A comprehensive regulatory framework to address the unmet need for new antibacterial treatments.

To bring new antibacterial drugs to the market is challenging because discovery of new agents is difficult, two large trials per indication are needed in accordance with traditional regulatory requirements, and the economic reward is limited if the use of new antibiotics is constrained. These challenges have resulted in an alarmingly thin antibiotic pipeline, despite the rapid and continued growth in the need for new drugs. Approaches that balance the quantity of data needed for registration with the unmet medical need would encourage work in this area. Therefore, a tiered regulatory framework that allows either disease-based or pathogen-based label indications is proposed, with label wording that promotes the most appropriate use of new agents. Such a framework is within the bounds of present regulatory approaches, is amenable to international harmonisation, and would be a welcome step towards the facilitation of a robust and sustainable discovery and development infrastructure.

Biomarkers for Alzheimer's disease: academic, industry and regulatory perspectives.

Advances in therapeutic strategies for Alzheimer's disease that lead to even small delays in onset and progression of the condition would significantly reduce the global burden of the disease. To effectively test compounds for Alzheimer's disease and bring therapy to individuals as early as possible there is an urgent need for collaboration between academic institutions, industry and regulatory organizations for the establishment of standards and networks for the identification and qualification of biological marker candidates. Biomarkers are needed to monitor drug safety, to identify individuals who are most likely to respond to specific treatments, to stratify presymptomatic patients and to quantify the benefits of treatments. Biomarkers that achieve these characteristics should enable objective business decisions in portfolio management and facilitate regulatory approval of new therapies.

Assessing proarrhythmic potential of drugs when optimal studies are infeasible.

Assessing the potential for a new drug to cause life-threatening arrhythmias is now an integral component of premarketing safety assessment. International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use Guideline (ICH) E14 recommends the "Thorough QT Study" (TQT) to assess clinical QT risk. Such a study calls for careful evaluation of drug effects on the electrocardiographic QT interval at multiples of therapeutic exposure and with a positive control to confirm assay sensitivity. Yet for some drugs and diseases, elements of the TQT Study may be impractical or unethical. In these instances, alternative approaches to QT risk assessment must be considered. This article presents points to consider for evaluation of QT risk when alternative approaches are needed.

A critical path approach to advance nanoengineered medical products.

Still needed in nanotechnology is a product development toolkit containing both scientific and business strategies to stimulate innovation. Among the scientific tools envisioned are evaluative and predictive test methods, such as animal- and computer-based predictive models, characterization assays, toxicity tests and quantitative imaging methods to track biodistribution of nanoparticles in complex biological systems. These tools will help bridge scientific gaps and elucidate potential benefits and risks related to use of nanoengineered medical products. In addition, relevant business strategies, if carefully designed, will help overcome many of the hurdles in this field. This article describes some needed scientific/regulatory and business tools of this field and introduces one collaborative effort underway - a Critical Path Initiative [FDA's Critical Path Initiative: //www.fda.gov/oc/initiatives/criticalpath/.] - structured to bridge some existing gaps.:

Drug eluting stents and the critical path initiative: Evolving paradigms for safety evaluation.

Recent discussions between FDA and other stakeholders have focused on the benefits and risks associated with drug eluting stents (DES). A particular topic of focus is DES thrombosis, a rare, but serious, clinical event that may occur months to years after the initial implantation. FDA continues vigilant postmarket surveillance of DES currently on the market and is working with stent manufactures to ensure that new DES platforms in the development pipeline are safe and effective. FDA is also taking steps, under its Critical Path Initiative (CPI) [FDA. Innovation or Stagnation: Challenge and Opportunity on the Critical Path to New Medical Products, March 2004.http://www.fda.gov/oc/initiatives/criticalpath/whitepaper.html], to help address current and future DES safety issues. This article describes some of these activities.: