ASEAN Guidelines on GMP for Traditional Medicines Health

ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements (TM/HS) EVALUATION OF CORRECTIVE ACTION AND PREVENTIVE ACTION (CAPA) Prepared by: Malaysia Approved by: ASEAN TMHS GMP Task Force Endorsed by: ASEAN TMHS Product Working Group

OUTLINE • • • What is CAPA Basic CAPA System Root Cause Analysis and the Tools CAPA Regulatory challenges and common issues Summary ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements – 2015 Evaluation of CAPA 2

INTRODUCTION: WHAT IS CAPA? ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements – 2015 Evaluation of CAPA 3

WHAT IS CAPA? (2) CORRECTIVE ACTION ØEliminate detected nonconformity PREVENTIVE ACTION Ø Prevent nonconformity occurrence ü The HEART of an effective quality management system ü CAPA methodology is for continuous improvement of product & process ü To enhance product & process understanding and eliminate potential non-conformance. As per ICH Q 10; Pharmaceutical Quality System ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements – 2015 Evaluation of CAPA 4

WHAT IS CAPA? (3) ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements – 2015 Evaluation of CAPA

CAPA INPUTS It all starts with INPUTs …. Out-Of-Specifications Product Complaints Product Recall Audit Findings Non-conformity Deviation Post Market Surveillance NCR Issue Review Data Gathering Risk Assessment/ Recommended Course of Action CAPA REQUIRED CAPA NOT REQUIRED INITIATE CAPA Containment/ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements – 2015 Evaluation of CAPA Correction

BASIC CAPA SYSTEM (1) ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements – 2015 Evaluation of CAPA 7

BASIC CAPA SYSTEM (2) 1. Initiate CAPA 5. Verify / Validate 2. Description of NC 6. Implement Cause Known Unknown 3. Investigate Root Cause 4. Solution 7. Effectiveness Check 8. Close CAPA (Action Plan) 9. Track & Trend ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements – 2015 Evaluation of CAPA

BASIC CAPA SYSTEM 1. Initiate CAPA 5. Verify / Validate 2. Description of NC 6. Implement Cause Known Unknown 3. Investigate Root Cause 4. Solution 7. Effectiveness Check 8. Close CAPA (Action Plan) 9. Track & Trend ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements – 2015 Evaluation of CAPA

DESCRIPTION OF NONCONFORMANCE • Describe the non-conformance precisely – What, when, where, who, why & how. ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements – 2015 Evaluation of CAPA

BASIC CAPA SYSTEM 1. Initiate CAPA 5. Verify / Validate 2. Description of NC 6. Implement Cause Known Unknown 3. Investigate Root Cause 4. Solution 7. Effectiveness Check 8. Close CAPA (Action Plan) 9. Track & Trend ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements – 2015 Evaluation of CAPA

INVESTIGATION CHECKLIST • Describe the fast fix that was taken, Is it working? • Identify owner and those involved. • Gather information: – – – Data Employee Input Flowcharts of the process Procedures Records – (quantitative data) • Has the problem occurred in the past? • Identify Root Cause. ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements – 2015 Evaluation of CAPA

RULES OF INVESTIGATION • Use proven root cause analysis tools • Think “out – of – the – box” • Take the time needed • Put a plan together ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements – 2015 Evaluation of CAPA

WHAT MAKES A GOOD ROOT CAUSE? • Document the primary cause (s) of the nonconformance – Understand the problem statement – Don’t assume that people know or understand the problem well enough to determine root cause – Data collection and analysis • Involve people who have an understanding of the problem • Used Cause and Effect principle • Facilitate the Root Cause Analysis – Provide the knowledge of RCA tools • When solved, the problem will not recur ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements – 2015 Evaluation of CAPA

ROOT CAUSE ANALYSIS (RCA) ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements – 2015 Evaluation of CAPA

RCA: COMMON TOOLS ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements – 2015 Evaluation of CAPA

RCA: CAUSE MAPPING ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements – 2015 Evaluation of CAPA

RCA: CAUSE MAPPING �Cause Mapping Ø Visual explanation the cause of an incident OR problem Ø Relationship between Cause-and-Effect Ø Can be too simple or too complex, depending on the issue Cause Effect Cause-Effect Relationship ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements – 2015 Evaluation of CAPA

CAUSE MAPPING - EXAMPLE RCA: CAUSE MAPPING Problem Caused by Cause Forest Fire Caused by Lightning Strike Car won’t start Why? Starter motor not turning Why? Dead battery No rain in 2 weeks Grass is dying Haven’t watered in 2 weeks Hot, Sunny weather for 2 weeks ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements – 2015 Evaluation of CAPA Why? No water in battery

RCA: FISHBONE DIAGRAM Ishikawa/ Fishbone Diagram ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements – 2015 Evaluation of CAPA

RCA: FISHBONE DIAGRAM ‘Ishikawa / Fishbone Diagram’ can be used to identify potential factors causing an overall effect. Can be use to analyze several causes based on: Ø Ø Ø Method Machine Personel Environment Material etc ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements – 2015 Evaluation of CAPA

FISHBONE DIAGRAM EXAMPLE FISHBONE DIAGRAM ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements – 2015 Evaluation of CAPA

FISHBONE DIAGRAM -EXAMPLE RCA: FISHBONE DIAGRAM ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements – 2015 Evaluation of CAPA

RCA: FISHBONE DIAGRAM ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements – 2015 24 Evaluation of CAPA

RCA: FISHBONE DIAGRAM (5 WHYs Method) Why, why, why Kaji Cegah ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements – 2015 Evaluation of CAPA

RCA: 5 WHYS METHOD Also known as ‘Why – why chart’ The main objective is to identify potential problem with the word of ‘why’ ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements – 2015 Evaluation of CAPA

