1995. OxyContin (oxycodone controlled-release) approved; first formulation of oxycodone that allowed dosing every 12 hours instead of every 4 to 6 hours.
1998. Actiq (fentanyl) approved; first pain medicine approved to treat cancer breakthrough pain, but with additional safety measures.
Early 2000s. Reports of overdose and death from prescription pain drugs, especially OxyContin, began to rise sharply.
2001. OxyContin label was changed to add and strengthen warnings about the drug’s potential for misuse and abuse.
2003. FDA issued a Warning Letter (PDF – 149KB) to OxyContin’s manufacturer for misleading advertisements.
2007. FDA Amendments Act granted FDA authority to require for certain drugs specified safety measures known as Risk Evaluation and Mitigation Strategies (REMS).
2009. FDA held several public and stakeholder meetings, including May 27-28 public meeting and December 4 stakeholder meeting, to discuss opioid risks, misuse, and abuse.
FDA partnered with U.S. Substance Abuse and Mental Health Services Administration (SAMHSA) to launch an initiative to help ensure the safe use of the opioid methadone.
FDA launched the Safe Use Initiative to reduce preventable harm by medications, including opioids.
FDA began working with U.S. Drug Enforcement Administration (DEA) and others to help educate the public on safe disposal of opioids.
2010. FDA approved a new formulation of OxyContin.
FDA held joint advisory committee meeting to discuss its proposal for a class-wide REMS for Extended-Release (ER)/Long acting (LA) opioids, such as OxyContin.
2011. FDA approved REMS for transmucosal immediate-release fentanyl (TIRF) products, such as Actiq.
2012. FDA implemented the ER/LA opioids REMS program, which includes voluntary training for prescribers.
2013. January: On January 9, FDA issued a draft guidance to assist industry in developing new formulations of opioid drugs with abuse-deterrent properties: Guidance for Industry: Abuse-Deterrent Opioids – Evaluation and Labeling (PDF – 463KB).
FDA held a January 24-25 meeting of its Drug Safety and Risk Management Advisory Committee (PDF – 69KB) to discuss the public health benefits and risks, including the potential for abuse, of drugs containing hydrocodone either combined with other analgesics or as an antitussive.
February: FDA held a public hearing on February 7-8 to obtain information on issues pertaining to the use of opioid drugs in the treatment of chronic pain. Impact of Approved Drug Labeling on Chronic Opioid Therapy: Part 15 Hearing.
In an open letter to prescribers on March 1, FDA and health professional organizations asked all prescribers of opioids to ensure they have thorough knowledge of the FDA-approved product labeling for the opioids they prescribe, and to ensure they have adequate training in opioid therapy. FDA also encouraged all prescribers to help curb our nation’s opioid epidemic.
April: On April 16, FDA took multiple actions related to OxyContin.
May: On May 10, FDA responded to a petition and decided that the original formulation of Opana ER (oxymorphone hydrochloride) Extended-Release Tablets was not withdrawn from the market for reasons of safety or effectiveness. As a result, generic versions of the original formulation can continue to be approved and marketed.
FDA held the Clinical Development Programs for Opioid Conversion; Public Workshop; Request for Comments on July 29. The scientific workshop was held to address public health concerns associated with the inclusion of equianalgesic opioid conversion tables in opioid product labeling.
September: On September 10, FDA announced a set of significant measures to enhance the safe and appropriate use of extended-release and long-acting (ER/LA) opioids, including class-wide safety labeling changes and new post-marketing requirements for all ER/LA opioid analgesics. FDA also responded to two citizen petitions regarding labeling of opioids.
October On October 24, FDA issued Statement on Proposed Hydrocodone Reclassification from Janet Woodcock, M.D., Director, Center for Drug Evaluation and Research.
2014. April: On April 3, FDA approved Evzio (naloxone hydrochloride injection) for the emergency treatment of known or suspected opioid overdose. Naloxone is a medication that rapidly reverses the effects of opioid overdose. Evzio is the first auto-injector designed to deliver a dose of naloxone outside of a healthcare setting.
On April 14, FDA finalized the proposed class-wide safety labeling changes for all extended-release and long-acting (ER/LA) opioid analgesics, and responded to two citizen petitions regarding labeling for neonatal opioid withdrawal syndrome (NOWS).
July: On July 23, FDA approved Targiniq ER, an extended-release pain reliever that contains a combination of oxycodone and naloxone. Targiniq ER is the second extended-release/long-acting (ER/LA) opioid analgesic with FDA-approved labeling describing the product’s abuse-deterrent properties.
