FDA Quality System Regulation General Training

Introduction to FDA’s QSR Quality Systems for US FDA regulated products are known as current Good Manufacturing Practices (cGMP’s). Appropriate Quality Systems are found in the Quality System Regulations (QSR) 21 CFR Part 820, last updated and published in the Federal Register in October 1996. It’s the LAW! FDA QSR Overview and Training

Introduction to FDA’s QSR 21 CFR Part 820 is just one section of many that apply to this industry Overall, the Food, Drug, and Cosmetic Act governs everything in our industry The Safe Medical Devices Act of 1990 has been the latest to modernize the requirements for the medical device industry What does the FDCA cover? Adulteration - Fines - Inspection Detention - Warning Letter Injunction - Seizure - Recall Prosecution FDA QSR Overview and Training

21 CFR Part 820 - The QSR There are 15 Subparts to the QSR General Provisions - Quality System Requirements Design Controls - Document Controls Purchasing Controls - ID and Traceability Production and Process Controls Acceptance Activities Nonconforming Product Corrective and Preventive Action Labeling and Package Control Handling, Storage, Distribution and Installation Records - Servicing Statistical Techniques FDA QSR Overview and Training

21 CFR Part 820 - The QSR FDA QSR Overview and Training Management Responsibility Personnel and Training Purchasing Controls Material Controls, ID, Traceability Installation & Service Design Controls Process Controls Documentation Control Customer Satisfaction CAPA Equipment Control Internal KPI’s, Complaints, etc. Facility Control Review/Analyze Act Acceptance Controls Production Contracts FDA QSR Overview and Training

21 CFR Part 820 - The QSR When FDA comes a’ callin’ An FDA inspection occurs every two years or so It’s been over three years for us. (Who’s that knockin’ at the door?) An FDA inspection utilizes a program called QSIT Quality System Inspection Technique It is a circular technique encompassing Management Responsibility Design Control Corrective and Preventive Action Production and Process Control FDA QSR Overview and Training

21 CFR Part 820 - The QSR The QSIT Circle of Control Management MDR’s CAPA MDR’s Corrections and removals Device Tracking Design Control Facility and Equipment Control Material Control Records Document Change Control Production & Process Control Sterilization Process Control The QSIT Circle of Control Management FDA QSR Overview and Training

21 CFR Part 820 - The QSR Management Responsibility A quality policy, management review and quality audit procedures, quality plan, and quality system procedures and instructions have been defined and documented. Quality policy and objectives have been implemented. An organizational structure includes provisions for responsibilities, authorities and necessary resources. A management representative has been appointed. FDA QSR Overview and Training

21 CFR Part 820 - The QSR Management Responsibility Management reviews, including a review of the suitability and effectiveness of the quality system, are being conducted. Quality audits, including re-audits of deficient matters, of the quality system are being conducted. All of the above should show that... Management with executive responsibility ensures that an adequate and effective quality system has been established and maintained. FDA QSR Overview and Training

21 CFR Part 820 - The QSR Design Controls Lack of proper design controls is major cause of all device recalls Intrinsic quality of devices, including their safety and effectiveness, is established during the design phase Applies to all pre-production stages of development of Class III, II, and some Class I devices Does not apply to development of concept and feasibility studies Devices deemed unsafe by FDA Inspectors during inspections will be reported to CDRH FDA QSR Overview and Training

21 CFR Part 820 - The QSR Design Controls Design Control Procedures must be established and maintained Design and Development Planning Design Input Establish and maintain procedures to ensure design requirements are Design Output Design outputs are the design specifications that meet the design inputs confirmed via verification and validation testing and ensured during design review FDA QSR Overview and Training

21 CFR Part 820 - The QSR Design Controls Design Verification Design verification is the testing required to determine whether the design outputs meet functional and operational requirements of the design inputs Design Validation Validation follows successful verification Verification is not a substitute for validation Validation means establishing by objective evidence that device specifications conform with user needs and intended uses FDA QSR Overview and Training

21 CFR Part 820 - The QSR Design Controls Design Validation Tested for performance under actual conditions or simulated use conditions or environments Conduct such tests when changes to device design or manufacturing processes are made that could affect safety and effectiveness Risk analysis must be conducted Any risks judged unacceptable must be mitigated or eliminated FDA QSR Overview and Training

