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U.S. Department of Health and Human Services

CFR - Code of Federal Regulations Title 21

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The information on this page is current as of April 1 2016.

For the most up-to-date version of CFR Title 21, go to the Electronic Code of Federal Regulations (eCFR).

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Help | More About 21CFR
[Code of Federal Regulations]
[Title 21, Volume 2]
[Revised as of April 1, 2016]
[CITE: 21CFR111]





TITLE 21--FOOD AND DRUGS
CHAPTER I--FOOD AND DRUG ADMINISTRATION
DEPARTMENT OF HEALTH AND HUMAN SERVICES
SUBCHAPTER B--FOOD FOR HUMAN CONSUMPTION
 
PART 111CURRENT GOOD MANUFACTURING PRACTICE IN MANUFACTURING, PACKAGING, LABELING, OR HOLDING OPERATIONS FOR DIETARY SUPPLEMENTS
 

Subpart F--Production and Process Control System: Requirements for Quality Control

Sec. 111.103 What are the requirements under this subpart F for written procedures?

You must establish and follow written procedures for the responsibilities of the quality control operations, including written procedures for conducting a material review and making a disposition decision, and for approving or rejecting any reprocessing.

Sec. 111.105 What must quality control personnel do?

Quality control personnel must ensure that your manufacturing, packaging, labeling, and holding operations ensure the quality of the dietary supplement and that the dietary supplement is packaged and labeled as specified in the master manufacturing record. To do so, quality control personnel must perform operations that include:

(a) Approving or rejecting all processes, specifications, written procedures, controls, tests, and examinations, and deviations from or modifications to them, that may affect the identity, purity, strength, or composition of a dietary supplement;

(b) Reviewing and approving the documentation setting forth the basis for qualification of any supplier;

(c) Reviewing and approving the documentation setting forth the basis for why meeting in-process specifications, in combination with meeting component specifications, will help ensure that the identity, purity, strength, and composition of the dietary supplement are met;

(d) Reviewing and approving the documentation setting forth the basis for why the results of appropriate tests or examinations for each product specification selected under 111.75(c)(1) will ensure that the finished batch of the dietary supplement meets product specifications;

(e) Reviewing and approving the basis and the documentation for why any product specification is exempted from the verification requirements in 111.75(c)(1), and for why any component and in-process testing, examination, or monitoring, or other methods will ensure that such exempted product specification is met without verification through periodic testing of the finished batch;

(f) Ensuring that required representative samples are collected;

(g) Ensuring that required reserve samples are collected and held;

(h) Determining whether all specifications established under 111.70(a) are met; and

(i) Performing other operations required under this subpart.

Sec. 111.110 What quality control operations are required for laboratory operations associated with the production and process control system?

Quality control operations for laboratory operations associated with the production and process control system must include:

(a) Reviewing and approving all laboratory control processes associated with the production and process control system;

(b) Ensuring that all tests and examinations required under 111.75 are conducted; and

(c) Reviewing and approving the results of all tests and examinations required under 111.75.

Sec. 111.113 What quality control operations are required for a material review and disposition decision?

(a) Quality control personnel must conduct a material review and make a disposition decision if:

(1) A specification established in accordance with 111.70 is not met;

(2) A batch deviates from the master manufacturing record, including when any step established in the master manufacturing record is not completed and including any deviation from specifications;

(3) There is any unanticipated occurrence during the manufacturing operations that adulterates or may lead to adulteration of the component, dietary supplement, or packaging, or could lead to the use of a label not specified in the master manufacturing record;

(4) Calibration of an instrument or control suggests a problem that may have resulted in a failure to ensure the quality of a batch or batches of a dietary supplement; or

(5) A dietary supplement is returned.

(b)(1) When there is a deviation or unanticipated occurrence during the production and in-process control system that results in or could lead to adulteration of a component, dietary supplement, or packaging, or could lead to the use of a label not specified in the master manufacturing record, quality control personnel must reject the component, dietary supplement, packaging, or label unless it approves a treatment, an in-process adjustment, or reprocessing to correct the applicable deviation or occurrence.

(2) When a specification established in accordance with 111.70 is not met, quality control personnel must reject the component, dietary supplement, package or label, unless quality control personnel approve a treatment, an in-process adjustment, or reprocessing, as permitted in 111.77.

(c) The person who conducts a material review and makes the disposition decision must, at the time of performance, document that material review and disposition decision.

Sec. 111.117 What quality control operations are required for equipment, instruments, and controls?

Quality control operations for equipment, instruments, and controls must include:

(a) Reviewing and approving all processes for calibrating instruments and controls;

(b) Periodically reviewing all records for calibration of instruments and controls;

(c) Periodically reviewing all records for calibrations, inspections, and checks of automated, mechanical, or electronic equipment; and

(d) Reviewing and approving controls to ensure that automated, mechanical, or electronic equipment functions in accordance with its intended use.

Sec. 111.120 What quality control operations are required for components, packaging, and labels before use in the manufacture of a dietary supplement?

Quality control operations for components, packaging, and labels before use in the manufacture of a dietary supplement must include:

(a) Reviewing all receiving records for components, packaging, and labels;

(b) Determining whether all components, packaging, and labels conform to specifications established under 111.70 (b) and (d);

(c) Conducting any required material review and making any required disposition decision;

(d) Approving or rejecting any treatment and in-process adjustments of components, packaging, or labels to make them suitable for use in the manufacture of a dietary supplement; and

(e) Approving, and releasing from quarantine, all components, packaging, and labels before they are used.

