Drug discovery strategies for acute radiation syndrome

Introduction: There are at the minimum two major, quite different approaches to advance drug discovery. The first being the target-based drug discovery (TBDD) approach that is commonly referred to as the molecular approach. The second approach is the phenotype-based drug discovery (PBDD), also known as physiology-based drug discovery or empirical approach.

Area covered: The authors discuss, herein, the need for developing radiation countermeasure agents for various sub-syndromes of acute radiation syndromes (ARS) following TBDD and PBDD approaches. With time and continuous advances in radiation countermeasure drug development research, the expectation is to have multiple radiation countermeasure agents for each sub-syndrome made available to radiation exposed victims.

Expert opinion: The majority of the countermeasures currently being developed for ARS employ the PBDD approach, while the TBDD approach is clearly under-utilized. In the future, an improved drug development strategy might be a ‘hybrid’ strategy that is more reliant on TBDD for the initial drug discovery via large-scale screening of potential candidate agents, while utilizing PBDD for secondary screening of those candidates, followed by tertiary analytics phase in order to pinpoint efficacious candidates that target the specific sub-syndromes of ARS.     

FDA’S Perspectives on Cardiovascular Devices

The Food and Drug Administration (FDA) decision process for approving or clearing medical devices is often determined by a review of robust clinical data and extensive preclinical testing of the device. The mission statement for the Center for Devices and Radiological Health (CDRH) is to review the information provided by manufacturers so that it can promote and protect the health of the public by ensuring the safety and effectiveness of medical devices deemed appropriate for human use (Food, Drug & Cosmetic Act, §903(b)(1, 2(C)), December 31, 2004; accessed December 17, 2008 ). For high-risk devices, such as ventricular assist devices (VADs), mechanical heart valves, stents, cardiac resynchronization therapy (CRT) devices, pacemakers, and defibrillators, the determination is based on FDA’s review of extensive preclinical bench and animal testing followed by use of the device in a clinical trial in humans. These clinical trials allow the manufacturer to evaluate a device in the intended use population. FDA reviews the data from the clinical trial to determine if the device performed as predicted and the clinical benefits outweigh the risks. This article reviews the regulatory framework for different marketing applications related to cardiovascular devices and describes the process of obtaining approval to study a cardiovascular device in a U.S. clinical trial.     

A simple technique for evaluation of methods of cell separation

A simple method is described for labelling cells with fluorescein and using them in artificial mixtures to assess cell separation procedures. The method facilitates the examination of the variables in a separation procedure. It is thus possible to tailor a separation procedure (for example panning with monoclonal antibody) to suit the specific requirements of the experiment.     

The structuring of an allergy index based on IgE-mediated skin sensitivity to common environmental allergens

We computed skin-test sensitivity levels in 485 adults puncture-tested with eight standardized, high-quality inhalant allergens tested at single concentrations. In order to quantitate the "average" IgE-mediated skin sensitivity of each subject, we used both nonparametric and parametric statistical methods to generate two "allergy indices" (Allergy Index I and Allergy Index II) based on sensitivity end-point data from the subpopulations of individuals positive to six of the eight allergens. For the 192 skin test-positive subjects, Allergy Index I and Allergy Index II were significantly correlated with each other (rs = 0.98, p less than 0.001) and with the number of positive skin-test reactions (rs congruent to 0.9, p less than 0.001) as well as with log[total serum IgE] (r congruent to 0.4, p less than 0.01). In 102 ragweed-positive subjects, log[specific IgE to ragweed] was significantly correlated with ragweed-specific "ragweed indices I and II" (r congruent to 0.6, p less than 0.01). Furthermore, the average daily symptom scores reported by 14 ragweed-positive subjects during the ragweed pollination season were significantly correlated with ragweed indices I and II (p less than 0.05). We propose the use of Allergy Index II in epidemiologic and genetic studies of allergic phenotypes as well as in clinical decisions for diagnosis and immunotherapeutic intervention.     

2002年美国FDA批准的新药

20 0 2年美国FDA批准了 2 5个新药 ,其中新分子实体 (Newmolecularentities ,NMEs) 16个 ,生物制品 9个 (表 1中用a表示 )。按疗效分类 :抗感染药物 6个 (2 4 % ) ,心血管系统药物 4个 (16 % ) ,抗肿瘤药物 3个 (12 % ) ,神经系统与精神药物 2个(8% ) ,其他类药物 10个 (4 0 % )。若按FDA对疗效类别的分类 ,其中有 10个为优先推荐类 (P) ,15个为与已上市药物疗效基本相似类 (S) ,治疗罕见病类药物 (orphandrug ,用V表示 )共 5个 (4个属于P类 )。见表 1。表 1　 2 0 0 2年美国FDA批准的新药新药名称 (商品名 )研发企业适应证与用途批…     

2004年美国FDA批准的新药

2004年美国FDA批准了32个新分子实体(Newmolecular entity,NMEs)及4个新生物制品(All BiologcLicense Application(BLA)).按照疗效分类,主要有抗肿瘤药物8个(占22.2%),抗感染药物4个(占11.1%),精神和神经系统用药6个(占16.7%),其他药物18个(占50%),具体见表1.     

美国FDA关于上市前化学药药学研究的技术要求

新药上市前的临床研究申请（Investigational Drug Application，IND）是药物研发的一个十分重要的阶段，也是药品监管工作中一项需要重点关注并加以认真研究的内容。对于新药上市前临床研究的申请，美国FDA要求对新药的药学研究与药理、毒理研究、临床研究分阶段平行进行，通过不断循序渐进的深入，达到对新药性质的全面了解，进而明确其质量控制的要求，保证上市药品达到安全、有效、质量可控。     

Cybersecurity for Cardiac Implantable Electronic Devices: What Should You Know?

Medical devices have been targets of hacking for over a decade, and this cybersecurity issue has affected many types of medical devices. Lately, the potential for hacking of cardiac devices (pacemakers and defibrillators) claimed the attention of the media, patients, and health care providers. This is a burgeoning problem that our newly electronically connected world faces. In this paper from the Electrophysiology Section Council, we briefly discuss various aspects of this relatively new threat in light of recent incidents involving the potential for hacking of cardiac devices. We explore the possible risks for the patients and the effect of device reconfiguration in an attempt to thwart cybersecurity threats. We provide an outline of what can be done to improve cybersecurity from the standpoint of the manufacturer, government, professional societies, physician, and patient.     

Postmarketing safety of biologics and biological devices

Background contextRegardless of study design, the approval process of biologics and biological devices cannot identify every possible safety concern. Postmarketing safety surveillance can provide information based on real-world use of medical products in heterogeneous populations and is critical for identifying potentially serious adverse events, events that are too rare to be detected during premarketing studies, late complications, and events involving individuals or uses that were not evaluated in clinical trials.PurposeTo review why adverse event reporting is important and how the information is used, with emphasis on the points that are most applicable for surgeons and other spine professionals.MethodsThis is an overview of postmarketing safety surveillance.ResultsReview of adverse event reports has resulted in safety notifications, label changes, and publications regarding the safety of biologics and biological devices, such as the risk of airway compromise after the use of recombinant human bone morphogenetic protein in cervical spine fusion, the occurrence of a fatal air embolism after the use of a fibrin sealant that had been applied with a spray device, and infections after allograft transplantation of human tissues.ConclusionsIn light of the rapid development of new biologics, postmarketing surveillance is imperative for ensuring that these products are as safe as possible. By reporting adverse events, surgeons and other health care professionals play a key role in improving and refining our understanding of the safety of biologics.