1. Corrective Action and Preventive Action Procedure Start

2. X 2 Welcome Welcome to the Corrective Action and Preventive Action (CAPA) Procedure eLearning! This course is designed to outline the principles which must be followed in order to accurately complete the CAPA process. Please make sure you have read SOP GL-GMP-203 prior to completing this training module. If you need instructions on navigating the program, please click here. here. This module will take approximately 60 minutes. Click next to start the course

3. X 3 Session Guidelines There will be a quiz at the end of this course! To help you prepare for the quiz, you will be able to collect points during the training. Hi, I’m CAPA! I will let you know where you can collect the points. You should aim to collect approximately 40 points in order to be ready to take the quiz at the end.

4. X 4 Objectives At the end of the program, you will be able to:  Define Corrective and Preventive Action and the Regulatory expectations.  Describe the CAPA Procedure.  Describe the CAPA form and its proper use.  Explain CAPA Procedure roles/responsibilities.  Identify CAPA benefits and impacts to clients and our organization.

5. X 5 GMP Review Good Manufacturing Practice (GMP) is concerned with the manufacture and subsequent testing of medicinal products to ensure they are fit for their intended purpose and do not place patients at risk due to inadequate safety, quality or efficacy. Quality Control (QC) is the part of GMP concerned with the sampling, specification and testing, documentation and release procedures thus ensuring products are not released for use until deemed of a suitable quality. GMP and QC – Assuring patient safety through a quality product, manufactured and tested in a consistent manner. First, a quick review about GMP…

6. X 6 Agenda Introduction to the CAPA Procedure CAPA Process & Form Review (SOP GL-GMP-203) Why is the CAPA Procedure important? The training is divided into these 3 main sections.

7. X 7  Overview  Benefits  Definitions Agenda Introduction to Good Documentation Practices CAPA Process & Form Review (SOP GL-GMP-203) Why is the CAPA Procedure important? Click on the first section, “Introduction to the CAPA Procedure” to get started. Introduction to the CAPA Procedure All sections are divided into 3 parts.

8. X 8 Agenda Introduction to Good Documentation Practices Applying Good Documentation Practices Why is Good Documentation Practice important? For this first section, we’ll start with an overview to clarify what we mean by CAPA. Introduction to the CAPA Procedure  Overview  Benefits  Definitions

9. X 9 Definition of CAPA Do you know what the acronym CAPA stands for and what it means? Yes No Since there is a test at the end of the course, let’s just remind ourselves of what it is. Click next to continue

10. X 10 Definition of CAPA Corrective Action Action taken to rectify a detected ‘quality defect’ or undesirable situation, mitigate its impact and eliminate the cause, in order to prevent recurrence. Preventive Action Action that corrects or eliminates the root cause of a potential non-conformity, defect or other undesirable situation and therefore prevents occurrence. Corrective Action Preventive Action The CAPA Procedure is found in SOP GL-GMP-203:

11. X 11 Policies So, why do you think we have the CAPA Procedure and its associated form? SOP: GL-GMP-203 Form: GL-GMP-203-1 When you see this notepad symbol, take out your notepad and pen so that you can jot down some notes. Be sure to write a few notes now before clicking next.

12. X 12 Policies We asked a colleague in the Regulatory department to make some notes. Click on the button below to reveal the notes they made. Reveal Notepad Quality Compliance Meet Client expectations Incorporate industry standards and best practices into our processes

13. X 13 Policies Quality Compliance Meet Client expectations Incorporate industry standards and best practices into our processes Did you have any of these words on your notepad? Give yourself 1 point for each word you wrote down. Maximum points is 5!

14. X 14 Agenda Introduction to Good Documentation Practices Applying Good Documentation Practices Why is Good Documentation Practice important? For the next part of the Introduction, let’s look at some of the benefits of the CAPA Procedure. Introduction to the CAPA Procedure  Overview  Benefits  Definitions Click next to continue.

15. X 15 Benefits What do you think are some of the benefits of the CAPA Procedure? Click next when you’re ready to continue.

16. X 16 Benefits We asked a colleague to make some notes. Click on the button below to reveal the notes they made. Reveal Notepad Improves quality Continual Improvement Prevents Potential Problems Reduces Recurring Problems Meets Regulatory Expectations Tracking of Remedial Actions Good Client Relationship

17. X 17 Benefits Did you have any of these words on your notepad? Give yourself 1 point for each of these words you wrote down. Maximum points is 7! Improves quality Continual Improvement Prevents Potential Problems Reduces Recurring Problems Meets Regulatory Expectations Tracking of Remedial Actions Good Client Relationship

18. X 18 Put into more detail, here are 3 benefits of following the CAPA Procedure: 1.Provides an effective tool to manage process improvements. Benefits our Clients. 2.Ensures quality and process excellence by preventing/addressing determined root causes. Benefits the quality of Processes. 3.Generates credible source documentation to meet the client and regulators' requirements. Benefits Your and the organization’s reputation with industry and Regulatory Agencies. Benefits

19. X 19 Agenda Introduction to Good Documentation Practices Applying Good Documentation Practices Why is Good Documentation Practice important? Besides Corrective and Preventive Action, there are a couple more definitions to know for CAPA. Introduction to the CAPA Procedure  Introduction  Benefits  Definitions Click next to continue.

20. X 20 Definitions Quality DefectRoot Cause We’ll review each of these separately, but first write your definition of these terms on your notepad. Then, starting with Quality Defect, click each box to check your answers!

21. X 21 Collective term used to describe any problem, observation, non- conformance, deviation, undesirable situation or trend that requires corrective or preventive action. Definition of Quality Defect Quality DefectRoot Cause Give yourself 1 point if your definition matches and then click on Root Cause!

22. X 22 An identified reason for the presence of a defect or problem, which if eliminated would prevent recurrence. Definition of Root Cause Quality DefectRoot Cause Give yourself 1 point if your definition matches and then click next to continue!

23. X 23 Agenda Introduction to the CAPA Procedure Applying Good Documentation Practices Why is Good Documentation Practice important? This second section is all about the CAPA process. Click on the agenda to the left to continue with the training.  Using the CAPA Procedure  GL-GMP-203-1 CAPA Form Review  CAPA Roles & Responsibilities CAPA Process & Form Review (SOP GL-GMP-203)

24. X 24 Using The CAPA Procedure Click here for a list of events that might require a CAPA. We’ll begin with a quick review of when to use the CAPA Procedure. Write down on your notepad any events that you think might require a CAPA.

25. X 25 Using The CAPA Procedure Give yourself 1 point for every correct answer. A CAPA might be generated: – To be proactive in response to potential issues observed. – To address recurrent deviations. – To address audit observation trends. – To prevent potential issues identified during risk assessment or process reviews. – As a result of management review.

26. X 26 –Inspection Observation Trends. –Deviations requiring longer term corrective action. –Out-Of-Specification, Out-Of- Trend, and Atypical Results. –Customer Complaints. –Product Recalls. –Issues or trends raised during Management Review. –Conclusions from Risk assessment. Using The CAPA Procedure You may therefore initiate CAPA to address:

27. X 27 Key actions to begin the CAPA process: The CAPA Process GL-GMP-203 CAPA Requestor Notify Line Management of an identified actual or potential quality defect that requires corrective OR preventive action. Manager Appoint a CAPA Owner. CAPA Owner Initiate a CAPA form and request a tracking number from GMP QA.

28. X 28 The CAPA Form GL-GMP-203-1 The accurate determination of root cause(s) is critical to successful CAPA outcomes! Step #1: Understand what the problem is by investigating and determining root cause(s). Step #2: Propose actions that will address the root cause(s). Key steps in completing the CAPA Form include:

29. X 29 Determining Root Cause(s) Why? To determine Root Cause(s) – ask the question ‘Why?’ at least five times. Click here to see how this works.

30. X 30 1.Why? –Because the Memorial is being washed more frequently. 2.Why? –To remove the increased number of bird droppings. 3.Why? –Because there’s an increased bird population. 4.Why? –Because there’s an increased spider population. 5.Why? –Because there’s an increased insects population. 6.Why? –Because insects are drawn to the light used to illuminate the memorials in hours of darkness, specifically at dust and dawn. A Real Example – Keep Asking ‘Why?’ Problem: The Jefferson Memorial is eroding at a higher rate than usual. Solution: Turn the lights on one hour later and turn them off one hour sooner.

