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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:
    • 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 adverse 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. 

Resources

FDA Surveillance Programs
Questions and Answers on FDA's Adverse Event Reporting System (FAERS) U. S. Food and Drug Administration (FDA) (link)
MedWatch: The FDA Safety Information and Adverse Event Reporting Program U. S. Food and Drug Administration (FDA) (link)
Safety Reporting Portal U. S. Food and Drug Administration (FDA) (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)
Medical Device Reporting (MDR): How to Report Medical Device Problems 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
Postmarketing Requirements and Commitments: Frequently Asked Questions (FAQ) U. S. Food and Drug Administration (FDA) (link)
Postmarket Requirements and Commitments Searchable Database U. S. Food and Drug Administration (FDA) (link)
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)
Best Practices in Drug and Biological Product Postmarket Safety Surveillance for FDA Staff U. S. Food and Drug Administration (FDA) (link)
FDA's Sentinel Initiative U. S. Food and Drug Administration (FDA) (link)