Advancements in Opioid Abuse Deterrence

Evolving Strategies Address Abuse Potential

According to the CDC, opioid abuse is the nation's fastest growing drug problem and it ranks among the top three for prescription drug abuse.3 Scientifically driven solutions are needed to help combat this serious public health epidemic, including:

  • Strategies to mitigate risk
  • Abuse deterrence technology, which is a modality to help reduce opioid abuse
  • Continued scientific research and development of abuse deterrent technologies5

In April 2015, the Food and Drug Administration (FDA) issued a guidance document to assist the pharmaceutical industry to develop new formulations of opioid drug products with potentially abuse-deterrent properties.5 The FDA encourages the development of abuse-deterrence formulations and believes that these products have promise to help reduce, though not necessarily prevent, opioid abuse.5 The FDA guidance document explains5:

  • Current thinking about studies designed to demonstrate abuse-deterrence properties in a given formulation
  • How studies will be evaluated
  • Labeling claims that may be approved based on study results

Studies Evaluate New Potential Abuse Deterrent Technologies

In order to assess the impact of a potentially abuse-deterrent product, the FDA recommends that premarket and postmarket studies should be performed.5 Data from each of the four categories are recommended.5

Category 1

Laboratory-based in vitro manipulation and extraction studies

Category 2

Pharmacokinetic studies

Category 3

Clinical abuse potential studies

Category 4

Postmarket studies

Category 1: Laboratory Manipulation and Extraction Studies

The goal of laboratory-based studies should be to evaluate how easily potentially abuse-deterrent properties of a formulation can be defeated or compromised.5 Such studies would examine how an abuser may alter the formulation to change the rate or amount of drug released.5 Extractability and solubility studies should be designed to determine whether any of the formulation components might be dissolved and extracted, allowing a user to bypass the drug’s abuse-deterrent properties.5

Category 2: Pharmacokinetic Studies

The goal of the clinical pharmacokinetic studies should be to understand the in vivo properties of the formulation by comparing the pharmacokinetic profiles of the manipulated formulation with the intact formulation and with manipulated and intact formulations of the comparator drugs through one or more routes of administration.5

Category 3: Clinical Abuse Potential Studies

Clinical Abuse Potential studies, also known as human abuse potential studies, human abuse liability studies, or “drug-liking” studies, evaluate the abuse liability or abuse potential for prescription drugs.5 These studies provide information on the relative abuse potential of a drug in the same class.5 Companies with abuse-deterrent formulations of opioid products are generally expected to conduct these studies to obtain an understanding of the impact of the technology on the product’s abuse potential.5

Methodology

These studies are usually conducted among experienced, recreational drug users who have a recent or current history of using a drug in the pharmaceutical class of the test drug. These studies are typically double-blind, double-dummy, placebo-controlled, and positive-comparator controlled, utilizing a crossover design.5 For the study to be interpretable, the subjects should be able to reliably report “drug­liking” of the test drug and rate the effects of the test drug compared with placebo and with the positive control, such as an immediate-release formulation.5

Several instruments have been used to measure the potential for abuse including overall drug-liking, abuse, and likelihood of using the drug again.5 Key instruments include5:

  • Visual Analogue Scale (VAS)—a 100-point bipolar scale that measures drug-liking, overall high, good effects or euphoria, bad effects or adverse events, and likelihood of repeated use
  • Profile of Mood States

Category 4: Postmarket Studies

The goal of postmarket studies is to determine whether the marketing of a product with abuse-deterrent properties results in meaningful reductions in abuse, misuse, and related adverse clinical outcomes, including addiction, overdose, and death in the post-approval setting.5 Currently, data on the impact of an abuse-deterrent product on drug abuse in the U.S. population are limited, and thus the optimal data sources, study variables, design features, analytical techniques, and outcomes of interest of postmarket epidemiologic studies are not fully established.5

Labeling for Abuse Deterrent Opioid Formulations

Labeling for an abuse-deterrent product should include a description of the abuse-deterrent properties as well as the specific routes of abuse that the product has been developed to deter to inform health care professionals, the patient community, and the public about a product’s abuse potential.5 The FDA also encourages pharmaceutical companies to include the results of premarket studies in Categories 1, 2, and 3, and formal Category 4 postmarket studies.5

When premarket data show that a product’s abuse-deterrent properties can be expected to result in a meaningful reduction in that product’s abuse, these data are included in product labeling.5 When postmarket data become available, that data may also be added to the product labeling.5 If the postmarket data do not demonstrate a reduction in abuse, or if the data demonstrate a shift in routes of abuse that represent a greater risk, the FDA may determine that labeling revisions are needed.5

For more information see the FDA’s Guidance for Industry: Abuse-Deterrence Opioids—Evaluation and Labeling