Regulatory Requirements for Elemental Iron Content in US ANDA Submissions (Module 3.2.P.1)
July 26, 2025
An ANDA must contain either a daily elemental iron calculation for products that contain iron or a statement that the amount of elemental iron ingested per day does not exceed 5 milligrams (mg), in accordance with 21 CFR 73.1200(c). A daily elemental iron calculation should be included in module 3.2.P.1 in addition to all other inactive ingredient justification data/information. If FDA does not receive either the calculation or aforementioned statement within 7 calendar days of notification of the omission(s) or product composition exceeds the elemental iron content more than 5 mg /day then FDA will RTR the ANDA.
21 CFR Part 73 LISTING OF COLOR ADDITIVES EXEMPT FROM CERTIFICATION
Subpart B – Drugs
Sec. 73.1200 Synthetic iron oxide.
(c) Uses and restrictions. The color additive synthetic iron oxide may be safely used to color ingested or topically applied drugs generally subject to the restriction that if the color additive is used in drugs ingested by man the amount consumed in accordance with labeled or prescribed dosages shall not exceed 5 milligrams, calculated as elemental iron, per day.
Hypothetical Examples of Calculating Elemental Iron Content:
The elemental iron content per day can be calculated as below:
Colouring Agent | Molecular Formulae | Molecular Weight | Elemental Iron Content |
Iron Oxide Yellow | FeHO2
| 88.85 | 55.85 |
Iron Oxide Black | Fe3O4 | 231.53 | 167.54 |
Iron Oxide Red | Fe2O3 | 159.69 | 111.69 |
- Quantity of Iron Oxide Red per Unit = 4 mg
- Quantity of Iron Oxide Red per Day = 4 mg X 3 = 12 mg
- Quantity of elemental iron per Day through Iron Oxide Red = 12 X 111.7 / 159.7 = 8.4 mg / day
Thus, this Drug product exceeds the FDA recommended limit of elemental iron content consumption per day limit of 5 mg.
Drug product formulae shall be revised so as to elemental iron content per day comes down within 5 mg/day. In case innovator products is also found to have elemental iron more than 5 mg/day than a controlled correspondence shall be filed before clearing the formulae.
Excerpt from the FDA guidance document ANDA Submissions —Content and Format:
“3.2.P.1Contains the description and composition of the drug product. For each drug strength, applicants should provide:
A daily elemental iron calculation or statement of adherence to 21 CFR 73.1200. FDA recommends that applicants provide a calculation of elemental iron intake based on the maximum daily dose of the drug product.”
Excerpt from the FDA guidance document ANDA Submissions – Refuse-to-Receive Standards:
“An ANDA must contain either a daily elemental iron calculation for products that contain iron or a statement that the amount of elemental iron ingested per day does not exceed 5 milligram (mg), in accordance with 21 CFR 73.1200(c). A daily elemental iron calculation should be included in module 3.2.P.1 in addition to all other inactive ingredient justification data/information. If FDA does not receive either the calculation or aforementioned statement within 7 calendar days of notification of the omission(s), FDA will RTR the ANDA.”