Writing the Actions Taken for Safety Reasons Section in a PBRER

Introduction

The "Actions Taken for Safety Reasons" section documents important measures implemented during the reporting interval in response to safety concerns. Although this section is relatively concise, it provides regulators with valuable insight into how emerging safety information has already influenced regulatory decision-making and pharmacovigilance activities.

The purpose of this section is not merely to list regulatory actions. Rather, it should provide sufficient information for assessors to understand what action was taken, why it was taken and how it relates to the subsequent scientific discussions presented elsewhere in the PBRER. Actions described here frequently influence later discussions regarding identified risks, signal evaluations, product information updates and the integrated benefit-risk assessment.

Authors should therefore regard this section as an important bridge between regulatory history and scientific evaluation. Every significant action described should be reflected consistently throughout the remainder of the report where appropriate.

Regulatory Basis

ICH E2C(R2) requires the Marketing Authorisation Holder to summarise significant actions taken for safety reasons during the reporting interval. Within the European Union, these expectations are implemented through GVP Module VII.

The emphasis is on actions taken because of safety concerns. Routine administrative changes, commercial decisions unrelated to safety and procedural updates that do not arise from evaluation of safety information generally do not belong in this section.

Regulatory Basis

• ICH E2C(R2): Actions Taken for Safety Reasons.

• EMA Good Pharmacovigilance Practices (GVP) Module VII.

Purpose of this Section

This section provides regulators with a chronological overview of important safety-related actions affecting the medicinal product during the reporting interval.

These actions may include changes initiated by the Marketing Authorisation Holder, requested by regulatory authorities or implemented jointly following scientific review. Regardless of who initiated the action, the objective is to provide context for the evolving benefit-risk assessment.

The section also demonstrates how important safety information has been translated into regulatory action where appropriate. It therefore provides an important link between pharmacovigilance activities and regulatory decision-making.

The emphasis should remain on actions that materially influence understanding or management of the medicinal product's safety profile rather than documenting every operational activity performed during the reporting interval.

What Qualifies as an Action Taken for Safety Reasons?

One of the first decisions an aggregate report author must make is whether a particular event should be included in this section. The title of the section is intentionally specific. It concerns actions taken for safety reasons, not every regulatory, commercial or operational activity that occurred during the reporting interval.

An action should normally be included when it represents a response to an identified or potential safety concern, a newly emerging safety issue or a reassessment of the medicinal product's benefit-risk balance. The action may be initiated voluntarily by the Marketing Authorisation Holder, requested by a regulatory authority or agreed following regulatory review. The important consideration is not who initiated the action but whether the action was taken because of safety considerations.

Actions frequently described in this section include significant changes to product information arising from safety evaluation, implementation of new or enhanced risk minimisation measures, suspension or withdrawal of marketing authorisations for safety reasons, restrictions of indications, introduction of new contraindications, Direct Healthcare Professional Communications (DHPCs), recalls undertaken because of safety concerns and other regulatory measures intended to protect patients.

The level of detail should be proportionate to the significance of the action. Routine editorial updates to the SmPC, minor wording revisions that do not alter clinical interpretation or administrative implementation of previously completed regulatory decisions generally require little or no discussion unless they represent an important development during the reporting interval.

The purpose of this section is not merely to catalogue actions. Instead, it should explain how the medicinal product's safety profile has already influenced regulatory decision-making and provide the context required for the detailed scientific discussions presented later in the PBRER.

Actions That Should Generally Not Be Included

Just as important as deciding what to include is recognising what should normally be excluded.

Commercial decisions, such as withdrawal from a market because of poor sales, portfolio rationalisation, company mergers or transfer of marketing authorisations, do not usually belong in this section unless they are directly related to a safety concern. These events may be relevant elsewhere in the PBRER, particularly within the Worldwide Marketing Authorisation Status section, but should not be presented as safety actions when no safety issue exists.

