CAPA Root Cause Analysis and Risk Management By

CAPA, Root Cause Analysis, and Risk Management By Joseph F. Tarsio, M. B. A. , Ph. D. March 17, 2015

What is CAPA? Corrective and Preventative Action (CAPA) is a system of quality procedures required to eliminate the causes of an existing nonconformity and to prevent recurrence of nonconforming product, processes, and other quality problems.

Regulatory Guidance “Corrective and Preventive Action, ” Quality System Regulation (QSR), 21 CFR Part 820, Medical Devices, Subpart J, Sec. 100, Became effective on June 1, 1997, Replacing the 1978 GMP for Medical Devices. http: //www. accessdata. fda. gov/scripts/cdrh/cfdocs/cf. CFR/CFRSearch. cfm? CFRPart=820 “Overview of the Quality System Regulation for Medical Devices, ” Kimberly Trautman – Food and Drug Administration, USA and Chair, Study Group 3, June 29, 1999. http: //www. fda. gov/cdrh/reuse/events/cdrom-9. ppt “QSIT Corrective & Preventive Actions, ” Quality System Inspection Techniques (QSIT) Guide, August 1999. http: //www. fda. gov/ora/inspect_ref/igs/qsitguide. pdf “Establishment and Maintenance of a Quality Program. ” Human Cells, Tissues, And Cellular And Tissue-Based Products (HCT/P's), 21 CFR Part 1271 Subpart D, Current Good Tissue Practice (c. GTP), Sec. 160, May 25, 2004. Revised as of April 1, 2006, http: //www. accessdata. fda. gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch. cfm? CFRPart=1271

CAPA is Part of the Seven Quality Subsystems

Terminology Nonconforming Material or Process (Discrepancy) - Any material or process that does not meet its required specifications or documented procedure. Correction – Refers to repair, rework, or adjustment and relates to the disposition of an existing nonconformity. Corrective Action - To identify and eliminate the causes of existing nonconforming product and other quality problems. Preventive Action - To identify and eliminate the causes of potential nonconforming product and other quality problems.

Nonconformance Control Steps 1. Identify nonconforming items. 2. Move items away from work area. 3. Decide what should be done. 4. Take remedial action.

Components Of Corrective Action ØCollect and analyze data to identify nonconforming product, incidents, concerns or other quality problems that would be worth the effort to correct ØInvestigate and identify root cause ØImplement the correct solution ØVerify or validate effectiveness

Corrective Action (CA) Steps 1. Would the correction be worth the effort. 2. Identify root cause. 3. Change the system. 4. See if it worked.

Ascertaining Root Cause Ø Root cause and the “weed”: Weeds can be difficult to remove once they start to grow and spread. On the surface, the weed is easy to see. However, the underlying cause of the weed, its root, lies below the surface and is not so obvious. To eradicate the weed you have to get below the surface, identify the root, and pluck it out. Thus, you have to go beyond the obvious, ascertain an accurate route cause, so the appropriate corrective action can be pursued to prevent recurrence.

Tools for Ascertaining Root Cause Include the following: Ø The five whys, a simplistic approach exhausting the question “Why? ”. Ø Fishbone diagram, a cause and effect diagram also known as the Ishikawa diagram. Ø Pareto analysis, the 80/20 rule premised on a predefined database of known problems. Ø Fault tree analysis, a quantitative diagram used to identify possible system failures. Ø Failure modes and effects analysis (FMEA), which lists all potential failure modes and the potential consequences associated with each failure mode.

The Five Whys Technique Ø The 5 Whys technique is a simpler form of fault tree analysis for investigations, especially investigations of specific accidents as opposed to chronic problems. Ø The 5 Whys technique is a brainstorming technique that identifies root causes of accidents by asking why events occurred or conditions existed. Ø The 5 Whys process involves selecting one event associated with an accident and asking why this event occurred. This produces the most direct cause of the event. Ø Drill down further indicating if their were any subcauses of the event, and ask why they occurred. Ø Repeat the process for the other events associated with the accident.

