Description
The Food and Drug Administration is announcing the availability of a final guidance for industry entitled “E6(R3) Good Clinical Practice.” This revision incorporates flexible, risk-based approaches and embraces innovations in trial design, conduct, and technology.
Key Topics
Terms and concepts identified from this document
Scope & Applicability
Product Classes
1Synonymous with drugs, medicines, medicinal products, vaccines, and biological products.; Product intended to benefit population groups once authorized; The product being tested in the clinical trial.; The product being studied in the clinical trial.; monitoring extent based on the nature of the investigational product; Management, storage, and accountability of the product being tested.; management should be arranged and conducted in accordance with applicable regulatory requirements; The produ
Stakeholders
10Governs top dose in clinical studies
Individuals whose willingness to volunteer may be unduly influenced.
Clinical trial team member designated to perform significant procedures.
An individual who participates in a clinical trial and receives investigational product or control.
Body that may propose protocol amendments or maintain trial integrity
A licensed physician who submits an expanded access IND and administers the drug.; Physician acting as a sponsor for an individual patient IND; An individual who both initiates and conducts a clinical investigation.; Role that may authorize expanded access protocols
Entities that must be informed of record retention requirements.; Entities to whom activities are transferred or delegated; Entities conducting delegated or transferred trial-related activities.; Person or organization providing a service to the sponsor or investigator.
assigned as contact point for each site
Qualified individuals assigned to trial activities.
Qualified individuals assigned to trial activities.
Regulatory Context
Regulatory Activities
10Risks relating to products that have a marketing authorization
FDA verification of qualified facility status, including for-cause inspections
Sponsor's independent function to assess trial conduct
Submissions where clinical trial reports must meet ICH E3 standards.
Inspection by authorities requiring access to source records.; Access to source records for assessment of trial conduct
Conducted by regulatory authorities to ensure compliance.
Submission of adverse event data to sponsors and authorities
Ongoing review of trials at appropriate intervals
Alternative process for review of minor changes
Submission for product approval
Document Types
10Defines the standard of veterinary practice and limits for anesthetic regimens
A documented description of a change to a protocol.
documented description of a trial of any investigational product conducted in human participants
The repository held by the investigator/institution
Repositories held by the sponsor for essential records
Contained in the IB for expedited reporting of SUSARs.; Contains a cumulative list of expected ADRs for the investigational product.
Metadata that must be maintained and not disabled to ensure data integrity.
Plans defining procedures for access to unblinded information.
Reports prepared for regulatory submission, including interim reports.
Records pertaining to the trial that must be retained.
Attributes
10Responsibility for the integrity of the trial data
A copy used to permanently replace an original essential record.
statistically justified calculation required in the plan
Criteria for participant selection
Requirements for enrolling subjects in sGERD trials
the effective and nontoxic dose findings in the same animal species should be compared (i.e., the therapeutic index should be discussed).
Assessment made by investigators regarding the appropriateness of the trial.
Data about data, including audit trails and system logs.
Determined by the sponsor for the investigational product.; investigational product(s) are stable over the period of use and only used within the current shelf life
whether blinding to treatment assignment was maintained
Technical Details
Substances
3Pharmaceutical form of an active ingredient or placebo being tested; Product being tested in the clinical trial; Pharmaceutical form of an active ingredient being tested in a trial
Accountability procedures for the investigational product including placebo; used as a reference in a clinical trial
Differences in excipients may affect product stability
Testing Methods
8Analyses of accumulating unblinded data at pre-specified points
Measure taken to minimize bias
Measure taken to minimize bias
A summary of the toxicological effects found in relevant studies conducted in different animal species.
Proof-of-concept studies may evaluate tolerability, pharmacokinetics, and preliminary clinical efficacy.
The testing should identify and characterize security-related issues
used in centralized monitoring to identify systemic issues
monitoring activity to review trial documents and information
Processes
10Process of assigning trial participants to treatment or control groups using an element of chance; Process of assigning participants to treatment groups.; Process of assigning participants to groups using chance to reduce bias.
Biomedical studies not performed on human participants.
process of establishing and documenting that the specified requirements of a computerized system can be consistently fulfilled
Process of demonstrating that a trial-specific computerized system is fit for purpose.
The results of all relevant nonclinical pharmacology, toxicology, pharmacokinetic, and investigational product metabolism studies should be provided.
Procedures used to manage system updates and subsequent validation.
Conducted for new impurities observed after registration toxicology studies
Used to supply investigational product to eligible participants.
foreign supplier verification activity
evaluation of accumulated data by qualified and trained persons
Clinical Concepts
10Reactions or events observed in patients; Information described in an ICSR; Information associated with the use of biopharmaceuticals; Clinical information corrected during an amendment; Section D describes the singular subject who experienced one or several adverse events/reactions.; Reactions or events observed in patients or foetuses; The onset of a reaction/event following drug administration.; Reporting of reactions to suspect drugs; Reaction or event reported by the primary source; Reactio
suspected by the reporter to have contributed to the adverse reaction described in Section E
An adverse reaction that is suspected, unexpected, and serious.
Adverse events resulting in death, hospitalization, or significant disability.
Description of the population to be studied.
Nonserious and serious ADRs from postmarketing sources
List included in the RSI to determine expectedness.
confirming consent was obtained before participation
Breaking the treatment code in emergencies or for analysis.
SAEs collected during interventional clinical trials
Identified Hazards
Hazards
7Safety concerns requiring management during a trial.; Urgent safety risk to trial participants requiring protocol deviation; Sponsor must take prompt action to address immediate hazards to participants.
Summary of the known and potential risks and benefits, if any, to human participants.
Risks to computerized systems that must be prevented, detected, or mitigated.
Risk to trial results that must be assessed and documented.
likelihood and impact on trial participant protection
Situations requiring protocol deviations to protect participants
Strategies to avoid, detect, and address noncompliance with GCP
Standards & References
External Standards
1Ethical principles that are the origin of GCP standards.; Ethical principles for medical research involving human subjects
Specifications
4Investigational products managed in accordance with specifications
Reference values for medical or laboratory procedures.
maintain records of batch sample analyses and characteristics
prespecified acceptable ranges at the trial level
ICH References (10)
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.
Statistical Principles for Clinical Trials: Addendum: Estimands and Sensitivity Analysis in Clinical Trials
Statistical Principles for Clinical Trials; Discourages deterministic procedures due to high risk of bias; Notes that the use of Bayesian methods in clinical trials may be considered.
A Selective Approach to Safety Data Collection in Specific Late-Stage Pre-Approval or Post-Approval Clinical Trials
Development Safety Update Report guidance
Provides definitions for seriousness criteria; ICH E2A recommends blinded therapy should not be reported
document remedial actions in the clinical trial report; Structure and Content of Clinical Study Reports standards.
Integrated Addendum to ICH E6(R1) document
Guideline for Clinical Safety Data Management: Definitions and Standards for Expedited Reporting
General Considerations for Clinical Studies
Related MFDS Guidelines
Korean regulatory guidelines covering similar topics
See Also (8)
- E11A Pediatric Extrapolation
- M15 General Principles for Model-Informed Drug Development
- Clinical Pharmacology Data to Support a Demonstration of Biosimilarity to a Reference Product
- Q6A Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances
- Rare Diseases: Considerations for the Development of Drugs and Biological Products
- Q3C Impurities: Residual Solvents_2011
- Providing Regulatory Submissions in Electronic Format --Content of the Risk Evaluation and Mitigation Strategies Document Using Structured Product Labeling: Guidance for Industry
- Q4B Annex 5: Disintegration Test General Chapter