BA BE Services

BA/BE Studies in Patients:

Conclusion:

Bioavailability and bioequivalence services in patients are essential for evaluating the pharmacokinetics of drugs in real-world clinical settings where disease pathology, concurrent medications, and altered metabolism may influence drug behaviour.

These studies ensure that drugs are safe, effective, and meet regulatory standards for specific patient populations, particularly when healthy volunteer studies are not sufficient.

BA/BE Studies in Special Populations:

Although BA/BE studies are typically conducted in healthy subjects, specific studies may involve special populations (e.g., elderly, paediatric, or renal-impaired populations) if required by the regulatory agency to further validate bioequivalence.

Drug Interaction BA/BE Studies:

Drug interaction studies are critical investigations designed to understand how different substances, such as medications or supplements, affect each other's pharmacokinetics and pharmacodynamics when administered together.

Standalone Bioanalytical and Clinical Studies

Although conduct of all phases of a clinical study at one site or organization establishes the ownership towards study conduct and projects ease of operations and supports proper coordination between sponsor and CRO, the conduct of standalone Clinical phase and Bioanalytical phase of the considerably difficult or challenging clinical studies are also being accepted at Indivirtus Global CRO Pvt. Ltd.

Female-alone and healthy human and Patient based Studies

Specific studies wherein drug requires evaluation with involvement of only female volunteers, whether it is healthy or patient-based study, Indivirtus Global CRO Pvt. Ltd. Accepts all such studies to conduct as per requirement of regulatory compliances and accomplishes it with grace.

Facility Audits and pre-regulatory inspection audits

Our experienced scientists also support sponsor or CRO assigned BA/BE setup audits and online monitoring of different phases of clinical study conduct along with review of all phase s of complete clinical study and reports before regulatory submission.

Services to help in resolving regulatory queries

We also provide extensive support to resolve regulatory queries and prepare investigational report and responses to regulatory queries. We do have thorough experience of resolving major and critical regulatory queries in association with operations and sponsors and setting up required CAPA to prevent recurrence of similar queries for future projects.

Pharmacokinetic and Statistical Analysis and Reporting Services

We also provide our services for Pharmacokinetic and Statistical data evaluations for BA/BE studies and provide report preparation facility for regulatory submissions.

Stages of Study Design and Conduct

Study Designs

Bioavailability (BA) Studies:

• Bioavailability is referred to as the extent and rate to which the active drug ingredient or active moiety from the drug product is absorbed and becomes available at the site of drug action. The relative bioavailability in terms of the rate and extent of drug absorption is considered predictive of clinical outcomes.

Bioequivalence (BE) Studies:

• Bioequivalence (relative bioavailability), a comparative bioavailability study of the drug product under investigation is predictive of clinical outcomes (i.e., safety and efficacy) of the drug product in clinical trials.

Single-Dose BE Studies:

• Conducting studies to compare the rate and extent of absorption of a generic drug to a reference (branded) drug.

Multiple-Dose BE Studies:

• Testing the bioequivalence of a drug after multiple doses, which may be required for drugs with complex absorption characteristics or modified-release formulations. “Multiple” indicates that each subject receives multiple doses of the study drug. The studies include ascending dose or dose escalation studies and steady state studies. “Ascending” indicates that the amount of drug increases for each new cohort of subjects (i.e., the dose level ascends as the study goes on).

Steady State BE Studies

• A multiple-dose study can be called as Steady state study, if the dose regimen allows drug concentrations built-up to reach the steady state conditions. Multiple Ascending Dose studies are intended to fully characterize the pharmacokinetics of a drug and its metabolites at steady state, investigate a drug’s accumulation potential, explore its dose proportionality, and determine the Maximum Tolerated Dose (MTD).

Crossover Designs:

• Comparative bioavailability or bioequivalence studies, in which two or more formulations of the same drug are compared, are usually designed as crossover studies. a crossover study or crossover trial is a longitudinal study in which subjects receive a sequence of different treatments.

Parallel Design:

• A parallel study is a type of clinical study where two groups of treatments, A and B, are given so that one group receives only A while another group receives only B.

Study Conduct:

Conduct of each study adheres to following steps

Study Design and Protocol Development:

• The starting point for a good study is developing a good research objective and applicable study design. Hence, it is important to write a good protocol to follow. A protocol is the core document that describes the objectives, design, methodology, statistical considerations, and organisation of a clinical trial.

Subject Recruitment and Screening:

• Recruiting healthy volunteers for BA/BE studies, often focusing on individuals who meet strict inclusion and exclusion criteria.
• Conducting comprehensive screening to ensure that subjects are healthy, with no physiological conditions that could interfere with the study results.

Clinical Conduct of the Study:

Dosing and Drug Administration:

• Administering the test and reference formulations to subjects under controlled conditions, either with or without food, depending on the study design.
• Allowing sufficient time between dosing periods in a crossover study to ensure the complete elimination of the drug from the body.

Bioanalytical Conduct of the Study:

Analytical Method Development and Validation:

• Developing and validating bioanalytical methods (e.g., liquid chromatography–mass spectrometry (LC-MS/MS)) to accurately quantify drug concentrations in biological samples (e.g., plasma, serum, or urine).
• Ensuring that these methods comply with international bioanalytical method validation guidelines.

Study Sample Analysis:

• Application of Validated bioanalytical method for quantification of analyte of interest in biological matrix samples collected during clinical phase of the study. Analysed data is being used for pharmacokinetic and statistical evaluations.

Data Management and Statistical Analysis:

Data Management:

• Collecting pharmacokinetic data, ensuring data integrity, and using electronic data capture (EDC) systems to manage the data efficiently.

Statistical Analysis:

• Performing statistical analysis to compare the test and reference formulations based on PK parameters such as Cmax, Tmax, and AUC.
• BE Criteria: Ensuring that the 90% confidence intervals for the ratio of the test to reference drug’s PK parameters fall within the accepted bioequivalence range (typically 80%–125% for Cmax and AUC).

Regulatory Compliance and Reporting:

• Ensuring full compliance with global regulatory requirements for BA and BE studies, including guidelines from the FDA, EMA, and other regulatory bodies.
• Preparing regulatory reports (e.g., Clinical Study Reports (CSRs)) that summarize the study results, including PK data, safety data, and statistical analysis.
• Submitting the study results to regulatory authorities for review and approval as part of a New Drug Application (NDA), Abbreviated New Drug Application (ANDA), or Marketing Authorization Application (MAA).

 Project Management and Oversight:

• Providing project management services to ensure that the BA/BE study is conducted according to the timeline and budget, while meeting all regulatory and ethical standards.
• Regularly communicating with sponsors and regulatory agencies to keep stakeholders informed of study progress and outcomes.

Pharmacokinetic (PK) Sampling and Analysis:

• Collecting blood or plasma samples at predefined time points post-dose to measure drug concentrations.

Pharmacokinetic Analysis: Using PK analysis to calculate key parameters, such as:

• Cmax (Maximum Concentration): The peak concentration of the drug in the bloodstream.
• Tmax (Time to Reach Cmax): The time it takes to reach peak concentration.
• AUC (Area Under the Curve): The total drug exposure over time.

Bioequivalence Analysis:

• Comparing the PK parameters of the test and reference formulations to assess bioequivalence.

Safety Monitoring:

• Continuous monitoring of healthy subjects for adverse events (AEs) and serious adverse events (SAEs) during the trial, ensuring their safety throughout the study.
• Conducting regular physical exams, vital sign assessments, and laboratory testing (e.g., blood and urine tests) to ensure subject safety.