Guest Column | May 16, 2024

New FDA Draft Guidance: Data Integrity For In Vivo Bioavailability And Bioequivalence Studies

By Md. Saddam Nawaz, ACI HealthCare Ltd.

FDA headquarter iStock-1213293784

In response to shifting pharmaceutical research and regulatory standards, the FDA released a draft guidance titled Data Integrity for In Vivo Bioavailability and Bioequivalence Studies. This guidance emphasizes the crucial role of maintaining data integrity throughout study life cycles and provides extensive recommendations for applicants and testing site management. Tailored for various drug application submissions, including INDs, NDAs, ANDAs, and BLAs, it extends to amendments, supplements, and bioanalytical portions of nonclinical studies. Encouraging broad adoption, the guidance emphasizes the necessity of accurate, complete, and reliable data submission. By outlining recommendations for stakeholders and advocating for a culture of data integrity,1 the FDA aims to enhance transparency, reliability, and compliance in BA/BE studies. This article explores the guidance's key considerations, offering insights into its implications for pharmaceutical entities, contract research organizations, and regulatory professionals. By embracing these recommendations, stakeholders can bolster the integrity and credibility of pharmaceutical research and development.

Background Of BA And BE Studies

Bioavailability and bioequivalence (BA/BE) studies are integral to pharmaceutical research for assessing drug products' pharmacokinetic properties and therapeutic equivalence. Bioavailability gauges how swiftly and effectively a drug enters systemic circulation and reaches its intended site of action, influenced by factors like formulation and administration route. Conversely, bioequivalence compares a test drug's bioavailability to that of a reference product, typically using metrics like AUC and Cmax. In recent years, the complexity of drug products and BA/BE studies has grown, with more firms participating. Regardless of whether applicants conduct studies internally or outsource to testing sites, they hold ultimate responsibility for data quality2 and integrity. Thus, ensuring data integrity and confidentiality throughout all study phases is paramount. Robust quality management systems are essential, incorporating efficient protocols and tools to uphold participant rights, safety, and data reliability.

Importance Of Data Integrity

Data integrity is pivotal in BA/BE studies, ensuring the trustworthiness and regulatory acceptance of study findings. It guarantees that study data accurately reflect drug behavior, free from manipulation or misrepresentation. Without it, study results lose credibility, endangering public health and regulatory decisions.

In BA/BE studies, data integrity entails accuracy, completeness, and consistency throughout the study. It requires adherence to protocols and regulatory standards, preventing data falsification. As the basis for regulatory decisions on drug approval and safety, compromised data integrity jeopardizes patient well-being and regulatory trust.

Moreover, data integrity upholds ethical and scientific standards, demonstrating transparency and accountability. Complying with regulations and ensuring accurate reporting instills confidence in study outcomes among stakeholders, including regulators and healthcare professionals.

Focus Of The New Guidance

The recommendations outlined in this guidance extend to both applicants and testing site management, emphasizing their shared responsibility in ensuring data integrity throughout BA/BE studies. Additionally, this guidance provides recommended elements for implementing a quality management system (QMS). In the context of this guidance, a QMS encompasses the organizational structure, delineation of responsibilities, establishment of procedures, and allocation of resources aimed at achieving and maintaining data integrity across the entire data life cycle.

Recommendations From The New Guidance For Applicants

Testing Site Selection

Selecting appropriate testing sites is a critical step in ensuring the validity and reliability of BA/BE studies. The choice of testing sites can significantly impact the quality and integrity of study data, making it essential to establish stringent criteria for site selection.

