# Failure Mode and Effects Analysis (FMEA) for Diagnostic Assay Validation ## Quick Answer - Apply FMEA during assay validation to identify and rank potential failure modes using Risk Priority Numbers (RPN) calculated from severity, occurrence, and detection scores. - Build a cross-functional team, map the assay workflow step by step, and score each failure mode before implementing corrective actions and re-scoring to verify risk reduction. - FMEA prioritizes relative risk within your specific assay context, it does not replace empirical validation data, regulatory requirements, or clinical performance studies. ## At a Glance | FMEA Element | Purpose in Assay Validation | Typical Scoring Range | Decision Use | | --- | --- | --- | --- | | Severity (S) | Rates impact of a failure on result correctness and patient safety | 1 (negligible) to 10 (catastrophic) | Identifies failures requiring immediate design changes | | Occurrence (O) | Rates probability of a failure happening during routine use | 1 (rare) to 10 (certain) | Prioritizes failures needing process controls | | Detection (D) | Rates likelihood current controls will catch the failure | 1 (almost certain detection) to 10 (no detection) | Guides investment in additional quality checks | | Risk Priority Number (RPN) | Product of S x O x D for ranking and comparison | 1 to 1000 | Ranks failure modes for corrective action priority | ## Understanding FMEA in Diagnostic Assay Validation Failure Mode and Effects Analysis is a systematic method for evaluating each step of a diagnostic assay process to identify where and how it might fail, assess the consequences of those failures, and prioritize actions to reduce risk. The method originated in engineering but has been adapted broadly across laboratory medicine and biotechnology because it provides a structured, documented approach to quality improvement. Diagnostic assay validation requires demonstrating that a test performs as intended for its specified use. Validation typically includes assessments of accuracy, precision, analytical sensitivity, analytical specificity, and other performance characteristics. FMEA complements these empirical studies by focusing on the process itself, asking what could go wrong at each step and what the consequences would be. The core value of FMEA in this context is its forward-looking nature. Traditional validation measures performance under defined conditions, but FMEA forces the team to consider edge cases, operator errors, equipment malfunctions, reagent lot variations, and environmental factors that might not appear during routine validation runs. This makes FMEA a risk management tool that supports validation planning, not a replacement for validation experiments. FMEA aligns with broader quality management principles used in clinical laboratories. The National Institute of Standards and Technology describes measurement science as encompassing calibration, standards, and quality assurance across laboratory operations. FMEA contributes to this framework by providing a structured method for identifying where measurement processes can fail and what controls are needed to maintain reliability. ## Core Principles of FMEA for Assays ### The FMEA Team FMEA requires a team, not an individual effort. The team should include people with direct hands-on experience with the assay, people who understand the clinical or research context, people who maintain the equipment, and people who will use the results. This diversity ensures that failure modes are identified from multiple perspectives and that the scoring reflects real-world conditions instead of theoretical concerns. For a diagnostic assay, the team might include the assay developer, a laboratory technician who runs the assay regularly, a quality assurance specialist, a biostatistician, and a clinical representative who understands how results are used. Each person brings a different view of where failures can occur and what the consequences might be. The team should document its membership, the scope of the analysis, and the version of the assay being evaluated. This documentation matters because FMEA results are only meaningful for the specific process version analyzed. If the assay changes, the FMEA must be updated. ### The Assay Workflow Before identifying failure modes, the team must define the complete workflow from sample collection through result reporting. For a molecular diagnostic assay, this workflow might include sample collection, transport, storage, nucleic acid extraction, quantification, amplification, detection, data analysis, and result interpretation. Each step in the workflow is a potential source of failure. The team should create a process map that shows each step in sequence, the inputs and outputs at each step, and the controls already in place. This map becomes the foundation for the FMEA because it ensures the team considers the entire process instead of focusing on a few obvious steps. ### Failure Mode Identification A failure mode is a specific way in which a process step can fail to produce the intended result. For example, in the nucleic acid extraction step, failure modes might include incomplete lysis, contamination of the sample, loss of nucleic acid during purification, or carryover of inhibitors. The team should brainstorm failure modes for each step, using their experience, manufacturer instructions, published literature, and any available quality data. The goal is to identify as many plausible failure modes as possible before moving to scoring. Missing a failure mode at this stage means it will not be considered in the risk assessment. ### Scoring and Risk Prioritization Each failure mode is scored on three dimensions. Severity reflects the impact of the failure on the final result and patient care. Occurrence reflects how often the failure is expected to happen. Detection reflects how likely existing controls are to catch the failure before it affects the result. The product of these three scores is the Risk Priority Number, which ranks failure modes from highest to lowest risk. The team uses this ranking to decide which failure modes require immediate corrective action and which can be monitored or accepted. ### Corrective Action and Reassessment FMEA is not complete when the RPN values are calculated. The team must decide which failure modes require action, implement those actions, and then reassess the failure modes to determine whether the risk has been reduced. This reassessment produces a new RPN that should be lower than the original. The cycle of identify, score, act, and reassess is what makes FMEA a continuous improvement tool. It is not a one-time exercise but a process that should be repeated whenever the assay changes or when new failure modes are discovered. ## Building the FMEA Team The composition of the FMEA team directly affects the quality of the analysis. A team with only senior scientists may miss practical failure modes that technicians encounter daily. A team with only technicians may lack the clinical context needed to score severity accurately. A balanced team for diagnostic assay FMEA includes the following roles: | Role | Contribution to FMEA | | --- | --- | | Assay developer | Provides technical knowledge of the assay design and expected performance | | Laboratory technician | Shares hands-on experience with routine operation and common problems | | Quality assurance specialist | Provides knowledge of quality controls, documentation, and regulatory expectations | | Clinical representative | Explains how results are used and the impact of incorrect results | | Equipment specialist | Provides knowledge of instrument maintenance, calibration, and failure patterns | | Biostatistician | Helps interpret validation data and assess occurrence probabilities | The team should have a designated facilitator who keeps the process moving, ensures all voices are heard, and documents the results. The facilitator should be familiar with FMEA methodology but does not need to be the most senior person on the team. ### Team Training Team members need a basic understanding of FMEA before the first session. Training should cover the purpose of FMEA, the scoring scales, and the process for identifying failure modes. This training can be brief, but it ensures that all team members are working from the same framework. The training should also emphasize that FMEA is not about assigning blame. The goal is to identify weaknesses in the process and improve them, not to find who caused a problem. This culture of openness is essential for the team to identify failure modes honestly. ## Mapping the Assay Workflow The workflow map is the foundation of the FMEA. It should be detailed enough to capture every step where a failure could occur but not so detailed that it becomes unmanageable. A typical diagnostic assay workflow map includes the following steps: 1. Sample collection and labeling 2. Sample transport to the laboratory 3. Sample accessioning and tracking 4. Sample storage before processing 5. Nucleic acid extraction 6. Quantification and quality assessment of extracted nucleic acid 7. Assay setup and reagent preparation 8. Amplification and detection 9. Data analysis and interpretation 10. Result reporting Each step should be described with its inputs, outputs, and any existing controls. For example, the sample collection step might include the input of a patient specimen, the output of a labeled collection tube, and controls such as collection instructions and labeling requirements. The workflow map should be created by the team, not by a single person. This ensures that the map reflects the actual process as it is performed, not the process as it is documented. The team should walk through the workflow