§600.2. Mailing addresses. — Inbound Citations

Manufacturers shall retain for a period of at least 6 months after the expiration date, unless a different time period is specified in additional standards, a quantity of representative material of each lot of each product, sufficient for examination and testing for safety and potency, except Whole Blood, Cryoprecipitated AHF, Platelets, Red Blood Cells, Plasma, and Source Plasma and Allergenic Products prepared to a physician's prescription. Samples so retained shall be selected at random from either final container material, or from bulk and final containers, provided they include at least one final container as a final package, or package-equivalent of such filling of each lot of the product as intended for distribution. Such sample material shall be stored at temperatures and under conditions which will maintain the identity and integrity of the product. Samples retained as required in this section shall be in addition to samples of specific products required to be submitted to the Center for Biologics Evaluation and Research or the Center for Drug Evaluation and Research (see mailing addresses in § 600.2). Exceptions may be authorized by the Director, Center for Biologics Evaluation and Research or the Director, Center for Drug Evaluation and Research, when the lot yields relatively few final containers and when such lots are prepared by the same method in large number and in close succession.

(2) For biological products regulated by the Center for Drug Evaluation and Research (CDER), send the completed Form FDA-3486 to the Division of Compliance Risk Management and Surveillance (HFD-330) (see mailing addresses in § 600.2). CDER does not currently accept electronic filings.

(1) As provided by this section, an applicant must inform the Food and Drug Administration (FDA) (see mailing addresses in § 600.2 of this chapter) about each change in the product, production process, quality controls, equipment, facilities, responsible personnel, or labeling established in the approved license application(s).

(b) Waiver requests under this section must be submitted in writing and must include the specific reasons why electronic submission is not reasonable for the registrant and a U.S. telephone number and mailing address where FDA can contact the registrant. All waiver requests must be sent to the Director of FDA's Center for Biologics Evaluation and Research through the Document Control Center (see addressesin § 600.2).

A U.S. Standard Antihemophilic Factor (Factor VIII) preparation may be obtained from the Center for Biologics Evaluation and Research, (HFM-407) (see mailing addresses in § 600.2 of this chapter) for use in the preparation of a working reference to be employed in a quality control potency test of Cryoprecipitated AHF.

(b) Waiver requests under this section must be submitted in writing and must include the specific reasons why electronic submission is not reasonable for the registrant and a U.S. telephone number and mailing address where FDA can contact the registrant. Waiver requests may be sent to the Center for Biologics Evaluation and Research (CBER), Document Control Center (see addresses in § 600.2 of this chapter).

(6) In cases of actual or suspected infection with foot and mouth disease, glanders, tetanus, anthrax, gas gangrene, equine infectious anemia; equine encephalomyelitis, or any of the pock diseases among animals intended for use or used in the manufacture of products, the manufacturer shall immediately notify the Director, Center for Biologics Evaluation and Research or the Director, Center for Drug Evaluation and Research (see mailing addresses in § 600.2(a) or (b)).

(1) For biological products regulated by the Center for Biologics Evaluation and Research (CBER), send the completed Form FDA 3486 to the CBER Document Control Center (see mailing address in § 600.2(a)), or submit electronically using CBER's electronic Web-based application.

(a) To obtain a biologics license under section 351 of the Public Health Service Act for any biological product, the manufacturer shall submit an application 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) or (b) of this chapter), on forms prescribed for such purposes, and shall submit data derived from nonclinical laboratory and clinical studies which demonstrate that the manufactured product meets prescribed requirements of safety, purity, and potency; with respect to each nonclinical laboratory study, either a statement that the study was conducted in compliance with the requirements set forth in part 58 of this chapter, or, if the study was not conducted in compliance with such regulations, a brief statement of the reason for the noncompliance; statements regarding each clinical investigation involving human subjects contained in the application, that it either was conducted in compliance with the requirements for institutional review set forth in part 56 of this chapter; or was not subject to such requirements in accordance with § 56.104 or § 56.105, and was conducted in compliance with requirements for informed consent set forth in part 50 of this chapter. A full description of manufacturing methods; data establishing stability of the product through the dating period; sample(s) representative of the product for introduction or delivery for introduction into interstate commerce; summaries of results of tests performed on the lot(s) represented by the submitted sample(s); specimens of the labels, enclosures, and containers, and if applicable, any Medication Guide required under part 208 of this chapter proposed to be used for the product; and the address of each location involved in the manufacture of the biological product shall be listed in the biologics license application. The applicant shall also include a financial certification or disclosure statement(s) or both for clinical investigators as required by part 54 of this chapter. An application for a biologics license shall not be considered as filed until all pertinent information and data have been received by the Food and Drug Administration. The applicant shall also include either a claim for categorical exclusion under § 25.30 or § 25.31 of this chapter or an environmental assessment under § 25.40 of this chapter. The applicant, or the applicant's attorney, agent, or other authorized official shall sign the application. An application for any of the following specified categories of biological products subject to licensure shall be handled as set forth in paragraph (c) of this section:

(1) Therapeutic DNA plasmid products;

(2) Therapeutic synthetic peptide products of 40 or fewer amino acids;

(3) Monoclonal antibody products for in vivo use; and

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) or (b) of this chapter):

(d) Submit two copies of the annual progress report of postmarketing studies to the Center for Biologics Evaluation and Research or Center for Drug Evaluation and Research (see mailing addresses in § 600.2(a) or (b) of this chapter).

(b) When a complication of blood collection or transfusion is confirmed to be fatal, the Director, Office of Compliance and Biologics Quality, CBER, must be notified by telephone, facsimile, express mail, or electronically transmitted mail as soon as possible. A written report of the investigation must be submitted to the Director, Office of Compliance and Biologics Quality, CBER, by mail, facsimile, or electronically transmitted mail (for mailing address, see § 600.2(a) of this chapter), within 7 days after the fatality by the collecting facility in the event of a donor reaction, or by the facility that performed the compatibility tests in the event of a transfusion reaction.

(1) If you make a paper filing, send the completed form to the CBER Document Control Center (see mailing address in § 600.2(a) of this chapter), and identify on the envelope that a BPDR (biological product deviation report) is enclosed; or

(3) 1.25 milligrams determined by assay provided that data demonstrating that the amount of aluminum used is safe and necessary to produce the intended effect are submitted to and approved by the Director, Center for Biologics Evaluation and Research or the Director, Center for Drug Evaluation and Research (see mailing addresses in § 600.2(a) or (b) of this chapter).

(iii) Mold manufacturers shall maintain written standard operating procedures, developed by a qualified individual, that will ensure the identity of the seed culture, prescribe adequate processing of the mold, and specify the acceptable limits and kinds of contamination. These limits shall be based on results of appropriate tests performed by the manufacturer on at least three consecutive lots of a mold that is a representative species of mold subject to the standard operating procedures. The tests shall be performed at each manufacturing step during and subsequent to harvest, as specified in the standard operating procedures. Before use of the mold as a source material for Allergenic Products, in accordance with 21 CFR 601.2, the standard operating procedures and test data from the three representative lots described above shall be submitted to and approved by the Director, Center for Biologics Evaluation and Research (see mailing address in § 600.2(a) of this chapter).

(6) In cases of actual or suspected infection with foot and mouth disease, glanders, tetanus, anthrax, gas gangrene, equine infectious anemia; equine encephalomyelitis, or any of the pock diseases among animals intended for use or used in the manufacture of products, the manufacturer shall immediately notify the Director, Center for Biologics Evaluation and Research or the Director, Center for Drug Evaluation and Research (see mailing addresses in § 600.2(a) or (b)).

(a) To obtain a biologics license under section 351 of the Public Health Service Act for any biological product, the manufacturer shall submit an application 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) or (b) of this chapter), on forms prescribed for such purposes, and shall submit data derived from nonclinical laboratory and clinical studies which demonstrate that the manufactured product meets prescribed requirements of safety, purity, and potency; with respect to each nonclinical laboratory study, either a statement that the study was conducted in compliance with the requirements set forth in part 58 of this chapter, or, if the study was not conducted in compliance with such regulations, a brief statement of the reason for the noncompliance; statements regarding each clinical investigation involving human subjects contained in the application, that it either was conducted in compliance with the requirements for institutional review set forth in part 56 of this chapter; or was not subject to such requirements in accordance with § 56.104 or § 56.105, and was conducted in compliance with requirements for informed consent set forth in part 50 of this chapter. A full description of manufacturing methods; data establishing stability of the product through the dating period; sample(s) representative of the product for introduction or delivery for introduction into interstate commerce; summaries of results of tests performed on the lot(s) represented by the submitted sample(s); specimens of the labels, enclosures, and containers, and if applicable, any Medication Guide required under part 208 of this chapter proposed to be used for the product; and the address of each location involved in the manufacture of the biological product shall be listed in the biologics license application. The applicant shall also include a financial certification or disclosure statement(s) or both for clinical investigators as required by part 54 of this chapter. An application for a biologics license shall not be considered as filed until all pertinent information and data have been received by the Food and Drug Administration. The applicant shall also include either a claim for categorical exclusion under § 25.30 or § 25.31 of this chapter or an environmental assessment under § 25.40 of this chapter. The applicant, or the applicant's attorney, agent, or other authorized official shall sign the application. An application for any of the following specified categories of biological products subject to licensure shall be handled as set forth in paragraph (c) of this section:

(1) Therapeutic DNA plasmid products;

(2) Therapeutic synthetic peptide products of 40 or fewer amino acids;

(3) Monoclonal antibody products for in vivo use; and

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) or (b) of this chapter):

(d) Submit two copies of the annual progress report of postmarketing studies to the Center for Biologics Evaluation and Research or Center for Drug Evaluation and Research (see mailing addresses in § 600.2(a) or (b) of this chapter).

