NDI Notification

This glossary term is part of the SG Systems Global regulatory & operations guide library.

Updated January 2026 • Dietary Supplements & Regulatory Readiness • NDI notification, new dietary ingredient determination, premarket submission discipline, identity/specification evidence, manufacturing control and supplier qualification, toxicology and safety rationale packaging, traceability-backed evidence packs, change control for formulas, complaint/adverse event linkage, audit trail defensibility • Supplement Brands, Private Label, Contract Manufacturing (QA/QC, regulatory, R&D, sourcing, leadership)

NDI notification is the formal premarket submission pathway used when a dietary ingredient is considered a new dietary ingredient and the business intends to market it in dietary supplements. Operationally, it is not “paperwork for a regulator.” It is a forcing function that tests whether you actually control the ingredient: identity, specifications, supply chain, manufacturing, and safety rationale. Companies that treat NDI work as a one-time regulatory memo get punished later because the supporting evidence doesn’t stay connected to day-to-day operations—supplier changes, spec drift, formula revisions, and customer complaints keep happening long after a notification is filed.

The hard truth is that most NDI failures are not about a missing paragraph. They are about weak control. If you cannot show that the ingredient you are selling is the ingredient you evaluated, and that you can keep it consistent across suppliers, lots, and years, your “safety story” is fragile. NDI discipline therefore belongs inside a quality system, not just inside regulatory. The NDI package is evidence, but the real control is the process that keeps the evidence true over time.

Tell it like it is: an NDI notification is a high-cost exercise if you don’t integrate it into the business. The value comes from turning NDI requirements into operational guardrails: defined identity tests, release rules, supplier qualification, controlled changes, and a traceability spine that can answer “what shipped” in minutes. If you do that, NDI work becomes a durability advantage rather than a recurring fire drill.

“NDI isn’t a filing. It’s a claim: ‘We understand this ingredient, we control it, and we can prove it.’”

1) What an NDI notification represents

An NDI notification represents a company’s claim that it has evaluated a specific ingredient (as it will be marketed) and can support its safety under the proposed conditions of use. The key words are “specific ingredient” and “as it will be marketed.” If your ingredient identity is fuzzy, your claim is fuzzy. If your intended use is vague, your claim is vague. Operationally, the submission is a structured narrative that ties identity, exposure, manufacturing, and safety rationale into one coherent story.

It also represents a commitment: once you’ve defined what the ingredient is, you must keep it that way—or manage changes under control. This is where many organizations stumble. They treat the NDI as the finish line, then they swap suppliers, change extraction methods, change active content, or change specs without realizing they’ve undermined the original evidence base.

2) Why NDI is a control problem, not a paperwork problem

NDI work lives at the intersection of regulatory, science, and manufacturing. The “paperwork” is just the artifact. The real requirement is control over variability. If your ingredient is botanical, variability comes from region, harvest, and processing. If it’s a mineral, variability comes from source and purification. If it’s a fermentation product, variability comes from strain, feedstock, and process parameters. A submission that doesn’t map to how you control variability is not operationally useful.

Tell it like it is: the regulator’s question is not “Did you write a document?” The question is “Do you understand what you are selling, and can you keep it consistent enough to defend safety?” A real NDI program therefore has to be anchored in your Part 111 quality system: identity testing, specifications, supplier qualification, and controlled changes.

3) NDI determination and “what counts as new” operationally

The determination step is where organizations either do the hard thinking or skip it. “New” is not a marketing label; it is a fact-specific determination tied to the ingredient and how it was used historically. Operationally, the determination should be documented as a decision record: what ingredient is being evaluated, what evidence was reviewed, what assumptions were made, and what conclusion was reached.

Even when legal teams drive the determination, manufacturing must be involved because manufacturing defines the real ingredient: process, specs, impurity profile, and consistency. If the determination is made on a conceptual ingredient (“turmeric extract”) but procurement buys a materially different extract, the business has set itself up for inconsistency. Your determination record should therefore include the practical differentiators: source, extraction method, standardization approach, and specification ranges.

