Assist With Monitoring Safety

Overview

Postmarket surveillance is the process of monitoring the safety of a therapy after it has received marketing approval by the U.S. Food and Drug Administration (FDA). Because clinical trials are conducted in small numbers of patients, new issues may arise when a treatment is used by a larger population after approval. Your patient group can provide a bridge between patients, industry, and the FDA to help with postmarket surveillance.

Purpose of Surveillance

You can ensure the FDA has the information it needs to protect your patient community by explaining the importance of postmarket surveillance to both your patient community and your network of health care providers. Postmarket surveillance can:

  • Detect unexpected side effects or an increase in severity including:
    • Adverse reactions
    • Poisonings
    • Medical complications
  • Monitor adherence to the terms and conditions of approval.
  • Track manufacturing consistency and control.
  • Lead to labeling updates. 
  • Trigger approval re-evaluation.

FDA Surveillance Programs

The FDA has several policies and programs in place that are intended to promote appropriate postmarket surveillance. Understanding these programs can help you guide your disease community on the ways to report side effects, medication errors, quality issues, and concerns about advertisements should any occur. 

  • FDA Adverse Event Reporting System (FAERS): FAERS is the database that contains adverse event reports, medication error reports, and reports of therapy quality issues that resulted in adverse events that were submitted to the FDA.
    • FAERS covers drugs and biologics. Medical devices and other regulated therapies have a separate database and reporting system, Manufacturer and User Facility Device Experience (MAUDE), which is described below in more detail.
    • Patients/families and health professionals may use the public friendly portals through MedWatch (more details about MedWatch are available below) to report adverse events. 
      • Printable forms to report events can be found on MedWatch in both English and Spanish. 
      • Adverse events can also be reported by phone (toll-free): 1-800-332-1088.
      • MedWatch includes linking to reporting systems for medical devices and other regulated therapies.
    • Adverse events may also be reported through the FDA Safety Reporting Portal.
    • Reports to the FDA can be made by:
      • Healthcare professionals
      • Patients, families, and caregivers (often referred to as consumers)
      • Manufacturers
    • Healthcare professionals and consumers may also report to the therapy’s manufacturers. 
      • If a manufacturer receives a report from a healthcare professional or consumer, they are required to send the report to the FDA as specified by regulations.  
    • The FDA provides a public-friendly FAQs that can be shared with your patient community at Questions and Answers on FDA’s Adverse Event Reporting System (FAERS)
    • The reports in FAERS are evaluated by clinical reviewers in the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) to monitor the safety of therapies after they are approved by FDA.
      • If a potential safety concern is identified in FAERS, further evaluation is performed.
      • Regulatory action(s) may be instituted to improve therapy safety and protect the public health, such as updating a therapy’s labeling information, restricting the use of the therapy, communicating new safety information to the public, or (in rare cases) removing a therapy from the market.
    • FAERS data does have limitations. FAERS should not be used to calculate the incidence of an adverse event or medication error in the U.S. population or causality of event to therapy.
      • FDA does not require that a causal relationship between a therapy and event be proven to be submitted as an adverse event.
      • Reports do not always contain enough detail to properly evaluate an event.
      • There may be multiple reports of the same event, for example, a report could be submitted by a patient/family member, medical professional, and manufacturer.
      • Not all adverse events or medication errors are reported.
  • MedWatch program: MedWatch is the FDA’s therapy safety reporting program for health professionals, patients/families, and consumers. 
    • MedWatch receives reports from the public and, when appropriate, publishes safety alerts for FDA-regulated therapies such as:
      • Human drugs
      • Medical devices
      • Vaccines
      • Biologics
      • Dietary supplements
      • Cosmetics
    • Mandatory reporting by manufacturers includes:
      • Error and accident reports or therapy quality reports when deviation from current good manufacturing practice regulations occurs.
      • Adverse event reports, medication error reports, and therapy quality complaints resulting in adverse events reported to the manufacturer by consumers or health care professionals. 
    • MedWatch Online Voluntary Reporting Form is for both health professionals and consumers. It contains data regarding: 
      • Unexpected side effects or adverse events including everything from skin rashes to more serious complications.
      • Therapy quality problems, such as whether a therapy isn’t working properly or it has a defect.
      • Therapy use or medication errors that can be prevented. 
        • These can be caused by various issues, including selecting the wrong therapy because of similar labels, packaging, brand names, or generic names.
        • Mistakes can also be caused by hard-to-read controls or displays on a medical device, which may cause an incorrect test result to be reported.
      • Therapeutic failures, such as a medical therapy seemingly not working as well when switching from brand name to generic or from one generic to another.
    • Printable versions of the reporting forms in English and Spanish as well as information about other reporting agencies of concerns about vaccines, tobacco, cigars, e-cigarettes/vaping and chewing tobacco and animal and veterinary products are available at Reporting Serious Problems to FDA.
    • Contact information for inquiries about specific products or questions regarding adverse event reporting as well as other FDA safety information resources are available on the webpage, Medical Product Safety Information.
