Application of FMCA as a Tool for Risk Assessment

Transcription

1 Application of FMCA as a Tool for Risk Assessment Carl A. Anderson; Robert P. Cogdill; and James K. Drennen, III IFPAC 0 January 007 Baltimore, MD

2 Outline Introduction PAT Process Role of risk assessment Risk assessment approaches FMECA CQA based FMCA Sample data Information IFPAC, Baltimore, MD 007

3 Tech PAT Philosophy IFPAC, Baltimore, MD 007

4 Risk Assessment Scope Risk to what? Quality, safety, business, etc. Must be defined at the outset Risk from what? Processing of raw materials to finished product the process Why? Establish priorities for process improvement and process understanding Provide a consistent metric for assessing risk within an organization (intra- and inter- product) IFPAC, Baltimore, MD 007

5 Risk Assessment is a Tool A tool to identify the greatest risks and the best opportunities for risk remediation Risks assessed for current systems Sources of information for risk assessment Data Experience Estimation... and continues with the next iteration of risk assessment (residual risk) IFPAC, Baltimore, MD 007 5

6 Risk Mitigation Philosophy Process understanding Identify CQAs Tabulate product characteristics vs. CQAs Improve process understanding Identify sources of variability Control strategy Tabulate CQAs vs. source of variability Tabulate variability vs. contol No Acceptable performance Record outcomes Yes Adapted from ASTM E55 OK IFPAC, Baltimore, MD 007 6

7 PAT Framework (from guidance) A system for (all are required for PAT) Design Analysis Control Through timely measurement of critical quality/process attributes (CQA/CPA) Raw materials In-process materials Processes Goal of ensuring final product quality IFPAC, Baltimore, MD 007 7

8 Risk to What? Quality, safety, business, etc. Product quality Product performance Efficacy, Purity, and Safety Customer satisfaction Regulatory compliance IFPAC, Baltimore, MD 007 8

9 Two Approaches for Describing Failure Modes/Effects Effects analysis Risk priorities are assigned to failure mode effects (failure mode effects analysis, FMEA) CQA Beginning Risk area Ending CQA (failure mode effect) Risk priorities established by critical quality attributes (CQA) of a product Beginning CQA Ending Mechanism of failure IFPAC, Baltimore, MD 007 9

10 Failure Mode Effects Table Risk areas The manufacturing process is divided into major areas Failure mode Within each risk area, specific mechanisms that cause failure effects Cause Failure effects The results of a failure mode Effect IFPAC, Baltimore, MD

11 Failure Mode Hierarchy Failure Mode Effects Unit Operation Risk Area Failure Mechanism Failure Mode 1 Failure Mode Failure Mode Failure Effect FM1 FM FM FM1 FM FM FM FM1 FM IFPAC, Baltimore, MD

12 CQA Based Failure Modes Critical quality attributes are the basis for identification and evaluation of failure modes Unit operation Unit operations that affect CQA Failure mode Means by which the unit operation causes CQA to fail Multiple levels are used until primary cause is established IFPAC, Baltimore, MD 007 1

13 Failure Mode Hierarchy CQA Failure effect CQA Unit Operation Dispensing Compression Failure Mode Levels FM1 FM FM FMa FMb FM1 FM FM FMa FMb FM1 FM FM IFPAC, Baltimore, MD 007 1

14 Risk Analysis by Criticality Analysis Criticality Analysis seeks to identify the potential for system failures by examining failure mechanisms associated with a predetermined consequence The failure modes for a system are ranked according to their Risk Priority Number (RPN), which is the product of severity (S), probability of occurrence (O), and detectability (D), for each failure mode: RPN = S x O x D IFPAC, Baltimore, MD 007 1

15 Criticality Analysis Criticality Analysis will be performed in a semi-quantitative manner, where S, O, and D are encoded using a 5-point qualitative scale: 1 = very low or none (e.g. low severity, or high detectability) = low or minor = moderate = high 5 = very high or catastrophic (e.g. extreme high severity, un-detectable) Scale must be established within each organization and applied consistently IFPAC, Baltimore, MD

16 Risk Assessment Process A 5-step method for assigning relevance of failure modes 1. For each CQA, determine likely failure modes for each unit operation. Assign a qualitative detectability (D) score for each failure mode. Determine the severity scores (S) for each failure mode. Determine the probability, or probability distribution, of occurrence (O) for each failure mode 5. Rank opportunities according RPN of modes IFPAC, Baltimore, MD

