[Code of Federal Regulations]
[Title 21, Volume 7]
[Revised as of April 1, 2008]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR601.91]

[Page 45-46]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                          SERVICES (CONTINUED)
 
PART 601_LICENSING--Table of Contents
 
 Subpart H_Approval of Biological Products When Human Efficacy Studies 
                       Are Not Ethical or Feasible
 
Sec. 601.91  Approval based on evidence of effectiveness from studies in 

animals.

    (a) FDA may grant marketing approval for a biological product for 
which safety has been established and for which the requirements of 
Sec. 601.90 are met based on adequate and well-controlled animal 
studies when the results of those animal studies establish that the 
biological product is reasonably likely to produce clinical benefit in 
humans. In assessing the sufficiency of animal data, the agency may take 
into account other data, including human data, available to the agency. 
FDA will rely on the evidence from studies in animals to provide 
substantial evidence of the effectiveness of these products only when:
    (1) There is a reasonably well-understood pathophysiological 
mechanism of the toxicity of the substance and its prevention or 
substantial reduction by the product;
    (2) The effect is demonstrated in more than one animal species 
expected to react with a response predictive for humans, unless the 
effect is demonstrated in a single animal species that represents a 
sufficiently well-characterized animal model for predicting the response 
in humans;
    (3) The animal study endpoint is clearly related to the desired 
benefit in humans, generally the enhancement of survival or prevention 
of major morbidity; and
    (4) The data or information on the kinetics and pharmacodynamics of 
the product or other relevant data or information, in animals and 
humans, allows selection of an effective dose in humans.
    (b) Approval under this subpart will be subject to three 
requirements:
    (1) Postmarketing studies. The applicant must conduct postmarketing 
studies, such as field studies, to verify and describe the biological 
product's clinical benefit and to assess its safety when used as 
indicated when such studies are feasible and ethical. Such postmarketing 
studies would not be feasible until an exigency arises. When such 
studies are feasible, the applicant must conduct such studies with due 
diligence. Applicants must include as part of their application a plan 
or approach to postmarketing study commitments in the event such studies 
become ethical and feasible.
    (2) Approval with restrictions to ensure safe use. If FDA concludes 
that a biological product shown to be effective under this subpart can 
be safely used only if distribution or use is restricted, FDA will 
require such postmarketing restrictions as are needed to ensure

[[Page 46]]

safe use of the biological product, commensurate with the specific 
safety concerns presented by the biological product, such as:
    (i) Distribution restricted to certain facilities or health care 
practitioners with special training or experience;
    (ii) Distribution conditioned on the performance of specified 
medical procedures, including medical followup; and
    (iii) Distribution conditioned on specified recordkeeping 
requirements.
    (3) Information to be provided to patient recipients. For biological 
products or specific indications approved under this subpart, applicants 
must prepare, as part of their proposed labeling, labeling to be 
provided to patient recipients. The patient labeling must explain that, 
for ethical or feasibility reasons, the biological product's approval 
was based on efficacy studies conducted in animals alone and must give 
the biological product's indication(s), directions for use (dosage and 
administration), contraindications, a description of any reasonably 
foreseeable risks, adverse reactions, anticipated benefits, drug 
interactions, and any other relevant information required by FDA at the 
time of approval. The patient labeling must be available with the 
product to be provided to patients prior to administration or dispensing 
of the biological product for the use approved under this subpart, if 
possible.