(3) 1.25 milligrams determined by assay provided that data demonstrating that the amount of aluminum used is safe and necessary to produce the intended effect are submitted to and approved by the Director, Center for Biologics Evaluation and Research or the Director, Center for Drug Evaluation and Research (see mailing addresses in § 600.2(a) or (b) of this chapter).

Random samples of each importation, obtained by the District Director of Customs and forwarded to the Director, Center for Biologics Evaluation and Research or the Director, Center for Drug Evaluation and Research (see mailing addresses in § 600.2(c) of this chapter) must be at least two final containers of each lot of product. A copy of the associated documents which describe and identify the shipment must accompany the shipment for forwarding with the samples to the Director, Center for Biologics Evaluation and Research or the Director, Center for Drug Evaluation and Research (see mailing addresses in § 600.2(c)). For shipments of 20 or less final containers, samples need not be forwarded, provided a copy of an official release from the Center for Biologics Evaluation and Research or Center for Drug Evaluation and Research accompanies each shipment.

(a) Samples of any lot of any licensed product together with the protocols showing results of applicable tests, may at any time be required to be sent to the Director, Center for Biologics Evaluation and Research (see mailing addresses in § 600.2(c) of this chapter). Upon notification by the Director, Center for Biologics Evaluation and Research, a manufacturer shall not distribute a lot of a product until the lot is released by the Director, Center for Biologics Evaluation and Research: Provided, That the Director, Center for Biologics Evaluation and Research, shall not issue such notification except when deemed necessary for the safety, purity, or potency of the product.

(a) The following shall be submitted to the Center for Biologics Evaluation and Research Sample Custodian (see mailing addresses in § 600.2(c) of this chapter), within 30 days after each routine establishment inspection by FDA.

(1) From a lot of final product, samples from a cell panel intended for identification of unexpected antibodies. The sample shall be packaged as for distribution and shall have at least 14 days remaining in the dating period when shipped to the Center for Biologics Evaluation and Research.

(2) A protocol which shall include the following:

(i) Complete test records of at least two donors of the samples submitted, including original and confirmation phenotyping records.

(2) Unless the Director, Center for Biologics Evaluation and Research, determines that the reliability and consistency of the finished product can be assured with a smaller quantity of sample or no sample and specifically reduces or eliminates the required quantity of sample, each manufacturer shall submit the following samples to the Director, Center for Biologics Evaluation and Research (see mailing addresses in § 600.2(c) of this chapter), within 5 working days after the manufacturer has satisfactorily completed all tests on the samples:

(i) One sample until written notification of official release is no longer required under paragraph (c)(2) of this section.

(ii) One sample of product at periodic intervals of 90 days, beginning after written notification of official release is no longer required under paragraph (c)(2) of this section. The sample submitted at the 90-day interval shall be from the first lot or filling, as applicable, released by the manufacturer, under the requirements of § 610.1 of this chapter, after the end of the previous 90-day interval. The sample shall be identified as “surveillance sample” and shall include the date of manufacture.

(iii) Samples may at any time be required to be submitted to the Director, Center for Biologics Evaluation and Research, if the Director finds that continued evaluation is necessary to ensure the potency, quality, and reliability of the product.

(2) Unless the Director, Center for Biologics Evaluation and Research, determines that the reliability and consistency of the finished product can be assured with a smaller quantity of sample or no sample and specifically reduces or eliminates the required quantity of sample, each manufacturer shall submit the following samples to the Director, Center for Biologics Evaluation and Research (see mailing addresses in § 600.2(c) of this chapter), within 5 working days after the manufacturer has satisfactorily completed all tests on the samples:

(i) One sample until written notification of official release is no longer required under paragraph (c)(2) of this section.

(ii) One sample at periodic intervals of 90 days, beginning after written notification of official release is no longer required under paragraph (c)(2) of this section. The sample submitted at the 90-day interval shall be from the first lot or filling, as applicable, released by manufacturer, under the requirements of § 610.1 of this chapter, after the end of the previous 90-day interval. The sample shall be identified as “surveillance sample” and shall include the date of manufacture.

(iii) Samples may at any time be required to be submitted to the Director, Center for Biologics Evaluation and Research, if the Director finds that continued evaluation is necessary to ensure the potency, quality, and reliability of the product.