21 CFR 111 Testing Requirements | Verified Analytical Laboratory

What is 21 CFR Part 111 and who must follow it?

Part 111 is FDA’s rule titled “Current Good Manufacturing Practice in Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements,” published on 25 June 2007 (72 FR 34752). FDA’s Small Entity Compliance Guide notes it took effect on 24 August 2007, with compliance dates phased by size: 25 June 2008 for firms with 500 or more full-time equivalent employees, 25 June 2009 for at least 20 but fewer than 500, and 25 June 2010 for fewer than 20.

Under 21 CFR 111.1 the rule applies if you manufacture, package, label or hold a dietary supplement, including supplements imported or offered for import. Brands that outsource production are not off the hook. In the compliance guide’s words, a distributor that contracts with a manufacturer and sells under its own label “has an obligation to know what and how manufacturing activities are performed so that the distributor can make decisions related to whether the packaged and labeled product conforms to its established specifications and whether to approve and release the product for distribution.”

Which Part 111 sections cover testing?

Part 111 testing requirements by section. Wording checked against eCFR Title 21 (up to date as of 30 October 2026) on 3 November 2026.

Requirement	Section	What it means in practice
Component specifications	111.70(b)	An identity specification for every component, plus specifications needed for finished-product purity, strength and composition, and limits on contamination
Finished product specifications	111.70(e)	Identity, purity, strength, composition and contaminant limits for each finished batch
Check the specifications	111.73	Writing specifications is not enough; you must determine whether they are met
Identity of dietary ingredients	111.75(a)(1)	At least one appropriate test or examination before use, unless FDA grants an exemption by petition under 21 CFR 10.30
Other components	111.75(a)(2)	Test them, or rely on a qualified supplier’s CoA that describes the methods, limits and actual results
In-process monitoring	111.75(b)	Monitor in-process control points to confirm in-process specifications are met and catch deviations
Finished batch verification	111.75(c)	Every batch, or a subset identified through a sound statistical sampling plan; test selected specifications and document why they verify all of them
Exempted specifications	111.75(d)	Allowed only where finished-batch tests cannot verify a specification and no scientifically valid method exists at that stage; quality control approves the reasoning
Test methods	111.75(h)	Appropriate, scientifically valid methods, including at least one of gross organoleptic, macroscopic, microscopic, chemical or other scientifically valid analysis
Corrective action plans	111.75(i)	Written plans for when a specification is not met
Failed specifications	111.77	Quality control rejects the material unless it approves treatment or reprocessing; a component that fails its identity specification must not be used
Representative samples	111.80	From each unique lot of components, in-process materials, finished batches (or the statistical subset), product received for packaging or labeling, packaging and labels, and packaged lots
Reserve samples	111.83	From each distributed lot, in the same container-closure system, labeled with the batch, lot or control number, held 1 year past the shelf life date (if used) or 2 years from distribution of the last batch, and at least twice the quantity needed for all product specification tests
Quality control of lab work	111.110	Quality control approves lab control processes, makes sure the 111.75 tests are done, and reviews and approves the results
Batch release	111.123(b)	No release of a batch containing a component that fails its identity specification, or of a batch that fails any product specification

Figures checked against the sources below on 3 November 2026; rules change, so confirm the current version before relying on them.

What does Subpart J require of the laboratory?

Subpart J, 21 CFR 111.303 to 111.325, covers laboratory operations:

111.303: written procedures for laboratory operations, including the tests and examinations used to determine whether specifications are met.
111.310: adequate laboratory facilities to test components, in-process specifications and finished supplements.
111.315: laboratory control processes approved by quality control, covering criteria for setting specifications, sampling plans for representative samples, criteria for selecting test methods, criteria for selecting standard reference materials, and use of methods in line with those criteria.
111.320: verify that methods are appropriate for their intended use, and identify and use an appropriate scientifically valid method for each specification that requires testing.
111.325: keep the written procedures, plus documentation made at the time of performance that the methodology was followed, including the results.

