Bioequivalence study protocol slideshare. Bioequivalence studies 1.

• Bioequivalence study protocol slideshare Sample collection schedule E. Design B. PURPOSE OF BIOAVAILABILITY AND BIOEQUIVALENCE STUDIES Bioavailability is defined as 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. 1 Bioavailability 11 4. 36. If bioequivalence testing was performed under contract, the contract research organization shall retain reserve samples of any test article and reference standard used in conducting an in vivo or in vitro bioequivalence study required for approval of the abbreviated application or supplemental application. Different approaches for determination of bioequivalence of a drug product are: An in vivo test in humans in which the concentration of the active ingredient and when appropriate, its active metabolites, in blood, plasma, serum or other suitable biological fluid is measured as a function of time. In vivo and in vitro bioequivalence studies are described, with in vivo requiring human subjects and in vitro using dissolution testing. The current study showed that a simulation study is important to determine the appropriate sample size and to select an efficient design for bioequivalence studies. • In early 1970s, research laboratories in the USA were found doing work in unethical ways, like: – data generation without conduct of study – falsification of laboratory work – 5. but there are also various drawbacks like diseases, other drugs, To investigate the bioequivalence of 2 drug products or compounds, the FDA considers PK studies that determine the area under the concentration-time curve (AUC), maximum concentration (Cmax), and time to Cmax (Tmax) for the study compound (generic) and a reference compound (innovator). This study reviews the requirements of bioequivalence with study parameters such as study design, fasting or fed state studies, volunteers recruitment, study dose, sampling points, analytical method validation parameters, moieties to be measured in plasma, pharmacokinetic parameters, criteria for bioequivalence, GCP requirements etc, which are needed for the pharmaceutical II. BA depends on several factors including route of administration, dosage form, physicochemical properties of the drug(s) and excipient(s), and the conduct of bioequivalence studies in US, Europe, Canada, India, South Africa and South East Asian Nations. Plasma Level- Time Studies: • Most common type of human bioavailability studies. , their plasma concentration-time profiles will be identical with out significant differences are statistically significant differences are observed in the bioavailability of two or more drug products, bio- 4. Bioavailability is the fraction of an administered dose of unchanged drug that reaches the systemic circulation. vilas kamble m. 3. INTRODUCTION • This study was undertaken to assess the bioequivalence (normally injectable don’t need to be checked for BS/BE cause they are 100% available since the beginning , but propolol is not a solution but an emulsion, drugs within emulsion aren’t 100% bioavailable since the start but is released slowly) between a new formulation of propofol 2% 3. Exclusion of outliers only possible if procedure stated in the protocol, and. – Bioequivalence may sometimes be demonstrated using an in-vitro bioequivalence standard, especially when such an in-vitro test has been correlated with human in-vivo bioavailability data. Introduction (background) Bioequivalence is defined as the absence of a difference (within predefined acceptance criteria) in the bioavailability of the active pharmaceutical ingredient (API) or its metabolite(s) at the site of action The study of drug absorption (e. It describes the objectives of such studies as determining if a test product is bioequivalent to a reference product when administered at A complete study report must be submitted for the bioequivalence study upon which the applicant relies for approval. BioPharma Services is a full-service clinical research organization (CRO) that competently and efficiently designs and performs human clinical trials for our clients’ drug development programs. Bioavailability and Bioequivalence Studies Submitted in NDAs or INDs — • Bioequivalence Experimental Study Design • The various types of test designs that are usually employed in clinical trials, (bioavailability and bioequivalence ) 1. pure drug of study (which is very costly) – and artificially prepare plasma of different concentration BIOEQUIVALENCE STUDY: EXEMPTIONS AND WAIVERS This presentation is based on: 1. 6%) for apalutamide in applesauce compared with whole tablets, despite a comparable extent of Human volunteer – healthy subject vs. Assessment of “interchangeability” between the generic and the innovator product is carried out by a study of “in vivo equivalence” or “bioequivalence” (BE). Study conditions 4. Study population a Objective of Bioequivalence study is to compare the test formulation with reference to standard CPS,IST,JNTUH 13031S0304 22. • Sponsors may also request meeting with FDA to review the study design for a specific drug product. Regulatory documents can be huge and are formulaic. The investigator (clinical part of the study) and the study director (bioanalytical part of the study) are then employees of the CRO. Comparing Generic and Innovator Drugs Bioequivalence (BE) study is required to show whether a generic copy product can be interchangeable with the brand innovator product. 9• 32 5th Scientific Conference “Clinical Trials in Ukraine” Kiev, 19 November 2015 Basic Designs for BE Studies Crossover Designs:Model MultiplicativeModel (withoutcarryover) Xijk:responseof j-th subject(j=1,,ni) in i-th sequence(i=1,2) and k-th period(k=1,2), µ: globalmean,µl:expected formulation means(l=1,2: µ l=µ test,µ 2=µ ref. Proof that drug is not only pharmaceutically equivalent (same active ingredient in same strength and dosage form), but also bioequivalent. c. BIOAVIALABILITY STUDY BIOAVAILABILITY STUDIES FOR NEW DRUGS In vivo Bioavailability studies are performed for new drugs to establish essential pharmacokinetic parameters including the rate of absorption, extent of absorption, rates of excretion and metabolism, and elimination half life after a single and multiple doses administration. The aim of bioavailability study is to find out the dosage form influence on the biological Bioequivalence is a term in pharmacokinetics used to assess the expected in vivo biological equivalence of two proprietary preparations of a drug. , a sequential design or scaled-average BE), Drug Regulations : Online Resource for Latest Information 12/11/2013 31 Importance of the field: The ultimate goal of bioequivalence is to assess the expected in vivo equivalence of two drug products of the same active moiety. , statistically insignificant) in the product's rate and extent of drug absorption, as determined by comparison of measured parameters (e. 1) Design 2. 