By: Christopher Parrella, Esq., CPC, CHC, CPCO
Parrella Health Law, Boston, MA
A Health Care Provider Defense and Compliance Firm

The FDA has just issued a new draft guidance entitled “Replacing Color Additives in Approved or Marketed Drug Products,” and while it may sound technical, it signals a meaningful shift in how drug manufacturers—particularly generics, compounded drug developers, and 503B outsourcing facilities—can navigate changes to inactive ingredients without major regulatory disruption.

You can read the full draft guidance here: Replacing Color Additives Draft Guidance – Federal Register Notice. Although Parrella Health Law primarily advises and represents providers and licensees, not drug manufacturers, many of our clients are impacted by how drugs are made, labeled, and regulated.

What’s in the Rule?

FDA’s new draft guidance outlines when drug makers can use a streamlined process—called a Changes Being Effected in 30 Days (CBE-30) supplement—to replace an existing color additive with another approved one. The agency has clarified that if the change does not adversely affect a drug’s identity, strength, quality, purity, or potency, it will likely qualify as a moderate—not major—change.

This is especially helpful for manufacturers looking to remove controversial dyes (like Red No. 3) or address evolving patient safety concerns without undergoing the longer Prior Approval Supplement process.

Key Recommendations in the Draft Guidance

• Conduct and document an internal review of how the new color additive aligns with FDA’s regulatory requirements (see 21 CFR parts 70-82).
• Update labeling, drug product specifications, and manufacturing batch records accordingly.
• Maintain documentation at the manufacturing site to support the change.
• Submit CBE-30 supplements to the FDA for approved NDAs or ANDAs, or follow appropriate regulatory pathways for OTC monographs or compounded drugs.

Takeaways for Providers and Pharmacies

Even though this rule is directed at manufacturers, downstream providers must:

• Monitor formulary and drug component changes, particularly when linked to patient sensitivities or adverse reactions.
• Educate staff on inactive ingredients, including color additives, in medications used in your practice.
• Communicate with suppliers about any changes and request updated product documentation or labeling where applicable.
• Stay compliant with your own obligations under HIPAA, OSHA, and state pharmacy regulations to ensure you’re not inadvertently administering a product that has materially changed without adequate documentation.

Final Thoughts

This draft rule, though narrow in scope, is another example of the FDA modernizing its approach to pharmaceutical oversight while keeping patient safety front and center. It also underscores the need for healthcare providers and suppliers to maintain tight communication with manufacturers and repackagers.

We’ll continue to monitor FDA activity as this guidance progresses toward finalization. In the meantime, if your organization administers, repackages, or compounds drug products, we recommend you review your processes for tracking formulation changes, especially where color additives are involved. If you have any questions, please contact Parrella Health Law at 857-328-0382 or email Chris directly at cparrella@parrellahealthlaw.com. We’re here to help ensure you’re protected from risk, whether from regulatory oversight or evolving industry standards.