Study of regulatory requirements for the conduct of bioequivalence. Guidance on triggers for inspections of bioequivalence trials. Several in vivo and in vitro methods are used to measure product quality. Introduction n indicate the rationale for the study eg, obtain marketing authorization in. Bioavailability and bioequivalence studies play a major role in the drug development phase for both new formulations and their generic equivalents. The recognised need for stringent criteria to support approval of generic drugs with an nti led the european medicines association and health canada to provide detailed information on requirements for bioequivalence studies and introduce tighter bioequivalence limits for these drugs, including tacrolimus. Objectives discuss the pharmacokinetic processes that determine absolute bioavailability discuss the basic fda requirements for approval of andas submitted by generic drug. Regulatory requirements in bioequivalence list of high impact. For both, these studies are also important in the postapproval period in the presence of certain manufacturing changes. Nagesh thudi is presenting on reserveretention sample requirements. The fda considers two products bioequivalent if the 90% ci of the relative mean cmax, auc0t and auc0. Information for applicants completing the bioequivalence study information form v1.
Monitoring bioequivalence studies part 1 pharmadesk. The fda considers two products bioequivalent if the 90% ci of the relative mean cmax, auc 0t and auc 0. Study of regulatory requirements for the conduct of bioequivalence studies in us, europe, canada, india, asean and sadc countries. Compliance to gcp requires that the sponsor ensure adequate oversight of the study, the nature and extent of which must be decided based on the critical aspects of the study that may affect human. The main focus of this lecture is to instruct students in process and requirements needed to attain the ab rating. Pdf investigation and need of bioequivalence study.
Bioavailability and bioequivalence studies submitted in. Tips for authors of bioequivalence studies abstract provide a structured abstract of 400 words or less with background, objective, methods, results, and conclusion sections, and 4 to 6 key words. Before sharing sensitive information, make sure youre on a federal government site. Regulatory requirements in bioequivalence list of high.
Summary of a bioavailability or bioequivalence study form. Bioavailability and bioequivalence studies intechopen. In bioequivalence studies, the plasma concentration time curve is generally to assess the rate and extent of absorption. Compliance to gcp requires that the sponsor ensure adequate oversight of the study, the nature and extent of which must be decided based on the critical aspects of the study. Bioequivalence concept regulations exist worldwide to assure quality, safety, and efficacy of medicines the bioequivalence be concept addresses the safety and efficacy issue for generic drug registration be provides the bridge from the generic product to the innovators clinical and nonclinical studies and labeling. Bioequivalence may sometimes be demonstrated using an invitro bioequivalence standard, especially when such an invitro test has been correlated with human invivo bioavailability data. Completing the bioequivalence study information form bsif. Tamboli am, todkar p, zope p, sayyad fj 2010 an overview on bioequivalence. Results in unnecessary human be studies 31 diliberti path to bioequivalence. State the criteria used to assume regulatory bioequivalence in the abstracts methods.
Proposal to waive in vivo bioequivalence requirements for who model list of essential medicines immediaterelease, solid oral dosage forms pdf 464kib annex 9. Global bioequivalence bioavailability regulatory guidance. Submission of application for new drugs under schedule y should be required to furnish the bioavailability and bioequivalence data, that is. As per gcp, monitoring is the act of overseeing the progress of a clinical trial or be study and ensuring that it is conducted, recorded, and reported in accordance with the protocol, standard operating procedures sops, good clinical practice gcp, and the applicable regulatory requirement s. Foodeffect bioavailability and fed bioequivalence studies. Bioavailability and bioequivalence studies are required by regulations to ensure therapeutic equivalence between a. Bioequivalence concept regulations exist worldwide to assure quality, safety, and efficacy of medicines the bioequivalence be concept addresses the safety and efficacy issue for generic drug registration be provides the bridge from the generic product to the innovators clinical and nonclinical studies and. This guideline specifies the requirements for the design, conduct, and evaluation. Guidelines for bioavailability and bioequivalence studies. In bioequivalence studies, the plasma concentration time curve is generally to assess the rate and extent of. By doing so, sahpra will reflect global best practice in terms of the safety, quality and efficacy of health product regulation. Meeting regulatory requirements for drugs with a narrow. In other situations, bioequivalence may sometimes be demonstrated through comparative clinical trials or pharmacodynamic studies. Pdf an overview on bioequivalence regulatory requirements of.
As the generic pharmaceutical industry continues to grow and thrive, so does the need to conduct adequate, efficient bioequivalence studies. Bioavailability and bioequivalence studies are required by regulations to ensure therapeutic equivalence between a pharmaceutically equivalent test product and a reference product. 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. The organization, conducting the bioequivalence bioavailability studies, or the. In recent years, there have been significant changes to the statistical models for evaluating bioequivalence. Bioequivalence bioequivalence is defined to the class using the terms provided in section 505j7b of the federal food, drug, and cosmetic act. There are various investigations to assess bioequivalence and each regulatory authority has its own guidance for the conduction of bioavailability and bioequivalence studies before approval of generic products. Handbook of bioequivalence testing 2nd edition sarfaraz k. Bioavailability andor bioequivalence studies play a key role in the drug development period for both new drug products and their generic equivalents. Regulatory requirements for the registration of generic. Conducting a bioequivalence study in india introduction. The path to bioequivalence great progress, great opportunities. The regulatory requirements of each country vary from each other.