2. surgical procedures 4. F. y. Bioavailability & bioequivalence . Therefore, a standard / normal breakfast or a high- fat, high-calorie breakfast are acceptable as long as they are 34. Submit a complete protocol for review and comment before commencing the study to the FDA to use variations of these study designs or analysis methods (e. 6/9/2020 11 Regulatory Medical Writing • It means creating the documentation that regulatory agencies require in the approval process for drugs, devices and biologics. e. 1) These rules may be called the New Drugs and Clinical Trials Rules, 2019 2) They shall come in to force from the date of their publication in the Official Gazette, except Chapter IV which shall come in to force after one hundred and 80 days 3) They shall apply to all new drugs, investigational new drugs for human use, clinical trial, bioequivalence study, 20. Informed Consent form. Bioavailability and Bioequivalence Assessment José A. 2) Key biostatistical concepts for bioequivalence studies including For this purpose, bioequivalence within the acceptance limits as defined in this document might not be needed and study designs other than those presented in this document might be found appropriate. 5. Hanoi, 2006-19-01 36 Helpful Guidelines FDA - Guidance for Industry: “Bioavailability and Bioequivalence Studies for Orally Administered Drug Products – General Considerations” (Oct. BIOEQUIVALENCE “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 of absorption) after administration in the same molar dose lie within acceptable predefined limits. For the products that are not intended to be absorbed into blood stream, bioavailability may be assessed by measurement intended to Biowaiver for Bioequivalence study If two product, containing the same , have the same concentration time profile at the intestinal membrane surface then they will have the same rate and extent of the absorption. 937, 2006. It outlines the elements of a bioequivalence study protocol and discusses study design, population, procedures, and data analysis. SAMPLING TIMES • Sampling times should be sufficiently frequent around the expected T Applicants planning to conduct bioequivalence (BE) studies for submission to PQT/MED should submit a final draft of the study protocol to PQT/MED for comment prior to undertaking the study Purpose: Assist applicants develop studies that will best be able to detect differences in in vivo performance between drug products of PK data must be pre-specified in the study protocol. Areas covered in this review: In this review, we present the classic approach of bioequivalence assessment, some situations of special importance such as the role of metabolites and highly variable drugs, and the current 21. INTRODUCTION • Biowaivers are considered as the waivers of clinical bioequivalence studies • Bioequivalence studies are as vital concern in drug development process • Biowaivers eliminates unnecessary exposure of healthy subjects to in- vitro studies • Instead of conducting expensive & time consuming in vivo studies, an in vitro dissolution test could be 8. Bioequivalence studies 1. The clinical trial protocol should cover at least the following areas: Clinical Protocol Development Before 1999, the FDA OGD published a large number of drug- specific guidances that provided the basic information needed to conduct a generic BE trial. Bioavailability and Bioequivalance • Bioavailability. Alfredo García - Arieta. 8. If the firm wants to conduct BE studies, then firm should submit detailed study protocol, EC registration, BA/BE Centre approval copy, Form- 44, Form-12 and other relevant documents as per applicable checklist. Similar findings were reported in a previous study as a test fluconazole 150-mg capsule manufactured by Laboratório Teuto Brasileiro Ltd. Study Protocol 1. Patient gets benefited from the study. Statistical techniques should be of sufficient sensitivity to detect differences in rate and extent of absorption that are not attributable to subject variability. Conventional acceptance 3. These limits are set to ensure comparable in vivo New generic standard procedure Study Protocol (BE Institute) Pharmaceutical equivalence Formulation / QC method of analysis / design of packaging In vitro dissolution / release profile study Stability of product In vivo bioequivalence BIOEQUIVALENCE FOR IMMEDIATE-RELEASE SOLID ORAL DOSAGE FORMS M13A Draft version Endorsed on 20 December 2022 69 The subject inclusion and exclusion criteria should be clearly stated in the study protocol. very rapid or rapid in vitro dissolution characteristics, CDSCO Eases Regulations For Bioavailability And Bioequivalence Studies Due To Covid-19 Outbreak. Both products are produced by the same manufacture at the same production site. – 2. Outline • Reasons for conducting comparative clinical endpoint bioequivalence (BE) studies • Role of product specific guidance (PSG) • Comparative Clinical Endpoint Study: 4. Step-wise process for regulatory approval for BA/BE studies in India. It also covers the study submission and drug review process. Peak Plasma Drug Concentration (Cmax) : Represent the maximum plasma drug concentration obtained after oral administration of drug. • In each urine sample of a collecting period, the drug concentration per milliliter is determined. 3 Study report 3. There are two types of bioequivalence testing: in vivo, – Single dose bioequivalence studies (fasted) is required for each strength – Food Effect Study and Steady State Study are required on higher strength (300 mg), possible biowaiver of lower This guideline is intended to provide recommendations on conducting bioequivalence (BE) studies during both development and post-approval phases for orally administered immediate-release This document discusses bioequivalence studies, which compare the bioavailability of generic drugs to their branded counterparts. ¾ 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. CDSCO or Central Drugs Standard Control Organization has clarified that validity of registration of BA/BE study centers will remain valid if the renewal application has been made 90 days before the expiry. • In early 1970s, research laboratories in the USA were found doing work in unethical ways, like: – data generation without conduct of study – falsification of laboratory work – Biowaiver for Bioequivalence study If two product, containing the same , have the same concentration time profile at the intestinal membrane surface then they will have the same rate and extent of the absorption. The objective of this article is to describe the recommendations from participating Bioequivalence Wor Bioavailability and bioequivalence studies guidelines (2018): Issued by CDSCO, these guidelines provide detailed instructions analysis, and reporting. 