While Congress works to develop a legislative fix to the growing opioid abuse problem facing the country, the Administration is hoping an FDA-CDC one-two punch will work to quickly address the situation. Late last week, the FDA announced the release of new draft guidance intended to ensure that generic versions of abuse-deterrent opioids meet the same standards for abuse deterrence as their brand-name counterparts. These new guidelines come just days after the CDC released the first-ever national prescribing guidelines for opioids and FDA announced new labeling guidelines applying to all opioids (not just those that are extended release).
The latest FDA draft guidance on generic opioids is part of a wider effort by the Administration to address the national opioid epidemic. In February, the FDA detailed its opioids action plan, saying it would require advisory committee meetings for all new opioid drugs that lack abuse-deterrent properties, strengthen warnings for all immediate-release formulations and increase postmarket requirements to include new studies and updated risk evaluation and mitigation strategy (REMS) requirements for opioids.
The goal of the latest FDA draft guidance, entitled “General Principles for Evaluating the Abuse Deterrence of Generic Solid Oral Opioid Drug Products,” is to ensure that generic versions of abuse-deterrent opioids are “no less abusedeterrent” than their reference products. Because FDA requires generic drugs to be therapeutically equivalent to their reference products, the draft guidance says it expects generic sponsors to conduct “comparative in vitro studies and, in some cases, in relevant pharmacokinetic or other studies to show that it is no less abuse-deterrent than the [reference drug].” These studies will follow a tierbased approach, starting with simple manipulations of the product and progressing to more destructive manipulations until the reference product’s abuse deterrence is defeated or compromised, or the generic product is shown to be less abuse-deterrent.
The idea behind abuse deterrent formulations (ADF) is to allow an opioid to work correctly when taken as prescribed, but is formulated in such a way that deters misuse and abuse, including making it difficult to inhale or inject the drug for a more intense high.
To encourage additional input from outside experts and the public, the agency will also hold a public meeting later this year to discuss the draft guidance on generic ADF products and a broad range of issues related to the use of abuse-deterrent technology as one tool to reduce prescription opioid abuse. FDA will take this feedback into consideration when developing the final guidance on this topic.
These FDA guidelines on generic opioids come just days after the agency announced mandatory class-wide safety labeling changes for immediate-release (IR) opioid pain medications. Immediate-release opioids account for about 90 percent of opioid prescriptions. This is not the first time the agency had tightened opioid labels. In 2013, the agency toughened labeling requirements for extended-release opioids, which are often seen as a bigger addiction risk because of their potency. Now, many of those changes are being applied to the immediate-release version.
Among the changes, the FDA is requiring a new boxed warning about the serious risks of misuse, abuse, addiction, overdose and death. The FDA is also requiring several additional safety labeling changes across all prescription opioid products to include additional information on the risk of these medications. The updated indication clarifies that because of these risks, IR opioids should be reserved for pain severe enough to require opioid treatment and for which alternative treatment options (such as non-opioid analgesics or opioid combination products, as appropriate) are inadequate or not tolerated. The dosing information also provides clearer instructions regarding patient monitoring and drug administration, including initial dosage, dosage changes during therapy and a warning not to abruptly stop treatment in a physically dependent patient.
Additionally, the FDA now requires a precaution that chronic maternal use of opioids during pregnancy can result in neonatal opioid withdrawal syndrome (NOWS). Additionally, the FDA is requiring updated labeling for all opioids (both ER/LA and IR products) to include safety information about potentially harmful drug interactions with other medicines that can result in a serious central nervous system condition called serotonin syndrome.
The CDC has also become involved in the Administration’s efforts to address the nation’s growing opioid addiction problems. Two weeks ago, the Centers for Disease Control and Prevention (CDC) published prescribing guidelines to address the epidemic of deaths and overdoses attributed to opioid painkillers. The guidelines, which focus on chronic pain except for cancer and end-of-life care, arrive amid increased concern over the growing number of Americans who abuse or misuse the drugs annually. The guidelines are targeted at primary care physicians, in particular, as family doctors write the vast majority of prescriptions for opioids.
The CDC guidelines, which are voluntary, urge primary care clinicians (which include doctors, physician assistants and nurse practitioners) to offer patients alternative treatments for chronic pain, such as non-opioid painkillers like ibuprofen and physical therapy, and to prescribe the lowest effective dosage possible to patients who do need opioid drugs and monitor the patient carefully. The agency also recommends doctors prescribe opioids only after those other therapies have failed. The CDC also recommends limiting opioid prescriptions for patients suffering short-term, acute pain to three days or less in most conditions, and says that more than seven days’ worth of opioid drugs “will rarely be needed.”
While the Administration seems to be moving ahead quickly with its plan to address the opioid abuse issue, the Congressional picture remains murky. Anti-addiction advocates are pressing the House to move forward on the Senate-passed Comprehensive Addiction and Recovery Act (CARA), although the Judiciary Committee has yet to schedule a hearing. The House version was introduced in February 2015 and currently has 107 co-sponsors (75 Democrats, 32 Republicans). Despite the topic being a major point of discussion in recent months, Congressional gridlock has, and continues to prevent the meaningful legislation addressing opioids from being passed.