  • Medical Device Report (MDR): The Manufacturer and User Facility Device Experience (MAUDE) database contains MDRs submitted to the FDA by mandatory reporters (manufacturers, importers, and device user facilities) and voluntary reporters such as health care professionals, patients, and consumers.
    • MDR provides more information about mandatory and voluntary reporting of adverse events on their website, Medical Device Reporting (MDR): How to Report Medical Device Problems
    • Patients, caregivers, and consumers are encouraged by FDA to submit voluntary reports of significant adverse events or medical device problems through MedWatch, the FDA’s Safety Information and Adverse Event Reporting Program (described in more detail in the section above).
    • The FDA requires that certain agencies to report when a medical device may have caused or contributed to a death or serious injury, including device malfunctions. Mandatory reporting is required by:
      • Manufacturer
      • Importers
      • Device User Facilities, which are defined as any hospital, ambulatory surgical facility, nursing home, outpatient diagnostic facility, or outpatient treatment facility, that is not a physician’s office.
        • Possibly associated deaths are required to be reported to both manufacturer and FDA.
        • Serious injuries can be reported to either the manufacturer or FDA. 
        • Malfunction reporting is not mandatory by device user facilities but can be voluntary.
    • The Voluntary Malfunction Summary Reporting (VMSR) program permits manufacturers to report certain device malfunction MDRs in summary form on a quarterly basis. 
  • Office of Prescription Drug Promotion (OPDP): OPDP monitors and regulates the labeling of approved drugs and biologics and  promotional efforts by the manufacturer/Sponsor.
    • OPDP does not regulate promotions for: 
      • Over-the-counter drugs
      • Dietary supplements
      • Medical devices
    • OPDP regulates the following types of promotions:
      • TV and radio advertisements
      • All written or printed prescription drug/biologic promotional materials
      • Speaker program presentations
      • Sales representative presentations
    • Responsibilities of OPDP include: 
      • Providing written comments to pharmaceutical Sponsors on proposed promotional materials to ensure clear and unambiguous communication of the laws and regulations relating to prescription drug/biologic promotion.
      • Reviewing complaints about alleged promotional violations.
      • Initiating enforcement actions on promotional materials that are false or misleading.
      • Comparing the therapy labeling and promotional materials of various closely related therapies to ensure that regulatory requirements are consistently and equitably applied.
      • Traveling to major medical meetings and pharmaceutical conventions to monitor promotional exhibits and activities.
      • Acting as a liaison between OPDP and other divisions within the FDA on promotional issues.
    • OPDP supports the FDA Bad Ad program, an outreach program designed to educate healthcare providers about the role they can play in ensuring that prescription drug/biologic advertising and promotion is truthful and not misleading.
      • Although the webpage Truthful Prescription Drug Advertising and Promotion is targeted towards health professionals and the Bad Ad Program, it provides information about:
        • Standards for drug/biologic promotions.
        • Common violations and examples.
        • How to report suspected violations.
    • Contact OPDP staff at +1-301-796-1200.
  • Division of Medication Error Prevention and Analysis (DMEPA): DMEPA is responsible for monitoring and preventing medication errors related to the naming, labeling, packaging, and design for CDER-regulated drugs and biologics.
    • FDA defines a medication error as any preventable event that may cause or lead to inappropriate medication use or patient harm while the medication is in the control of a healthcare provider, patient, or consumer.
    • The deliberate or intentional use of a therapy in a manner that is inconsistent with FDA-required labeling (e.g., abuse, misuse, off label use) isn’t generally considered a medication error.
    • A medication error may or may not result in an adverse event.
    • Reporting is currently voluntary, but the FDA encourages reporting by healthcare providers, patients, caregivers, consumers, and manufacturers. 
      • Reports can be filed through MedWatch, the FDA’s safety information and adverse event reporting program (described in more detail in the section above).
    • Examples of reportable medication errors include:
      • Look-alike container labels.
      • Confusing prescribing information that may cause or lead to a medication error.
    • DMEPA monitors and analyzes medication error reports associated with marketed drug therapies, including:
      • Over-the-counter
      • Prescription, generics, and biosimilars and other therapeutic biologics.
    • FDA may take regulatory action, such as:
      • Revising the labeling or issuing a safety communication to help prevent errors. 
      • Changing the proprietary name to address safety issues resulting from name confusion errors.
    • The FDA provides more information about DMEPA on their webpage, Medication Errors Related to CDER-Regulated Drug Products
  • Therapy shortages: FDA’s policy attempts to prevent or alleviate shortages of medically necessary therapies.
    • Therapy shortages may arise from varying causes, such as the unavailability of raw materials or packaging components, marketing decisions, and enforcement issues.
    • Manufacturers provide the FDA with the most current therapy shortage information, and the agency works closely with the manufacturers to prevent or reduce the impact of shortages.
    • The FDA provides more information about policies related to preventing and minimizing therapy shortages on their webpage, Drug Shortages
    • CDER provides an overview of therapy shortage management responsibilities and how therapy shortage reports are processed related to therapy shortages in the PDF, MAPP on Drug Shortage Management
      • This resource is written using legal, technical language, but may be helpful if your disease community experiences a therapy shortage. 
      • Depending on your own background and experience, you may wish to share this resource with your Scientific/Medical Advisory Board.

