GHTF study group 3
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The document outlines guidance for a standardized nonconformity grading system and corrective action for medical devices, developed by the IMDRF, a collaboration of medical device regulators worldwide. It details processes for auditing nonconformities within quality management systems, grading their risk impact, and procedures for corrective and preventive actions. The intent is to promote regulatory harmonization, ensure medical device safety, and facilitate international trade through a structured approach to nonconformities and quality management.
GHTF study group 3
- 1. GHTF Study Group 3:- Quality Management System STANDARDIZED NONCONFORMITY GRADING SYSTEM AND CORRECTIVE ACTION AND PREVENTIVE ACTION GUIDANCE FOR MEDICAL DEVICES
- 2. IMDRF IMDRF is a voluntary group of medical device regulators from around the world who have come together to build on the strong foundational work of the Global Harmonization Task Force on Medical Devices (GHTF) and aims to accelerate international medical device regulatory harmonization and convergence IMDRF Members Asia Pacific • China • Japan • Singapore • South Korea • Austrailia North America •United States of America •Brazil •Canada European • Europe • Russia Fig. 1 Members of IMDRF
- 3. GHTF GHTF – Stands for Global Harmonization Task Force Was a voluntary group of representatives from national medical device regulatory authorities and the regulated industry Consists of 5 founding members grouped from 3 geographic zones:- Asia pacific, Europe, North America The purpose of the GHTF is to encourage the convergence in regulatory practices related to ensuring the safety, effectiveness/performance and quality of medical devices, promoting technological innovation and facilitating international trade, and the primary way in which this is accomplished is via the publication and dissemination of harmonized guidance documents on basic regulatory practices
- 4. Steering Commitee Study Groups(1 to5) Study Group Chair Membership Founding Members Participating Members Observers Liaison Bodies Fig.2 Members of GHTF Fig.4 Operating structure of GHTF Study Groups Study Group 1-Premarket Evaluation Study Group 2 - Post-Market Surveillance/Vigilance Study Group 3 - Quality Systems Study Group 4 – Auditing Study Group 5 - Clinical Safety/Performance Fig.3 Different Study Groups
- 5. Standardized Nonconformity Grading System This guidance document helps in : 1. Introducing nonconformity grading systems for regulatory purposes 2. Method to present outcomes of regulatory audits Definitions 1. Manufacturer- “Any natural or legal person with responsibility for design and/or manufacture of a medical device with the intention of making the medical device available for use, under his name; whether or not such a medical device is designed and/or manufactured by that person himself or on his behalf by another person(s)” 2. Nonconformity- “Non fulfillment of a requirement” 3. Quality management system (QMS)- “Management system to direct and control an organization with regard to quality”
- 6. Writing Nonconformities • All Regulatory audits must be conducted in accordance of GHTF SG4 Documents • To successfully employ this grading system, its essential that the nonconformities are clearly worded with factual and precise language that enables the reader to comprehend the actual nonfulfillment that was detected during the audit The nonconformity should: be a statement written in a clear, concise manner be supported by objective evidence identify the specific requirements which aren’t fulfilled Fig.5 Characteristics of a nonconformity
- 7. Grading of Nonconformities A two step approach, i.e. Step 1- Provides initial grading using grading matrix Step 2- additional escalation rules applied to get final grade
- 8. Step 1: Grading matrix Y Axis- Related to influence of QMS clause on device safety and performance. Divided in two parts: Indirect QMS Impact(Quality management system, Documentation, Management responsibility & commitment, Customer focus, Quality policy, Planning, Responsibility, authority and communication, Resource management, Infrastructure, Human resources) Direct QMS Impact(Work environment, Product realization, Customer-related processes, Design and development, Production and service provision, Control of monitoring and measuring devices, Measurement, analysis and improvement, Control of nonconforming product, Analysis of data) X Axis- Related to Occurrence and divided in two parts First: The first category addresses a nonconformity in a particular sub-clause identified for the first time Repeat: The second category is a nonconformity that has been identified within either of two previous QMS audits which evaluated the same sub-clause (X.X.X). Such a nonconformity poses an increased risk because it is an indicator that a corrective action has not been adequately taken or implemented
- 9. Nonconformities can often be written up against more than one clause. Therefore, it is the auditor’s obligation to determine the impact of the non-conformity on the QMS and assign the appropriate clause The QMS impact of the nonconformity will determine whether the resulting clause will be Direct or Indirect
- 10. Step 2 Grading – Escalation Rules The resultant grading from Step 1 is carried forward to Step 2, which is a rules-based escalation process to address areas of higher risk that have a potential to affect product safety and performance Under this grading system the Step 1 grade is increased by 1 for each rule: Absence of a documented process or procedure, will fundamentally affect consistency and effective implementation of any process Release of a Nonconforming Medical Device, A nonconformity which resulted in the release of a nonconforming medical device to the market is direct evidence of a QMS failure. This rule in the grading system is assessing the QMS nonconformity at a higher risk, because nonconforming product is on the market and outside the control of the manufacturer’s QMS
