Quality System Regulation (QSR) Training

Transcription

1 Quality System Regulation (QSR) Training Or How to Ensure Development, Production and Sale of Safe, Effective, Consistent Product FDLI February 2003

2 Overview QSR History, Purpose and Scope Changes from Prior GMPs Regulatory Requirements FDA Inspectional Focus QSIT Management Responsibility Design Controls Production and Process Controls Corrective and Preventative Action Integration of all QSR systems

3 Quality System U.S. FDA Quality System Regulation (QSR) - 21 CFR Part 820 Harmonized with European Requirements ISO 9001 EN Medical Devices Directive (MDD) ISO 13485

4 Regulation Evolution Current regulation covers design through commercialization of product GMP Regulation 1978, 1982, 1990 ISO Regulation 1990 QSR Regulation 1997 (SMDA 1990) ISO Regulation 1990 Ensure Consistency of Manufacturing Controls for Tracking Design Ensure Consistency of Manufacturing Medical Device Amendments 1976 (Law) Approval for Commercialization Approval for Commercialization Approval for Commercialization PAST CURRENT

5 Quality System Elements Management Responsibility Quality Audit Personnel Design Controls Document Controls Purchasing Controls Identification and Traceability Production and Process Control Inspection, Measuring and Test Equipment Process Validation Acceptance Activities Acceptance Status Nonconforming Product Corrective and Preventive Action Labeling and Packaging Control Handling, Storage, Distribution and Installation Records Servicing Statistical Techniques

6 Quality System Design Specification Development Testing Prototyping Selection of Suppliers Transfer to Production Tracking of Design Changes Manufacture Establishing Production Processes Testing Developing Acceptance Criteria Equipment Calibration and Maintenance Labeling Tracking Changes Final Release Inspection Criteria Segregation and Storage Product Shipment Tracking of Product Distribute Device tracking/ handling of complaints Corrective Action as needed Servicing Monitor Performance

7 Quality System Elements Management Responsibility: Establish policy and objectives for, and commitment to, quality Establish Organizational Structure Designate a Management Representative Conduct Management Reviews

8 Management Responsibility (Cont.) Organizational Chart - Example President and CEO Operations Sales and Marketing Research and Development Manufacturing Sales Engineering QA/QC (Management Rep) Regulatory Research Lab

9 Management Responsibility (Cont.) Establish a Quality Plan Additional Management Considerations Defineappropriate responsibility, authority, and interrelationships of all personnel who manage, perform, and assess work affecting quality Provide adequate resources for management, performance of work and assessment activities (including internal audits) Display management commitment in decision-making and involvement in management reviews

10 Quality System Element Internal Quality Audits Audits of all QS elements shall be periodically conducted to: Demonstrate compliance of the quality system to regulations, and/or Identify nonconformities and areas for improvement in processes Reports of audits must be documented and reviewed by management of the areas that were audited

11 Quality System Element Personnel and Training Employees, who s work affects quality, must have appropriate education, background, training and experience to do their jobs Records of education, training, background and experience must be maintained

12 Quality System Element Design Controls Procedures to control and verify design of all products to ensure design requirements are met Develop a design/development plan Develop and document design input Design input = Design requirements or specs

13 Design Controls (cont.) Develop and document design output Design output = Finished product and DMR (i.e., finished product specification) Plan formal reviews of the design throughout the development process Develop procedures for ensuring correct translation into routine production

14 Design Controls (cont.) Document changes implemented in the design during development phase, and test as needed Include regression analysis Maintain records of design process Conduct validation and verification testing

15 Design Controls (cont.) User Needs Design Reviews Design Inputs Design Process Validation Does it Work? Verification Is it Done Right? Design Outputs Final Device

16 Quality System Element Document Controls Establish and maintain a Quality System that is appropriate for devices designed and manufactured and meets regulatory requirements. Ensure documentation developed is adequate for its intended purpose or requirement Make documents accessible to those who need them Ensure control of the accuracy and usage of current versions of documents Maintain records of document changes

17 Quality System Element Purchasing Document requirements, including quality requirements that suppliers must meet Evaluate Suppliers, Contractors and Consultants on ability to meet requirements Define type and extent of controls over products, services and suppliers Maintain records for each supplier

18 Quality System Element Identification & Traceability Maintain procedures to identify product during all stages of receipt, production, distribution, and installation to prevent mix-ups Each unit or lot of finished device has a lot number Systems can be complex or simple FDA judges this system to be a measure of your control over your production system