August: On August 19, FDA approved revisions to the ER/LA Opioid Analgesics REMS to incorporate information from the ER/LA opioid analgesic safety labeling changes (SLCs) announced on September 10, 2013, and approved on April 16, 2014. The most significant changes were to clarify the approved indications for use and limitations of use, and to revise warnings, including boxed warnings.
October: On October 17, FDA approved new labeling for Embeda (morphine sulfate and naltrexone hydrochloride), an extended-release (ER) opioid analgesic to treat pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. Embeda is the third ER opioid analgesic to be approved with labeling describing the product’s abuse-deterrent properties consistent with the FDA’s 2013 draft guidance, Abuse- Deterrent Opioids – Evaluation and Labeling. The new labeling includes a claim indicating that Embeda has properties that are expected to reduce oral and intranasal abuse when the product is crushed.
November: On November 20, FDA approved Hysingla ER (hydrocodone bitartrate), an extended-release (ER) opioid analgesic to treat pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. Hysingla ER is the fourth ER opioid analgesic to be approved with labeling describing the product’s abuse-deterrent properties consistent with the FDA’s 2013 draft guidance for industry, Abuse-Deterrent Opioids – Evaluation and Labeling. Hysingla ER has properties that are expected to reduce, but not totally prevent, abuse of the drug when chewed and then taken orally, or crushed and snorted or injected.
2015. January: January: On January 30, FDA approved a modified formulation of Zohydro ER (hydrocodone bitartrate extended-release capsules). The FDA has not approved an abuse-deterrent labeling claim for Zohydro ER.
April: On April 1, FDA issued a final guidance to assist industry in developing opioid drug products with potentially abuse-deterrent properties. Guidance for Industry: Abuse-Deterrent Opioids” (PDF – 227KB) explains the FDA’s current thinking about the studies that should be conducted to demonstrate that a given formulation has abuse-deterrent properties, makes recommendations about how those studies should be performed and evaluated, and discusses what labeling claims may be approved based on the results of those studies.
August: On August 13, FDA approved OxyContin for certain pediatric patients for pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. This approval is limited to opioid-tolerant pediatric patients 11 and up who are already taking and tolerating a minimum daily dose of at least 20 mg oxycodone orally or its equivalent. These patients can be expected to remain on treatment with an opioid for several weeks or more.
October: On October 2, FDA approved MorphaBond (morphine sulfate), an extended-release (ER) opioid analgesic to treat pain severe enough to require daily, around-the-clock, long-term opioid treatment for which alternative treatment options are inadequate. MorphaBond is the fifth ER opioid analgesic to be approved with labeling describing the product’s abuse-deterrent properties consistent with the FDA’s 2015 guidance for industry, Abuse-Deterrent Opioids – Evaluation and Labeling. MorphaBond has properties that are expected to reduce, but not eliminate, abuse of the drug when crushed and snorted or injected.
November On November 18, FDA approved Narcan nasal spray, the first FDA-approved nasal spray version of naloxone hydrochloride, a life-saving medication that can temporarily stop or reverse the effects of an opioid overdose, including an overdose from heroin.
2016. February: On February 4, FDA leaders, in response to the opioid abuse epidemic, called for a far-reaching action plan to reassess the agency’s approach to opioid medications. The plan will focus on policies aimed at reversing the epidemic, while still providing patients in pain access to effective relief.
On February 4, FDA released five postmarketing (PMR) requirements announced on September 13, 2013, and replaced them with 11 PMRs (10 postmarketing studies and one clinical trial) because the 10 postmarketing observational studies and one clinical trial include refined measures for assessing the known serious risks of misuse, abuse, addiction, overdose, and death.
On February 19 the FDA announced that during the April 12th meeting of the Pediatric Advisory Committee (PAC) they will present a framework of current plans for a 2-day joint meeting of the PAC, the Anesthetic and Analgesic Drug Products Advisory Committee, and the Drug Safety and Risk Management Advisory Committees. This joint meeting is scheduled for September 15 and 16, 2016 and during this meeting the FDA will be calling on a broad range of independent experts with real-world experience to provide recommendations on how to address the unique needs of children in pain.
March: On March 1, the FDA convened the Science Board to hear about and discuss a range of pressing issues related to the current opioid epidemic, including: (1) the role of opioids in pain management; (2) scientific challenges facing FDA in supporting the development of pain medications (3) scientific challenges facing FDA in seeking to understand the real-world use of opioids to treat pain (4) the role that FDA plays as a part of a larger Federal, State and local response to the challenges of providing appropriate pain treatment while reducing opioid abuse; and (5) postmarket surveillance activities related to opioids.