- 11. Applying the Nonconformity Grading System Step 1 – Using the Nonconformity Grading Matrix Direct or Indirect Impact: When a nonconformity is written and the clause assigned, identify whether it is “direct impact” (score of 3) or “indirect impact” (score of 1), as defined before Repeat nonconformities against the same QMS sub-clause (X.X.X): The auditor should check the previous two audit reports which evaluated the same sub-clause to see if a nonconformity that is identified in the current audit was previously raised. The nonconformity does not have to be identical to the nonconformity in the previous audit, just cited to the same QMS sub clause (X.X.X). If the nonconformity is a repeat, the grade increases by 1 Step 2 – Application of Escalation Rules- Each rule below is applied to determine the final grade of the nonconformity: Rule 1 - Absence: Absence of a documented process or procedure of any requirement, the grade increases by 1 Rule 2 - Medical Device: Release of a Nonconforming Medical Device outside of the controls of the manufacturer’s QMS, the grade increases by 1
- 12. The final grade for a nonconformity under this grading scheme will be a number between 1 and 6 However, the grade of “5” was determined to be the maximum, because this represents a significantly high enough risk that some intervention is required. The differentiation between 5 and 6 was not felt to be of benefit in the grading system. Therefore, if a grade of 6 is achieved, the final grade is documented as “5”
- 13. Regulatory Audit Information Exchange Form To enable information exchange between regulators This Form consists of three sections : List of Nonconformities - It is important to provide sufficient insight into the context and relevance of each nonconformity listed on the Form. The list of nonconformities provided in the Form should be identical to that provided in the audit report Nonconformity Grading - The details of how the final nonconformity grade was obtained for nonconformities specifically against ISO 13485:2003. The use of this section of the Form provides transparency in the calculation process Medical Device Country Specific Regulatory Requirements - Nonconformities that are within the manufacturer’s QMS but are outside the specific requirements within the clauses of ISO 13485:2003 should be identified in the Medical Device Country Specific Regulatory Requirements section of the Form. This area is not graded, but the auditor should reference the specific section of the applicable Regulation or Legislation against which the nonconformity is cited
- 14. Fig.8 Regulatory Audit Information Exchange Form
- 15. Corrective Action and Preventive Action and related QMS processes This document will help in establishing adequate processes for measurement, analysis and improvement within the QMS as related to correction and/or corrective action for non-conformities or preventive action for potential non- conformities of systems, processes or products Definitions Nonconformity - Non fulfillment of a requirement Correction - Action to eliminate a detected nonconformity Corrective action - Action to eliminate the cause of a detected nonconformity or other undesirable situation Data Sources - The processes within a Quality Management System that provide quality information that could be used to identify nonconformities, or potential nonconformities Concession - Permission to use or release a product that does not conform to specified requirements
- 16. Preventive action - Action to eliminate the cause of a potential nonconformity or other undesirable situation, preventive action is taken to prevent occurrence whereas corrective action is taken to prevent recurrence Verification - Confirmation through provision of objective evidence that specified requirements have been fulfilled, the term “verified” is used to designate the corresponding status Validation - Confirmation through provision of objective evidence that the requirements for a specific intended use or application have been fulfilled
- 17. Overview When a nonconformity is identified, the manufacturer will determine the significance, the associated risk and the potential for recurrence Once these have been determined the manufacturer may decide the nonconformity has little associated risk or is unlikely to recur. In such cases the manufacturer may decide only to carry out a correction Should the nonconformity recur within the QMS, during manufacture or after the medical device has been delivered to a customer, it is an indication that improvement action(s) may be needed The manufacturer may encounter situations that have not actually caused a nonconformity, but may do so in the future. Such situations may call for preventive action Actions taken to eliminate observed nonconformities within the scope of a single QMS would be considered corrective actions. However, similar actions applied within another QMS that has not yet experienced these nonconformities, would be considered preventive actions
- 18. Following illustrates typical Phases to be considered when planning, implementing and maintaining effective processes for measurement, analysis, improvement and providing input to management. Report to management Management review Phase 4 – Input to Management Investigate Identify root cause Identify actions Verify identified actions Implement actions Determine effectiveness of implemented actions Phase 3 – Improvement Measure Analyze Phase 2 – Measurement and analysis within and across Data Sources Establish Data Sources and Criteria Phase 1 - Plan For Measurement, Analysis and Improvement process Fig.9 Phases of Planning and Implementing CAPA.