31. X 31 Agenda Introduction to Good Documentation Practices Applying Good Documentation Practices Why is Good Documentation Practice important? Let’s now take a look at how to complete each section of the CAPA form GL-GMP-203-1. CAPA Process & Form Review (SOP GL-GMP-203)  Using the CAPA Procedure  GL-GMP-203-1 CAPA Form Review  CAPA Roles & Responsibilities

32. X 32 Section 1 Form GL-GMP-203-1 Record the outcome of the investigation in Section 1 of the CAPA form and attach any supporting documentation. Determine and agree upon proposed actions and target date(s). CAPA Owners determine which departments/individuals will need to contribute to the investigation and complete the following: Assign responsibilities for each action to an Action Owner and provide details.

33. X 33 The Manager/GMP QA signs and dates Section 1 of the CAPA to pre-approve the form. Always make sure that you are using the most up to date form. Section 1 Form GL-GMP-203-1 CAPA Owners must sign and date the pre-approval portion of Section 1, and get Pre-approval from the Manager and GMP QA. Purpose: to review the proposed corrective or preventive actions to ensure the quality defect is fully addressed and the timelines and responsibilities are appropriate.

34. X 34 Section 1 Form GL-GMP-203-1 Action Owners (or designee) confirm completion of each action in Section 1. Initial and date each action in Section 1 to confirm completion. Provide evidence of action completion as required.

35. X 35 Section 2 Post Approval GL-GMP-203-1 On completion of all actions (confirmed in Section 1) the CAPA is post-approved by completion of Section 2. Completed CAPA forms are stored within GMP QA and archived in accordance with the site records retention policy.

36. X 36 Key actions for CAPA implementation: CAPA Implementation CAPA Owner Coordinate the implementation of the CAPA in accordance with the approved actions. Keep GMP QA appraised of progress and completion. Action Owner Sign and date each action in Section 1 of the CAPA form to confirm completion. Record any deviations to the pre-approved actions in the comments section of the form.

37. X 37 Always make sure that all the appropriate information is included in all sections. And remember: Effective actions eliminate root cause(s)! Section 1 GL-GMP-203-1 REMINDER #1: Each action will be signed for and closed on a case by case basis on completion of the action, by the: – Action Owner or Designee REMINDER #2: Section 2 (Post-approval) is completed after all actions in Section 1 have been closed.

38. X 38 1.CAPA Owners 2.GMP QA Monitoring CAPA Progress That’s right – and they do so on a quarterly basis as well as raise (with the CAPA Owner and Line Management if necessary) CAPAs that are nearing or have passed their target completion dates. Give yourself 2 points if you got this correct! Do you know who monitors the progress of an open CAPA?

39. X 39 Agenda Introduction to Good Documentation Practices Applying Good Documentation Practices Why is Good Documentation Practice important? This next section is an activity that provides you with descriptions of different responsibilities associated with the CAPA process and you’ll be choosing which role is being described. CAPA Process & Form Review (SOP GL-GMP-203)  Using the CAPA Procedure  GL-GMP-203-1 CAPA Form Review  CAPA Roles & Responsibilities Click next to continue and good luck!

40. X 40 Reveal Answer Senior Management CAPA Owner Coordinates the completion of a CAPA. Ensures all Action Owners are aware of their responsibilities and action timelines. Which role does this apply to? CAPA Roles & Responsibilities Action OwnerGMP Quality Assurance Section Manager / Area Manager / Supervisor Well done 1 point!

41. X 41 Senior Management CAPA Roles & Responsibilities Action OwnerGMP Quality Assurance Section Manager / Area Manager / Supervisor CAPA Owner Coordinates the completion of a CAPA. Ensures all Action Owners are aware of their responsibilities and action timelines. Which role does this apply to?

42. X 42 Reveal Answer CAPA Owner Action Owner Ensures the action assigned to them is completed within agreed timelines. Which role does this apply to? CAPA Roles & Responsibilities Senior ManagementGMP Quality Assurance Section Manager / Area Manager / Supervisor Well done 1 point!

43. X 43 CAPA Owner CAPA Roles & Responsibilities Senior ManagementGMP Quality Assurance Section Manager / Area Manager / Supervisor Action Owner Ensures the action assigned to them is completed within agreed timelines. Which role does this apply to?

44. X 44 Reveal Answer Senior Management GMP Quality Assurance CAPA Roles & Responsibilities Well done 1 point! CAPA OwnerAction Owner Section Manager / Area Manager / Supervisor Manages the CAPA system, participates in CAPA investigations, pre/post approves CAPAs, acts as CAPA Owner for CAPAs related to Regulatory Inspections & Client Audits and monitors the status of CAPAs. Which role does this apply to?