On March 22, FDA announced required class-wide safety labeling changes for immediate-release (IR) opioid pain medications. Among the changes, the FDA is requiring a new boxed warning about the serious risks of misuse and abuse, which can lead to 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.
On March 24, FDA issued a draft guidance titled “General Principles for Evaluating the Abuse Deterrence of Generic Solid Oral Opioid Drug Products.” This guidance recommends studies a generic applicant should conduct so FDA can evaluate the abuse deterrence of certain generic opioid drug products and help ensure that generic versions of approved opioids with abuse-deterrent formulations (ADFs) are no less abuse-deterrent than the brand named drug.
April: On April 26, FDA approved Xtampza ER (oxycodone), an extended-release (ER) opioid analgesic to treat pain severe enough to require daily, around-the-clock, long-term opioid treatment for which alternative treatment options are inadequate. Xtampza ER is the sixth ER opioid analgesic to be approved with labeling describing the product’s abuse-deterrent properties consistent with the FDA’s 2015 guidance for industry, Abuse-Deterrent Opioids – Evaluation and Labeling. Xtampza ER has properties that are expected to reduce, but not eliminate, abuse of the drug when crushed and snorted or injected.
May: On May 3-4, FDA convened a joint meeting of the Drug Safety and Risk Management Advisory Committee and the Anesthetic and Analgesic Drug Products Advisory Committee to discuss results from assessments of the extended-release and long-acting (ER/LA) Opioid Analgesics Risk Evaluation and Mitigation Strategies (REMS). The committees provided comments as to whether this REMS with Elements to Assure Safe Use (ETASU) assures safe use, is not unduly burdensome to patient access to the drugs, and to the extent practicable, minimizes the burden to the healthcare delivery system.
On May 26, FDA announced required safety labeling changes for methadone and buprenorphine products when used by pregnant women for medication-assisted treatment (MAT) of opioid use disorder to ensure providers have complete information about the benefits and risks of these products.
On May 26, FDA approved Probuphine, the first buprenorphine implant for the maintenance treatment of opioid dependence. Probuphine, an implant designed to provide a constant, low level of buprenorphine for six months, should be used in patients who are already stable on low-to-moderate doses of other forms of buprenorphine and as part of a complete treatment program that includes counseling and psychosocial support.
August: On August 19, FDA approved Troxyca ER (oxycodone hydrochloride and naltrexone hydrochloride extended-release capsules), an extended-release (ER) opioid analgesic to treat pain severe enough to require daily, around-the-clock, long-term opioid treatment for which alternative treatment options are inadequate. Troxyca ER is the seventh ER opioid analgesic to be approved with labeling describing the product’s abuse-deterrent properties consistent with the FDA’s 2015 guidance for industry, Abuse-Deterrent Opioids – Evaluation and Labeling. Troxyca ER has properties that are expected to reduce, but not eliminate, abuse of the drug when crushed and then taken orally, snorted, or injected.
On August 31, FDA announced required class-wide changes to drug labeling to help inform health care providers and patients of the serious risks associated with the combined use of certain opioid medications and a class of central nervous system depressant drugs called benzodiazepines. Among the changes, the FDA is requiring boxed warnings and Medication Guides for prescription opioid analgesics, opioid-containing cough products, and benzodiazepines with information about the serious risks, including extreme sleepiness, respiratory depression, coma and death, associated with using these medications at the same time.
September: On September 15-16, the FDA convened a joint meeting of the Anesthetic and Analgesic Drug Products Advisory Committee, the Drug Safety and Risk Management Advisory Committee, and the Pediatric Advisory Committee to discuss the appropriate development plans for establishing the safety and efficacy of prescription opioid analgesics for pediatric patients, including obtaining pharmacokinetic data and the use of extrapolation.
October: On October 5, the FDA convened a joint meeting of the Anesthetic and Analgesic Drug Products Advisory Committee and the Drug Safety and Risk Management to discuss naloxone products intended for use in the community, specifically the most appropriate dose or doses of naloxone to reverse the effects of life-threatening opioid overdose in all ages, and the role of having multiple doses available in this setting. The committees also discussed the criteria prescribers will use to select the most appropriate dose in advance of an opioid overdose event and the labeling to inform this decision, if multiple doses are available.
