FDA Issues Guidance on Warning and Precautions Labeling for Drugs and Biological Products

  • By: Staff Editor
  • Date: November 11, 2011

The FDA issued its final guidance on Warnings and Precautions, Contraindications, and Boxed Warning Sections of Labeling for Prescription Drugs and Biological Products in October 2011.

The recommendations contained in the guidance will help manufacturers decide:
  • Which adverse reactions or other potential safety hazards are significant enough to be included in the WARNINGS AND PRECAUTIONS section of drug/biologics labels
  • What information should be included when describing those adverse reactions and organize the WARNINGS AND PRECAUTIONS section
  • Which situations warrant a contraindication
  • What information to provide in those situations when the use of the product is contraindicated
  • How to organize the CONTRAINDICATIONS section
  • When to include a boxed warning
  • What information to include in the BOXED WARNING section
Summary of Recommendations
Adverse reactions to be included in the WARNINGS AND PRECAUTIONS section
The WARNINGS AND PRECAUTIONS section on a drug/biologics label is intended to indentify and describe adverse reactions and other potential safety hazards that are serious or otherwise clinically significant because they have implications for prescribing decisions or for patient management.
The following adverse reactions which should be included in the WARNINGS AND PRECAUTIONS sections are detailed in the FDA guidance:
  • Serious Adverse Reactions
  • Otherwise Clinically Significant Adverse Reactions
  • Anticipated Adverse Reactions
  • Adverse Reactions Associated with Unapproved Uses
Risks and other hazards to be included in WARNINGS AND PRECAUTIONS
The following risks and other hazards should be included in this section:
  • Laboratory Test Interference: This means that a lab test result is inaccurate because the drug interferes with the assay. Only clinically significant interferences should be included in this section.
  • Drug Interactions: The WARNINGS AND PRECAUTIONS section must briefly describe any known or predicted drug interactions with serious or otherwise clinically significant outcomes.
  • Need for Monitoring to Assess Safety: The WARNINGS AND PRECAUTIONS section must identify any lab tests that would be helpful or necessary to identify possible adverse reactions or to prevent a serious adverse reaction
Information to Provide in the Description of an Adverse Reaction
The description of adverse reactions in the WARNINGS AND PRECAUTIONS section must be limited to the following information:
  • A succinct description of the adverse reaction and outcome
  • A numerical estimate of risk or adverse reaction rate
  • Known risk factors for adverse reactions
  • Steps to take to decrease the likelihood, shorten the duration, or minimize the severity of an adverse reaction
  • How to treat or otherwise manage an adverse reaction that has occurred
  • Each adverse reaction, syndrome or group of reactions with a common pathogenesis included in the WARNINGS AND PRECAUTIONS section should have its own numbered subsection
  • The order in which adverse reactions are presented in the WARNINGS AND PRECAUTIONS section should reflect the clinical significance of the adverse reaction
  • When detailed information about adverse reactions is included in another section, then it should be cross-referenced in the WARNINGS AND PRECAUTIONS section rather than being repeated
  • Bolded text or other emphasis can be used to highlight particular adverse reactions
Need to understand the FDA’s labeling regulations? Attend any of the following ComplianceOnline webinars:
Contraindications Section
According to the FDA guidance:
  • Only known hazards and not theoretical possibilities can be the basis of a contraindication.
  • If there are no known contraindications for a drug, the section should state “None”.
  • Contraindications should also be worded in precise language.
 Boxed Warning
According to the FDA guidance, a boxed warning can only be used in the following situations:
  • There is an adverse reaction so serious in proportion to the benefits of the drug that it is essential to take this into consideration when weighing the risks of the drug against its benefits; or
  • There is a serious adverse reaction to the drug that can be prevented or reduced in frequency or severity by the appropriate use of the drug
  • The FDA approved the drug with restrictions to ensure safe use because it concluded that the drug can be safely used only if distribution or use is restricted
Additional Resources
Read the FDA guidance in full


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