07 June (Day 6) PBRS 2015 PMS & DS
•
14 j'aime•1,503 vues
The document discusses post-marketing drug safety and surveillance. It begins by discussing the thalidomide tragedy in the 1950s and 1960s that led to increased regulation. It then discusses several more recent drug safety issues in the 21st century. The bulk of the document focuses on the importance of pharmacovigilance and post-marketing surveillance in monitoring drug safety, identifying new risks, and ensuring drug quality after approval. It describes the goals, principles, and methods of post-marketing surveillance and emphasizes its critical role in balancing drug efficacy and safety.
Recommandé
Contenu connexe
Tendances
Tendances (20)
En vedette
En vedette (20)
Similaire à 07 June (Day 6) PBRS 2015 PMS & DS
Similaire à 07 June (Day 6) PBRS 2015 PMS & DS (20)
Plus de Obaid Ali / Roohi B. Obaid
Plus de Obaid Ali / Roohi B. Obaid (20)
Dernier
Dernier (20)
07 June (Day 6) PBRS 2015 PMS & DS
- 2. Post Marketing Surveillance & Drug Safety Day 6 Pharmaceutical & Biological Regulatory Sciences (PBRS 2015) 07th June 2015 Obaid Ali & Roohi B. Obaid
- 4. Opening Question Is dying from a disease unavoidable? Is dying from an adverse drug reaction unacceptable? Yes, Sometimes No, Not acceptable
- 6. Thalidomide Tragedy …. Paradigm Shift 1954, Synthesis in West Germany by Grunenthal Available to patient in 1957 in West Germany Available in 46 countries till early 1960s Withdrawal in Dec 1961 Available in Canada till 1962 Called as “wonder drug” for safe and sound sleep
- 7. Thalidomide Tragedy …. Paradigm Shift Effective against symptoms associated with morning sickness Thalidomide crossed the placental wall Peripheral neuritis Killer and disabler of thousands of babies
- 8. Thalidomide Tragedy …. Paradigm Shift Birth malformation, some survived with Deafness BlindnessDisfigurement Cleft palate Phocomelia
- 9. Thalidomide Tragedy …. Paradigm Shift 5000 survivors
- 10. In 21st Century
- 11. In 21st Century
- 12. …… in 21st Century Vioxx
- 13. …… in 21st Century Heparin
- 14. …… in 21st Century Aprotinin
- 15. …… in 21st Century Rosiglitazone
- 16. …… in 21st Century Sibutramine
- 18. Balance in Safety & Efficacy Furazolidone
- 19. Balance in Safety & Efficacy
- 20. Balance in Safety & Efficacy
- 23. Efficacy & Quality Bupripion HCl tab • Study on low dose and waiver on high dose Failure • Desired kinetics was not achieved Teva • FDA asked to stop distribution in sep 2012
- 24. Efficacy & Quality In 2006, Generic version Mfg by Impax/Teva were approved Based on evidence demonstrating BE with low strength Bupripion SR Tab 1996 & XL Tab 2003 Bupripion (Wellbutrin) IR Tab of SKB 1985 Re-switched on brand Increased side effects, Decreased therapeutic effect Experienced undesirable effects 85 post marketing reports from Jan-Jun 2007 B U P R I P I O N
- 25. Efficacy & Quality Withdrawal of Teva drug in Mar 2013 against Sep 2012 FDA advice Conducted study FDA re-examined BE data Temporal relationship under question Its life, please care General rule will not work always A new challenge Also generic of Actavis withdraw their version B U P R I P I O N
- 30. Efficacy & Quality Metoprolol Succinate Tabs ER Recall due to dissolution Tropol XL (Sandoz) approved in 1992 Therapeutic failure reported in 2007 Formulation had not been properly validated (FDA 2008) 2009 Ethex (KV Pharmaceuticals) 2014 Wockhardt & Ranbaxy Recalled due to dissolution What do you think? What should we learn?
- 32. Quality: Tablets Mix up Child resistant caps Less quantity Wrong label Discoloration Chipping Broken edges Empty pockets in blister Sticking Cracking of tablet Material release from within the tablet etc.
