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Investigator Brochures and Package Inserts

Investigator Brochures (IBs) and Package Inserts (PIs) provide important safety information about study drugs. This page explains when each document is required, how to identify the information the IRB needs, and when updated versions must be submitted for IRB review.

Which Document Does My Study Require?

Table 1. Documents to submit to the IRB for study drugs based on whether the drug is investigational or FDA approved.
Type of Study Drug Document to Submit to the IRB
Investigational drug (not FDA approved for the indication being studied) Investigator Brochure (IB)
FDA-approved drug (whether used on-label or off-label) Current FDA Package Insert (PI)
Study includes both investigational and FDA-approved drugs Submit the appropriate document for each study drug (IB for investigational drugs and PI for FDA-approved drugs).

Note: Studies conducted under an IND may still use FDA-approved drugs supplied commercially. In these cases, submit the current FDA Package Insert for the approved drug. An Investigator Brochure is required only for investigational products. If your study includes both investigational and FDA-approved drugs, submit the appropriate document for each drug.

What Is the Difference?

Investigator Brochure (IB)

An Investigator Brochure summarizes all available information about an investigational (unapproved) drug, including:

  • Nonclinical studies
  • Clinical studies
  • Known and potential risks
  • Guidance for investigators
  • Safety monitoring recommendations

IBs are updated as new safety information becomes available.

Package Insert (PI)

A Package Insert is the FDA-approved prescribing information for an approved drug.

It includes:

  • Approved indications
  • Dosage and administration
  • Contraindications
  • Warnings and precautions
  • Adverse reactions
  • Use in specific populations

Why Does the IRB Need These Documents?

The IRB uses the IB or PI to verify that:

  • Risks described in the protocol are accurate.
  • Risks described in the consent form are complete and current.
  • New safety information is appropriately communicated to participants when necessary.

Where Can I Find Important Safety Information?

Table 2. Where to find key information in Investigator Brochures and FDA Package Inserts.
Information Needed Investigator Brochure (IB) Package Insert (PI)
Common adverse reactions Guidance for Investigator or safety sections Adverse Reactions
Serious Risks Guidance sections and appendices Warnings and Precautions (including Boxed Warnings, if applicable)
Pregnancy/contraception Guidance for Investigator Use in Specific Populations or Warnings
Recent changes Summary of Changes or redlined version Recent Major Changes and revision marks

When Do I Need to Submit Updates to the IRB?

Initial Review or when adding a new product

Submit the current version of the applicable IB and/or PI with your initial IRB submission.

Updated Investigator Brochures

If the updated IB contains new or increased risks, submit it to the IRB within 7 days.

If the updated IB does not contain new or increased risks, submit it within 60 days of receipt or with your next Modification (MOD), whichever comes first.

Updated Package Inserts

Submit updated Package Inserts to the IRB as soon as they are received.

Note: Stack all new versions on top of the previously approved version in PROTECT. Include a redlined version/summary of changes for IBs.

Important Submission Note

When submitting updates via a cover memo or the PROTECT SmartForm, you must include:

  1. Your assessment of any new or changed risks.
  2. Your plan for informing current participants, if needed.
  3. An explanation of any differences between the IB/PI and the protocol or consent form.

Key Takeaway

Always ensure that the risks described in your protocol and consent form are consistent with the most current Investigator Brochure or Package Insert. Review updated documents promptly and submit them to the IRB according to the required timelines

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