7 In vitro dissolution complementary to a bioequivalence study 10 3. Contains Nonbinding Recommendations . Interventions include but are not restricted to drugs, 2. Differences of less than 20% in AUC & Cmax between drug products are unlikely to be clinically significant in patients. Completely Randomised Designs • In a completely randomised design, all treatments (factor levels) are randomly allocated among all experimental subjects. • Students will able to understand the various applications of BA and BE in the pharmaceutical sciences etc. 5 Bioequivalence Procedures For Determining Bioavailability Or Bioequivalence. Define a reference standard (RS) in abbreviated new drug application (ANDA) Globally applied standard protocol for bioequivalence, drug-drug interaction, food effect studies. The tmax can be used as an approximate indication of drug excretion rate. CURRENT PRACTICES 12. Dosage regimen D. To determine the efficacy and safety from the bioequivalence data. 6. Study protocol development: Develop a detailed protocol outlining the study design 1. They are often costly. 2) Key biostatistical concepts for bioequivalence studies including descriptive statistics, parametric assumptions of normality and homoscedasticity, study designs, and tests of significance. 3 Handling deviations from the study plan 10 3. Introduction • Therapeutic effectiveness of a drug depends upon the ability of the dosage form to deliver the medicament to its site of action at a rate and amount sufficient to elicit the desired pharmacological response • This attribute of the dosage form is referred to as physiological availability, biological 2. Single-dose bioequivalence studies evaluate Bioequivalence - Download as a PDF or view online for free. Saudi Pharmaceut. PDF | On Sep 12, 2019, Divvela Hema Nagadurga published Bioavailability and Bioequivalence Studies | Find, read and cite all the research you need on ResearchGate The contents of protocol to conduct BA/BE study including ICF, CRF, PIS, IB, IU and preclinical study of volunteers along with procedure for reporting SAE have been discussed in details. Statutory/Regulatory. Bioequivalence has been established via bioavailability testing. Fasted/fed: The bioequivalence study should be conducted in the fasting state. Equivalent drug product performance is generally demonstrated by an in vivo bioequivalence study in normal healthy volunteers. their plasma concentration – time profiles will be identical without significant statistical differences. patients Ideally, the bioavailability study should be carried out in patients for whom the drug is intended to be used. Avoids ethical quandary. Characteristics to be investigated 4. cells and other biological products 3. 2 Bioequivalence 11 5. 1 Each of these values for the study compound are 1. when a medication is Bioavailability and bioequivalence studies guidelines (2018): Issued by CDSCO, these guidelines provide detailed instructions analysis, and reporting. Office of Study Integrity and Surveillance. Bioequivalence is a comparison with predetermined bioequivalence limits. Good Laboratory Practices (GLP) • Good Laboratory Practices or GLPs were initially invoked in a reaction to malpractices in laboratories conducting safety experiments of medicines. Anda - Download as a PDF or view online for free. Guimarães Morais Faculdade de Farmácia, Universidade de Lisboa INFARMED (Portugal) CPMP Efficacy Working Party Therapeutics Subgroup on Pharmacokinetics RETENTION OF BIOEQUIVALENCE SAMPLES: 1. , Brazil, and a reference Zoltec 150-mg capsule manufactured by Laboratórios Pfizer Ltd. Investigator’s Brochure, if applicable. The protocol provides a clear description of the study’s processes such that a clinical trial can be well executed. Once bioequivalence is established, it is likely that both the generic and brand name dosage 2. In a previous single-dose study conducted in healthy male volunteers (n = 12) a larger peak exposure was observed (+ 27. Reflects better therapeutic efficacy. The test products used in the bioequivalence study must be prepared in accordance with GMP regulations. During the development stage of a new drug product, safety and efficacy studies can be carried out with a simple pharmaceutical dosage form; later, if the new active pharmaceutical ingredient (API) proves that it is 4. • The investigator should be sure that the study has been properly designed, the objectives are clearly defined, and the method of analysis has been validated (i. 1 . In vitro bioequivalence studies The ratio between active substance and the excipient is the same , or(in the case of small strengths) the ratio between the excipients is the same. Patient is benefited from the study. Full study reports for pilot studies should be available upon request. Reflects better therapeutic efficacy of drug. 5. Dissolution Testing, Bioavailability & Bioequivalence | Budapest, 24 May 2007 18 Outliers zProblems • Parametric methods (ANOVA, GLM) are very sensitive to outliers A single outlier may underpower a properly sized study. Measurement of plasma level of a drug with the help of HPLC • Before HPLC actually begins to measure plama level of any drug whose level is to be monitored , we calibrate or validate its measurement. 