Judging Science & Prior Knowledge Beyond the Line
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Thursday, September 22, 2022, Pearl Continental Hotel, Karachi
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Judging Science & Prior Knowledge Beyond the Line
- 1. Judging Science & Prior Knowledge Beyond the Line Roohi B. Obaid 22 September 2022
- 2. Disclaimer We discuss science, nothing more, nothing less It is experience based learning expression received during last 25 years while dealing hundreds of foreign & domestic inspections, regulatory compliance & enforcements, dozen of meetings with international experts (FDA, EU, Japan, Canada, MHRA) etc. etc. Thoughts represent the current thinking of Centre for Quality Sciences Obaid Ali & Roohi B. Obaid
- 3. April 2021 April 2022
- 4. April 2021 April 2022 16 Sept 2022
- 5. April 2021 April 2022 16 Sept 2022 Is something bigger than these challenges … Corporate companies, FDA, Critical time, highest technology
- 8. New Drug • Non Clinical Studies • Clinical Studies • Product Development • Technology Transfer • Process Validation • Commercial Manufacturing • Change Management • Periodical Reviews • Knowledge Management • Life cycle
- 9. Generic Drug Product Development & Bio-studies only
- 10. Relation between New & Generic Drug New Generic Bio-studies of generic are surrogate for all clinical studies done by innovator
- 11. • Non Clinical Studies • Clinical Studies ….. BioStudies • Product Development • Technology Transfer • Process Validation • Commercial Manufacturing • Change Management • Periodical Reviews • Knowledge Management • Life cycle G M P Zone
- 12. 1 2 3 Technology Transfer Process Validation Controlled Manufacturing GMP Zone
- 13. A B C Specifications Critical Processing Parameters Critical Quality Attributes How …….
- 14. All products that were recalled or withdrawn anywhere, were released after testing Remember, quality cannot be tested but it should be built in the product
- 15. Drug which is tested is not used & The drug which is used is not tested
- 17. Dose 500 mg / day for adult
- 18. Dose 500 mg / day for adult Assay limit 95 – 105%
- 19. Dose 500 mg / day for adult Assay limit 95 – 105%
- 20. Dose 500 mg / day for adult Assay limit 95 – 105% Means 475 – 525 mg
- 21. Dose 500 mg / day for adult
- 22. 01 02 03 04 Dose 500 mg / day for adult
- 23. 01 02 03 04 Dose 500 mg / day for adult Male 50 kg Male 100 kg Female 45 kg Female 90 kg
- 24. 01 02 03 04 Dose 500 mg / day for adult Male 50 kg Male 100 kg Female 45 kg Female 90 kg
- 25. 01 02 03 04 Dose 500 mg / day for adult Male 50 kg Male 100 kg Female 45 kg Female 90 kg
- 26. 01 02 03 04 Dose 500 mg / day for adult Male 50 kg Male 100 kg Female 45 kg Female 90 kg 10 mg 5 mg
- 27. 01 02 03 04 Dose 500 mg / day for adult Male 50 kg Male 100 kg Female 45 kg Female 90 kg 10 mg 5 mg 8 mg 4 mg
- 29. 5% 150%
- 33. Taste is different If … What, How & How Much
- 34. Taste is different If … What, How & How Much
- 35. Taste is different If … What, How & How Much Learning Space
- 38. Consistent Pure < ZERO Mix up DRUG 1 2 3 Batch after Batch Within Batch Time after Time
- 43. Contamination Carcinogenic Hypersensitivity reactions Teratogenic effect Hormonal complications Infections Injury ……..
- 44. Mix up Life crisis
- 45. Effect Cause
- 46. Cause Effect Cause and effect are self-evident, don’t need specialized education, training and experience to know what causes what.
- 47. Cause Effect Cause and effect are self-evident, don’t need specialized education, training and experience to know what causes what. Simple System
- 48. Cause Effect Multivariate Multiple causes & effects Interactions and multiple interrelationships This needs good practices, process validation, scientific education, training and experience.
- 49. Cause Effect Multivariate Multiple causes & effects Interactions and multiple interrelationships This needs good practices, process validation, scientific education, training and experience. Complicated System
- 50. Cause Effect Cause and effect are only known after research beside training & experience. A complex system has property called emergence which comes up that is never expected.
