Risk Management Plan
-Bayer Experience :
Organization & Processes
Najoua ADYEL
Introduction:
Pharmacovigilance toward maturity
50’s and 60’s: from nothing to reacting late
70’s’: foundation of Pharmacovigilance principles 80’s to 90’s : From reacting late to reacting earlier 2000’ Getting proactive and fast reacting
Guideline on Risk Management Planning
Proactive Risk Evaluation and Risk Mitigation measures
Use of IT systems aimed at earlier detection of safety signals Use of large scale databases for signal detection
Pharmacovigilance nowadays
Increasingly stringent heavy and complex
Collection and evaluation of Individual Case Safety Reports (ICSRs) Wider array of source of safety information under scope
Compilation of aggregate reports as (PSURs)
Earlier detection and analysis of potential safety signals
New Pharmacovigilance activities
Proactive Risk Identification
Proactive Risk Management plan Post-approval safety studies
Proactive Risk Minimization measures
> 500 FTEs worldwide (+ external FTE) > 70 sites
5 global centers + 1 outsourcing center
Bayer Global Pharmacovigilance:
Organization with a global footprint
Montville Montville Sao Paulo Sao Paulo Berlin Berlin Wuppertal Wuppertal Beijing Beijing Mumbai Mumbai
Bayer Global Pharmacovigilance
Partnering for Compliance
fu n c ti o n a l C o m m u n ic a ti o n C o m m u n ic a ti o n R is k M a n a g e m e n t T ru s tf u l p a rt n e r
Pharmacovigilance supports business success
C ro s s -f u n c ti o n a l p a rt n e ri n g S a fe ty C o m m u n ic a ti o n S a fe ty C o m m u n ic a ti o n P ro a c ti v e R is k M a n a g e m e n t T ru s tf u l p a rt n e r fo r H A s
Processes involved in Risk
Management at Bayer
Scheduled review of the accumulating safety information Evaluation of the outcome of computerized signal detection Scheduled delivery of Risk Management documents
Structured process for the review of RM documents Safety Risk Management decision gate process Safety Risk Management decision gate process
Structured process for escalating safety observations and assess whether they constitute safety signals
All processes apply during clinical development and afterwards, throughout the entire life cycle of the product
Bayer Responsibilities at Local level:
Regulatory
Interact with Local HA regarding RM activities
Adapt Safety RMP to Country requirements
Prepare Country-specific RM document if required
Prepare RMP for local products if required
Decide whether the Safety RMP should be submitted if not formally required by regulation
Address country-specific RM requirements and escalate them to the Global Safety Leader
Bayer Responsibilities at Local level:
Implementation
Verify whether safety interventions (e.g. risk mitigation measures) stipulated in the global Safety RMP are locally feasible; if not, alternative interventions should be defined
Implement and supervise the execution of the safety interventions stipulated Implement and supervise the execution of the safety interventions stipulated in the Safety RMP or the alternative interventions agreed upon with the Core SMT
Implement safety interventions according to core RMP and/or according to alternative interventions defined. Provide feed-back to the Core SMT
Risk Management Plan in summary
A set of Pharmacovigilance activities designed to:
Identify, characterize, prevent, or minimize risks related to the medicine Assess the effectiveness of those interventions
Communicate those risks to patients and health care providers
Components of the RMP Components of the RMP
Detection of the risk Assessment of the risk Minimization of the risk
Safety Risk Management Activities
Safety Risk Management activities have one of the following three major objectives: Increase knowledge
Influence behavior on appropriate use of the product Restrict access to the product
For each of these objectives there is a set of activities / tools that are generally appropriate to meet those objectives.
Risk Management guidance and tools
according to the ICH Guidelines
Aid planning PV activities in preparing early postmarketing period
Focus on a Safety Specification and Pharmacovigilance Plan that might be submitted at the time of the MA application
Describes a method for summarizing
Important identified risks Important potential risks
Important missing information including potentially at-risk
populations/situations where the product is likely to be used that have
not been studied prior to approval
Proposes a structure for a Pharmacovigilance Plan and sets out
principles of good practice for the design and conduct of observational studies.
