21 CFR Part 111 is FDA's current good manufacturing practice regulation for dietary supplements. It applies to anyone who manufactures, packages, labels, or holds a dietary supplement, and it requires a production and process control system built on written specifications, identity testing, master manufacturing and batch production records, and quality control review.
Who Part 111 applies to
Part 111 covers firms that manufacture, package, label, or hold dietary supplements sold in the United States, including foreign facilities and contract manufacturers. Brands that outsource manufacturing are still responsible for making sure the products they release meet Part 111. Finished drugs, including OTC drugs, fall under Part 211 instead.
The full text is on the eCFR.
The 16 subparts at a glance
| Subpart | What it covers |
|---|---|
| A · General provisions | Scope and definitions |
| B · Personnel | Qualifications, training, hygiene |
| C · Physical plant and grounds | Facility design, sanitation, pest control |
| D · Equipment and utensils | Design, calibration, cleaning, automated equipment |
| E · Production and process control system | Specifications and testing that the system is built on |
| F · Quality control | What quality control personnel must review, approve, or reject |
| G · Components, packaging, and labels | Receiving, testing, and quarantining incoming materials |
| H · Master manufacturing record | One record for each formulation and batch size |
| I · Batch production record | A record for every batch made |
| J · Laboratory operations | Lab controls and test methods |
| K · Manufacturing operations | Controls during manufacturing |
| L · Packaging and labeling operations | Controls during packaging and labeling |
| M · Holding and distributing | Storage and distribution conditions |
| N · Returned dietary supplements | Handling returned product |
| O · Product complaints | Review and investigation of complaints |
| P · Records and recordkeeping | Retention and record format |
Specifications and identity testing
Section 111.70 requires written specifications for each component, for in-process points, for labels and packaging, and for each finished batch, covering identity, purity, strength, composition, and limits on contaminants.
Section 111.75 then requires at least one appropriate test or examination to verify the identity of every dietary ingredient before use. Specification and identity-testing requirements are among the most frequently cited Part 111 observations on FDA Form 483s.
Relying on a supplier's certificate of analysis
For component specifications other than dietary ingredient identity, 111.75(a)(2) lets you rely on a supplier's CoA if you first qualify the supplier by confirming the results of their tests, the CoA describes the test methods, limits, and actual results, you keep documentation of the qualification, and you periodically reconfirm it. See the certificate of analysis guide and incoming material disposition.
Records, reserve samples, and quality control review
- Master manufacturing record (Subpart H): one for each unique formulation and batch size.
- Batch production record (Subpart I): created every time a batch is made, following the master record.
- Quality control review (Subpart F): quality control personnel approve or reject components, in-process material, and finished batches, and make material review and disposition decisions when a specification is not met.
- Reserve samples (111.83): held for one year past the shelf-life date, or two years past distribution of the last batch if there is no shelf-life date.
- Record retention (111.605): the same one-year-past-shelf-life or two-years-past-distribution rule applies to required records.
Where Ovada fits
Ovada does the evidence-heavy work Part 111 creates: checking CoAs against specifications, tracking supplier qualification, rebuilding deviations from batch records, and monitoring procedures for gaps. Quality control personnel keep every disposition. See Ovada for supplement manufacturers, or start with a gap assessment.
Questions
Who has to comply with 21 CFR Part 111?
Anyone who manufactures, packages, labels, or holds a dietary supplement sold in the United States, including contract manufacturers and foreign facilities. Brands that outsource manufacturing remain responsible for the products they release.
Can we rely on a supplier's certificate of analysis under Part 111?
For specifications other than the identity of dietary ingredients, yes, if you qualify the supplier, the CoA shows methods, limits, and results, and you periodically reconfirm the supplier. Identity of each dietary ingredient must still be verified.
How long must Part 111 records be kept?
One year past the shelf-life date, or two years past the date of distribution of the last batch if no shelf-life date is used.