Issue link: https://www.e-digitaleditions.com/i/922724
18 January 2018 Tablets & Capsules While the focus of these technologies remains on opioid- related products, there is also now some consideration for other drug products at increased risk for abuse. The science of abuse deterrence is relatively new, and the formulation technologies and the analytical, clinical, and statistical methods for evaluating those technologies are rapidly evolving. Based on the developing nature of the field, the FDA continues to take a flexible, adaptive approach to the evaluation and labeling of potentially abuse-deterrent products. Methods for evaluating the abuse-deterrent properties of new molecular entities may have to be adapted based on the characteristics of those products and the anticipated routes of abuse. Pharmaceutical companies, drug delivery companies, and CDMOs are evaluating the evolving regulatory environment and developing ADF technologies that better address the abuse of opioid painkillers. This article examines how the pharmaceutical industry, and CDMOs in particular, are working with the FDA to design, develop, and produce drug products that are more abuse- resistant; establish guidelines on labeling; and promote the safe and proper use of such products. Understanding the FDA regulatory actions The FDA's "Guidance for Industry: Abuse-Deterrent Opioids—Evaluation and Labeling," issued in April 2015, provides a framework for the development of ADF testing, though it principally addressed ER products. Draft guidelines introduced in March 2016 and finalized in November 2017—"General Principles for Evaluating the Abuse Deterrence of Generic Solid Oral Opioid Drug Products, Guidance for Industry"—establish more prescription opioid overdose, misuse, and addiction cost $78.5 billion [1]. Since 1999, the volume of drug products prescribed and sold in the USA has nearly quadrupled, and the rate of overdose deaths and of admissions to treat substance- abuse disorders related to prescription pain relievers have increased in parallel [2]. Due to the need to curtail opioid abuse, drug delivery technology companies and contract development and manufacturing organizations (CDMOs) have developed technologies that can deter abuse. The US FDA states that "The agency recognizes that abuse-deterrent opioids are not abuse-proof but are a step toward products that will help reduce abuse" [3]. Abuse-deterrent formulations (ADFs) make manipulation for abuse by routes such as snorting (insufflation), injection, or dose dumping more difficult and/or less rewarding. Yet these technologies must also allow the product to deliver the prescribed, effective pain-relieving dosage when taken by patients through the correct route of administration. Abuse deterrence, promoted through new FDA regulations and guidelines, has shaped how manufacturers address painkiller development and production, especially for controlled-release dosage forms. These products are most often abused in order to immediately obtain their drug loads, which are larger than those of immediate-release (IR) products. The FDA has been encouraging the development of abuse-resistant formats for both IR and extended-release (ER) forms of opioids, and promoting labeling that identifies the abuse- deterrent technologies used in the drug formulation in order to further deter abuse. Figure 1 Drugs involved in US overdose deaths, 2006 to 2016 25,000 20,000 15,000 10,000 5,000 0 Synthetic opioids other than methadone, 20,145 Heroin, 15,446 Natural and semi-synthetic opioids, 14,427 Cocaine, 10,619 Methamphetamine, 7,663 Methadone, 3,314 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 Source: CDC WONDER