Journal of opioid management
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Three concurrent public health problems coexist in the United States: endemic nonmedical use/misuse of opioid analgesics, epidemic overdose fatalities involving opioid analgesics, and endemic chronic pain in adults. These intertwined issues comprise an opioid crisis that has spurred the development of formulations of opioids with abuse-deterrent properties and label claims (OADP). To reduce abuse and misuse of prescription opioids, the federal Food and Drug Administration (FDA) has issued a formal Guidance to drug developers that delineates four categories of testing to generate data sufficient for a description of a product's abuse-deterrent properties, along with associated claims, in its Full Prescribing Information (FPI). ⋯ Such technologies include physical and chemical barriers to abuse, combined formulations of opioid agonists and antagonists, inclusion of aversive agents, use of delivery systems that deter abuse, development of new molecular entities and prodrugs, and formulation of products that include some combination of these approaches. Opioids employing these novel technologies are one part of a comprehensive intervention strategy that can deter abuse of prescription opioid analgesics without creating barriers to the safe use of prescription opioids. The maximal public health contribution of OADP will probably occur only when all opioids have FDA-recognized abuse-deterrent properties and label claims.
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The US Food and Drug Administration (FDA) considers the development of abuse-deterrent formulations of solid oral dosage forms a public health priority and has outlined a series of premarket studies that should be performed prior to submitting an application to the Agency. Category 1 studies are performed to characterize whether the abuse-deterrent properties of a new formulation can be easily defeated. ⋯ Recent Advisory Committee meetings at FDA have shown that Category 1 tests play a critical role in FDA's evaluation of an investigational formulation. In this article, we will provide a general overview of the methods of manipulation and routes of administration commonly utilized by prescription drug abusers, how those methods and routes are evaluated in a laboratory setting, and discuss data intake, analysis, and reporting to satisfy FDA's Category 1 testing requirements.
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Randomized Controlled Trial Comparative Study
Intranasal abuse potential of an abuse-deterrent oxycodone formulation compared to oxycodone immediate release and placebo in nondependent, recreational opioid users.
To assess the intranasal (IN) human abuse potential of ELI-200, a novel immediate-release (IR) oxycodone formulation containing sequestered naltrexone. ⋯ IN administration of ELI-200 demonstrated significantly decreased effects on subjective and physiologic measures, and greater nasal irritation, compared to IN oxycodone IR. These findings, along with the PK profile of naltrexone, demonstrated that when ELI-200 capsules were ground and administered intranasally, the naltrexone component was rapidly released and conferred meaningful abuse-deterrent properties.
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It is the current policy of the US Food and Drug Administration (FDA) to convene expert Advisory Committees to provide input on key regulatory decisions regarding opioid products, including approval and labeling of opioid abuse-deterrent formulations (ADFs). Advisory Committee meetings on ADF opioids consider whether the laboratory and clinical data submitted by the sponsor are sufficient to support marketing approval and labeling of the product with properties expected to deter abuse by specific routes of abuse (ie, oral, intranasal, intravenous). The FDA has typically followed the approval and labeling recommendations for ADFs reviewed by its Advisory Committees, highlighting the importance of these meetings in the regulatory approval process. This review describes common issues considered by Advisory Committees for ADF opioids as well as insights on how to prepare for these meetings based on recent relevant experience and regulatory decisions.
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With the development of opioid abuse-deterrent formulations (ADFs), there is a need to conduct well-designed human abuse potential studies to evaluate the effectiveness of their deterrent properties. Although these types of studies have been conducted for many years, largely to evaluate inherent abuse potential of a molecule and inform drug scheduling, methodological approaches have varied across studies. The focus of this review is to describe current "best practices" and methodological adaptations required to assess abuse-deterrent opioid formulations for regulatory submissions. ⋯ Based on these studies, key methodological considerations were reviewed and summarized according to participant demographics, study prequalification, comparator and dose selection, route of administration and drug manipulation, study blinding, outcome measures and training, safety, and statistical analyses. The authors recommend careful consideration of key elements (eg, a standardized definition of a "nondependent recreational user"), as applicable, and offer key principles and "best practices" when conducting human abuse potential studies for opioid ADFs. Careful selection of appropriate study conditions is dependent on the type of ADF technology being evaluated.