Criteria for Qualified Testing Sites: Testing sites should meet predefined criteria to ensure they have the necessary expertise, infrastructure, and capabilities to conduct BA/BE studies effectively. These criteria typically include:

  • Accreditation and Compliance: Testing sites should be accredited by regulatory agencies and comply with good clinical practice (GCP) guidelines and other relevant regulations.3,4 Accreditation ensures that testing sites adhere to standardized protocols and quality standards, enhancing the reliability and credibility of study data.
  • Experience and Expertise: Testing sites should have a proven track record of conducting BA/BE studies and possess expertise in relevant therapeutic areas. Experience and expertise are crucial for ensuring the accurate execution and interpretation of study protocols, minimizing the risk of errors or deviations that could compromise data integrity.
  • Facilities and Resources: Testing sites should have adequate facilities, equipment, and resources to support BA/BE study activities. This includes well-equipped laboratories, trained personnel, and access to necessary supplies and materials. Adequate facilities and resources are essential for conducting sample analysis, data collection, and study procedures in compliance with regulatory requirements.

Importance of Communication and Agreement with Testing Sites: Effective communication and mutual agreement between sponsors and testing sites are essential for ensuring alignment on study objectives, methodologies, and expectations. Clear communication helps establish a shared understanding of study requirements and fosters collaboration between stakeholders throughout the study process. Key aspects of communication and agreement include:

  • Study Protocols: Testing sites should have a thorough understanding of study protocols, including procedures for subject recruitment, sample collection, and data analysis. Sponsors should communicate study protocols clearly and ensure that testing sites adhere to protocol requirements to maintain data integrity and consistency across sites.
  • Timelines and Expectations: Clear timelines and expectations should be established regarding study milestones, data submission deadlines, and reporting requirements. Sponsors and testing sites should agree on timelines up front and communicate any deviations or delays promptly to ensure timely completion of the study and submission of quality data.

By adhering to stringent criteria for testing site selection and fostering effective communication and agreement between sponsors and testing sites, stakeholders can enhance the validity, reliability, and integrity of BA/BE study data. Selecting qualified testing sites lays the foundation for successful study execution and regulatory acceptance of study outcomes.

Monitoring And Oversight

Effective monitoring and oversight are essential components of ensuring the integrity and quality of BA/BE studies. Robust monitoring and oversight mechanisms help detect and address deviations from study protocols, ensure compliance with regulatory requirements, and maintain the credibility and reliability of study data.

Development and Use of a Monitoring Plan: A comprehensive monitoring plan should be developed to outline procedures for monitoring study conduct, data collection, and adherence to protocols. Key components of a monitoring plan include:

  • Frequency and Methods: The monitoring plan should specify the frequency and methods of monitoring, such as on-site visits, remote monitoring, or data review meetings. The frequency of monitoring should be based on the complexity and risk level of the study, with more intensive monitoring for high-risk studies.
  • Roles and Responsibilities: The monitoring plan should define the roles and responsibilities of monitoring personnel, including sponsors, monitors, and investigators. Clear delineation of responsibilities ensures that monitoring activities are conducted effectively and efficiently.
  • Criteria for Identifying Deviations: The monitoring plan should outline criteria for identifying deviations from study protocols, including protocol violations, data discrepancies, or noncompliance with regulatory requirements. Deviations should be documented, reported, and addressed promptly to maintain data integrity and regulatory compliance.

Understanding Data Flow and Computerized Systems: A thorough understanding of data flow within BA/BE studies is essential for effective monitoring and oversight.5,6 This includes understanding how data are generated, collected, processed, and analyzed throughout the study process. Additionally, sponsors should ensure that computerized systems used for data management and analysis comply with regulatory requirements for data integrity, security, and validation.

Systems Level Assessment: Assessing data integrity risks at the systems level involves evaluating the integrity, security, and reliability of computerized systems and infrastructure used in BA/BE studies. Key considerations include:

  • Validation and Compliance: Ensure that computerized systems used for data management, analysis, and reporting are validated and compliant with regulatory requirements, such as 21 CFR Part 11 for electronic records and signatures.
  • Data Security: Implement measures to protect data confidentiality, integrity, and availability, such as access controls, encryption, and audit trails. Securing computerized systems against unauthorized access, data breaches, and cyber threats is essential for maintaining data integrity.

