[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: 21CFR320.1]

[Page 185-186]
 
                        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 A_General Provisions
 
Sec. 320.1  Definitions.




                      Subpart A_General Provisions

Sec.
320.1 Definitions.

      Subpart B_Procedures for Determining the Bioavailability or 
                     Bioequivalence of Drug Products

320.21 Requirements for submission of in vivo bioavailability and 
          bioequivalence data.
320.22 Criteria for waiver of evidence of in vivo bioavailability or 
          bioequivalence.
320.23 Basis for measuring in vivo bioavailability or demonstrating 
          bioequivalence.
320.24 Types of evidence to measure bioavailability or establish 
          bioequivalence.
320.25 Guidelines for the conduct of an in vivo bioavailability study.
320.26 Guidelines on the design of a single-dose in vivo bioavailability 
          or bioequivalence study.
320.27 Guidelines on the design of a multiple-dose in vivo 
          bioavailability study.
320.28 Correlation of bioavailability with an acute pharmacological 
          effect or clinical evidence.
320.29 Analytical methods for an in vivo bioavailability or 
          bioequivalence study.
320.30 Inquiries regarding bioavailability and bioequivalence 
          requirements and review of protocols by the Food and Drug 
          Administration.
320.31 Applicability of requirements regarding an ``Investigational New 
          Drug Application.''
320.32 Procedures for establishing or amending a bioequivalence 
          requirement.
320.33 Criteria and evidence to assess actual or potential 
          bioequivalence problems.
320.34 Requirements for batch testing and certification by the Food and 
          Drug Administration.
320.35 Requirements for in vitro testing of each batch.
320.36 Requirements for maintenance of records of bioequivalence 
          testing.
320.38 Retention of bioavailability samples.
320.63 Retention of bioequivalence samples.

    Authority: 21 U.S.C. 321, 351, 352, 355, 371.



    (a) Bioavailability means the rate and extent to which the active 
ingredient or active moiety is absorbed from a drug product and becomes 
available at the site of action. For drug products that are not intended 
to be absorbed into the bloodstream, bioavailability may be assessed by 
measurements intended to reflect the rate and extent to which the active 
ingredient or active moiety becomes available at the site of action.
    (b) Drug product means a finished dosage form, e.g., tablet, 
capsule, or solution, that contains the active drug ingredient, 
generally, but not necessarily, in association with inactive 
ingredients.
    (c) Pharmaceutical equivalents means drug products in identical 
dosage forms that contain identical amounts of the identical active drug 
ingredient, i.e., the same salt or ester of the same therapeutic moiety, 
or, in the case of modified release dosage forms that require a 
reservoir or overage or such forms as prefilled syringes where residual 
volume may vary, that deliver identical amounts of the active drug 
ingredient over the identical dosing period; do not necessarily contain 
the same inactive ingredients; and meet the identical compendial or 
other applicable standard of identity, strength, quality, and purity, 
including potency and, where applicable, content uniformity, 
disintegration times, and/or dissolution rates.
    (d) Pharmaceutical alternatives means drug products that contain the 
identical therapeutic moiety, or its precursor, but not necessarily in 
the same amount or dosage form or as the same salt or ester. Each such 
drug product individually meets either the identical or its own 
respective compendial or other applicable standard of identity, 
strength, quality, and purity, including potency and, where applicable, 
content uniformity, disintegration times and/or dissolution rates.
    (e) Bioequivalence means the absence of a significant difference in 
the rate and extent to which the active ingredient or active moiety in 
pharmaceutical equivalents or pharmaceutical alternatives becomes 
available at the site of drug action when administered at the same molar 
dose under similar conditions in an appropriately designed study. Where 
there is an intentional difference in rate (e.g., in certain extended 
release dosage forms), certain

[[Page 186]]

pharmaceutical equivalents or alternatives may be considered 
bioequivalent if there is no significant difference in the extent to 
which the active ingredient or moiety from each product becomes 
available at the site of drug action. This applies only if the 
difference in the rate at which the active ingredient or moiety becomes 
available at the site of drug action is intentional and is reflected in 
the proposed labeling, is not essential to the attainment of effective 
body drug concentrations on chronic use, and is considered medically 
insignificant for the drug.
    (f) Bioequivalence requirement means a requirement imposed by the 
Food and Drug Administration for in vitro and/or in vivo testing of 
specified drug products which must be satisfied as a condition of 
marketing.

[42 FR 1634, Jan. 7, 1977, as amended at 42 FR 1648, Jan. 7, 1977; 57 FR 
17997, Apr. 28, 1992; 67 FR 77672, Dec. 19, 2002]