45. X 45 Senior Management CAPA Roles & Responsibilities CAPA OwnerAction Owner Section Manager / Area Manager / Supervisor GMP Quality Assurance Manages the CAPA system, participates in CAPA investigations, pre/post approves CAPAs, acts as CAPA Owner for CAPAs related to Regulatory Inspections & Client Audits and monitors the status of CAPAs. Which role does this apply to?

46. X 46 Senior Management Reveal Answer Appoints a CAPA Owner. Pre/post approves CAPAs within their area of responsibility. Ensures resources are available so that actions can be completed within agreed timelines. Which role does this apply to? CAPA Roles & Responsibilities Well done 1 point! CAPA OwnerAction OwnerGMP Quality Assurance Section Manager /Area Manager / Supervisor

47. X 47 Senior Management CAPA Roles & Responsibilities CAPA OwnerAction OwnerGMP Quality Assurance Section Manager /Area Manager / Supervisor Appoints a CAPA Owner. Pre/post approves CAPAs within their area of responsibility. Ensures resources are available so that actions can be completed within agreed timelines. Which role does this apply to?

48. X 48 Section Manager /Area Manager / Supervisor Reveal Answer Ensures that there is sufficient resource to complete CAPAs initiated within the department. Agrees to any significant capital expenditure proposed as a result of a CAPA. Which role does this apply to? CAPA Roles & Responsibilities Well done 1 point! CAPA OwnerAction OwnerGMP Quality Assurance Senior Management

49. X 49 Section Manager / Area Manager / Supervisor CAPA Roles & Responsibilities CAPA OwnerAction OwnerGMP Quality Assurance Senior Management Ensures that there is sufficient resource to complete CAPAs initiated within the department. Agrees to any significant capital expenditure proposed as a result of a CAPA. Which role does this apply to?

50. X 50 Agenda Introduction to the CAPA Procedure CAPA Process & Form Review (SOP GL-GMP-203) Why is Good Documentation Practice important? Let’s look at the third and final section of this module. Click on the agenda to the left to learn why CAPA is so important. Why is the CAPA Procedure important?  Client expectations  Importance to our organization  Possible consequences

51. X 51 Agenda Introduction to Good Documentation Practices Applying Good Documentation Practices Why is Good Documentation Practice important? The CAPA Procedure is important to our clients. Why is the CAPA Procedure important?  Client expectations  Importance to our organization  Possible consequences

52. X 52 Client expectations CAPA is an industry standard (regulatory requirement, etc.) Clients expect that reoccurring negative events are corrected and/or prevented.  That means identifying root causes and addressing them via CAPA! Don’t forget… Anyone can request a CAPA.

53. X 53 Importance to Clients and Regulators CAPA is important to our clients and the Regulators. Which of the following do you think they expect? Click on each answer that you think is correct and then click next to continue. Quality ProductProcess ExcellenceThorough PlanningTimely Follow ThroughEliminate Root CausesAccurate/Legible Data

54. X 54 Importance to Clients and Regulators Quality Product Process Excellence Thorough Planning Timely Follow Through Eliminate Root Causes Accurate/Legible Data Give yourself 1 point for each one that you got correct! The answer is all of them. Our clients and the Regulators expect: (This list is not inclusive. Check with your manager about other expectations.)

55. X 55 Global Regulatory Requirements United States Code of Federal Regulations –21 CFR 210, 211 & 600 European Regulations –Rules Governing Medicinal products in the European Union Volume 4 – Medicinal products for human and veterinary Use: Good Manufacturing Practices International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use –ICH Q10 – Pharmaceutical Quality System.ICH Q10 – Pharmaceutical Quality System. What regulatory authorities do we mean? Click to review.

56. X 56 The pharmaceutical company should have a system for implementing corrective actions and preventive actions resulting from the investigation of complaints, product rejections, non-conformances, recalls, deviations, audits, regulatory inspections and findings, and trends from process performance and product quality monitoring. A structured approach to the investigation process should be used with the objective of determining root cause. The level of effort and formality of the investigation should be commensurate with the level of risk. CAPA methodology should result in product and process improvements and enhanced product and process understanding. Global Regulatory Requirements ICH Q10 Corrective Action and Preventive Action System

57. X 57 Agenda Introduction to Good Documentation Practices Applying Good Documentation Practices Why is Good Documentation Practice important? The CAPA Procedure is important to our organization.  Client expectations  Importance to our organization  Possible consequences Why is the CAPA Procedure important?

