Many studies reported in the late 70s and early 80s established the basic concept of ivivc 6. Importance of bioavailability in the pharmaceutical world rita b 1, akhilesh t 2. Test methods appropriate study protocol including the required number of subjects and sampling intervals should be determined according to preliminary studies and previously reported data. Bioavailability and bioequivalence studies are required to ensure therapeutic equivalence between a pharmaceutically equivalent test drug and a generic drug or reference drug. Bioavailability ba and bioequivalence be studies are essential in oral dosage form development.
Study report synopses for bioequivalence or comparative bioavailability studies conducted during formulation development should also be included in module 2. Bioequivalence studies are very important for the development of a. The search output of bioequivalence study is together with the pharmaceutical quality data of. For both, these studies are also important in the postapproval period in the presence of certain manufacturing changes. Fulfilling bioequivalence criteria with highly variable drugs is difficult.
Noteworthy, the demonstration of bioequivalence is the biggest concern for the approval and use of generic products, and the possibility of a biowaiver for in vivo bioequivalence studies must be approached with caution and careful supervision to ensure the safety and efficacy of these drugs ramirez et al. Methods an attempt was made to obtain the available published data regarding the clinical significance of bioequivalence and interchangeability of the narrow. Bioequivalence may sometimes be demonstrated using an invitro bioequivalence standard, especially when such an invitro test has been correlated with human invivo bioavailability data. The importance of bioequivalence studies is increasing also due to the large growth of the production and consumption of generic products. What is bioavailability and bioequivalence generics 2009. This paper will discuss one of those debated topics, namely, the clinical significance of bioequivalence and interchangeability of narrow therapeutic range drugs, focusing on warfarin. This chapter provides readers an overview of general concept of ba and be. Importance of biopharmaceutics and pharmacokinetics in.
When equivalence studies are necessary and types of study required 191 5. Two important considerations in the design of bioequivalence studies with atorvastatin. Despite the paucity of biopharmaceutic and pharmacokinetic data for many old drugs, these areas of scientific research have demonstrated an immense value in clinical medicine, and can be expected to expand mans knowledge of drug action and the influence of. Bioequivalence study is important for generic drug approval process. Focus on clopidogrel article pdf available in medical journal of indonesia 202. Importance of bioequivalence studies for enhancing. In other situations, bioequivalence may sometimes be demonstrated through comparative clinical trials or pharmacodynamic studies. Bioequivalence be study is required to show whether a generic copy product can be interchangeable with the brand innovator product. Bioequivalence studies of pharmaceutical preparations. Bioequivalence studies for postponed discharge drug items are like those for developed discharge drug items. In a simple parallel study design, the statistical analysis should be conducted including the betweensubject variability to calculate the 90% confidence interval of the treatment mean difference. In determining bioequivalence, for example, between two products such as a commercially available brand product and a potential tobemarketed generic product, pharmacokinetic studies are conducted whereby each of the preparations are administered in a crossover study to volunteer subjects, generally healthy individuals but occasionally in patients. Bioequivalence study needed as a result of changes in the.
A similarity between two drugs meaning that they both have the same effect on the patient. Bioequivalence if two medicines are bioequivalent there is no clinically significant difference in their bioavailability. E 3 structure and content of clinical study reports. Applications inds, new drug applications ndas, abbreviated new. Bioavailability and bioequivalence studies intechopen. Ensuring uniformity in standards of quality, efficacy, and safety of pharmaceutical products is the fundamental responsibility of central drugs standard control.
For extendedrelease and delayedrelease drug products, the following studies are recommended. Full study reports for pilot studies should be available upon request. Bioequivalence study protocol the elements of in vivo bioequivalence study protocol are listed the in vivo bioequivalence study requires determination of relative bioavailability after administration of a single dose of test and reference formulations by the same route in equal doses but at different times. Significance of be studies bioequivalence studies are intended to look at the in vivo execution of a test pharmaceutical item multisource contrasted with a reference pharmaceutical item. For broadened discharge and postponed discharge drug items, the accompanying studies are prescribed. Though bioequivalence is determined by the fda, generic substitution laws and practices are determined on the state level. Their justification is the observing of pharmacokinetic and pharmacodynamic parameters after the organization of tried medications. The use of stereoselective method in bioequivalence studies is an important goal to be realized in future. Bioequivalence who prequalification of medicines programme. Pdf bioequivalence be study is required to show whether a generic copy product can be interchangeable with the brand innovator product. Importance of in vitro in vivo studies in pharmaceutical formulation development chandrasekaran arcot ravindran.