Operational Level Assessment: Assessing data integrity risks at the operational level involves evaluating human factors, processes, and procedures that may impact data integrity. Key considerations include:

  • Training and Competency: Ensure that personnel involved in BA/BE studies receive adequate training and possess the necessary knowledge, skills, and competencies to maintain data integrity and comply with regulatory requirements.
  • Documentation and Record-keeping: Establish robust documentation practices, including standardized procedures, record-keeping, and documentation controls, to ensure accurate and complete recording of study data and activities.
  • Quality Control Measures: Implement quality control measures, such as data verification, review, and reconciliation, to detect and correct errors, inconsistencies, or deviations from study protocols promptly.

By implementing robust monitoring and oversight mechanisms, stakeholders can enhance the quality, integrity, and regulatory compliance of BA/BE studies. Effective monitoring and oversight help ensure that study data are accurate, reliable, and credible, supporting informed decision-making in drug development and regulatory evaluation processes.


Conducting audits is a critical component of ensuring compliance, transparency, and data integrity in BA/BE studies. Audits provide an independent evaluation of study processes, procedures, and documentation to verify compliance with regulatory requirements, study protocols, and quality standards. By identifying areas for improvement and addressing noncompliance promptly, audits help enhance the reliability and credibility of study data.

Conducting Audits for Compliance Verification: Audits should be conducted periodically throughout the BA/BE study process to verify compliance with regulatory requirements and study protocols. Key aspects of conducting audits for compliance verification include:

  • Scope and Objectives: Define the scope and objectives of the audit, including the areas, processes, and activities to be evaluated. This ensures that the audit focuses on critical aspects of the study that may impact data integrity and regulatory compliance.
  • Audit Planning: Develop an audit plan that outlines the audit approach, methodology, timelines, and resources required. The audit plan should be tailored to the specific requirements of the study and consider factors such as the complexity of the study, the number of testing sites involved, and the regulatory requirements applicable.
  • Audit Execution: Conduct the audit according to the predefined audit plan, including conducting interviews, reviewing documentation, and observing study procedures. Auditors should gather evidence to verify compliance with regulatory requirements, identify areas of noncompliance or potential risks, and document findings accurately.

Audit Findings Documentation and Communication: Documenting and communicating audit findings are essential for ensuring transparency, accountability, and corrective action in BA/BE studies. Key aspects of documenting and communicating audit findings include:

  • Audit Reports: Prepare comprehensive audit reports that summarize audit findings, observations, and recommendations. Audit reports should clearly identify areas of noncompliance, deviations from study protocols, and opportunities for improvement. They should also include recommendations for corrective actions and preventive measures to address identified deficiencies.
  • Communication with Stakeholders: Communicate audit findings and recommendations to relevant stakeholders, including sponsors, testing sites, regulatory agencies, and internal quality assurance departments. Timely communication ensures that corrective actions are implemented promptly and that stakeholders are aware of any issues that may impact study outcomes or regulatory compliance.

By conducting audits for compliance verification and documenting and communicating audit findings effectively, stakeholders can identify and address noncompliance, mitigate risks, and enhance the integrity and credibility of BA/BE study data. Audits play a vital role in promoting transparency, accountability, and continuous improvement in pharmaceutical research and regulatory processes.

Recommendations From The New Guidance For Testing Sites

Testing Site Management

Managing testing sites effectively is vital for ensuring the integrity, reliability, and regulatory compliance of BA/BE studies. By implementing best practices, stakeholders can optimize processes, mitigate risks, and enhance study data quality.

Organizational Structure and Resources: Establishing a robust structure and allocating resources are crucial. Recommendations include:

  • Designated Study Personnel: Assign qualified personnel responsible for overseeing study activities, including coordination, recruitment, data collection, and reporting. Clear roles streamline processes and ensure accountability.
  • Infrastructure and Facilities: Provide testing sites with adequate infrastructure and resources, including laboratories, secure storage, and necessary equipment.

