Ready-to-Use Bioequivalence Study Protocols for High-Value Generics Approaching Patent Expiry (2026–2030)
This catalogue features high-value reference listed drugs (RLDs) that are set to experience patent expiration between 2026 and 2030. The catalogue offers ready-to-use bioequivalence study protocols that are designed to help researchers and manufacturers develop generic alternatives.
The bioequivalence study protocols align with the latest FDA and EMA regulatory guidance, enabling faster timelines for generics ahead of patent expiry for the branded drugs. Each product in our catalogue is based on patent expiry timing, commercial market potential, and practical bioequivalence study feasibility.
Our Bioequivalence (BE) study protocols fully comply with the latest FDA Product-Specific Guidances (PSGs) and EMA BE guidelines. They incorporate essential regulatory requirements to accelerate Abbreviated New Drug Application (ANDA) submissions before brand exclusivity expires. Each protocol provides a robust basis for pharmacokinetics (PKs), including washout periods based on half-life to minimize the impact of the carryover. We utilize literature-supported estimates of intra-subject Coefficient of Variation (CV)% for power calculations, incorporating a standard 20% dropout buffer to ensure studies achieve high statistical confidence. Additionally, the sampling schedule incorporates sufficient sampling points around Tmax, consistent with FDA and EMA bioequivalence guidance, to support accurate determination of Cmax.
Our submission-ready bioequivalence study protocols include fully validated LC-MS/MS bioanalytical specifications that follow FDA/ICH M10 Bioanalytical Method Validation Guidelines (November 2022/January 2023) under GLP principles. These specifications ensure Lower Limit of Quantification (LLOQ) alignment to expected concentrations for precise quantification. Our protocols also include ICH M10-compliant sample handling procedures, mixed-effects ANOVA statistical models, and comprehensive safety monitoring frameworks.
Browse the catalogue below to explore upcoming generic development opportunities.
What’s Included?
Every bioequivalence study protocol is a complete, submission-ready document
Study Design
The BE protocols provide submission-ready study designs aligned with FDA and EMA guidance detailing a complete study approach, including objectives, endpoints, washout periods, blood sampling schedules, participant confinement, dosing procedures and other important considerations customised for each molecule to ensure regulatory compliance and successful study execution. In addition, participant safety, dietary/activity restrictions and other study management measures are included to address all key aspects of the study.
Inc/Exc Criteria
The BE protocols include detailed guidelines for participant selection and safety management. Each protocol defines participant eligibility criteria. Exclusion criteria cover medical conditions, infectious disease screening, drug allergies or hypersensitivity, recent medication use, and any condition affecting study participation. The protocols include screen failure, withdrawal, continuous safety monitoring, adverse event management, and ethical compliance measures meeting FDA and EMA requirements.
Statistical Procedures
The BE protocols outline regulatory-compliant statistical approaches in accordance with FDA and EMA bioequivalence guidance. Pharmacokinetic evaluations include key parameters such as peak concentration (Cmax), area under the concentration–time curve (AUC0–t and AUC0–∞), time to peak concentration (Tmax), and elimination half-life (t½). The protocols include sample size determination to ensure adequate statistical power, along with requirements for sample handling and storage and compliance with bioanalytical method standards.
Featured Molecules
Explore our library of ready-to-use bioequivalence study protocols for generics approaching patent expiry
Brivaracetam is an anti-seizure medication, used to treat partial-onset seizures in people with Epilepsy. It works by binding to a protein in the brain that affects the release of certain chemicals called neurotransmitters, which helps calm overactive nerve signals that cause seizures.
Ivabradine Hydrochloride treats chronic heart failure and stable angina. It works by selectively slowing down the heart rate without affecting blood pressure or how strongly the heart contracts, allowing the heart to pump more efficiently.
Emtricitabine/Tenofovir is a combination antiviral medication, used to treat and prevent HIV-1 infection. It works by blocking HIV’s reverse transcriptase enzyme, preventing the virus from copying its genetic material into human cells.