Importance of bioequivalence studies for enhancing pharmacokinetic parameters rita b 1, akhilesh t 2. Guidance for industry handling and retention of bioavailability ba and bioequivalence be testing samples, generics. Establishing bioequivalence comparative pharmacokinetic studies in vivo comparative bioavailability studies comparison of performance of products based rate and extent of absorption of drug substance from each formulation area under the concentrationtime curve auc maximal concentration cmax time to maximal concentration. Some of the important terms relevant in this context will be defined. Importance of in vitro in vivo studies in pharmaceutical. Importance of bioavailability in the pharmaceutical world. Ba and bioequivalence be studies, as required by 21 cfr 320.
In summary, bioequivalence as determined by the fda is not therapeutic equivalence a much more clinically important measure. A list of all bioequivalence studies, including pilot studies, conducted with the proposed product i. Stereoselective methods should be used in two situation. The target of such study is to evaluate the therapeutic compatibility of tested drugs. Importance of bioequivalance studies to evaluate the absolute bioavailability of dosage form compared with reference dosage forms. In bioequivalence studies, the study design also determines the appropriate statistical model for data analysis. Intrainter subject variability intervention study to examine effect of e.
Pulla reddy college of pharmacy, osmania university, hyderabad, india 2 department of pharmaceutical analysis, vathsalya college of pharmacy, jawaharlal nehru technology university, hyderabad, india. Pdf importance of bioequivalence studies for enhancing. Bioequivalence and bioavailability studies are important during drug development of both new drug products and their generic equivale nts. Commentary sexbyformulation interaction in bioequivalence studies. It is a relative term that compares drug products with respect to a specific characteristic or function or to a defined set of standards. The aim of this article is to provide the rationale for conducting be studies, the main products requiring be studies, the design and conduct of be studies in general, with focus on clopidogrel. Bioequivalence studies are not needed for a powder for reconstitution as a solution solution. Bioequivalence and bioavailability studies are important during drug development of both new drug products and their generic equivalents. Like many regulatory studies, the assessment of bioavailability and bioequivalence can generally be achieved by.
Various definitions of in vitroin vivocorrelation have been proposed by. Provision of bioavailability andor bioequivalence study data is an important element in support of investigational new drug applications inds, new drug applications ndas, abbreviated new drug applications. A typical outline for a bioequivalence study includes organization of the test and. Importance of bioequivalance studies to evaluate the absolute. Bioequivalence of sodium levothyroxine endocrine society. Pulla reddy college of pharmacy, osmania university, hyderabad, india. Guideline o the investigation of bioequivalence european. Study conditions standardization of the study environment, diet, fluid intake, postdosing postures, exercise, sampling schedules etc.
Study of regulatory requirements for the conduct of. The aim of this study was to compare the importance of sample size, intrasubject variability, and the point estimate of test and reference formulations with regard to meeting bioequivalence be criteria maximum observed plasma concentration cmax and area under the concentrationtime curve auc. The objective of such study is to assess the remedial similarity of tried medications pharmaceutical counterparts or pharmaceutical options. When there is high first pass metabolism of the active enantiomer eutomer suggests that both total. In bioequivalence studies comparison of innovator and reference drug show similar concentration time profile in the bloodplasma of both the rate and extent of absorption of various multisource drug formulations in terms of various. The current definition for generic medicinal products. Extended release items can be cases, tablets, granules, pellets and suspensions. Although bioequivalence is most commonly discussed in relation to generic medicines, it is important to note that bioequivalence studies are also performed for innovator medicines in some situations such as. Federal institute for drugs and medical devices general requirements statistics covering average bioequivalence. Extendedrelease products can be capsules, tablets, granules, pellets, and suspensions.
Generic products represent approximately 50 % of the whole consumption in many european countries and usa. Fasting and fed state considerations generally, a single dose study should be conducted after an overnight fast at least 10 hours, with subsequent fast of 4 hours. Statistical issues in bioavailabilitybioequivalence studies. Dose proportionality study to determine if bioavailability parameters are linear over proposed dosage range. Bioavailability and bioequivalence studies submitted in. Bioequivalence studies are essential for the improvement of a pharmaceutical readiness in the pharmaceutical business. Pdf the importance of sample size, logmean ratios, and. The importance of sample size, logmean ratios, and intrasubject variability in the acceptance criteria of 108 bioequivalence studies. Conclusion of bioequivalence studies study design appropri ate and study conduct satisfactory no critical deficiencies or abnormalities methods or statistical analysis bioequivalence established. Guideline for bioequivalence studies of generic products. Bioavailability andor bioequivalence studies play a key role in the drug development period for both new drug products and their generic equivalents. Details on typical babe study designs, study conducts, bioassays, and data analyses are discussed, with a primary focus on orally administered drugs.