[Code of Federal Regulations]

[Title 21, Volume 1]

[Revised as of April 1, 2006]

From the U.S. Government Printing Office via GPO Access

[CITE: 21CFR99.205]



[Page 449-450]

 

                        TITLE 21--FOOD AND DRUGS

 

CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 

                                SERVICES

 

PART 99_DISSEMINATION OF INFORMATION ON UNAPPROVED/NEW USES FOR MARKETED 

DRUGS, BIOLOGICS, AND DEVICES--Table of Contents

 

    Subpart C_Manufacturer's Submissions, Requests, and Applications

 

Sec.  99.205  Application for exemption from the requirement to file a 

supplemental application.



    (a) In certain circumstances, described in paragraph (b) of this 

section, a manufacturer may submit an application for an exemption from 

the requirement to submit a supplemental application for a new use for 

purposes of disseminating information on that use.

    (b) The manufacturer's application for an exemption shall identify 

the basis for the proposed exemption and shall include materials 

demonstrating that it would be economically prohibitive or that it would 

be unethical to conduct the studies necessary to submit a supplemental 

application for the new use.

    (1) If the basis for the manufacturer's application for exemption is 

that it would be economically prohibitive to incur the costs necessary 

to submit a supplemental application for a new use, the manufacturer 

shall, at a minimum, provide:

    (i) Evidence explaining why existing data characterizing the safety 

and effectiveness of the drug or device, including data from the study 

described in the information to be disseminated, are not adequate to 

support the submission of a supplemental application for the new use. 

Such evidence shall include an analysis of all data relevant to the 

safety and effectiveness of the use, a summary of those data, and any 

documentation resulting from prior discussions with the agency 

concerning the adequacy of the existing data; and

    (ii) Evidence demonstrating that the cost of the study or studies 

for the new use reasonably exceeds the expected revenue from the new use 

minus the costs of goods sold and marketing and administrative expenses 

attributable to the new use of the product. Such evidence shall include:

    (A) A description of the additional studies that the manufacturer 

believes are necessary to support the submission of a supplemental 

application for the new use, including documentation from prior 

discussions, if any, with the agency concerning the studies that



[[Page 450]]



would be needed, and an estimate of the projected costs for such 

studies;

    (B) The expected patient population for the new use;

    (C) The expected revenue for the new use, including an explanation 

of the price at which the drug or device will be sold;

    (D) Any exclusivity for the drug or device for the new use; and

    (E) Any other information that the manufacturer has showing that 

conducting the studies on the new use would be economically prohibitive; 

and

    (iii) An attestation by a responsible individual of the manufacturer 

or an individual acting on the manufacturer's behalf verifying that the 

estimates included with the submission are accurate and were prepared in 

accordance with generally accepted accounting procedures. The data 

underlying and supporting the estimates shall be made available to FDA 

upon request. Alternatively, a manufacturer may submit a report of an 

independent certified public accountant in accordance with the Statement 

of Standards for Attestation established by the American Institute of 

Certified Public Accountants and agreed upon procedures performed with 

respect to the estimates submitted under this section.

    (2) If the basis for the manufacturer's application for exemption is 

that it would be unethical to conduct the studies necessary for the 

supplemental application for a new use, the manufacturer shall provide 

evidence:

    (i) Explaining why existing data characterizing the safety and 

effectiveness of the drug or device, including data from the study 

described in the information to be disseminated, are not adequate to 

support the submission of a supplemental application for the new use. 

Such evidence shall include an analysis of all data relevant to the 

safety and effectiveness of the new use, a summary of those data, and 

any documentation resulting from prior discussions with the agency 

concerning the adequacy of the existing data; and

    (ii) Explaining why it would be unethical to conduct the further 

studies that would be necessary for the approval of the new use. Such 

evidence shall establish that, notwithstanding the insufficiency of 

available data to support the submission of a supplemental application 

for the new use, the data are persuasive to the extent that withholding 

the drug or device in a controlled study (e.g., by providing no therapy, 

a placebo, an alternative therapy, or an alternative dose) would pose an 

unreasonable risk of harm to human subjects. In assessing the 

appropriateness of conducting studies to support the new use, the 

manufacturer may provide evidence showing that the new use is broadly 

accepted as current standard medical treatment or therapy. The 

manufacturer shall also address the possibility of conducting studies in 

different populations or of modified design (e.g., adding the new 

therapy to existing treatments or using an alternative dose if 

monotherapy studies could not be conducted).