Tutotrial - 3; Creating & Sustaing a Culture of Quality
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This document provides a summary of a presentation on creating a sustainable culture of quality. It discusses regulatory science and includes 166 slides on topics like quality control procedures, laboratory testing, batch records, and responses to inspection observations. Several scenarios are presented where a regulatory inspector found issues like a lack of written quality control procedures, failure to test incoming raw materials, and releasing drug products without meeting specifications. Groups are asked to discuss and respond to defend these cases. The overall document aims to facilitate learning through discussion and sharing of experiences regarding quality systems and regulatory compliance.
![Creating a Sustainable Culture of Quality
(Tutorial-3)
Roohi B. Obaid
05 May 2018, Karachi
[166 slides]](https://image.slidesharecdn.com/creatingsustainingacultureofqualitytutorial3-180507080038/85/Tutotrial-3-Creating-Sustaing-a-Culture-of-Quality-1-320.jpg)
Tutotrial - 3; Creating & Sustaing a Culture of Quality
- 1. Creating a Sustainable Culture of Quality (Tutorial-3) Roohi B. Obaid 05 May 2018, Karachi [166 slides]
- 3. Knowledge Sharing Exercise To Learn through Debate, Discussion & Experience of others
- 4. This presentation discusses Regulatory Science, nothing more & nothing less Reference: US-FDA Documents / Scientific Articles Thanks to Mary Oates, VP Global Quality Operations, Pfizer (Slide 103-140) Personal point of view & nothing to disclose Disclaimer
- 7. Do not confirm to GMP Methods, Facilities, Controls for manufacturing, processing, packing, or holding Adulterated
- 8. Flow 1 Mix-up 3 Consistency 2 Contamination Air Pressure Maintenance of Machine Cleaning Labeling
- 9. Methods, Facilities, Controls for manufacturing, processing, packing, or holding outside the GMP spirit DS or DP is adulterated Your
- 10. One password for multiple access
- 11. One password for multiple access Out of Control
- 12. One password for multiple access Out of Control Out of Track
- 13. One password for multiple access Out of Control Out of Track
- 14. One password for multiple access Out of Control Out of Track Contributed to conclude DS is adulterated
- 15. Do not confirm to GMP Methods, Facilities, Controls for manufacturing, processing, packing, or holding Adulterated
- 16. What Harm If one password for multiple use? Take an example of HPLC
- 18. Developed Who?
- 21. Why independent password for each individual ?
- 22. Why independent password for each individual ? Regulatory
- 23. Why independent password for each individual ? Regulatory Identification to track
- 24. Why independent password for each individual ? Regulatory Identification to track Explore to Excel
- 25. 18 April 2018
- 26. Povidone Iodine preparation 10% solution
- 27. Testing of each batch for objectionable microorganisms
- 28. Testing of each batch for objectionable microorganisms Testing of Microbial Attributes
- 29. Testing of each batch for objectionable microorganisms Testing of Microbial Attributes Manufacturing in suitable environment
- 30. Testing of each batch for objectionable microorganisms Testing of Microbial Attributes Manufacturing in suitable environment
- 31. Testing of each batch for objectionable microorganisms Testing of Microbial Attributes Manufacturing in suitable environment Inappropriate laboratory testing may lead to … adulterated
- 32. Laboratory record not in place
- 33. Laboratory record not in place Raw data
- 34. Laboratory record not in place Raw data Weight of samples, test methods
- 35. Laboratory record not in place Raw data Record of calculations Weight of samples, test methods
- 36. Laboratory record not in place Raw data Record of calculations Deficiency may lead to …. adulterated Weight of samples, test methods
- 37. Quality Unit have to demonstrate ability to fully exercise its authority & responsibility Authority Resources Staff Remember
- 38. If a batch fails on 01 June 2016, draw the map & let us know how much time is required to declare fail & to reach at destruction site?
