[Code of Federal Regulations]
[Title 21, Volume 5]
[Revised as of April 1, 2004]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR320.21]

[Page 186-187]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                          SERVICES (CONTINUED)
 
PART 320_BIOAVAILABILITY AND BIOEQUIVALENCE REQUIREMENTS--Table of Contents
 
      Subpart B_Procedures for Determining the Bioavailability or 
                     Bioequivalence of Drug Products
 
Sec. 320.21  Requirements for submission of in vivo bioavailability and 
bioequivalence data.

    Source: 42 FR 1648, Jan. 7, 1977, unless otherwise noted.


    (a) Any person submitting a full new drug application to the Food 
and Drug Administration (FDA) shall include in the application either:
    (1) Evidence measuring the in vivo bioavailability of the drug 
product that is the subject of the application; or
    (2) Information to permit FDA to waive the submission of evidence 
measuring in vivo bioavailability.
    (b) Any person submitting an abbreviated new drug application to FDA 
shall include in the application either:
    (1) Evidence demonstrating that the drug product that is the subject 
of the abbreviated new drug application is bioequivalent to the 
reference listed drug (defined in Sec. 314.3(b) of this chapter); or
    (2) Information to show that the drug product is bioequivalent to 
the reference listed drug which would permit FDA to waive the submission 
of evidence demonstrating in vivo bioequivalence as provided in 
paragraph (f) of this section.
    (c) Any person submitting a supplemental application to FDA shall 
include in the supplemental application the evidence or information set 
forth in paragraphs (a) and (b) of this section if the supplemental 
application proposes any of the following changes:
    (1) A change in the manufacturing site or a change in the 
manufacturing process, including a change in product formulation or 
dosage strength, beyond the variations provided for in the approved 
application.
    (2) A change in the labeling to provide for a new indication for use 
of the drug product, if clinical studies are required to support the new 
indication for use.
    (3) A change in the labeling to provide for a new dosage regimen or 
for an additional dosage regimen for a special patient population, e.g., 
infants, if clinical studies are required to support the new or 
additional dosage regimen.
    (d) FDA may approve a full new drug application, or a supplemental 
application proposing any of the changes set forth in paragraph (c) of 
this section, that does not contain evidence of in vivo bioavailability 
or information to permit waiver of the requirement for in vivo 
bioavailability data, if all of the following conditions are met.
    (1) The application is otherwise approvable.
    (2) The application agrees to submit, within the time specified by 
FDA, either:
    (i) Evidence measuring the in vivo bioavailability and demonstrating 
the in vivo bioequivalence of the drug product that is the subject of 
the application; or
    (ii) Information to permit FDA to waive measurement of in vivo 
bioavailability.
    (e) Evidence measuring the in vivo bioavailability and demonstrating 
the in vivo bioequivalence of a drug product shall be obtained using one 
of the approaches for determining bioavailability set forth in Sec. 
320.24.
    (f) Information to permit FDA to waive the submission of evidence 
measuring the in vivo bioavailability or

[[Page 187]]

demonstrating the in vivo bioequivalence shall meet the criteria set 
forth in Sec. 320.22.
    (g) Any person holding an approved full or abbreviated new drug 
application shall submit to FDA a supplemental application containing 
new evidence measuring the in vivo bioavailability or demonstrating the 
in vivo bioequivalence of the drug product that is the subject of the 
application if notified by FDA that:
    (1) There are data demonstrating that the dosage regimen in the 
labeling is based on incorrect assumptions or facts regarding the 
pharmacokinetics of the drug product and that following this dosage 
regimen could potentially result in subtherapeutic or toxic levels; or
    (2) There are data measuring significant intra-batch and batch-to-
batch variability, e.g., plus or minus 25 percent, in the 
bioavailability of the drug product.
    (h) The requirements of this section regarding the submission of 
evidence measuring the in vivo bioavailability or demonstrating the in 
vivo bioequivalence apply only to a full or abbreviated new drug 
application or a supplemental application for a finished dosage 
formulation.

[57 FR 17998, Apr. 28, 1992, as amended at 67 FR 77672, Dec. 19, 2002]