Responsibility, Authority, and Personnel Roles: Defining responsibility, authority, and roles is crucial for clarity and accountability in testing site management.7 Key recommendations include:

  • Clear Lines of Authority: Establishing clear decision-making processes to facilitate efficient study conduct and issue resolution.
  • Training and Competency: Provide ongoing training and development opportunities to enhance personnel knowledge, skills, and compliance.

Quality Culture and Quality Management System: Fostering a culture of quality and implementing a quality management system (QMS) are crucial for compliance and continuous improvement in testing site management. Key recommendations include:

  • Quality Policy and Objectives: Establish a quality policy aligned with regulatory requirements and organizational goals, emphasizing data integrity and continuous improvement.
  • Documented Procedures: Develop documented procedures for all study aspects to ensure consistency, reproducibility, and compliance.

Implementing these recommendations optimizes study processes, enhances data integrity, and ensures compliance in BA/BE studies. Effective management fosters quality culture and continuous improvement, benefiting pharmaceutical research and public health.

Elements Of A Quality Management System

FDA recommends that testing sites implementing BA and BE studies utilize a quality management system (QMS) to ensure data integrity. Applicants should consider this when selecting a testing site. Key elements of a QMS include the following.

Data Governance and Life Cycle: Effective data governance and management are crucial for maintaining the integrity and reliability of BA/BE study data. By implementing robust practices throughout the data life cycle, stakeholders can ensure compliance and enhance study credibility.

Importance of Data Governance: Data governance involves establishing policies, procedures, and controls to ensure data quality, integrity, and security. Key aspects include:

  • Policy Development: Develop policies for data management, including collection, storage, analysis, and reporting, outlining roles, responsibilities, and standards.
  • Data Ownership: Clarify data ownership and accountability, ensuring adherence to policies and standards.

Data Life Cycle and Risk Management: Managing data throughout its life cycle involves systematically addressing risks and ensuring integrity, confidentiality, and accessibility. Key phases and risk management considerations include:

  • Data Collection: Implement standardized procedures to ensure accuracy and completeness. Activities may include instrument validation and personnel training.
  • Data Analysis: Conduct robust analysis using validated methods. Activities may include method validation and data integrity review.
  • Data Reporting: Communicate findings accurately and transparently. Activities may include data accuracy verification and documentation.

Effective data governance and life cycle management ensure integrity, reliability, and regulatory compliance of BA/BE study data.

Records Management: In BA/BE studies, effective records management is essential for maintaining the integrity, accessibility, and traceability of study data. The following aspects are critical for sound records management practices:

  • Data retention and protection: Establishing policies and procedures for the retention and protection of study records is paramount. This includes defining retention periods for different types of records, ensuring secure storage and access controls, and implementing measures to protect against loss, damage, or unauthorized disclosure of sensitive data.
  • Duties segregation for data integrity: Clear segregation of duties helps prevent conflicts of interest and ensures accountability in records management. Assigning specific roles and responsibilities for data handling, documentation, and review reduces the risk of errors, omissions, or fraudulent activities that could compromise data integrity.

By adhering to rigorous records management practices, stakeholders can uphold the integrity and reliability of study data throughout its life cycle. This facilitates compliance with regulatory requirements and supports the transparency, reproducibility, and credibility of BA/BE study outcomes.

Computer Systems in BA/BE Studies: Computerized systems are vital for data management in BA/BE studies.8 Considerations include:

  • System Validation: Use validated systems compliant with regulatory requirements (21 CFR Part 11) to ensure data accuracy and reliability.
  • Data Collection and Documentation: Accurately document data, including metadata, to ensure traceability and support data integrity and compliance.

Implementing robust computer systems and documentation practices enhances data integrity and security in BA/BE studies, supporting regulatory compliance and study credibility.

Sample Analysis: Sample analysis is a critical component of BA/BE studies, as it involves quantifying drug concentrations in biological samples to assess pharmacokinetic parameters.9 The following considerations are essential for ensuring the integrity and accuracy of sample analysis:

  • Study Protocols and Test Methods: Follow validated protocols and methods approved by regulatory authorities to ensure consistency and reproducibility of results.
  • Equipment Calibration and Maintenance: Regular calibration and maintenance of analytical equipment ensure accuracy and reliability.