58. X 58 CAPA is important to our clients, regulatory authorities and to our organization. When CAPA is not followed, write down on your notepad some potential impacts to our organization. Importance Click here to reveal a list of potential impacts.

59. X 59 Potential impact:  Damaged reputation resulting in loss of business and revenue.  Lack of confidence in our organization’s ability to provide quality.  Negative impact on studies and productivity.  Negative impact on client relationships.  Litigation by client.  Regulatory Agency may question our organization’s ability to effectively solve root cause issues.  Questions raised about the quality of the rest of our work.  Inspection Findings and Warning Letters could be issued and made public knowledge. Importance to Our Organization Give yourself 1 point for each correct answer.

60. X 60 CAPA is important to everyone: Our organization, our clients and the Regulatory Authorities. The Importance Of CAPA Remember If appropriate actions aren’t taken, processes can not be improved!

61. X 61 The Importance of CAPA As you can see, effective CAPA management has a direct impact on all aspects of our business. The CAPA Procedure is essential to ensure integrity, quality and compliance.

62. X 62 Agenda Introduction to Good Documentation Practices Applying Good Documentation Practices Why is Good Documentation Practice important? Let’s look at an example of a possible consequence in more detail.  Client expectations  Importance to our organization  Possible consequences Why is the CAPA Procedure important?

63. X 63 Consequences Click next to see the outcome when the CAPA process is applied! Each deviation: – consisted of a 5 page deviation form and 48 page sample inventory. – involved approximately 10 people in the investigations and impact assessments (metrology, study management, supervisors, managers, trainers). – required a number of face-to-face meetings. Result: – Significant time spent and expense (in total approximately $12,000). – Loss of business from clients as a result of some sample integrity issues. When CAPAs don’t address root causes, examples such as these actual events can happen. -20°C freezer door was left open on a number of occasions which resulted in numerous deviations:

64. X 64 1.Why? –Because the freezer door is being left open. 2.Why? –The door is opening of it’s own accord. 3.Why? –Inconsistent locking mechanism. 4.Why? –The freezer door fittings are not properly aligned. 5.Why? –The freezer unit is not levelled correctly. A Real Example – Keep Asking ‘Why?’ Problem: Multiple temperature deviations for a particular freezer Solution: Level the unit so door fittings correct and fit a door alarm.

65. X 65 Agenda Introduction to the CAPA Procedure CAPA Process & Form Review (SOP GL-GMP-203) Why is the CAPA Procedure important? And Finally… Here’s a quick recap And Finally… We’ve been through all 3 sections of this training. Click next for a quick review of some of the key points.

66. X 66 Key Points CAPA is a regulatory standard, an expected practice, and a GMP organizational Core Value. Notify management immediately of any issues, problems, questions, or concerns that you have. It is everyone’s responsibility to ensure that the CAPA process is followed. NEVER be afraid to request a CAPA. ANYONE can request a CAPA. ALWAYS investigate to determine the true root cause(s) by asking “Why?” at least five times.

67. X 67 And Finally Agenda Introduction to Good Documentation Practices CAPA Process & Form Review (SOP GL-GMP-203) Why is the CAPA Procedure important? To review a section again, click on the item on the agenda to the left. Did you get all 40 points? If you got less than 32 points, you may want to review a section again before you take the quiz.

68. X 68 Questions If you have questions or would like additional information, please contact your Quality Assurance contact.

69. X 69 Thank you!  Thank you for taking the time to complete this training.  Please follow your business unit specific process to document your training.  Click on the Exit button (X) at the top right of your screen to exit the course.  The quiz is available as the next item for this session in iLearn.

70. X 70 Navigation The Question button takes you back to this Navigation page. References regarding questions about content can be found at the end of the program. The Home button returns you to the beginning of the program. The Exit button takes you out of the course. When returning, you'll come back to the page at which you exited. The Back button takes you back one page. The Forward button takes you forward one page. The Return button takes you to the last viewed page. Click the RETURN button now to the left to return to the page you just left. X