A Glossary of REMS-Related Terms
Adverse Drug Event (AE) – Any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease associated with the use of a drug, whether or not the problem is considered drug related (also referred to as an adverse drug experience).
Adverse Drug Reaction (AR) – An ADE for which there is a reasonable possibility that the medical problem may have been caused by the drug
Baycol – A drug withdrawn from the market in August 2001 after fatal risk of muscle wasting was identified
Benefit-Risk Profile – An assessment of whether the therapeutic benefits of taking a medicine outweigh the risks involved.
Black-Box Warning – Warning text required by FDA that is placed at the top of the prescribing information to indicate that the drug carries a risk of a serious, possibly life-threatening adverse event.
Class REMS – A REMS program for a class of drugs that share a common set of risks where a single REMS system can be used by different manufacturers. To date, the safety risks of 6 classes of drugs are managed through a “class” REMS: long-acting opioids, fluoroquinolone antibiotics, anti-epileptic drugs, tumor necrosis factor (TNF) blocking drugs/inhibitors, botulinum toxins, and erythropoiesis-stimulating agents.
Communication Plan – Developed by the drug’s sponsor to support implementation of a REMS program, a communications plan is intended to inform key audiences (health care providers) about the risks of the drug. The communication plan may include sending letters to healthcare providers; disseminating information about REMS elements to encourage implementation by healthcare providers or to explain certain safety protocols; and disseminating information to healthcare providers through professional societies about any serious risks of the drug and any protocol to assure safe use.
Consumer Medical Information (CMI) – Written information about prescription medicines developed by organizations or individuals other than a drug’s manufacturer that is intended for distribution to consumers at the time of drug dispensing. CMI is currently not reviewed or approved by FDA.
Elements to Assure Safe Use (ETASU) – The most extensive elements of a REMS, “Elements to Assure Safe Use” (ETASU) are carefully planned safety protocols required when the Food and Drug Administration (FDA) determines that a medication can only be marketed with stringent controls to ensure a serious or fatal risk can be avoided by proper use of the drug. ETASU elements include physician qualification and registration, patient informed consent, and pharmacist distribution limitations as well as controls to ensure the safe return and disposal of unused medications.
Expedited Reporting – Safety reports about serious adverse events associated with a drug that require reporting within a short timeframe to FDA.
FDA Adverse Event Reporting System (FAERS) – A database operated by FDA that contains information on adverse event and medication error reports submitted to the agency. FDA evaluates the reports in FAERS to monitor the safety of drugs and biologics after they are approved. Based on the potential safety risks identified through FAERS, FDA may require new information on the product’s labeling, restrict the use of the drug, and in rare cases, take the drug off the market.
Food and Drug Administration Amendments Act (FDAAA) – Legislation enacted in 2007 in which Congress gave FDA many new authorities and responsibilities to enhance drug safety, including the power to require a Risk Evaluation and Mitigation Strategy (REMS).
FDASIA – Food and Drug Administration Safety and Innovation Act, legislation signed into law in July 2012 that gives the Food and Drug Administration the authority to collect user fees from the medical industry to fund reviews of innovator drugs and medical devices
Generics – A consumer product bearing no brand name or trademark. Generic versions of name-brand drugs are often sold at a lower cost to the consumer.
Implementation Plan – A description of how certain ETASUs will be implemented.
Isotretinoin – An acne drug found to cause severe birth defects and which consequently has REMS put in place for its prescribers and users.
Medication Guide – Not usually required unless the REMS program includes ETASU, a Medication Guide contains information for patients written in non-technical language on how to take a drug safely. Healthcare providers are required to dispense a Medication Guide with each prescription as a review tool in counseling the patient on the risks of the prescribed medicine.
MedWatch – A system maintained by FDA for the voluntary reporting of adverse events, potential and actual medical product errors, and product quality problems associated with the use of drugs, biologics, devices, and dietary supplements.
New Safety Information – Defined as a serious risk associated with use of a drug of which FDA has become aware since the drug was approved, since a REMS was required, or since the last assessment of the REMS.