21 CFR Part 820 - The QSR Design Controls Design Transfer Ensures that the design basis for the device is correctly translated into production methods and procedures Design Changes Applies to all design changes after initial design review that approves initial design inputs Design History File Contains or references all the records necessary to establish compliance with the design plan and the regulation FDA QSR Overview and Training

21 CFR Part 820 - The QSR Corrective and Preventive Action CAPA system procedure(s) address the requirements of the quality system regulation and have been defined and documented. Appropriate sources of product and quality problems have been identified; data from these sources are analyzed to identify existing product and quality problems that may require corrective action. Sources of product and quality information that may show unfavorable trends have been identified and are analyzed to identify potential product and quality problems that may require preventive action.

21 CFR Part 820 - The QSR Corrective and Preventive Action Appropriate statistical methods are employed (where necessary) to detect recurring quality problems. Results of analyses are compared across different data sources to identify and develop the extent of product and quality problems. FDA QSR Overview and Training

21 CFR Part 820 - The QSR Corrective and Preventive Action Failure investigation procedures are followed. The degree to which a quality problem or nonconforming product is investigated is commensurate with the significance and risk of the nonconformity. Failure investigations are conducted to determine root cause (where possible). Verify that there is control for preventing distribution of nonconforming product. FDA QSR Overview and Training

21 CFR Part 820 - The QSR Corrective and Preventive Action Appropriate actions have been taken for significant product and quality problems identified from data sources. Corrective and preventive actions are effective and verified or validated prior to implementation. Corrective and preventive actions do not adversely affect the finished device. FDA QSR Overview and Training

21 CFR Part 820 - The QSR Corrective and Preventive Action Information regarding nonconforming product and quality problems and corrective and preventive actions has been properly disseminated, including dissemination for management review. FDA QSR Overview and Training

21 CFR Part 820 - The QSR Be careful when implementing corrective action Without proper planning or proper judgement, the best intentions can go wrong…. FDA QSR Overview and Training

Nonconforming product 21 CFR Part 820 - The QSR 820.100 Corrective and Preventive Action Product Nonconforming product Processes (including audits) Review of issue Safety, systemic, or trend issue identified? CAPA Investigation KPI’s Yes Complaints Quality Records Service, installation feedback Returned Product No Third party information Perform necessary actions and continue to monitor Management Review FDA QSR Overview and Training

21 CFR Part 820 - The QSR Product and Process Controls There’s the management stuff and the RA/QA stuff…. And then there’s the rest These are the elements that control the day to day functions of a business FDA QSR Overview and Training

21 CFR Part 820 - The QSR Document Control Document approval and distribution Ensure control of the accuracy and usage of current versions of the documents Document and data changes Maintain change records Approved changes must be communicated in a timely manner to appropriate personnel FDA QSR Overview and Training

21 CFR Part 820 - The QSR Purchasing Controls Evaluate and select suppliers on the basis of their ability to meet the specified requirements. Evaluation must be documented Establish and maintain records of acceptable suppliers, contractors and consultants. Purchasing Data Approval of the purchasing data or information on the purchasing document used to purchase a product or service FDA QSR Overview and Training

21 CFR Part 820 - The QSR Identification Traceability Ensure that all products, including manufacturing materials, used in the manufacture of finished devices are properly identified Traceability Establish and maintain procedures for identifying devices for surgical implant into the body with a control number, and where appropriate, components. FDA QSR Overview and Training

21 CFR Part 820 - The QSR Production and Process Controls Intended to ensure that each manufacturer produces devices that conform to their specifications. Where deviations from device specifications could occur, establish and maintain process control procedures that describe any process controls necessary to ensure conformance to specification Documented instructions, SOP’s, methods monitoring and control of process parameters and other characteristics FDA QSR Overview and Training

21 CFR Part 820 - The QSR Production and Process Changes Establish and maintain procedures for changes to specifications, methods, process, or procedures Verify, or where appropriate, validate changes before implementation Environmental Control Establish and maintain procedures where environmental conditions could reasonably be expected to have an adverse effect on product quality FDA QSR Overview and Training