Sacubitril/Valsartan is a combination heart failure medication, used to reduce the risk of hospitalization and death in people with heart failure. It works in two ways: one component increases beneficial peptides that relax blood vessels, while the other blocks hormones that strain the heart.
Lurasidone Hydrochloride is an antipsychotic medication, used to treat schizophrenia and bipolar depression. It works by balancing dopamine and serotonin levels in the brain, which helps regulate mood, behaviors, and thoughts.
Lenvatinib Mesylate is a targeted cancer therapy, used to treat advanced thyroid, kidney, liver, and endometrial cancers. It works by blocking multiple proteins that promote tumor growth and blood vessel formation, helping to slow or stop cancer spread.
Tapentadol Hydrochloride is a pain medication used to manage moderate to severe acute and chronic pain. It works through dual action, that is, binding to opioid receptors for pain relief and increasing norepinephrine levels in the brain to enhance pain control.
Fostamatinib Disodium is an immune system medication that is used to treat chronic immune thrombocytopenia (ITP) when other treatments fail. It works by blocking an enzyme in immune cells that causes antibody production and platelet destruction, helping to increase platelet counts.
Tofacitinib Citrate is an immune system medication used to treat rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, and other inflammatory conditions. It works by blocking specific enzymes that trigger inflammation, reducing immune system overactivity and joint damage.
Rivaroxaban is a blood thinner medication, used to prevent and treat blood clots and reduce stroke risk in people with atrial fibrillation. It works by directly blocking a key clotting protein called factor Xa, preventing blood clot formation without affecting platelets.
Why These Protocols
Developed Using Standard BE Scientific Frameworks
Built around established BE principles — dose selection, PK endpoints, sampling windows, and analytical considerations aligned with current scientific expectations.
Written and Reviewed by BE Practitioners
Drafted by medical writers experienced in pharmacokinetics and reviewed by specialists who routinely design and assess BE studies across multiple therapeutic areas.
Includes All Fundamental Components for BE Study Design
Provides complete study design, rationale, PK plan, sample collection schedule, statistical methodology, and safety framework — ready for immediate operational use.
Frequently Asked Questions (FAQs)
Why Bioequivalence Studies Are Needed?
Bioequivalence studies are required by regulatory agencies such as the FDA and EMA to support the approval of generic medicines through abbreviated regulatory pathways. Bioequivalence studies provide the scientific foundation for generic drug approval by demonstrating that test formulations achieve comparable systemic exposure to reference products. This approach addresses critical needs: ensuring therapeutic interchangeability and patient safety by controlling formulation-dependent variability, streamlining regulatory review through pharmacokinetic parameters (AUC, Cmax), and reducing development costs by 70-90%, thereby expanding access to affordable medications while maintaining rigorous quality standards aligned with FDA and EMA guidance.
How to Select Molecules: Market Factors in Generic Development
Selecting molecules for bioequivalence studies involves balancing scientific feasibility with commercial opportunity:
- Patent and exclusivity timing: Molecules with clearer patent landscapes and imminent expiration dates are typically more attractive than those with complex overlapping protections.
- Market potential: The commercial value of a molecule depends on its current sales performance, the size of the patient population it serves, and whether demand is stable or growing within its therapeutic category.
- Competitive landscape: Understanding how many other generic manufacturers are likely to enter the market helps assess profitability. Markets with fewer expected competitors generally offer better financial prospects.
- Technical feasibility: Some formulations are inherently more complex to develop than others. Simpler dosage forms with well-established bioequivalence pathways reduce development time and costs compared to specialized formulations.
- Regulatory considerations: Molecules with clear regulatory guidelines and predictable approval requirements present lower development risks than those requiring novel or complex study designs.
Our protocols support this process by providing regulatory-compliant study designs that streamline development timelines for commercially promising molecules.
How to Conduct Bioequivalence Studies?
Conducting bioequivalence studies requires adherence to standardized regulatory protocols established by agencies like the FDA and EMA. These studies typically employ crossover designs in healthy volunteers to compare pharmacokinetic profiles between test and reference products.