Similarly, manufacturing changes, packaging updates, supply interruptions, changes in distributors or routine organisational restructuring are generally outside the scope of this section unless they have resulted in a safety-related regulatory action.

Regulatory procedures also require careful consideration. The initiation of a referral procedure, safety review or health authority request does not automatically constitute an action taken for safety reasons. The focus should instead be on the actions arising from those procedures, such as implementation of revised product information, introduction of additional monitoring requirements or changes to risk minimisation measures.

Writing Tip

Ask a simple question before including any event:

"Was this action taken because of a safety concern?"

If the answer is no, the event probably belongs elsewhere in the PBRER.

Relationship to Other Sections of the PBRER

This section should never be read in isolation. It establishes the regulatory context for many of the scientific discussions that follow.

Actions described here frequently reappear later in the report when discussing signal evaluations, characterisation of risks, changes to the safety specification, effectiveness of risk minimisation measures and the integrated benefit-risk evaluation.

Consistency between sections is therefore essential. A safety-related suspension described here should be reflected, where appropriate, in later discussions explaining the evidence that led to the action. Similarly, implementation of new educational materials or additional monitoring should be discussed consistently within the sections addressing risk minimisation activities.

Authors should avoid repeating the same information verbatim throughout the report. Instead, this section should introduce the action, while later sections explain the scientific evidence and regulatory rationale in greater detail.

Medical Review Consideration

During final review, verify that every important safety action described in this section is supported by the corresponding scientific discussion elsewhere in the PBRER, and that no major safety-related regulatory action has been omitted.

Organising the Section

One of the most common mistakes made by inexperienced aggregate report authors is preparing this section as a chronological list of regulatory events. Although this approach documents what occurred during the reporting interval, it often fails to communicate the regulatory significance of each action or the relationship between different actions.

Instead, the section should be organised so that the reader can rapidly understand the major safety-related developments affecting the medicinal product during the reporting interval.

Closely related actions should be grouped together and presented as part of a coherent regulatory narrative rather than as isolated events. For example, introduction of a new contraindication, revision of the SmPC, distribution of a Direct Healthcare Professional Communication (DHPC) and implementation of educational materials may all arise from evaluation of the same important safety concern. Presenting these actions together allows the reviewer to understand how the identified risk translated into regulatory action.

Conversely, unrelated actions affecting different risks should generally be described separately to avoid creating an inaccurate impression that they arose from the same scientific concern.

The objective is not simply to document actions but to explain how safety information has influenced regulatory decision-making.

Presenting Safety Actions

Each safety action should answer several fundamental questions.

• What action was taken?

• Why was the action necessary?

• Which authority or organisation initiated the action?

• Which countries or regions were affected?

• When was the action implemented?

• Does the action influence interpretation of later sections of the PBRER?

Providing these elements allows the reader to understand both the regulatory event and its significance without requiring unnecessary operational detail.

For significant actions, authors should briefly summarise the scientific rationale while avoiding duplication of the detailed discussions presented later in the report.

For example, rather than reproducing the complete signal assessment, the section should simply explain that evaluation of an identified safety concern resulted in implementation of a new contraindication or strengthening of existing warnings. The detailed scientific evidence supporting that decision should be discussed within the appropriate later section.

Grouping Similar Safety Actions

Several regulatory measures may arise from a single safety concern.

For example, identification of an important hepatotoxicity signal may lead to:

• revision of the Summary of Product Characteristics (SmPC);

• revision of the Package Leaflet (PL);

• distribution of a Direct Healthcare Professional Communication (DHPC);

• implementation of additional educational materials;

• enhanced laboratory monitoring recommendations.

Although these represent multiple regulatory actions, they address a common scientific issue and should normally be discussed together.

Similarly, implementation of a Pregnancy Prevention Programme may involve educational materials, patient reminder cards, prescriber checklists and amendments to product information. These activities should generally be presented as components of a single risk minimisation strategy rather than as unrelated actions.