Benefits expected from a Risk
Management Plan
Increase knowledge and raise awareness on:
The safety profile of the product
The sub-populations at risk who require more cautious use The proper way to use the product in patients at risk
Influence behavior on appropriate use of the product: Influence behavior on appropriate use of the product:
Ensure prescription in safe conditions
Ensure cautious prescription and use in patients at risk
Restrict access to the product
Prevent the use of the drug in patients to whom risks would exceed benefits
Key terminology
Risk mitigation: measure to minimize the impact of AEs which have occurred e.g.
Pedicure care to patients experiencing drug-induced hand and foot skin reaction
Risk minimization: measure to prevent the occurrence of an identified risk e.g.
risk e.g.
Ensuring that only patients with positive risk vs benefit receive the drug
Special attention to patients at higher risk of occurrence of an AE to ensure early detection of the AE and timely intervention
Risk management: broader term covering standard pharmacovigilance practice, risk assessment, risk minimization and risk mitigation measures
Routine risk minimization activities
Routine risk minimization activities are those which apply to every medicinal product. These relate to:
• the summary of product characteristics; • the labelling;
• the package leaflet; • the package leaflet;
• the pack size and design
• the legal (prescription) status of the product.
The summary of product characteristics (SmPC) and the package leaflet are important tools for risk minimization as they constitute a controlled and standardized format for informing healthcare professionals and patients about the medicinal product.
Additional risk minimization activities
Those risk minimization measures which are not the routine risk minimization activities. They should only be suggested when essential for the safe and effective use of the medicinal product and these should be science based, and developed and provided by suitably qualified people.
If additional risk minimization activities are proposed, these should be detailed and a justification of why they are needed provided.
and a justification of why they are needed provided.
Any communication material should be clearly focused on the risk
minimization goals, and should not be confused or combined with promotional
material for marketing campaigns.
Additional risk minimization measures can include:
Educational programs
Controlled access programs
Methods for Risk Minimization
If provision of information and education is sufficient to achieve risk reduction
SmPC and Package Leaflet (routine risk management)
Additional Educational Material (additional risk management)
The need for additional material beyond the Summary of Product
Characteristics and Package Leaflet depend upon the risk and should be considered case-by-case
considered case-by-case
Otherwise, if provision of information/education is not sufficient to achieve risk reduction
Legal Status of a Medicine Control at Pharmacy Level
Control of Prescription Size or Validity
Risk Minimization Measures: Examples
In addition to regular labeling (SmPC, Package insert)
Box warning and special contraindication
Additional information and educational measures
Providing HCPs with specific training
Providing HCPs with non-promotional education brochures/letter Providing HCPs with non-promotional education brochures/letter Medication guide/ Education brochure for patients
Restriction measures
Restricting prescription to certified physicians Restricting delivery to certified pharmacists
Restricting dispensing the drug to specific specialized medical institutions
Risk Minimization Measures: Examples
cont’d
Special measures applying to patients
Special patient monitoring Patient enrolled in registry
Periodical monitoring laboratory tests Periodical monitoring laboratory tests
Effectiveness of risk minimization
activities
MAH are encouraged to discuss risk minimization activities with the
competent authorities as early as is feasible when it is likely that specific risk minimization activities will need to be adapted to the different health care systems in place.
For very complex risk minimization measures, it may be appropriate to contact competent authorities, in the countries where it is planned to
market the product, either prior to submitting risk minimization proposals or during the course of the evaluation procedure.
market the product, either prior to submitting risk minimization proposals or during the course of the evaluation procedure.
The need for a strong and dedicated structure for evaluating risk minimization activities
The success of risk minimization activities in delivering these objectives needs to be evaluated throughout the lifecycle of a product to ensure that the burden of adverse reactions is minimized and hence the overall risk-benefit balance is optimized.
Conclusion
The Safety Risk Management process is obviously one of the most complex processes with very far-reaching cross-functional involvement.
Bayer Healthcare Safety Risk Management process takes this into account by alignment to already existing processes, involvement of cross-functional teams, and clear assignment of accountabilities and cross-functional teams, and clear assignment of accountabilities and responsibilities.
