21 CFR 111.70 through 21 CFR 111.75 establishes the specifications, testing, and examination requirements for components (raw material ingredients), in-process materials, packaging materials, and finished dietary supplement products. These provisions are the operational core of the supplement cGMP system.
Component Specifications
Under 21 CFR 111.70(a), a manufacturer must establish written specifications for each component used in a dietary supplement, including:
Identity — the component's established name or common name
Purity — acceptable limits for contaminants or impurities
Strength — potency or concentration where applicable
Composition — other relevant quality attributes
Limits for contaminants that may adulterate or lead to adulteration of the finished product (e.g., heavy metals, pesticides, microbial limits)
Specifications must be established before manufacturing begins and must be based on the intended use of the component in the finished product.
Identity Testing: The Non-Delegable Requirement
Under 21 CFR 111.75(a)(1), before using any component in the manufacture of a dietary supplement, a manufacturer must:
Conduct at least one appropriate test or examination to verify the identity of each component.
This is one of the most important and most frequently misunderstood requirements in supplement cGMP:
A supplier's COA does not satisfy the identity testing requirement — it may supplement the manufacturer's testing program but cannot replace it
Identity testing must be conducted by the supplement manufacturer (or its contract laboratory) — it cannot be fully outsourced to the supplier
The identity test must be able to distinguish the component from other materials that could be a substitute or contaminant
What Counts as Identity Testing
For botanical raw materials, acceptable identity tests include:
Macroscopic and microscopic examination
HPTLC (High Performance Thin Layer Chromatography)
DNA barcoding (for species-level botanical authentication)
HPLC with authentic reference standards
Organoleptic examination (appearance, odor, color) — acceptable for some materials but not typically sufficient alone for botanicals with adulteration history
For vitamins, minerals, and other defined chemical entities:
Wet chemistry tests (e.g., titrimetric, colorimetric)
Spectroscopic methods (FTIR, UV-Vis)
Chromatographic methods
Supplier Qualification as an Alternative Testing Pathway
Under 21 CFR 111.75(a)(2), for components other than identity, a manufacturer may rely on the supplier's COA to avoid conducting its own testing — if:
The manufacturer establishes the reliability of the supplier's COA through a qualification program (e.g., periodic auditing of the supplier's analytical methods, or periodic confirmatory testing by the manufacturer)
The manufacturer reviews and maintains the supplier's COA for each received lot
This pathway covers testing for purity, strength, composition, and contaminant limits — but not identity. Identity testing must always be conducted by the manufacturer.
In-Process Testing
Under 21 CFR 111.75(c), a manufacturer must examine or test in-process materials to determine whether they meet in-process specifications. In-process specifications must address:
Blend uniformity — for blended supplements, verifying that components are uniformly distributed
Capsule fill weight — for encapsulated supplements, verifying fill weight is within specification
Tablet hardness, disintegration, and friability — for tablet dose forms
pH and viscosity — for liquid supplements
Other process parameters relevant to the product type and specifications
Finished Product Testing
Under 21 CFR 111.75(d), before releasing a finished batch for distribution, a manufacturer must test or examine the finished batch to verify it meets all finished product specifications, including:
Identity of the dietary ingredients declared on the Supplement Facts panel
Potency of nutrients and dietary ingredients (where a label claim is made)
Purity — contaminant testing (heavy metals, pesticides, microbial limits, residual solvents as applicable)
Composition and physical attributes (e.g., tablet appearance, fill weight, liquid clarity)
Stability — the specification must ensure the product meets label claims through the product's expiration date
If any specification test shows the product does not meet specifications, the batch cannot be released. The batch must be reviewed for disposition — reprocessing (if permitted by the master manufacturing record), rejection, or resampling with full investigation.
Reserve Samples
Under 21 CFR 111.83, reserve samples of finished products must be:
Retained in the same container-closure system as the commercial product (or one that offers equivalent protection)
Retained for 1 year after the product expiration date or 2 years from the date of distribution, whichever is longer
Made available to FDA upon request
Reserve samples allow for investigation of consumer complaints, adverse event reports, or regulatory inquiries after the product has shipped.
Common FDA Warning Letter Findings Related to Component Testing
FDA has issued warning letters for supplement companies citing:
Failing to establish identity of components through any testing — relying entirely on supplier COAs
Using a single physical attribute (e.g., appearance) as the only identity test for a botanical raw material
Not conducting in-process testing for blend uniformity on homogeneous blend supplements
Finished product testing that doesn't include potency testing for the declared dietary ingredients
No established specifications for components or finished products
How Truli Helps with Component Testing Compliance
Specification documentation review: Truli evaluates whether written specifications have been established for all components and finished products, covering identity, purity, strength, and composition
Identity testing program assessment: Truli identifies components for which supplier COAs are being used as the sole identity verification, which is not compliant, and recommends appropriate testing methods
Supplier qualification documentation: Truli reviews supplier qualification records to verify that the alternate testing pathway (relying on COAs) has been properly established for eligible non-identity tests
Finished product release records: Truli verifies that batch release records include documentation of required testing and passing results for all finished product specifications
Related Regulations
21 CFR Part 111 — Supplement cGMP — Full cGMP framework for dietary supplements
FDA FSVP — Foreign Supplier Verification — FSVP requirements for imported supplement ingredients
21 CFR Part 117 FSMA Preventive Controls — FSMA framework for food safety hazard controls that overlaps with supplement testing
Frequently Asked Questions
Our supplier sends a COA with every lot. Isn't that enough?
Not for identity testing. The supplier's COA can satisfy your testing obligations for purity, strength, and composition (with a qualified supplier program), but you must independently verify the identity of each component. This is a hard requirement — relying solely on supplier COAs for identity is one of the most common FDA warning letter findings in the supplement industry.
What is the minimum acceptable identity test for a botanical raw material?
FDA has not prescribed a specific test method, but the test must be appropriate for the material. For botanicals, HPTLC, macroscopic/microscopic examination against authenticated reference materials, or DNA barcoding are common approaches. Simple organoleptic examination (look and smell) is generally not considered adequate for botanicals with adulteration histories — such as Panax ginseng (often adulterated with American ginseng) or turmeric (adulterated with synthetic dyes).
Do we need to test every single lot, or can we do periodic testing?
Identity testing must be performed on every received lot of each component — not periodic testing. For other specifications (purity, strength), periodic confirmatory testing may be acceptable within a qualified supplier program, but you should consult FDA guidance on supplier qualification to ensure your approach is compliant.
A note from Truli: Truli is not a law firm, and this article does not constitute or contain legal advice or create an attorney-client relationship. When determining your obligations and compliance with respect to relevant laws and regulations, you should consult a licensed attorney.
Last updated: April 2026. Reflects 21 CFR 111.70–111.75 as of April 2026. Book a demo to see how Truli monitors supplement cGMP compliance.