On October 31 – November 1, the FDA held a public meeting, Pre-Market Evaluation of Abuse-Deterrent Properties of Opioid Drug Products, to discuss scientific and technical issues relating to formulation development and pre-market evaluation of opioid drug products with abuse-deterrent properties. The meeting was intended to give FDA the opportunity to discuss, and seek public input from stakeholders on, the approach to testing FDA recommended in its draft guidance General Principles for Evaluating the Abuse Deterrence of Generic Solid Oral Opioid Drug Products. The meeting also provided an opportunity to discuss FDA’s efforts to develop standardized in vitro testing methodologies for evaluating the abuse deterrence of opioid drug products.
December: On December 16, the FDA approved several safety labeling changes (SLCs) about the serious risks of prescription opioid analgesics and opioids approved for medication assisted treatment (MAT) of opioid addiction including class-wide SLCs for immediate-release (IR) opioid pain medications, SLCs for methadone and buprenorphine products, and class-wide SLCs about the serious risks associated with the combined use of certain opioid medications with benzodiazepines or other central nervous system (CNS) depressants.
2017. January: On January 9, FDA approved Arymo ER (morphine sulfate extended-release tablets), an extended-release (ER) opioid analgesic to treat pain severe enough to require daily, around-the-clock, long-term opioid treatment for which alternative treatment options are inadequate. Arymo ER is the eighth ER opioid analgesic to be approved with labeling describing the product’s abuse-deterrent properties consistent with the FDA’s 2015 guidance for industry, Abuse-Deterrent Opioids – Evaluation and Labeling. Arymo ER is formulated to give it physicochemical properties expected to make abuse by injection difficult.
On January 17, FDA approved Vantrela ER (hydrocodone bitartrate extended-release tablets), an extended-release (ER) opioid analgesic to treat pain severe enough to require daily, around-the-clock, long-term opioid treatment for which alternative treatment options are inadequate. Vantrela ER is the ninth ER opioid analgesic to be approved with labeling describing the product’s abuse-deterrent properties consistent with the FDA’s 2015 guidance for industry, Abuse-Deterrent Opioids – Evaluation and Labeling. The physical and chemical properties of Vantrela ER are expected to make intravenous (injection) abuse difficult and are expected to reduce, but not eliminate, abuse by nasal and oral routes. However, abuse of Vantrela ER by these routes is still possible.
April: On April 20, FDA announced the restricted the use of codeine and tramadol medicines in children because these medicines carry serious risks, including slowed or difficult breathing and death, which appear to be a greater risk in children younger than 12 years, and should not be used in these children. These medicines should also be limited in some older children. The FDA also recommended against the use of codeine and tramadol medicines in breastfeeding mothers due to possible harm to their infants.
On April 20, the FDA approved RoxyBond (oxycodone hydrochloride), an opioid analgesic indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. RoxyBond is the first immediate-release opioid analgesic approved with labeling describing its abuse-deterrent properties consistent with the FDA’s 2015 Guidance for Industry: Abuse-Deterrent Opioids – Evaluation and Labeling. Based on laboratory studies, RoxyBond tablets are resistant to certain forms of manipulation such as crushing, grinding, or otherwise extracting oxycodone from the tablet that are typically used to make opioids easier to abuse by the nasal and intravenous routes.
On April 27, FDA held an expert roundtable for healthcare professionals to discuss their experiences with the use of cough suppressants in children (<18 years of age), particularly opioid containing antitussive products, as well as the data available to support recommendations made by various professional societies regarding the treatment of cough in children.
May: On May 9-10, FDA held a public meeting, Training Health Care Providers on Pain Management and Safe Use of Opioid Analgesics – Exploring the Path Forward, to obtain input on issues and challenges associated with Federal efforts to support training on pain management and the safe prescribing, dispensing, and patient use of opioids (safe use of opioids) for health care providers.
On May 10, FDA released the “FDA Education Blueprint for Health Care Providers Involved in the Management or Support of Patients with Pain” (draft revisions to the Blueprint), which broadens the current Blueprint to include information on pain management, including the principles of acute and chronic pain management; non-pharmacologic treatments for pain; and pharmacologic treatments for pain (both non-opioid analgesic and opioid analgesic).
June: On June 8, FDA requested that Endo Pharmaceuticals remove its opioid pain medication, reformulated Opana ER (oxymorphone hydrochloride), from the market based on its concern that the benefits of the drug may no longer outweigh its risks.
July: On July 6, the JAMA Viewpoint article by Dr. Scott Gottlieb and Dr. Janet Woodcock entitled, “Marshaling FDA Benefit-Risk Expertise to Address the Current Opioid Abuse Epidemic,” was published.
