September 21, 2018
On Monday September 17, 2018, with almost unanimous support, the Senate passed a package of 70 bills that collectively seek to address the myriad of challenges posed by the current opioid public health crisis. The bills will now undergo alignment with a similar package passed by the House in June before being presented to the White House. Only minimal changes, including adjustments to the Institutions for Mental Diseases exclusion rule, are expected. The bills focus the proposed $8.4 billion in funding across many federal agencies to execute a broad array of new and established opioid programs geared towards preventing deadly fentanyl shipments through the U.S. Postal Service, increasing the number of available behavioral health providers, and providing access to wrap around transitional recovery services including life-saving antidotes to opioid overdose.
Distinct from the more publicly-discussed initiatives is a pithy section 1302, providing clarification of the U.S. Food and Drug Administration’s (FDA’s) authority to require both Risk Evaluation and Mitigation Strategies (REMS) and post-approval packaging changes for drugs for which there is a serious risk of adverse event experience. For several years, the FDA has been actively engaged with stakeholders to explore how opioid drug products are packaged, stored, and disposed of. The Agency has been poised to act, waiting on this clarification to avoid potential challenges such as those threatened by the Pharmaceutical Research and Manufacturers of America (PhRMA). In its March 16, 2018, comments (filed in response to Dockets No. FDA–2017–N–5897 and FDA-2017-N-6502), PhRMA questioned the FDA’s authority to collectively compel manufacturers to revise the packaging of their approved drugs, notwithstanding the precedential value of the Agency having done just that in the context of oral contraceptives some 50 years earlier.[1] With this clarification, the FDA is proceeding with haste, approving the final Opioid Analgesic REMS on March 18, just one day after the bill package was passed.[2] This new plan, focused on communicating the serious risks associated with opioid pain medication to patients and health care professionals, applies to both immediate-release opioid analgesics intended for use in an outpatient setting as well as extended-release and long-acting opioid analgesics. Given the immediacy of the REMS finalization, a packaging mandate is expected shortly.
The FDA has already made significant progress in the type of packaging stakeholder consultation mandated under section 1302, and that work provides at least a directional read on what FDA will likely require. FDA initially engaged stakeholders to advance the conversation about packaging through meetings convened at the Duke-Margolis Center for Health Policy. With a published notice for public comment in the Federal Register in April 2014,[3] and again through a public and private sector workshop that was held in June 2017,[4] the Agency has explored packaging innovation, focusing on calendared blister packaging (CBP). In contemplation of the FDA’s initiatives, the Johns Hopkins Bloomberg School of Public Health and the Clinton Foundation, Clinton Health Matters Initiative issued a report entitled “THE OPIOID EPIDEMIC: From Evidence to Impact” in October 2017.[5] One of the key recommendations for action in this report is that funding should be secured to research and assess the effectiveness of existing innovative packaging designs as well as to inform future engineering developments.
Opioid packaging “prototypes” for (hydromorphone hydrochloride) Extended-Release Tablets USP, CII – 12 mg (chronic pain treatment) and (oxycodone hydrochloride) Tablets USP, CII – 30 mg (acute pain treatment) were developed to assist the Agency in considering how the design features of CBP could have an impact on prescribing habits (limited pill counts) as well as other risk mitigation factors. Complimentary to the newly-issued Opioid Analgesic REMS plan, the large, flat, readable billboard space of these prototypes accommodates educational and warning information that stays with the drug product throughout the intended life cycle and encounters the patient upon each drug taking event. The prototype designs were based largely upon in-market packages that had been extensively evaluated in both non-clinical and clinical published research to validate the proposition that the Child-Resistant / Senior Friendly CBPs are both safe and effective at improving patient medication adherence and persistent and associated health outcomes. At the state level, projects are ongoing to evaluate these opioid-specific prototypes. For example, through its Medication Adherence and Anti-Diversion Strategies Task Force, the State of Connecticut has begun work on a clinical trial to evaluate the impact of the prototype packaging on post dental surgery and post orthopedic surgery opioid therapy. It’s likely that these packaging innovations will change the way that drugs for which there is a serious risk of adverse event experience are packaged.
If you have any questions about anticipated FDA packaging requirements, please contact a member of Hancock Daniel’s Life Sciences team.
The information contained in this advisory is for general educational purposes only. It is presented with the understanding that neither the author nor Hancock, Daniel & Johnson PC, is offering any legal or other professional services. Since the law in many areas is complex and can change rapidly, this information may not apply to a given factual situation and can become outdated. Individuals desiring legal advice should consult legal counsel for up-to-date and fact-specific advice. Under no circumstances will the author or Hancock, Daniel & Johnson PC be liable for any direct, indirect, or consequential damages resulting from the use of this material.
[1] https://www.regulations.gov/document?D=FDA-2017-N-5897-0045.
[2] https://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm163647.htm?utm_campaign=FDA%20takes%20important%20steps%20to%20encourage%20appropriate%20and%20rational%20prescribing%20of%20opioids&utm_medium=email&utm_source=Eloqua&elqTrackId=EFA3F04E70ABA26B028D0DDFB7860C50&elq=fb60b788a58747a49eb8183c08d915e8&elqaid=5126&elqat=1&elqCampaignId=4100.
[3] Food and Drug Administration. Center for Drug Evaluation and Research; Use of innovative packaging, storage, and/or disposal systems to address the misuse and abuse of opioid analgesics; request for comments; establishment of a Public Docket. Federal Register. 2014;79(68):19619-19620.
[4] Exploring Packaging, Storage and Disposal Solutions to Enhance Opioid Safety. Duke-Margolis Center for Health Policy – Event Summary. June 1, 2017. Available at: https://healthpolicy.duke.edu/sites/default/files/atoms/files/6_1_17_discussion_guide.pdf (Accessed September 22, 2017)
[5] America’s Opioid Epidemic: From Evidence to Impact, Oct 30, 2017.
https://www.jhsph.edu/events/2017/americas-opioid-epidemic/index.html.
