Evaluation of Therapeutics for Severely Debilitating or Life-Threatening Diseases or Conditions: Defining Scope to Enable Global Guidance Development.

A significant regulatory gap exists to facilitate global development of therapeutics for nononcology severely debilitating or life-threatening diseases or conditions (SDLTs). In a 2017 publication, a streamlined approach to the development of treatments for SDLTs was proposed to facilitate earlier and continued patient access to new, potentially beneficial therapeutics.1 However, a major hindrance to broad adoption of this streamlined approach has been the lack of universally accepted, objective criteria to define SDLTs. This article serves to extend the 2017 publication by further addressing the challenge of defining SDLT scope in order to stimulate broader discussion and facilitate development of regional and ultimately international guidelines on the development of therapeutics for SDLTs. Using case examples, we describe key attributes of SDLTs and provide criteria for consideration of an SDLT scope definition.

The integration of emerging omics approaches to advance precision medicine: How can regulatory science help?

Building on the recent advances in next-generation sequencing, the integration of genomics, proteomics, metabolomics, and other approaches hold tremendous promise for precision medicine. The approval and adoption of these rapidly advancing technologies and methods presents several regulatory science considerations that need to be addressed. To better understand and address these regulatory science issues, a Clinical and Translational Science Award Working Group convened the Regulatory Science to Advance Precision Medicine Forum. The Forum identified an initial set of regulatory science gaps. The final set of key findings and recommendations provided here address issues related to the lack of standardization of complex tests, preclinical issues, establishing clinical validity and utility, pharmacogenomics considerations, and knowledge gaps.

Building a roadmap for developing combination therapies for Alzheimer's disease.

Combination therapy has proven to be an effective strategy for treating many of the world's most intractable diseases. A growing number of investigators in academia, industry, regulatory agencies, foundations and advocacy organizations are interested in pursuing a combination approach to treating Alzheimer's disease. A meeting co-hosted by the Accelerate Cure/Treatments for Alzheimer's Disease Coalition, the Critical Path Institute and the Alzheimer's Association addressed challenges in designing clinical trials to test multiple treatments in combination and outlined a roadmap for making such trials a reality.

Charting a path toward combination therapy for Alzheimer's disease.

It is acknowledged that progress in combined therapeutic approaches for Alzheimer's disease (AD) will require an unprecedented level of collaboration. At a meeting co-hosted by the Accelerate Cure/Treatments for Alzheimer's Disease Coalition and the Critical Path Institute, investigators from industry, academia and regulatory agencies agreed on the need for combinatorial approaches to treating AD. The need for advancing multiple targets includes recognition for novel adaptive trial designs that incorporate existing and new biomarkers to evaluate drug effects independently and in combination. A combination trial now being planned may test drugs targeting different pathogenic pathways or multiple targets along a common pathway. Collaborations and consortia-based strategies are pivotal for success and a regulatory framework is recommended for success.

Perspectives on an alternative career path in regulatory science.

Perspectives are provided on an alternative career path in regulatory science for those currently involved in basic biology research. This path is compared and contrasted with basic research, and factors to be examined if one is considering such a path are discussed.

Use of Bacteriocins in Food: Regulatory Considerations.

The authority under which a given bacteriocin will be regulated for use in food will depend on the foods in which it is used and the purpose for which it is used. Use of (i) purified bacteriocins, (ii) cells producing bacteriocins, or (iii) genetic expression of bacteriocins in food-producing organisms to serve a preservative effect in processed foods are under the jurisdiction of the Food and Drug Administration (FDA) and are regulated as food ingredients under the Federal Food, Drug, and Cosmetic Act (FFDCA). Under the FFDCA, those substances that are generally recognized as safe (GRAS) by qualified experts (either based on scientific principles or because they have been historically and safely present in food) are exempt from mandatory premarket approval. Substances used in processed food that are not GRAS are defined as "food additives" under the FFDCA and require premarket approval by the FDA. Bacteriocins used in meat products will require an additional suitability assessment by the U.S. Department of Agriculture (USDA) Food Safety and Inspection Service (FSIS). Bacteriocins which are used on whole fruits or vegetables (or genetically expressed in whole fruits and vegetables and intended to act in the whole food) fall within the definition of "pesticide" found in the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and are therefore regulated by the Environmental Protection Agency (EPA). Bacteriocins which are genetically expressed in food-producing domestic animals may be regulated as animal drugs if they are intended for use in preventing disease in animals.