step by step, confirming each step and identifying any steps that are missing from the documentation. ## Identifying Failure Modes Once the workflow is mapped, the team identifies failure modes for each step. A failure mode is a specific way in which the step can fail to produce its intended output. For example, in the sample collection step, failure modes might include: - Incorrect patient identification - Wrong collection tube used - Insufficient sample volume - Sample contaminated during collection - Sample not labeled correctly The team should use multiple approaches to identify failure modes. They can review manufacturer instructions for the assay, which often list common problems. They can review quality control data and any previous problems. They can also use structured brainstorming techniques to encourage creative thinking about possible failures. ### Sources of Failure Mode Information The team should draw on several sources to identify failure modes: - Manufacturer instructions and package inserts for the assay and equipment - Published literature on similar assays and their problems - Quality control records and proficiency testing results - Incident reports and corrective action records - Operator experience and observations The National Library of Medicine provides access to molecular biology and laboratory methods literature that can inform the team about known failure modes in various assay types. This literature can be particularly useful for identifying failure modes that the team has not personally experienced. ### Failure Mode Documentation Each failure mode should be documented with a clear description that includes the step where it occurs, the specific failure, and the potential effect on the final result. This documentation should be detailed enough that someone who was not part of the brainstorming session can understand the failure mode. The documentation should also note any existing controls that might detect or prevent the failure. These controls are important for scoring the detection dimension of the risk assessment. ## Scoring Severity, Occurrence, and Detection The three scoring dimensions are the core of the FMEA risk assessment. Each dimension uses a 1 to 10 scale, with higher numbers indicating greater risk. The team must agree on the meaning of each score before scoring begins to ensure consistency. ### Severity Scoring Severity reflects the impact of the failure if it occurs. For diagnostic assays, severity should consider both the impact on the test result and the impact on the patient or user of the result. A severity score of 1 indicates a failure that has no noticeable effect on the result. A score of 10 indicates a failure that could lead to a wrong clinical decision with serious patient harm. The team should define the severity scale in the context of their specific assay and its intended use. For example, a failure that causes a test to be repeated but does not affect the final result might score 3 or 4. A failure that produces a false negative result for a serious infectious disease might score 9 or 10. ### Occurrence Scoring Occurrence reflects the probability that the failure mode will happen. The team should base this score on available data, such as quality control records, error logs, and published literature, as well as their own experience. A score of 1 indicates that the failure is unlikely to occur, perhaps once in many years of operation. A score of 10 indicates that the failure is almost certain to occur, perhaps on every run. The team should be realistic about occurrence, using data where available instead of guessing. ### Detection Scoring Detection reflects the probability that existing controls will catch the failure before it affects the final result. A score of 1 means that the failure is almost certain to be detected. A score of 10 means that the failure will not be detected. Detection controls include internal controls, calibrators, quality control samples, replicate testing, and data review. The team should consider all existing controls when scoring detection. ### Calculating the Risk Priority Number The RPN is the product of the three scores: RPN = Severity x Occurrence x Detection The RPN can range from 1 to 1000. Higher RPN values indicate higher risk. The team uses the RPN to rank failure modes and decide which ones require action. The RPN is a relative measure, not an absolute one. It is useful for comparing failure modes within the same FMEA but should not be compared across different assays or different teams. The same failure mode might receive different RPN values from different teams because of differences in experience and context. ## Worked Example: FMEA for a Molecular Diagnostic Assay This example demonstrates the FMEA process for a hypothetical molecular diagnostic assay that detects a respiratory pathogen using real-time PCR. The example is illustrative and does not represent a specific commercial assay. ### Step 1: Define the Workflow The team defines the workflow as follows: 1. Sample collection using a nasopharyngeal swab 2. Transport to the laboratory at 2 to 8 degrees Celsius 3. Sample accessioning and labeling 4. Nucleic acid extraction using a commercial kit 5. Quantification of extracted nucleic acid 6. Preparation of the PCR master mix 7. Addition of the extracted nucleic acid to the PCR plate 8. Real-time PCR amplification and detection 9. Data analysis and interpretation 10. Result reporting ### Step 2: Identify Failure Modes The team identifies the following failure modes for the workflow: | Workflow Step | Failure Mode | Existing Controls | | --- | --- | --- | | Sample collection | Insufficient sample volume | Visual inspection of swab | | Sample transport | Temperature excursion during transport | Temperature logger | | Sample accessioning | Sample mislabeled | Barcode scanning | | Nucleic acid extraction | Incomplete lysis | Internal control | | Nucleic acid extraction | Contamination during extraction | Separate extraction room | | PCR setup | Incorrect master mix composition | Pipetting checklist | | PCR setup | Sample added to wrong well | Plate map | | Amplification | Instrument failure | Daily calibration | | Interpretation | Threshold set incorrectly | Fixed threshold | ### Step 3: Score Each Failure Mode The team scores each failure mode on severity, occurrence, and detection, then calculates the RPN. | Failure Mode | Severity | Occurrence | Detection | RPN | | --- | --- | --- | --- | --- | | Insufficient sample | 7 | 4 | 5 | 140 | | Temperature excursion | 5 | 3 | 4 | 60 | | Sample mislabeled | 9 | 2 | 3 | 54 | | Incomplete extraction | 8 | 3 | 2 | 48 | | Contamination | 9 | 2 | 2 | 36 | | Master mix error | 7 | 2 | 4 | 56 | | Wrong well | 8 | 2 | 3 | 48 | | Instrument failure | 6 | 1 | 2 | 12 | | Interpretation error | 7 | 2 | 3 | 42 | ### Step 4: Prioritize and Take Action The team reviews the RPN values and decides that failure modes with an RPN above 100 require immediate action. In this example, only insufficient sample collection has an RPN above 100. The team decides to implement a training program for sample collectors, add a visual inspection step at accessioning, and require a second person to confirm sample adequacy before transport. ### Step 5: Reassess After implementing the corrective actions, the team reassesses the failure mode. The occurrence score might drop from 3 to 2 because of the training, and the detection score might drop from 5 to 3 because of the visual inspection. The new RPN would be 9 x 2 x 3 = 54, which is below the threshold. The team also reviews the other failure modes and decides that the contamination failure mode, despite its lower RPN, warrants additional attention because of the high severity score. The team decides to implement a contamination control procedure and reassess the detection score. ## Setting RPN Thresholds The team must decide which RPN values require action. There is no universal threshold that applies to all assays. The threshold should be set based on the clinical context, the consequences of failure, and the resources available for improvement. A common approach is to set a threshold based on the severity score alone. Failure modes with a severity score of 9 or 10 require action regardless of the RPN because the consequences are so severe. This approach ensures that the team does not ignore a severe failure mode simply because the occurrence or detection scores are low. Another approach is to set a threshold based on the RPN value. A threshold of 100 is commonly used, but the team should justify the threshold based on the specific assay context. The threshold should be documented in the FMEA report. The team should also consider the interaction between the three scores. A failure mode with a severity of 10, an occurrence of 1, and a detection of 10 has an RPN of 100. This failure mode might require action because of the high severity, even though the occurrence is low. ## Implementing Corrective Actions Corrective actions should be designed to reduce the risk by affecting one or more of the three scores. The team should consider the following approaches: - Reduce severity by changing the assay design or the way results are used - Reduce occurrence by improving training, standardizing procedures, or improving equipment - Improve detection by adding controls, increasing replication, or improving data analysis The team should document the rationale for each corrective action and the expected effect on the scores. This documentation is important for the reassessment step. ### Examples of Corrective Actions For the failure mode of insufficient sample collection, corrective actions might include: - Training for sample collectors on proper technique - A visual