On July 6, following the FDA’s request, Endo announced that it would voluntarily remove reformulated Opana ER from the market.
On July 10-11, FDA held a public meeting, Data and Methods for Evaluating the Impact of Opioid Formulations with Properties Designed to Deter Abuse in the Postmarket Setting: A Scientific Discussion of Present and Future Capabilities, to discuss ways to improve the analysis and interpretation of existing data, as well as to discuss opportunities and challenges for collecting and/or linking additional data to improve national surveillance and research capabilities in this area.
On July 13, the National Academies of Science, Engineering, and Medicine release the consensus report, commissioned by the FDA, which outline the state of the science regarding prescription opioid abuse and misuse, as well as the evolving role that opioids play in pain management.
September: On September 11, FDA held a Pediatric Advisory Committee meeting to discuss the use of prescription opioid products containing hydrocodone or codeine for the treatment of cough in pediatric patients. The discussion included current practice for the treatment of cough in children and benefit-risk considerations regarding the use of prescription opioid products in pediatric patients.
On September 20, FDA advised that the opioid addiction medications buprenorphine and methadone should not be withheld from patients taking benzodiazepines or other drugs that depress the central nervous system (CNS). The combined use of these drugs increases the risk of serious side effects; however, the harm caused by untreated opioid addiction can outweigh these risks. Careful medication management by health care professionals can reduce these risks.
On September 28, after determining that a REMS is necessary for IR opioid analgesics to ensure that the benefits of these drugs continue to outweigh the risks, FDA sent letters to IR opioid analgesic manufacturers informing them that their products that are intended to be used in the outpatient setting will be subject to the same REMS requirements as the ER/LA opioid analgesics.
November: On November 21, FDA issued a final guidance titled “General Principles for Evaluating the Abuse Deterrence of Generic Solid Oral Opioid Drug Products.” This guidance recommends studies, including comparative in vitro and pharmacokinetic studies, that the potential abbreviated new drug application (ANDA) applicant should conduct and submit to FDA in an ANDA to 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.
On November 30, FDA approved Sublocade, the first once-monthly injectable buprenorphine product for the treatment of moderate-to-severe opioid use disorder in adult patients who have initiated treatment with a transmucosal (absorbed through mucus membrane) buprenorphine-containing product. It is indicated for patients that have been on a stable dose of buprenorphine treatment for a minimum of seven days.
December: On December 11-12, FDA hosted a public workshop regarding the role of packaging, storage, and disposal options within the larger landscape of activities aimed at addressing abuse, misuse, or inappropriate access of prescription opioid drug products; guiding principles and considerations for the design of packaging, storage, and disposal options for opioids; integrating packaging, storage, and disposal options into existing health care and pharmacy systems, including both open and closed health care systems; data needs and how to address challenges in assessing the impact of packaging, storage, and disposal options in both the premarket and postmarket settings; and ways in which FDA could encourage the development and assessment of packaging, storage, and disposal options for opioids that have the potential to enhance opioid safety.
2018. January: On January 11, FDA Commissioner, Scott Gottlieb, M.D., announced the 2018 Strategic Policy Roadmap, which provides an overview of some of the key priorities the agency will pursue advance FDA’s public health mission. Part of the Roadmap is reducing misuse and abuse of opioid drugs.
On January 11, FDA announced that it is requiring safety labeling changes for prescription cough and cold medicines containing codeine or hydrocodone to limit the use of these products to adults 18 years and older because the risks of these medicines outweigh their benefits in children younger than 18. The agency is also requiring the addition of safety information about the risks of misuse, abuse, addiction, overdose, death, and slowed or difficult breathing to the Boxed Warning of the drug labels for prescription cough and cold medicines containing codeine or hydrocodone.
On January 24, FDA and the Federal Trade Commission posted joint warning letters to the marketers and distributors of 12 opioid cessation products, for illegally marketing unapproved products with claims about their ability to help in the treatment of opioid addiction and withdrawal.
On January 30, FDA held a public hearing, “Opioid Policy Steering Committee: Prescribing Intervention—Exploring a Strategy for Implementation,” to receive stakeholder input on how FDA might, under its REMS authority, improve the safe use of opioid analgesics by curbing overprescribing to decrease the occurrence of new addictions and limit misuse and abuse of opioid analgesics.
On January 30, FDA announced limits to packaging for anti-diarrhea medicine Loperamide (Imodium) to encourage safe use.