Adhering to validated protocols and rigorous quality control measures ensures integrity and reliability in sample analysis, supporting regulatory compliance and accurate assessment of drug bioavailability and bioequivalence.

Data Storage in BA/BE Studies: Proper data storage is essential for maintaining the integrity and security of study data. Considerations include:

  • Secure Storage: Store data securely to prevent unauthorized access, loss, or damage. Physical documents should be locked up, and electronic data should be stored on secure servers with access controls and encryption.
  • Metadata and Data Reconstruction: Capture metadata along with primary data to enable traceability and facilitate data reconstruction if needed, ensuring integrity and authenticity.

Implementing secure data storage practices and capturing comprehensive metadata safeguards study data integrity and confidentiality, supporting regulatory compliance and ensuring reliable study outcomes.

Data Backup: Reliable data backup procedures are crucial for preserving the integrity of study data. Key considerations include:

  • Backup Procedures: Establish regular and systematic data backup procedures to create copies of study data at specified intervals. Store backups securely on-site or off-site to protect against data loss due to hardware failure or disasters. Periodically test backup systems to verify reliability.
  • Backup and Recovery Logs: Maintain detailed logs of backup operations to track dates, times, and contents of backups. These logs provide an audit trail and facilitate monitoring and troubleshooting of backup systems. Document data recovery procedures for swift restoration in case of data loss.

Implementing robust data backup procedures and thorough documentation minimizes the risk of data loss, ensuring the integrity and availability of study data. This supports regulatory compliance and enhances the reliability of study outcomes.

Archival and Retrieval in BA/BE Studies: Proper archival and retrieval procedures are vital for maintaining the long-term integrity and accessibility of study data. Key considerations include:

  • Archiving Study Data: Upon completion of BA/BE studies, archive data securely in controlled environments such as secure servers or physical archives. Transfer data and associated documentation to long-term storage media or systems designed for preservation.
  • Data Archive Management: Organize and index archival systems for efficient retrieval of data. Implement access controls to restrict retrieval to authorized personnel. Document and periodically test retrieval procedures to ensure effectiveness.

Implementing robust archival and retrieval procedures ensures the long-term preservation and accessibility of study data. This supports regulatory compliance, facilitates data reuse, and enhances the integrity of study outcomes.

Training for BA/BE Studies: Comprehensive training programs are essential to equip personnel involved in BA/BE studies with the necessary knowledge and skills for maintaining data integrity and regulatory compliance. Key considerations include:

  • Importance of Data Integrity Training: Ensure all personnel receive training on data integrity principles, regulatory requirements, and best practices for data management. Cover topics such as documentation practices, data security, and adherence to study protocols to ensure data accuracy and reliability.
  • Training Needs Assessment and Documentation: Conduct a needs assessment to tailor training programs to personnel requirements. Maintain training records documenting completion of activities, including dates, topics covered, and personnel trained, to demonstrate regulatory compliance.

Investing in comprehensive training programs empowers personnel to uphold data integrity and regulatory compliance in BA/BE studies. This fosters a culture of quality, enhances study credibility, and supports reliable regulatory submissions.

Access and Privilege Management: Controlling access and privileges to data and systems is critical for maintaining the integrity, confidentiality, and security of BA/BE study data. Key considerations include:

  • Defining Access and Privileges: Define access rights based on job roles and responsibilities, granting users only the minimum access necessary. Implement access controls to restrict unauthorized access to sensitive data or systems.
  • Unique Login Credentials and Password Management: Assign each user unique login credentials and enforce strong password policies. This ensures accountability and mitigates the risk of unauthorized access.

By implementing robust access and privilege management practices, stakeholders can minimize the risk of data breaches and enhance the integrity and reliability of study data. This supports compliance with regulatory requirements and safeguards data security and confidentiality.