0 Bioequivalence CPMP/EWP/QWP/1401/98 Rev. The aim of bioavailability study is to find out the dosage form influence on the biological performance of the drug. pharm. Most of these guidances provide some protocol design considerations, but CDSCO Eases Regulations For Bioavailability And Bioequivalence Studies Due To Covid-19 Outbreak. Test methods Appropriate study protocol including the required number of subjects and sampling intervals should be determined according to pilot studies and previously reported data. The objective of this article is to describe the recommendations from participating Bioequivalence Wor 3. , shown to measure precisely and accurately the plasma drug concentration). Bioequivalence & Bio-similarity Biosimilar means “high similar” to Pioneer not withstanding minor differences in clinically inactive components; and no clinically meaningful differences with Pioneer in terms of safety, purity and potency. • The results are analyzed both statistically and pharmacokinetically. E. radiological 3. Bioequivalence means that two products do not show a significant difference in absorption rate or extent. Study objective 3. If the drug product is intended for use in both sexes attempt should not be included in the studies. However, the concept of bioavailability and bioequivalence did not become a public issue until the late 1960s, when concern was raised that a generic drug product might not be as bioavailable as that manufactured by the innovator. Bioequivalence Def: It refers to a procedure that compares the bioavailability of a drug from different formulations. If two formulations are to be compared, a two-period, two-sequence crossover design is the design of choice which should ideally be equal to or more than five half- lives that have to be measured Alternative study 14. b. Dose: As the EoI includes Gatifloxacin tablets of 200 mgand 400 mg (scored), the bioequivalence study should be conducted with the highest strength. Clinical phase of a study 2. • Widely used and based on assumption that Pharmacokinetic profile reflects the therapeutic effectiveness of a drug. This study, known as a Phase I bridging study, is used to compare the human pharmacokinetic profile of the proposed drug product with that of the reference product (a clinical bioequivalence study). The objective is to show that the test and reference drug products have similar The document discusses the benefits of exercise for mental health. Statistical evaluation 4. 6. PDF | On Apr 20, 2012, Aisha Qayyum published Bioequivalence Studies | Find, read and cite all the research you need on ResearchGate Phase I In certain instances, the 505(b)(2) pathway enables the Phase I process to be reduced to a single study. Disadvantages Frequently not suitable for studies in Def: It refers to a procedure that compares the bioavailability of a drug from different formulations. patil college of pharmacy akurdi pune. It states that regular physical activity can help reduce anxiety and depression and improve mood and The document outlines the key elements that should be included in a bioequivalence study protocol. 21 C. BIOEQUIVALENCE STUDIES Clinical interpretation is important in evaluating the results of a bioequivalence study. when a medication is administered intravenously, its bioavailability is 100%. , RAC Senior Staff Fellow. , Brazil, demonstrated bioequivalence despite a median t max of 3 hours for the test capsule and 6 hours for the reference capsule. 8 Reporting of results 10 4 APPLICATIONS FOR PRODUCTS CONTAINING NEW ACTIVE SUBSTANCES. Bioavailability. • Refresh the concepts of pharmaceutical equivalence bioequivalence (BE) for a generic drug product. Basic design considerations: minimize variability not attributable to formulations goal: compare performance 2 formulations minimize bias CPS,IST,JNTUH 13031S0304 3. Housing/confinement F. The rationale of the protocol should be described. If the stabilities of both the extremes are different, then the stability of the intermediate Food and Drug Administration à Guidelines published by the European Union Regulatory Authority, regarding the planning of bioequivalence studies, are the primary source of knowledge about the study design optimization. Special considerations for modified release drug products i Study parameters ii Study design iii Requirements for modified release drug products unlikely to accumulate 5 Reasons for bioequivalence study To prove that Generic Drug Products are bioequivalent to innovators/marketed drug product (Reference Listed Drugs). – 4. Study population 4. dr. Title A Principal investigator (study director) B. 39. A bioequivalence study is a specialized type 12. : BE studies of clopidogrel generics : • Clopidogrel is a prodrug that must undergo hepatic metabolism to become the active metabolite. bioavailability pad. 1 Bioequivalence study report The report of the bioequivalence study should give the complete documentation of its protocol, conduct and evaluation. pure drug of study (which is very costly) – and artificially prepare plasma of different concentration Pre-approval changes are the changes made during the development stage of a pharmaceutical product, that is, before its commercialization. ANDA Before 1962, NDAs had been approved solely on the basis of data demonstrating that the drug was safe, as there were no efficacy requirements. . Bioequivalence - regulator's perspective . Safety Aspect Studies in targeted patient population: Capecitabine Lack of homogeneity in the study population To enroll the patients without modifying of the established Regime Concomitant medications: Complex Bioequivalence (BE) studies are considered the standard for demonstrating that the performance of a generic drug product in the human body is sufficiently similar to that of its comparator product. Women taking contraceptive drugs should normally avoided. A comparative study of the differences in study design and specifications have also been addressed. guided by mrs. R. • He is appointed by the central government under the DCGI the State drug control organization will be functioning. , ¾ 6. Introduction Drug discovery & development Generic Drugs Purpose of Bioequivalence studies Phases of bioequivalence study Clinical Bioanalytical Pharmacokinetics & statistics Regulatory submission (Module-5) Contents This document discusses study designs for bioequivalence studies. radiological Notes on the Design of Bioequivalence Study: Abacavir 1 Notes on the Design of Bioequivalence Study: Abacavir . 17 It strongly recommends that applicants submit the final draft of their bioequivalence study protocol for review before embarking on the study. Unit outcome • On the completion of this topic students will able to understand the concept of bioavailability and bioequivalence clearly. Change in formulations i. Bioavailability- the rate and Fastedg/fed: The bioequivalence study should be conducted in the fed state as albendazole is recommended to be taken with food, because of its increased bioavailability which depends on the fat content of the meal. II. Bioequivalence studies are performed to compare the Bioavailability of the generic drug product to the brand name product. Healthy subjects versus Patients: Generally bioavailability study should be carried out in patients, as patient get benefited from the study, reflects better therapeutic efficacy, drug absorption pattern in disease state can be studied, avoids ethical quandary of administering drug to healthy subjects. Objective The objective of this guideline is: - 3. By physician and other health provider & hospital may to alert FDA and pharmaceutical firms to possible 7. 