Title 21 CFR reference

(a) The criteria set forth in subparts B, C, and D of this part prescribe the steps that manufacturers shall take under section 412(b)(2) and (b)(3) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 350a(b)(2) and (b)(3)) in processing infant formula. If the processing of the formula does not comply with any regulation in subparts B, C, or D of this part, the formula will be deemed to be adulterated under section 412(a)(3) of the Federal Food, Drug, and Cosmetic Act. (b) The criteria set forth in subpart E of this part prescribe the requirements for quality factors that infant formula shall meet under section 412(b)(1) of the Federal Food, Drug, and Cosmetic Act. If the formula fails to comply with any regulation in subpart E of this part, it will be deemed to be adulterated under section 412(a)(2) of the Federal Food, Drug, and Cosmetic Act. (c) The criteria set forth in subpart F of this part prescribe records requirements for quality factors under section 412(b)(1) of the Federal Food, Drug, and Cosmetic Act and for good manufacturing practices and quality control procedures, including distribution and audit records, under section 412(b)(2). If an infant formula…

(a) A manufacturer shall employ sufficient personnel, qualified by education, training, or experience, to perform all operations, including all required recordkeeping, in the manufacture, processing, packing, and holding of each infant formula and to supervise such operations to ensure that the operations are correctly and fully performed. (b) Personnel working directly with infant formula, infant formula raw materials, infant formula packaging, or infant formula equipment or utensil contact surfaces shall practice good personal hygiene to protect the infant formula against contamination. Good personal hygiene includes: (1) Wearing clean outer garments and, as necessary, protective apparel such as head, face, hand, and arm coverings; and (2) Washing hands thoroughly in a hand washing facility with soap and running water at a suitable temperature before starting work, after each absence from the work station, and at any other time when the hands may become soiled or contaminated. (c) Any person who reports that he or she has, or appears by medical examination or supervisory observation to have, an illness, open lesion (including boils, sores, or infected wounds), or any other…

(a) Every manufacturer of infant formula shall maintain the records specified in this regulation in order to permit the Food and Drug Administration to determine whether each manufacturer is in compliance with section 412 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 350a)). (b) The manufacturer shall maintain all records that pertain to food-packaging materials subject to § 174.5 of this chapter and that bear on whether such materials would cause an infant formula to be adulterated within the meaning of section 402(a)(2)(C) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 342(a)(2)(C)). (c) The manufacturer shall maintain all records that pertain to nutrient premix testing that it generates or receives. Such records shall include, but are not limited to: (1) Any results of testing conducted to ensure that each nutrient premix is in compliance with the premix certificate and guarantee and specifications that have been provided to the manufacturer by the premix supplier, including tests conducted when nutrients exceed their expiration date or shelf life (retest date). (2) All certificates and guarantees given by premix suppliers concerning the nutrients required…

(a) Before a new infant formula may be introduced or delivered for introduction into interstate commerce, including a new infant formula for export only, the manufacturer of the formula shall register with the Food and Drug Administration, Center for Food Safety and Applied Nutrition, Office of Nutrition, Labeling, and Dietary Supplements, Infant Formula and Medical Foods Staff (HFS-850), 5001 Campus Dr., College Park, MD 20740-3835. (b) The new infant formula registration shall include: (1) The name of the new infant formula; (2) The name of the manufacturer; (3) The street address of the place of business of the manufacturer; and (4) The name and street address of each establishment at which the manufacturer intends to manufacture such new infant formula.

(a) At least 90 days before a new infant formula is introduced or delivered for introduction into interstate commerce, a manufacturer shall submit notice of its intent to do so to the Food and Drug Administration at the address given in § 106.110(a). An original and two paper copies of such notice of intent shall be submitted, unless the notice is submitted in conformance with part 11 of this chapter, in which case a single copy shall be sufficient. (b) The new infant formula submission shall include: (1) The name and description of the physical form (e.g., powder, ready-to feed, or concentrate) of the infant formula; (2) An explanation of why the formula is a new infant formula; (3) The quantitative formulation of each form of the infant formula that is the subject of the notice in units per volume or units per weight for liquid formulas, specified either as sold or as fed, and units per dry weight for powdered formulas, and the weight of powder to be reconstituted with a specified volume of water, and, when applicable, a description of any reformulation of the infant formula, including a listing of each new or changed ingredient and a discussion of the effect of such changes…

