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Important Identified Risks

A practical guide to Important Identified Risks, including classification criteria, regulatory expectations and common RMP writing mistakes.

Important Identified Risks

Introduction

Important Identified Risks are one of the three categories of safety concerns used within the Safety Specification of a Risk Management Plan (RMP). They represent risks for which sufficient evidence supports a causal association with the medicinal product and which are considered important for ongoing risk management activities.

The concept appears straightforward, but in practice it is one of the most misunderstood aspects of RMP development.

A common misconception is that every known adverse reaction should be listed as an Important Identified Risk. Regulatory expectations are considerably more selective. Only risks that are both identified and important should appear in this category.

The quality of an RMP depends heavily on appropriate selection and justification of Important Identified Risks.

Regulatory Definition

An Important Identified Risk is:

An undesirable clinical outcome for which adequate evidence supports an association with the medicinal product and which is important for risk management purposes.

Two distinct elements are required:

Identified
        +
Important
        =
Important Identified Risk

If either element is absent, the risk should not be classified as an Important Identified Risk.

What Does "Identified" Mean?

An identified risk is a risk for which sufficient evidence supports a causal association with the product.

Evidence may arise from:

The evidence should be sufficiently robust to support the conclusion that the medicinal product causes or contributes to the outcome.

The standard is not absolute certainty.

However, the evidence should extend beyond mere suspicion.

What Does "Important" Mean?

Importance is evaluated separately from causality.

Not every identified risk is important for risk management purposes.

Factors commonly considered include:

The purpose of the Safety Specification is to identify risks requiring active management rather than cataloguing all known adverse reactions.

Why Importance Matters

Modern regulatory guidance encourages focused RMPs.

Large lists of safety concerns often create several problems:

The question is not:

Is this an adverse reaction?

The question is:

Does this risk require ongoing management activities?

Only then should inclusion as an Important Identified Risk be considered.

Characteristics of Important Identified Risks

Although no universal checklist exists, Important Identified Risks often possess one or more of the following characteristics:

These characteristics help distinguish important risks from routine adverse reactions.

Examples of Potential Important Identified Risks

Examples may include:

Whether a risk qualifies depends upon product-specific context and available evidence.

The same event may be important for one product and not for another.

Importance Within Therapeutic Context

Importance should always be assessed within the context of the product's indication and expected benefits.

For example:

A serious adverse reaction associated with a treatment for a minor condition may have very different implications than the same reaction associated with treatment of a life-threatening disease.

Benefit-risk considerations therefore influence risk classification decisions.

Relationship to Product Information

Many Important Identified Risks are reflected within:

However, inclusion within product information does not automatically make a risk an Important Identified Risk.

Likewise, not every Important Identified Risk requires identical product information measures.

The relationship is important but not absolute.

Relationship to Signal Management

Signal management frequently contributes to the identification of Important Identified Risks.

A signal may:

Potential Signal
        ↓
Validated Signal
        ↓
Assessment
        ↓
Identified Risk
        ↓
RMP Update

Consequently, signal management and RMP maintenance are closely linked.

Many Important Identified Risks originate from signal assessments.

Relationship to Additional Pharmacovigilance Activities

Important Identified Risks may justify:

However, not every Important Identified Risk requires additional pharmacovigilance activities.

The need for additional activities depends on residual uncertainty.

Well-characterised risks may require only routine pharmacovigilance.

Relationship to Risk Minimisation Measures

Important Identified Risks frequently support risk minimisation activities.

Examples include:

Risk minimisation measures should be proportionate to the nature and significance of the risk.

Risk Characterisation

For each Important Identified Risk, organisations should understand:

Risk characterisation supports both benefit-risk evaluation and risk management planning.

Lifecycle Management

Important Identified Risks should be reviewed periodically.

New information may result in:

A risk should not remain indefinitely without ongoing justification.

Lifecycle management is therefore an important component of RMP maintenance.

Removal of Important Identified Risks

Removal requires scientific justification.

Potential reasons may include:

Removal should not occur simply because the risk has become familiar.

The question remains whether active risk management is still required.

Common Classification Errors

Several recurring mistakes occur during RMP preparation.

Listing Every Adverse Reaction

The Safety Specification becomes an extension of the SmPC.

Failure to Demonstrate Importance

A causal association is established but importance is not justified.

Confusing Frequency With Importance

Common events are not automatically important.

Failure to Consider Benefit-Risk Context

Risk significance is assessed without considering therapeutic setting.

Retaining Historical Risks Indefinitely

Safety concerns remain despite limited relevance to current risk management.

These errors often attract regulatory comments.

Inspection Considerations

Inspectors may examine:

The objective is to determine whether Important Identified Risks remain scientifically justified and relevant.

Role of the QPPV

The QPPV should understand:

Inspectors frequently explore how the QPPV maintains awareness of major product risks and associated management activities.

Characteristics of Well-Justified Important Identified Risks

A well-justified Important Identified Risk generally demonstrates:

The objective is not to create extensive lists but to identify risks that genuinely require active management.

Key Takeaways

An Important Identified Risk is a risk for which sufficient evidence supports a causal association and which is important for risk management purposes.

Not all adverse reactions qualify as Important Identified Risks.

Importance depends on factors such as seriousness, public health impact, benefit-risk implications and the need for ongoing management.

Important Identified Risks frequently drive pharmacovigilance activities, risk minimisation measures and RMP updates.

Appropriate classification is essential for development of focused and scientifically justified Risk Management Plans.

References

  1. EMA Good Pharmacovigilance Practices (GVP) Module V – Risk Management Systems.
  2. EMA Risk Management Plan Template.
  3. Commission Implementing Regulation (EU) No 520/2012.
  4. Regulation (EC) No 726/2004.
  5. Directive 2001/83/EC.
  6. ICH E2E Pharmacovigilance Planning.
  7. EMA Guidance on Safety Concerns and Risk Management Planning.

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Last reviewed: 2026-06-11