- 39. Quality Unit have to demonstrate ability to fully exercise its authority & responsibility Authority Resources Staff Remember
- 40. 18 April 2018
- 41. Absence in Repackaging of OTC Transdermal Patches Quality Control Unit Procedure for repackaging operation Establishment of QC Unit is not an option, but obligation …. adulterated
- 42. Absence in Repackaging of OTC Transdermal Patches Mix up potential Record of operations Correct label, …. To prevent mix up & cross contamination by physical or spatial separation is an obligation, not choice …. adulterated
- 43. Absence in Repackaging of OTC Transdermal Patches Distribution record Qualification of recall System by which the distribution of each lot can be readily determined to facilitate its recall when necessary is an obligation, not option …. adulterated
- 44. If expiry of packet is June 2020 What will be the expiry of product taken out from strip?
- 45. How much delay (in days or months) can be appropriate to put product in a stability chamber?
- 46. 09 April 2018
- 47. Inappropriate laboratory testing for conformance to final specifications (OTC) Identity & Strength Analytical data to support release Drug product conformance with the final specifications for identity, strength of each API prior to release is an obligation, cannot be ignored … adulterated Testing procedures & specifications
- 49. Lets think for CAPA Written Policy & SOPs for testing
- 50. Lets think for CAPA Testing requirements Written Policy & SOPs for testing
- 51. Lets think for CAPA Testing requirements Written Policy & SOPs for testing Testing methods & its validation
- 52. Lets think for CAPA Testing requirements Written Policy & SOPs for testing Testing methods & its validation Release Specifications, Acceptance Criteria & justification
- 53. Scenario Inspector wrote You failed to test the incoming raw materials (used to manufacture drug products) to determine their identity, purity, strength and other appropriate specifications
- 54. Scenario Inspector wrote You failed to test the incoming raw materials (used to manufacture drug products) to determine their identity, purity, strength and other appropriate specifications Inspector further wrote Instead you used results from supplier’s COA without establishing the reliability of supplier’s analysis through appropriate validation & without conducting at least one specific identity test
- 55. Scenario Company responded We identified all incoming materials used in the manufacture of our products against known standards
- 56. Scenario Company responded We identified all incoming materials used in the manufacture of our products against known standards Lets think What will be next, how Regulatory Authority will respond
- 57. Scenario You did not provide procedure for testing of incoming materials
- 58. Scenario You did not provide procedure for testing of incoming materials You did not provide results from any testing
- 59. Scenario You did not provide procedure for testing of incoming materials You did not provide results from any testing You did not provide any information on how you will establish the reliability of your supplier’s test results
- 60. Scenario You did not provide procedure for testing of incoming materials You did not provide results from any testing You did not provide any information on how you will establish the reliability of your supplier’s test results Reliance on supplier’s COA to verify the identity of components is not acceptable
- 61. Scenario Provide plan to test each component for conformity with all specifications for identity, purity, strength & quality Explain how you intent to perform at least one identity test for each component If you accept supplier COA for purity, strength & quality, specify how you plan to establish reliability of your supplier’s COA
- 62. Scenario Inspector identified Lacking in written procedure for QCU operations
- 63. Scenario Inspector indicated examples GMP training, change control, annual product reviews, complaint handling & oversight of various other basic drug manufacturing & testing operations Inspector identified Lacking in written procedure for QCU operations
- 64. Scenario Company responded Our firm is a small company & does not have the resources for Quality Unit. We are responsible for reviewing and approving all quality related documents
- 65. Scenario Company responded Our firm is a small company & does not have the resources for Quality Unit. We are responsible for reviewing and approving all quality related documents Lets think What will be next, how Regulatory Authority will respond
- 66. Scenario Size of company does not matter at all Quality Unit is a mandatory requirement Authority & responsibility must be clear to carry out the operation
- 67. Quality Unit have to demonstrate ability to fully exercise its authority & responsibility Authority Resources Staff Remember
- 68. Tea Break
- 69. Lets try to respond in a way that observation may be waived
- 70. Scenario Batch record did not include information such as
- 71. Scenario Batch record did not include information such as Identity of the equipment Actual time of process Actual temperature Filling operation steps Packaging operation steps Yield % age specifications
- 72. Lets discuss in group for three to five minutes & respond how would you defend the case
- 73. Understand & amend accordingly Implement correctly in true spirit Submit factual position with evidence 1 2 3
- 74. Scenario OTC drug product released without testing, identity & strength
- 75. Scenario OTC drug product released without testing, identity & strength Total aerobic microbial count & objectionable microorganisms were not tested before release
- 76. Lets discuss in group for three to five minutes & respond how would you defend the case
- 77. Understand & amend accordingly Implement correctly in true spirit Submit factual position with evidence 1 2 3
- 78. Submit detail specification of product Demonstrate capability & validity of your analytical methods Submit plan for conducting Retrospective testing of all batches with valid shelf life
- 79. In case of failure, customer notification to facilitate recall may be attached Lesson learned Same approach is extended to other products too if required
- 80. 29 March 2018
- 81. OTC Drug Product Raw data not available to verify? Credibility of microbiological testing?