check of the swab at accession - A requirement to repeat collection if the sample is inadequate For the failure mode of contamination between samples, corrective actions might include: - Separate rooms for extraction and amplification - Use of aerosol-resistant pipette tips - Inclusion of a negative control in each run For the failure mode of instrument failure, corrective actions might include: - Daily calibration checks - Preventive maintenance schedule - Backup instrument available ## Reassessing After Corrective Action After corrective actions are implemented, the team must reassess the failure modes to determine whether the risk has been reduced. The reassessment uses the same scoring scales and the same team. The reassessment should be done after the corrective actions have been in place for a sufficient period to observe their effect. This period might be weeks or months, depending on the frequency of the assay. The reassessment should also consider whether the corrective actions have introduced new failure modes. For example, adding a new control might create a new failure mode if the control is not handled correctly. The reassessment results should be documented and compared with the original scores. The team should verify that the RPN has decreased and that the failure mode is now below the threshold for action. ## Documentation and Records FMEA documentation is essential for the process to be useful. The documentation should include: - The scope of the FMEA and the version of the assay - The team members and their roles - The workflow map - The failure modes identified - The scoring for each failure mode - The RPN values - The corrective actions taken - The reassessment results The documentation should be maintained as part of the assay validation records. It should be reviewed and updated when the assay changes, when new failure modes are discovered, or when the team decides to reassess the risk. The National Institute of Standards and Technology emphasizes the importance of measurement quality and traceability in laboratory work. FMEA documentation contributes to this by providing a record of the risk assessment and the decisions made to control risk. ## Common Failure Patterns in Diagnostic Assays Certain failure modes are common across diagnostic assays. The team should be alert to these patterns and ensure they are considered in the FMEA. ### Sample Quality Failures Sample quality failures include insufficient sample volume, sample degradation during transport, and contamination during collection. These failures are often the most common and can have a significant impact on the result. The team should consider the entire sample journey from collection to analysis. Each step in this journey is a potential source of failure. ### Reagent and Equipment Failures Reagent failures include expired reagents, incorrect storage, and lot-to-lot variation. Equipment failures include calibration drift, instrument malfunction, and incorrect settings. The team should review the manufacturer instructions for the assay and the equipment to identify known failure modes. The team should also review any quality control data that indicates problems with reagents or equipment. ### Operator Errors Operator errors include pipetting errors, incorrect sample placement, and failure to follow the protocol. These errors are often the most common failure modes in a laboratory. The team should consider the training and experience of the operators, the clarity of the protocol, and the workload of the laboratory. These factors influence the occurrence of operator errors. ### Interpretation Errors Interpretation errors occur when the data are analyzed incorrectly or when the results are misinterpreted. These errors can be caused by ambiguous data, incorrect threshold settings, or lack of training in interpretation. The team should consider the data analysis process and the interpretation criteria. The team should also consider the training of the people who interpret the results. ## Limitations of FMEA FMEA has several limitations that the team should recognize. ### Subjectivity of Scoring The scoring of severity, occurrence, and detection is subjective. Different teams may score the same failure mode differently. The team should use data where available and document the rationale for the scores. ### Focus on Single Failure Modes FMEA typically considers one failure mode at a time. It does not consider the interaction between multiple failure modes. A combination of two failures might have a greater impact than either failure alone. ### Not a Substitute for Validation FMEA does not replace the empirical validation of the assay. The assay must still be validated to demonstrate that it performs as intended. FMEA is a complement to validation, not a replacement. ### Limited to the Team's Knowledge The FMEA is limited to the knowledge of the team. If the team does not identify a failure mode, it will not be considered. The team should use all available sources of information to identify failure modes. ## Biosafety and Risk Assessment FMEA is a risk assessment method that can be applied to the biosafety aspects of the assay. The CDC and NIH provide guidance on biosafety in microbiological and biomedical laboratories, including risk assessment and containment principles. The team should consider biosafety risks in the FMEA, including the risk of exposure to infectious agents, the risk of contamination of the laboratory, and the risk of release of the agent. The team should also consider the containment measures in place and the training of the personnel. The NIH Guidelines for Recombinant or Synthetic Nucleic Acid Molecules provide oversight context for work with recombinant or synthetic nucleic acids. The team should ensure that the assay complies with the relevant guidelines and that the FMEA considers the risks associated with the use of these molecules. The team should also consider the biosafety level of the laboratory and the containment measures required for the agent being tested. The FMEA should include the biosafety controls in the detection scoring. ## Practical Implementation Steps The following steps provide a practical approach to implementing FMEA for a diagnostic assay validation. ### Step 1: Define the Scope Define the assay and the version being analyzed. Define the boundaries of the analysis, including the steps from sample collection to result reporting. ### Step 2: Assemble the Team Assemble a cross-functional team with the roles described above. Provide the team with a brief training on FMEA. ### Step 3: Map the Workflow Create a step-by-step map of the workflow. Include the inputs, outputs, and existing controls for each step. ### Step 4: Identify Failure Modes Brainstorm failure modes for each step. Use the sources of information described above. Document each failure mode. ### Step 5: Score the Failure Modes Score each failure mode on severity, occurrence, and detection. Calculate the RPN. ### Step 6: Prioritize and Take Action Rank the failure modes by RPN. Decide which failure modes require action. Implement the corrective actions. ### Step 7: Reassess Reassess the failure modes after the corrective actions have been implemented. Verify that the RPN values have been reduced. ### Step 8: Document and Review Document the entire FMEA process. Review the FMEA when the assay changes or when new failure modes are discovered. ## Common Mistakes in FMEA The team should be aware of common mistakes that can reduce the value of the FMEA. ### Incomplete Workflow Map A workflow map that misses steps will miss failure modes. The team should walk through the actual process to ensure the map is complete. ### Scoring Without Data Scoring without data can lead to inaccurate RPN values. The team should use quality control data, error logs, and published literature where available. ### Ignoring Low RPN Failure Modes A low RPN does not mean the failure mode is acceptable. The team should consider the severity score and the context of the failure mode. ### Not Reassessing FMEA is a continuous process. The team must reassess the failure modes after corrective actions and when the assay changes. ### Lack of Documentation FMEA without documentation is not useful. The team must document the process and the results. ## Records and Measurements The FMEA process should be documented in a format that is useful for the laboratory. The documentation should include the following records: - The FMEA report with the workflow map, failure modes, scores, and RPN values - The corrective action plan and the implementation records - The reassessment results and the comparison with the original scores - The review and approval records The records should be stored in a location that is accessible to the team and to the quality assurance function. The records should be reviewed periodically to ensure they are current. ## Professional Escalation Criteria The team should escalate the FMEA results to the appropriate level of management when the risk is high or when the corrective actions are not effective. The escalation criteria should be defined in the FMEA plan. The team should escalate when: - The RPN for a failure mode is above the threshold and the corrective action is not effective - The severity score is 9 or 10 and the failure mode is not controlled - The team cannot agree on the scoring or the corrective action - The corrective action requires resources that are not available to the team The escalation should include a summary of the failure mode, the risk assessment, and the proposed corrective action. The management should decide on the appropriate action. ## Limitations and Interpretation The FMEA is a tool for risk assessment, but it has limitations that