The NDI Notification Process for Custom Supplement Formulations: A Practical Guide for Brand Owners

When your supplement formula includes an ingredient that was not marketed in the United States before October 15, 1994, you cannot simply launch it and hope for the best. Under the Dietary Supplement Health and Education Act (DSHEA) of 1994, the Dietary Fiber (US FDA) requires a pre-market safety evaluation called the New Dietary Ingredient (NDI) Notification. Getting this right is one of the most consequential regulatory steps for brands sourcing custom formulations from overseas manufacturers.

In this article, we break down exactly what the NDI notification process involves, who needs to file, what documentation your Chinese OEM partner must prepare, and how to avoid the most common reasons FDA rejects NDIN submissions.

What Is an NDI, and When Does It Apply?

A dietary ingredient is considered “new” if it was not present in the food supply as an article used for food in a form for consumption prior to October 15, 1994. This includes:

• Synthetic copies of naturally occurring ingredients, where the synthetic form was not consumed before the cutoff date
• Botanical extracts at concentrations or forms not historically consumed (e.g., highly concentrated ashwagandha root extract vs. traditional whole root)
• Probiotics, prebiotics, or postbiotics with strain designations not previously marketed
• Novel proteins or amino acid derivatives
• Combination ingredients where the specific combination has no history of use

The key test is history of use. If the ingredient or a chemically identical form was not consumed as a dietary supplement prior to 1994, it is an NDI — and you must file an NDI notification before commercial distribution.

The NDI Notification Process: Step by Step

Step 1: Determine If Your Ingredient Qualifies for the Grandfathered Exception

Before filing, confirm whether your ingredient is genuinely “new.” FDA recognizes a grandfathered exception for ingredients that were marketed as dietary ingredients in a dietary supplement prior to October 15, 1994. If grandfathered, no NDI notification is required. However, the burden of proof lies with the manufacturer or brand. Common evidence includes historical import records, marketing materials, and published literature predating the cutoff.

Step 2: Conduct a Thorough Safety Review

FDA does not “approve” NDIs in the traditional sense — it evaluates whether there is a reasonable expectation of safety under the labeled or recommended conditions of use. Your notification package must include:

• Description of the dietary supplement containing the NDI — ingredient identity, source, form, and specifications
• History of use or other evidence of safety — this is critical and should come from your OEM manufacturer
• Full safety narrative — a comprehensive discussion of the scientific literature, including adverse event data, toxicological studies, and any clinical trial results
• Analytical data confirming the identity, purity, and specifications of the NDI as used in the finished product

Step 3: Prepare the Notification Document

The NDI notification must be submitted in writing to FDA at least 75 days before the intended commercial marketing date. The document is submitted to the Office of Dietary Supplement Programs (ODSP). Key elements include:

• Cover letter with brand/manufacturer contact information
• Executive summary of the ingredient and the safety basis
• Manufacturing process description — identity, specifications, purity, batch analysis data (your OEM partner must provide this)
• History of use documentation — published literature, trade records, or human study data
• Safety data package — toxicology, genotoxicity, subchronic toxicity where applicable
• Proposed labeling and recommended conditions of use

Step 4: Submit and Wait for FDA Review

FDA has 75 days to review the notification. If FDA does not respond within this window, the ingredient may be marketed — but this does not constitute FDA approval. FDA may also issue an acknowledgment letter, a no objection letter, or request additional information (RAI). If FDA raises safety concerns or issues an insufficient basis letter, you cannot legally market the product until the concerns are resolved.

Step 5: Maintain Records and Ongoing Compliance

Once your NDI is in commercial distribution, ongoing compliance obligations include:

• Consistent manufacturing to the specifications in your notification
• Adverse event monitoring and reporting under 21 CFR Part 111
• Updated stability and COA data for every production batch
• Notifying FDA of any safety-related changes to the product

What Your Chinese OEM Partner Must Provide

Your contract manufacturer plays a central role in the NDI process. Before selecting an OEM partner, confirm they can supply the following:

• Full specifications sheet for each NDI ingredient — identity, assay, purity, heavy metals, microbiology limits
• Certificate of Analysis (COA) for each raw material lot used in the NDI
• Manufacturing process flow — extraction, isolation, synthesis, or fermentation method used to produce the NDI
• History of use dossier — documentation of the ingredient’s use in other markets (e.g., EU, Australia, Japan) if available
• Stability data supporting the claimed shelf life under the finished product’s packaging conditions
• Third-party lab testing from an ISO 17025 accredited laboratory — especially for novel botanicals and concentrated extracts

A reputable OEM manufacturer will have these documents ready or be able to generate them within a defined timeline. Be wary of partners who promise to “handle the NDI” without transparent documentation — the safety data package is the foundation of your notification and cannot be fabricated.

Common Reasons FDA Rejects NDI Notifications

FDA’s NDI review process is rigorous. Based on FDA’s published NDI Database and warning letters, the most common grounds for rejection include:

• Insufficient history of use evidence — vague references to traditional use without specific documentation
• Inadequate safety data — missing toxicology studies for high-dose or novel-ingredient applications
• Identity concerns — FDA cannot confirm the ingredient’s identity from the information provided
• Conditions of use mismatch — the notification covers different use levels or populations than what is described in the safety data
• Failure to disclose — incomplete ingredient description or undisclosed processing agents used in manufacturing

Working with a manufacturer who has prior NDI experience — including successful notifications — dramatically reduces the risk of a rejected submission.

The GRAS Alternative: When NDI Is Not Required

For some ingredients — particularly those used in conventional foods prior to 1994 — a Generally Recognized As Safe (GRAS) determination may be an alternative pathway. GRAS allows an ingredient to be used in dietary supplements without NDI notification, provided the use is supported by either:

• Qualified experts (scientific procedures) — similar to FDA’s food GRAS program
• A GRAS exemption petition submitted to FDA

Whether NDI or GRAS is the correct pathway depends on the ingredient’s history, form, and intended use. A regulatory affairs consultant with US market experience should make this determination before you finalize your product formula.

Final Thoughts: Plan Ahead for NDI

The NDI notification process adds 3–6 months to your product development timeline and requires close collaboration between your brand team, regulatory consultants, and your OEM manufacturer. Brands that plan for NDI from the beginning — rather than retrofitting documentation after the formula is locked — are far more likely to receive a smooth FDA review.

At Dongying Zuoning Bio-Tech Co., Ltd., we help international supplement brands navigate the NDI notification process by preparing complete, submission-ready documentation packages. Our regulatory team works alongside your advisors to ensure the safety dossier, COA package, and manufacturing data meet FDA’s expectations.

📧 Wade@zuoningbio.com | 📞 +86 187 5469 6289 | 🌐 www.zuoningbio.com