On January 30, FDA posted the revised Blueprint, “Opioid Analgesic REMS Education Blueprint for Health Care Providers Involved in the Treatment and Monitoring of Patients with Pain,” which broadens the current Blueprint to include information on pain management, including the principles of acute and chronic pain management; non-pharmacologic treatments for pain; and pharmacologic treatments for pain. (It is important to note that the revised Blueprint will not be considered final until the Opioid Analgesic Risk Evaluation and Mitigation Strategy is approved.)
On February 14, FDA held a joint meeting of the Anesthetic and Analgesic Drug Products Advisory Committee and the Drug Safety and Risk Management Advisory Committee to discuss the new drug application for Hydexor (proposed tradename), a fixed-dose combination oral tablet, submitted by Charleston Laboratories, Inc., that contains hydrocodone, acetaminophen, and promethazine, for the short-term management of acute pain severe enough to require an opioid analgesic while preventing and reducing opioid-induced nausea and vomiting. The committees also discussed the abuse potential of this non-abuse-deterrent product and whether it should be approved.
February: On February 15, through a cooperative agreement with the FDA, the Duke-Margolis Center hosted a public workshop, “Strategies for Promoting the Safe Use and Appropriate Prescribing of Prescription Opioids,” to examine the landscape of health system and payer interventions to promote safe and appropriate prescribing of opioids; discuss how health systems and payers are using data and health IT tools to support interventions; discuss how health system approaches were implemented, barriers to their adoption, and potential unintended consequences of adoption; and discuss how to build an evidence base to support existing health system and payer interventions as well as how success may be defined and measured.
March: On March 27, FDA held a meeting of the Psychopharmacologic Drugs Advisory Committee to discuss the new drug application for lofexidine hydrochloride, submitted by US WorldMeds, LLC, for mitigation of symptoms associated with opioid withdrawal and facilitation of completion of opioid discontinuation treatment.
April: On April 17, FDA is hosting a public meeting on Patient-Focused Drug Development for Opioid Use Disorder (OUD), in collaboration with National Institute of Drug Abuse (NIDA). In addition to NIDA, FDA is also working closely with patient advocacy and community organizations to encourage participation from individuals with OUD. This meeting aligns with FDA’s ongoing work aimed at reducing the impact of opioid abuse and addiction.
On April 20, FDA issued the draft guidance, “Opioid Dependence: Developing Buprenorphine Depot Products for Treatment,” which reflects the agency’s current thinking regarding drug development and trial design issues relevant to the study of depot buprenorphine products (i.e. modified-release products for injection or implantation).
May: On May 16, FDA approved Lucemyra (lofexidine hydrochloride), the first non-opioid treatment for the mitigation of withdrawal symptoms associated with abrupt discontinuation of opioids.
On May 22, FDA convened a joint meeting of the Anesthetic and Analgesic Drug Products Advisory Committee and the Drug Safety and Risk Management Advisory Committee to discuss the new drug application for buprenorphine sublingual spray, submitted by INSYS Development Company, Inc., for the treatment of moderate-to-severe acute pain where the use of an opioid analgesic is appropriate. The committees will also be asked to discuss whether this product should be approved.
May: On May 30, FDA launched an innovation challenge to spur development of medical devices ‒ including digital health and diagnostics ‒ that target pain, addiction and diversion.
June: On June 1, FDA sent safety labeling change notification letters to drug companies with approved opioid analgesic products intended for use in an outpatient setting, which require the companies to include new safety information regarding the Opioid Analgesic REMS in the Boxed Warning and Warnings and Precautions sections of prescribing information due to a general lack of awareness of the REMS among all opioid analgesic prescribers.
June: On June 5, FDA took action against 53 websites marketing unapproved opioids as part of a comprehensive effort to target illegal online sales.
June: On June 14, FDA approved the first generic versions of Suboxone sublingual film.
June: On June 26, FDA convened a joint meeting of the Anesthetic and Analgesic Drug Products Advisory Committee and the Drug Safety and Risk Management Advisory Committee to discuss the new drug application for oxycodone extended-release capsules, submitted by Pain Therapeutics, with the proposed indication of the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. The product is intended to have abuse-deterrent properties based on its physicochemical properties. The committees will be asked to discuss whether the data submitted by the Applicant are sufficient to support labeling of the product with the properties expected to deter abuse.
June: On June 27, FDA convened internet stakeholders, government entities, academic researchers, and advocacy groups at a one-day Online Opioid Summit to discuss ways to collaboratively take stronger action in combatting the opioid crisis by reducing the availability of illicit opioids online.
