--- kind: "range" citation: "21 C.F.R. §§ 601.21–601.33" title: "21" from: "601.21" to: "601.33" count: 9 url: "https://uscodex.org/cfr/21/601.21..601.33" --- # §601.21. Products under development. A biological product undergoing development, but not yet ready for a biologics license, may be shipped or otherwise delivered from one State or possession into another State or possession provided such shipment or delivery is not for introduction or delivery for introduction into interstate commerce, except as provided in sections [505(i)](/cfr/21/505.md?p=i) and [520(g)](/cfr/21/520.md?p=g) of the Federal Food, Drug, and Cosmetic Act, as amended, and the regulations thereunder (21 CFR parts [312](/cfr/21/part312.md) and [812](/cfr/21/part812.md)). # §601.22. Products in short supply; initial manufacturing at other than licensed location. A biologics license issued to a manufacturer and covering all locations of manufacture shall authorize persons other than such manufacturer to conduct at places other than such locations the initial, and partial manufacturing of a product for shipment solely to such manufacturer only to the extent that the names of such persons and places are registered with the Commissioner of Food and Drugs and it is found upon application of such manufacturer, that the product is in short supply due either to the peculiar growth requirements of the organism involved or to the scarcity of the animal required for manufacturing purposes, and such manufacturer has established with respect to such persons and places such procedures, inspections, tests or other arrangements as will ensure full compliance with the applicable regulations of this subchapter related to continued safety, purity, and potency. Such persons and places shall be subject to all regulations of this subchapter except §§ [601.2 to 601.6](/cfr/21/601.2..601.6.md), [601.9](/cfr/21/601.9.md), [601.10](/cfr/21/601.10.md), [601.20](/cfr/21/601.20.md), [601.21 to 601.33](/cfr/21/601.21..601.33.md), and [610.60 to 610.65](/cfr/21/610.60..610.65.md) of this chapter. For persons and places authorized under this section to conduct the initial and partial manufacturing of a product for shipment solely to a manufacturer of a product subject to licensure under [§ 601.2(c)](/cfr/21/601.2.md?p=c), the following additional regulations shall not be applicable: §§ [600.10(b)](/cfr/21/600.10.md?p=b) and [(c)](/cfr/21/600.10.md?p=c), [600.11](/cfr/21/600.11.md), [600.12](/cfr/21/600.12.md), [600.13](/cfr/21/600.13.md), and [610.53](/cfr/21/610.53.md) of this chapter. Failure of such manufacturer to maintain such procedures, inspections, tests, or other arrangements, or failure of any person conducting such partial manufacturing to comply with applicable regulations shall constitute a ground for suspension or revocation of the authority conferred pursuant to this section on the same basis as provided in [§§ 601.6 to 601.8](/cfr/21/601.6..601.8.md) with respect to the suspension and the revocation of licenses. # §601.27. Pediatric studies. - (a) **Required assessment.** Except as provided in paragraphs [(b)](#b), [(c)](#c), and [(d)](#d) of this section, each application for a new active ingredient, new indication, new dosage form, new dosing regimen, or new route of administration shall contain data that are adequate to assess the safety and effectiveness of the product for the claimed indications in all relevant pediatric subpopulations, and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective. Where the course of the disease and the effects of the product are similar in adults and pediatric patients, FDA may conclude that pediatric effectiveness can be extrapolated from adequate and well-controlled effectiveness studies in adults, usually supplemented with other information in pediatric patients, such as pharmacokinetic studies. In addition, studies may not be needed in each pediatric age group, if data from one age group can be extrapolated to another. Assessments required under this section for a product that represents a meaningful therapeutic benefit over existing treatments must be carried out using appropriate formulations for the age group(s) for which the assessment is required. - (b) **Deferred submission.** - (1) FDA may, on its own initiative or at the request of an applicant, defer submission of some or all assessments of safety and effectiveness described in [paragraph (a)](#a) of this section until after licensing of the product for use in adults. Deferral may be granted if, among other reasons, the product is ready for approval in adults before studies in pediatric patients are complete, pediatric studies should be delayed until additional safety or effectiveness data have been collected. If an applicant requests deferred submission, the request must provide an adequate justification for delaying pediatric studies, a description of the planned or ongoing studies, and evidence that the studies are being or will be conducted with due diligence and at the earliest possible time. - (2) If FDA determines that there is an adequate justification for temporarily delaying the submission of assessments of pediatric safety and effectiveness, the product may be licensed for use in adults subject to the requirement that the applicant submit the required assessments within a specified time. - (c) **Waivers—** - (1) **General.** FDA may grant a full or partial waiver of the requirements of [paragraph (a)](#a) of this section on its own initiative or at the request of an applicant. A request for a waiver must provide an adequate justification. - (2) **Full waiver.** An applicant may request a waiver of the requirements of [paragraph (a)](#a) of this section if the applicant certifies that: - (i) The product does not represent a meaningful therapeutic benefit over existing therapies for pediatric patients and is not likely to be used in a substantial number of pediatric patients; - (ii) Necessary studies are impossible or highly impractical because, e.g., the number of such patients is so small or geographically dispersed; or - (iii) There is evidence strongly suggesting that the product would be ineffective or unsafe in all pediatric age groups. - (3) **Partial waiver.