SAFETY REPORTSADDENDUM TO THE

CLINICAL OVERVIEW (ACO)

INDEX

1. ACO Definition2. How to prepare an ACO3. Structure of ACO

ADDENDUM TO THE CLINICAL OVERVIEW (ACO)

Critical discussion addressing the current benefit/risk balance for theproduct on the basis of a consolidated version of safety/efficacy dataaccumulated since the initial MA or the last renewal, taking intoaccount PSURs submitted, suspected adverse reactions reports,additional pharmacovigilance activities and the effectiveness of riskminimization measures contained in the RMP, if applicable.

New signal assessment and new potential or identified risks raisedduring the renewal period that have not been subject to previousassessment should be clearly highlighted in the data provided. Inaddition, it should make reference to any relevant new information inthe public domain.

1. ACO Definition

INFORMATION TO TAKE INTO CONSIDERATION:

• History of pharmacovigilance system inspections.

• Worldwide marketing authorization status.

• Actions taken for safety reasons during the period covered since theinitial marketing authorization or since the last renewal until 90days prior to renewal submission.

• Significant changes made to the SmPC during the period coveredsince the initial marketing authorization or since the last renewal.

• Sales of this product (to calculate the patient exposure).

2. How to prepare an ACO

• Data in summary tabulations: Summary tabulations of seriousadverse events from clinical trials as well as of adverse reactionsfrom post-marketing data sources reported during the periodcovered.

• Overview of signals.

• Relevant information on patterns of medication errors and potentialmedication errors during the period covered.

• Literature.

• Late-breaking information.

THIS ADDENDUM SHOULD BE SIGNED AND ACCOMPANIED BY THE CVOF THE EXPERT (MODULE 1.4.3)

2. How to prepare an ACO

Worldwide existinginformation

• PSURs• Actions taken during

last covered period.• Literature

• Worlwide marketing authorization status

• Global exposure and adverse reactions.

Evaluation

Findings

Discussionand

conclussion

Evidences

Addendum to theclinical overview

Obtention of the Marketing Authorization Renewal.

2. How to prepare an ACO

1.History of Pharmacovigilance system inspections(date, inspecting authority, site inspected, type of inspection and if theinspection is product specific, the list of products concerned) and ananalysis of the impact of the findings overall on the benefit/risk balanceof the medicinal product.

2.Worldwide marketing authorization statusOverview of number of countries where the product has beenauthorized and marketed worldwide.

3. Structure of ACO

3.Actions taken for safety reasons during the period covered since theinitial marketing authorization or since the last renewal until 90 daysprior to renewal submission.

Description of significant actions related to safety that had a potentialinfluence on the benefit-risk balance of the authorized medicinalproduct (e.g. suspension, withdrawal, temporary halt or prematureending of clinical trial for safety reasons, etc.).

Actions taken from the DLP of the last PSUR up to the DLP of therenewal should be clearly identified and highlighted.

3. Structure of ACO

4.Significant changes in SmPCIt should be clearly identified the changes included in the PSURs andthe new changes made from the DLP of the last PSUR up to the DLP ofthe renewal.

5.Patient exposure• Data on cumulative exposure of subjects in clinical trials as

well as of patients from worldwide post-marketing exposureper EU and non EU regions.

• If the MAH becomes aware of a pattern of use of themedicinal product considered relevant for the interpretationof the safety data, a brief description should be provided; suchpatterns may include in particular off-label use.

3. Structure of ACO

6.Data in summary tabulationsSummary tabulations of serious adverse events from clinical trials aswell as summary tabulations of adverse reactions from post-marketingdata sources reported during the period covered since the initialmarketing authorization or since the last renewal up to the DLP of therenewal.

7.Findings from clinical trials and non-interventional studiesSummaries of significant safety and efficacy studies.

3. Structure of ACO

8.LiteratureReview of important literature references published during the periodcovered since the initial marketing authorization or since the lastrenewal until 90 days prior to renewal submission that had a potentialimpact on the benefit/risk of the medicinal product.

3. Structure of ACO

9.Risk evaluationMAH should summarize signals for which evaluation was completedduring the reporting period of the renewal. For signals that becameimportant identified or potential risks or are related to a known risk, acharacterization of the risk should be provided.

The MAH should discuss whether any changes are considerednecessary in the existing safety concerns and whether any additionalrisk minimization activities for the product are warranted, consideringthe data collected during the period covered by the renewal.

3. Structure of ACO

10.Benefit evaluationMAH should summarize important efficacy and effectivenessinformation (including information on lack of efficacy) for the periodcovered since the initial marketing authorization or since the lastrenewal until 90 days prior to renewal submission.

11.Benefit-risk balanceA discussion on the benefit-risk balance for the approved indicationshould be presented, based on the above information.

12.Conclusion

3. Structure of ACO

We are safety experts, if you want to get to know us better visit us on:

Azierta

O follow us on:Azierta @Azierta