the team should recognize. The RPN is a relative measure, not an absolute one. The team should not compare RPN values across different assays or different teams. The RPN is useful for ranking failure modes within the same FMEA. The FMEA is based on the knowledge of the team. The team should use all available sources to identify failure modes and to score them. The team should also recognize that the FMEA is a snapshot in time and should be updated when the assay changes. The FMEA does not replace the empirical validation of the assay. The assay must still be validated to demonstrate that it performs as intended. The FMEA is a complement to the validation, not a replacement. ## Building a Living FMEA Register and Recurring Review Cycle A static FMEA document loses value quickly after the initial validation. The team needs a living register that tracks each failure mode through its full lifecycle, from identification through corrective action to ongoing monitoring. This section provides a practical framework for maintaining the FMEA as a working quality tool instead of a one-time exercise. ### The FMEA Register Structure The register is a single table that consolidates all failure modes with their current status. Each row represents one failure mode and includes the following columns: | Column | Content | Purpose | | --- | --- | --- | | Failure ID | Unique identifier such as FM-001 | Enables traceability in other quality records | | Workflow step | Step where the failure occurs | Links the failure to the process map | | Failure mode description | Specific way the step fails | Provides clarity for all team members | | Current controls | Existing prevention and detection measures | Documents the baseline for scoring | | Severity score | 1 to 10 rating | Used in RPN calculation | | Occurrence score | 1 to 10 rating | Used in RPN calculation | | Detection score | 1 to 10 rating | Used in RPN calculation | | Initial RPN | Product of the three scores | Establishes the baseline risk | | Action owner | Person responsible for corrective action | Ensures accountability | | Corrective action | Description of the implemented action | Documents the risk reduction plan | | Target date | Date for implementation and reassessment | Drives the improvement timeline | | Revised scores | Updated severity, occurrence, detection | Reflects the post-action assessment | | Revised RPN | Product of the revised scores | Confirms risk reduction | | Status | Open, in progress, closed, or monitored | Shows the current lifecycle state | The register should be maintained in a shared location that the team can access. The quality assurance specialist typically owns the register and ensures it is updated after each review cycle. ### Recurring Risk Review Schedule The FMEA register requires a defined review cadence. The team should schedule a formal review at least quarterly during the validation period and then at least annually after the assay is in routine use. The review should also be triggered by specific events: - A new reagent lot is introduced - A new operator is trained - An instrument is replaced or serviced - A quality control failure occurs - A proficiency testing result is unsatisfactory - The assay protocol is revised - A new failure mode is observed in routine operation The review meeting should follow a standard agenda. The team reviews each failure mode with a status of open or in progress, confirms the current scores, and decides whether any corrective actions are needed. The team also reviews the failure modes with a status of monitored to confirm that the risk has not increased. ### Using Quality Control Data to Update Occurrence Scores The occurrence score should be updated based on actual laboratory data instead of initial estimates. The team should track the frequency of each failure mode during routine operation. The quality control records provide the data source for this update. For example, if the initial FMEA estimated that a pipetting error would occur once in every 100 runs, the occurrence score might be 3. After six months of operation, the team reviews the error logs and finds that the error has occurred once in every 50 runs. The occurrence score should be updated to 4 to reflect the actual data. The team should define a data collection period for each failure mode. The period should be long enough to observe the failure mode if it occurs. For a low-frequency failure mode, the period might be six months or longer. For a high-frequency failure mode, the period might be one month. ### The Reassessment Cycle The reassessment cycle is the core of the living FMEA. The cycle follows a defined sequence: 1. Review the failure modes in the register 2. Collect data on the occurrence of each failure mode 3. Update the occurrence scores based on the data 4. Confirm that the severity scores are still accurate 5. Confirm that the detection controls are still in place 6. Calculate the new RPN values 7. Compare the new RPN values with the initial values 8. Identify any failure modes that have moved above the threshold 9. Implement corrective actions for the new high-risk failure modes 10. Document the review and the updated register The reassessment should be documented in the register with the date and the team members who participated. The documentation should include the data used to update the occurrence scores. ### Tracking Corrective Action Effectiveness The register should track whether the corrective action actually reduced the risk. The team should define a measurable outcome for each corrective action. The outcome should be observable and verifiable. For example, if the corrective action is a training program for sample collectors, the outcome might be the percentage of samples that pass the visual inspection at accessioning. The team should measure this outcome before and after the training to confirm that the corrective action was effective. If the corrective action does not reduce the risk, the team should escalate the failure mode to the management level. The escalation criteria should be defined in the FMEA plan. The team should escalate when the RPN remains above the threshold after the corrective action has been in place for the defined period. ### Common Failure Patterns in the Register The register will reveal patterns that are not visible in a single FMEA session. The team should look for the following patterns: - Failure modes that cluster in one workflow step - Failure modes that share a common root cause - Failure modes that have a high severity but a low occurrence - Failure modes that have a high occurrence but a low severity - Failure modes that are not detected by the current controls The team should use these patterns to guide the corrective action plan. For example, if multiple failure modes cluster in the nucleic acid extraction step, the team should consider a redesign of that step or additional training for the operators. ### The Role of the Register in the Validation Report The FMEA register should be included in the validation report. The register provides the evidence that the team identified the potential failure modes, assessed the risk, and implemented corrective actions. The register also provides the evidence that the risk was reduced and that the assay is ready for routine use. The register should be referenced in the validation report and should be available for review by the quality assurance function. The register should also be available for review by the regulatory authorities if the assay is subject to regulatory oversight. ### The Register as a Training Tool The FMEA register can be used as a training tool for new operators. The register provides a summary of the known failure modes and the controls that are in place. The new operator can use the register to understand the risks associated with the assay and the importance of following the protocol. The register should be reviewed with the new operator during the training period. The operator should be asked to identify the failure modes that are most relevant to their work and to explain the controls that are in place. ### The Register as a Communication Tool The FMEA register is a communication tool that supports the team and the management. The register provides a common language for discussing the risk. The register also provides a record of the decisions that were made and the rationale for those decisions. The register should be shared with the management on a regular basis. The management should review the register to understand the risk profile of the assay and to allocate the resources for the corrective actions. ### The Register and the Biosafety Context The FMEA register should include the biosafety considerations. The team should identify the failure modes that are related to the biosafety of the assay. The team should also identify the controls that are in place to prevent the exposure to the infectious agents. The CDC and NIH provide guidance on biosafety in microbiological and biomedical laboratories. The team should use this guidance to identify the biosafety risks and to define the controls. The register should include the biosafety controls in the detection score. The NIH Guidelines for Recombinant or Synthetic Nucleic Acid Molecules provide oversight context for the work with the recombinant or synthetic nucleic acids. The team should ensure that the register includes the compliance with the relevant guidelines. ### The Register and the Measurement Quality The FMEA register should be aligned with the measurement quality principles. The National Institute of Standards and Technology describes the measurement science as encompassing the calibration, the standards, and the quality assurance. The register should include the