To provide assurance that an infant formula meets the requirements for quality factors set forth in § 106.96, the manufacturer shall submit the following data and information: (a) Unless the manufacturer of a new infant formula can claim an exemption under § 106.96(c)(1) or (c)(2), the following assurances shall be provided to ensure that the requirements of § 106.96(a) and (b) have been met: (1) An explanation, in narrative form, setting forth how requirements for quality factors in § 106.96(b) have been met; (2) Records that contain the information required by § 106.96(b) to be collected during the study for each infant enrolled in the study. The records shall be identified by subject number, age, feeding group, gender, and study day of collection. (3) Data, which shall include: (i) Statistical evaluation for all measurements, including group means, group standard deviations, and measures of statistical significance for all measurements for each feeding group at the beginning of the study and at every point where measurements were made throughout the study, and (ii) Calculations of the statistical power of the study before study initiation and at study completion. (4) A…

(a) A manufacturer shall, after the first production and before the introduction into interstate commerce of a new infant formula (except for a new infant formula that is for export only for which a submission is received in compliance with § 106.120(c)), verify in a written submission to the Food and Drug Administration at the address given in § 106.110(a) that the infant formula complies with the requirements of the Federal Food, Drug, and Cosmetic Act and is not adulterated. (b) The verification submission shall include the following information: (1) The name of the new infant formula; the filing date for the new infant formula submission, in accordance with § 106.120, for the subject formula; and the identification number assigned by the Agency to the new infant formula submission: (2) A statement that the infant formula to be introduced into interstate commerce is the same as the infant formula that was the subject of the new infant formula notification and for which the manufacturer provided assurances in accordance with the requirements of § 106.120; (3) A summary of test results of the level of each nutrient required by § 107.100 of this chapter and any nutrient added…

(a) When a manufacturer makes a change in the formulation or processing of the formula that may affect whether the formula is adulterated under section 412(a) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 350a(a)), the manufacturer shall, before the first processing of such formula, make a submission to the Food and Drug Administration at the address given in § 106.110(a). An original and two copies shall be submitted. (b) The submission shall include: (1) The name and physical form of the infant formula (i.e., powder, ready-to-feed, or concentrate); (2)(i) An explanation of why the change in formulation or processing may affect whether the formula is adulterated; and (ii) What steps will be taken to ensure that, before the formula is introduced into interstate commerce, the formula will not be adulterated; and (3) A statement that the submission complies with § 106.120(b)(3), (b)(4), (b)(5), and (b)(6). When appropriate, a statement to the effect that the information required by § 106.120(b)(3), (b)(4), (b)(5), or (b)(6) has been provided to the Agency previously and has not been affected by the changes that are the subject of the current submission, together with…

(a) A manufacturer shall promptly notify the Food and Drug Administration in accordance with paragraph (b) of this section when the manufacturer has knowledge (that is, actual knowledge that the manufacturer had, or the knowledge which a reasonable person would have had under like circumstances or which would have been obtained upon the exercise of due care) that reasonably supports the conclusion that an infant formula that has been processed by the manufacturer and that has left an establishment subject to the control of the manufacturer: (1) May not provide the nutrients required by section 412(i) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 350a(i)) or by regulations issued under section 412(i)(2); or (2) May be otherwise adulterated or misbranded. (b) The notification made according to paragraph (a) of this section shall be made by telephone, to the Director of the appropriate Food and Drug Administration district office. After normal business hours (8 a.m. to 4:30 p.m.), the Food and Drug Administration's emergency number, 1-866-300-4374 shall be used. The manufacturer shall promptly send written confirmation of the notification to the Food and Drug…

Federal Register04http://www.archives.gov/federal_register/code_of_federal_regulations/ibr_locations.html.(a) Certain material is incorporated by reference into this part with the approval of the Director of the Federal Register under 5 U.S.C. 552(a) and 1 CFR part 51. To enforce any edition other than that specified in this section, the Food and Drug Administration must publish notice of change in the and the material must be available to the public. All approved material is available for inspection at the Food and Drug Administration library at 10903 New Hampshire Ave., Building 2, Third Floor, Silver Spring, MD 20993, 301-796-2039, and is available from the sources listed below. This material is also available for inspection at the National Archives and Records Administration (NARA). For information on the availability of this material at NARA, call 202-741-6030 or go to: http://www.3-a.org/(b) 3-A Sanitary Standards, Inc., 6888 Elm St., Suite 2D, McLean, VA 22101-3829, 703-790-0295, and may be ordered online at : (1) 3-A Sanitary Standards, No. 609-03: A Method of Producing Culinary Steam, adopted November 21, 2004, into § 106.20(h). (2) [Reserved]…

