Related Experiment Video
Updated: May 15, 2026
07:25
In Vitro Methods for Comparing Target Binding and CDC Induction Between Therapeutic Antibodies: Applications in Biosimilarity Analysis
Published on: May 4, 2017
Risk analysis in bioequivalence and biowaiver decisions
Marlies Kubbinga1, Peter Langguth, Dirk Barends
1National Institute of Public Health and the Environment, Bilthoven, the Netherlands.
Biopharmaceutics & Drug Disposition
|January 3, 2013
Summary
This study uses Failure Mode and Effect Analysis (FMEA) to assess regulatory biowaiver guidance. The risk assessment shows current guidelines effectively minimize risks of bioinequivalent drugs.
Area of Science:
- Pharmaceutical Sciences
- Regulatory Science
- Risk Management
Background:
- Biowaivers are crucial for efficient drug product approval.
- Current biowaiver guidance from FDA, EU, and WHO requires risk-based evaluation.
- Ensuring bioequivalence without clinical studies is a key regulatory challenge.
Purpose of the Study:
- To evaluate existing biowaiver guidance documents using a risk-based approach.
- To introduce Failure Mode and Effect Analysis (FMEA) as a tool for biowaiver risk assessment.
- To identify potential future extensions for in vitro comparative tools in biowaiver applications.
Main Methods:
- A risk-based perspective was applied to analyze FDA, EU, and WHO biowaiver guidance.
- Failure Mode and Effect Analysis (FMEA) risk calculation tool was utilized.
- The FMEA tool was employed to assess the implicit risk mitigation in current biowaiver strategies.
Main Results:
- Current biowaiver guidance implicitly reduces the risk of bioinequivalence.
- Risk is managed through decreased incidence, improved detection, and limited severity of issues.
- The FMEA tool revealed opportunities for expanding in vitro comparative methods for biowaivers.
Conclusions:
- Existing regulatory biowaiver frameworks effectively manage risks associated with bioinequivalence.
- FMEA provides a robust method for assessing and enhancing biowaiver risk management.
- Further development of in vitro tools can expand the scope and reliability of biowaivers.
Related Concept Videos
01:13Bioequivalence studies: Biowaivers
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...
01:16Bioequivalence Data: Statistical Interpretation
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...
01:23Types of Biopharmaceutical Studies: Controlled and Non-Controlled Approaches
Biopharmaceutical studies constitute a vital field aiming to enhance drug delivery methods and refine therapeutic approaches, drawing upon diverse interdisciplinary knowledge. In research methodologies, the choice between controlled and non-controlled studies significantly influences the study's reliability and accuracy.
Non-controlled studies, commonly employed for initial exploration, lack a control group, rendering them susceptible to biases and external influences. In contrast, controlled...
Non-controlled studies, commonly employed for initial exploration, lack a control group, rendering them susceptible to biases and external influences. In contrast, controlled...
01:28Drug Products: Biologics, Biosimilars and Interchangeables
Biologics, derived from living sources such as humans, animals, or microorganisms, represent a significant category of pharmaceuticals. These complex molecules, developed through advanced biotechnological methods or purified from natural sources, include essential medical treatments like insulin and growth hormones. The complexity of biologics arises from their large molecular structures and the intricate processes required for their production, making them distinct from conventional...
01:16Bioequivalence: Overview
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,...
01:09Bioequivalence of Drugs: Drugs with Multiple Indications
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 indication due to...