FDA’s compliance guide describes a scientifically valid method as “a scientific method that is accurate, precise, and specific for its intended purpose.” When an outside lab tests for you, ask how its method was shown to suit your product form, such as a gummy, softgel or powder, and keep its report with your Subpart J records.

Does Part 111 require testing by an outside lab?

No. Part 111 does not say who must run the tests. Section 111.310 refers to “the laboratory facilities that you use,” and 111.3 defines quality control personnel as “any person, persons, or group, within or outside of your organization” that you designate. Manufacturers test in-house, send work to a contract lab, or combine the two.

What Part 111 does insist on is that the results exist, come from scientifically valid methods, and are reviewed and approved by quality control. Requirements for testing by a lab outside the company usually come from buyers and marketplaces instead; see testing requirements by sales channel.

What records does Part 111 require for testing?

Subpart E records (111.95(b)): the specifications, how you qualified any supplier whose CoA you rely on, why your in-process and finished-batch tests ensure product specifications are met, the basis for any exempted specification, and FDA’s response to any identity-testing petition.
Laboratory records (111.325(b)): written lab procedures and documentation, made at the time of performance, that the methods were followed, with the results.
Retention (111.605(a)): 1 year past the shelf life date, if shelf life dating is used, or 2 years beyond the date of distribution of the last batch associated with the records.
Form (111.605(b) and (c)): originals, true copies or electronic records; electronic records must comply with 21 CFR Part 11.
Access (111.610): records must be readily available for FDA inspection and copying during the retention period.

How do you check your own program against Part 111?

Is there a written specification for every component and finished product, including contaminant limits?
Is every lot of every dietary ingredient identity-tested before use? See identity testing.
Where you rely on supplier CoAs for other components, is the qualification documented and periodically re-confirmed?
Is the finished-batch plan written down, with its statistical basis and quality control approval, and does it cover strength, heavy metals and microbial specifications?
Has each method been shown to suit your product form?
Are reserve samples at least twice the testing quantity, stored in the market package, and held for the full period?
Could you hand FDA every result for every distributed lot today?

Any “no” points to the matching row in the table above. For what each result should look like on paper, see certificate of analysis.

Questions about this page

Does 21 CFR 111 apply to brands that do not manufacture?

It reaches them. Part 111 covers anyone who manufactures, packages, labels or holds a supplement, and FDA's compliance guide says a distributor selling under its own label must know what and how manufacturing activities are performed so it can decide whether the product meets its specifications and whether to release it.

Does Part 111 set numeric limits for heavy metals or microbes?

No. Sections 111.70(b)(3) and 111.70(e) require you to set limits on contamination that may adulterate the product, but Part 111 lists no numbers. Brands draw them from sources such as USP general chapters, California Prop 65 safe harbor levels and buyer specifications, then write them into their own specifications.

What counts as a sound statistical sampling plan under Part 111?

Part 111 does not define one or set a sample size. Under 111.75(c), you choose which finished batches to test through a sound statistical sampling plan, or test every batch, then document why the specifications you test verify all product specifications. Quality control personnel must review and approve that documentation.

How long must reserve samples be kept?

Under 21 CFR 111.83(b)(3), for 1 year past the shelf life date if shelf life dating is used, or for 2 years from the date of distribution of the last batch associated with the reserve sample. They must also be held in the market container-closure system and be at least twice the quantity needed for product specification testing.

Is a supplement CGMP audit certificate the same as meeting Part 111?

No. Part 111 is the legal requirement, enforced by FDA. Audit programs run by outside organizations check a facility against Part 111 or a related standard and issue their own certificate, which some buyers and marketplaces ask for. Holding one does not replace the records and testing Part 111 itself requires.

Sources: 21 CFR Part 111, dietary supplement CGMP rule (eCFR) · 21 CFR 111.75, What must you do to determine whether specifications are met? (eCFR) · 21 CFR Part 111 Subpart J, Laboratory operations (eCFR) · FDA Small Entity Compliance Guide: CGMP for dietary supplements · Federal Register, 72 FR 34752, dietary supplement CGMP final rule (25 June 2007)
Last reviewed: 3 November 2026

21 CFR 111 testing requirements for dietary supplements