Requirement and Commitment

Postmarket surveillance can be officially part of the marketing approval requirements or can be part of a commitment made by the Sponsor when applying for marketing approval in the New Drug Application (NDA). Required and committed postmarket surveillance may involve Phase IV clinical trials. Patient registries and natural history studies may also be used to collect data. Additionally, you may wish to learn more about Sentinel, an FDA initiative to provide real world evidence for therapy approval and postmarket surveillance.

  • Postmarket requirement: The FDA may require postmarket surveillance for newly approved therapies to ensure its safety and efficacy in the general patient population, often in a less controlled environment. 
    • Postmarket studies or clinical trials are required to confirm clinical benefit for therapies approved using:
      • Accelerated approval.
      • Deferred pediatric studies. Clinical trials in the pediatric population may be required for therapies that treat or prevent diseases that affect both adults and children.
        • A Sponsor may request clinical trials involving children be deferred until after FDA marketing approval for the therapy in adults is received.  
      • Animal Efficacy Rule. For more information see the FDA webpage, Animal Rule Information.
        • Applies to therapies that cannot be ethically tested in humans at the time of approval.
        • For example, consider the FDA approval in 2018 of a therapy to treat smallpox: FDA approves the first drug with an indication for treatment of smallpox
          • Efficacy was established through well-controlled animal studies. 
          • Safety in humans was established by giving the investigational therapy to several hundred human volunteers.
          • Human volunteers were not exposed to smallpox however to determine efficacy in humans. 
          • Efficacy and safety are required to be closely monitored in the event it is used.
    • Postmarket studies or clinical trials may also be required to:
      • Assess a known serious risk related to the use of the therapy identified in clinical trials prior to approval.
      • Assess signals of serious risk related to the use of the therapy  identified in clinical trials prior to approval.
      • Identify an unexpected serious risk when available data indicate the potential for a serious risk.
      • Monitor safety issues that are biologically plausible based on a therapy’s known pharmacological action.
    • Other factors that may influence the requirement of postmarket surveillance include:
      • Complexity of the therapy’s manufacturing process and the therapy’s composition.
      • Whether the dose of the therapyneeded to produce its intended beneficial effect is close to a dose that can cause safety issues.
      • Use in special populations (e.g., during pregnancy, in children, or in elderly patients).
      • Therapies with novel mechanisms of action for which safety issues are less predictable.
    • Postmarket Requirements and Commitments is a searchable database.
  • Postmarket commitment: A Sponsor may propose performing postmarket studies or clinical trials during the New Drug Application (NDA) or during the marketing review process. In most cases these studies remain a commitment and  are not required by statute or regulation.
    • Further studies typically gather additional information about a medicine’s safety, efficacy, or optimal use.
  • Safety studies can include studies using healthcare data collected through the Sentinel System, patient registry and natural history studies, and Phase IV clinical trials. 
    • The Sentinel System is FDA CDER’s active surveillance program and is used to efficiently monitor the safety of therapies on a massive scale.
      • Sentinel System Website 
      • Sentinel brings together public, academic, and private organizations that provide access to healthcare data and expertise.
      • The FDA provides the following resources to learn more about the current and expanding program:
        • FDA’s Sentinel Initiative provides an overview of the initiative and its expansion in September 2019, including links to the Sentinel System Five-Year Strategy 2019 to 2023 and Framework for FDA’s Real-World Evidence Program.
        • Sentinel, FDA CDER’s active surveillance program is a short video (under 3 minutes) describing how Sentinel efficiently monitors safety of therapies on a massive scale.
    • Your patient registry or natural history study can be used as part of the postmarket surveillance. 
      • May be more likely to be successful in systematically collecting interpretable long-term safety data.
      • Include information not only on therapies or procedures of interest, but also on similar patients who receive other treatments, other procedures, or no treatment for the same clinical indications. 
      • By characterizing events in the broad population with conditions of interest, disease registries can make a meaningful contribution to the understanding of adverse event rates by providing large, systematic data collection for target populations of interest.
    • Not all Phase IV clinical trials are postmarket surveillance, but many are. 
      • The main objective of the Phase IV trial focused on postmarket surveillance is to:
        • Check the therapy’s performance in real life scenarios.
        • Study the long-term risks and benefits of using the therapy.
        • Discover any rare side effects.
      • Selection of patients is defined by permissible indications and contra-indications of the therapy as stated in the text of prescribing information rather than inclusion and exclusion criteria of previous clinical trials.
      • Patients do not have to be a participant in a Phase IV clinical trial to receive the therapy since it has already received FDA marketing approval. 