- 82. OTC Drug Product Raw data not available to verify? Credibility of microbiological testing? Subject to regulatory action
- 84. Scenario OTC Drug Product Accelerated studies for 6 weeks Did not perform long term study
- 85. Lets discuss in group for three to five minutes & respond how would you defend the case
- 86. 15 March 2018
- 87. Failure to adequately investigate OOS results and to implement appropriate corrective actions
- 88. Failure to adequately investigate OOS results and to implement appropriate corrective actions What happened Retest result were recorded & original fail results were disregarded Phase 2 investigation failed to evaluate manufacturing operations for potential root cause Phase 1 laboratory investigation did not support invalidation of results
- 89. Failure to adequately investigate OOS results and to implement appropriate corrective actions Retroscopic review of OOS result A pattern of recurring similar OOS result with insufficient investigation & CAPA exist
- 90. Firm responded that it was impossible to
- 91. Firm responded that it was impossible to Make reliable Retroscopic root cause determination for the failing results
- 92. Firm responded that it was impossible to Make reliable Retroscopic root cause determination for the failing results Provide scientific rational for decision because considerable time has elapsed since the original OOS occurrence
- 93. Lets see how Regulatory Authority will respond
- 94. 26 March 2018
- 95. Failure to thoroughly investigate any unexplained discrepancy What happened 5 lots failed in dissolution (May – Nov 2016) Methyl Phenidate HCl ER suspension Dissolution test method declared as cause of failure, not manufacturing Failed 3 lots in release testing & 2 when tested for stability
- 96. Failure to thoroughly investigate any unexplained discrepancy What happened Firm modified dissolution test method several times 1 lot upon retest also failed even by new method Deviated from the original one that was used for approval
- 97. Please discuss & list down the questions & concerns
- 98. Lets see how Regulatory Authority will move & respond Retrospective review of dissolution for all lots with valid shelf life Risk assessment that evaluate quality of distributed batches Investigation & CAPA plans for Mfg process variability & dissolution method
- 99. Your response to regulatory authority must provide sufficient evidence of corrective actions to bring operations into compliance with GMP Moreover, interim measures during implementation of CAPA must be in black & white Take Home Message
- 100. Testing is essential to ensuring that the drug product manufactured meets established specifications for the chemical & microbial attributes they purport to possess Take Home Message
- 101. Remember, process performance qualification alone no longer protects from regulatory observations, unless an approach for monitoring batch to batch variation on an on-going basis is in place Take Home Message
- 102. Lunch & Prayer Break
- 103. Strength and Elasticity in Sustaining the Quality
- 104. 1 Quality of Product & Safety of Consumer 2Birth of Quality Culture 5 Quality Culture Indicators 6Closing Words 3 Criticality of Quality Culture 4Maintaining Quality Culture
- 105. Quality Drugs: A Continuous Concern Quality Culture is the keystone
- 107. SYSTEM CONTROLS Ensures every product meets quality standards Is it enough ???
- 108. Your decision impacts product quality Uncounted decisions taken daily Every decision is not supported by SOPs Complex manufacturing environment Potential risks
- 109. Does compliance not guarantee? Is compliance not enough? Are System & Controls meaningless? Is Experience not bullet proof?