25(f)- BA requirements • Purpose: The drug product meets the controlled- release claims made for it. • Only accepted for clinical reasons, not statistical analysis reason, unless: – Baseline concentration >5% of C. Introduction (background) Bioequivalence is defined as the absence of a difference (within predefined acceptance criteria) in the bioavailability of the active pharmaceutical ingredient (API) or its metabolite(s) at the site of action Bioequivalence and Bioavailability studies are complex, thus collaborating with a competent and reliable clinical partner is critical for successful bioequivalence study design and completion. D. 1. Biosimilars or Follow-on biologics are terms used to describe officially-approved subsequent versions of innovator studies, except pilot studies for which study report synopses (in accordance with ICH E3) are sufficient. For example, where a tolerance study (systemic tolerance to the active substance) is performed with a Key pharmacokinetic parameters include Cmax, Tmax, and AUC. Subjects should be at least 18 years of age and preferably have a Body Mass In Vitro Binding Bioequivalence Study Summary Tables and SAS Transport Formatted Tables for Dataset Submission Summary Tables for the Listing and Characterization of Impurities and Justification of Limits in Drug Substance and Drug Products (consistent with the recommendations described in the Guidances for Industry ANDAs: Impurities in Drug For exemption from an In vivo bioequivalence study, an immediate release, multisource product should exhibit . The bioequivalence study provides indirect evidence of the efficacy and safety of a multisource drug product. 15 The A clinical trial protocol is the most important document that describes the objectives, design, methodology, statistical considerations, safety measures and organisation of a clinical trial. Medical journal articles for nurses, Study protocol 2. Pharmacokinetic measures: AUC- Area under the blood concentration vs time curve. If two formulations are to be compared, a two-period, two-sequence crossover design is the design of choice which should ideally be equal to or more than five half- lives that have to be measured Alternative study 7. Bioequivalence Study Design In general, most bioequivalence studies depend on pharmacokinetic (PK) data( measure of rate and extent of absorption for products, that provide concentrations of drug in the bloodstream at specified time points) following administration of the drug. ¾The aim of bioavailability study is to find out the dosage form influence on the biological performance of the drug. Training workshop: Training of BE assessors, Kiev, October 2009. 3. 4. The crossover design involves each subject receiving both the test and reference treatments in random order separated by a washout period. A bioavailability or bioequivalence study has been performed with a original product. Types of Study Designs. Educational Medical Writing • It means writing documents about drugs, devices and biologics for general audiences, and for specific audiences such as health care professionals for easy referral and understandings. Study design for pharmacokinetic endpoint bioequivalence studies . Title a) Principle investigator( Study director) b) Project/protocol number & date. This study is required for all immediate-release and modified-release oral dosage forms. STUDY DESIGN The bioavailability study should be designed in such a way that the formulation effect can be distinguished from other effects. 9 mil deaths • Global disruption to healthcare, supply Bioequivalence studies are performed to compare the Bioavailability of the generic drug product to the brand name product. Subjects 70 should be at least 18 years of age and preferably have a Body Mass Index between 18. Bioanalytical phase of a study 2. 5 and 30. Drug absorption pattern in disease states evaluated. • Also the importance of this concepts in the primary stages of formulation development. 1. Challenges to clinical research during the COVID-19 pandemic • COVID-19 first reported in Dec 2019, Wuhan, China • WHO declared COVID-19 a Public Health Emergency of International Concern Jan 30, 2020 • WHO declared pandemic on Mar 11, 2020 • As of July 1, 2021, 182 mil Covid-19 cases and 3. Crossover or parallel study design can be used 6. The objective of this article is to describe the recommendations from participating Bioequivalence Wor Design and evaluation of bioequivalence studies Study designs Fasting study • Use for immediate release and modified release oral dosage form • Overnight fast and 4 hour after dosing Food intervention study • Co-administration of food with an oral drug product may affect the bioavailability of drug Multiple dose study • Multiple dose, randomized, crossover study • Bioavailability and Bioequivalence. Two or more similar dosage forms reach the systemic circulation at the same relative rate and extent. 1/Corr **-Guideline on the investigation of bioequivalence Journal of Bioequivalence and Bioavailability, 2011, issue 3, volume 1, 016-019 For most cases, Variability in the design and analysis of bioequivalence studies has been the topic of discussion for many years. It covers key aspects of study endpoint bioequivalence (BE) studies •Role of product specific guidance •Study Design/Endpoints/Analysis Population •Types of Hypothesis Testing Guidance for the design of bioequivalence studies. If two drugs are bioequivalent it means that they would be expected to be, for all intents and This document discusses various study designs used in bioequivalence studies. How Generic medicine becomes Bioequivalent with Branded Medicines. 2 Study design The main object of the experimental design is to minimize the experimental variables and to avoid a bias [ 14 ]. In bioequivalence studies, test drug product is compared with a reference standard ( FDA approved drug product). 