Grouping related actions improves readability, reduces unnecessary repetition and allows regulators to appreciate the complete regulatory response to a particular safety concern.

Describing the Scientific Rationale

The purpose of this section is not to reproduce the detailed scientific evaluation supporting each regulatory action. Nevertheless, readers should understand why the action was taken.

The explanation should therefore be proportionate to the importance of the action.

For example, a brief statement that revised contraindications were introduced following evaluation of an identified risk may be sufficient in this section, with the complete evaluation presented later within the Signal Evaluation or Characterisation of Risks sections.

Authors should avoid introducing new scientific evidence here that is not discussed elsewhere within the report. Likewise, conclusions presented later in the PBRER should remain consistent with the actions described in this section.

Writing Tip

Think of this section as introducing the regulatory consequences of new safety information. The detailed scientific evidence belongs later in the report; this section explains how that evidence has already influenced regulatory action.

Categories of Safety Actions

Safety actions may differ considerably in their regulatory implementation, but they generally pursue one or more common objectives. Understanding these objectives helps authors present actions logically and allows reviewers to appreciate how emerging safety information has influenced regulatory decision-making.

Rather than describing every action individually, related actions should be grouped according to the regulatory outcome they are intended to achieve.

Product Information Changes

The most common safety actions involve changes to approved product information.

These may include revisions to the Summary of Product Characteristics (SmPC), Package Leaflet (PL), United States Prescribing Information (USPI) or equivalent national product information documents.

Examples include:

• addition of new adverse reactions;
• introduction of contraindications;
• strengthening of warnings and precautions;
• revised recommendations regarding dose adjustment;
• additional monitoring recommendations;
• changes to use in pregnancy or lactation;
• revisions to paediatric use;
• recommendations regarding laboratory monitoring.

Although these actions may appear administrative, they frequently represent the final outcome of extensive signal evaluation and benefit-risk assessment.

Authors should briefly explain the underlying safety concern while avoiding repetition of the detailed scientific assessment presented elsewhere in the report.

Risk Minimisation Measures

Some safety concerns cannot be adequately managed through product information alone.

Additional risk minimisation measures may therefore be implemented to reduce the frequency or severity of important risks.

Examples include:

• educational materials;
• prescriber guides;
• patient information booklets;
• patient alert cards;
• pregnancy prevention programmes;
• controlled distribution programmes;
• physician certification programmes;
• additional laboratory monitoring;
• patient monitoring programmes.

Where several measures are introduced as part of a single risk minimisation strategy, they should normally be described together.

The discussion should explain the objective of the risk minimisation programme rather than listing every educational document individually.

Authors should also ensure consistency with the corresponding discussions later within the PBRER and, where applicable, the Risk Management Plan.

Regulatory Communications

Communication of important safety information is itself an important regulatory action.

Examples include:

• Direct Healthcare Professional Communications (DHPCs);
• Dear Healthcare Professional Letters;
• Drug Safety Communications;
• national safety alerts;
• public health advisories.

These communications usually reflect completion of a regulatory assessment rather than representing independent safety actions.

Accordingly, the report should briefly explain the safety issue that prompted the communication, identify the regions where it was distributed and, where relevant, describe its relationship to associated changes in product information or risk minimisation measures.

Routine publication of safety newsletters or periodic communications that do not arise from a specific safety concern generally do not belong in this section.

Marketing Authorisation Actions

Certain safety concerns require regulatory action affecting the marketing authorisation itself.

Examples include:

• suspension of the marketing authorisation;
• revocation;
• withdrawal for safety reasons;
• restriction of approved indications;
• limitation of the treated population;
• introduction of specialist prescribing requirements.

These actions usually represent significant regulatory decisions and should therefore receive proportionately greater discussion than routine product information updates.

The report should distinguish clearly between actions taken because of safety concerns and commercial decisions such as portfolio rationalisation or strategic withdrawal from a market.

