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Development and Use of Risk Minimization Action Plans: Guidance for Industry

FinalCenter for Drug Evaluation and Research Center for Biologics Evaluation and Research03/29/2005
Risk Managementrisk assessmentRisk Minimization Action PlansPostmarketing SurveillanceRiskMAP

Description

This document provides guidance to industry on the development, implementation, and evaluation of risk minimization action plans for prescription drug products, including biological drug products. In particular, it gives guidance on (1) initiating and designing plans called risk minimization action plans or RiskMAPs to minimize identified product risks, (2) selecting and developing tools to minimize those risks, (3) evaluating RiskMAPs and monitoring tools, and (4) communicating with FDA about RiskMAPs, and (5) the recommended components of a RiskMAP submission to FDA.

Key Topics

Terms and concepts identified from this document

Scope & Applicability

Product Classes

4
Prescription drug products

Products with approved NDAs or ANDAs subject to SLC provisions.

Biological drug products

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

Opiate drug products

Associated with significant risk of overdose, abuse, and addiction.

Schedule II controlled substances

labeling for Schedule II controlled substances typically includes a BOXED WARNING

Stakeholders

8
Healthcare practitioners

Participants in name simulation studies including physicians and pharmacists.

patients

Stakeholders involved in collecting patient experience data

prescribers

REMS participants can include prescribers, dispensers, health care settings, patients; Health care providers who prescribe the drug under REMS; health care providers who prescribe the drug

Sponsors

Assist sponsors in the nonclinical evaluation

Industry

Guidance for Industry

Sponsor

Entity responsible for submitting applications under section 524B

Healthcare Practitioner

Target audience for professional labeling and education

FDA advisory committee

discussed potential liver toxicity of ximelagatran in September 2004

Regulatory Context

Regulatory Activities

7
RiskMAP submission

Recommended components of a submission to FDA

IND

Investigational New Drug submissions

BLA

Biologics License Application

NDA

New Drug Application

Phase 3 trials

Guidance describes recommendations regarding phase 3 trials for prescription non-opioid analgesic products.

product recalls

FDA-requested tool to minimize risks

PDUFA III

Prescription Drug User Fee Act reauthorization involving risk management goals

Document Types

9
RiskMAP Progress Report

Reporting on the effectiveness of risk minimization tools; FDA recommends that a RiskMAP progress report contain specific sections including Summary, Methodology, Data, Results, and Discussion.

periodic safety update reports

Reports containing RiskMAP evaluation progress

SOPs

Standard Operating Procedures must identify circumstances of potential plasma dilution.

Manuals of Policies and Procedures

Internal FDA documents (MaPPs) regarding review consistency

FDA-approved professional labeling

Information on conditions in which medical products can be used safely

Consent forms

Patient education tools that include acknowledgment and agreement to follow instructions.

Professional Labeling

Cornerstone of risk management efforts for prescription drugs

Medication Guides

Required patient labeling

Patient package inserts

PPIs should be included at the end of the SPL file

Attributes

3
Performance Measures

Evidence-based measures for RiskMAP evaluation; Sponsor's comparison of tool, objective, and/or goal achievement relative to targeted performance measures.

benefit-risk balance

Late stage development consideration

Benefit/risk balance

Assessment of drug safety and efficacy in the geriatric population

Technical Details

Substances

1
Human teratogens

Drugs that cause birth defects and require RiskMAPs to minimize in utero exposure.

Testing Methods

10
Laboratory testing results

Used in performance-linked access systems to gate product access.

statistical estimation

Analytical methods used in the Results section of the report.

process audits

Evaluation methods used in RiskMAP methodology.

patient surveys

Evaluation methods used in RiskMAP methodology.

comprehension testing

Evaluation methods used in RiskMAP methodology.

registries

Data collection method for RiskMAP evaluation

surveys

Evaluation method for assessing RiskMAP effectiveness

focus group testing

Method to determine acceptance or comprehension of a RiskMAP tool

computer modeling

used to determine temperature or local SAR

Failure Modes and Effect Analysis

Systematic program evaluation model for RiskMAP components

Processes

4
Targeted education and outreach

Category of RiskMAP tools employing specific efforts to increase knowledge.

pharmacovigilance

Efforts to identify new serious risks after marketing

Reminder systems

Category of tools that prompt or double-check healthcare practitioners and patients.

Performance-linked access systems

Systems that link product access to laboratory testing results or documentation.

Clinical Concepts

2
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

adverse event monitoring

FDA requirement for risk management

Identified Hazards

Hazards

7
Identified product risks

Risks that RiskMAPs are designed to minimize

teratogen

A risk identified early requiring formal risk management

Teratogenicity

Significant unanticipated safety finding suggesting human risk

In utero exposure

Risk associated with human teratogens that RiskMAPs aim to minimize.

Overdose

Risk prevented by administration of opioid blockers

Abuse

Risk associated with self-administered formulations

Addiction

Significant risk associated with opiate drug products.

ICH References (1)

ICH E2E

Pharmacovigilance Planning

View on FDA.govDownload PDF

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
1

Recent Cases

Related Warning Letters (10)

Related MFDS Guidelines

Korean regulatory guidelines covering similar topics

See Also (8)