17 Detectability (D) scale Detectability assumptions Detectability (given current systems are we detecting, not could we detect ) Detection opportunity is within the span of the current unit operation (from entry into operation through exit to next operation) 1. Readily apparent. Between 1 and. Detected, but not always, or not in a timely manner. Between and 5 5. Not detectible within (current) manufacturing operation IFPAC, Baltimore, MD

18 Severity (S) scale Severity assumptions Failure has occurred e.g., When it does happen (or has happened), how bad was it? Failure is detected 1. Has no appreciable consequences to quality (change mid-process, change next batch, root cause is well understood and adjustments will remediate). Between 1 and. Requires action, (product saleable with reconciliation, rework, extensive analysis/adjustments, further product inspection, sell/no sell, gray area between clear batch loss and saleable product). Batch loss, unrecoverable 5. Multiple batch loss ( >10) IFPAC, Baltimore, MD

19 Occurrence (O) scale Based on number of events per batch/campaign: Occurrence is independent of detectability Occurrence probability frequency How often do you think this happens? 1. Has not happened, but there is a finite (albeit small) probability that it will. Between 1 and. Sporadically (often enough to be quantifiable, but not often enough to be routine). Between and 5 5. Happens with regularity (e.g., every batch? Every month? Every campaign?) IFPAC, Baltimore, MD

20 Failure Mode Hierarchy CQA Failure effect CQA Unit Operation Dispensing Compression Failure Mode Levels FM1 FM FM FMa FMb FM1 FM FM FMa FMb FM1 FM FM Risk Priority Number S O D IFPAC, Baltimore, MD 007 0

21 Example of Failure Mode Table /Dispensing (CQA/Unit Op) CQA: Unit operation: Dispensing Failure mode: What can happen in dispensing? (Placing the product at risk for poor quality and resulting in an unacceptable assay.) Example: Incorrect quantity of material dispensed IFPAC, Baltimore, MD 007 1

22 Failure mode example ( /) API Sticking Static charge Wet equipment Spillage Charging» At transfer» Discharge valve open While blending» Discharge valve failure» Operator error Discharging Underblend Wrong blend time Inadequate blend time Overblend Wrong blend time Blend time too long IFPAC, Baltimore, MD 007

23 Risk Priority Number (RPN) CQA Unit Op FM 1 FM FM S O D RPN API Sticking Static charge API Sticking Wet equipment 5 0 Spillage Charging At transfer Spillage Charging Discharge valve open 1 Spillage While blending Discharge valve failure 1 1 Spillage While blending Operator error 1 6 Spillage Discharging 1 1 Underblend Wrong blend time Underblend Inadequate blend time 5 60 Overblend Wrong blend time Overblend Blend time too long IFPAC, Baltimore, MD 007

24 Risk Priority Number (RPN) CQA Unit Op FM 1 FM FM S O D RPN API Sticking Static charge API Sticking Wet equipment 5 0 Spillage Charging At transfer Spillage Charging Discharge valve open 1 Spillage While blending Discharge valve failure 1 1 Spillage While blending Operator error 1 6 Spillage Discharging 1 1 Underblend Wrong blend time Underblend Inadequate blend time 5 60 Overblend Wrong blend time Overblend Blend time too long IFPAC, Baltimore, MD 007

25 Data Summary Underblend - Inadequate blend time API Sticking - Wet equipment Spillage - Charging - At transfer Underblend - Wrong blend time Overblend - Wrong blend time API Sticking - Static charge Overblend - Blend time too long Spillage - Charging - Discharge valve open Spillage - While blending - Operator error Spillage - While blending - Discharge valve failure Spillage - Discharging RPN IFPAC, Baltimore, MD 007 5

26 Data Summary Risk Priority Number (RPN) High Risk Low Risk Unit Operation < 10 Dispensing Blend Compression Reorganize data by unit operations Summarize number of high risk failure modes in each unit operation Identifies unit operations with greatest potential for risk mitigation IFPAC, Baltimore, MD 007 6

27 Data summary 0 5 Frequency Dispensing Blend Compression < 10 RPN Category IFPAC, Baltimore, MD 007 7