(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 on the nutrient levels in the formulation;

(4) A description, when applicable, of any change in processing of the infant formula. Such description shall identify the specific change in processing, including side-by-side, detailed schematic diagrams comparing the new processing to the previous processing and processing times and temperatures;

(5) Assurance that the infant formula will not be marketed unless the formula meets the requirements for quality factors of section 412(b)(1) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 350a(b)(1)) and the nutrient content requirements of section 412(i) of the Federal Food, Drug, and Cosmetic Act.

(i) Assurance that the formula meets the requirements for quality factors, which are set forth in § 106.96, shall be provided by a submission that complies with § 106.121;

(ii) Assurance that the formula complies with the nutrient content requirements, which are set forth in § 107.100 of this chapter, shall be provided by a statement that the formula will not be marketed unless it meets the nutrient requirements of § 107.100 of this chapter, as demonstrated by testing required under subpart C of this part; and

(6) Assurance that the processing of the infant formula complies with section 412(b)(2) of the Federal Food, Drug, and Cosmetic Act. Such assurance shall include:

(i) A statement that the formula will be produced in accordance with subparts B and C of this part; and

(ii) The basis on which each ingredient meets the requirements of § 106.40(a), e.g. that it is an approved food additive, that it is authorized by a prior sanction, or that it is generally recognized as safe (GRAS) for its intended use. Any claim that an ingredient is GRAS shall be supported by a citation to the Agency's regulations or by an explanation, including a list of published studies and a copy of those publications, for why, based on the published studies, there is general recognition of the safety of the use of the ingredient in infant formula.

(7) If the manufacturer is requesting an exemption under § 106.91(b)(1)(ii), the manufacturer shall include the scientific evidence that the manufacturer is relying on to demonstrate that the stability of the new infant formula will likely not differ from the stability of formulas with similar composition, processing, and packaging for which there are extensive stability data.

(c) For a new infant formula for export only, a manufacturer may submit, in lieu of the information required under paragraphs (b)(5) and (b)(6) of this section, a statement certifying that the infant formula meets the specifications of the foreign purchaser, the infant formula does not conflict with the laws of the country to which it is intended for export, the infant formula is labeled on the outside of the shipping package to indicate that it is intended for export only, and the infant formula will not be sold or offered for sale in domestic commerce. Such manufacturer shall also submit a statement certifying that it has adequate controls in place to ensure that such formula is actually exported.

(d) The submission will not constitute notice under section 412 of the Federal Food, Drug, and Cosmetic Act unless it complies fully with paragraph (b) of this section, as applicable, and the information that it contains is set forth in a manner that is readily understandable. The Agency will notify the manufacturer if the notice is not complete because it does not meet the requirements in section 412(c) and (d) of the Federal Food, Drug, and Cosmetic Act.

(e) If a new infant formula submission contains all the information required by paragraph (b) of this section, as applicable, the Food and Drug Administration will acknowledge its receipt and notify the manufacturer of the date of receipt. The date that the Agency receives a new infant formula submission that is complete is the filing date for such submission. The manufacturer shall not market the new infant formula before the date that is 90 days after the filing date. If the information in the submission does not provide the assurances required under section 412(d)(1) of the Federal Food, Drug, and Cosmetic Act and the regulations of this chapter, the Food and Drug Administration will so notify the manufacturer before the expiration of the 90th day.

(f) If the manufacturer provides additional information in support of a new infant formula submission, the Agency will determine whether the additional information is a substantive amendment to the new infant formula submission. If the Agency determines that the new submission is a substantive amendment, the Food and Drug Administration will assign the new infant formula submission a new filing date. The Food and Drug Administration will acknowledge receipt of the additional information and, when applicable, notify the manufacturer of the new filing date, which is the date of receipt by the Food and Drug Administration of the information that constitutes the substantive amendment to the new infant formula submission.

(g) Submissions relating to exempt infant formulas are subject to the provisions of § 107.50 of this chapter.

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 report on attrition and on all occurrences of adverse events during the study, which shall include:

(i) Identification of the infant by subject number and feeding group and a complete description of the adverse event, including comparisons of the frequency and nature of occurrence in each feeding group and information on the health of the infant during the course of the study, including the occurrence and duration of any illness;

(ii) A clinical assessment by a health care provider of the infant's health during each suspected adverse event; and

(iii) A list of all subjects who did not complete the study, including the subject number and the reason that each subject did not complete the study.

(b) If the manufacturer is requesting an exemption from the growth monitoring study requirements under § 106.96(c)(1), the manufacturer shall include a detailed description of the change made by the manufacturer to an existing infant formula and an explanation of why the change made by the manufacturer to an existing infant formula satisfies the criteria of § 106.96(c)(1).

(c) If the manufacturer is requesting an exemption under § 106.96(c)(2)(i), the manufacturer shall include a detailed description of the alternative method or alternative study design, an explanation of why the method or study design is based on sound scientific principles, and data that demonstrate that the formula supports normal physical growth in infants when the formula is fed as the sole source of nutrition.

(d) If the manufacturer is requesting an exemption under § 106.96(c)(2)(ii), the manufacturer shall include a detailed description of the change and an explanation of why the change made by the manufacturer to an existing infant formula does not the affect the ability of the formula to support normal physical growth.

