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Real-World Data: Assessing Registries To Support Regulatory Decision-Making for Drug and Biological Products

FinalCenter for Drug Evaluation and Research Center for Biologics Evaluation and Research Oncology Center of Excellence12/22/2023
Real-World EvidenceAudit TrailData IntegrityReal-World DataTraceability

Description

The 21st Century Cures Act (Cures Act), signed into law on December 13, 2016, was intended to accelerate medical product development and bring innovations and advances faster and more efficiently to the patients who need them.  Among other provisions, the Cures Act added section 505F to the Federal Food, Drug, and Cosmetic Act (FD&C Act).   In response to the requirements in section 505F, FDA created a framework for a Real-World Evidence (RWE) Program to evaluate the potential use of RWE to help support the approval of a new indication for a drug already approved under section 505(c) of the FD&C Act or to help support or satisfy postapproval study requirements.  In the context of this program, this guidance provides considerations for sponsors proposing to design a new registryor use an existing registry to support regulatory decision-making about a drug’s effectiveness or safety.  This guidance does not provide recommendations on choice of study design or statistical methods used to analyze data from registries.

Key Topics

Terms and concepts identified from this document

Scope & Applicability

Product Classes

2
Drug

Defined in section 201(g) of the FD&C Act; Articles intended for use in diagnosis, cure, mitigation, treatment, or prevention of disease; Product classification based on chemical action or specific intended uses like altering pH

Biological Products

Requires analytical comparability per ICH Q5E

Stakeholders

3
Independent Ethics Committee

Responsible for submission and communication oversight; Safeguard the rights, safety and well-being of trial participants; Reviewing trial conduct and records

Sponsor

Entity responsible for submitting applications under section 524B

Institutional Review Board

Governs top dose in clinical studies

Regulatory Context

Regulatory Activities

5
Postapproval Study Requirements

RWE may help support or satisfy these requirements

Sponsor inspections

available for FDA to review during sponsor inspections

Type C meeting

Mechanism for applicants to discuss total nitrosamine limits with FDA.

Clinical Trials

The regulatory activity where inclusion of specific populations is discussed; The primary vehicle for generating robust clinical data for these populations.; Trials including pregnant participants for non-obstetric or obstetric indications; Inclusion of breastfeeding women in clinical trials; Research studies where breastfeeding women may be included.; The context in which these outcome parameters are collected.

Observational Studies

Alternate strategy for data collection

Document Types

7
Medical Claims

Administrative data used as a source of RWD.

Data Dictionary

An established data dictionary, which is available for those who intend to use the registry data

Electronic Health Records

Source of RWD for evaluation of safety or effectiveness.

Registry

System where patients using the drug are enrolled; A surveillance strategy to evaluate the incidence and severity of risk.

Informed Consent

Process by which a subject voluntarily confirms his or her willingness to participate in a particular trial; Integral feature of the ethical conduct of a trial

Statistical Analysis Plan

Document for protocol execution; The sponsor should develop a statistical analysis plan that is consistent with the trial protocol; Deviations from this plan must be justified

Protocol

Defines the standard of veterinary practice and limits for anesthetic regimens

Attributes

5
Fitness-for-use

Attributes of a registry that support collection of relevant and reliable data

Interoperability

Considerations for cybersecurity when devices connect to other systems

Relevance

relevance includes the availability of data for key study variables

Reliability

reliability includes accuracy, completeness, and traceability

Data Integrity

Responsibility for the integrity of the trial data

Technical Details

Substances

1
Biomarkers

Used to increase development efficiency

Processes

1
Validation of the electronic systems

Validation of the electronic systems used to collect registry data

Clinical Concepts

1
Natural History of a Disease

Characterizing disease progression using registries

Standards & References

External Standards

2
Public Health Service Act

Licensing of biological products

21st Century Cures Act

Legislation that amended the FD&C Act regarding patient experience data

Specifications

2
Sample Size

Number of subjects needed to achieve pre-specified power

Study Endpoints

Planning interventional study endpoints using registry data

Related CFR Sections (3)

Enforcement Impact

Deficiencies cited in Warning Letters referencing the same regulations

Failure to adequately investigate and document out-of-specification results
1
Failure of your quality unit to exercise its responsibility
1
Failure to establish identity specifications for each component
1
Failure to establish product specifications
1
Failure to prepare and follow a written master manufacturing record
1
Failure to prepare a batch production record
1
Failure to make and keep written procedures for product complaints
1
Failure to collect and hold reserve samples
1
Misbranded dietary supplement
1
Failure to perform repackaging of API under appropriate CGMP to avoid potential cross-contamination
1

Related Warning Letters (3)

Related MFDS Guidelines

Korean regulatory guidelines covering similar topics

See Also (8)

Real-World Data: Assessing Registries To Support Regulatory Decision-Making for Drug and Biological Products | Guideline Explorer | BioRegHub