Good Pharmacovigilance Practices and Pharmacoepidemiologic Assessment: Guidance for Industry

Description

This document provides guidance to industry on good pharmacovigilance practices and pharmacoepidemiologic assessment of observational data regarding drugs, including biological drug products (excluding blood and blood components). Specifically, this document provides guidance on (1) safety signal identification, (2) pharmacoepidemiologic assessment and safety signal interpretation, and (3) pharmacovigilance plan development.

Key Topics

Terms and concepts identified from this document

Scope & Applicability

Product Classes

1

Biological drug products

Includes therapeutic proteins and recombinant DNA products.; Encouraged to use enhanced modelling

Stakeholders

2

Sponsor

Entity responsible for submitting applications under section 524B

Drug Safety and Risk Management Advisory Committee

FDA advisory committee that reviewed name testing approaches.

Regulatory Context

Regulatory Activities

3

PDUFA III

Prescription Drug User Fee Act reauthorization involving risk management goals

Postmarketing surveillance

Monitoring drug safety after product approval

Clinical trials

Development program for drugs intended for sGERD treatment

Document Types

10

Registries

Organized systems using observational study methods

15-day reports

Expedited submission of specific serious adverse event reports

Risk Minimization Action Plan

Strategic plan to minimize known safety risks

Medication Guide

FDA-approved patient labeling

Protocol

Defines the standard of veterinary practice and limits for anesthetic regimens

Surveys

type of non-randomized observational study

Pharmacovigilance Plan

applicants submit a PVP as described in the FDA Guidance for Industry

Risk Minimization Action Plans

Also referred to as RiskMAP Guidance

Case Report

most common source of reports of adverse pregnancy outcomes

Case Series

Assembly of case reports for interpretation and descriptive clinical information

Attributes

3

Incidence rate

Single cohort studies can measure incidence

Benefit-risk balance

Assessment for approval in a limited population

Reporting rate

sponsors calculate crude adverse event reporting rates

Technical Details

Testing Methods

8

Data Mining

Used to identify product-event combinations; systematic examination of the reported adverse events by using statistical or mathematical tools; Technique employed to further characterize a safety signal.

Controlled clinical trials

Additional trials to evaluate safety risks

Observational Studies

Source of efficacy/effectiveness evidence

Pharmacoepidemiologic Study

Case-control and cohort studies to examine potential associations

Multi-Item Gamma Poisson Shrinker

MGPS algorithm used for data mining

Proportional Reporting Ratio

PRR method for signal generation

Neural Network approach

Data mining method for adverse drug reaction signal generation

Pharmacoepidemiologic studies

Traditional studies including medical record validation

Processes

2

Pharmacoepidemiologic Assessment

Assessment of observational data regarding drugs

Pharmacoepidemiologic studies

Observational studies used to evaluate safety signals after approval.

Clinical Concepts

7

Safety Signals

Identification and interpretation of potential safety risks

Acute liver failure

indication for xenotransplantation products

Adverse events

Safety findings including deaths and post-mortem examinations

Renal impairment

Patient condition increasing risk of aluminum toxicity.; Patient population sensitive to aluminum exposure

Hepatic impairment

Condition assessed in clinical studies for PK/PD influence

Adverse Event

Reactions 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

Medication Error

Errors in IP administration to be monitored

Identified Hazards

Hazards

2

Safety signal

Identified after approval, leading to the initiation of studies.

Safety risk

The focus of FDA's review to ensure the NDI is reasonably expected to be safe.

Standards & References

External Standards

5

International Classification of Diseases (ICD-9)

Standard medical coding system used to identify conditions of interest.

45 CFR Part 46

compliance with regulations for human subject protections

Health Insurance Portability and Accountability Act of 1996

Patient privacy protection

NCC MERP Taxonomy

Standard language and structure for medication error-related data

MedDRA

Used for coding indications, reactions, and causes of death; Coding for indications and sender's diagnosis; Medical Dictionary for Regulatory Activities used for coding medical sections; Medical Dictionary for Regulatory Activities used to classify adverse event information; terminologies include MedDRA for medical history, indication, and reaction; Used for coding medical history, indications, reactions, and causes of death.; Standard terminology used for coding medical history, indications, an

ICH References (2)

ICH E2E

Pharmacovigilance Planning

ICH E2C

Covers periodic reporting of aggregated safety data and Company Core Safety Information.; Guidelines for periodic reports where observations in the absence of an AE/ADR should be discussed

Enforcement Impact

Deficiencies cited in Warning Letters referencing the same regulations

Failure to obtain informed consent

5

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

4

Failure to submit an Investigational New Drug application (IND)

2

Failure to ensure proper monitoring of the investigation

1

Failure to submit an IDE application and obtain FDA approval

1

Failure to secure clinical investigator's compliance

1

Failure to immediately conduct an evaluation of unanticipated adverse device effects

1

Failure to obtain permission from the subjects' parent or guardian

1

Failure to review proposed research at convened meetings with a majority of members present

1

Failure to prepare and maintain adequate documentation of IRB activities, including minutes of IRB meetings