19 Quality System Element Production and Process Controls Production processes must be developed, conducted, controlled and monitored to ensure the device conforms to its specs Process control procedures are necessary where deviations from the device specification could result from the production process Significant changes to these procedures must be verified or validated prior to implementation

20 Production /Process Control (cont.) Control environment when it can adversely affect product Ensure equipment meets specified requirements and is adequately maintained Process validation is required when results of process cannot be fully verified by inspection/test Document validation activities and results

21 Quality System Element Inspection and Testing Maintain procedures for acceptance activities Upon receipt, incoming material is inspected, tested or otherwise verified to demonstrate that it meets specified requirements In-process material must: meet specified requirements, where appropriate be controlled until inspection and test is completed Each production run or lot of finished devices must meet the stated acceptance criteria

22 Quality System Element Inspection, Measuring and Test Equipment Ensure that equipment is suitable for use and capable of producing valid results Specific and detailed calibration procedures Calibration standards must be traceable to national or international standards, if possible

23 Quality System Element Inspection, Test and Acceptance Status Identification of acceptance status is required throughout manufacturing, packaging, labeling, installation and service Product must be clearly identified as conforming or nonconforming to the acceptance criteria

24 Quality System Element Nonconforming Product Maintain procedures for control of product that does not conform to specifications Disposition of non-conforming product must be documented

25 Quality System Element Corrective and Preventive Action (CAPA) Maintain procedures for implementing corrective and preventive action Analyze data to identify and investigate areas requiring action - get to the root cause process analysis quality audits service and complaint record analysis management reviews non-conformities

26 Corrective and Preventive Action (cont.) Identify the action(s) needed to address the root cause of nonconformities in the Quality System VERIFY or VALIDATE the action to ensure it is effective & does not adversely affect product Confirm changes to documentation Follow up audit Review of production or field reports

27 Corrective and Preventive Action (cont.) Documentation shall include identified problem, investigation, root cause, action plan and verification results Report CAPA information relating to quality problems: To those directly responsible for assuring the quality of such product As part of Management Review meetings

28 Quality System Element Labeling and Packaging Control Maintain procedures for: Label integrity: legibility and adhesive adequacy Labeling inspection: accuracy of information Labeling storage: identification and accessibility Labeling operations: track label and labeling used for each lot/batch of product Control number: must accompany the unit through manufacturing and distribution Packaging/shipping containers: ensure proper construction to protect device during processing and distribution

29 Quality System Element Handling, Storage, Installation and Delivery Maintain procedures to minimize mix-ups, damage, deterioration, contamination or other adverse effects during handling Maintain distribution records Maintain installation and servicing procedures and records

30 Quality System Element Quality Records Maintain all records required by the Quality System in an area reasonably accessible to the manufacturer and auditors Records must be legible and stored to minimize deterioration and to prevent loss Records stored electronically are backed up

31 Quality System Element Complaint Handling Maintain procedures for receiving, reviewing, investigating, and responding to complaints Records shall be maintained for each complaint Document details of event, investigation, corrective action, and response to complainant Must be reasonably accessible to the manufacturing facility

32 Quality System Element Statistical Techniques Establish, where appropriate, procedures for using valid statistical techniques for establishing, controlling and verifying the acceptability of process capability and product characteristics Inspection samples Test quantities Sampling plans must be based on valid statistical rationale (e.g., ANSI/ASQC Z1.4, 1993, LTPD)

33 FDA Inspection Process - QSIT FDA is responsible for inspecting firms who manufacture devices cleared for use in humans PMA Approval process 510(k) Clearance Notices Registration and Listing Requirements FDA targets firms who have had previously violative inspections and firms with whom they have no history

34 FDA Inspection Process FDA has modified their inspection processes - became more interactive Pre-announcements: 3-5 days prior to beginning their inspection New techniques: QSIT/HACCP QSIT: Quality System Inspection Technique HACCP: Hazard Analysis and Critical Control Points Discussion of their findings during the inspection process so there should be NO surprises

35 Quality System Inspection Technique More similar to the ISO inspectional method Evaluates seven main subsystems by focusing on four inspectional areas Significantly more interaction between the Investigator and all levels of the company to determine objective compliance

36 Quality System Inspection Four Inspectional Areas Technique Management Responsibility Design Controls Production and Process Controls Corrective and Preventive Action Secondary Areas Facility and Equipment Control Material Controls Records/Document Controls

37 Facility & Equipment Controls Medical Device Reporting Reports of Corrections and Removals Corrective & Preventive Action Management Medical Device Tracking Design Controls Material Controls Records/ Documents/ Change Controls Production & Process Controls Sterilization Process Control

