Scientifically driven solutions are needed to help combat opioid abuse, including potential abuse deterrent technologies.
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, and continued scientific research.5
In April 2015, the Food and Drug Administration (FDA) issued guidance to assist the pharmaceutical industry in developing new formulations of opioid drug products with potentially abuse-deterrent properties,5 which it believes have promise to help reduce, though not necessarily prevent, opioid abuse.5
In order to assess the impact of a potentially abuse-deterrent product, the FDA recommends looking at data from the below categories of pre-and postmarket 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. 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.
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
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
For more information see the FDA’s Guidance for Industry: Abuse-Deterrence Opioids--Evaluation and Labeling
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
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 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 healthcare professionals, the patient community, and the public about a product’s abuse potential. 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.
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. When postmarket data become available, that data may also be added to the product labeling. 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.
Abuse deterrence technology must continue to adapt to the changing chronic pain management landscape, though this technology does not completely eliminate the risk of abuse.5 Abuse deterrence technologies are just one of the measures physicians can employ to help mitigate the risk of opioid abuse and misuse. This video provides an overview of opioid abuse, including the FDA guidance on abuse deterrence technology.5
In April 2015, the FDA issued guidance to assist the pharmaceutical industry to develop new formulations of opioid drugs with abuse-deterrence properties.5 Most abuse-deterrence technologies developed to date are designed to make product manipulation more difficult, and abuse of the manipulated product less attractive or rewarding.
Physical and chemical barriers can limit drug release following mechanical manipulation, or change the physical form of a drug, rendering it less amenable to abuse.5
An opioid antagonist can be added to an opioid agonist to interfere with, reduce, or defeat the euphoria (or high) associated with abuse. For example, a drug may be formulated such that the antagonist is not clinically active when swallowed but becomes active if the product is crushed and injected or snorted.5
Substances can be combined to produce an unpleasant effect if the dosage form is manipulated prior to ingestion or if a higher dosage than directed is used.5
The properties of a new molecular entity (NME) or prodrug could include the need for enzymatic activation, different receptor binding profiles, slower penetration into the central nervous system, or other novel effects that would make the formulation less attractive for specific routes of abuse.5
Drug delivery systems can also offer resistance to abuse.5 For example, a sustained-release depot injectable formulation that is administered intramuscularly or subcutaneous implants can be more difficult to manipulate.5
Two or more of the technologies described in this section may be combined to deter abuse.5
Novel approaches include technologies that are not captured in the previous categories.5