June 07, 2025

Color additives are important in drugs for identification, branding, and patient compliance. Sometimes, manufacturers may need—or choose—to replace a color additive due to safety, supply, or quality reasons. To make this process clearer and faster, the FDA released draft guidance titled “Replacing Color Additives in Approved or Marketed Drug Products.”

Key Points from the Draft Guidance

1. Easier Regulatory Path

  • In the past, changing a color additive was considered a major change, needing a Prior Approval Supplement (PAS) and long FDA review.
  • Now, most color changes are moderate changes, allowing manufacturers to use the Changes Being Affected in 30 Days (CBE-30) pathway.
  • This speeds up approval for implementing color changes.

2. Who It Applies To

  • New Drug Applications (NDAs)
  • Abbreviated New Drug Applications (ANDAs)
  • Over the Counter (OTC) monograph drugs
  • Certain compounded drugs under Section 503B of the FD&C Act

3. Conditions for Using the Faster Path
 The CBE-30 pathway can be used if:

  • The new color additive is already FDA-approved (listed in 21 CFR Parts 70–82).
  • The change does not affect safety, effectiveness, or bioavailability of the drug.
  • The total excipient change, including the color additive, is less than 5% of the unit dose weight.

4. Exceptions / Special Cases
 Some changes still need full prior approval, such as:

  • Drugs for sensitive groups (like newborns or children).
  • Using a color additive not listed by the FDA.
  • Changes over 5% of excipient weight.

5. Documentation and Quality Checks
 Manufacturers must:

  • Update labels and product descriptions with the new color.
  • Provide at least 3 months of stability data at room and accelerated temperatures.
  • Keep records proving that product quality and performance are not affected.

6. Removing vs. Replacing

  • If the color additive is removed entirely (not replaced), it is a minor change.
  • Minor changes can be reported in the annual report instead of submitting a supplement.

Conclusion

The FDA’s draft guidance makes replacing color additives easier and faster while keeping drugs safe and effective. It provides clear rules and pathways, helping manufacturers respond to safety, supply, or market needs without unnecessary delays.