Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Bioequivalence Data: Statistical Interpretation01:16

Bioequivalence Data: Statistical Interpretation

307
The statistical interpretation of bioequivalence data is a significant aspect of pharmaceutical research. Bioequivalence refers to the absence of any significant difference in the rate and extent to which the active ingredient in pharmaceutical products becomes available at the site of drug action when administered at the same molar dose under similar conditions. This helps determine if different drug products have similar absorption rates, ensuring their interchangeability.Statistical...
307
Dosage Regimen: Individualization01:24

Dosage Regimen: Individualization

256
Individualization in dosing regimens is the customization of medication doses for individual patients. Its necessity arises from the goal of maximizing therapeutic benefits while minimizing risks. This approach is pivotal because human responses to drugs can vary widely; what is effective for one person may be inadequate or excessive for another. Interpatient (intersubject) variability refers to differences in drug responses between individuals, while intrapatient (intrasubject) variability...
256
Bioequivalence of Drugs: Drugs with Multiple Indications01:09

Bioequivalence of Drugs: Drugs with Multiple Indications

204
The concept of therapeutic equivalence (TE) in drugs with multiple indications is complex. A generic drug may be therapeutically equivalent to a brand-name product for one specific indication, but this doesn't necessarily mean it's equivalent for all other indications. Evidence of TE in one patient group and bioequivalence shown in healthy volunteers can support—but not confirm—TE for other indications. However, definitive proof requires individual clinical studies for each...
204
Bioequivalence studies: Biowaivers01:13

Bioequivalence studies: Biowaivers

367
In certain scenarios, in vitro dissolution tests can replace in vivo bioequivalence studies. This is particularly true when a drug product, though available in varying strengths, maintains proportional similarity in its active and inactive ingredients. In such cases, the need for in vivo bioequivalence studies for lower strength variants may be waived, provided dissolution tests and in vivo studies on the highest strength yield satisfactory results.Bioequivalence can be indicated through...
367
Dosage Regimens: Partial Pharmacokinetic Parameters01:01

Dosage Regimens: Partial Pharmacokinetic Parameters

246
It is not uncommon for complete drug pharmacokinetic profiles to remain elusive in pharmacokinetics. This necessitates certain educated assumptions by pharmacokineticists to determine appropriate dosage regimens without comprehensive pharmacokinetic data from animal or human studies. One prevalent assumption is setting the bioavailability factor, denoted as F, to 1 or 100%. This assumption caters to the scenario where a drug doesn't achieve full systemic absorption, resulting in the patient...
246
Bioequivalence: Overview01:16

Bioequivalence: Overview

2.2K
Pharmaceutical equivalents, by definition, are drug products with the same active ingredient in the same quantities, encapsulated in identical dosage forms, and intended for the same administration routes. These pharmaceutical equivalents are deemed bioequivalent if the bioavailability of the active entity in the drug preparations is similar. Moreover, pharmaceutical equivalents demonstrating bioequivalence are also regarded as therapeutically equivalent. This means that when used as directed,...
2.2K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Effects of an antiperspirant with emollients on foot-sweat accumulation and blister formation while walking in the heat.

Journal of the American Academy of Dermatology·1995
Same author

The achievement of isoeffective bronchial mucosal dose during endobronchial brachytherapy.

International journal of radiation oncology, biology, physics·1995
Same author

Entry of microbes into the host: using M cells to break the mucosal barrier.

Current opinion in immunology·1995
Same author

Derivation of the optimum dose per fraction from the linear quadratic model.

The British journal of radiology·1995
Same author

On the nature of the mutation in the nude rat.

Trends in genetics : TIG·1995
Same author

Radiotherapy and chemotherapy for inoperable non-small cell lung cancer.

Postgraduate medical journal·1995

Related Experiment Video

Updated: Mar 13, 2026

In Vitro Methods for Comparing Target Binding and CDC Induction Between Therapeutic Antibodies: Applications in Biosimilarity Analysis
07:25

In Vitro Methods for Comparing Target Binding and CDC Induction Between Therapeutic Antibodies: Applications in Biosimilarity Analysis

Published on: May 4, 2017

18.3K

Between-Batch Pharmacokinetic Variability Inflates Type I Error Rate in Conventional Bioequivalence Trials: A

E Burmeister Getz1, K J Carroll2, J Mielke3

  • 1Oriel Therapeutics, Inc, Berkeley, California, USA.

Clinical Pharmacology and Therapeutics
|October 12, 2016
PubMed
Summary

Manufacturing variations in Advair Diskus cause significant pharmacokinetic differences, leading to bio-inequivalence between batches. Current FDA bioequivalence testing methods are unreliable, risking false conclusions of product similarity.

More Related Videos

Enhanced Reproducibility and Precision of High-Throughput Quantification of Bacterial Growth Data Using a Microplate Reader
09:15

Enhanced Reproducibility and Precision of High-Throughput Quantification of Bacterial Growth Data Using a Microplate Reader

Published on: July 27, 2022

2.8K
Improving IV Insulin Administration in a Community Hospital
12:08

Improving IV Insulin Administration in a Community Hospital

Published on: June 11, 2012

19.5K

Related Experiment Videos

Last Updated: Mar 13, 2026

In Vitro Methods for Comparing Target Binding and CDC Induction Between Therapeutic Antibodies: Applications in Biosimilarity Analysis
07:25

In Vitro Methods for Comparing Target Binding and CDC Induction Between Therapeutic Antibodies: Applications in Biosimilarity Analysis

Published on: May 4, 2017

18.3K
Enhanced Reproducibility and Precision of High-Throughput Quantification of Bacterial Growth Data Using a Microplate Reader
09:15

Enhanced Reproducibility and Precision of High-Throughput Quantification of Bacterial Growth Data Using a Microplate Reader

Published on: July 27, 2022

2.8K
Improving IV Insulin Administration in a Community Hospital
12:08

Improving IV Insulin Administration in a Community Hospital

Published on: June 11, 2012

19.5K

Area of Science:

  • Pharmaceutical Sciences
  • Pharmacokinetics
  • Regulatory Science

Background:

  • Previous studies indicated pharmacokinetic differences between manufacturing batches of Advair Diskus 100/50.
  • These differences were substantial enough to suggest potential bio-inequivalence between batches.

Purpose of the Study:

  • To independently confirm pharmacokinetic bio-inequivalence among Advair Diskus 100/50 batches.
  • To quantify variance components and assess their impact on regulatory bioequivalence testing.
  • To evaluate the type I error rate of the U.S. Food and Drug Administration's (FDA) recommended two-way crossover design.

Main Methods:

  • Pharmacokinetic analysis of Advair Diskus 100/50 manufacturing batches.
  • Statistical modeling to estimate residual and between-batch variance components.
  • Simulation or analysis of type I error rates under different variability scenarios.

Main Results:

  • Independent confirmation of pharmacokinetic bio-inequivalence between Advair Diskus 100/50 batches.
  • Quantification of significant between-batch variance components.
  • Demonstration that the conventional two-way crossover design inflates the type I error rate to approximately 25% when between-batch variability is present.

Conclusions:

  • The FDA's current two-way crossover design for bioequivalence testing is inadequate when substantial between-batch pharmacokinetic variability exists.
  • The design leads to an artificially narrow confidence interval and a significantly increased risk of false bioequivalence conclusions.
  • Regulatory standards for acceptable consumer risk (5%) are not met, highlighting a critical issue in pharmaceutical quality control and regulatory assessment.