Guidance is specifically for companies submitting ANDAs for generic solid oral opioid drug products.
Abuse of opiod-based pain medications is a serious problem in the United States. Academic and pharmaceutical industry researchers are urgently seeking to develop non-opiod alternatives that can provide pain management without the risk of addiction. Until new products are brought to the market, however, other actions must be taken to reduce the risk of abuse.
“Until we’re able to find new non-opioid forms of pain management for those who need treatment for pain, it’s critical that we also continue to promote the development of opioids that are harder to manipulate and abuse and take steps to encourage their use over opioids that don’t offer any form of abuse deterrence,” said US Food and Drug Administration (FDA) Commissioner Scott Gottlieb.
One approach has involved the development of opiod drugs in abuse-deterrent formulations (ADFs) that are intended to make it difficult for manipulation of the product, such as crushing of tablets to allow snorting or dissolution of capsules to allow injection, or the effects of the drug if abused to be less intense.
Ten such ADFs have been approved by the FDA, but according to Gottlieb, the uptake by physicians has been slow. “The reason for their more limited use is likely multifold. We know there can be a learning curve that comes with new technologies. Some prescribers may not be aware of the existence of these drugs, or may be uncertain of when to prescribe the abuse-deterrent versions. But we also know a significant barrier to use can be price. Because these new formulations are currently only available as brand-name products, they’re inherently more expensive than the numerous non-abuse deterrent formulations that are also available in generic formulations,” he said.
“Transitioning from the current market, dominated by conventional opioids, to one in which most opioids have abuse-deterrent properties, holds significant promise for a meaningful public health benefit,” said Gottlieb. “But to transition this market more quickly to the ADFs, and consider permanently withdrawing the older formulations that lack abuse-deterrent features in the event these products were judged to be less safe ‒ there are a number of factors we must consider. One of the factors that the FDA would consider relates to generic access. We must have the potential to improve access to the newer formulations, for appropriately selected and monitored patients, through the introduction of generic competitors.”
To increase access to generics, FDA recently issued final guidance on generic drugs with abuse-deterrent properties. The guidance, General Principles for Evaluating the Abuse Deterrence of Generic Solid Oral Opioid Drug Products, is intended to aid companies intending to file abbreviated new drug applications (ANDA) for generic versions of solid oral opioid drug products that reference opioid drug products with abuse-deterrent properties described in their labeling.
There are seven types of technologies for creating ADFs - physical/chemical barriers, agonist/antagonist combinations, aversion, delivery system, new molecular entities (NMEs) and prodrugs, combinations, and novel approaches. The final guidance addresses the abuse deterrence of generic solid oral opioid drug products formulated to incorporate physical or chemical barriers, agonist/antagonist combinations, aversive agents, or a combination of two or more of these technologies. For the remaining technologies, FDA has indicated it may provide testing recommendations in future product-specific guidance
Included in the guidance are recommended comparative in vitro and pharmacokinetic studies that demonstrate that a generic solid oral opioid drug product is no less abuse deterrent than its reference listed drug with respect to all potential routes of abuse.
In addition to the new guidance, FDA is taking further steps to support the rapid approval of generic ADFs, including the development of testing methodologies for evaluating complex features, such as abuse deterrence for both brand name (innovator) and generic opioid drug products, a new approach for the evaluation and labeling of ADF opioids and the introduction of new review policies to provide a more efficient pathway for the generic entry of opioid ADFs. Generic drug developers are encouraged to meet with the agency to discuss scientific and regulatory issues before submitting their applications.