38 Quality System Inspection Technique Based on Top Down Approach Inspector reviews a sampling of records statistically determined number Follows record trail to conclusion Monitors strict compliance to procedural tasks Evaluates raw data to confirm conclusions

39 Quality System Inspection Technique Typical Inspection Process Opening Meeting minutes Plant Tour minutes Overview of Product minutes Meeting with Top Management: 1/2 day Design Controls: 1 day Corrective and Preventive Action: 1-11/2 days Document and Data Control 11/2-2 days Closeout Meeting

40 Top Ten FDA 483 Items Records (20%) CAPA (50%) PAPC (30%) Non-QSIT Inspections

41 Top Ten FDA 483 Items PAPC (20%) Records (10%) CAPA (30%) Mgmt (40%) QSIT Inspections

42 Verify existence of quality policy, management review and quality audit procedures. Confirm implementation of quality policy and objectives. Confirm establishment of org structure. Does it have provisions for: - responsibility and authority? - resources? Management Controls Confirm that management review procedures ensure that executive management reviews the suitability and effectiveness with sufficient frequency Confirm that Management Rep has been appointed? Does this person have authority over and responsibility for: - ensuring QS is effectively established and maintained? - reporting on the performance of the QS to management with executive responsibility? Confirm that quality audit procedures ensure that audits and reaudits of deficient matters are conducted. Suspend inspection of Management Controls - Return to Management Controls Subsystem after completing inspection of other subsystems. Evaluate whether management with executive responsibility ensures that an adequate and effect QS has been established.

43 For a selected design project, confirm that procedures have been defined and documented Review the design plan and assess the firm s conduct of risk analysis Confirm that the design inputs were established Confirm that design outputs essential to the proper function of the device were identified Confirm that acceptance criteria were established prior to test activities Confirm that device software was validated? Determine if any unresolved discrepancies remain from design validation Confirm that validation demonstrated the approved design met user needs and intended uses - and that activities were conducted on production devices or equivalent Confirm that verification demonstrated that outputs met inputs Confirm that risk analysis was performed Confirm that design changes were controlled - including validation or verification, where appropriate Confirm that design reviews were conducted Confirm that design was correctly transferred to production Design Controls

44 Confirm that procedures have been defined and documented Select a process and confirm that process is controlled and monitored Confirm that process is operating within specified limits - per review of DHR or other records Confirm that if process cannot be fully verified, it was validated Confirm that: -nonconformances were handled appropriately - equipment was adjusted, calibrated and maintained -process was adequately validated Confirm that if process is software controlled, the software was validated Confirm that personnel are qualified or trained to implement processes Production and Process Controls

45 Confirm that procedures have been defined and documented Confirm that quality data sources have been identified and analyzed to identify existing product and quality problems that require corrective action Confirm that sources of product and quality information that may show unfavorable trends have been identified and analyzed to identify issues that may require preventive action Confirm that failure investigation procedures are followed -is investigation level commensurate with risk? - is investigation conducted to root cause? - is product controlled to prevent distribution until resolution? Confirm that data received by the CAPA system are complete, accurate and timely -appropriate statistical methods used? - results compared across different data sources Confirm that appropriate action has been taken for identified problems Confirm that action taken is: - effective - verified or validated prior to implementation - not detrimental to the finished device - implemented and documented Confirm that information has been properly disseminated, including reports at management review CAPA Controls

46 Audit Conduct Assign escort for Inspector(s) Typically QA personnel (Quality Management Rep) Capture questions, comments from Inspector and any documents reviewed Intervene/clarify for auditee Seek department head for initial questions Prepare and coach department heads to understand audit process Be truthful, but not volunteering Convince FDA that operation meets QS requirements

47 At the Conclusion of the Inspection... Evaluate whether management with executive responsibility ensures that an adequate and effective quality system has been established and maintained.

48 Integration of all QSR Systems Comprehensive coverage of all essential functions of a manufacturing facility Design Development Manufacture Distribution Post-market monitoring Intended to ensure Continuous Improvement

49 Continuous Improvement Design Improve/ Innovate Develop Monitor Manufacture Distribute

50 Quality System Regulation Develop a system that is appropriate for YOU Lots of flexibility in requirements for how the system can be configured Don t be afraid to make changes if something is not working Can t implement the changes until the documentation is done Most of these requirements make good business sense - use it to your advantage!

51 Who Should Care? FDA expects that a company producing product for use in humans is meeting the Quality System Regulation Non-compliance may result in Warning Letter, negative publicity, submission hold, civil penalties FDA holds Company Management responsible for function of the Quality System FDA specifically meets with the most responsible person in the company to discuss the commitment to quality

52 Questions??