Post on 13-Jan-2016
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!