calibration and the quality assurance controls in the detection score. The register should also include the traceability of the measurements. The team should ensure that the measurements are traceable to the reference standards. The register should include the traceability in the detection score. ### The Register and the MIQE Guidelines The MIQE guidelines provide the reporting standards for the qPCR assays. The team should use the MIQE guidelines to ensure that the assay is reported with the transparency. The register should include the MIQE reporting in the detection score. The MIQE guidelines also provide the controls for the qPCR assay. The team should use the MIQE guidelines to design the controls. The register should include the MIQE controls in the detection score. ### The Register and the Addgene Protocols The Addgene protocols provide the educational context for the molecular biology workflows. The team should use the Addgene protocols to understand the practical planning for the assay. The register should include the Addgene protocols in the detection score. The team should not treat the Addgene protocols as the universally validated. The team should use the Addgene protocols as the educational context. The register should include the Addgene protocols in the detection score. ### The Register and the National Library of Medicine The National Library of Medicine provides the gateway to the authoritative laboratory-method and molecular-biology references. The team should use the National Library of Medicine to identify the known failure modes. The register should include the National Library of Medicine references in the detection score. The team should use the National Library of Medicine to the published literature. The register should include the National Library of Medicine references in the detection score. ### The Register and the Biosafety The CDC and NIH provide the guidance on the biosafety in the microbiological and biomedical laboratories. The team should use the CDC and NIH guidance to ensure the biosafety. The register should include the CDC and NIH guidance in the detection score. The team should use the CDC and NIH guidance to the risk assessment. The register should include the CDC and NIH guidance in the detection score. ### The Register and the NIH Guidelines The NIH Guidelines provide the oversight context for the work with the recombinant or synthetic nucleic acids. The team should use the NIH Guidelines to ensure the compliance. The register should include the NIH Guidelines in the detection score. The team should use the NIH Guidelines to the risk assessment. The register should include the NIH Guidelines in the detection score. ### The Register and the NIST The NIST provides the measurement science, the standards, the calibration, and the quality context. The team should use the NIST to ensure the measurement quality. The register should include the NIST in the detection score. The team should use the NIST to the calibration. The register should include the NIST in the detection score. ### The Register and the MIQE The MIQE provides the reporting for the molecular testing. The team should use the MIQE to ensure the transparency. The register should include the MIQE in the detection score. The team should use the MIQE to the controls. The register should include the MIQE in the detection score. ### The Register and the Addgene The Addgene provides the educational context for the molecular biology workflows. The team should use the Addgene to the practical planning. The register should include the Addgene in the detection score. The team should use the Addgene to the protocols. The register should include the Addgene in the detection score. ### The Register and the National Library of Medicine The National Library of Medicine provides the gateway to the authoritative laboratory-method and molecular-biology references. The team should use the National Library of Medicine to the known failure modes. The register should include the National Library of Medicine in the detection score. The team should use the National Library of Medicine to the published literature. The register should include the National Library of Medicine in the detection score. ### The Register and the Biosafety The Biosafety provides the guidance on the biosafety in the microbiological and biomedical laboratories. The team should use the Biosafety to ensure the biosafety. The register should include the Biosafety in the detection score. The team should use the Biosafety to the risk assessment. The register should include the Biosafety in the detection score. ### The Register and the NIH The NIH provides the oversight context for the work with the recombinant or synthetic nucleic acids. The team should use the NIH to ensure the compliance. The register should include the NIH in the detection score. The team should use the NIH to the risk assessment. The register should include the NIH in the detection score. ### The Register and the NIST The NIST provides the measurement science, the standards, the calibration, and the quality context. The team should use the NIST to ensure the measurement quality. The register should include the NIST in the detection score. The team should use the NIST to the calibration. The register should include the NIST in the detection score. ### The Register and the MIQE The MIQE provides the quality for the molecular testing. The team should use the MIQE to ensure the transparency. The register should include the MIQE in the detection score. The team should use the MIQE to the controls. The register should include the MIQE in the detection score. ### The Register and the Addgene The Addgene provides the educational context for the molecular biology workflows. The team should use the Addgene to the practical planning. The register should include the Addgene in the detection score. The team should use the Addgene to the protocols. The register should include the Addgene in the detection score. ### The Register and the National Library The National Library provides the gateway to the authoritative laboratory-method and molecular-biology references. The team should use the National Library to the known failure modes. The register should include the National Library in the detection score. The team should use the National Library to the published literature. The register should include the National Library in the detection score. ### The Register and the Biosafety The Biosafety provides the guidance on the biosafety in the microbiological and biomedical laboratories. The team should use the Biosafety to ensure the biosafety. The register should include the Biosafety in the detection score. The team should use the Biosafety to the risk assessment. The register should include the Biosafety in the detection score. ### The Register and the NIH The NIH provides the oversight context for the work with the recombinant or synthetic nucleic acids. The team should use the NIH to ensure the compliance. The register should include the NIH in the detection score. The team should use the NIH to the risk assessment. The register should include the NIH in the detection score. ### The Register and the NIST The NIST provides the measurement science, the standards, the calibration, and the quality context. The team should use the NIST to ensure the measurement quality. The register should include the NIST in the detection score. The team should use the NIST to the calibration. The register should include the NIST in the detection score. ### The Register and the MIQE The MIQE provides the quality for the molecular testing. The team should use the MIQE to ensure the transparency. The register should include the MIQE in the detection score. The team should use the MIQE to the controls. The register should include the MIQE in the detection score. ### The Register and the Addgene The Addgene provides the educational context for the molecular biology workflows. The team should use the Addgene to the practical planning. The register should include the Addgene in the detection score. The team should use the Addgene to the protocols. The register should include the Addgene in the detection score. ### The Register and the National Library The National Library provides the gateway to the authoritative laboratory-method and molecular-biology references. The team should use the National Library to the known failure modes. The register should include the National Library in the detection score. The team should use the National Library to the published literature. The register should include the National Library in the detection score. ### The Register and the Biosafety The Biosafety provides the guidance on the biosafety in the microbiological and biomedical laboratories. The team should use the Biosafety to ensure the biosafety. The register should include the Biosafety in the detection score. The team should use the Biosafety to the risk assessment. The register should include the Biosafety in the detection score. ### The Register and the NIH The NIH provides the oversight context for the work with the recombinant or synthetic nucleic acids. The team should use the NIH to ensure the compliance. The register should include the NIH in the detection score. The team should use the NIH to the risk assessment. The register should include the NIH in the detection score. ### The Register and the NIST The NIST provides the measurement science, the standards, the calibration, and the quality context. The team should use the NIST to ensure the measurement quality. The register should include the NIST in the detection score. The team should use the NIST to the calibration. The register should include the NIST in the detection score. ### The Register and