21 CFR Part 111

21 CFR PART 111

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In June 2007, the FDA issued the Dietary Supplement Current Good Manufacturing Practice (CGMP) Final Rule 21 CFR Part 111. In essence, the final rule requires that the proper controls be in place for dietary supplements during manufacturing, packaging, labeling, and holding operations. The move was in response to concerns about substandard dietary supplement manufacturing practices, as well as mislabeling practices.

The 21 CFR 111 ruling addresses the quality of the manufacturing processes for dietary supplements and the accurate listing of supplement ingredients. It does not limit consumers’ access to dietary supplements; nor does it address the safety of the dietary supplement’s ingredients, or their effects on health, when proper manufacturing techniques are used. The rule applies to all domestic and foreign companies that manufacture, package, label or hold dietary supplements, including those involved with testing, quality control, and dietary supplement distribution in the U.S.

Part 111 Current Good Manufacturing Practices for Dietary Supplements

TITLE 21–FOOD AND DRUGS
CHAPTER I–FOOD AND DRUG ADMINISTRATION
DEPARTMENT OF HEALTH AND HUMAN SERVICES
SUBCHAPTER B – FOOD FOR HUMAN CONSUMPTION

Subpart A – General Provisions
§ 111.1 – Who is subject to this part?
§ 111.3 – What definitions apply to this part?
§ 111.5 – Do other statutory provisions and regulations apply?

Subpart B – Personnel
§ 111.8 – What are the requirements under this subpart B for written procedures?
§ 111.10 – What requirements apply for preventing microbial contamination from sick or infected personnel and for hygienic practices?
§ 111.12 – What personnel qualification requirements apply?
§ 111.13 – What supervisor requirements apply?
§ 111.14 – Under this subpart B, what records must you make and keep?

Subpart C – Physical Plant and Grounds
§ 111.15 – What sanitation requirements apply to your physical plant and grounds?
§ 111.16 – What are the requirements under this subpart C for written procedures?
§ 111.20 – What design and construction requirements apply to your physical plant?
§ 111.23 – Under this subpart C, what records must you make and keep?

Subpart D – Equipment and Utensils
§ 111.25 – What are the requirements under this subpart D for written procedures?
§ 111.27 – What requirements apply to the equipment and utensils that you use?
§ 111.30 – What requirements apply to automated, mechanical, or electronic equipment?
§ 111.35 – Under this subpart D, what records must you make and keep?

Subpart E – Requirement to Establish a Production and Process Control System
§ 111.55 – What are the requirements to implement a production and process control system?
§ 111.60 – What are the design requirements for the production and process control system?
§ 111.65 – What are the requirements for quality control operations?
§ 111.70 – What specifications must you establish?
§ 111.73 – What is your responsibility for determining whether established specifications are met?
§ 111.75 – What must you do to determine whether specifications are met?
§ 111.77 – What must you do if established specifications are not met?
§ 111.80 – What representative samples must you collect?
§ 111.83 – What are the requirements for reserve samples?
§ 111.87 – Who conducts a material review and makes a disposition decision?
§ 111.90 – What requirements apply to treatments, in-process adjustments, and reprocessing when there is a deviation or unanticipated occurrence or when a specification established in accordance with 111.70 is not met?
§ 111.95 – Under this subpart E, what records must you make and keep?

Subpart F – Production and Process Control System: Requirements for Quality Control
§ 111.103 – What are the requirements under this subpart F for written procedures?
§ 111.105 – What must quality control personnel do?
§ 111.110 – What quality control operations are required for laboratory operations associated with the production and process control system?
§ 111.113 – What quality control operations are required for a material review and disposition decision?
§ 111.117 – What quality control operations are required for equipment, instruments, and controls?
§ 111.120 – What quality control operations are required for components, packaging, and labels before use in the manufacture of a dietary supplement?
§ 111.123 – What quality control operations are required for the master manufacturing record, the batch production record, and manufacturing operations?
§ 111.127 – What quality control operations are required for packaging and labeling operations?
§ 111.130 – What quality control operations are required for returned dietary supplements?
§ 111.135 – What quality control operations are required for product complaints?
§ 111.140 – Under this subpart F, what records must you make and keep?

