Data Integrity for In Vivo Bioavailability and Bioequivalence Studies | Guideline Explorer

Description

The purpose of this guidance is to provide recommendations to applicants and testing site management on achieving and maintaining data integrity for the clinical and bioanalytical portions of bioavailability (BA) and bioequivalence (BE) studies submitted in support of investigational new drug applications (INDs), new drug applications (NDAs), and abbreviated new drug applications (ANDAs), and the bioanalytical portion of clinical pharmacologic studies supporting CDER-regulated biologic license applications (BLAs) as well as amendments and supplements to these applications. In addition, the recommendations in this guidance apply to the bioanalytical portion of nonclinical studies. FDA also encourages applicants and testing sites to consider these recommendations when conducting other studies, including in vitro and pharmacology and toxicology studies.

Key Topics

Terms and concepts identified from this document

Scope & Applicability

Product Classes

1

Biologic Therapeutic

Data governance should address roles throughout the data lifecycle of the product or biologic therapeutic.

Stakeholders

5

Applicant

Entity submitting development data and knowledge; Entity performing the work process for change

Quality Assurance Personnel

Independent personnel engaged in ensuring data integrity

Archivist

Individual responsible for management of data archives

System Administrator

Role authorized to change system date/time and receive discrepancy notifications

Testing Site Management

Responsible for organization and functioning of clinical and analytical sites; Responsible for implementing and maintaining the quality management system.

Regulatory Context

Regulatory Activities

6

IND

Investigational New Drug submissions

FDA Inspection

The process of evaluating a facility for compliance

NDA

New Drug Application

ANDA

Abbreviated New Drug Application

BLA

Biologics License Application

Inspection

FDA verification of qualified facility status, including for-cause inspections

Document Types

5

Audit Trails

Element of a Quality Management System for data integrity

Audit Trail

Storage of electronic signature execution records

Standard Operating Procedures

IRB's documented procedures for reviewing documents.

SOP

Standard Operating Procedures for evaluating suppliers; Based on the manufacturer's established SOP for evaluating suppliers.; Standard Operating Procedures for regulatory compliance

Study Protocol

Document defining the design and conduct of the trial

Attributes

1

Metadata

Data about data, including audit trails and system logs.

Technical Details

Testing Methods

1

Bioanalysis

Analysis of participant samples from in vivo BA and BE studies.

Processes

3

Bioavailability

In vivo studies to measure drug absorption

Bioequivalence

In vivo studies to establish equivalence between products

Bioanalysis

Analysis of participant samples from in vivo BA and BE studies.

Identified Hazards

Hazards

2

Data Integrity Risks

Potential for data to be deleted, amended, or excluded without authorization.

Data Loss

Resulting from system failure, requiring backup and recovery logs.

Standards & References

External Standards

2

OECD Advisory Document on GLP Data Integrity

External standard discussing ALCOA and data integrity

OECD GLP Data Integrity

Advisory document on Good Laboratory Practice data integrity.

ICH References (2)

ICH E6(R3)

Good Clinical Practice (GCP) Guidance for Industry; Good Clinical Practice (GCP) guidance providing a unified standard for clinical trial data acceptance.; Good Clinical Practice (GCP) guideline; The document being analyzed regarding Good Clinical Practice.; The primary document being analyzed regarding Good Clinical Practice.

ICH E8(R1)

General Considerations for Clinical Studies

Related CFR Sections (2)

21CFR320.63§ 320.63 Retention of bioequivalence samples.
The applicant of an abbreviated application or a supplemental application submitted under section 505 of the Federal Food, Drug, and Cosmetic Act, or, if bioequivalence testing was performed under contract, the contract research organization shall retain reserve samples of any test article and referRead full regulation →
21CFR320.38§ 320.38 Retention of bioavailability samples.
(a) The applicant of an application or supplemental application submitted under section 505 of the Federal Food, Drug, and Cosmetic Act, or, if bioavailability testing was performed under contract, the contract research organization shall retain an appropriately identified reserve sample of the drugRead full regulation →

Enforcement Impact

Deficiencies cited in Warning Letters referencing the same regulations

Failure to ensure that the investigation was conducted according to the investigational plan

21

Failure to submit an Investigational New Drug application (IND)

9

Failure to obtain informed consent

5

Unapproved new drug

5

Misbranded drug

4

Failed to ensure that the investigation was conducted according to the investigational plan

3

Enrollment of subjects who do not meet eligibility criteria

3

Failure to submit INDs for the conduct of clinical investigations

3

Unlicensed biological product

2

unapproved new drugs

2

Recent Cases

Related Warning Letters (10)

Related MFDS Guidelines

Korean regulatory guidelines covering similar topics