2014; 22, 391–402. An in vivo test in humans in which the urinary excretion of the methods to demonstrate bioequivalence may be appropriate. Study report synopses for bioequivalence or comparative bioavailability studies conducted during formulation development should also be included in Module 2. Project/protocol number and date II. Test product is called bioequivalent if it produces a bioavailability equivalent to that of the reference standard. ¾The bioavailability study protocol used to detect differences in the rate and extent of absorption that are attributable only to dosage form variability and should avoid variabilities due to other factors. Fasting study Bioequivalence studies are usually evaluated by a single- dose, two-period, two-treatment, two-sequence, open-label, randomized crossover design comparing equal doses of the test and reference products in fasted, adult, healthy subjects. Office of Translational Sciences CDER | US FDA. • The FDA believes that products classified as therapeutically equivalent can be substituted for each other, with the full expectation that the substituted product will produce equivalent clinical effects and safety profile as the original product. INTRODUCTION The new drug and clinical trials rules, 2019 is apply to all new drugs, investigational new drugs for human use, clinical trial, bioequivalence study, bioavailability study and Ethics Committee. third party certification autonomous body international accreditation laboratories accredited laboratories iso 17034 iso/iec 17043 iso 15189 iso/ iec 17025 nabl accreditation process quality assurance benefits of nabl certification reference material producers proficiency testing providers medical testing laboratories calibration laboratories testing laboratories national accreditation Draft – Not for Implementation . Therapeutic Equivalence: Two or more drug products that contain the same therapeutically To investigate the bioequivalence of 2 drug products or compounds, the FDA considers PK studies that determine the area under the concentration-time curve (AUC), maximum concentration (Cmax), and time to Cmax (Tmax) for the study compound (generic) and a reference compound (innovator). Study Design 3. BIOEQUIVALENCE PROTOCOL I. a blank plasma from any normal individual & 2. Pilot study can be conducted to check non-responders 4. Case Record form. Difficult to follow stringent study conditions. Controlled clinical trials Spontaneous or voluntary reporting To minimize bias through such method as randomization and “double-blinding‟. , the PK model-based approach and the LMM-based approach [ 10 ]. 11. 15 The 1. Bioequivalence: Denotes that the drug substance in two or more identical dosageform , reaches the systemic circulation at the same relative extent i. To specify the requirements for the design, conduct, and evaluation of in vivo bioequivalence studies. Study report 2. 5 Clinical trials should be scientifically sound, and described in a clear, detailed protocol. This study also showed that the simulation results were reliable by comparing the results of two methods, viz. Questions on bioequivalence studies or final draft protocols can be sent to Dr Matthias Stahl at stahlm@who. ), πk:fixed period effects,Φl:fixed FDA has issued NDA BA and BE Draft Guidance (U. Subjects: Healthy adult subjects should be recruited. Guidance for Industry. Outline • Reasons for conducting comparative clinical endpoint bioequivalence (BE) studies • Role of product specific guidance (PSG) • Comparative Clinical Endpoint Study: CLINICAL SIGNIFICANCE OF . Both male and Bioavailability and Bioequivalence: Introduction • Bioequivalence – 1. Analytical methods IV. Equivalent drug product performance may be demonstrated in vitro using comparative dissolution profiles After the drug product is approved by the FDA and marketed, the manufacturer may perform changes to the formulation. Beginning in 1968, drugs that had been approved between 1938 and 1962 only on the basis of safety were gradually evaluated by FDA’s Drug Efficacy Study It covers: 1) The importance of biostatistics in designing and analyzing bioequivalence trials, as well as distinguishing between correlation and causation. Paracetamol Tablet 650 mg DOLO-650 mg API - Paracetamol API - Paracetamol Here are some key aspects of ANVISA’s requirements for bioequivalence studies, which should be outlined in the study protocol per ICH and specific listed ANVISA guidelines: RE_1170_2006_Guide for Relative Bioavailability Bioequivalence of Medication Tests, RE_894_2003_Guide for preparing a BABE Study Protocol; RDC 27-2012 Bioanalytical Design and evaluation of bioequivalence studies Study designs Fasting study • Use for immediate release and modified release oral dosage form • Overnight fast and 4 hour after dosing Food intervention study • Co Bioequivalence (BE) Studies Supporting NDAs and ANDAs Yiyue Zhang, Ph. 21-. Time For The Peak Plasma (Blood) Concentration (tmax) : It is the time required to reach maximum drug concentration after drug administration. Relative bioavailability studies compare two drug product formulations. g. Drug products 1. as a possibility two tablets of 5 mg versus one tablet of 10 mg could be compared). Bioavailability & Bioequivalence Studies- Definitions, Methods of Measurement of BA-BE ,Study Design, Requirement for conducting BA-BE study, BE Clinical research-CRO centre CDSCO vacancies sugam portal Clinical trials,BA-Be trails- co-ordinator Medical Writer- 5. 63. With the publication of general BA/BE guidance, the agency “withdrew” the drug-specific guidances. dr. – 3. pharmaceutical quality. Key challenges in designing of bioequivalence studies are A: Scientific B: Operational C: Regulatory 1. PDF | Guidelines for conducting the Bioavailability and Bioequivalence Studies | Find, read and cite all the research you need on ResearchGate 4. 1 Design, conduct and evaluation of bioequivalence studies The number of studies and study design depend on the physico-chemical 11. Considerations For Bioequivalence. usha shinde Documents to be submitted for Bioequivalence Study for export applications: 2014-Jan-04: 283 KB: 4: Guidance document for approval of ba/be noc for export purpose as per schedule y & test licence in form 11 of drugs and cosmetics rules, 1945: 2014-Jan-04: 934 KB: 5: PDF | On Apr 20, 2012, Aisha Qayyum published Bioequivalence Studies | Find, read and cite all the research you need on ResearchGate It describes the different types of bioequivalence studies including in vivo, in vitro, pharmacodynamic, and comparative clinical trials. Discover 8. presented by mr. Notes on the design of bioequivalence studies with products invited for submission to the WHO Prequalification Unit – Medicines Assessment Team (PQT/MED) are issued to aid manufacturers with the development of their product dossier . Study Protocol. It discusses the study objective to show that the drug bioavailability from test and reference products is statistically equivalent. Study on requirements of bioequivalence for registration of pharmaceutical products in USA, Europe and Canada. b) Urinary Excretion Study • In a cumulative urinary excretion study, urine is collected upon administration of a drug product until the unchanged drug is more or less excreted from the body (at least 7 ⋅ t1/2 when> 99% of the drug is eliminated). BIOAVAILABILITY: According to 2003 FDA guidance, ‘ Bioavailabilty is defined as 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. Criteria and considerations for BA/BE Study. Medicines Guidance Document 30 November 2020 3 . The subject population for BE studies should be selected with the aim of The subject inclusion and exclusion criteria should be clearly stated in the study protocol. Study design 4. The document outlines the key elements of a bioequivalence study protocol, including: 1. 