Tips for Success

  • Talk to the Sponsor about including your patient registry or natural history study as part of its postmarket commitment or requirement if included in the NDA.
  • Keep your disease community aware of any postmarket surveillance and the importance of participating in any Phase IV Clinical Trials, patient registry, or natural history studies that are part of the surveillance. 
  • Reach out to other group leaders who may have a therapy currently in postmarket surveillance or recently completed required or committed phase of postmarket surveillance.
  • Share the contact information of the FDA Division of Drug Information with your disease community.
    • Staffed by pharmacists who can assist in answering questions about specific drugs and biologics as well as assist in reporting adverse events.
    • Email: druginfo@fda.hhs.gov 
    • Telephone: 1-855-543-3784 or +1-301-796-3400
  • Stay current with FDA programs and resources. For example:
    • Best Practices in Drug and Biological Product Postmarket Safety Surveillance for FDA Staff (2019) is a draft published by the FDA. This document is written in technical language, but may be of interest to you or those in your patient community who prefer to understand as much as possible about a topic. 
      • Includes sections for different types of therapies and specific patient populations.
      • Discusses safety signal identification, evaluation and documentation.
    • FDA’s Sentinel Initiative is a growing FDA initiative which has transformed the way researchers monitor the safety of FDA-regulated therapies, including drugs, biologics, and medical devices.

Resources

FDA Surveillance Programs
Safety Reporting Portal U.S. Department of Health and Human Services (link)
Reporting Serious Problems to FDA U.S. Food and Drug Administration (FDA) (link)
Medical Product Safety Information U.S. Food and Drug Administration (FDA) (link)
Manufacturer and User Facility Device Experience (MAUDE) U.S. Food and Drug Administration (FDA) (link)
Truthful Prescription Drug Advertising and Promotion U.S. Food and Drug Administration (FDA) (link)
Medication Errors Related to CDER-Regulated Drug Products U.S. Food and Drug Administration (FDA) (link)
Drug Shortages U.S. Food and Drug Administration (FDA) (link)
CDER MAPP on Drug Shortage Management U.S. Food and Drug Administration (FDA) (link)
Requirement and Commitment
FDA's Sentinel Initiative U.S. Food and Drug Administration (FDA) (link)
Sentinel, FDA CDER’s active surveillance program video U.S. Food and Drug Administration (FDA) (link)
Tips for Success
CDER Division of Drug Information U.S. Food and Drug Administration (FDA) (link)
FDA's Sentinel Initiative U.S. Food and Drug Administration (FDA) (link)

Postmarket surveillance is the process of monitoring the safety of a therapy after it has received marketing approval by the U.S. Food and Drug Administration (FDA). Because clinical trials are conducted in small numbers of patients, new issues may arise when a treatment is used by a larger population after approval. Your patient group can provide a bridge between patients, industry, and the FDA to help with postmarket surveillance.