Disadvantages of the 5 Whys Technique Ø This time consuming brainstorming process may be tedious for team members trying to reach consensus. This is especially true for large teams. Ø Results are not reproducible or consistent. Another team analyzing the same issue may reach a different solution. The particular brainstorming process that was utilized may be difficult, if not impossible, to duplicate. Ø Root causes may not be identified. The 5 Whys technique does not provide a means to ensure that root causes have been identified.

Creating a Fishbone Diagram – Initial Steps Ø A fishbone diagram is a cause and effect diagram that looks much like a skeleton of a fish. Ø It is also called a Ishikawa diagram after the inventor of the tool, Kaoru Ishikawa who first used the technique in the 1960 s. Ø To draw the diagram, first list the problem/issue to be studied in the head of the fish. Ø Label each bone of the fish. The major categories typically used are: The 6 M’s: Machines, Methods, Materials, Measurements, Mother Nature (Environment), Manpower (People). Ø Repeat this procedure with each factor under the category to produce sub-factors. Ø Continue asking, “Why is this happening? ” and put additional segments under each sub-factor.

Simple Fishbone Diagram Bioburden Levels Out of Specifications

Creating a Fishbone Diagram – Further Steps Ø Continue adding sub-factors to your diagram until you no longer get useful information as you ask, “Why is that happening? ” Ø Analyze the results of the fishbone after team members agree that an adequate amount of detail has been provided under each major category. Do this by looking for those items that appear in more than one category. These become the ‘most likely causes”. Ø For those items identified as the “most likely causes”, the team should reach consensus on listing those items in priority order with the first item being the most probable” cause.

More Detailed Fishbone Diagram

Simple Fishbone Diagram Patient Received Incorrect Dose of Medication Equipment needs not met

Very Detailed Fishbone Diagram Increased Outpatient Department Waiting Time

Advantages of Fishbone Diagrams Fishbone diagrams do provide value in that they: Ø (1) organize potential causes, Ø (2) help a team to think through causes they might otherwise miss, and Ø (3) provide a living document that shows the status of all potential causes and whether they have been proved/disproved/acted upon.

Limitations of Fishbone Diagrams Ø One danger with fishbone diagrams is that they create a divergent approach to problem solving, where the team expends a great deal of energy speculating about potential causes, many of which have no significant effect on the problem. Ø This approach may leave a team feeling frustrated and hopeless. Ø Therefore in deciding which problems to explore the team needs to closely look at the evidence in order to separate fact from opinion.

Pareto Charts Ø The Pareto chart is a bar graph whose invention is attributed to the Italy economist, Mr. Vilfredo Pareto. Ø In 1906, Vilfredo Pareto made the well-known observation that 20% of the population owned 80% of the property in Italy. Ø This was later generalized by Joseph M. Juran and others into the so-called Pareto principle – that for many phenomena, 80% of consequences stem from 20% of the causes. Ø In the Pareto chart, the lengths of the bars represent frequency or cost (time or money), and are arranged with longest bars on the left and the shortest to the right. In this way the chart visually depicts which situations are more significant (a Pareto analysis).

Pareto Frequency Chart Shipping Documents Complaints 4 th Quarter 2014 Results: This Pareto Chart shows that approx. 70% of the document complaints reported involve quality certificates. Significance: More care should be given to how quality certificates are written and added to the shipping package.

When to Use a Pareto Chart Ø When analyzing data about the frequency of problems or causes in a process. Ø When there are many problems or causes and you want to focus on the most significant. Ø When analyzing broad causes by looking at their specific components. Ø When communicating with others about your data.

Advantages of Pareto Charts Ø The main advantages of Pareto charts are that they are easy to understand as well as to present. Ø Many managers prefer to see an analysis that is easy to represent and understand a Pareto chart is strong tool for that.

Disadvantages of Pareto Charts Ø Focusing on the Pareto chart alone may lead to the exclusion from further consideration of minor sources driving defects and non-conformances. Ø Another disadvantage of generating Pareto charts is that they cannot be used to calculate the average of the data, its variability or changes in the measured attribute over time. Without quantitative data it isn't possible to mathematically test the values or to determine whether or not a process can stay within a specification limit.

