[Code of Federal Regulations]
[Title 21, Volume 1]
[Revised as of April 1, 2004]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR99.205]

[Page 477-478]
 
                        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 would 
be needed, and an estimate of the projected costs for such studies;
    (B) The expected patient population for the new use;

[[Page 478]]

    (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).