July: On July 9, FDA hosted a public meeting on Patient-Focused Drug Development for chronic pain to hearing patients’ perspectives on chronic pain, views on treatment approaches, and challenges or barriers to accessing treatments for chronic pain.
August: On August 3, FDA convened a joint meeting of the Anesthetic and Analgesic Drug Products Advisory Committee and the Drug Safety and Risk Management Advisory Committee to discuss results from assessments of the transmucosal immediate-release fentanyl (TIRF) medicines’ risk evaluation and mitigation strategy (REMS), approved in December 2011. The TIRF REMS requires that healthcare providers who prescribe TIRF medicines for outpatient use are specially certified, that pharmacies that dispense TIRF medicines for inpatient and outpatient use are specially certified, and that completion of the prescriber-patient agreement form occurs prior to dispensing TIRF medicines for outpatient use. The Agency will seek the committees’ assessment as to whether this REMS with elements to assure safe use (ETASU) assures safe use, is not unduly burdensome to patient access to the drugs, and to the extent practicable, minimizes the burden to the healthcare delivery system. The Agency will also seek the committees’ input on any possible modifications to the TIRF REMS goals and requirements, as well as input on the adequacy of the evaluations conducted in the REMS assessments to determine whether the TIRF REMS goals are being met.
On August 6, FDA issued the draft guidance for industry, “Opioid Use Disorder: Endpoints for Demonstrating Effectiveness of Drugs for Medication-Assisted Treatment,” which is intended to assist sponsors in developing drugs for medication-assisted treatment of opioid use disorder (OUD) and addresses the clinical endpoints acceptable to demonstrate effectiveness of such drugs.
On August 22, FDA awarded a contract to the National Academies of Sciences, Engineering, and Medicine (NASEM) to help advance the development of evidence-based guidelines for appropriate opioid analgesic prescribing for acute pain resulting from specific conditions or procedures.
On August 28, FDA took action against 21 websites marketing unapproved opioids as part of agency’s effort to target illegal online sales.
September: On September 7, FDA approved a new dosage strength of buprenorphine and naloxone sublingual film as maintenance treatment for opioid dependence.
On September 18, FDA approved the Opioid Analgesic REMS.
On September 20, through a cooperative agreement with the FDA, the Duke Margolis Center for Health Policy convened a public workshop, “Expanding Access to Effective Treatment for Opioid Use Disorder: Provider Perspectives on Reducing Barriers to Evidence-Based Care.”
On September 27-28, FDA’s Office of Women’s Health, in collaboration with CDER and CTP, hosted a 2-day public meeting, “Opioid and Nicotine Use, Dependence, and Recovery: Influences of Sex and Gender.”
On October 11, FDA convened a meeting of the Anesthetic and Analgesic Drug Products Advisory Committee to discuss new drug application 210730, for oliceridine 1 milligram/milliliter injection, submitted by Trevena, Inc., for the management of moderate-to-severe acute pain in adult patients for whom an intravenous opioid is warranted. The committee also discussed the efficacy and safety data and benefit-risk considerations.
On October 12, FDA convened a meeting of the Anesthetic and Analgesic Drug Products Advisory Committee to discuss new drug application 209128, sufentanil sublingual tablets, submitted by AcelRx Pharmaceuticals, Inc., for the management of moderate-to-severe acute pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate, in adult patients in a medically supervised setting. The committee also discussed risk-benefit considerations and whether this product should be approved.
On November 1, FDA convened a joint meeting of the Psychopharmacologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee to discuss efficacy, safety and risk-benefit profile of new drug application 210417 for buprenorphine and samidorphan sublingual tablets, submitted by Alkermes, Inc., for adjunctive treatment of major depressive disorder.
On November 2, FDA approved first oral sufentanil pain medication for use in a medically supervised setting.
On November 14, FDA convened a joint meeting of the Anesthetic and Analgesic Drug Products Advisory Committee and the Drug Safety and Risk Management Advisory Committee to discuss new drug application 209774, for an immediate-release oral tablet formulation of oxycodone, which is intended to resist common methods of physical or chemical manipulation and to deter intravenous and intranasal abuse, submitted by SpecGx Inc., for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. The committees also determined whether the Applicant adequately demonstrated that the abuse-deterrent properties of the proposed product are sufficient to include this information in the product label, and whether the product should be approved.
