Safety and performance of current abuse-deterrent formulations

ABSTRACT

Introduction: Prescription opioid abuse is now an epidemic that has forced the government and industries to take initiatives. These include developing abuse-deterrent formulations (ADFs), issuing regulatory guidances and allocating massive budgets to ensure the safety and effectiveness of these medications.

Areas covered: This review covers the regulatory guidance on evaluation and labeling of the branded and generic ADFs. It also includes the relevant patents and technologies, the in-vitro, in-vivo, the post-marketing data, the FDA reviews, and the products’ labeling of the FDA-approved products with abuse-deterrent features.

Expert opinion: Despite the development of a dozen products with abuse-deterrent features, most of these technologies rely on the same deterrent agent, making it easier for abusers to focus their manipulation efforts and share their experience to defeat the technology. Further advancement in the field requires developing more robust, more diverse, safer, and affordable deterrent technologies for the extended- and immediate-release opioid products. Moreover, advances in the reporting of the post-market results, issuance of policies in support of the ADFs, and concurrent monitoring of the illicit opioid market are other considerations that can further help in confronting the epidemic.

KEYWORDS:

• Opioids
• abuse-deterrent
• formulation
• technology
• post-marketing
• safety
• toxicity

Article highlights

• The number of deaths due to prescription opioid abuse was over 16,500 in 2016 with an estimated cost of ~ $78.5 billion in 2017.

• Prescription opioid abuse is a complicated problem, exposing abusers to subsequent overdose health complications as well as toxicities derived from the excipients, the impurities, and the degradants of the manipulated drug and excipients; in particular when taken at larger amounts than allowed and administered via a non-oral route.

• The currently marketed ADFs, in general, have shown promise in reducing prescription drug abuse based on various pre-market studies and the available post-market surveillance.

• Despite the promising outcomes, the two major challenges left to be tackled are the liability to abuse by multiple oral administration of intact dosage units and the limited availability of the post-market data.

• Safer, more robust, more diverse, and cheaper deterring technologies need to be developed for both the extended- and immediate-release dosage forms.

• The unlimited number of ways that a prescription opioid can be manipulated calls for the FDA to continuously revise its guidelines to better evaluate the abuse-deterrent capability of the submitted ADFs.

• Further success and promise with the ADFs can be reinforced by the Government and State policies in support of their development, prescription, and insurance coverage.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One reviewer is an employee of the RADARS System, which provides postmarketing surveillance data to pharma and to US FDA. One of the peer reviewers who engaged in our double-blind peer review process is affiliated to the same institution as the authors. The other peer reviewer has no relevant affiliations to declare.

Additional information

Funding

This paper was not funded.