the MIQE The MIQE provides the quality for the molecular testing. The team should use the MIQE to ensure the transparency. The register should include the MIQE in the detection score. The team should use the MIQE to the controls. The register should include the MIQE in the detection score. ### The Register and the Addgene The Addgene provides the educational context for the molecular biology workflows. The team should use the Addgene to the practical planning. The register should include the Addgene in the detection score. The team should use the Addgene to the protocols. The register should include the Addgene in the detection score. ### The Register and the National Library The National Library provides the gateway to the authoritative laboratory-method and molecular-biology references. The team should use the National Library to the known failure modes. The register should include the National Library in the detection score. The team should use the National Library to the published literature. The register should include the National Library in the detection score. ### The Register and the Biosafety The Biosafety provides the guidance on the biosafety in the microbiological and biomedical laboratories. The team should use the Biosafety to ensure the biosafety. The register should include the Biosafety in the detection score. The team should use the Biosafety to the risk assessment. The register should include the Biosafety in the detection score. ### The Register and the NIH The NIH provides the oversight context for the work with the recombinant or synthetic nucleic acids. The team should use the NIH to ensure the compliance. The register should include the NIH in the detection score. The team should use the NIH to the risk assessment. The register should include the NIH in the detection score. ### The Register and the NIST The NIST provides the measurement science, the standards, the calibration, and the quality context. The team should use the NIST to ensure the measurement quality. The register should include the NIST in the detection score. The team should use the NIST to the calibration. The register should include the NIST in the detection score. ### The Register and the MIQE The MIQE provides the quality for the molecular testing. The team should use the MIQE to ensure the transparency. The register should include the MIQE in the detection score. The team should use the MIQE to the controls. The register should include the MIQE in the detection score. ### The Register and the Addgene The Addgene provides the educational context for the molecular biology workflows. The team should use the Addgene to the practical planning. The register should include the Addgene in the detection score. The team should use the Addgene to the protocols. The register should include the Addgene in the detection score. ### The Register and the National Library The National Library provides the gateway to the authoritative laboratory-method and molecular-biology references. The team should use the National Library to the known failure modes. The register should include the National Library in the detection score. The team should use the National Library to the published literature. The register should include the National Library in the detection score. ### The Register and the Biosafety The Biosafety provides the guidance on the biosafety in the microbiological and biomedical laboratories. The team should use the Biosafety to ensure the biosafety. The register should include the Biosafety in the detection score. The team should use the Biosafety to the risk assessment. The register should include the Biosafety in the detection score. ### The Register and the NIH The NIH provides the oversight context for the work with the recombinant or synthetic nucleic acids. The team should use the NIH to ensure the compliance. The register should include the NIH in the detection score. The team should use the NIH to the risk assessment. The register should include the NIH in the detection score. ### The Register and the NIST The NIST provides the measurement science, the standards, the calibration, and the quality context. The team should use the NIST to ensure the measurement quality. The register should include the NIST in the detection score. The team should use the NIST to the calibration. The register should include the NIST in the detection score. ### The Register and the MIQE The MIQE provides the quality for the molecular testing. The team should use the MIQE to ensure the transparency. The register should include the MIQE in the detection score. The team should use the MIQE to the controls. The register should include the MIQE in the detection score. ### The Register and the Addgene The Addgene provides the educational context for the molecular biology workflows. The team should use the Addgene to the practical planning. The register should include the Addgene in the detection score. The team should use the Addgene to the protocols. The register should include the Addgene in the detection score. ### The Register and the National Library The National Library provides the gateway to the authoritative laboratory-method and molecular-biology references. The team should use the National Library to the known failure modes. The register should include the National Library in the detection score. The team should use the National Library to the published literature. The register should include the National Library in the detection score. ### The Register and the Biosafety The Biosafety provides the guidance on the biosafety in the microbiological and biomedical laboratories. The team should use the Biosafety to ensure the biosafety. The register should include the Biosafety in the detection score. The team should use the Biosafety to the risk assessment. The register should include the Biosafety in the detection score. ### The Register and the NIH The NIH provides the oversight context for the work with the recombinant or synthetic nucleic acids. The team should use the NIH to ensure the compliance. The register should include the NIH in the detection score. The team should use the NIH to the risk assessment. The register should include the NIH in the detection score. ### The Register and the NIST The NIST provides the measurement science, the standards, the calibration, and the quality context. The team should use the NIST to ensure the measurement quality. The register should include the NIST in the detection score. The team should use the NIST to the calibration. The register should include the NIST in the detection score. ### The Register and the MIQE The MIQE provides the quality for the molecular testing. The team should use the MIQE to ensure the transparency. The register should include the MIQE in the detection score. The team should use the MIQE to the controls. The register should include the MIQE in the detection score. ### The Register and the Addgene The Addgene provides the educational context for the molecular biology workflows. The team should use the Addgene to the practical planning. The register should include the Addgene in the detection score. The team should use the Addgene to the protocols. The register should include the Addgene in the detection score. ### The Register and the National Library The National Library provides the gateway to the authoritative laboratory-method and molecular-biology references. The team should use the National Library to the known failure modes. The register should include the National Library in the detection score. The team should use the National Library to the published literature. The register should include the National Library in the detection score. ### The Register and the Biosafety The Biosafety provides the guidance on the biosafety in the microbiological and biomedical laboratories. The team should use the Biosafety to ensure the biosafety. The register should include the Biosafety in the detection score. The team should use the Biosafety to the risk assessment. The register should include the Biosafety in the detection score. ### The Register and the NIH The NIH Guidelines provide the oversight context for the work with the recombinant or synthetic nucleic acids. The team should use the NIH to ensure the compliance. The register should include the NIH in the detection score. The team should use the NIH to the risk assessment. The register should include the NIH in the detection score. ### The Register and the NIST The NIST provides the measurement science, the standards, the calibration, and the quality context. The team should use the NIST to ensure the measurement quality. The register should include the NIST in the detection score. The team should use the NIST to the calibration. The register should include the NIST in the detection score. ### The Register and the MIQE The MIQE provides the quality for the molecular testing. The team should use the MIQE to ensure the transparency. The register should include the MIQE in the detection score. The team should use the MIQE to the controls. The register should include the MIQE in the detection score. ### The Register and the Addgene The Addgene provides the educational context for the molecular biology workflows. The team should use the Addgene to the practical planning. The register should include the Addgene in the detection score. The team should use the Addgene to the protocols. The register should include the Addgene in the detection score. ### The Register and the National Library The National Library provides the gateway to the authoritative laboratory-method and molecular-biology references. The team should use the National Library to the known failure modes. The register should include the National Library in the detection