You can ensure the FDA has the information it needs to protect your patient community by explaining the importance of postmarket surveillance to both your patient community and your network of health care providers. Postmarket surveillance can:

  • Detect unexpected side effects or an increase in severity including:
    • Adverse reactions
    • Poisonings
    • Medical complications
  • Monitor adherence to the terms and conditions of approval.
  • Track manufacturing consistency and control.
  • Lead to labeling updates. 
  • Trigger approval re-evaluation.

The FDA has several policies and programs in place that are intended to promote appropriate postmarket surveillance. Understanding these programs can help you guide your disease community on the ways to report side effects, medication errors, quality issues, and concerns about advertisements should any occur. 

  • FDA Adverse Event Reporting System (FAERS): FAERS is the database that contains adverse event reports, medication error reports, and reports of therapy quality issues that resulted in adverse events that were submitted to the FDA.
    • FAERS covers drugs and biologics. Medical devices and other regulated therapies have a separate database and reporting system, Manufacturer and User Facility Device Experience (MAUDE), which is described below in more detail.
    • Patients/families and health professionals may use the public friendly portals through MedWatch (more details about MedWatch are available below) to report adverse events. 
      • Printable forms to report events can be found on MedWatch in both English and Spanish. 
      • Adverse events can also be reported by phone (toll-free): 1-800-332-1088.
      • MedWatch includes linking to reporting systems for medical devices and other regulated therapies.
    • Adverse events may also be reported through the FDA Safety Reporting Portal.
    • Reports to the FDA can be made by:
      • Healthcare professionals
      • Patients, families, and caregivers (often referred to as consumers)
      • Manufacturers
    • Healthcare professionals and consumers may also report to the therapy’s manufacturers. 
      • If a manufacturer receives a report from a healthcare professional or consumer, they are required to send the report to the FDA as specified by regulations.  
    • The FDA provides a public-friendly FAQs that can be shared with your patient community at Questions and Answers on FDA’s Adverse Event Reporting System (FAERS)
    • The reports in FAERS are evaluated by clinical reviewers in the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) to monitor the safety of therapies after they are approved by FDA.
      • If a potential safety concern is identified in FAERS, further evaluation is performed.
      • Regulatory action(s) may be instituted to improve therapy safety and protect the public health, such as updating a therapy’s labeling information, restricting the use of the therapy, communicating new safety information to the public, or (in rare cases) removing a therapy from the market.
    • FAERS data does have limitations. FAERS should not be used to calculate the incidence of an adverse event or medication error in the U.S. population or causality of event to therapy.
      • FDA does not require that a causal relationship between a therapy and event be proven to be submitted as an adverse event.
      • Reports do not always contain enough detail to properly evaluate an event.
      • There may be multiple reports of the same event, for example, a report could be submitted by a patient/family member, medical professional, and manufacturer.
      • Not all adverse events or medication errors are reported.
  • MedWatch program: MedWatch is the FDA’s therapy safety reporting program for health professionals, patients/families, and consumers. 
    • MedWatch receives reports from the public and, when appropriate, publishes safety alerts for FDA-regulated therapies such as:
      • Human drugs
      • Medical devices
      • Vaccines
      • Biologics
      • Dietary supplements
      • Cosmetics
    • Mandatory reporting by manufacturers includes:
      • Error and accident reports or therapy quality reports when deviation from current good manufacturing practice regulations occurs.
      • Adverse event reports, medication error reports, and therapy quality complaints resulting in adverse events reported to the manufacturer by consumers or health care professionals. 
    • MedWatch Online Voluntary Reporting Form is for both health professionals and consumers. It contains data regarding: 
      • Unexpected side effects or adverse events including everything from skin rashes to more serious complications.
      • Therapy quality problems, such as whether a therapy isn’t working properly or it has a defect.
      • Therapy use or medication errors that can be prevented. 
        • These can be caused by various issues, including selecting the wrong therapy because of similar labels, packaging, brand names, or generic names.
        • Mistakes can also be caused by hard-to-read controls or displays on a medical device, which may cause an incorrect test result to be reported.
      • Therapeutic failures, such as a medical therapy seemingly not working as well when switching from brand name to generic or from one generic to another.
    • Printable versions of the reporting forms in English and Spanish as well as information about other reporting agencies of concerns about vaccines, tobacco, cigars, e-cigarettes/vaping and chewing tobacco and animal and veterinary products are available at Reporting Serious Problems to FDA.
    • Contact information for inquiries about specific products or questions regarding adverse event reporting as well as other FDA safety information resources are available on the webpage, Medical Product Safety Information.
  • Medical Device Report (MDR): The Manufacturer and User Facility Device Experience (MAUDE) database contains MDRs submitted to the FDA by mandatory reporters (manufacturers, importers, and device user facilities) and voluntary reporters such as health care professionals, patients, and consumers.