Where marketing authorisation actions affect only selected countries, the geographical scope should be explained together with the reasons for regional differences where these are known and relevant.

Medical Review Consideration

Confirm that marketing authorisation actions described in this section are reflected consistently throughout the remainder of the PBRER, particularly within the benefit-risk evaluation and conclusions.

Complex Regulatory Scenarios

Preparation of the "Actions Taken for Safety Reasons" section is often straightforward when a single regulatory action has been implemented in response to a clearly defined safety concern. However, many aggregate reports involve more complex situations where multiple actions, different regulatory authorities or varying regional decisions must be presented in a balanced and scientifically coherent manner.

The objective in these situations is not to describe every operational activity but to explain clearly how safety concerns have influenced regulatory decision-making.

One Safety Concern Leading to Multiple Regulatory Actions

A single safety issue frequently results in several related regulatory actions.

For example, identification of an important hepatotoxicity risk may lead to revision of the Summary of Product Characteristics, amendments to the Package Leaflet, distribution of a Direct Healthcare Professional Communication (DHPC), implementation of educational materials and enhanced liver function monitoring.

Although these represent separate regulatory activities, they should generally be discussed together because they form part of a single regulatory response.

The emphasis should remain on the underlying safety concern and the overall regulatory strategy rather than producing separate descriptions for each individual action.

Different Regulatory Decisions in Different Countries

Regulatory authorities may reach different conclusions during the same reporting interval.

For example, one authority may approve revised product information while another requests additional data before implementing similar changes. Likewise, certain countries may introduce additional monitoring requirements that are not adopted elsewhere.

Authors should accurately describe these regional differences without implying that one regulatory position is necessarily more appropriate than another.

Where differences are important to interpretation of the benefit-risk profile, they should be explained objectively together with any known scientific or regulatory reasons.

The section should avoid becoming a country-by-country regulatory history unless such detail is necessary to understand the overall safety evaluation.

Company-Initiated and Authority-Requested Actions

Safety actions may be initiated voluntarily by the Marketing Authorisation Holder or requested by one or more regulatory authorities.

Examples of company-initiated actions include voluntary strengthening of warnings following internal signal evaluation, implementation of educational materials before completion of formal regulatory review or temporary suspension of product distribution while additional investigations are undertaken.

Authority-requested actions may arise following review by PRAC, national competent authorities, the FDA, MHRA, PMDA or other regulatory agencies.

The emphasis should not be on attributing responsibility but on explaining the safety concern, the action implemented and its significance for the ongoing benefit-risk evaluation.

Temporary and Permanent Regulatory Measures

Not all safety actions are intended to remain in place indefinitely.

Some measures are implemented as temporary precautions while additional information is collected. Examples include temporary suspension of distribution, interim prescribing restrictions, enhanced laboratory monitoring or temporary contraindications pending completion of further investigations.

Other actions, such as permanent contraindications, withdrawal of indications or revocation of marketing authorisations, represent enduring regulatory decisions.

Where the regulatory status of an action remains under review at the data lock point, authors should clearly describe the current position and avoid implying that temporary measures represent final regulatory conclusions.

Ongoing Regulatory Procedures

A medicinal product may be undergoing formal regulatory review during preparation of the PBRER.

Examples include referrals under European Union legislation, ongoing safety reviews, requests for additional analyses or emerging discussions regarding potential changes to product information.

The existence of an ongoing procedure does not itself constitute a safety action.

Instead, this section should describe actions that have already been implemented during the reporting interval.

Ongoing evaluations that have not yet resulted in regulatory action are generally discussed more appropriately within the relevant scientific sections of the report or, where applicable, as late-breaking information.

Authors should therefore distinguish carefully between regulatory review and regulatory action.

Writing Tip

Do not confuse a regulatory procedure with the outcome of that procedure. Report implemented actions here; discuss ongoing scientific evaluation in the appropriate later sections.

Safety and Quality Issues Occurring Together

Occasionally, a quality defect also has important safety implications.