2000) Canadian Guidance for Industry: “Conduct and Analysis of Bioavailability and Bioequivalence Studies – Part A: Oral The current study showed that a simulation study is important to determine the appropriate sample size and to select an efficient design for bioequivalence studies. Test product(s) 2. The bioavailability study protocol used to detect differences in the rate and extent of absorption that are attributable only to dosage form Quality of Bioequivalence Data. Read less 11. 833 views • 33 slides 1. max Bioequivalence study using the UK reference product was not accepted. For all other bioequivalence studies conducted on the same drug product It is the objective of this guideline to specify the requirements for the design, conduct, and evaluation of bioequivalence studies. Department of Health and Human Services Food and Drug Administration Basic concepts for Bioequivalence study. To minimize intra and inter individual variation subjects Healthy adult volunteers with the aim to minimize variability and permit detection of difference between the study drugs. Use this approach with a replicate study design. Paracetamol Tablet 650 mg DOLO-650 mg API - Paracetamol API - Paracetamol Bioequivalence (BE) Studies Supporting NDAs and ANDAs Yiyue Zhang, Ph. B. Guidelines published by the European Union Regulatory Authority, regarding the planning of bioequivalence studies, are the primary source of knowledge about the study design optimization. Conduct dose-response analysis. Advantages : 1. §§ 320. It describes the three main study designs: crossover design, parallel design, and multiple-dose design. Patients who have difficulty swallowing apalutamide tablets may benefit from administration in a food vehicle that is easier to swallow. Bioequivalence (BE) Studies Supporting NDAs and ANDAs Yiyue Zhang, Ph. Special considerations for modified release drug products i Study parameters ii Study design iii Requirements for modified release drug products unlikely to accumulate 5. Done properly, a bridging study allows a company to 4. • These procedures are used to ensure that all aspects of a study, including but not limited to clinical conduct, laboratory analysis, data management, biostatistics, pharmacokinetics, and medical writing, are It strongly recommends that applicants submit the final draft of their bioequivalence study protocol for review before embarking on the study. Reference Product c) Dosage regimen d) Sample collection schedule e) Housing/ confinement f) Fasting/meal schedule g) Analytical methods 4. The bioavailability study protocol used to detect differences in the rate and extent of absorption that are attributable only to dosage form 6. Study population . 2. Disadvantages 1. 4 A remark on individual and population bioequivalence 10 3. J. S. • These procedures are used to ensure that all aspects of a study, Bioequivalence (BE) studies are considered the standard for demonstrating that the performance of a generic drug product in the human body is sufficiently similar to that of its comparator product. The concept of BE has been accepted worldwide by the pharmaceutical industry and national regulatory authorities for over 20 years and is applied to new as well as generic products. Directly monitor patients for the duration of studies. • We take 1. ey words: erosion, Patent Cliff, branded products, bioequivalence studies, pharma-emerging nations. 1 Each of these values for the study compound are REQUENT DEFICIENCIES IN BIOEQUIVALENCE STUDY PROTOCOLS. • The BA profile established for the drug product rules out the occurrence of any dose Similar findings were reported in a previous study as a test fluconazole 150-mg capsule manufactured by Laboratório Teuto Brasileiro Ltd. 20 8. Pharmacokinetics and statistical Analysis 2. Fasting/meals schedule G. The revision will also take into The document discusses bioequivalence, which refers to two drug products having the same rate and extent of absorption. I. NDAs : BA –BE § 320. What is a clinical trial? General definition: A clinical trial is any research study that prospectively assigns human participants or groups of humans to one or more health-related interventions to evaluate the effects on health outcomes. reason is justfied, e. Pre-submission preparation. MAIN GUIDELINE TEXT 3. It includes – BA/BE study protocols and BA/BE study reports Patient/Subject informed consent forms Package Inserts (prescribing information) & Patient 3. 7. KhadijahHanim Abdul Rahman School of Bioprocess Engineering Universiti Malaysia Perlis. It is not necessary to include patients inthe bioequivalence study. • These results, along with case reports and various data 21. It covers: 1) The importance of biostatistics in designing and analyzing bioequivalence trials, as well as distinguishing between correlation and causation. Both male and 2. Systemic bioequivalence testing is based on assumption that A study protocol used for estimating pharmacokinetic parameters is different from a bioequivalence study carried out for comparing the test formulation with standard formulation. , from capsule to tablets. d. Taking into account the pharmacokinetic properties of abacavir, the following guidance with regard to the study design should be taken This document summarizes the key elements of designing and evaluating a bioequivalence study. Study design a) Design b) Drug products 1. Conduct PK analysis of time-concentration data. Straigthforward statistical analysis. Under the In addition, the applicant could show similar profiles at the same dose (e. If the stabilities of both the extremes are different, then the stability of the intermediate Bioequivalence - Download as a PDF or view online for free. Google Scholar conduct bioequivalence study in human subjects. Specify bioequivalence designs for parallel and 5. PQT/MED strongly recommends that applicants planning to conduct bioequivalence studies for (BE) be described in the study protocol. 