APPENDIX

Comparison of FDA and WHO Definitions

Term	FDA	WHO
Pharmaceutical Equivalents	Drug products are considered pharmaceutical equivalents if they contain the same active ingredient(s), are of the same dosage form, have the same route of administration, and are identical in strength or concentration. Pharmaceutically equivalent drug products are formulated to contain the same amount of active ingredient in the same dosage form and to meet the same or compendial or other applicable standards (strength, quality, purity, and identity); but they may differ in characteristics such as shape, scoring configuration, release mechanisms, packaging, excipients, expiration time, and, within certain limits, labeling.	Products are pharmaceutical equivalents if they contain the same molar amount of the same API(s) in the same dosage form; if they meet comparable standards; and if they are intended to be administered by the same route. Pharmaceutical equivalence does not necessarily imply therapeutic equivalence, because differences in the excipients and/or the manufacturing process and some other variables can lead to differences in product performance.
Pharmaceutical Alternatives	Drug products are considered pharmaceutical alternatives if they contain the same therapeutic moiety but are different salts, esters, or complexes of that moiety or are different dosage forms or strengths.	Products are pharmaceutical alternative(s) if they contain the same molar amount of the same active pharmaceutical moiety or moieties but differ in dosage form (e.g., tablets vs. capsules) and/or chemical form (e.g., different salts, different esters). Pharmaceutical alternatives deliver the same active moiety by the same route of administration but are otherwise not pharmaceutically equivalent. They may or may not be BE or TE with the comparator product.
Therapeutic Equivalents	Drug products are considered to be therapeutic equivalents only if they are pharmaceutical equivalents and if they can be expected to have the same clinical effect and safety profile when administered to patients under the conditions specified in the labeling.	Two pharmaceutical products are considered to be therapeutically equivalent if they are pharmaceutically equivalent or pharmaceutical alternatives and after administration in the same molar dose, their effects, with respect to both efficacy and safety, are essentially the same when administered to patients by the same route under the conditions specified in the labeling.
Bioavailability (BA)	This term 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.	The rate and extent to which the active pharmaceutical ingredient or active moiety is absorbed from a pharmaceutical dosage form and becomes available [at the site(s) of action] in the general circulation.
Bioequivalent Drug Products (BE)	This term describes pharmaceutical equivalent or pharmaceutical alternative products that display comparable BA when studied under similar experimental conditions.	Two pharmaceutical products are BE if they are pharmaceutically equivalent or pharmaceutical alternatives and their BA, in terms of peak concentration (Cmax), time to peak concentration (Tmax), and total exposure (AUC) after administration of the same molar dose under the same conditions, are similar to such a degree that their effects can be expected to be essentially the same.
RLD (Reference Product) or Comparator Product	An RLD [21 CFR 314.94(a)(3)] means the listed drug identified by FDA as the drug product upon which an applicant relies in seeking approval of its ANDA.	The comparator product is a pharmaceutical product with which the multisource product is intended to be interchangeable in clinical practice. The comparator product normally will be the innovator product for which efficacy, safety, and quality have been established. The selection of the comparator product usually is made at the national level by the drug regulatory authority.
Generic Product	A generic product is a product that is therapeutically equivalent to the RLD and is intended to be interchangeable with the innovator product.
Multisource Pharmaceutical Products		Pharmaceutically equivalent or pharmaceutically alternative products that may or may not be therapeutically equivalent. Multisource pharmaceutical products that are therapeutically equivalent are interchangeable.
Interchangeable Pharmaceutical Product		An interchangeable pharmaceutical product is one that is therapeutically equivalent to a comparator product and can be interchanged with the comparator in clinical practice.