Examples include contamination, particulate matter, sterility failures or incorrect product strength that result in recalls or additional patient monitoring.

In these situations, the section should focus upon the safety-related regulatory actions rather than providing a detailed investigation of manufacturing deficiencies.

The manufacturing investigation belongs elsewhere within the quality system, whereas the PBRER should explain how the quality issue affected patient safety and what regulatory measures were implemented to mitigate the associated risk.

Generic Products, Biosimilars and Licensing Partners

Products marketed under different commercial arrangements may require coordinated regulatory actions across several Marketing Authorisation Holders.

For example, a safety concern identified for an originator product may result in harmonised updates to generic products or biosimilars. Similarly, licensing partners may implement aligned changes to product information according to contractual pharmacovigilance responsibilities and local regulatory requirements.

Authors should describe the safety action relevant to the medicinal product within the scope of the PBRER while ensuring consistency with globally agreed safety positions where appropriate.

Commercial relationships should only be described where they are necessary to explain differences in implementation or regulatory timing.

Inspection Insight

Inspectors frequently review whether important safety actions have been implemented consistently across affiliated companies, licensing partners and regional Marketing Authorisation Holders. Organisations should therefore maintain clear documentation demonstrating how global regulatory decisions were communicated, assessed and implemented locally.

Writing High-Quality Narratives

The quality of this section depends not only upon selecting the correct regulatory actions but also upon presenting them in a manner that allows assessors to understand the evolution of the medicinal product's safety profile.

Well-written narratives explain the relationship between emerging safety information and the regulatory response without overwhelming the reader with unnecessary operational detail. The emphasis should remain on regulatory significance rather than chronology alone.

The section should answer four questions for every important safety action.

• What happened?
• Why did it happen?
• What action was taken?
• How does this influence interpretation of the remainder of the PBRER?

If these questions are answered clearly, the section will usually achieve its regulatory objective.

Maintain an Objective Scientific Tone

Aggregate reports are regulatory scientific documents rather than advocacy documents.

Authors should therefore describe regulatory actions objectively without attempting to justify, defend or criticise decisions made by the Marketing Authorisation Holder or regulatory authorities.

Statements should be factual, balanced and supported by the available evidence.

Avoid language suggesting certainty where uncertainty remains.

For example, phrases such as "following evaluation of the available safety data" or "based on the current benefit-risk assessment" are generally preferable to definitive statements that extend beyond the available evidence.

Distinguish Facts from Interpretation

One of the easiest ways to improve clarity is to separate observed regulatory events from scientific interpretation.

For example:

Fact:

"A Direct Healthcare Professional Communication was distributed in the European Union during the reporting interval."

Interpretation:

"The communication was introduced to increase awareness of the identified risk while additional pharmacovigilance activities continued."

Separating these concepts reduces ambiguity and allows readers to distinguish documented regulatory actions from the author's interpretation of their significance.

Avoid Repetition

This section introduces important regulatory actions.

It should not reproduce detailed discussions that belong elsewhere within the PBRER.

For example:

• detailed signal evaluation belongs within Signal Evaluation;

• comprehensive discussion of identified risks belongs within Characterisation of Risks;

• detailed assessment of educational programmes belongs within the Effectiveness of Risk Minimisation section;

• overall regulatory conclusions belong within the Integrated Benefit-Risk Evaluation.

Brief cross-referencing of concepts is appropriate, but unnecessary repetition should be avoided.

Maintain Consistency Throughout the Report

Safety actions described in this section should be reflected consistently throughout the remainder of the PBRER.

Important considerations include:

• consistent terminology;

• identical implementation dates where relevant;

• consistent description of affected indications, formulations and populations;

• consistent naming of regulatory authorities;

• consistent description of risk minimisation measures.

Inconsistencies between sections may reduce confidence in the overall quality of the report even when the underlying scientific conclusions remain correct.

Use Appropriate Levels of Detail

Not every safety action requires the same degree of discussion.

