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Bioequivalence Study Design

 Bioequivalence and Bioavailability studies are complex, thus collaborating with a competent and reliable clinical partner is critical for successful study design and completion. 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. We provide unparalleled support for all aspects of bioequivalence and bioavailability studies, including study design, recruitment, clinical conduct, bioanalysis, statistical support, and regulatory guidance. 

What are Generic Drugs and Bioequivalence Studies?

Generic drugs are created with the goal of having the same dosage form, quality, strength, safety, administration route, performance characteristics, and intended use as their reference brand-name drugs. A key component of evaluating generic drug candidates is the assessment of their bioequivalence to the corresponding reference drugs. In addition, bioequivalence studies can also be conducted to assess changes in drug formulation or manufacturing processes that occur during drug development or post-approval.

The term bioequivalence indicates that there is no significant difference in the rate and extent to which an active ingredient or moiety in a pharmaceutical equivalent or alternative becomes available at the site of action when delivered at the same molar dose as a reference drug and under similar conditions. 

Requirements & Considerations for Bioequivalence Study Design

When doing bioequivalence study design, the need to evaluate drug absorption and differentiate between formulations should be considered. A two-way, single-dose, crossover design with randomly assigned sequences is commonly used in bioequivalence studies because it limits the possible interference of patient-specific factors. A long washout period should be planned when using a crossover design.

Other possible study designs include parallel and replicate bioequivalence studies. The selection and recruitment of study participants, as well as the required sample size, should be planned carefully.

Pharmacokinetic Parameters Used to Assess Bioequivalence

This includes maximum (peak) concentration (Cmax), the area under the curve t (AUCt), AUCinf, and the time to reach Cmax (Tmax). Cmax is the maximum observed concentration (most commonly in blood) and is an indicator of the rate with which the drug becomes available at the target site. 

To assess Cmax appropriately, adequate blood sampling time points should be selected. The AUC measures the extent of drug exposure. AUCt is an indicator of the drug exposure to the body until the final sampling time point. In contrast, AUCinf is an indicator of the total drug exposure to the body from administration until drug elimination.

In instances where the Tmax differs between the two compared products, additional data analyses of partial AUCs, clinical studies, or an exposure-response evaluation may be needed to assess the bioequivalence.

Most bioequivalence studies are performed under fasting conditions unless there are concerns about the drug tolerability without food, in which case the study may be conducted under fed conditions. If a pharmacokinetic bioequivalence studies are not feasible because the drug levels cannot be measured or are not relevant, pharmacodynamic bioequivalence studies can be planned.

Extensive Multidisciplinary Team for Bioequivalence Studies

BioPharma’s bioequivalence team includes pharmacokinetic scientists, clinical investigators, clinical operation specialists, bioanalytical scientists, statisticians, and regulatory scientists. Its members are selected among the CRO’s 250-plus multidisciplinary experts, including at least 8 Ph.D. graduates. Our medical team is also supported by Dr. Isabella Szeto and Dr. Artan Markollari, who have served as PIs in numerous clinical trials. Our PIs have more than 50 years of combined experience.

Dr. John Oldenhof

Dr. John Oldenhof

Chief Scientific Officer

 Dr. John Oldenhof has extensive senior management experience in Phase 1 clinical pharmacology, product development, biostatistics, clinical trial data management, and regulatory and scientific affairs.

Dr. Fathi Abuzgaya

Dr. Fathi Abuzgaya

Chief Medical Officer & Principal Investigator

Our chief medical officer (CMO) Dr. Fathi Abuzgaya has over 15 years of experience serving as a Principal Investigator (PI) or sub-investigator for over 100 clinical trials in a wide range of therapeutic areas.

Proficiency With Various Formulations and Routes of Administration

Changes in the formulation of drug candidates may be one of the reasons for the performance of bioequivalence studies. BioPharma has extensive experience backed by our internal experts and external collaborators to assessment various drug formulations. 

Routes of drug delivery image.

Comprehensive Statistical Support

Bioequivalence studies require statistical and data management expertise, both during the planning phases and during the statistical analysis of the findings. Our expert statistician and data management specialists deliver advanced statistical and programming support for client generic drugs development programs. They provide input into the calculation of the study sample size and statistical power, test null hypotheses of non-equivalence, and estimate the 90% confidence intervals (CIs) for the AUCt, AUCinf, and Cmax values. 

The sample size to achieve the desired power and significance level is calculated considering the expected deviation between the test and reference products and the error variance associated with the drug substance bioavailability parameters. The criteria for bioequivalence of two drug products require the 90% confidence interval of the ratio of geometric means of the primary pharmacokinetic (PK) responses (after log-transformation) to be within the bioequivalence limits of 80%–125%.

Efficient Recruitment and Large Database of Study Volunteers

Most bioequivalence studies are conducted in normal healthy volunteers (NHVs) who are at least 18 years old, unless drug-specific factors require the restriction of study participants to a specific population subgroup.

BioPharma Services has established an extensive volunteer database with over 18,000 potential study participants, including male and female NHVs and individuals from special populations. Based on our well-established volunteer database, our recruitment and screening specialists can recruit participants for client bioequivalence studies promptly and efficiently.

 

Uncompromised Regulatory Compliance

At BioPharma Services, our regulatory scientists ensure that bioequivalence studies on generic drug products or in relation to formulation or manufacturing changes comply with all regulatory requirements. Our regulatory team has experience working with numerous regulatory agencies, including the United States Food and Drug Administration (FDA), European Medicines Agency (EMA), Health Canada, United Kingdom MHRA, and ANVISA.

Safe State-of-the-Art Clinical Facilities

BioPharma Services has established two state-of-the-art Phase I clinical centers in Toronto, Canada, and St. Louis, Missouri. They have all the necessary infrastructure for conducting bioequivalence studies to support both generic and hybrid drug filings and 505(b)(2) New Drug Applications

Participant safety is the highest priority of our PIs and staff working in both centers. Our centers’ infrastructure and equipment include dedicated Phase 1 intensive monitoring units, 24-hour monitoring, a telemetric option, a crash cart, a limited number of beds, and a nursing station in the rooms. In addition, our clinical team includes highly qualified and broadly experienced PIs, ER physicians, anesthesiologists, and ALCS-trained staff.

Modern In-House Bioanalytical Capabilities

BioPharma has established an in-house bioanalytical laboratory that can analyze samples from bioequivalence and bioavailability studies with high sensitivity and specificity.

 

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Passing Batch Rate

Led by Dr. Nicki Hughes, who has 20-plus years of experience in bioanalytical research. Our in-house laboratory is equipped with a modern liquid chromatography with tandem mass spectrometry (LC/MS/MS) platform to carry out analyzes in various matrices. We continue to develop novel LC-MS/MS-based assays to meet client-specific bioanalytical needs.

biopharma clinical research toronto office
biopharma st. Louis Illinois clinic front building
Dr. Nicki Hughes

Dr. Nicki Hughes

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