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Bioequivalence studies: Biowaivers

Bioequivalence studies: Biowaivers

Body: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...

Bioequivalence of Drugs: Drugs with Multiple Indications

Bioequivalence 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...

Pharmaceutical Alternatives: Stability-Related Therapeutic Nonequivalence

Pharmaceutical Alternatives: Stability-Related Therapeutic Nonequivalence

Generic intravenous (IV) drugs are considered bioequivalent to their branded counterparts due to their 100% bioavailability upon administration. However, variations in stability among different drug products can significantly influence their therapeutic performance, even if they are pharmaceutically equivalent.Cefuroxime, a prophylactic antimicrobial, is often used as a single-dose IV injection for patients undergoing coronary artery bypass grafting surgery. A 3 g dose typically provides...

Bioequivalence: Overview

Bioequivalence: 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,...

Bioequivalence Data: Statistical Interpretation

Bioequivalence Data: Statistical Interpretation

Body: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...

Bioavailability: Influencing Factors

Bioavailability: Influencing Factors

Bioavailability refers to the extent and rate at which a drug reaches systemic circulation in its active form. Extent refers to the amount of the drug that makes it into circulation, while rate is the speed at which it enters circulation. It is influenced by several factors critical for optimizing drug formulations, dosing regimens, and therapeutic outcomes.Physicochemical properties of drugs and formulationsThe solubility, stability, and dissolution rate of a drug significantly impact its...

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Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation

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Increased Patient's Risk Associated with the Canadian Bioequivalence Guidance Due to Outlier Removal.

Anders Fuglsang¹

¹, Beckersvej 13, Vejle Ø, Denmark. a.fuglsang@ymail.com.

Therapeutic Innovation & Regulatory Science

|October 31, 2021

Summary

Outlier removal in bioequivalence studies may inflate the type I error rate (patient

Keywords:

Bioequivalence Biosimilars Canada Patient’s risk Residuals

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

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Published on: May 4, 2017

Area of Science:

Pharmacokinetics and Pharmaceutical Sciences
Biostatistics
Regulatory Science

Background:

Canadian bioequivalence guidelines permit outlier exclusion based on studentized residuals.
These guidelines mandate maintaining type I errors (patient's risk) at 5%.

Purpose of the Study:

To investigate if outlier removal procedures inflate type I errors when using a 5% alpha level for confidence interval construction.
To assess the impact of outlier identification on the reliability of bioequivalence assessments.

Main Methods:

Numerical simulations were employed to model the effects of outlier removal.
The study analyzed the type I error rates under different scenarios.

Main Results:

Patient's risk can exceed the 5% threshold with traditional 90% confidence intervals.
Simulations showed type I errors slightly above 7%, indicating potential inflation.
Sponsors may need to avoid outlier removal or adjust alpha levels to preserve the 5% patient's risk.

Conclusions:

This study highlights a potential inflation of type I errors in bioequivalence assessments under Canadian guidelines.
The findings have implications for patient safety in Canada and potentially the USA due to drug importation policies.
Awareness of this issue is crucial for regulatory bodies and pharmaceutical sponsors to ensure accurate bioequivalence determinations.