Fault Tree Analysis (FTA) Ø Fault tree analysis was first introduced by Bell Laboratories and is one of the most widely used methods in system reliability, maintainability and safety analysis. Ø It is a deductive procedure used to determine the various combinations of hardware and software failures and human errors that could cause undesired events (referred to as top events) at the system level. Ø The deductive analysis begins with a general conclusion, then attempts to determine the specific causes of the conclusion by constructing a logic diagram called a fault tree. This is also known as taking a top-down approach.

Fault Tree Analysis (continued) Ø The main purpose of the fault tree analysis is to help identify potential causes of system failures before the failures actually occur. Ø It can also be used to evaluate the probability of the top event using analytical or statistical methods. Ø After completing an FTA, you can focus your efforts on improving system safety and reliability.

To do a comprehensive FTA, follow these steps: 1. Define the fault condition, and write down the top level failure. 2. Using technical information and professional judgments, determine the possible reasons for the failure to occur. These are level two elements because they fall just below the top level failure in the tree. 3. Continue to break down each element with additional gates to lower levels. Consider the relationships between the elements to help you decide whether to use an "and" or an "or" logic gate. 4. Finalize and review the complete diagram. The chain can only be terminated in a basic fault: human, hardware or software. 5. If possible, evaluate the probability of occurrence for each of the lowest level elements and calculate the statistical probabilities

A Simple Fault Tree Analysis And gate - represents a condition in which all the events shown below the gate (input gate) must be present for the event shown above the gate (output event) to occur. This means the output event will occur only if all of the input events exist simultaneously. Or gate - represents a situation in which any of the events shown below the gate (input gate) will lead to the event shown above the gate (output event). The event will occur if only one or any combination of the input events exists.

Medical Device Fault Tree Analysis

Advantages of Fault Tree Analysis Ø FTA focuses on the judgment of experts from varied disciplines and provides a common language and perspective for the problem. Ø Both agreements and differences in opinion on the inputs and importance are accounted for in FTA. Ø Members are not likely to feel threatened, due to the focus on how the system operates, not personnel. Ø Graphic description clearly communicates the possible causes of failure.

Disadvantages of Fault Tree Analysis Ø FTA relies on several expert opinions and judgments at several stages. This makes it very prone to inaccuracy. Ø In large systems, computer algorithms are needed to accomplish the quantitative analysis.

Failure Modes and Effects Analysis (FMEA) Ø Begun in the 1940 s by the United States military, FMEA was further developed by the aerospace and automotive industries. Ø FMEA is a step-by-step approach for identifying all possible failures: - in a design (“design FMEA”), - in a manufacturing or assembly process (“process FMEA”), - or in a final product or service (“use FMEA”). Ø “Failures” are any errors or defects, especially ones that affect the customer, and can be potential or actual. Ø “Failure modes” means the ways, or modes, in which something might fail. Ø “Effects analysis” refers to studying the consequences, or effects, of those failures.

Analyzing Failure Effects through FMEA Ø Failure can be represented by a Risk Priority Number (RPN). Ø Risk Priority Numbers (RPN’s), can be ranked according to the following: RPN = (Potential Severity) x (Likelihood of Occurrence) x (Ability to Detect). Ø For all numerical weights, a common industry standard is to us a 1 to 5 scale. For likelihood of occurrence for example use 1 to represent “practically impossible” and 5 to indicate “occurs frequently. ” Ø When applying FMEA, the high-priority failures— identified by higher RPN’s—are examined first. For the failure, a root cause is identified and a corrective action is developed to eliminate the root cause.

Corrective Action for High Ranking Failures Ø Recommended action(s) to address potential failures that have a high RPN could include for example: -specific inspection, testing or quality procedures; -selection of different components or materials; -limiting the operating range or environmental stresses; -redesign of the item to avoid the failure mode; -monitoring mechanisms; -performing preventative maintenance; -operator retraining; -inclusion of back-up systems or redundancy. Ø Assign responsibility and a target completion date for the above actions. This makes responsibility clear-cut and facilitates tracking.

