BA-bioavailability refers to the extent and rate of release and absorption of the active pharmaceutical ingredient from the formulation into the systemic circulation. Generally divided into absolute bioavailability and relative bioavailability: the absolute bioavailability is the relative amount of the active pharmaceutical ingredients absorbed into the body circulation obtained from the intravenous preparation (usually considered to be 100% bioavailability of the intravenous preparation) as the reference preparation; Relative bioavailability is the relative amount of the active pharmaceutical ingredient absorbed into the systemic circulation obtained from other non-intravenous routes of administration (such as tablets and oral solutions) as the reference preparation.
BE-bioequivalence refers to the fact that there is no statistically significant difference in the degree and speed of absorption of the active ingredient of a pharmaceutically equivalent preparation or an alternative drug under the same test conditions and taking the same dose. A BE study in the usual sense refers to a comparative study using the BA study method, with pharmacokinetic parameters as endpoint indicators, according to predetermined equivalence standards and limits. When the pharmacokinetic method is really infeasible, a comparative study based on clinical comprehensive efficacy, pharmacodynamic indicators or in vitro test indicators can also be considered, but it is necessary to fully confirm that the method used is scientific and feasible.
Differences and connections between BA and BE
BA emphasizes reflecting the relative amount and speed of active pharmaceutical ingredients reaching the body’s circulation, which is one of the important basis for selecting the appropriate route of administration and determining the medication regimen (such as dosage and interval) in the process of new drug research. BE focuses on the comparison based on predetermined equivalence standards and limits, which is the basis for ensuring the consistency of in vivo behavior of different preparations containing the same active ingredient, and the basis for judging whether the later-developed product can be used as a substitute for the marketed drug.
The obvious difference between BA and BE is in their application: in the new drug research stage, in order to determine the rationality of the new drug prescription and process, it is usually necessary to compare whether the preparation can achieve the expected bioavailability after changing the above factors; Conduct bioavailability studies on the dosage form to be marketed to determine the rationality of the dosage form, determine the dosage of the new dosage form through a BA study comparing with the original dosage form, and confirm whether the new dosage form is equivalent to the original dosage form through a BE study; During clinical trials, BE studies can be used to verify the consistency of products of the same drug in different periods, such as: early and late clinical trial drugs, clinical trial drugs (especially those used to determine doses) and proposed drugs. Listed drugs, etc. In simple terms, BE can be considered as part of BA, BA applications are biased towards new drug development, and BE applications are biased towards generic drug development.
BA and BE studies have different roles at different stages of drug development:
In the new drug research stage, in order to determine the rationality of the new drug prescription and process, it is usually necessary to compare whether the preparation can achieve the expected bioavailability after changing the above factors; when a new dosage form is developed, the bioavailability study of the proposed dosage form should be carried out to determine the bioavailability of the dosage form. Rationality, the dosage of the new dosage form can be determined by the BA study compared with the original dosage form, and the BE study can also be used to confirm whether the new dosage form is equivalent to the original dosage form; in the course of the clinical trial, the same drug can be verified by the BE study The consistency of products in different periods, such as: early and late clinical trial drugs, clinical trial drugs (especially the experimental drugs used to determine the dose) and drugs to be marketed, etc.
When imitating the existing national standard drugs, BE studies can be used to prove whether the imitation products are bioequivalent to the original drugs, and whether they can be used interchangeably with the original drugs. After the drug is approved for marketing, if there is a certain degree of change in the composition, proportion and process of the formulation, the researcher needs to determine whether to conduct a BE study according to the degree of product change to examine whether the product is bioequivalent after and before the change. . For new formulations developed for the purpose of improving bioavailability, BA studies are required to understand the changes in bioavailability before and after the change.