(a) Buildings used in the manufacture, processing, packing, or holding of infant formula shall be maintained in a clean and sanitary condition and shall have space for the separation of incompatible operations, such as the handling of raw materials, the manufacture of the product, and packaging and labeling operations. (b) Separate areas or another system of separation, such as a computerized inventory control, a written card system, or an automated system of segregation, shall be used for holding raw materials, in-process materials, and final infant formula product at the following times: (1) Pending release for use in infant formula production or pending release of the final product; (2) After rejection for use in, or as, infant formula; and (3) After release for use in infant formula production or after release of the final product. (c) Lighting shall allow easy identification of raw materials, packaging, labeling, in-process materials, and finished products that have been released for use in infant formula production and shall permit the easy reading of instruments and controls necessary in processing, packaging, and laboratory analysis. Any lighting fixtures directly…

The definitions in this section and the definitions contained in section 201 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321) shall apply to infant formula requirements in 21 CFR parts 106 and 107 of this chapter. Eligible infant formula means an infant formula that could be lawfully distributed in the United States on December 8, 2014. Final product stage means the point in the manufacturing process, before distribution of an infant formula, at which the infant formula is homogeneous and is not subject to further degradation due to processing. Indicator nutrient means a nutrient whose concentration is measured during the manufacture of an infant formula to confirm complete addition and uniform distribution of a premix or other substance of which the indicator nutrient is a part. Infant means a person not more than 12 months of age. Infant formula means a food which purports to be or is represented for special dietary use solely as a food for infants by reason of its simulation of human milk or its suitability as a complete or partial substitute for human milk. In-process production aggregate means a combination of ingredients at any point in the manufacturing…

(a) A manufacturer shall ensure that equipment and utensils used in the manufacture, processing, packing, or holding of an infant formula are of appropriate design and are installed to facilitate their intended function and their cleaning and maintenance. (b) A manufacturer shall ensure that equipment and utensils used in the manufacture, processing, packing, or holding of an infant formula are constructed so that surfaces that contact ingredients, in-process materials, or infant formula are made of nontoxic materials and are not reactive or absorptive. A manufacturer shall ensure that such equipment and utensils are designed to be easily cleanable and to withstand the environment of their intended use and that all surfaces that contact ingredients, in-process materials, or infant formula are cleaned and sanitized, as necessary, and are maintained to protect infant formula from being contaminated by any source. All sanitizing agents used on such equipment and utensils that are regulated as pesticide chemicals under 21 U.S.C. 346a(a) shall comply with the Environmental Protection Agency's regulations established under such section, and all other such sanitizers shall comply with…

(a) For the purposes of this section: (1) “Hardware” means all automatic equipment, including mechanical and electronic equipment (such as computers), that is used in production or quality control of infant formula. (2) “Software” means any programs, procedures, rules, and associated documentation used in the operation of a system. (3) “System” means a collection of components (including software and hardware) organized to accomplish a specific function or set of functions in a specified environment. (4) “Validation” means establishing documented evidence that provides a high degree of assurance that a system will consistently produce a product meeting its predetermined specifications and quality characteristics. Validation can be accomplished through any suitable means, such as verification studies or modeling. (b) All systems shall be designed, installed, tested, and maintained in a manner that will ensure that they are capable of performing their intended function and of producing or analyzing infant formula in accordance with this subpart and subpart C of this part. (1) A manufacturer shall ensure, at any point, step, or stage where control is necessary to prevent…

(a) The only substances that may be used in an infant formula are substances that are safe and suitable for use in infant formula under the applicable food safety provisions of the Federal Food, Drug, and Cosmetic Act; that is, a substance is used in accordance with the Agency's food additive regulations, is generally recognized as safe (GRAS) for such use, or is authorized by a prior sanction. (b) Infant formula containers and closures shall not be reactive or absorptive so as to affect the safety of the infant formula. The following substances may be used as packaging material that comes in contact with an infant formula: (1) A food additive that is the subject of a regulation issued under section 409(c) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 348(c)) and is used consistent with the conditions of use of that regulation; (2) A food contact substance that is the subject of an effective notification under section 409(h) of the Federal Food, Drug, and Cosmetic Act and is used consistent with the conditions of use in that notification; (3) A substance that is exempt from regulation as a food additive under § 170.39 of this chapter and its use conforms to the use…

(a) The regulations set forth in this subpart define the minimum current good manufacturing practices that are to be used in, and the facilities or controls that are to be used for, the manufacture, processing, packing, or holding of an infant formula. Compliance with these provisions is necessary to ensure that such infant formula provides the nutrients required under § 107.100 of this chapter and is manufactured in a manner designed to prevent its adulteration. A liquid infant formula that is a thermally processed low-acid food packaged in a hermetically sealed container is also subject to the regulations in part 113 of this chapter, and an infant formula that is an acidified food, as defined in § 114.3(b) of this chapter, is also subject to the regulations in part 114 of this chapter. (b) The failure to comply with any regulation in this subpart in the manufacture, processing, packing, or holding of an infant formula shall render such infant formula adulterated under section 412(a)(3) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 350a(a)(3)); the failure to comply with any regulation in part 113 of this chapter in the manufacture, processing, packing, or holding of a…