- 19. Phase I: Planning Involves specifying processes and associated resources to meet specific objectives Plan for Measurement, Analysis and Improvement Processes Factors to consider should be aligned with the manufacturer’s overall business planning and as a minimum include the type of device being manufactured, intended markets and users, and regulatory requirements During planning, a manufacturer needs to take into account data sources, the measurement of the data elements within each data source, the frequency of monitoring, and the analysis to be performed within a data source, or across data sources Planningphaseshouldensurethe following: Identification of relevant internal and external data sources Provision for adequate resources and establish responsibilities and authorities to enable the necessary actions. Definition of requirements for each identified data source, including limits, acceptance criteria, escalation criteria and mechanisms for reporting of nonconformities or potential nonconformities Analysis of data elements within data sources Coordination and analysis of data across data sources Fig.10 Aspects of Planning
- 20. Acceptance criteria should be based on system, product and process specifications or requirements which are typically identified during design and development activities Escalation criteria used for the purpose of initiating the improvement process may often be called action levels, trigger points, thresholds, etc. These escalation criteria should be proceduralized and would likely include certain generic action levels as well as specific action levels resulting from risk management activities The manufacturer should identify and document relevant data sources and their data elements, both internal and external to the organization. Data elements provide information regarding nonconformities, potential nonconformities and the effectiveness of the established processes within the data sources Examples of data sources: Regulatory Requirements, Management Review, Supplier (performance/controls), Complaint Handling, Adverse Event Reporting, Process Controls, Finished Product, Quality Audits (internal/external), Product Recall etc.
- 21. Phase II: Measurement and Analysis within and across Data Sources After planning, the manufacturer is required to perform measurement, monitoring and analysis processes to determine conformity or nonconformity Software used in measurement, monitoring and analysis, whether purchased (Off-The-Shelf) or custom developed, should be validated for its intended use Measure It’s a set of operations to determine a value of a data element (i.e. quantity, quality) Monitoring is the systematic and regular collection of a measurement. The manufacturer should define during the planning phase what, when and how data should be monitored The data should be defined such that it can be analysed for further action. The monitoring of data may be continuous or periodic, depending on the type of data source and elements The monitoring processes should be periodically reviewed for their continued suitability
- 22. Analyse Systematic review and evaluation of data from measurements to derive a conclusion Analysis is performed to identify nonconformity or potential nonconformity or identify areas where further investigation should be initiated The results of the analysis should be documented After it is determined what will be measured, statistical techniques should be identified to help understand variability and thereby help the manufacturer to maintain or improve effectiveness and efficiency Examples for statistical techniques are: Statistical Process Control (SPC) charts Linear and non-linear regression analysis Experimental design (DOE – Design of Experiments) and analysis of variance Graphical methods (histograms, scatter plots, etc.)