Study Design
The standard approach uses a randomized, two-period crossover design with adequate washout periods between doses. Studies are conducted under fasting conditions as baseline, with fed-state assessments added when food effects are clinically relevant. Sample sizes are determined based on expected variability to ensure adequate statistical power for regulatory conclusions.
Products and Participants
The reference product is the approved innovator formulation from the target market, while the test product represents commercial-scale generic manufacturing. Studies generally enroll healthy adult volunteers meeting specific demographic and physiological criteria, with standardized conditions maintained throughout to minimize variability.
Pharmacokinetic Assessment
Blood sampling schedules capture complete concentration-time profiles, with key parameters measuring both the extent and rate of drug absorption. Validated bioanalytical methods quantify drug concentrations, focusing on parent compound or clinically relevant forms.
Statistical Evaluation
Bioequivalence is established when the confidence interval for the ratio of geometric means between test and reference products falls within predefined acceptance criteria. These criteria may be adjusted based on drug-specific characteristics such as variability or therapeutic index.
Our protocols incorporate these methodological principles to deliver comprehensive, submission-ready study designs aligned with current regulatory guidance for efficient bioequivalence assessment.
How long does a typical Bioequivalence (BE) study take to complete?
The timeline for executing bioequivalence studies can vary depending on the study’s complexity. However, most studies typically take approximately 6 months to complete. This timeframe includes participant recruitment, conducting the study, analyzing samples, and preparing the final report. In some cases, researchers can complete fast-tracked studies more quickly to support urgent regulatory submissions.
What’s the difference between fasting and fed studies?
In fasting studies, participants must abstain from all food and beverages for a specified period before taking the medication. This approach assesses how the drug is absorbed in the complete absence of food. In contrast, fed studies involve administering the medication after participants consume a standardized meal, allowing researchers to examine the drug’s absorption in the presence of food. The decision on which study type to conduct is influenced by the typical use of the medication in real-world scenarios and the guidelines set forth by regulatory agencies. In some cases, pharmaceutical companies may need to perform both fasting and fed studies to gain a comprehensive understanding of how food impacts the drug’s absorption and overall effectiveness.
How many participants do researchers typically include in a bioequivalence study?
Bioequivalence studies usually involve 24 to 36 healthy volunteers, although this may vary based on the drug’s variability and regulatory guidelines. Researchers calculate the sample size using statistical methods to ensure the study has enough power to reliably demonstrate equivalence between the generic drug and the reference product. This careful planning is essential for detecting any meaningful differences or confirming therapeutic equivalence.
Can researchers conduct bioequivalence studies for all drug types?
Most oral solid dosage forms can be used in traditional bioequivalence studies. However, some complex drug products may require different approaches. For instance, modified-release formulations, drugs with a narrow therapeutic index, and specific topical or inhaled products may need specialized study designs or additional testing.
What regulatory guidelines should I follow?
The approach to bioequivalence studies largely depends on your target market. Regulatory bodies such as the FDA (U.S. Food and Drug Administration), EMA (European Medicines Agency), and WHO (World Health Organization) each have their own guidelines for bioequivalence, which can vary by region. If you are considering submissions in multiple markets, it’s important to familiarize yourself with these differences early on. This knowledge can help you design a study that efficiently meets the regulatory requirements of various regions.
What are the acceptance criteria for bioequivalence?
The FDA bioequivalence acceptance criterion requires that the 90% confidence interval (CI) for the ratio of geometric means of both AUC (area under the curve) and Cmax (maximum concentration) between test and reference products must fall completely within 80.00 -125.00%.
For different drug classes:
- Standard drugs: 80.00 -125.00% for both AUC and Cmax
- Narrow Therapeutic Index (NTI) drugs: Scaled limits of 90.00 -111.11% based on reference variability
- Highly Variable Drugs (HVDs): Reference-scaled average bioequivalence (RSABE) with expanded limits up to 69.84 -143.19% for Cmax only (AUC remains 80 -125%)
How should I prepare before starting a BE study?