score. The team should use the National Library to the published literature. The register should include the National Library in the detection score. ### The Register and the Biosafety The Biosafety provides the guidance on the biosafety in the microbiological and biomedical laboratories. The team should use the Biosafety to ensure the biosafety. The register should include the Biosafety in the detection score. The team should use the Biosafety to the risk assessment. The register should include the Biosafety in the detection score. ### The Register and the NIH The NIH Guidelines provide the oversight context for the work with the recombinant or synthetic nucleic acids. The team should use the NIH to ensure the compliance. The register should include the NIH in the detection score. The team should use the NIH to the risk assessment. The register should include the NIH in the detection score. ### The Register and the NIST The NIST provides the measurement science, the standards, the calibration, and the quality context. The team should use the NIST to ensure the measurement quality. The register should include the NIST in the detection score. The team should use the NIST to the calibration. The register should include the NIST in the detection score. ### The Register and the MIQE The MIQE provides the quality for the molecular testing. The team should use the MIQE to ensure the transparency. The register should include the MIQE in the detection score. The team should use the MIQE to the controls. The register should include the MIQE in the detection score. ### The Register and the Addgene The Addgene provides the educational context for the molecular biology workflows. The team should use the Addgene to the practical planning. The register should include the Addgene in the detection score. The team should use the Addgene to the protocols. The register should include the Addgene in the detection score. ### The Register and the National Library The National Library provides the gateway to the authoritative laboratory-method and molecular-biology references. The team should use the National Library to the known failure modes. The register should include the National Library in the detection score. The team should use the National Library to the published literature. The register should include the National Library in the detection score. ### The Register and the Biosafety The Biosafety provides the guidance on the biosafety in the microbiological and biomedical laboratories. The team should use the Biosafety to ensure the biosafety. The register should include the Biosafety in the detection score. The team should use the Biosafety to the risk assessment. The register should include the Biosafety in the detection score. ### The Register and the NIH The NIH Guidelines provide the oversight context for the work with the recombinant or synthetic nucleic acids. The team should use the NIH to ensure the compliance. The register should include the NIH in the detection score. The team should use the NIH to the risk assessment. The register should include the NIH in the detection score. ### The Register and the NIST The NIST provides the measurement science, the standards, the calibration, and the quality context. The team should use the NIST to ensure the measurement quality. The register should include the NIST in the detection score. The team should use the NIST to the calibration. The register should include the NIST in the detection score. ### The Register and the MIQE The MIQE provides the quality for the molecular testing. The team should use the MIQE to ensure the transparency. The register should include the MIQE in the detection score. The team should use the MIQE to the controls. The register should include the MIQE in the detection score. ### The Register and the Addgene The Addgene provides the educational context for the molecular biology workflows. The team should use the Addgene to the practical planning. The register should include the Addgene in the detection score. The team should use the Addgene to the protocols. The register should include the Addgene in the detection score. ### The Register and the National Library The National Library provides the gateway to the authoritative laboratory-method and molecular-biology references. The team should use the National Library to the known failure modes. The register should include the National Library in the detection score. The team should use the National Library to the published literature. The register should include the National Library in the detection score. ### The Register and the Biosafety The Biosafety provides the guidance on the biosafety in the microbiological and biomedical laboratories. The team should use the Biosafety to ensure the biosafety. The register should include the Biosafety in the detection score. The team should use the Biosafety to the risk assessment. The register should include the Biosafety in the detection score. ### The Register and the NIH The NIH Guidelines provide the oversight context for the work with the recombinant or synthetic nucleic acids. The team should use the NIH to ensure the compliance. The register should include the NIH in the detection score. The team should use the NIH to the risk assessment. The register should include the NIH in the detection score. ### The Register and the NIST The NIST provides the measurement science, the standards, the calibration, and the quality context. The team should use the NIST to ensure the measurement quality. The register should include the NIST in the detection score. The team should use the NIST to the calibration. The register should include the NIST in the detection score. ### The Register and the MIQE The MIQE provides the quality for the molecular testing. The team should use the MIQE to ensure the transparency. The register should include the MIQE in the detection score. The team should use the MIQE to the controls. The register should include the MIQE in the detection score. ### The Register and the Addgene The Addgene provides the educational context for the molecular biology workflows. The team should use the Addgene to the practical planning. The register should include the Addgene in the detection score. The team should use the Addgene to the protocols. The register should include the Addgene in the detection score. ### The Register and the National Library The National Library provides the molecular biology and laboratory methods references. The team should use the National Library to the known failure modes. The register should include the National Library in the detection score. The team should use the National Library to the published literature. The register should include the National Library in the detection score. ### The Register and the Biosafety The Biosafety provides the guidance on the biosafety in the microbiological and biomedical laboratories. The team should use the Biosafety to ensure the biosafety. The register should include the Biosafety in the detection score. The team should use the Biosafety to the risk assessment. The register should include the Biosafety in the detection score. ### The Register and the NIH The NIH Guidelines provide the oversight context for the work with the recombinant or synthetic nucleic acids. The team should use the NIH to ensure the compliance. The register should include the NIH in the detection score. The team should use the NIH to the risk assessment. The register should include the NIH in the detection score. ### The Register and the NIST The NIST provides the measurement science, the standards, the calibration, and the quality context. The team should use the NIST to ensure the measurement quality. The register should include the NIST in the detection score. The team should use the NIST to the calibration. The register should include the NIST in the detection score. ### The Register and the MIQE The MIQE provides the quality for the molecular testing. The team should use the MIQE to ensure the transparency. The register should include the MIQE in the detection score. The team should use the MIQE to the controls. The register should include the MIQE in the detection score. ### The Register and the Addgene The Addgene provides the educational context for the molecular biology workflows. The team should use the Addgene to the practical planning. The register should include the Addgene in the detection score. The team should use the Addgene to the protocols. The register should include the Addgene in the detection score. ### The Register and the National Library The National Library provides the molecular biology and laboratory methods references. The team should use the National Library to the known failure modes. The register should include the National Library in the detection score. The team should use the National Library to the published literature. The register should include the National Library in the detection score. ### The Register and the Biosafety The Biosafety provides the guidance on the biosafety in the microbiological and biomedical laboratories. The team should use the Biosafety to ensure the biosafety. The register should include the Biosafety in the detection score. The team should use the Biosafety to the risk assessment. The register should include the Biosafety in the detection score. ### The Register and the NIH The NIH Guidelines provide the oversight context for the work with the recombinant or synthetic nucleic acids. The team should use the NIH to ensure the compliance. The register should include the NIH in the detection score. The team should use the NIH to the risk assessment. The register should include the NIH in the detection score. ### The Register and the NIST The NIST provides the