New FDA Directions – Part 3 – Opioids

In this third, and final installment on new directions for FDA under the watch of a new Commissioner, we turn to the issue of opioids. When Dr. Robert Califf was being considered for confirmation as FDA Commissioner he faced a great deal of concerns from members of Congress about opioids, even facing a hold on his nomination over the issue. Just prior to his confirmation hearing, FDA issued an Opioid Action Plan  that included a range of policy options designed to mitigate some of the risks of abuse. 

However, likewise this year Dr. Scott Gottlieb made clear during this confirmation process – in answer to the same concerns being addressed by members of Congress – that addressing issues associated with the opioid epidemic in the U.S. were for him a top priority. Since then, FDA has added to the body of actions undertaken in 2016 with respect to opioids. Here is a brief overview of where we are.

• Opening Salvo – Sworn in on May 11, Commissioner Gottlieb put up his first posting on the FDA blog – FDA Voice – outlining his first steps that he was taking to address the opioid crisis. He began laying out some policy parameters, advocating for opioid prescriptions to be given only for the durations of treatment that are needed – in other words not to set up prolonged use with a prescription that goes beyond the likely therapeutic need. As a practical matter, he stated that he was establishing an Opioid Policy Steering Committee that would assemble people within the agency to consider what additional tools or strategies are needed and posed three questions to the committee – (1) Are there circumstances under which FDA should require some form of mandatory education for healthcare professionals; (2) Should FDA take additional steps under risk management authorities such as requiring the dispensing of opioids in line with the clinical need and (3) is FDA using the proper framework for considering risk and abuse in the review process? What was not clear in the posting was which internal experts served on the committee, what the makeup was, procedures for meeting and making recommendations or a timeline. 
• Product Removal – A few weeks later on June 8, FDA requested the removal from market of Opana ER (oxymorphone hydrochloride) based on the concern that the benefits no longer outweighed the risks and followed FDA’s review of postmarketing data which suggested a shift in the route of abuse for the product from nasal to injection.
• Public Input on Deterrence – Five days later, Commissioner Gottlieb issued a statement announcing a public meeting to be held on July 10-11 focus a discussion on whether there is a secure understanding of whether abuse deterrent opioid products are having their intended impact – in other words – do we know if abuse deterrence deters? The transcript has been made available and is located here for the first day and here for the second, though not easy to find on the FDA site as the meeting is not posted in FDA’s Recent Meetings page.  
• Next Steps – In his opening remarks to the meeting, the Commissioner gave a more complete picture of where the agency was heading by (1) looking at ways to address exposure of people to opioids – in other words – addressing the risk associated with their normal use – not opioids that are being diverted – to make sure that appropriate patients get prescribed the appropriate amount of medication for their specific clinical need, with an aim of getting fewer prescriptions written in the first lace; (2) addressing the way we go about assessing the risk and benefit of pain relief products – looking at both individual risks as well as societal risk, and (3) to look at training for prescribers and other healthcare providers involved in pain management and whether existing programs are appropriate. He also stated that FDA intends to update the existing REMS on extended release opioid products as well as on immediate release.

On July 13, the Commissioner reiterated the position that his highest priority as Commissioner is to reduce the scope of the epidemic of opioid addiction. Naturally FDA by itself cannot address the breadth and depth of this epidemic. That said, in terms of new directions, what has so far transpired is really an investigational or information gathering phase. It is almost the inverse of the announcement of an Opioid Action Plan made prior to the Califf confirmation when FDA issued several steps it was taking to address the issue. This approach is more of a process than an event.

Right now, FDA is soliciting input, conducting studies and assessing the status quo. Early indications for manufacturers are clear however, that the environment for approval and marketing is going to change and that abuse deterrence, while a factor, is not a comprehensive solution, but only a part of a greater piece of the landscape. Beyond the information gathering phase we now seem to be in, if there is to be meaningful impact, the next phase regarding opioids will be the enunciation of additional new policies and their execution.