Major regulatory actions, such as suspension of a marketing authorisation, introduction of a Pregnancy Prevention Programme or implementation of important contraindications, generally warrant more explanation than routine updates to existing product information.

The amount of detail should therefore reflect the potential impact of the action upon patient safety and the overall benefit-risk profile of the medicinal product.

Avoid presenting every action with identical prominence.

Instead, allow the scientific and regulatory importance of the action to determine the level of discussion.

Present Related Actions Together

Readers should be able to understand the complete regulatory response to an important safety concern without searching throughout the report.

Where several actions arise from the same issue, present them together.

For example, a new identified risk may lead to:

• revisions to the SmPC;

• revisions to the Package Leaflet;

• a Direct Healthcare Professional Communication;

• additional educational materials;

• enhanced laboratory monitoring.

These should normally be described as components of a coordinated regulatory response rather than as unrelated regulatory events.

Explain Regional Differences Clearly

Regional differences are common within global aggregate reports.

Different authorities may approve regulatory actions at different times or implement different measures based upon local legislation, available evidence or national clinical practice.

Authors should describe these differences objectively without implying inconsistency or error.

Where appropriate, explain that regulatory review remained ongoing in certain regions at the data lock point.

The objective is to provide regulatory context rather than compare regulatory authorities.

Writing Tip

A reviewer reading only this section should understand how the medicinal product's safety profile evolved during the reporting interval. A reviewer reading the entire PBRER should never encounter contradictory descriptions of the same regulatory action.

Common Mistakes

Although the "Actions Taken for Safety Reasons" section is usually concise, it is frequently associated with deficiencies identified during internal quality review, regulatory assessment and pharmacovigilance inspections. Most deficiencies arise not because important actions were omitted, but because the purpose of the section was misunderstood.

Understanding these common pitfalls helps authors prepare reports that are scientifically accurate, internally consistent and easier for regulators to assess.

Including Actions That Were Not Taken for Safety Reasons

Perhaps the most common mistake is including events that are unrelated to patient safety.

Examples include:

• commercial withdrawal from markets;
• portfolio rationalisation;
• transfer of marketing authorisations;
• changes in distributors;
• manufacturing site transfers;
• routine packaging updates;
• organisational restructuring.

These activities may be important elsewhere within the PBRER but should not be presented as safety actions unless they occurred because of an identified or potential safety concern.

Before including any event, authors should ask:

"Would this action have occurred if the safety concern had not existed?"

If the answer is no, the event probably belongs elsewhere within the report.

Confusing Regulatory Procedures with Regulatory Actions

Initiation of a regulatory review is not itself a safety action.

For example, referral procedures, requests for additional information, ongoing safety reviews or committee discussions represent regulatory processes.

The actions resulting from those processes—such as revised product information, new contraindications or implementation of additional risk minimisation measures—are the events that normally belong in this section.

This distinction is important because ongoing procedures may continue beyond the reporting interval without resulting in immediate regulatory action.

Presenting Every Label Change

Not every amendment to product information represents an important safety action.

Minor editorial revisions, harmonisation of wording, correction of typographical errors or administrative updates usually add little value to the reader's understanding of the evolving safety profile.

The emphasis should remain on clinically meaningful changes arising from safety evaluation.

Excessive Operational Detail

Another common mistake is describing internal operational activities rather than regulatory outcomes.

For example, detailed descriptions of committee meetings, internal governance processes, document approval workflows or implementation planning rarely assist regulators in understanding how the medicinal product's safety profile evolved.

The report should describe the regulatory action and its significance rather than the internal administrative processes that preceded implementation.

Inconsistency Between Sections

Important regulatory actions described here should appear consistently throughout the remainder of the PBRER.

For example, introduction of a new contraindication should also be reflected within the evaluation of risks, risk minimisation discussions and integrated benefit-risk assessment where appropriate.