5 WHYs Method -Example RCA: 5 WHYS METHOD ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements – 2015 Evaluation of CAPA

5 WHYs Method -Example RCA: 5 WHYS METHOD Root Cause ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements – 2015 Evaluation of CAPA

5 WHYs Method -Example RCA: 5 WHYS METHOD ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements – 2015 Evaluation of CAPA

5 WHYs Method -Example RCA: 5 WHYS METHOD Finding: A cockroach was found under a mixer in Mixing Room 1 Why the cockroach died? Answer: Eating bait Why it ate bait? Answer: There was a bait in the Mixing Room 1 Why there was a bait in Mixing Room 1? Answer: Requirement of pest control procedure. Why the SOP required cockroach bait inside the production area? Answer: The personnel who prepared the SOP didn’t aware the GMP principle. Why he didn’t aware the GMP requirement? Answer: The personnel never been trained accordingly. Root Cause ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements – 2015 Evaluation of CAPA

BASIC CAPA SYSTEM 1. Initiate CAPA 5. Verify / Validate 2. Description of NC 6. Implement Cause Known Unknown 3. Investigate Root Cause 4. Solution 7. Effectiveness Check 8. Close CAPA (Action Plan) 9. Track & Trend ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements – 2015 Evaluation of CAPA

CORRECTIVE ACTION PREVENTIVE ACTION Type Positive Negative Trial & Error § feels good § easier… more doing than thinking § might be fast § reactive § may add complexity to problem § risks Expert/ Experiential § uses company wisdom/ lessons learned § employs reasoning § use experience § tunnel-vision § expensive and possibly slow § Does not work as well for start up problems § no deductive thinking or testing logically Comparative § § fact-based § requires discipline Objective § need to focus more on process very proactive § people may resist new method leverages experience/expertise ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements – 2015 Evaluation of CAPA

CORRECTIVE ACTION PREVENTIVE ACTION Specific • Precise action to eliminate the root cause • No ambiguity Timely • The action has to be time bound • Accomplishing date/time Realistic • Action has to be logic and practical • All the resources required are considered Measurable • Responsible person will carry out the task by when • Quantifiable result Attainable • Capability to implement should be reviewed • Action should be feasible & achievable ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements – 2015 Evaluation of CAPA

CORRECTIVE ACTION PREVENTIVE ACTION • Implement a solution to address the cause … not the symptom • Implementation of a solution that does not address the cause of the problem is costly ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements – 2015 Evaluation of CAPA

BASIC CAPA SYSTEM 1. Initiate CAPA 5. Verify / Validate 2. Description of NC 6. Implement Cause Known Unknown 3. Investigate Root Cause 4. Solution 7. Effectiveness Check 8. Close CAPA (Action Plan) 9. Track & Trend ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements – 2015 Evaluation of CAPA

EFFECTIVENESS CHECKS • Effectiveness Checks – Criteria applies based on case or nature of CAPA – Plan of effectiveness check is specific to CAPA – Early detection points are identified to monitor for recurrence/occurrence ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements – 2015 Evaluation of CAPA

EFFECTIVENESS CHECKS • What to do when a effectiveness check fails, and what are the consequences? – Close the CAPA and open a new one? – Get an extension? – Leave the CAPA open and investigate why? ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements – 2015 Evaluation of CAPA

REGULATORY CHALLENGES • No submission of CAPA feedback • Feedback too simple or no cover letter e. g. One Page • Insufficient CAPA feedback e. g. : ‘We take note on your comment’ • No dateline/ timeframe • No CAPA • No supporting document ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements – 2015 Evaluation of CAPA

COMMON CAPA ISSUES • • • No procedure Did not understand the issue No commitment from top management No monitoring Did not identify RCA or wrong RCA ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements – 2015 Evaluation of CAPA

EXAMPLE OF CAPA FORMAT 1. Introduction Report Date Manufacturer Report Number Inspection Date GMP Status : (Versi terkini) : ABC Sdn. Bhd. : GMP 300/ Record-10/YY/XXX – (CAPA) : dd/mm/yyyy : Acceptable/ Unacceptable 2. CAPA Implementation Finding Root Cause 1. 1 Personnel not aware of GMP Requirement Correction Corrective Action Preventive Action Training ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements – 2015 Evaluation of CAPA Timeline of Completion Jan 2018

EXAMPLE OF CAPA FORMAT (2) Chapter 1 2 3 Prepared by: Date: Finding status Critical Major Minor Total Open 0 0 Closed 1 0 0 1 Open Closed Checked by: Approved by: Date: ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements – 2015 Evaluation of CAPA

CAPA CLOSURE • The CAPA implementation need to follow by the monitoring of its effectiveness • Various source of data need to be considered when analyze the CAPA • CAPA documentation need to be checked and verify accurately before being stored ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements – 2015 Evaluation of CAPA

CONTINUOUS IMPROVEMENT I can close the CAPA because have taken the action I’m confident that I’ve solved the problem and ensure it won’t be repeat again ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements – 2015 Evaluation of CAPA

CONFIRMATION OF CAPA The next inspection? ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements – 2015 Evaluation of CAPA

BENEFITS OF GOOD CAPA SYSTEM • • • Assurance that quality issues are resolved Customer complaints are reduced Promotion of continuous improvement An aligned method for problem solving Regulatory requirements are met Business needs are met ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements – 2015 Evaluation of CAPA

SUMMARY • A mature CAPA system can serve as a useful tool for analysing past events, correcting existing non conformities and preventing future events. • CAPA will be useless if there is no commitment from top management of company or just simply prepared to meet the regulatory requirement ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements – 2015 Evaluation of CAPA

ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements – 2015 Evaluation of CAPA 47