Audit Trails Management: Maintaining comprehensive audit trails is crucial for transparency, accountability, and data integrity in BA/BE studies. Key considerations include:

  • Enabling Audit Trails for Data Changes: Implement audit trails within computerized systems to track and record changes to study data. This ensures a complete record of actions taken within the system and facilitates traceability of data modifications over time.
  • Documentation and Restriction: Securely store audit trail data and restrict access to authorized personnel. Implement controls to prevent unauthorized modification or deletion of audit trail records. Retain audit trail data for the required retention period as per regulatory requirements.

By maintaining robust audit trails, stakeholders demonstrate compliance with regulatory requirements for data integrity and accountability. Audit trails aid in identifying unauthorized actions, supporting regulatory inspections, and enhancing the credibility of study data.

Quality Assurance and Quality Control: In BA/BE studies, QA and QC programs are essential for ensuring integrity, reliability, and compliance. Key considerations include:

  • QA Program: This encompasses policies, procedures, and activities to ensure studies adhere to regulations and standards. This includes QA protocols for study design, conduct, and data management, along with internal audits for compliance verification.
  • QC Program for Data Integrity: This focuses on monitoring and verifying data integrity and accuracy. This involves validating methods, calibrating equipment, and implementing data verification procedures to ensure reliable results.

By implementing robust QA and QC programs, stakeholders can identify and mitigate risks, ensure regulatory compliance, and enhance data integrity. This supports confidence in study outcomes and regulatory submissions, advancing drug development and public health.


Maintaining data integrity throughout BA/BE studies is paramount for ensuring the reliability, credibility, and regulatory compliance of study outcomes. By adhering to rigorous standards, implementing best practices, and fostering a culture of quality and accountability, stakeholders can uphold the integrity of study data and promote public health and safety.

Key considerations include selecting qualified testing sites, implementing robust monitoring and oversight mechanisms, conducting thorough risk assessments, and fostering a culture of quality management. Additionally, effective documentation, communication, and training are essential for ensuring transparency, accountability, and compliance with regulatory requirements.

By addressing these considerations comprehensively, stakeholders can enhance the integrity, reliability, and reproducibility of BA/BE study data, supporting informed decision-making in drug development and regulatory evaluations. Ultimately, prioritizing data integrity safeguards public health, strengthens regulatory confidence, and advances scientific knowledge in pharmaceutical research and development.

The FDA is accepting public comments on the draft guidance through July 3, 2024.* Comments can be submitted online via the FDA docket.


  1. The Data Integrity and Compliance with Drug cGMP – Questions and Answers (December 2018),
  2. Advisory Document of the Working Party on Good Laboratory Practice on GLP Data Integrity (September 2021),
  3. ICH E6(R3) Good Clinical Practice (June 2023),
  4. E8 (R1) General Considerations for Clinical Studies (April 2022),
  5. Computerized Systems Used in Clinical Investigations (May 2007),
  6. Electronic Systems, Electronic Records, and Electronic Signatures in Clinical Investigations: Questions and Answer (March 2023),
  7. Quality Systems Approach to Pharmaceutical cGMP Regulations (September 2006),
  8. General Principles of Software Validation (January 2002),
  9. M10 Bioanalytical Method Validation and Study Sample Analysis (November 2022),

About The Author:

Md. Saddam Nawaz serves as the site quality management head at ACI HealthCare Limited. He is an experienced GMP, regulatory, and quality management systems (QMS) expert with experience in developing, implementing, and improving QMSs. He has extensive knowledge of GMP regulations and technical processes, has led greenfield pharmaceutical projects, and has secured several generic drug approvals. He has implemented initiatives to streamline operations, reduce costs, and enhance compliance. At conferences, he frequently speaks on the topics of data integrity, pharma 4.0, and quality culture. You can reach him on LinkedIn.

*Editor's Note: While the deadline for public comments is listed as July 3 on the FDA webpage here, the deadline is listed as June 3 on the FDA docket page here. The public comment deadline is typically 60 days from the date of publication in the Federal Register, so we recommend submitting your comments to the FDA by June 3 in case July is a typo.