- 33. Quality: Tablets
- 34. Quality: Capsules Caps locking problem Disintegration Dissolution Uniformity of weight Content uniformity
- 40. Quality: Cosmetic Issues Label color Shape of secondary packaging
- 43. Surveillance & Pharmaco-epidemiology Use & off label use
- 44. Surveillance & Pharmaco-epidemiology Therapeutic Effect & Adverse Reactions
- 45. Pharmacovigilance is here The science and activities relating to the detection, evaluation, understanding and prevention of adverse drug reactions or any other drug-related problems
- 46. Humans are Best Creatures of God
- 47. Look at the magnitude from documented References Adverse Drug Reactions are among the top ten causes of mortality The percentage of hospital admissions due to drug related events in some countries is about or more than 10%. Drug related morbidity and mortality expenses exceeded US$ 177.4 billion in the USA in 2000 50% can be avoided/ managed
- 48. Pharmacovigilance is here Post- market adverse event safety evaluation Serious AE-about 3 to 4,000 reports/day Perform overall safety reviews Perform reviews of specific safety issues FDA Increase per year 160, 000 > 3.5 million per year
- 49. Pharmacovigilance Aim Early detection of unknown safety signals Detection of elevated safety issues Risk factors Identification Risk Assessment Management & Mitigation Strategy
- 50. Pharmacovigilance Practice Applies to post-marketing activities Involves all activities relating to monitoring of product safety • Collection • Detection • Assessment of adverse effects or risks of products
- 51. Elements of AE Report Temporal relationship to drug Therapy details (dose, dates/duration of use) Baseline patient status (age, co- morbid conditions, concomitant medications, risk factors) Details of adverse event (AE) Lab results at baseline and during event Clinical course of AE including outcomes Method of diagnosis of AE Dechallenge and rechallenge information
- 52. Assessment of previously unrecognized (unlabeled) serious adverse events Hands-on daily assessment direct reports, monitors all safety issues including known adverse events Extensive monitoring in initial years of New Molecular Entities but continued
- 53. Principles of Case Evaluation Disease occurrence in expected time Absence of symptoms prior to exposure Positive de-challenge or re- challenge
- 54. Principles of Case Evaluation Consistent with pharmacological effects Consistent with known effects in the class Event identified in clinical trials Absence of alternative explanations
- 55. Surveillance & Pharmaco-epidemiology Signals of Safety
- 56. Safety Signals New unlabeled adverse events An observed increase in a labeled event in its severity or specificity New drug or food interactions Newly identified at-risk population Catch
- 57. Identifying Safety Signals Depends on Good Reporting Practice to acquire quality case information to perform case- level review or case-series • Acquire complete information during initial contacts and subsequent follow up • Entail a focused line of questioning
- 58. Evaluating Potential Signals Safety issue of interest identified AE literatures search for related cases Case definition established; cases assessed Additional cases: Literature, WHO, foreign regulators
- 59. Data Mining Provides additional support to the case report evaluation and other safety information Comparison of observed frequency of reports for specific drug/event combination to expected frequency of reports for that AE in entire database
- 60. Epidemiological Analysis Review and analysis of Phase IV studies Additional study in longitudinal databases Cooperative Agreements Reporting Rates cases/estimated usage Comparison with background rates Comparison to drugs within the same class Comparison to drugs for similar indication Interpretation difficult to make
- 61. Potential Regulatory Radar Modification in Labeling Alert to Doctors & Pharmacists Mitigation strategy Ban & withdrawal
- 62. Aim of Regulation PMR: Assessment of safety and effectiveness of new medical technology PS&C: Inspection of manufacturing facilities and products to assure safety, quality & compliance with regulations C&PS: Post-marketing surveillance to ensure the safety of consumers & patients who use regulated products
- 63. Science speaks & is visible Drug Risks Safe Use EvaluateBalance
- 64. Gravity of Regulation • Passive spontaneous surveillance • Adverse Event Reporting • Spontaneous reports Assessment Pharmacovigilance • Understand case series • Epidemiological studies • Drug use analyses Epidemiological analyses • Trade name, packaging, & labeling Assessment • Medication errors examination Medication Error Prevention • Proposed plans Evaluation • Ongoing plans Monitoring Risk Management Plans
- 65. Medicine Safety
- 66. Pharmacovigilance is soul of Regulation Animal Experiments: Relevant? Clinical Trials: Complete? Pre marketing Safety Data
- 67. Pharmacovigilance is soul of Regulation Post marketing ……. Unexpected AR Interactions Risk factors Quality of life Long-term efficacy Cost assessment
- 68. Surveillance & Pharmaco-epidemiology Use Pattern
- 69. Surveillance & Pharmaco-epidemiology New Interactions
- 75. Pharmaco-Metrics Supportive experiment Clinical trial Clinical experience in post marketing Data informing the decisions are complex and diverse Efficiency of drug development
- 77. Drug Safety
- 78. Drug Safety From Clinical Trial
- 80. Drug Safety Risk Evaluation & Mitigation Strategies
- 85. Drug Safety Drug Information & Poison Centres
- 87. Drug Safety Periodic Safety Update Report
- 88. Drug Safety Adverse Event Followed by Immunization
- 89. Stay Safe , live attention & go healthy
- 90. Stay Safe , Live Attention & Go Healthy Proton Pump Inhibitors Fluoroquinolones
- 91. Stay Safe, Live Attention & Go Healthy Domperidone Ketoconazole
- 92. If you don’t have further question