- 51. Cause Effect Cause and effect are only known after research beside training & experience. A complex system has property called emergence which comes up that is never expected. Complex System
- 52. Cause Effect Unpredictable beyond average. Exhibit extreme sensitivity to initial or starting conditions. Starting conditions are raw materials, excipients, equipment, people (education, training and experience)
- 53. Cause Effect Chaotic System Unpredictable beyond average. Exhibit extreme sensitivity to initial or starting conditions. Starting conditions are raw materials, excipients, equipment, people (education, training and experience)
- 55. System Complicated Complex Chaotic Simple Identify blind spots & target them Make evidence reproducible
- 56. A Case Study
- 57. Cardiovascular Affairs A B C D M* ACE Inhibitors Beta Blockers Calcium Blockers Diuretics CNS Drugs
- 58. ACE inhibitors I Captopril, Enalpril, Lisinopril etc. II Losartan, Candesartan, Valsartan … Angiotensin II Receptor Blockers
- 59. Angiotensin II Receptor Blockers Losartan Valsartan Candesartan Innovator / New Drugs
- 60. Angiotensin II Receptor Blockers Losartan Valsartan Candesartan Merck Innovator / New Drugs
- 61. Angiotensin II Receptor Blockers Valsartan Candesartan Novartis Innovator / New Drugs Losartan Merck
- 62. Angiotensin II Receptor Blockers Valsartan Candesartan Novartis Astra Zeneca Innovator / New Drugs Losartan Merck
- 63. Generic Several generics entered in market after expiry of patent Meta- analysis reported ….
- 64. When data speaks
- 66. Data Before entry of generic in market 24 Months data
- 67. Data Before entry of generic in market 24 Months data 10% visited emergency or hospitalized/month
- 68. Data Before entry of generic in market 24 Months data 10% visited emergency or hospitalized/month 136177 patients 66 & above age 60% women & 40% men
- 69. 10 use drug 9 live healthy 1 visits hospital
- 71. Data extended After 12 months entry of generic in market 36 Months data
- 72. Data extended After 12 months entry of generic in market 36 Months data Visited emergency or hospitalized/month
- 73. Data extended After 12 months entry of generic in market 36 Months data Visited emergency or hospitalized/month 18% for Losratan 22% for Valsartan 24% for Candesartan
- 74. 10 use drug 8 live healthy 2 visit hospital
- 76. Innovator 10% Innovator Generic 21% 24 month 36 month Hospitalization
- 77. What went wrong? What may go wrong? Lets think
- 79. Concentration Levels in blood
- 83. The test drug is compared with innovator & its profile falls on the innovator scale in between 80 to 125% If
- 84. The test drug is compared with innovator & its profile falls on the innovator scale in between 80 to 125% It is Generic If
- 85. The test drug is compared with innovator & its profile falls on the innovator scale in between 80 to 125% We expect same therapeutic effect as established by the innovator in their clinical studies done earlier It is Generic If
- 86. Lets have a Critical Review
- 87. 90 - 100 80 - 90 100 - 110 110 - 125
- 88. 90 - 100 80 - 90 100 - 110 110 - 125
- 89. 90 - 100 80 - 90 100 - 110 110 - 125 Reference
- 90. 90 - 100 80 - 90 100 - 110 110 - 125 Reference
- 91. 90 - 100 80 - 90 100 - 110 110 - 125 Reference Generic
- 92. 90 - 100 80 - 90 100 - 110 110 - 125 Reference Qualifying Zone Generic
- 93. 90 - 100 80 - 90 100 - 110 110 - 125 Reference Qualifying Zone Generic Generic
- 94. 90 - 100 80 - 90 100 - 110 110 - 125 Reference Qualifying Zone Generic Generic Qualifying Zone
- 95. 90 - 100 80 - 90 100 - 110 110 - 125 Reference Qualifying Zone Generic Generic Qualifying Zone
- 96. Information to Knowledge Take an example of a Tablet 1 mg
- 97. Information to Knowledge Shelf life limit is 90 – 110% Take an example of a Tablet 1 mg
- 98. Information to Knowledge Shelf life limit is 90 – 110% 0.9 mg – 1.1 mg is acceptable Take an example of a Tablet 1 mg
- 99. Information to Knowledge If a generic is 80% BA & 90% of Potency
- 100. Information to Knowledge It will be expected max. 72% If a generic is 80% BA & 90% of Potency
- 101. 72% instead of 100% Remember !!! clinical studies done on 100%
- 102. Information to Knowledge If a generic is 125% BA & 110% of Potency
- 103. Information to Knowledge It will be expected max. 137.5% If a generic is 125% BA & 110% of Potency
- 104. 137.5% instead of 100% Remember !!! clinical studies done on 100%
- 105. 72% to 137.5% instead of 100%
- 106. 72% to 137.5% instead of 100% May be Under Dose
- 107. 72% to 137.5% instead of 100% May be Over Dose May be Under Dose
- 108. 72% to 137.5% instead of 100% May be Under Dose May be Over Dose May not be in every case but …
- 109. 72% to 137.5% instead of 100% Drug in Blood Minimum effective concentration Over maximum concentration Every breath deserve quality
- 110. Innovator 10% Innovator Generic 21% 24 month 36 month Hospitalization We were here
- 111. Innovator 10% Innovator Generic 21% 24 month 36 month Hospitalization We were here Learning Space
- 112. 01 Bioequivalence study & 03 validation batches may not assure drug quality for lifetime. Different people with different level of knowledge, skill & experience may not manufacture equal drug.
- 113. Thanks