Conflicting dates, inconsistent terminology or contradictory descriptions reduce confidence in the overall quality of the report and may prompt unnecessary regulatory questions.

Omitting Regional Context

Global aggregate reports frequently involve regional differences in regulatory implementation.

Failure to identify the geographical scope of an action may create confusion regarding whether the action applies worldwide or only within selected jurisdictions.

Where implementation differs between regions, the report should describe those differences clearly and objectively.

Overstating Regulatory Significance

Authors should avoid implying that every safety action represents a major change in the benefit-risk profile.

Many actions represent precautionary measures intended to optimise safe use while the overall benefit-risk balance remains favourable.

The narrative should therefore remain balanced and proportionate to the available evidence.

Inspection and Regulatory Assessment Considerations

Although this section is relatively short, inspectors and regulatory assessors frequently examine it because it provides a concise summary of how important safety information has been translated into regulatory action.

During review, assessors commonly evaluate whether:

• all important safety actions implemented during the reporting interval have been included;
• actions are described accurately and consistently;
• implementation dates correspond with regulatory records;
• product information changes are reflected correctly;
• actions are supported by the scientific discussions presented later in the PBRER;
• regional implementation has been described appropriately;
• important risk minimisation measures are consistent with the current Risk Management Plan where applicable.

During pharmacovigilance inspections, organisations may also be expected to demonstrate how safety actions were identified, approved, communicated and implemented across relevant functions and territories.

Where global companies operate through affiliated Marketing Authorisation Holders or licensing partners, inspectors may review evidence that significant regulatory actions were communicated appropriately and implemented consistently according to local regulatory requirements.

Inspection Insight

Inspectors are rarely interested only in whether a safety action occurred. They are equally interested in whether the organisation can demonstrate an effective governance process linking signal evaluation, regulatory decision-making, implementation and ongoing effectiveness monitoring.

Key Takeaways

The "Actions Taken for Safety Reasons" section explains how important safety information has already influenced regulatory decision-making during the reporting interval.

Its purpose is not to catalogue every regulatory event but to present clinically meaningful actions that contribute to understanding of the evolving benefit-risk profile of the medicinal product.

High-quality reports distinguish clearly between safety actions and unrelated commercial or administrative activities, present related actions together, maintain consistency throughout the PBRER and provide sufficient context to support subsequent scientific discussions.

When written effectively, this section acts as the regulatory bridge between emerging safety information and the detailed scientific evaluation presented later within the report.

Continue Reading

The concepts discussed in this article are closely related to the following guides:

• [[writing-the-changes-to-reference-safety-information-section-in-a-pbrer]]
• [[writing-the-estimated-exposure-section-in-a-pbrer]]
• [[writing-the-signal-evaluation-section-in-a-pbrer]]
• [[writing-the-characterisation-of-risks-section-in-a-pbrer]]
• [[writing-the-integrated-benefit-risk-evaluation-section-in-a-pbrer]]
• [[risk-management-plans]]
• [[benefit-risk-evaluation]]

References

Primary Regulatory References

1. ICH. E2C(R2): Periodic Benefit-Risk Evaluation Report (PBRER).

2. European Medicines Agency. Good Pharmacovigilance Practices (GVP) Module VII – Periodic Safety Update Report.

3. Directive 2001/83/EC on the Community code relating to medicinal products for human use.

4. Regulation (EC) No 726/2004.

5. Commission Implementing Regulation (EU) No 520/2012.

Supporting Regulatory Guidance

1. EMA Questions and Answers on Periodic Safety Update Reports (latest version).

2. EMA Procedural Guidance for PSUSA procedures.

3. Relevant PRAC procedural guidance documents where applicable.

Scientific References

1. CIOMS Working Group reports relevant to aggregate reporting and benefit-risk evaluation.

2. Edwards IR, Aronson JK. Adverse drug reactions: definitions, diagnosis and management. Lancet.

3. Hauben M, Aronson JK. Defining 'signal' and its subtypes in pharmacovigilance.