Apr 01, 2020 a any person submitting a full or abbreviated new drug application, or a supplemental application proposing any of the changes set forth in 320. Guideline for bioequivalence studies of generic products december,2006. Regulatory consideration for generic drug products. 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. Cros and laboratories conducting bioequivalence studies and analysis of. Regulations and requirements for conducting clinical.
Comparative bioavailability studies should be conducted in accordance with generally accepted clinical practices that are designed to ensure the protection of the rights, safety and wellbeing of subjects and the good clinical practices referred to in division 5 of the regulations and described in the international conference on harmonisation ich guidance topic e6 on good clinical practice. Requirements for registration of pharmaceuticals for human use ich. The sites conducting the analysis are not required to be certified as part of the glp. Galgatte uc, jamdade vr, aute pp, chaudhari pd 2014 study on requirements of bioequivalence for registration of pharmaceutical products in usa, europe and canada. Guideline on the conduct of bioequivalence studies for veterinary. This master thesis aims to compare the regulatory requirements for bioequivalence studies in the european union and the united states of america that need to be fulfilled in. Informal communication by the center for drug evaluation and research cder, march 2003 rani s, pargal a. Guidance on triggers for inspections of bioequivalence. Bioequivalence trials conducted in the eueea have to be carried out in accordance with directive 200120ec. Study of regulatory requirements for the conduct of.
Additional guidance for organizations performing in vivo bioequivalence studies pdf 371kib. Fda regulations in part 320 21 cfr part 320 establish definitions and requirements for bioavailability and bioequivalence studies. Pdf study of regulatory requirements for the conduct of. Bioequivalence studies are the primary needs for generic products to enter in the market. Draft guidance for industry on bioequivalence recommendations. Design and analysis of bioavailability and bioequivalence. Like many regulatory studies, the assessment of bioavailability and bioequivalence can generally be achieved by considering. Compare medicinal product requirements for generics to those of new drug products, and discuss the influence of ich guidelines q9 q11 on generics documentation recognise the elements and the effects of the current eu guidance on bioequivalence and identify particularities of the eu bioequivalence guidance as compared to current us fda.
The investigator clinical part of the study and the study director bioanalytical part of the study are then employees of the cro. Review article bioequivalence requirements in the european. An overview on bioequivalence regulatory requirements of orally. Aug 26, 2015 informal communication by the center for drug evaluation and research cder, march 2003 rani s, pargal a. The test products used in the bioequivalence study must be prepared in accordance with gmp regulations including eudralex volume 4. Nov 01, 2012 animal bioequivalence studies ab guideline on the conduct of bioequivalence studies for veterinary medicinal products 1 two medicinal products containing the same active substance are considered bioequivalent if they are pharmaceutically equivalent or pharmaceutical alternatives and their bioavailabilities rate and extent after. This guidance has been updated relative to 164 the previous version of this document. Guideline for bioequivalence studies of generic products. Ema versus usfda regulatory requirements regarding. Bioequivalence study will be carried out in healthy volunteer unless drug carried safety issue it will carry out in patientus fda general consideration babe, 2003. The regulatory expectations and norms for proving bioequivalence as a marker for therapeutic equivalence are generally standardised with some country specific regulations or requirements that may differ.
In the context of this guidance document, bioequivalence studies are often contracted by the sponsor to a cro, which will perform some of the tasks of the sponsor, but which will also perform the trial. In this study, document requirements for approval of generic products, approval timelines, and consideration of bioequivalence andor biowaiver data by regulatory authorities ras of 10 selected jurisdictions was studied. Design and analysis of bioavailability and bioequivalence studies. In order to blow away the doubts and reestablishing the credibility of generics in market, bioequivalence be guidelines with stricter regulation should be the demand. The guidance also makes other revisions for clarification. Guidance for organizations performing in vivo bioequivalence studies.
Impact on generic drug substitution may 2016 journal of applied. Scientific and regulatory considerations for bioequivalence. In addition, advances in the analytical technology used to detect drug and metabolite levels have made bioequivalence testing more complex. Annex 9 additional guidance for organizations performing in vivo. Comparison of bioequivalence study regulatory requirements. Study on requirements of bioequivalence for registration. In case there are identified t riggers for inspection for a particular site or cro, the assessor or gcp. Study on requirements of bioequivalence for registration of. The present study highlights the relevant regulatory guidelines for the conduct of bioequivalence studies in us, europe, canada, india, south africa and south east asian nations. Oct 15, 2008 preeminent experts update a wellrespected book taking into account the regulatory and scientific developments that have occurred since the second edition, design and analysis of bioavailability and bioequivalence studies, third edition provides a complete presentation of the latest progress of activities and results in bioavailability and bioequivalence on regulatory requirements, scientific. Regulatory agencies world over rely on the data from bioequivalence studies as an important component of granting marketing approval for generic products. There are various investigations to assess bioequivalence and each regulatory authority has its own guidance for the conduction of bioavailability and bioequivalence studies before approval of.
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