§ 99.201 Manufacturer's submission to the agency. ( a ) Sixty days before disseminating any written information concerning the safety, effectiveness, or benefit of a new use for a drug or device, a manufacturer shall submit to the agency: ( 1 ) An identical copy of the information to be disseminated, including any information (e.g., the bibliography) and statements required under § 99.103;
( 2 ) Any other clinical trial information which the manufacturer has relating to the effectiveness of the new use, any other clinical trial information that the manufacturer has relating to the safety of the new use, any reports of clinical experience pertinent to the safety of the new use, and a summary of such information. For purposes of this part, clinical trial information includes, but is not limited to, published papers and abstracts, even if not intended for dissemination, and unpublished manuscripts, abstracts, and data analyses from completed or ongoing investigations. The reports of clinical experience required under this paragraph shall include case studies, retrospective reviews, epidemiological studies, adverse event reports, and any other material concerning adverse effects or risks reported for or associated with the new use. If the manufacturer has no knowledge of clinical trial information relating to the safety or effectiveness of the new use or reports of clinical experience pertaining to the safety of the new use, the manufacturer shall provide a statement to that effect;
( 3 ) An explanation of the manufacturer's method of selecting the articles for the bibliography (e.g., the databases or sources and criteria (i.e., subject headings/keywords) used to generate the bibliography and the time period covered by the bibliography); and
( 4 ) If the manufacturer has not submitted a supplemental application for the new use, one of the following: ( i ) If the manufacturer has completed studies needed for the submission of a supplemental application for the new use: ( A ) A copy of the protocol for each completed study or, if such protocol was submitted to an investigational new drug application or an investigational device exemption, the number(s) for the investigational new drug application or investigational device exemption covering the new use, the date of submission of the protocol(s), the protocol number(s), and the date of any amendments to the protocol(s); and
( B ) A certification stating that, “On behalf of [insert manufacturer's name], I certify that [insert manufacturer's name] has completed the studies needed for the submission of a supplemental application for [insert new use] and will submit a supplemental application for such new use to the Food and Drug Administration no later than [insert date no later than 6 months from date that dissemination of information under this part can begin]”; or
( ii ) If the manufacturer has planned studies that will be needed for the submission of a supplemental application for the new use: ( A ) The proposed protocols and schedule for conducting the studies needed for the submission of a supplemental application for the new use. The protocols shall comply with all applicable requirements in parts 312 of this chapter (investigational new drug applications) and 812 of this chapter (investigational device exemptions). The schedule shall include the projected dates on which the manufacturer expects the principal study events to occur (e.g., initiation and completion of patient enrollment, completion of data collection, completion of data analysis, and submission of the supplemental application); and
( B ) A certification stating that, “On behalf of [insert manufacturer's name], I certify that [insert manufacturer's name] will exercise due diligence to complete the clinical studies necessary to submit a supplemental application for [insert new use] and will submit a supplemental application for such new use to the Food and Drug Administration no later than [insert date no later than 36 months from date that dissemination of information under this part can begin or no later than such time period as FDA may specify pursuant to an extension granted under § 99.303(a)];” or
( iii ) An application for exemption from the requirement of a supplemental application; or
( 5 ) If the manufacturer has submitted a supplemental application for the new use, a cross-reference to that supplemental application.
( b ) The manufacturer's attorney, agent, or other authorized official shall sign the submission and certification statement or application for exemption. If the manufacturer does not have a place of business in the United States, the submission and certification statement or application for exemption shall contain the signature, name, and address of the manufacturer's attorney, agent, or other authorized official who resides or maintains a place of business in the United States.
( c ) The manufacturer shall send three copies of the submission and certification statement or application for exemption to FDA. The outside of the shipping container shall be marked as “Submission for the Dissemination of Information on an Unapproved/New Use.” The manufacturer shall send the submission and certification statement or application for exemption to the appropriate FDA component listed in paragraphs (c)(1) through (c)(3) of this section. ( 1 ) For biological products and devices regulated by the Food and Drug Administration, Center for Biologics Evaluation and Research, Document Control Center, 10903 New Hampshire Ave., Bldg. 71, Rm. G112, Silver Spring, MD 20993-0002;
( 2 ) For human drug products, biological products, and devices regulated by the Center for Drug Evaluation and Research, the Division of Drug Marketing, Advertising, and Communications (HFD-42), Center for Drug Evaluation and Research, Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857; or
( 3 ) For medical devices, the Promotion and Advertising Policy Staff (HFZ-302), Office of Compliance, Center for Devices and Radiological Health, Food and Drug Administration, 2098 Gaither Rd., Rockville, MD 20850.
( d ) The 60-day period shall begin when FDA receives a manufacturer's submission, including, where applicable, a certification statement or an application for an exemption.
[63 FR 64581, Nov. 20, 1998, as amended at 70 FR 14980, Mar. 24, 2005; 80 FR 18090, Apr. 3, 2015]