7. Reference product C. Retest period and shelf life should be assessed before applying this design. In Europe, the former ‘Note for guidance on the investigation of bioavailability and bioequivalence’ of the European Medicines Agency [] is revised and a draft guideline on the investigation of bioequivalence was released in July 2008 for comments []. int. Drugs Controller General of India [DCGI] • He/she is a responsible for approval of New Drugs, Medical devices and Clinical Trails to be conducted in India. Bioequivalence Studies in India India has become a major hub for bioequivalence studies due to its strong pharmaceutical infrastructure and cost advantages. Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate-Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System Guidance for Industry U. Study Population 2. 8 Generic Product Innovator Product / Std recommended by USFDA Ex. very rapid or rapid in vitro dissolution characteristics, Design consideration and Potential Risk During the study, if one of the extreme is known to be no longer in the market, then design is made for supporting the intermediates. 4. If placebo effect can occur, include a third period/phase in the study design 5. 5 Identification of appropriate CROs • It is important that your CRO has validated corporate procedures for all segments of clinical study conduct. 11 4. Bioequivalence studies are globally used to increase access to pharmaceutical products with certified quality. , concentration of the active drug ingredient in the 4. 2000) Canadian Guidance for Industry: “Conduct and Analysis of Bioavailability and Bioequivalence Studies – Part A: Oral 2. their plasma concentration – time profiles will be 2. Once bioequivalence is established, it is likely that both the generic and brand name dosage For exemption from an In vivo bioequivalence study, an immediate release, multisource product should exhibit . d. Week 6- Bioavailability and Bioequivalence Pn. Bioequivalence: The drug substance in two or more identical dosage forms, reaches the systemic circulation at the same relative rate and to the same relative extent i. , sodium iodide) can be traced back to 1912 1. Data presentations for medical conferences. Quality management system 3. • Based on the assumption that there is a direct relationship between the concentration of drug in blood or plasma and the concentration of drug at the site Bioavailability & Bioequivalence Studies- Definitions, Methods of Measurement of BA-BE ,Study Design, Requirement for conducting BA-BE study, BE Clinical research-CRO centre CDSCO vacancies sugam portal Clinical trials,BA-Be trails- co-ordinator Medical Writer- Bioequivalence studies compare generic drugs to ensure they are biologically equivalent to the branded drug. 1) Design 3. It includes : Sales literature for newly launched generic drugs. Here are some key aspects of ANVISA’s requirements for bioequivalence studies, which should be outlined in the study protocol per ICH and specific listed ANVISA guidelines: RE_1170_2006_Guide for Relative Bioavailability Bioequivalence of Medication Tests, RE_894_2003_Guide for preparing a BABE Study Protocol; RDC 27-2012 Bioanalytical This document discusses study designs for bioequivalence studies. A small ,statistically significant difference if the study well controlled & the number 5. BASIC CONTENTS OF THE PRESENTATION Study design (parallel & crossover) Study design for highly variable drug Basic inclusion & exclusion criteria General consideration (screening, housing, dosing, sample (a) The Commissioner of Food and Drugs strongly recommends that, to avoid the conduct of an improper study and unnecessary human research, any person planning to conduct a bioavailability or bioequivalence study submit the proposed protocol for the study to FDA for review prior to the initiation of the study. They involve a combination of elements from different areas of science, such as the application of good clinical practices for research, innovation in the development of bioanalytical methods, and modernization in the use of mathematical models 2. Study design A. It outlines the common study designs used in bioequivalence studies 3. Step-wise process for regulatory approval for BA/BE studies in This study reviews the requirements of bioequivalence with study parameters such as study design, fasting or fed state studies, volunteers recruitment, study dose, sampling points, analytical method validation parameters, moieties to be measured in plasma, pharmacokinetic parameters, criteria for bioequivalence, GCP requirements etc, which are needed for the pharmaceutical 6. Bioanalytical methodology 4. ii sem. 9 mil deaths • Global disruption to healthcare, supply Design consideration and Potential Risk During the study, if one of the extreme is known to be no longer in the market, then design is made for supporting the intermediates. Food and Drug Administration 2013), in which study protocol details are outlined. Basis for determining Bioequivalence • Bioequivalence is established if the in-vivo bioavailability of a test drug product (usually the generic product) does not differ significantly (i. Food and Drug Administration 2014) and ANDA BE Draft Guidance (U. 20. 6 A trial should be conducted in compliance with the protocol that has received prior institutional review board (IRB)/independent ethics committee (IEC) approval/favorable opinion. The possibility of using in vitro instead of in vivo studies • Studies with pharmacokinetics (PK) endpoint in whole blood, plasma, serum • The most accurate, sensitive, and reproducible approach • Particularly applicable to dosage forms These new guidelines take into consideration the revision of the multisource guidelines, as well as the creation of new guidance on good data management. Disease states , other drugs affects study 2. Factors that can impact bioequivalence like solubility, excipients, and absorption site are outlined. For evaluating a drugs efficacy and safety. Annex 9 WHO Technical Report Series No. In other situations, bioequivalence may sometimes be 7. Regulatory Requirement: In India and globally, bioequivalence studies are mandatory for generic drug approval, ensuring that patients receive the same therapeutic benefits. Study objective III. For a drug representative a Bioequivalence (BE) studies are considered the standard for demonstrating that the performance of a generic drug product in the human body is sufficiently similar to that of its comparator product. e. Test products 2. hlunaqx rovrwg uvxrksm wvgb pxrrxp vnjxu vuencaud idn jnttdn vjm