Tell it like it is: “NDI or not” is a business risk decision. Treat it like one—document it, control it, and re-evaluate when you change what you sell.

4) Identity and specification discipline that makes the case defensible

Identity is the spine of the NDI story. If you can’t define identity tightly, you can’t define exposure, and you can’t define safety. That means your identity controls must go beyond a vendor CoA. Your internal identity program should be designed to detect substitution, dilution, and meaningful spec drift. What “meaningful” means depends on the ingredient, but the logic is consistent: identity tests confirm you have the right thing; specs confirm it’s the right thing within acceptable bounds.

Strong NDI programs write specifications like decision rules. They aren’t just numbers; they are gates: pass, hold, investigate, reject. They define critical quality attributes (active content, marker compounds, key impurities, moisture, micro limits, heavy metals where relevant) and they define actions when values trend toward limits.

Tell it like it is: if your NDI relies on a CoA you don’t verify, you don’t control identity—you rent it from your supplier.

5) Supplier and supply chain controls that keep the ingredient “the same”

Supply chain control is where NDI programs get tested in the real world. Suppliers change, secondary sources appear, and procurement pressure creates shortcuts. A defensible program makes it hard to “swap in” a new supplier without re-evaluating the evidence base. That is exactly what supplier qualification and CoA verification are for.

Operationally, supplier controls should include: approved supplier lists for the NDI ingredient, defined incoming verification frequency, periodic full-panel testing (not just the supplier’s panel), and a mechanism to detect process changes at the supplier. That last part matters. A supplier can keep the same “ingredient name” but change extraction solvents, purification steps, or standardization targets. If you don’t have a detection mechanism, you will drift without noticing.

Tell it like it is: if procurement can buy a “similar” ingredient on price, your NDI story is vulnerable. Control has to be designed into the system, not into people’s intentions.

6) Manufacturing consistency: bridging R&D claims to production reality

NDI work often begins in R&D, but it must survive production. That means the conditions of use, dosage, and formulation assumptions used in the safety rationale have to match what you actually sell. If the product form changes (tablet to gummy), if bioavailability changes, if excipients change exposure, your underlying assumptions can shift. The correct response is not panic—it’s controlled change evaluation.

Manufacturing control also matters because cross-contact, labeling mix-ups, and process deviations can create safety signals that look like “ingredient harm” but are actually operational failures. That’s why NDI readiness should link to production controls: recipe versioning, batch record discipline, line clearance, and hold/release governance. When a safety report arrives, you need to rule out process causes quickly before you assume the ingredient is the cause.

7) Change control: preventing silent drift after filing

Change control is the “NDI survival system.” After submission, the business changes. New supplier. New spec range. New assay method. New extraction method. New dosage. New product claims. Any of these can matter. Without change control, these changes happen quietly and the NDI evidence becomes stale.

Strong programs define “NDI-impacting change criteria.” That is, a list of changes that automatically trigger review by regulatory/quality leadership and potentially trigger re-evaluation of the safety rationale. The criteria should be boring and explicit. If a supplier changes process steps, it triggers review. If spec limits change, it triggers review. If dosage increases materially, it triggers review. If a new population is targeted (pregnancy, children), it triggers review.

Tell it like it is: if your change control doesn’t know what NDI is, your NDI doesn’t stay true.

8) Post-market signals: complaints, adverse events, and continuous evidence

Once the product is in market, your evidence base continues to evolve. Complaints and adverse events are not just liabilities; they are feedback loops. If you capture them as structured data, you can detect patterns early. If you treat them as isolated customer interactions, you discover patterns late—after cost and risk have expanded.

NDI programs should link to complaint triage and adverse event intake. When a serious signal appears, you should be able to answer quickly: which lots were involved, what suppliers fed those lots, what other SKUs share those inputs, and what the retain samples show. If signals repeat, the correct response is CAPA, not hope.

Tell it like it is: the best post-market system doesn’t “avoid reports.” It converts reports into prevention.