(a) A manufacturer shall prepare and follow a written master manufacturing order that establishes controls and procedures for the production of an infant formula. (1) The manufacturer shall make and retain records, in accordance with § 106.100(e), that include complete information relating to the production and control of the production aggregate. An individual qualified by education, training, or experience shall conduct an investigation of any deviations from the master manufacturing order and document any corrective action taken. (2) Changes made to the master manufacturing order shall be reviewed and approved by a responsible official and include an evaluation of the effect of the change on the nutrient content and the suitability of the formula for infants. (b) A manufacturer shall establish controls to ensure that each raw or in-process ingredient required by the master manufacturing order is examined by one person and checked by a second person or system. This checking shall ensure that the correct ingredient is added during the manufacturing process, that the ingredient has been released for use in infant formula, and that the correct weight or measure of the ingredient…

(a) A manufacturer of infant formula shall establish a system of process controls covering all stages of processing that is designed to ensure that infant formula does not become adulterated due to the presence of microorganisms in the formula or in the processing environment. (b) A manufacturer of liquid infant formula shall comply, as appropriate, with the procedures specified in part 113 of this chapter for thermally processed low-acid foods packaged in hermetically sealed containers and part 114 of this chapter for acidified foods. (c) A manufacturer of powdered infant formula shall test representative samples of each production aggregate of powdered infant formula at the final product stage, before distribution, to ensure that each production aggregate meets the microbiological quality standards in the table in paragraph (e) of this section. (d) A manufacturer shall make and retain records, in accordance with § 106.100(e)(5)(ii) and (f)(7), on the testing of infant formulas for microorganisms. Bacteriological Analytical Manualhttp://www.fda.gov/Food/FoodScienceResearch/LaboratoryMethods/BacteriologicalAnalyticalManualBAM/default.htm(e) A powdered infant formula that…

(a) A manufacturer shall conform to the requirements of this subpart by implementing a system of production and in-process controls. This production and in-process control system shall cover all stages of processing, from the receipt and acceptance of the raw materials, ingredients, and components through the storage and distribution of the finished product and shall be designed to ensure that all the requirements of this subpart are met. (b) The production and in-process control system shall be set out in a written plan or set of procedures that is designed to ensure that an infant formula is manufactured in a manner that will prevent adulteration of the infant formula. (c) At any point, step, or stage in the production process where control is necessary to prevent adulteration, a manufacturer shall: (1) Establish specifications to be met; (2) Monitor the production and in-process control point, step, or stage; (3) Establish a corrective action plan for use when a specification established in accordance with paragraph (c)(1) of this section is not met; (4) Review the results of the monitoring required by paragraph (c)(2) of this section, and review and evaluate the public…

(a) A manufacturer shall examine packaged and labeled infant formula during finishing operations to ensure that all containers and packages in the production aggregate have the correct label, the correct use-by date, and the correct code established under § 106.80. (b) Labels shall be designed, printed, and applied so that the labels remain legible and attached during the conditions of processing, storage, handling, distribution, and use. (c) Packaging used to hold multiple containers of an infant formula product shall be labeled as follows: (1) Where all containers are the same infant formula product and all bear the same code established under § 106.80, the packaging label shall include the product name, the name of the manufacturer, distributor, or shipper, and the code established under § 106.80. (2) Where the containers are not the same infant formula product or do not all bear the same code established under § 106.80, the packaging label shall: (i) Include the product name of each product, the name of the manufacturer, distributor, or shipper of each product, the code established under § 106.80 for each product, and a “use by” date that is no later than the “use by”…

(a) A manufacturer shall control under a quarantine system designed to prevent use or distribution of each production aggregate of infant formula until it determines that the production aggregate meets all of the manufacturer's specifications, including those adopted to meet the standards of § 106.55 on microbiological contamination and of § 106.91(a) on quality control procedures, or until the documented review of the failure to meet any of the manufacturer's specifications finds that the failure does not result in, or could not lead to, adulteration of the product. (b) Any production aggregate of infant formula that fails to meet any of the manufacturer's specifications shall be quarantined under a system designed to prevent its use in the manufacture of infant formula or its distribution until an individual qualified by education, training, or experience has conducted a documented review and has made and documented a material disposition decision to reject the infant formula; to reprocess or otherwise recondition the infant formula; or to approve and release the infant formula. Any production aggregate of infant formula that is reprocessed or otherwise reconditioned shall be…

Each production aggregate of infant formula shall be coded with a sequential number that identifies the product and the establishment where the product was packed and that permits tracing of all stages of manufacture of that production aggregate, including the year, the days of the year, and the period during those days that the product was packed, and the receipt and handling of raw materials used.