    • MDR provides more information about mandatory and voluntary reporting of adverse events on their website, Medical Device Reporting (MDR): How to Report Medical Device Problems
    • Patients, caregivers, and consumers are encouraged by FDA to submit voluntary reports of significant adverse events or medical device problems through MedWatch, the FDA’s Safety Information and Adverse Event Reporting Program (described in more detail in the section above).
    • The FDA requires that certain agencies to report when a medical device may have caused or contributed to a death or serious injury, including device malfunctions. Mandatory reporting is required by:
      • Manufacturer
      • Importers
      • Device User Facilities, which are defined as any hospital, ambulatory surgical facility, nursing home, outpatient diagnostic facility, or outpatient treatment facility, that is not a physician’s office.
        • Possibly associated deaths are required to be reported to both manufacturer and FDA.
        • Serious injuries can be reported to either the manufacturer or FDA. 
        • Malfunction reporting is not mandatory by device user facilities but can be voluntary.
    • The Voluntary Malfunction Summary Reporting (VMSR) program permits manufacturers to report certain device malfunction MDRs in summary form on a quarterly basis. 
  • Office of Prescription Drug Promotion (OPDP): OPDP monitors and regulates the labeling of approved drugs and biologics and  promotional efforts by the manufacturer/Sponsor.
    • OPDP does not regulate promotions for: 
      • Over-the-counter drugs
      • Dietary supplements
      • Medical devices
    • OPDP regulates the following types of promotions:
      • TV and radio advertisements
      • All written or printed prescription drug/biologic promotional materials
      • Speaker program presentations
      • Sales representative presentations
    • Responsibilities of OPDP include: 
      • Providing written comments to pharmaceutical Sponsors on proposed promotional materials to ensure clear and unambiguous communication of the laws and regulations relating to prescription drug/biologic promotion.
      • Reviewing complaints about alleged promotional violations.
      • Initiating enforcement actions on promotional materials that are false or misleading.
      • Comparing the therapy labeling and promotional materials of various closely related therapies to ensure that regulatory requirements are consistently and equitably applied.
      • Traveling to major medical meetings and pharmaceutical conventions to monitor promotional exhibits and activities.
      • Acting as a liaison between OPDP and other divisions within the FDA on promotional issues.
    • OPDP supports the FDA Bad Ad program, an outreach program designed to educate healthcare providers about the role they can play in ensuring that prescription drug/biologic advertising and promotion is truthful and not misleading.
      • Although the webpage Truthful Prescription Drug Advertising and Promotion is targeted towards health professionals and the Bad Ad Program, it provides information about:
        • Standards for drug/biologic promotions.
        • Common violations and examples.
        • How to report suspected violations.
    • Contact OPDP staff at +1-301-796-1200.
  • Division of Medication Error Prevention and Analysis (DMEPA): DMEPA is responsible for monitoring and preventing medication errors related to the naming, labeling, packaging, and design for CDER-regulated drugs and biologics.
    • FDA defines a medication error as any preventable event that may cause or lead to inappropriate medication use or patient harm while the medication is in the control of a healthcare provider, patient, or consumer.
    • The deliberate or intentional use of a therapy in a manner that is inconsistent with FDA-required labeling (e.g., abuse, misuse, off label use) isn’t generally considered a medication error.
    • A medication error may or may not result in an adverse event.
    • Reporting is currently voluntary, but the FDA encourages reporting by healthcare providers, patients, caregivers, consumers, and manufacturers. 
      • Reports can be filed through MedWatch, the FDA’s safety information and adverse event reporting program (described in more detail in the section above).
    • Examples of reportable medication errors include:
      • Look-alike container labels.
      • Confusing prescribing information that may cause or lead to a medication error.
    • DMEPA monitors and analyzes medication error reports associated with marketed drug therapies, including:
      • Over-the-counter
      • Prescription, generics, and biosimilars and other therapeutic biologics.
    • FDA may take regulatory action, such as:
      • Revising the labeling or issuing a safety communication to help prevent errors. 
      • Changing the proprietary name to address safety issues resulting from name confusion errors.
    • The FDA provides more information about DMEPA on their webpage, Medication Errors Related to CDER-Regulated Drug Products
  • Therapy shortages: FDA’s policy attempts to prevent or alleviate shortages of medically necessary therapies.
    • Therapy shortages may arise from varying causes, such as the unavailability of raw materials or packaging components, marketing decisions, and enforcement issues.
    • Manufacturers provide the FDA with the most current therapy shortage information, and the agency works closely with the manufacturers to prevent or reduce the impact of shortages.
    • The FDA provides more information about policies related to preventing and minimizing therapy shortages on their webpage, Drug Shortages
    • CDER provides an overview of therapy shortage management responsibilities and how therapy shortage reports are processed related to therapy shortages in the PDF, MAPP on Drug Shortage Management
      • This resource is written using legal, technical language, but may be helpful if your disease community experiences a therapy shortage. 
      • Depending on your own background and experience, you may wish to share this resource with your Scientific/Medical Advisory Board.