9) Inspection-ready NDI evidence pack

NDI readiness is not a binder. It is the ability to assemble a coherent evidence pack quickly, with current truth. A practical evidence pack typically includes:

• NDI determination record: the decision logic, assumptions, and conclusion.
• Ingredient definition: source, process description, standardization approach, and specifications.
• Identity program: internal identity testing approach and acceptance rules.
• Supplier controls: approved supplier list, qualification records, and CoA verification approach.
• Change control map: NDI-impacting changes and the review workflow.
• Lot traceability: ability to map ingredient lots into finished lots and shipments.
• Post-market linkage: complaint/adverse event case linkage, trending, and CAPA when warranted.
• Audit trail: who approved what, when, and what changed.

Tell it like it is: if it takes weeks to assemble this, you don’t control it—you archive it.

10) Copy/paste readiness scorecard

11) Common failure modes

• Conceptual ingredient definitions that don’t match what sourcing actually buys.
• CoA dependency without internal verification or trend monitoring.
• Supplier drift blindness (process changes happen, nobody notices).
• Spec creep (limits widen over time without revisiting the evidence base).
• Formula changes that change exposure but aren’t reviewed for NDI impact.
• Traceability gaps so scope can’t be proven during a safety signal.
• Binder syndrome (beautiful submission package, disconnected from operations).

Tell it like it is: most NDI pain comes from weak operational integration, not weak writing.

12) How this maps to V5 by SG Systems Global

V5 makes NDI discipline operational by connecting ingredient definition, supplier control, lot-level traceability, and change governance into one enforceable system. Practically, V5 can treat an NDI ingredient as a controlled master data object with locked specifications, required identity tests, and an approved supplier list—so procurement and receiving can’t quietly swap “similar” materials without triggering change control. At receipt, V5 can enforce quarantine until required verification steps are completed, bind CoA data to the exact incoming lot, and preserve an audit trail for all approvals and overrides. The part that matters most during scrutiny is scope: if a complaint or adverse event signal arises, V5 can traverse end-to-end lot genealogy to show which finished lots consumed the ingredient, which shipments those lots went to, and which other SKUs share the same ingredient lots or suppliers—so you can contain narrowly when evidence allows, instead of quarantining everything. V5 also ties NDI to continuous control: formula versions are governed, supplier performance can be trended, and post-market signals (complaints and adverse events) can be linked back to ingredient lots and supplier history to trigger targeted investigations and CAPA. Put bluntly: V5 turns NDI from a one-time narrative into a living control system that stays true as your business changes.

• Platform overview: V5 Solution Overview
• Quality governance: Quality Management System (QMS)
• Warehouse controls: Warehouse Management System (WMS)
• Traceability: V5 Traceability
• Integration layer: V5 Connect (API)

13) Extended FAQ

Q1. What is an NDI notification in practical terms?
A structured premarket submission that ties ingredient identity, intended use, manufacturing consistency, and safety rationale into one coherent record—then expects you to keep the “ingredient evaluated” consistent with the “ingredient marketed.”

Q2. What usually makes NDI work fail operationally?
Weak identity control and uncontrolled drift: supplier swaps, process changes, widened specs, or formula/dose changes that aren’t reviewed against the original evidence base.

Q3. Why is traceability relevant to NDI?
Because when a safety signal appears, you must define scope fast. Lot genealogy and shipment mapping are what keep actions narrow and defensible instead of broad and expensive.

Q4. How should changes be managed after an NDI is filed?
Through explicit NDI-impacting change criteria inside change control: supplier/process/spec/dose/population changes should automatically trigger review and documentation.

Q5. What does “inspection-ready” look like for NDI?
The ability to produce a current evidence pack quickly: determination record, ingredient definition and specs, identity testing rules, supplier qualification and CoA verification, change control history, traceability scope, post-market signal linkage, and audit trails.

Related Reading
Strengthen operational control with Supplier Qualification, Identity Testing, and Change Control. Reduce scope risk using End-to-End Lot Genealogy plus Complaint Triage and Adverse Event Intake.