0000011131 00000 n
Introduction. 0000063276 00000 n
Because drug clearance typically shows large between-subject variabilities, analyzing pharmacokinetic results for two products within the same subject is usually more powerful. 0000158577 00000 n
Bioequivalence studies 1. trailer
Iscriviti alla Newsletter!!! 0000006100 00000 n
0000000016 00000 n
In a simple parallel study design, the statistical analysis should be conducted including the between-subject variability to calculate the 90% confidence interval of the treatment mean difference. Main topic of this collection is Bioavailability / (in-vivo-) Bioequivalence, although GCP/GLP, dissolution/BCS, pharmacokinetics, bioanalytics and -statistics are covered to some minor extent as well.Linked guidances/guidelines are in English, unless stated otherwise. 0000118438 00000 n
x�b```b``������U� Ā B@16���Ӿ�W(HO�|�XVq1�?�2Pp�e�( startxref
0000012677 00000 n
2.02_Quality and Bioequivalence Guideline_Jul19_v7 Page 10 of 35 the discretion of SAHPRA, based on the documents (and quality thereof) available for reliance-based evaluation. 0000014445 00000 n
0000157616 00000 n
The physical processes of drug absorption for solid oral dosage forms are usually the same in patients as they are in healthy subjects. 0000001840 00000 n
u�청�~GR���E�K����$�wx�+(�ԭ��ĺ�zY��II���l��E�N�,�,�'q�і�[���"���K!������u@@D�QPP.wChh(�"f�GG�o�@�����6b+��$?�>�� However, a well justified PD studies can be used to demonstrate BA or BE if measurements of drug concentrations cannot be used as surrogate endpoints for the demonstration of efficacy and safety of the particular pharmaceutical product, e.g., for topical products without an intended absorption of the drug into the systemic circulation An essential component of a BA or BE study based on a PD response is documentation of a dose-response relationship. 0000012238 00000 n
0000001903 00000 n
Standard bioequivalence study designs, therefore, include parallel and crossover designs. 0000004983 00000 n
0000005987 00000 n
For the drug to be absorbed it must be soluble in the absorption site. PK endpoints are generally a more accurate, sensitive, and reproducible approach and are therefore preferred. In a parallel study, subjects are randomly assigned to one of two treatment groups (i.e., T or R), and both treatment groups are followed in parallel. 0000004518 00000 n
0000013477 00000 n
Thus, demographic characteristics of subjects enrolled in a BE study should represent the patient population, taking into account age, sex, and race. A population bioequivalence approach may also be used in a non-replicated study, since the test and reference products are given to different subjects. For example, if an oral dosage form is intended for both male and female patients, a BE study should be conducted in subjects with both sexes.Healthy volunteers are generally preferred in a BE study over patients for several reasons. ИНН – это индивидуальный налоговый номер, который должен быть у каждого человека. For most drugs, the PK processes are affected by demographic characteristics of patients. 0000002407 00000 n
For example, clozapine is approved for treatment-resistant schizophrenia. This section provides the key information for gaining approval of an ANDA.Bioavailability is the rate and extent of drug available at the site of action.In BE studies, the plasma concentration time curve is generally used to assess the rate and extent of absorption. Bioequivalence studies are cross-over studies in which each subject acts as their own control. 0000017643 00000 n
0000010489 00000 n
In terms of statistical analysis criteria, therefore, an average bioequivalence approach is generally sufficient. Cmax, the maximum plasma concentration or peak exposure, and the time to maximum plasma concentration, tmax, are parameters that are influenced by absorption rate The assessment of BE of two drug products is based on the fundamental assumption that two drug products are equivalent when the rate and extent of absorption of the test product is not significantly different from that of the reference drug when the two drugs are administered at the same molar dose of the therapeutic ingredient under similar experimental conditions in either a single dose or multiple doses.BE studies are generally recommended by using the following endpoints, listed in order of preference The therapeutic effect of a solid drug product is the function of the concentration of the active ingredient in the systemic circulation and is therefore related to its bioavailability.