CTD, Safety

Tanja BraakmanGenzyme Europe BVPharmacovigilance Department

CTD, Safety

2.7.4 Summary of Clinical Safety

1.x EU-RMP

2.7.4 Summary of Clinical Safety

Summary of data relevant to safety in the intended patient population; integration of individual CSRs or other reports

2.7.4 Summary of Clinical Safety

Exposure to the Drug Adverse Events Clinical Laboratory Evaluations Vital Signs, Physical Findings, and

Other Observations Safety in Special Groups and

Situations Post-Marketing Data Appendix

Exposure to the Drug Overall Safety Evaluation Plan and

Narratives of Safety Studies Special considerations, non clinical data,

relevant pharmacological class effects, sources of safety data

Overall Extent of Exposure Demographic and Other Characteristics of

Study Population Age ranges ( ICH E7/ICH E11) Severity of disease, hospitalisation, impaired

renal function, concomitant illnesses or medications, geographical location

Adverse Events Analysis of Adverse Events

Frequency of adverse events (drug vs comperator vs placebo)

By dose (by severity, by time, by causality) Pooling of safety data

Common adverse events Deaths Other Serious Adverse Events Other Significant Adverse Events (substantial

intervention) Analysis of Adverse Events by Organ System or

Syndrome (potential related events) Narratives

Clinical Laboratory Evaluations

Mean and median (central tendencies) Range of values; number of patients

with abnormal values Clinically important abnormal lab

value (discontinuations) Relationship to dose, drug concentration,

disappearance with continued treatment, positive dechallenge, positive rechallenge, concomitant medication

Vital Signs, Physical Findings, and Other Observations

See previous slide QT interval prolongation

Safety in Special Groups and Situations Intrinsic Factors (demographic and other factors –ICH

E5) Extrinsic Factors (patient environment)

Drug Interactions Use in Pregnancy and Lactation Overdose Drug Abuse Withdrawal and Rebound Effects on Ability to Drive or Operate

Machinery or Impairment of Mental Ability

Post-Marketing Data

PSURs

1.X EU-RMP

Guideline on Risk Management Systems for Medicinal Products for Human Use (Draft)

A set of pharmacovigilance activities and interventions designed to proactively identify, characterise and prevent or minimise risks relating to medicinal products, including risk communication and the assesment of the effectiveness of risk minimisation interventions.

EU-RMP

Part I (ICH –E2E)

A Safety Specification A Pharmacovigilance Plan, and

Part II Evaluation of the need for risk

minimisation measures, and if there is such a need:

A risk minimisation plan

EU-RMP Safety Specification (basis of risk minimisation)

Important identified risks, Important potential risks, and important missing information

Non-clinical Clinical

Limitations of the human safety database Populations not studied pre-authorisation (children,

elderly, pregnant or lactating women, different disease severity)

Adverse Events/Adverse Reactions (identified and potential risks, potential for overdose, presentation of risk data, potential for medication error, potential for illegal use, potential for transmission of infectious agents, interactions, epidemiology, pharmacological class effects)

Summary

EU-RMP Pharmacovigilance Plan

Routine Pharmacovigilance Practice Additional pharmacovigilance activities

and action plans Action Plan for safety concern

Evaluation of the need for a Risk Minimisation Plan Risk(s) of particular nature and

seriousness that minimisation actions are needed

EU-RMP

Risk minimisation plan Actions taken to reduce the risk

associated with an individual safety concern Risk minimization tools (risk

communication) Marketing authorisation Ensuring the effectiveness of risk

minimisation tools

Thank you!