Consequence x Likelihood Risk Matrix

Follow Up on Corrective Actions for High RFP Failures Ø Indicate the action(s) taken for each high ranking failure (those having a high RPN). Ø After those actions have been taken, re-assign a new RPN based on the likelihood for the failure to occur again, and to what severity, and also as to how easy or harder it would be to detect again. Ø Determine with the new RPNs to what extent the failures are now under control. Are any further actions required? Ø Update the FMEA as to how the design, process, or final product/service has been improved.

Advantages of FMEA Ø Stimulates open communication of potential failures and their outcomes. Ø Requires that all known or suspected potential failures be considered. Ø Ranks failures according to risk. Ø Results in actions to reduce failure. Ø Results in actions to reduce risk. Ø Includes a follow up system and re-evaluation of potential failures that favors continual improvement.

Limitations of FMEA Ø FMEA may not be able to discover complex failure modes involving multiple failures or subsystems. Ø Without follow up sessions, the process will not be effective. Ø Follow up RPNs may be less instructive regarding improvement from severe failure since detection and occurrence can always be reduced but it is only in rare cases that severity ratings can be reduced.

Preventive Action and Risk Management Ø It involves the gathering of precursor data & the analysis of their risk. Ø Risk is a combination of likelihood of those or similar events happening at your site, how easy they are to detect, and what would be the consequences (as can be seen in the RPNs for example).

Preventive Action and Risk Management (continued) Ø Determine your risk tolerance (also called risk appetite) Ø Apply resources to lower unacceptable risks through ATM: accept – if the risk is acceptable let it go & reevaluate it later transfer – if the risk is unacceptable, the risk should perhaps be transferred to an insurance carrier mitigate – use change management principles to mitigate reoccurrence (the preventive action). Ø Refresh your data by adjusting the risk profile achieved after ATM and whether the risks are now within your risk tolerance.

Preventive Action and Risk Management (continued) 1. Gather and analyze precursor data. 2. Determine risk tolerance. Compare the risk you are facing versus your risk tolerance. 4. Follow-up on the appropriateness and effectiveness of the actions taken. 3. Accept risk, transfer risk, or decrease risk through preventive action.

Quality Data Sources

Communications Component Of Corrective And Preventive Action (CAPA) ØCommunicate information about quality problems, changes made, outcomes, and trends to those persons directly responsible and to the staff in general ØForward information for management review ØWork with staff and management to produce continuous quality improvement

CAPA Case Studies Ø Weak CA, Weak PA (Common) Ø Weak CA, Strong PA (Unusual) Ø Strong CA, Weak or Unlinked PA (Common) Ø Strong PA Linked to a Strong CA (Ideal)

Case Study No. 1 Ø The company develops biopharmaceuticals Ø The company has a CAPA program Ø A review of existing internal and external audits reveal that: • nonconformities are documented • corrections are proposed (a temporary or permanent change, repair, rework, or scrap) • corrections made are timely • but the same nonconformities seem to reoccur over and over again • customers are complaining

Ø The current investigation indicates that: • nonconformities are not adequately categorized and trended • the root causes of existing nonconformities are not adequately investigated or addressed • preventive actions are not sufficient to eliminate the reoccurrence of the nonconformity • discrepancy and CAPA procedures are not well-written or difficult to follow • the forms utilized don’t follow the flow of the procedure • the forms do not provide enough space for more than a brief entry • verbal decisions are not written down • responsible people are assigned but a timelines for the follow-ups is not given or is vague

The Solution Ø Revise all Quality Assurance Procedures to emphasize CAPA and to link discrepancy reporting and disposition to preventive action Ø Initiate a trending and root cause analysis program Ø Present these programs to management and to the staff Ø Revise the nonconformity, CA, and PA forms Ø Conduct formal CAPA training Ø Reinforce CAPA awareness in verbal communications Ø Provide a “Quality Update” at the company’s monthly staff meeting

The Results Ø Easier to follow quality procedures Ø More user-friendly forms Ø A better understanding of processes obtained through root cause analysis Ø More proactive thinking vs. reactive thinking Ø Fewer nonconformities Ø Less scrap and rework Ø Fewer customer complaints

Pre-CAPA Post-CAPA

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