21 CFR Part 111

21 CFR Part 111 – Dietary Supplement cGMPs

This topic is part of the SG Systems Global regulatory glossary series.

Updated October 2025 • FDA / cGMP • Dietary Supplements

21 CFR Part 111 sets FDA’s current Good Manufacturing Practice (cGMP) requirements for dietary supplements—covering personnel, facilities/sanitation, equipment, production/process control, quality control operations, specifications and testing, MMR/BPR documentation, labeling/packaging, holding/distribution, returns, complaints, and recordkeeping. If you manufacture, package, label, or hold supplements, Part 111 applies. See our Dietary Supplements industry overview and 21 CFR 210/211 comparison for context.

1) What It Is

Part 111 demands a documented, controlled system ensuring supplements are manufactured consistently to specifications and that records credibly support product disposition. It requires a qualified Quality Control unit, written specifications for components, in-process controls and finished products, adequate MMRs/BPRs, supplier qualification, label/packaging controls, complaint handling, and recordkeeping. For a digital approach, see V5 QMS and eBMR.

TL;DR: Part 111 is the supplement-specific cGMP rule. It requires a functioning QC unit, written specs and testing (including identity testing for dietary ingredients), controlled MMR/BPRs, supplier qualification, labeling/packaging controls, complaint handling, and retention of complete records that justify release decisions.

Key expectations (selected):

  • Quality Control (QC) operations. QC approves/rejects components, in-process materials, labels/packaging, finished products; reviews and approves MMRs and BPRs; evaluates deviations, reprocessing, material review & disposition; and oversees investigations/CAPA via QMS.
  • Specifications & testing. Written specs for identity, purity, strength, composition, and contaminant limits for components and finished goods. Dietary ingredients require at least one appropriate identity test. Use CoA intelligently with supplier qualification.
  • MMR/BPR control. Each product/size has an approved MMR; each batch executes a compliant BPR with complete data, sign-offs, yields/reconciliation, and label accountability. Consider eBR/eBMR to enforce steps and capture e-signatures.
  • Supplier controls & receiving. Qualify suppliers, verify component identity (especially actives), and quarantine until released. See Quality-Enforced Receiving.
  • Process controls. Documented procedures, validated/verified critical steps, in-process checks, environmental/cleaning controls, and equipment calibration/maintenance managed in MES and QMS.
  • Labeling & packaging control. Approved master labels, version control, issuance/reconciliation, line clearance; WMS helps block mis-labeled lots and enforce FEFO.
  • Complaints & product returns. Evaluate, investigate, and document; escalate to medical events as applicable; manage Material Review & Disposition with traceability.
  • Recordkeeping. Keep complete manufacturing/quality records for each batch; retain for the required period (e.g., at least 1 year past shelf-life or 2 years beyond distribution of the last batch when no shelf-life is set).

Authoritative references. The live rule text is at the eCFR: 21 CFR Part 111. For interplay with electronic records/signatures, see 21 CFR Part 11. If your operation also makes drugs or devices, compare with 210/211 (Drugs) and 820 (Devices).

2) FAQ

Q1. Do I have to test every component?
You must establish specs and appropriate tests/exams. At least one identity test is required for each dietary ingredient. For other components, you may rely on qualified-supplier CoAs plus appropriate verification.

Q2. What’s the difference between Part 111 and 210/211?
210/211 are drug GMPs; Part 111 is supplement-specific. It emphasizes identity testing of dietary ingredients, MMR/BPR rigor, QC authority, and labeling/packaging controls tailored to supplements. See our detailed comparison.

Q3. MMR vs BPR (Batch Record)?
The MMR is the approved master recipe and instructions; the BPR documents actual execution, results, yields, reconciliations, variances, and sign-offs for each batch. Digital options: eBMR/eBR.

Q4. How should I handle supplier qualification?
Risk-based approval, ongoing verification (e.g., periodic testing), performance monitoring, and documentation. Gate unreleased lots in WMS until QC release.

Q5. Do I need LIMS?
Not mandated, but highly effective. Use Sample Labeling & LIMS Scheduling to auto-quarantine, trigger tests, track methods/instruments, and link results to CoAs and batch disposition.

Q6. How long must I keep records?
Keep batch/manufacturing/quality records for at least 1 year past the product’s shelf-life, or 2 years beyond distribution of the last batch if no shelf-life is set.

Q7. How does Part 11 interact with Part 111?
Part 111 defines what you must document and control; Part 11 governs how you manage electronic records/signatures (validation, audit trails, e-signatures, security).

Q8. What do inspectors focus on?
QC independence, adequacy of specs and identity testing, completeness of MMR/BPRs (including yields/reconciliation and label accountability), supplier qualification evidence, complaint handling, and whether records are complete, contemporaneous, and reviewable.

3) How It Relates to V5

V5 by SG Systems Global operationalizes Part 111 via enforced workflows, auditable records, and integrated QC checkpoints across receiving, production, lab, and warehouse.

End-to-end example. On receipt, an incoming botanical is quarantined and sampled. Identity testing is scheduled in LIMS; QC reviews results and releases the lot. The eBMR enforces weigh/verify tolerances and label checks. Finished-product CoA compiles from controlled tests. WMS blocks shipment of unreleased/expired lots and reconciles labels before distribution.

Primary References:
• FDA eCFR: 21 CFR Part 111
• Electronic Records/Signatures: 21 CFR Part 11
• V5 Modules: QMS • MES • WMS • V5 Connect API



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