Patient Package Insert (PPI) – Contains information for patients’ understanding of how to safely use a drug product. Today, the Medication Guide has largely replaced the PPI as an element of a REMS.
PDUFA (Prescription Drug User Fee Act) – First enacted in in 1992 (PDUFA I), this legislation gives FDA the authority to collect fees from industry to accelerate its drug evaluation process without compromising review quality. Reauthorized by the Congress every 5 years, the most recent PDUFA reauthorization (PDUFA IV) was under the Food and Drug Administration Safety and Innovation Act (FDASIA) of 2012.
PDUFA V – Signed into law on July 9, 2012, the Food and Drug Administration Safety and Innovation Act (FDASIA) of 2012 reauthorized PUDFA through September 30, 2017. FDASIA also specifies FDA’s performance goals in 5 general areas: (1) drug review performance goals, communication, and timing; (2) regulatory science; (3) risk-benefit assessment in decision-making; (4) drug safety; and (5) information technology and performance management.
Post Approval Study (PAS) – Under FDA’s REMS authority, the agency may require the manufacturer to conduct studies after the drug is approved to obtain further evidence of its safety and effectiveness. The studies are often required when newly acquired information raise concerns about potential unanticipated safety risks.
Post-market – Once a drug has been released onto the market to be prescribed, purchased, and used
REMS (Risk Evaluation and Mitigation Strategy) – A REMS is a risk management plan that goes beyond the requirements in the drug prescribing information to manage serious risks associated with a drug and to enable patients to have continued access to such medicines by managing their safe use.
REMS Supporting Document – Includes a thorough explanation of the rationale for, and supporting information about, the content of the Proposed REMS.
Restricted Distribution – Classified as one of the “Elements to Assure Safe Use,” restricted distribution systems are rare and only required by FDA to ensure a medicine known to cause birth defects, organ damage and other serious or life-threating events is only acquired and used by patients under carefully controlled conditions. These systems may require physician qualification and registration, patient informed consent, pharmacist distribution limitations, controls to ensure the safe return and disposal of unused medications, patients enrolling in a registry and patients undergoing routine testing, such as women having a monthly pregnancy test.
Risk Management – The application of scientifically-based methodologies to identify, assess, communicate and minimize the risks of a medicine in order to maintain the drug’s favorable benefit-risk profile in patients.
Risk Management Plan (RMP) – A set of activities designed to identify, characterize, prevent, or minimize the risks of medicine use; to assess the effectiveness of these interventions; and to communicate the risks to patients and health care providers.
Serious Adverse Event (Serious Adverse Experience) – Any unfavorable and unintended sign, symptom, or medical problem occurring at any dose of a drug that results in death, a life-threatening adverse drug experience, hospitalization, a significant disability/incapacity, or a congenital anomaly/birth defect.
Soliris – The only drug available to treat a rare blood disease and which carries a risk of meningitis.
Subpart H approval – An alternate approval process put in place by the Food and Drug Administration to avoid delaying approval for risky but important drugs.
Timetable for Submission of Assessments – The schedule for evaluating the effectiveness of the manufacturer’s REMS safety measures. FDA requires that assessments be conducted at 18 months, 3 years, and 7 years after the REMS is approved with the results reported to the agency. Results may be used to modify the REMS, or even eliminate it, if the assessment shows changes are needed or that the REMS has met its goals.
Toxicity – The capability of a drug or other substance to cause death or injury. The level of toxicity associated with a medicine may vary with the condition for which the medicine is used, as well as the dosage.
Trasylol – A drug withdrawn from the market in November 2007 after risk of death was identified.
Unsuspected Serious Risk – A serious adverse event that is not listed in the labeling of a drug or differs from the adverse drug experience identified in the labeling due to greater severity, specificity, or prevalence.
Vioxx – A widely-used arthritis drug that was discovered to have dangerous cardiovascular risks and revealed the Food and Drug Administration’s limited authority to regulate drugs after their release onto the market.