- 23. In addition to the analysis within the data sources there should also be a level of analysis across data sources to determine the extent and significance of nonconformity or potential nonconformity The linkage of data from different data sources will be referred to as “horizontal analysis”. The horizontal analysis may: Determine that the action proposed from the data source analysis is appropriate without further progress into Phase III; or, Provide additional information warranting progress into Phase III, regardless of whether the data source analysis escalated the nonconformity or potential nonconformity There may be predefined events that due to the significance of the risk will be escalated to Phase III without any delay that can not be justified. In the event a potential nonconformity is identified, it may be escalated into Phase III for consideration of actions to prevent the occurrence of the potential nonconformity
- 24. Phase III: Improvement This phase is designed to eliminate or mitigate a nonconformity or potential nonconformity Improvement activities are dependent on the specific nonconformity
- 25. Investigate The purpose of investigation is to determine the root cause of existing or potential nonconformities, whenever possible, and to provide recommendations of solutions Good practice shows that a documented plan should be in place prior to conducting the investigation. The plan should include: Description of the nonconformity expressed as a problem statement Scope of the investigation Investigation team and their responsibilities Description of activities to be performed Resources Methods and tools Timeframe
- 26. The investigation should include the collection of data to facilitate analysis and should build upon any analysis, evaluation and investigation that were previously performed Many of the tools used in investigations rely upon a cause and effect relationship between an event and a symptom of that event. To ensure that causes are identified, not symptoms, the following should be considered: There must be a clear description of a cause and its effect. The link between the cause and the undesirable outcome needs to be described Each description of a cause must also describe the combined conditions that contribute to the undesired effect The outcome of an investigation should include: Clearly defined problem statement What information was gathered, reviewed and/or evaluated Results of the reviews/evaluations of the information Identification of cause(s) or contributing factors Solutions to address the cause(s) or contributing factor(s) Commontoolsof investigation Cause and effect diagrams 5 Why’s analysis Pareto charting Fishbone/Ishikawa cause and effect diagrams Change analysis Risk analysis techniques Is/Is Not Fig.12 Tools of investigation
- 27. Identify Root Cause When the root cause(s) has been determined, the manufacturer should identify and document the necessary corrections and/or corrective actions or preventive actions As a result of this step, a list of action items should be documented. These may include: A detailed description of the implementation Review regulatory requirements (e.g. submissions, licensing, certifications) Roles and responsibilities for execution of action items Identification of the necessary resources (e.g. IT, infrastructure, work environment) Implementation schedule, including timelines Identify the starting point of monitoring, and end point of correction and/or corrective action or preventive action as described above The outcomes that are possible and should be documented No further action necessary (provided that no safety issue exists and regulatory requirements are met) 1. With continuous monitoring 2. Acceptance under concession and continuance of monitoring Correction It may be necessary to take initial corrections in order to address an immediate risk or safety issue. Corrective action Corrective action should address systemic problems. Preventive action By its very nature preventive action can not follow a nonconformity. Fig.13 Outcomes of a root cause analysis
- 28. Verify Identified Actions Prior implementation of actions its important verify the identified action(s) and approve their implementation Verification is to ensure that all the elements of the proposed action will satisfy the requirements of the proposed action Performed by persons who are knowledgeable in the design that is the subject of corrective or preventive action Validation activities generate data and information that confirm the likelihood of the effective-ness of the corrective action to eliminate the nonconformity or proposed nonconformity
- 29. Implement Actions The following items that may be considered at implementation should be documented: Parties involved Materials Processes Training Communications Tools Timelines for the implementation of the approved action
- 30. Determine Effectiveness of Implemented Actions The manufacturer should gather data over a period of time related to the effectiveness of the implemented action Management should ensure and be involved in a review and confirmation that actions taken were effective and did not introduce new issues or concerns The following questions should be considered throughout the process Has the problem been comprehensively identified? Has the extent of the problem been identified (e.g. range of affected devices, patient out-come, process, production lines, operator)? Have the root cause/contributing factors of the problem been identified and addressed? Has the improvement action(s) been defined, planned, documented, verified and implemented? If the manufacturer finds the actions are not effective, the manufacturer should reinitiate Phase III activities
- 31. Phase IV: Input to Management Report to Management The manufacturer should have a mechanism/procedure that expeditiously raises safety related issues or other risk issues to management Management Review The manufacturer needs to define what meaningful data is to be reported for a management review. Data be specific to the quality objectives of the manufacturer and be reported regularly Included in this review would be an assessment of any opportunities for improvement of the de-vice, manufacturing process, QMS or the organization itself
- 32. References http://www.imdrf.org/index.asp http://www.imdrf.org/docs/ghtf/final/sg3/technical-docs/ghtf-sg3-n19-2012-nonconformity-grading- 121102.pdf http://www.imdrf.org/docs/ghtf/final/sg3/technical-docs/ghtf-sg3-n18-2010-qms-guidance-on- corrective-preventative-action-101104.pdf
- 33. Thank-you