[Code of Federal Regulations]
[Title 21, Volume 5]
[Revised as of April 1, 2001]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR320.21]

[Page 187-188]
 
                        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 demonstrating 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 
demonstrating 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)); 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 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 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 was under review by FDA on July 7, 1977.
    (2) The application is otherwise approvable.
    (3) The application agrees to submit, within the time specified by 
FDA, either:
    (i) Evidence demonstrating the in vivo bioavailability of the drug 
product that is the subject of the application; or
    (ii) Information to permit FDA to waive demonstration of in vivo 
bioavailability.
    (e) Evidence demonstrating the in vivo bioavailability and 
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 
demonstrating the in vivo bioavailability or bioequivalence shall meet 
the criteria set forth in Sec. 320.24.
    (g) Any person holding an approved full or abbreviated new drug 
application shall submit to FDA a supplemental application containing 
new evidence demonstrating the in vivo bioavailability or bioequivalence 
of the drug product that is the subject of the application if notified 
by FDA that:

[[Page 188]]

    (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 demonstrating 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 demonstrating in vivo bioavailability and 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]