1. Regulatory Consultation & Gap Analysis:

Evaluate ingredient compliance with NDI/GRAS requirements and identify submission risks.

2. Documentation Preparation & Report Drafting:

Assist in completing NDIN or GRAS reports (including toxicology study design and expert panel formation).

3. FDA Communication & Submission:

Submit applications on behalf of clients and address FDA inquiries/supplemental requests.

4. Compliance Training & Updates:

Provide NDI/GRAS regulatory training and monitor FDA policy changes.

5. Manufacturing Process Compliance Support:

Guide manufacturers on re-submission requirements for process changes.

For customized solutions, contact us for professional support.

1. Definition and Background

NDI (New Dietary Ingredient):

NDI, defined under the Dietary Supplement Health and Education Act (DSHEA 1994), refers to dietary supplement ingredients not marketed in the U.S. before October 15, 1994. Manufacturers must submit an NDI Notification (NDIN) to the FDA at least 75 days before marketing, demonstrating safety.

GRAS (Generally Recognized as Safe):

GRAS, established by the 1958 Food Additives Amendment, applies to food additives or ingredients proven safe through scientific evaluation or long-term use. No FDA pre-approval is required, but companies may choose self-affirmation or submit a GRAS Notice for FDA review.

2. Applicable Scope

NDI:

Applies only to new ingredients in dietary supplements (e.g., vitamins, minerals, herbal extracts), requiring safety and compliance evidence.

GRAS:

Covers conventional foods or food additives (e.g., preservatives, fortifiers), subject to the FD&C Act’s definition of "food additives."

3. Basic Requirements

NDI Requirements:

·Provide chemical characterization, manufacturing process, toxicology data, and safety assessment reports.

·Include historical use evidence or supporting scientific literature.

·After NDIN submission, FDA may request additional data or reject the application (high rejection rate).

GRAS Requirements:

·Self-affirmation: Independent expert panel assessment (no public disclosure).

·FDA GRAS Notice: Submit chemical analyses, exposure assessments, and toxicology data for "No Questions" response.

·Re-submission required for major process changes (e.g., biotech methods).

4. Registration Process

NDI Process:

1）Prepare NDIN report (ingredient description, usage conditions, safety data).

2）Submit via FDA’s COSM system.

3）FDA review (39% approval rate).

4）Receive "No Questions" letter or data request.

GRAS Process:

1）Choose self-affirmation or FDA GRAS Notice.

2）Prepare GRAS report (toxicology, exposure analysis, expert conclusions).

3）Submit to FDA for filing/evaluation.

4）Obtain "No Questions" response or deficiency letter.

5. Regulatory Basis

NDI:

·DSHEA (1994)

·21 U.S.C. 350b(d) (Premarket notification)

·FDA NDI Draft Guidance (2011)

GRAS:

·FD&C Act Section 201(s) (Food additive exemptions)

·21 CFR Part 170 (Safety standards)

·FDA GRAS Notice Guidance (1997)