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Outline
Background S f t Surveillance i th Lif Safety S ill in the Lifecycle of l f CDER-regulated Products Postmarketing Safety Surveillance
Postmarketing Safety Regulations
Pharmacovigilance1
The science and activities relating to the g detection, assessment, understanding, and prevention of adverse effects or any other drug-related problems.
A P P R O V A L
PostMarketing
Phase 1
Safety & Dosage
Phase 2
Safety & Efficacy
Phase 3
Safety & Efficacy
A P P R O V A L
PostMarketing
Safety Surveillance
Safety Concerns S f t C
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OSE Mission
The Office of Surveillance and Epidemiology evaluates drug risks and promotes the safe use of drugs by the American People To carry out its mission, OSE works y , together with other offices in CDER
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OSEs Roles
Most of OSEs work = Postmarketing Safety OSE always reviews new product proprietary names from a medication error perspective OSE is sometimes involved with evaluation of p premarketing safety of new p g y products
Examples: risk management, epidemiology studies, specific safety issues f f
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Identifies error-prone aspects of labels, labeling, & packaging of drug products & provides recommendations t minimize user error d ti to i i i
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Laws
The Federal Food, Drug, and Cosmetic Act (including amendments)
includes the basis for most regulatory activities for human drug products, including postmarketing drug safety Recently amended by the Food and Drug Administration Amendments A t (FDAAA) of 2007 Ad i i t ti A d t Act f
FDAAA
Title IX Postmarket Safety of Drugs
Subtitle A Postmarket Studies and Surveillance A, contains new FDA authorities to:
Require postmarketing studies and clinical trials Require sponsors to make safety related labeling changes Require sponsors to develop and comply with risk evaluation and mitigation strategies (REMS)
Subtitle A took effect March 25, 2008 FDAAA mandated FDA to develop an enhanced ability d t d t d l h d bilit to monitor the safety of drugs after these products reach the market (Sentinel Initiative)
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Nonserious: Not serious Unexpected: Not in the current labeling E Expected: I the current labeling t d In th t l b li
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Drugs with approved applications also have requirements to submit Periodic reports of other q p adverse events, including other safety-related info (actions taken due to adverse events)
Every 3 months or every year
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Guidances
Guidances further describe FDAs current thinking on a particular topic
External audience Non-binding on the industry http://www.fda.gov/Drugs/GuidanceComplianceR egulatoryInformation/Guidances/default.htm
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How does post-marketing adverse event & medication error reports get to FDA?
Patients, consumer, Patients consumer and healthcare professionals
Voluntary V l t Voluntary V l t
FDA MedWatch
Manufacturer
regulatory requirements
FDA
AERS Database
5% of all reports
AERS
Adverse Event Reporting System Database
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AERS is a computerized information database designed to support the FDA's postmarketing safety surveillance program for all approved drugs and therapeutic biologic products. The FDA uses AERS to monitor for new adverse events and medication errors that might occur with these marketed products.
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What is in AERS ?
Individual Case Safety Reports (ICSRs)
Adverse Events Medication Errors Product Problems with adverse events
FOR:
D Drugs and therapeutic bi l i (R + OTC) d h i biologics (Rx Homeopathic Products Tissue products, therapeutic blood products
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What is in AERS ?
Paper submissions
3500 (voluntary) and 3500A (mandatory) forms
*I t International C f ti l Conference on H Harmonisation of T h i l Requirements for i ti f Technical R i t f Registration of Pharmaceuticals for Human Use
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Safety Evaluators
Postmarketing Adverse Events Medication Errors Events,
Signal Identification g
Trigger could be AERS or other originating source Review/analyze event reports using AERS
Signal Evaluation
Provide evaluation of safety issues (adverse events and medication errors)
C ll b t with other OSE disciplines Collaborate ith th di i li Collaborate with OND and other CDER offices as appropriate for safety issue Provide recommendations regarding potential regulatory actions
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mmt6
Diapositiva 39 mmt6 suggest moving this bullet point follow under the Signal Identification bullet above
TRUFFAM; 08/08/2011
When a Serious AE is Rare in the Population Spontaneous Reports are M S t R t More U f l Useful
Rare b t serious adverse event R but i d t
Market Introduction Pre-marketing Safety Data
Post-marketing Period
When a Serious AE is Common in the Population Spontaneous Reports are Less Useful
AE common in the population OR is a manifestation of the underlying disease
Market Introduction Pre-marketing Safety Data
Post-marketing Period
Epidemiologists
Risk identification
Provide context for potential signals p g
Drug use data (denominator) Background rates of adverse events (medical literature)
Risk quantification
Review studies/protocols submitted by sponsors for epidemiologic studies to quantify risks Review published studies Conduct population-based epidemiologic studies to quantify risk and identify risk factors
Through direct access to population-based data population based Through collaborations with outside investigators
Integrate active surveillance with current post-market safety I i ill ih k f monitoring systems
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Risk Management
Risk management is an iterative process of
Assessing a products benefit-risk balance product s balance, Developing and implementing strategies to minimize its risks while preserving its benefits, Evaluating tool effectiveness and reassessing the benefit-risk balance, and , Making adjustments, as appropriate, to the risk minimization strategies to further improve the benefit-risk balance 49
What is a REMS* ?
Risk Evaluation and Mitigation Strategy (REMS) may require to include:
Medication Guide (patient labeling) C Communication plan (h lth i ti l (healthcare providers) id ) Elements to assure safe use (ETASU) Implementation system
Social Scientists
Review behavioral or comprehension studies/protocols submitted by sponsors
Often relates to risk management program assessment
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Post-marketing requirement (PMR) studies Risk evaluation and mitigation strategies (REMS) Removal of product from market
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Publish an FDA analysis in a medical journal Postmarket Drug Safety Information for Patients and Providers website
http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationf p g g g y g y orPatientsandProviders/default.htm
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Questions
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