(a) A manufacturer of an infant formula, or an agent of such manufacturer, shall conduct regularly scheduled audits to determine whether the manufacturer has complied with the current good manufacturing practice regulations in this subpart. Such audits shall be conducted at a frequency that is required to ensure compliance with such regulations. (b) The audits required by paragraph (a) of this section shall be performed by an individual or a team of individuals who, as a result of education, training, or experience, is knowledgeable in all aspects of infant formula production and of the Agency's regulations concerning current good manufacturing practice that such individual or team is responsible for auditing. This individual or team of individuals shall have no direct responsibility for the matters that such individual or team is auditing and shall have no direct interest in the outcome of the audit.

(a) During manufacture, a manufacturer shall test each production aggregate for nutrients as follows: (1) Each nutrient premix used in the manufacture of an infant formula shall be tested for each nutrient (required under § 107.100 of this chapter or otherwise added by the manufacturer) that the manufacturer is relying on the premix to provide, to ensure that the premix is in compliance with the manufacturer's specifications; (2) During the manufacturing process, after the addition of the premix, or at the final product stage but before distribution, each production aggregate of infant formula shall be tested for at least one indicator nutrient for each of the nutrient premixes used in the infant formula to confirm that the nutrients supplied by each of the premixes are present, in the proper concentration, in the production aggregate of infant formula. (3) At the final product stage, before distribution of an infant formula, each production aggregate shall be tested for vitamins A, C, E, and thiamin. (4) During the manufacturing process or at the final product stage, before distribution, each production aggregate shall be tested for all nutrients required to be included in…

(a) A manufacturer of an infant formula, or an agent of such a manufacturer, shall conduct regularly scheduled audits to determine whether the manufacturer has complied with the requirements for quality control procedures that are necessary to ensure that an infant formula provides nutrients in accordance with section 412(b) and (i) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 350a(b) and (i)) and is manufactured in a manner designed to prevent adulteration of the infant formula under section 412(a)(1) and (a)(3) of the Federal Food, Drug, and Cosmetic Act. Such audits shall be conducted at a frequency that is required to ensure compliance with the requirements for quality control procedures. (b) The audits required by paragraph (a) of this section shall be performed by an individual or a team of individuals who, as a result of education, training, or experience, is knowledgeable in all aspects of infant formula production and of the regulations concerning quality control procedures that such individual or team is responsible for auditing. This individual or team of individuals shall have no direct responsibility for the matters that such individual or team is auditing…

(a) A manufacturer shall develop and follow a written audit plan that is available at the manufacturing facility for Food and Drug Administration inspection. (b) The audit plan shall include audit procedures that set out the methods the manufacturer uses to determine whether the facility is operating in accordance with current good manufacturing practice, with the quality control procedures that are necessary to ensure that an infant formula provides nutrients in accordance with sections 412(b) and (i) of the Federal Food, Drug, and Cosmetic Act, and in a manner designed to prevent adulteration of the infant formula. (c) The audit procedures shall include: (1) An evaluation of the production and in-process control system established under § 106.6(b) by: (i) Observing the production of infant formula and comparing the observed process to the written production and in-process control plan required under § 106.6(b); (ii) Reviewing records of the monitoring of points, steps, or stages where control is deemed necessary to prevent adulteration; and (iii) Reviewing records of how deviations from any specification at points, steps, or stages where control is deemed necessary to…

The regulations set forth in this subpart define the minimum requirements for quality factors for infant formulas: (a) An infant formula shall meet the quality factor of normal physical growth. (b) A manufacturer of an infant formula that is not an eligible infant formula shall demonstrate that a formula supports normal physical growth in infants when fed as a sole source of nutrition by conducting, in accordance with good clinical practice, an adequate and well-controlled growth monitoring study of the infant formula that: (1) Is no less than 15 weeks in duration, enrolling infants no more than 2 weeks old at time of entry into the study; (2) Includes the collection and maintenance of data on formula intake and anthropometric measures of physical growth, including body weight, recumbent length, head circumference, average daily weight increment, and average daily recumbent length increment; (3) Includes anthropometric measurements made at the beginning and end of the study, and at least four additional measurements made at intermediate time points with three of the six total measurements made within the first 4 weeks of the study and three measurements made at approximately…