- 110. An environment where every person understands Product Quality & Patient Safety Without quality culture, product & public safety cannot be assured Single most important indicator to determine the ability of delivering the quality drugs Q U A L I T Y C U L T U R E
- 111. Quality is built in from the beginning Risk to providing quality medicines are understood & mitigated Performance is monitored in real time & course corrections are made as needed CoQ
- 112. An eagerness to solve problem Share learning and drive to RFT Issues are escalated and resolved collaboratively CoQ
- 113. No pointing of finger or laying blame Difficult decisions are made to do the right things Don’t care about obstacles for right things CoQ
- 114. Report mistakes fearlessly Learn from mistakes Quality is everyone’s responsibility CoQ
- 115. Birth of Quality Culture Does not happen by accident It has to be created Relevant process & control must be in place Understood & Followed
- 116. Numerous workarounds Numerous waivers Lack of Control Please close your eyes & try to visualize the operation floor
- 117. Kindly remember Quality Culture builds on the expertise & processes in the organization and results in behaviors & decision making that will result in quality outcome
- 118. Doing the right things and doing things right is valued above …. Continuous improvement is the priority resulting in eagerness to …. Must create an environment in which Culture driven by leadership … Must provide the fundamentals to product quality Cost Speed Identify Address Issues
- 119. Strong management oversight Adequate resources Training of colleagues Maintenance of plant & equipment Focus on continual improvement An organization capable of making right decisions to protect product quality Provide Fundamentals
- 120. Is Quality Culture Measurable? The concept is not new • What’s your inner (gut) feeling whether it exists or not? Challenges of current environment urged to quantitatively evaluate • A semi-quantitative tool was developed that uses data gathered mainly from interviews of employees across all levels in the firm together with observations of operations and review of supporting documentation The tool can be used both internally & externally
- 121. A relationship with a third party was under evaluation Due diligence identified the acceptability of all relevant systems, controls and processes at a potential partner The quality culture assessment identified significant weaknesses Cont’d Hypothetical External Example 1
- 122. Particularly, on this basis the business agreement was not pursued The potential partner later experienced significant quality failures Hypothetical External Example 1
- 123. Open, eager to learn, committed to continuous improvement, management focused on delivery of quality product Systems & controls were inadequate but culture was strong Third party partnership under evaluation Cont’d Hypothetical External Example 2
- 124. When combined with existing culture, product quality was assured The firm worked diligently to improve systems, resulting in acceptable controls Hypothetical External Example 2
- 125. Management must proclaim the value of escalating issues & opening deviation investigations Management must help employees recognize deviations & implement a process for effectively raising them Management must establish a monitoring mechanism and track and publish metrics What if Lack of Culture: Symptoms & Actions
- 126. Management must celebrate an increase in deviations and hold accountable those who do not bring them forward Management must ensure that deviation investigations get to true root cause and define full scope of the issue What if Lack of Culture: Symptoms & Actions
- 127. Management must ensure that holistic corrective actions are implemented to prevent recurrence Management must reinforce the criticality of continuous improvement What if Lack of Culture: Symptoms & Actions
- 128. Its about behaviors, not SOPs • Without a strong quality culture, risks to product quality cannot be fully mitigated Criticality of Quality Culture
- 129. Quality culture cannot be externally imposed and is not introduced only through changes to GMP systems • Quality culture cannot be changed in the near-term but can be lost very quickly if focus on it is lost Criticality of Quality Culture
- 130. Management must be vigilant in keeping the organization focused on the right behaviors and decisions Pressures exist and culture can change quickly if not protected • Supply demands • Supply chain complexity • Cost reduction Maintaining Quality Culture
- 131. May result in organizational & procedural changes The risk of such changes must be understood and mitigated • Risk assessment tools can be utilized • Assessment may indicate the risk is too great to take • Can be utilized retrospectively Cost Pressures