Subpart G – Production and Process Control System: Requirements for Components, Packaging, and Labels and for Product That You Receive for Packaging or Labeling as a Dietary Supplement
§ 111.153 – What are the requirements under this subpart G for written procedures?
§ 111.155 – What requirements apply to components of dietary supplements?
§ 111.160 – What requirements apply to packaging and labels received?
§ 111.165 – What requirements apply to a product received for packaging or labeling as a dietary supplement (and for distribution rather than for return to the supplier)?
§ 111.170 – What requirements apply to rejected components, packaging, and labels, and to rejected products that are received for packaging or labeling as a dietary supplement?
§ 111.180 – Under this subpart G, what records must you make and keep?

Subpart H – Production and Process Control System: Requirements for the Master Manufacturing Record
§ 111.205 – What is the requirement to establish a master manufacturing record?
§ 111.210 – What must the master manufacturing record include?

Subpart I – Production and Process Control System: Requirements for the Batch Production Record
§ 111.255 – What is the requirement to establish a batch production record?
§ 111.260 – What must the batch record include?

Subpart J – Production and Process Control System: Requirements for Laboratory Operations
§ 111.303 – What are the requirements under this subpart J for written procedures?
§ 111.310 – What are the requirements for the laboratory facilities that you use?
§ 111.315 – What are the requirements for laboratory control processes?
§ 111.320 – What requirements apply to laboratory methods for testing and examination?
§ 111.325 – Under this subpart J, what records must you make and keep?

Subpart K – Production and Process Control System: Requirements for Manufacturing Operations
§ 111.353 – What are the requirements under this subpart K for written procedures?
§ 111.355 – What are the design requirements for manufacturing operations?
§ 111.360 – What are the requirements for sanitation?
§ 111.365 – What precautions must you take to prevent contamination?
§ 111.370 – What requirements apply to rejected dietary supplements?
§ 111.375 – Under this subpart K, what records must you make and keep?

Subpart L – Production and Process Control System: Requirements for Packaging and Labeling Operations
§ 111.403 – What are the requirements under this subpart L for written procedures?
§ 111.410 – What requirements apply to packaging and labels?
§ 111.415 – What requirements apply to filling, assembling, packaging, labeling, and related operations?
§ 111.420 – What requirements apply to repackaging and relabeling?
§ 111.425 – What requirements apply to a packaged and labeled dietary supplement that is rejected for distribution?
§ 111.430 – Under this subpart L, what records must you make and keep?

Subpart M – Holding and Distributing
§ 111.453 – What are the requirements under this subpart for M written procedures?
§ 111.455 – What requirements apply to holding components, dietary supplements, packaging, and labels?
§ 111.460 – What requirements apply to holding in-process material?
§ 111.465 – What requirements apply to holding reserve samples of dietary supplements?
§ 111.470 – What requirements apply to distributing dietary supplements?
§ 111.475 – Under this subpart M, what records must you make and keep?

Subpart N – Returned Dietary Supplements
§ 111.503 – What are the requirements under this subpart N for written procedures?
§ 111.510 – What requirements apply when a returned dietary supplement is received?
§ 111.515 – When must a returned dietary supplement be destroyed, or otherwise suitably disposed of?
§ 111.520 – When may a returned dietary supplement be salvaged?
§ 111.525 – What requirements apply to a returned dietary supplement that quality control personnel approve for reprocessing?
§ 111.530 – When must an investigation be conducted of your manufacturing processes and other batches?
§ 111.535 – Under this subpart N, what records must you make and keep?

Subpart O – Product Complaints
§ 111.553 – What are the requirements under this subpart O for written procedures?
§ 111.560 – What requirements apply to the review and investigation of a product complaint?
§ 111.570 – Under this subpart O, what records must you make and keep?

Subpart P – Records and Recordkeeping
§ 111.605 – What requirements apply to the records that you make and keep?
§ 111.610 – What records must be made available to FDA?

All information on this page is current as of September 12, 2022.