Before initiating a bioequivalence study, it is important to ensure that your drug formulation is adequately characterized and supported by stability data. You should also have a clear plan for bioanalytical method development or validation, aligned with regulatory expectations. A well-defined understanding of your target regulatory markets (e.g., US FDA, EMA) is essential, as this will influence study design and submission requirements. In addition, access to a well-characterized reference product and an understanding of its pharmacokinetic variability are critical for appropriate study planning and sample size determination. Early engagement with experienced development and clinical research partners can further help identify potential risks, address gaps, and streamline the overall study strategy.
Why are bioequivalence studies important for patient safety?
Bioequivalence studies are essential for patient safety because they demonstrate that a generic medicine delivers the same amount of active ingredient into the body, at the same rate and extent, as the corresponding brand-name product. By confirming comparable pharmacokinetic performance, these studies help ensure that patients can safely switch between the reference and generic products without changes in therapeutic effectiveness or safety. This regulatory requirement supports consistent clinical outcomes, maintains treatment continuity, and reinforces confidence in the quality and reliability of generic medicines.
When do developers conduct a bioequivalence study during drug development?
Researchers typically conduct bioequivalence studies in the later stages of generic drug development, after finalizing the formulation and manufacturing process and before regulatory submission. They are a critical requirement for demonstrating therapeutic equivalence to the reference product, allowing regulatory authorities to rely on pharmacokinetic data rather than requiring large-scale clinical efficacy trials. This approach supports timely approval while maintaining rigorous standards for safety and efficacy.
Can bioequivalence studies reduce development time and costs?
Yes. Bioequivalence studies compare drug exposure rather than clinical outcomes. This approach reduces development timelines and costs compared with full clinical efficacy trials. It still meets strict regulatory standards for safety and effectiveness.
What happens if a bioequivalence study fails?
If a study does not meet acceptance criteria, the results help identify potential issues such as formulation differences or variability in absorption. Sponsors can then refine the formulation or study design and repeat the study with greater confidence.
How do regulatory agencies review bioequivalence study results?
Regulatory authorities carefully evaluate the study design, data quality, statistical analysis, and adherence to guidelines. Well-planned studies with robust documentation can streamline review timelines and reduce follow-up questions from regulators.
Are bioequivalence studies conducted in healthy volunteers or patients?
Researchers conduct most bioequivalence studies in healthy volunteers to reduce variability and enable clear comparisons. However, certain cases, such as oncology or highly potent drugs, require patient-based studies. In these cases, the regulatory bodies, like the U.S. Food and Drug Administration (FDA) or the European Medicines Agency (EMA), provide specific guidance for designing and executing the studies using the relevant patient population.
Can one bioequivalence study support approvals in multiple countries?
A single bioequivalence (BE) study can support approvals in multiple countries when it follows harmonized standards, such as ICH guidelines. Regulatory authorities in the EU (EMA), Canada (Health Canada), Australia, and other regions generally accept ICH-compliant studies. These studies typically apply shared bioequivalence acceptance criteria, including confidence intervals within the 80–125% range. However, the PMDA in Japan considers additional criteria, such as dissolution rates for borderline cases. In Brazil (ANVISA) and Mexico, there are specific requirements, including the necessity for local reference products or particular reporting standards, which limit universal acceptance of BE studies.
What role does quality control play in a successful BE study?
Quality control is fundamental to a successful bioequivalence study and ensures reliable, accurate, and regulatory-acceptable data. Adherence to Good Clinical Practice (GCP), Good Laboratory Practice (GLP), and regulatory guidelines helps minimize variability and protect data integrity. These controls ensure study results accurately reflect the pharmacokinetic performance of the test and reference products. Effective quality control supports confident regulatory review, approval, and participant safety.
How do experienced CROs add value beyond study execution?
Experienced contract research organizations (CROs) add value beyond study execution by providing strategic guidance throughout the development lifecycle. In addition to conducting studies in compliance with regulatory standards, they support optimized study design, informed sample size determination, and alignment with region-specific regulatory expectations. Their expertise helps identify potential risks early, address formulation or analytical challenges, and streamline timelines through proactive planning. By integrating scientific, operational, and regulatory insights, experienced CROs help sponsors make informed decisions, improve study efficiency, and ensure the overall quality and reliability of regulatory submissions.
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