- 132. May erode quality culture by driving decisions that can adversely affect product quality Early indicators should be in place • Quantitative (e.g. over-due items) • Decision-making at the operational level If early signals indicate potential impact, corrective actions should be implemented immediately Cost Pressures
- 133. Quality Pyramid based on safety Regulatory body action Notification to Management/ Market Action Recordable event Near miss At risk behavior Quality Culture/leadership
- 134. Resource & System Maturity 1 • An expedited complaint becomes overdue 2 • ↑ in number of operator errors/ batch 3 • ↑ in Doc. Errors corrected before lot release 4 • ↑ in # of unplanned quarantine shipments 5 • ↑ in % employee turnover 6 • Relative degree of experience with staff Quality indicators from the Pyramid characterized by key focus area
- 135. Leadership Quality 1 • Leadership drives programs that enhance quality culture, RFT. etc. 2 • % of reported near misses addressed, this means action defined & communicated & colleague rewarded for reporting Quality indicators from the Pyramid characterized by key focus area
- 136. Change Impact 1 • ↑ in number of rejected lots 2 • ↑ in % complaints per units produced 3 • # of capital projects linked to GMP or compliance being delayed 4 • ↓ in process robustness/ capability (% products that have defined capabilities that are tracked Quality indicators from the Pyramid characterized by key focus area
- 137. Regulatory Impact 1 • Self-identified risk areas (Internal Audits)-step back from tactical findings from audits & look more across the board Quality indicators from the Pyramid characterized by key focus area
- 138. Cultural Aspects 1 • ↓ in compliance to training curriculum 2 • ↓ in investigation effectiveness ratio 3 • Feedback loop Quality indicators from the Pyramid characterized by key focus area
- 139. Resource Availability 1 • ↑ in average disposition cycle time 2 • ↓ in % PM completed on time 3 • Minimum staffing requirements met 4 • Staffing per workload unit Quality indicators from the Pyramid characterized by key focus area
- 140. Keep walking & talking on… Respect values Come out from fear to report Celebrate mistakes Be knowledgeable Understand your product & process Closing words Thank you of your attention
- 141. Concluding Talk
- 142. Why Pharmaceutical Manufacturers face Compliance Issues Fire fighting 1
- 143. Why Pharmaceutical Manufacturers face Compliance Issues Fire fighting Right first time 1 2
- 144. Why Pharmaceutical Manufacturers face Compliance Issues Fire fighting Right first time Maintaining a reliable state of quality & compliance 1 2 3
- 145. Right first time from top to bottom
- 146. The management must identify
- 147. The management must identify Complaint handling Change Management Review Strategies
- 148. The management must identify Monitored Reviewed Effective
- 149. Global Radar & Navigation Data Integrity Culture of Quality
- 150. Trustworthiness / Integrity of Data Data that is reliable Data that is authentic Data that is useable Complete & Accurate Proven to be what it say, it is Can be located, retrieved, presented & interpreted
- 151. Culture of Quality Quality Metrics Lagging Metrics & Leading Metrics
- 152. Lagging Metrics Batch Failure Right First Time OOS Investigation Leading Metrics Quality System Effectiveness Process Capability Quality Culture Index
- 153. Lets move beyond regulatory compliance & explain opportunity to capture unexpected event before it happens Respect & use knowledge, experience, data, pattern, trend & good science to improve efficiency & maintaining culture of quality
- 154. 1/5 Tie with Quality is a Core Value Simple, loud & clear
- 155. No matter what the situation is, quality will always be placed above all
- 156. Think beyond compliance Gather knowledge & learn from others Be proactive Utilize the best of capacity to identify signals
- 157. 2/5 Setting ethical standards & Training
- 158. Policy Procedures Training Implementation Quality Mission Data IntegrityWHO, ICH Q10 To ensure S E Q Reconstruction of activities
- 160. Blocks in Reporting Fear to report 1 I don’t think there is an impact Impact exists, but nobody bother to response 2 3
- 161. Blocks in Reporting Howto Overcome Direct / cross functional reporting (seniors, leadership) Reward for reporting Give recognition through training that it has impact Feedback on reporting, update with progress Report Collection Unit 1 2 3
- 164. 5/5 Hear the gut & ground sound
- 165. Check engagement of people on the floor Are they fearlessly reporting? Are they celebrating mistakes? Are they learning or not? Report to Senior Management
- 166. Thank you