November 15, FDA convened a meeting of the Anesthetic and Analgesic Drug Products Advisory Committee to discuss the assessment of opioid analgesic sparing outcomes in clinical trials of acute pain. The committee also commented on the trial design and endpoints of these studies and how to determine the clinical relevance of the results.
2019. January: On January 17, FDA announced the results of unprecedented work to design, test, and validate the key labeling requirements necessary to approve an over-the-counter (OTC) version of naloxone, including posting two model Drug Facts labels (DFLs) and the supporting FDA review. Overall, the study demonstrated that the model DFL was well-understood by consumers and is acceptable for use by manufacturers in support of their OTC naloxone development programs.
February: On February 6, FDA issued the final guidance, “Opioid Use Disorder: Developing Depot Buprenorphine Products for Treatment,” which reflects the agency’s current thinking regarding drug development and trial design issues relevant to the study of depot buprenorphine products (i.e. modified-release products for injection or implantation).
On February 12, FDA announced ongoing efforts to stop the spread of illicit opioids, further secure the U.S. drug supply chain and forcefully confront opioid epidemic.
March: On March 19, FDA took action against marketer of unapproved products claiming to treat addiction, chronic pain and other serious conditions.
On March 27, FDA announced new steps to strengthen agency’s safety requirements aimed at mitigating risks associated with transmucosal immediate-release fentanyl products.
April: On April 2, FDA took new enforcement actions as part of the agency’s ongoing effort to combat the illegal online sales of opioids.
On April 2, FDA hosted internet stakeholders, thought leaders, government entities, academic researchers, and advocacy groups at its second Online Opioid Summit.
On April 9, FDA announced harm reported from sudden discontinuation of opioid pain medicines and required label changes to guide prescribers on gradual, individualized tapering.
On April 19, FDA approved first generic naloxone nasal spray to treat opioid overdose.
On April 25, FDA launched a public education campaign to encourage safe removal of unused opioid pain medicines from homes.
May: On May 30, FDA opened a public docket to request information on requiring fixed-quantity blister packaging for certain opioid pain medicines to help decrease unnecessary exposure to opioids.
June: On June 11-12, FDA convened a joint meeting of the Drug Safety and Risk Management Advisory Committee and the Anesthetic and Analgesic Drug Products Advisory Committee to seek input on the clinical utility and safety concerns associated with the higher range of opioid analgesic dosing (both in terms of higher strength products and higher daily doses) in the outpatient setting. The FDA is interested in better understanding current clinical use; situations that may warrant use of higher doses of opioid analgesics; and the magnitude and frequency of harms associated with higher doses of opioid analgesics relative to lower doses, as well as optimal strategies for managing these risks while ensuring access to appropriate pain management for patients.
On June 20, FDA issued draft guidance, “Opioid Analgesic Drugs: Considerations for Benefit-Risk Assessment Framework,” which describes the application of the benefit-risk assessment framework that the agency uses in evaluating applications for opioid analgesic drugs and summarizes the information that can be supplied by opioid analgesic drug applicants to assist the agency with its benefit-risk assessment, including considerations about the broader public health effects of these products in the context of this crisis.
July: On July 2, FDA warned repackers distributing pharmaceutical ingredients, including opioids, for putting consumers at risk with significant violations of manufacturing quality standards.
On September 20, FDA issued a statement on the agency’s continued efforts to increase availability of all forms of naloxone to help reduce opioid overdose deaths.
On September 20, FDA announced the approval of new packaging for brand-name over-the-counter loperamide to help curb abuse and misuse.
On September 26, FDA held a joint meeting of the Pediatric and Drug Safety and Risk Management Advisory Committees to discuss the pediatric-focused safety review for OxyContin (oxycodone hydrochloride) extended-release tablets, as mandated by the Food and Drug Administration Safety and Innovation Act (Pub. L. 112-144), and to discuss pediatric data considerations for opioid analgesics labeling and Pediatric Research Equity Act studies for opioids generally, using Opana IR as an example.
On September 30, 2019 FDA and DEA warned website operators illegally selling opioids
October: On October 24, FDA outlined the agency’s first year accomplishments implementing SUPPORT Act authorities to address the opioids crisis
November: On November 26, FDA issues warning letter for products illegally marketed for the treatment of health conditions, including opioid withdrawal symptoms
December: On December 11, FDA issued warning letter for not including the most serious risks in advertisement for medication-assisted treatment drug
On December 19, the National Academies of Sciences, Engineering, and Medicine released a consensus report, commissioned by the FDA, on framing opioid prescribing guidelines for acute pain.