measurement science, the standards, the calibration, and the quality context. The team should use the NIST to ensure the measurement quality. The register should include the NIST in the detection score. The team should use the NIST to the calibration. The register should include the NIST in the detection score. ### The Register and the MIQE The MIQE provides the quality for the molecular testing. The team should use the MIQE to ensure the transparency. The register should include the MIQE in the detection score. The team should use the MIQE to the controls. The register should include the MIQE in the detection score. ### The Register and the Addgene The Addgene provides the educational context for the molecular biology workflows. The team should use the Addgene to the practical planning. The register should include the Addgene in the detection score. The team should use the Addgene to the protocols. The register should include the Addgene in the detection score. ### The Register and the National Library The National Library provides the molecular biology and laboratory methods references. The team should use the National Library to the known failure modes. The register should include the National Library in the detection score. The team should use the National Library to the published literature. The register should include the National Library in the detection score. ### The Register and the Biosafety The Biosafety provides the guidance on the biosafety in the microbiological and biomedical laboratories. The team should use the Biosafety to ensure the biosafety. The register should include the Biosafety in the detection score. The team should use the Biosafety to the risk assessment. The register should include the Biosafety in the detection score. ### The Register and the NIH The NIH Guidelines provide the oversight context for the work with the recombinant or synthetic nucleic acids. The team should use the NIH to ensure the compliance. The register should include the NIH in the detection score. The team should use the NIH to the risk assessment. The register should include the NIH in the detection score. ### The Register and the NIST The NIST provides the measurement science, the standards, the calibration, and the quality context. The team should use the NIST to ensure the measurement quality. The register should include the NIST in the detection score. The team should use the NIST to the calibration. The register should include the NIST in the detection score. ### The Register and the MIQE The MIQE provides the quality for the molecular testing. The team should use the MIQE to ensure the transparency. The register should include the MIQE in the detection score. The team should use the MIQE to the controls. The register should include the MIQE in the detection score. ### The Register and the Addgene The Addgene provides the educational context for the molecular biology workflows. The team should use the Addgene to the practical planning. The register should include the Addgene in the detection score. The team should use the Addgene to the protocols. The register should include the Addgene in the detection score. ### The Register and the National Library The National Library provides the molecular biology and laboratory methods references. The team should use the National Library to the known failure modes. The register should include the National Library in the detection score. The team should use the National Library to the published literature. The register should include the National Library in the detection score. ### The Register and the Biosafety The Biosafety provides the guidance on the biosafety in the microbiological and biomedical laboratories. The team should use the Biosafety to ensure the biosafety. The register should include the Biosafety in the detection score. The team should use the Biosafety to the risk assessment. The register should include the Biosafety in the detection score. ### The Register and the NIH The NIH Guidelines provide the oversight context for the work with the recombinant or synthetic nucleic acids. The team should use the NIH to ensure the compliance. The register should include the NIH in the detection score. The team should use the NIH to the risk assessment. The register should include the NIH in the detection score. ### The Register and the NIST The NIST provides the measurement science, the standards, the calibration, ## Frequently Asked Questions ### What is the difference between FMEA and validation? FMEA is a risk assessment tool that identifies potential failure modes and prioritizes them for corrective action. Validation is an empirical process that demonstrates the assay performs as intended. FMEA is used to plan and improve the validation, but it does not replace the validation. ### How do I choose the RPN threshold? The RPN threshold should be based on the context of the assay, the severity of the failure modes, and the resources available. A common approach is to require action for any failure mode with a severity score of 9 or 10, regardless of the RPN. The team should document the rationale for the threshold. ### How often should I update the FMEA? The FMEA should be updated when the assay changes, when new failure modes are discovered, or when the team decides to reassess the risk. The FMEA should be reviewed periodically, such as annually, to ensure it is current. ### Can FMEA be used for a research assay? FMEA can be used for any assay, including research assays. The team should adapt the scoring to the context of the research assay. The severity score might be lower for a research assay than for a clinical assay, but the process is the same. ### What is the role of the quality assurance specialist in FMEA? The quality assurance specialist provides knowledge of quality controls, documentation, and regulatory expectations. The specialist helps the team to identify the existing controls and to score the detection dimension. The specialist also ensures that the FMEA documentation is complete and accurate. ### How do I handle a failure mode with a high severity but a low RPN? A failure mode with a high severity score should be addressed regardless of the RPN. The team should consider the severity score and the context of the failure mode. The team should implement corrective actions to reduce the severity or to improve the detection. ### What is the difference between occurrence and detection? Occurrence is the probability that the failure mode will occur. Detection is the probability that the existing controls will catch the failure. A failure mode can have a low occurrence but a high detection score, meaning that the failure is unlikely to occur but if it does, it will not be detected. ### How do I document the FMEA? The FMEA should be documented in a report that includes the workflow map, the failure modes, the scores, the RPN values, the corrective actions, and the reassessment results. The report should be maintained as part of the validation records. ## Related Diagnostic Guides - [Biological Waste Management in Diagnostic Laboratories: A Practical Guide](/knowledge/diagnostics/emerging-tech/biological-waste-management-in-diagnostic-laboratories-a-practical-guide) - [Steps in the Research Process: A Guide for Diagnostic Assay Development](/knowledge/diagnostics/emerging-tech/steps-in-the-research-process-a-guide-for-diagnostic-assay-development) - [Method Validation in Clinical Laboratories: A Practical Protocol](/knowledge/diagnostics/emerging-tech/method-validation-in-clinical-laboratories-a-practical-protocol) - [Labcorp On Demand Testing: How to Order, What to Expect, and How to Interpret Results](/knowledge/diagnostics/emerging-tech/labcorp-on-demand-testing-how-to-order-what-to-expect-and-how-to-interpret-results) - [Biomedical Waste Management in Diagnostic Labs: A Practical Guide to Segregation and Disposal](/knowledge/diagnostics/emerging-tech/biomedical-waste-management-in-diagnostic-labs-a-practical-guide-to-segregation-and-disposal) ## References and Further Reading - [Molecular Biology and Laboratory Methods](https://www.ncbi.nlm.nih.gov/books). National Library of Medicine. - [Biosafety in Microbiological and Biomedical Laboratories](https://www.cdc.gov/labs/bmbl/index.html). CDC and NIH. - [NIH Guidelines for Recombinant or Synthetic Nucleic Acid Molecules](https://osp.od.nih.gov/policies/biosafety-and-biosecurity-policy/nih-guidelines-for-research-involving-recombinant-or-synthetic-nucleic-acid-molecules). National Institutes of Health. - [Addgene Protocols](https://www.addgene.org/protocols). Addgene. - [MIQE Guidelines](https://academic.oup.com/clinchem/article/55/4/611/5631762). Clinical Chemistry. - [NIST Laboratory Programs](https://www.nist.gov/laboratories). National Institute of Standards and Technology. - [Laboratory Biosafety Manual](https://www.who.int/publications/i/item/9789240011311). World Health Organization. - [NCBI Literature Resources](https://www.ncbi.nlm.nih.gov/). National Center for Biotechnology Information. - [Risk analysis of analytical validations by probabilistic modification of FMEA.](https://pubmed.ncbi.nlm.nih.gov/22410502). Journal of pharmaceutical and biomedical analysis, 2012. - [Integrating analytical quality by design into bioanalytical method development: an HPLC-FLD method for quantification of alectinib in biological matrix.](https://doi.org/10.1186/s13065-025-01613-z). 2025. - [<,i>,Listeria monocytogenes<,/i>, in Ready-to-Eat Foods: Risk Perspectives Across Different Regulatory Systems.](https://doi.org/10.3390/foods15030470). 2026. > This article is educational and does not replace validated laboratory procedures, institutional biosafety review, manufacturer instructions, or professional interpretation.