Sec. 111.123 What quality control operations are required for the master manufacturing record, the batch production record, and manufacturing operations?

(a) Quality control operations for the master manufacturing record, the batch production record, and manufacturing operations must include:

(1) Reviewing and approving all master manufacturing records and all modifications to the master manufacturing records;

(2) Reviewing and approving all batch production-related records;

(3) Reviewing all monitoring required under subpart E;

(4) Conducting any required material review and making any required disposition decision;

(5) Approving or rejecting any reprocessing;

(6) Determining whether all in-process specifications established in accordance with 111.70(c) are met;

(7) Determining whether each finished batch conforms to product specifications established in accordance with 111.70(e); and

(8) Approving and releasing, or rejecting, each finished batch for distribution, including any reprocessed finished batch.

(b) Quality control personnel must not approve and release for distribution:

(1) Any batch of dietary supplement for which any component in the batch does not meet its identity specification;

(2) Any batch of dietary supplement, including any reprocessed batch, that does not meet all product specifications established in accordance with 111.70(e);

(3) Any batch of dietary supplement, including any reprocessed batch, that has not been manufactured, packaged, labeled, and held under conditions to prevent adulteration under section 402(a)(1), (a)(2), (a)(3), and (a)(4) of the act; and

(4) Any product received from a supplier for packaging or labeling as a dietary supplement (and for distribution rather than for return to the supplier) for which sufficient assurance is not provided to adequately identify the product and to determine that the product is consistent with your purchase order.

Sec. 111.127 What quality control operations are required for packaging and labeling operations?

Quality control operations for packaging and labeling operations must include:

(a) Reviewing the results of any visual examination and documentation to ensure that specifications established under 111.70(f) are met for all products that you receive for packaging and labeling as a dietary supplement (and for distribution rather than for return to the supplier);

(b) Approving, and releasing from quarantine, all products that you receive for packaging or labeling as a dietary supplement (and for distribution rather than for return to the supplier) before they are used for packaging or labeling;

(c) Reviewing and approving all records for packaging and label operations;

(d) Determining whether the finished packaged and labeled dietary supplement conforms to specifications established in accordance with 111.70(g);

(e) Conducting any required material review and making any required disposition decision;

(f) Approving or rejecting any repackaging of a packaged dietary supplement;

(g) Approving or rejecting any relabeling of a packaged and labeled dietary supplement; and

(h) Approving for release, or rejecting, any packaged and labeled dietary supplement (including a repackaged or relabeled dietary supplement) for distribution.

Sec. 111.130 What quality control operations are required for returned dietary supplements?

Quality control operations for returned dietary supplements must include:

(a) Conducting any required material review and making any required disposition decision; including:

(1) Determining whether tests or examination are necessary to determine compliance with product specifications established in accordance with 111.70(e); and

(2) Reviewing the results of any tests or examinations that are conducted to determine compliance with product specifications established in accordance with 111.70(e);

(b) Approving or rejecting any salvage and redistribution of any returned dietary supplement;

(c) Approving or rejecting any reprocessing of any returned dietary supplement; and

(d) Determining whether the reprocessed dietary supplement meets product specifications and either approving for release, or rejecting, any returned dietary supplement that is reprocessed.

Sec. 111.135 What quality control operations are required for product complaints?

Quality control operations for product complaints must include reviewing and approving decisions about whether to investigate a product complaint and reviewing and approving the findings and followup action of any investigation performed.

Sec. 111.140 Under this subpart F, what records must you make and keep?

(a) You must make and keep the records required under this subpart F in accordance with subpart P of this part.

(b) You must make and keep the following records:

(1) Written procedures for the responsibilities of the quality control operations, including written procedures for conducting a material review and making a disposition decision and written procedures for approving or rejecting any reprocessing;

(2) Written documentation, at the time of performance, that quality control personnel performed the review, approval, or rejection requirements by recording the following:

(i) Date that the review, approval, or rejection was performed; and

(ii) Signature of the person performing the review, approval, or rejection; and

(3) Documentation of any material review and disposition decision and followup. Such documentation must be included in the appropriate batch production record and must include:

(i) Identification of the specific deviation or the unanticipated occurrence;

(ii) Description of your investigation into the cause of the deviation from the specification or the unanticipated occurrence;

(iii) Evaluation of whether or not the deviation or unanticipated occurrence has resulted in or could lead to a failure to ensure the quality of the dietary supplement or a failure to package and label the dietary supplement as specified in the master manufacturing record;

(iv) Identification of the action(s) taken to correct, and prevent a recurrence of, the deviation or the unanticipated occurrence;

(v) Explanation of what you did with the component, dietary supplement, packaging, or label;

(vi) A scientifically valid reason for any reprocessing of a dietary supplement that is rejected or any treatment or in-process adjustment of a component that is rejected; and

(vii) The signature of the individual(s) designated to perform the quality control operation, who conducted the material review and made the disposition decision, and of each qualified individual who provides information relevant to that material review and disposition decision.

Authority: 21 U.S.C. 321, 342, 343, 371, 374, 381, 393; 42 U.S.C. 264.
Source: 72 FR 34942, June 25, 2007, unless otherwise noted.

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