Postmarket surveillance can be officially part of the marketing approval requirements or can be part of a commitment made by the Sponsor when applying for marketing approval in the New Drug Application (NDA). Required and committed postmarket surveillance may involve Phase IV clinical trials. Patient registries and natural history studies may also be used to collect data. Additionally, you may wish to learn more about Sentinel, an FDA initiative to provide real world evidence for therapy approval and postmarket surveillance.

  • Postmarket requirement: The FDA may require postmarket surveillance for newly approved therapies to ensure its safety and efficacy in the general patient population, often in a less controlled environment. 
    • Postmarket studies or clinical trials are required to confirm clinical benefit for therapies approved using:
      • Accelerated approval.
      • Deferred pediatric studies. Clinical trials in the pediatric population may be required for therapies that treat or prevent diseases that affect both adults and children.
        • A Sponsor may request clinical trials involving children be deferred until after FDA marketing approval for the therapy in adults is received.  
      • Animal Efficacy Rule. For more information see the FDA webpage, Animal Rule Information.
        • Applies to therapies that cannot be ethically tested in humans at the time of approval.
        • For example, consider the FDA approval in 2018 of a therapy to treat smallpox: FDA approves the first drug with an indication for treatment of smallpox
          • Efficacy was established through well-controlled animal studies. 
          • Safety in humans was established by giving the investigational therapy to several hundred human volunteers.
          • Human volunteers were not exposed to smallpox however to determine efficacy in humans. 
          • Efficacy and safety are required to be closely monitored in the event it is used.
    • Postmarket studies or clinical trials may also be required to:
      • Assess a known serious risk related to the use of the therapy identified in clinical trials prior to approval.
      • Assess signals of serious risk related to the use of the therapy  identified in clinical trials prior to approval.
      • Identify an unexpected serious risk when available data indicate the potential for a serious risk.
      • Monitor safety issues that are biologically plausible based on a therapy’s known pharmacological action.
    • Other factors that may influence the requirement of postmarket surveillance include:
      • Complexity of the therapy’s manufacturing process and the therapy’s composition.
      • Whether the dose of the therapyneeded to produce its intended beneficial effect is close to a dose that can cause safety issues.
      • Use in special populations (e.g., during pregnancy, in children, or in elderly patients).
      • Therapies with novel mechanisms of action for which safety issues are less predictable.
    • Postmarket Requirements and Commitments is a searchable database.
  • Postmarket commitment: A Sponsor may propose performing postmarket studies or clinical trials during the New Drug Application (NDA) or during the marketing review process. In most cases these studies remain a commitment and  are not required by statute or regulation.
    • Further studies typically gather additional information about a medicine’s safety, efficacy, or optimal use.
  • Safety studies can include studies using healthcare data collected through the Sentinel System, patient registry and natural history studies, and Phase IV clinical trials. 
    • The Sentinel System is FDA CDER’s active surveillance program and is used to efficiently monitor the safety of therapies on a massive scale.
      • Sentinel System Website 
      • Sentinel brings together public, academic, and private organizations that provide access to healthcare data and expertise.
      • The FDA provides the following resources to learn more about the current and expanding program:
        • FDA’s Sentinel Initiative provides an overview of the initiative and its expansion in September 2019, including links to the Sentinel System Five-Year Strategy 2019 to 2023 and Framework for FDA’s Real-World Evidence Program.
