, the impact of biomarkers has been transforming in many ways: from business and economics to policy and planning of disease management. Clinical applications of biomarkers in medical practice are also coming more into focus through diagnostics and molecularly targeted therapies. This article discusses the medical research history that led to the shaping of new directions that is captured simply by the term biomarker, a biological indicator of health or disease.
Quantitative Multiplexed Patterning of Immune‐Related Biomarkers
Authors: Eisinger Dominic , McDade Ralph , Joos Thomas 
Published: March 2010

AbstractImmune‐related biomarker patterning has great potential to improve the success rate of drug approval in a highly cost‐effective manner. The efficiency of simultaneous profiling of multiple immune‐related biomarkers with very small sample volumes has revolutionized our ability to discover and validate biomarker patterns in order to stratify patients and find markers of efficacy and safety. This article focuses on the multiplexed immunoassay measurement technologies as well as some recent and relevant examples of successful biomarker patterning.
Gene Expression Profiles as Preclinical and Clinical Cancer Biomarkers of Prognosis, Drug Response, and Drug Toxicity
Authors: Sprowl Jason A. , Parissenti Amadeo M. 
Published: March 2010

AbstractMeasurement of the expression level of specific genetic or protein biomarkers in patient serum or biopsies can be extremely valuable in the diagnosis and treatment of a variety of human neoplasms. However, tumor or serum level of large groups of proteins or transcripts is necessary to predict patient prognosis or outcome reliably after chemotherapy. This article focuses on the current progress made in the use of gene profiling to predict patient prognosis and response or toxicity to specific chemotherapy regimens.
Characterization and Validation Biomarkers in Drug Development: Regulatory Perspective
Authors: Goodsaid Federico 
Published: March 2010

Abstract
Novel approaches are being tested continuously for the successful integration of biomarkers in drug development. However, integration of these novel biomarkers into routine nonclinical and clinical practice, and regulatory submissions, have often been slow due to fear about how comprehensive data support these applications and regulatory interpretation of the context of use for these applications. This article focuses on the regulatory paths in biomarker evaluation and qualification, including ICH harmonization procedures.
New Markers of Kidney Injury
Authors: Beushausen Sven A. 
Published: March 2010

AbstractThe current biomarker standards for assessing acute kidney injury (AKI) include blood urea nitrogen (BUN) and serum creatinine (SC), which lack sensitivity and specificity for kidney injury. The combined shortcomings of BUN and SC aspredictorsof nephrotoxicity and the propensity for many classes of medicines to cause drug‐induced nephrotoxicity underscore the urgent need for the development and qualification of more sensitive and specific biomarkers. This article focuses on the importance of new biomarkers of nephrotoxicity in predicting and monitoring early or acute kidney injury.
Biomarkers in Pharmaceutical Development: The Essential Role of Project Management and Teamwork
Authors: King Lena , Jurima‐Romet Mallé , Ichhpurani Nita 
Published: March 2010

Abstract
The successful launch of a novel pharmaceutical product represents the culmination of years of discovery and development work driven by knowledgeable people passionate about their project and the pharmaceutical. The development process requires perseverance, and cannot be successful without coordination and teamwork. This article focuses on the role of project management and teamwork in development of pharmaceutical and consequences of employing novel biomarkers or a unique biomarker strategy in pharmaceutical development.
From Gene to Product: the Advantage of Integrative Biotechnology
Authors: Schmidt Frank‐Ranier 
Published: March 2010

Abstract
Biotechnology is gaining in increasing importance in pharmaceutical production processes by replacing chemical production procedures for economical and ecological reasons and in the development and commercialization of novel therapeutic principles. To fully exploit the potential of biotechnological production methods, an integrated process design will be necessary considering the downstream processing requirement during the design of upstream operations and vice versa. This chapter aims is to give insights into the typical issues and problems encountered in the manufacture of biopharmaceuticals, to mediate general ideas and current strategies on how to proceed in the design and development of biotechnological processes.
Overview: Differentiating Issues in the Development of Macromolecules Compared with Small Molecules
Authors: Blaich Günter , Janssen Bernd , Roth Gregory , Salfeld Jochen 
Published: March 2010

AbstractThe fundamental overall structural differences dictate unique approaches for discovery and development of small‐molecule and macromolecule drug. The overall drug discovery/development process can be divided into four convenient steps: target selection and validation; choice between small‐molecule and macromolecule platforms; definition of target product profile; and drug discovery and development. This article focuses on various issues associated with development of macromolecules compared small molecules.
Integrated Development of Glycobiologics: from Discovery to Applications in the Design of Nanoparticular Drug Delivery Systems
Authors: Vauthier Christine , Bertholon Isabelle , Labarre Denis 
Published: March 2010

AbstractThe interactions of nanoparticle drug carriers with the surrounded biological environment are key factors controlling the in vivo fate of the transported drugs. Three levels of interactions may be distinguished and all involve surface phenomena between nanoparticle surface and compounds of the surrounding environment. This article focuses on the main stages of the development of carbohydrates and polysaccharides as a targeted drug or as a component entering the design of drug delivery systems.
R&DParadigm Shift and Billion‐Dollar Biologics
Authors: Maggon Krishan 
Published: March 2010

AbstractR&D success has been linked to the development and creation of billion‐dollar human medication. The blockbuster drugs are the main driver of industrial R&D and contribute a major share of the total pharmaceutical sales, profits, and market value of the successful companies. This article describes successes and failures of biotechnology R&D, criteria for blockbuster brands, global sales of biologics blockbuster brands, changing regulations, cost constraints, public‐private partnership to deliver and develop low‐cost treatments for tropical diseases, and information resources for biologics.
Basic Issues in the Manufacture of Macromolecules
Authors: Lengsfeld Corinne , Anchordoquy Thomas 
Published: March 2010

AbstractThe manufacturing methods for proteins and plasmid DNA require a cellular medium to either express a protein or replicate genetic material. Cell culture plays a large role in the efficiencies of macromolecular production as well as in the separation process. This article describes the initial manufacturing steps involved in the production of therapeutic proteins and plasmid DNA.
Protein Posttranslational Modification: A Potential Target in Pharmaceutical Development
Authors: Huq M.D. Mostaqul , Wei Li‐Na 
Published: March 2010

Abstract
Protein posttranslational modification (PTM) is a hallmark of signal transduction and it allows the cells to rapidly respond to extracellular signals. These modifications, which involve stable and sometimes irreversible additions of non‐amino acid to primary translation products, occur in a large proportion of the cellular protein pool. This article focuses on important issues in PTM studies, such as need for protein modification, how proteins are modified, and basic tools for studying PTM.