(e) If the manufacturer is requesting an exemption under § 106.96(c)(2)(iii), the manufacturer shall include a detailed description of the two formulations and an explanation of why the quality factor requirement of normal physical growth is met by the form of the formula that is processed using the method that has the greatest potential for adversely affecting nutrient content and bioavailability.

(f) Unless the manufacturer of a new infant formula is requesting an exemption under § 106.96(g), the results of the Protein Efficiency Ratio bioassay shall be provided in accordance with § 106.96(f).

(g) If the manufacturer is requesting an exemption under § 106.96(g)(1), the manufacturer shall include a detailed description of the change made by the manufacturer to an existing infant formula and an explanation of why the change made by the manufacturer to an existing infant formula satisfies the criteria listed in § 106.96(g)(1).

(h) If the manufacturer is requesting an exemption under § 106.96(g)(2), the manufacturer shall include a detailed description of the change and an explanation of why the change made by the manufacturer to an existing infant formula does not affect the bioavailability of the protein.

(i) If the manufacturer is requesting an exemption under § 106.96(g)(3), the manufacturer shall include a detailed explanation of the alternative method, an explanation of why the method is based on sound scientific principles, and the data that demonstrate that the quality factor for the biological quality of the protein has been met.

(j) A statement certifying that the manufacturer has collected and considered all information and data concerning the ability of the infant formula to meet the requirements for quality factors and that the manufacturer is not aware of any information or data that would show that the formula does not meet the requirements for quality factors.

(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 by the manufacturer in the formula, presented in units per 100 kilocalories at the final product stage.

(4) A certification that the manufacturer has established current good manufacturing practices, including quality control procedures and in-process controls, and testing required by current good manufacturing practice, designed to prevent adulteration of this formula in accordance with subparts B and C of this part.

(c) The submission shall not constitute written verification under section 412(d)(2) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 350a(d)(2)) when any data prescribed in paragraph (b) of this section are lacking or are not set forth so as to be readily understood. In such circumstances, the Agency will notify the manufacturer that the notice is not adequate.

(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 the identification number assigned by the Agency to the relevant infant formula submission, may be provided in lieu of such statement.

(c) The submission shall not constitute notice under section 412 of the Federal Food, Drug, and Cosmetic Act unless it complies fully with paragraph (b) of this section, and the information that it contains is set forth in a manner that is readily understandable. The Agency will notify the manufacturer if the notice is not adequate because it does not meet the requirements of section 412(d)(3) of the Federal Food, Drug, and Cosmetic Act.

(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 Administration, Center for Food Safety and Applied Nutrition, Office of Compliance, Division of Enforcement (HFS-605), Recall Coordinator, 5001 Campus Dr., College Park, MD 20740, and to the appropriate Food and Drug Administration district office.

(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 Federal Register 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.archives.gov/federal_register/code_of_federal_regulations/ibr_locations.html.

(b) 3-A Sanitary Standards, Inc., 6888 Elm St., Suite 2D, McLean, VA 22101-3829, 703-790-0295, and may be ordered online at http://www.3-a.org/:

(1) 3-A Sanitary Standards, No. 609-03: A Method of Producing Culinary Steam, adopted November 21, 2004, into § 106.20(h).

(2) [Reserved]

(c) American Society for Nutrition, 9650 Rockville Pike, Bethesda, MD 20814-3998, 301-634-7279, http://www.nutrition.org:

(1) Physical growth: National Center for Health Statistics percentiles, Hamill, P.V.V., T.A. Drizd, C.L. Johnson, R.B. Reed, A.F. Roche, and W.M. Moore, American Journal of Clinical Nutrition, vol. 32, pp. 607-614, dated March 1979, into § 106.96(i)(1)(ii)(c).

(2) [Reserved]

(d) AOAC International, 481 North Frederick Ave., suite 500, Gaithersburg, MD 20877-2417, 301-924-7078:

(1) Official Methods of Analysis of AOAC International, 16th ed., dated 1995, into § 106.96(i)(2)(ii):

(i) Section 45.3.04, AOAC Official Method 960.48 Protein Efficiency Ratio Rat Bioassay, and

(ii) Section 45.3.05, AOAC Official Method 982.30 Protein Efficiency Ratio Calculation Method.

(2) Official Methods of Analysis of AOAC International, 18th ed., dated 2005, into § 106.96(f):

(i) Section 45.3.04, AOAC Official Method 960.48 Protein Efficiency Ratio Rat Bioassay, and

(ii) Section 45.3.05, AOAC Official Method 982.30 Protein Efficiency Ratio Calculation Method.

(e) Centers for Disease Control and Prevention, 1600 Clifton Rd., Atlanta, GA 30333, 1-800-232-4636, http://www.cdc.gov/growthcharts/who_charts.htm.

(1) Birth to 24 months: Boys Head circumference-for-age and Weight-for-length percentiles, dated November 1, 2009, into § 106.96(b)(4).

(2) Birth to 24 months: Boys Length-for-age and Weight-for-age percentiles, dated November 1, 2009, into § 106.96(b)(4).

(3) Birth to 24 months: Girls Head circumference-for-age and Weight-for-length percentiles, dated November 1, 2009, into § 106.96(b)(4).

(4) Birth to 24 months: Girls Length-for-age and Weight-for-age percentiles, dated November 1, 2009, into § 106.96(b)(4).