        • Sentinel, FDA CDER’s active surveillance program is a short video (under 3 minutes) describing how Sentinel efficiently monitors safety of therapies on a massive scale.
    • Your patient registry or natural history study can be used as part of the postmarket surveillance. 
      • May be more likely to be successful in systematically collecting interpretable long-term safety data.
      • Include information not only on therapies or procedures of interest, but also on similar patients who receive other treatments, other procedures, or no treatment for the same clinical indications. 
      • By characterizing events in the broad population with conditions of interest, disease registries can make a meaningful contribution to the understanding of adverse event rates by providing large, systematic data collection for target populations of interest.
    • Not all Phase IV clinical trials are postmarket surveillance, but many are. 
      • The main objective of the Phase IV trial focused on postmarket surveillance is to:
        • Check the therapy’s performance in real life scenarios.
        • Study the long-term risks and benefits of using the therapy.
        • Discover any rare side effects.
      • Selection of patients is defined by permissible indications and contra-indications of the therapy as stated in the text of prescribing information rather than inclusion and exclusion criteria of previous clinical trials.
      • Patients do not have to be a participant in a Phase IV clinical trial to receive the therapy since it has already received FDA marketing approval. 
  • Talk to the Sponsor about including your patient registry or natural history study as part of its postmarket commitment or requirement if included in the NDA.
  • Keep your disease community aware of any postmarket surveillance and the importance of participating in any Phase IV Clinical Trials, patient registry, or natural history studies that are part of the surveillance. 
  • Reach out to other group leaders who may have a therapy currently in postmarket surveillance or recently completed required or committed phase of postmarket surveillance.
  • Share the contact information of the FDA Division of Drug Information with your disease community.
    • Staffed by pharmacists who can assist in answering questions about specific drugs and biologics as well as assist in reporting adverse events.
    • Email: druginfo@fda.hhs.gov 
    • Telephone: 1-855-543-3784 or +1-301-796-3400
  • Stay current with FDA programs and resources. For example:
    • Best Practices in Drug and Biological Product Postmarket Safety Surveillance for FDA Staff (2019) is a draft published by the FDA. This document is written in technical language, but may be of interest to you or those in your patient community who prefer to understand as much as possible about a topic. 
      • Includes sections for different types of therapies and specific patient populations.
      • Discusses safety signal identification, evaluation and documentation.
    • FDA’s Sentinel Initiative is a growing FDA initiative which has transformed the way researchers monitor the safety of FDA-regulated therapies, including drugs, biologics, and medical devices.

Resources

FDA Surveillance Programs
Safety Reporting Portal U.S. Department of Health and Human Services (link)
Reporting Serious Problems to FDA U.S. Food and Drug Administration (FDA) (link)
Medical Product Safety Information U.S. Food and Drug Administration (FDA) (link)
Manufacturer and User Facility Device Experience (MAUDE) U.S. Food and Drug Administration (FDA) (link)
Truthful Prescription Drug Advertising and Promotion U.S. Food and Drug Administration (FDA) (link)
Medication Errors Related to CDER-Regulated Drug Products U.S. Food and Drug Administration (FDA) (link)
Drug Shortages U.S. Food and Drug Administration (FDA) (link)
CDER MAPP on Drug Shortage Management U.S. Food and Drug Administration (FDA) (link)
Requirement and Commitment
FDA's Sentinel Initiative U.S. Food and Drug Administration (FDA) (link)
Sentinel, FDA CDER’s active surveillance program video U.S. Food and Drug Administration (FDA) (link)
Tips for Success
CDER Division of Drug Information U.S. Food and Drug Administration (FDA) (link)
FDA's Sentinel Initiative U.S. Food and Drug Administration (FDA) (link)