[Code of Federal Regulations]
[Title 21, Volume 5]
[Revised as of April 1, 2008]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR312.44]

[Page 69-71]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF 
 
PART 312_INVESTIGATIONAL NEW DRUG APPLICATION--Table of Contents
 
                    Subpart C_Administrative Actions
 
Sec. 312.44  Termination.

    (a) General. This section describes the procedures under which FDA 
may terminate an IND. If an IND is terminated, the sponsor shall end all 
clinical investigations conducted under the IND and recall or otherwise 
provide for

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the disposition of all unused supplies of the drug. A termination action 
may be based on deficiencies in the IND or in the conduct of an 
investigation under an IND. Except as provided in paragraph (d) of this 
section, a termination shall be preceded by a proposal to terminate by 
FDA and an opportunity for the sponsor to respond. FDA will, in general, 
only initiate an action under this section after first attempting to 
resolve differences informally or, when appropriate, through the 
clinical hold procedures described in Sec. 312.42.
    (b) Grounds for termination--(1) Phase 1. FDA may propose to 
terminate an IND during Phase 1 if it finds that:
    (i) Human subjects would be exposed to an unreasonable and 
significant risk of illness or unjury.
    (ii) The IND does not contain sufficient information required under 
Sec. 312.23 to assess the safety to subjects of the clinical 
investigations.
    (iii) The methods, facilities, and controls used for the 
manufacturing, processing, and packing of the investigational drug are 
inadequate to establish and maintain appropriate standards of identity, 
strength, quality, and purity as needed for subject safety.
    (iv) The clinical investigations are being conducted in a manner 
substantially different than that described in the protocols submitted 
in the IND.
    (v) The drug is being promoted or distributed for commercial 
purposes not justified by the requirements of the investigation or 
permitted by Sec. 312.7.
    (vi) The IND, or any amendment or report to the IND, contains an 
untrue statement of a material fact or omits material information 
required by this part.
    (vii) The sponsor fails promptly to investigate and inform the Food 
and Drug Administration and all investigators of serious and unexpected 
adverse experiences in accordance with Sec. 312.32 or fails to make any 
other report required under this part.
    (viii) The sponsor fails to submit an accurate annual report of the 
investigations in accordance with Sec. 312.33.
    (ix) The sponsor fails to comply with any other applicable 
requirement of this part, part 50, or part 56.
    (x) The IND has remained on inactive status for 5 years or more.
    (xi) The sponsor fails to delay a proposed investigation under the 
IND or to suspend an ongoing investigation that has been placed on 
clinical hold under Sec. 312.42(b)(4).
    (2) Phase 2 or 3. FDA may propose to terminate an IND during Phase 2 
or Phase 3 if FDA finds that:
    (i) Any of the conditions in paragraphs (b)(1)(i) through (b)(1)(xi) 
of this section apply; or
    (ii) The investigational plan or protocol(s) is not reasonable as a 
bona fide scientific plan to determine whether or not the drug is safe 
and effective for use; or
    (iii) There is convincing evidence that the drug is not effective 
for the purpose for which it is being investigated.
    (3) FDA may propose to terminate a treatment IND if it finds that:
    (i) Any of the conditions in paragraphs (b)(1)(i) through (x) of 
this section apply; or
    (ii) Any of the conditions in Sec. 312.42(b)(3) apply.
    (c) Opportunity for sponsor response. (1) If FDA proposes to 
terminate an IND, FDA will notify the sponsor in writing, and invite 
correction or explanation within a period of 30 days.
    (2) On such notification, the sponsor may provide a written 
explanation or correction or may request a conference with FDA to 
provide the requested explanation or correction. If the sponsor does not 
respond to the notification within the allocated time, the IND shall be 
terminated.
    (3) If the sponsor responds but FDA does not accept the explanation 
or correction submitted, FDA shall inform the sponsor in writing of the 
reason for the nonacceptance and provide the sponsor with an opportunity 
for a regulatory hearing before FDA under part 16 on the question of 
whether the IND should be terminated. The sponsor's request for a 
regulatory hearing must be made within 10 days of the sponsor's receipt 
of FDA's notification of nonacceptance.
    (d) Immediate termination of IND. Notwithstanding paragraphs (a) 
through (c) of this section, if at any time FDA concludes that 
continuation of the investigation presents an immediate and

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substantial danger to the health of individuals, the agency shall 
immediately, by written notice to the sponsor from the Director of the 
Center for Drug Evaluation and Research or the Director of the Center 
for Biologics Evaluation and Research, terminate the IND. An IND so 
terminated is subject to reinstatement by the Director on the basis of 
additional submissions that eliminate such danger. If an IND is 
terminated under this paragraph, the agency will afford the sponsor an 
opportunity for a regulatory hearing under part 16 on the question of 
whether the IND should be reinstated.

[52 FR 8831, Mar. 19, 1987, as amended at 52 FR 23031, June 17, 1987; 55 
FR 11579, Mar. 29, 1990; 57 FR 13249, Apr. 15, 1992; 67 FR 9586, Mar. 4, 
2002]