** An applicant may request a waiver of the requirements of [paragraph (a)](#a) of this section with respect to a specified pediatric age group, if the applicant certifies that: - (i) The product does not represent a meaningful therapeutic benefit over existing therapies for pediatric patients in that age group, and is not likely to be used in a substantial number of patients in that age group; - (ii) Necessary studies are impossible or highly impractical because, e.g., the number of patients in that age group is so small or geographically dispersed; - (iii) There is evidence strongly suggesting that the product would be ineffective or unsafe in that age group; or - (iv) The applicant can demonstrate that reasonable attempts to produce a pediatric formulation necessary for that age group have failed. - (4) **FDA action on waiver.** FDA shall grant a full or partial waiver, as appropriate, if the agency finds that there is a reasonable basis on which to conclude that one or more of the grounds for waiver specified in paragraphs [(c)(2)](#c-2) or [(c)(3)](#c-3) of this section have been met. If a waiver is granted on the ground that it is not possible to develop a pediatric formulation, the waiver will cover only those pediatric age groups requiring that formulation. If a waiver is granted because there is evidence that the product would be ineffective or unsafe in pediatric populations, this information will be included in the product's labeling. - (5) **Definition of “meaningful therapeutic benefit”.** For purposes of this section, a product will be considered to offer a meaningful therapeutic benefit over existing therapies if FDA estimates that: - (i) If approved, the product would represent a significant improvement in the treatment, diagnosis, or prevention of a disease, compared to marketed products adequately labeled for that use in the relevant pediatric population. Examples of how improvement might be demonstrated include, e.g., evidence of increased effectiveness in treatment, prevention, or diagnosis of disease; elimination or substantial reduction of a treatment-limiting drug reaction; documented enhancement of compliance; or evidence of safety and effectiveness in a new subpopulation; or - (ii) The product is in a class of products or for an indication for which there is a need for additional therapeutic options. - (d) **Exemption for orphan drugs.** This section does not apply to any product for an indication or indications for which orphan designation has been granted under [part 316](/cfr/21/part316.md), [subpart C](/cfr/21/subpartC.md), of this chapter. # §601.28. Annual reports of postmarketing pediatric studies. Sponsors of licensed biological products shall submit the following information each year within 60 days of the anniversary date of approval of each product under the license to the Director, Center for Biologics Evaluation and Research or the Director, Center for Drug Evaluation and Research (see mailing addresses in § [600.2(a)](/cfr/21/600.2.md?p=a) or [(b)](/cfr/21/600.2.md?p=b) of this chapter): - (a) **Summary.** A brief summary stating whether labeling supplements for pediatric use have been submitted and whether new studies in the pediatric population to support appropriate labeling for the pediatric population have been initiated. Where possible, an estimate of patient exposure to the drug product, with special reference to the pediatric population (neonates, infants, children, and adolescents) shall be provided, including dosage form. - (b) **Clinical data.** Analysis of available safety and efficacy data in the pediatric population and changes proposed in the labeling based on this information. An assessment of data needed to ensure appropriate labeling for the pediatric population shall be included. - (c) **Status reports.** A statement on the current status of any postmarketing studies in the pediatric population performed by, or on behalf of, the applicant. The statement shall include whether postmarketing clinical studies in pediatric populations were required or agreed to, and, if so, the status of these studies shall be reported to FDA in annual progress reports of postmarketing studies under [§ 601.70](/cfr/21/601.70.md) rather than under this section. # §601.29. Guidance documents. - (a) FDA has made available guidance documents under [§ 10.115](/cfr/21/10.115.md) of this chapter to help you comply with certain requirements of this part. - (b) The Center for Biologics Evaluation and Research (CBER) maintains a list of guidance documents that apply to the center's regulations. The lists are maintained on the Internet and are published annually in the Federal Register. You may request a copy of the CBER list from the Food and Drug Administration, Center for Biologics Evaluation and Research, Office of Communication, Outreach and Development, 10903 New Hampshire Ave., Bldg. 71, Rm. 3103, Silver Spring, MD 20993-0002. # §601.30. Scope. This subpart applies to radiopharmaceuticals intended for in vivo administration for diagnostic and monitoring use. It does not apply to radiopharmaceuticals intended for therapeutic purposes. In situations where a particular radiopharmaceutical is proposed for both diagnostic and therapeutic uses, the radiopharmaceutical must be evaluated taking into account each intended use. # §601.31. Definition. For purposes of this part,diagnostic radiopharmaceutical means: - (a) An article that is intended for use in the diagnosis or monitoring of a disease or a manifestation of a disease in humans and that exhibits spontaneous disintegration of unstable nuclei with the emission of nuclear particles or photons; or - (b) Any nonradioactive reagent kit or nuclide generator that is intended to be used in the preparation of such article as defined in [paragraph (a)](#a) of this section. # §601.32. General factors relevant to safety and effectiveness. FDA's determination of the safety and effectiveness of a diagnostic radiopharmaceutical includes consideration of the following: - (a) The proposed use of the diagnostic radiopharmaceutical in the practice of medicine; - (b) The pharmacological and toxicological activity of the diagnostic radiopharmaceutical (including any carrier or ligand component of the diagnostic radiopharmaceutical); and - (c) **The estimated absorbed radiation dose of the diagnostic radiopharmaceutical.** # §601.33. Indications. - (a) For diagnostic radiopharmaceuticals, the categories of proposed indications for use include, but are not limited to, the following: - (1) Structure delineation; - (2) Functional, physiological, or biochemical assessment; - (3) Disease or pathology detection or assessment; and - (4) **Diagnostic or therapeutic patient management.** - (b) Where a diagnostic radiopharmaceutical is not intended to provide disease-specific information, the proposed indications for use may refer to a biochemical, physiological, anatomical, or pathological process or to more than one disease or condition.