21 CFR Part 820 - The QSR Personnel Contamination Control Establish and maintain requirements for health and hygiene of personnel where such conditions could reasonably be expected to have an adverse effect on product quality Contamination Control Establish and maintain procedures to prevent contamination of equipment or product by any substance that could reasonably be expected to have an adverse effect on product quality FDA QSR Overview and Training

21 CFR Part 820 - The QSR Buildings Equipment Buildings shall be of suitable design and contain sufficient space to allow for the proper manufacture of devices Equipment Equipment must be appropriately designed to facilitate maintenance, adjustment, cleaning, and use Ensure that maintenance is carried out on schedule FDA QSR Overview and Training

21 CFR Part 820 - The QSR Manufacturing Material Automated Processes Ensure removal of materials that could reasonably be expected to have an adverse effect on product quality Maintain procedures for the use and removal of such materials Automated Processes Required to validate computers or automated data processing systems that are part of production or the quality system Software used in production or quality system, whether it be in the designing, manufacturing, distributing, or tracing, must be validated FDA QSR Overview and Training

21 CFR Part 820 - The QSR Inspection, Measuring, and Test Equipment Control of Inspection, Measuring, and Test Equipment Establish and maintain procedures to ensure equipment is routinely calibrated, inspected, checked and maintained, and documented Include specific directions and limits for accuracy and precision FDA QSR Overview and Training

21 CFR Part 820 - The QSR Process Validation Where the results of a process cannot be fully verified, it shall be validated with a high degree of assurance and approved according to established procedures Validation activities shall be documented, including date and signature Specification Controls Establish and maintain procedures for monitoring and control of process parameters Validated processes are performed by qualified personnel Revalidate when changes or process deviations occur FDA QSR Overview and Training

21 CFR Part 820 - The QSR Receiving, In-Process and Finished Device Acceptance Used in conjunction with Purchasing Controls to ensure suppliers, services, and contractors have the capability to provide quality product and services Inspections and tests and other verification tools are also important to ensure components and finished devices conform to approved specifications FDA QSR Overview and Training

21 CFR Part 820 - The QSR Acceptance Status Identify by suitable means the acceptance status of product indicate conformance status maintained during manufacturing, packaging, labeling, installation, and servicing of product FDA QSR Overview and Training

21 CFR Part 820 - The QSR Nonconforming Product Control of nonconforming product Nonconforming material must be identified, documented, segregated, and have proper disposition evaluation should consider the need for an investigation and notification of persons or organizations responsible for the nonconformance The evaluation and investigation must be documented FDA QSR Overview and Training

21 CFR Part 820 - The QSR Nonconforming Product Nonconformity review and disposition Establish and maintain procedures that define responsibility for review and the authority for the disposition of product Disposition is documented include justification for use of nonconforming product (signature and date of authorizing person) Establish and maintain procedures for rework include re-testing and re-evaluation rework and any determination of adverse effects shall be documented in the DHR. FDA QSR Overview and Training

21 CFR Part 820 - The QSR Labeling and Packaging Control Establish and maintain procedures to control labeling activities FDA QSR Overview and Training

21 CFR Part 820 - The QSR Device Packaging Handling Ensure that device packaging and shipping containers are designed and constructed to protect the device from alteration or damage during the customary conditions of processing, storage, handling, and distribution Handling Establish and maintain procedures to ensure that mix-ups, damage, deterioration, contamination, or other adverse effects to product do not occur during handling FDA QSR Overview and Training

21 CFR Part 820 - The QSR Distribution Establish and maintain procedures for the control and distribution of finished devices ensure only those devices approved for release are distributed ensure purchase orders are reviewed to resolve ambiguities and errors before distribution ensure expired product is not shipped FDA QSR Overview and Training

21 CFR Part 820 - The QSR Installation Establish and maintain adequate installation and inspection instructions, and where appropriate, test procedures Instructions shall include directions for ensuring proper installation so that the device will perform as intended Manufacturer shall distribute the instructions and procedures with the device or otherwise make them available to the installer FDA QSR Overview and Training

21 CFR Part 820 - The QSR Installation The person installing the device shall ensure that the installation, inspection, and any required testing are performed in accordance with the manufacturer’s instructions and procedures The inspection and any test results shall be documented to demonstrate proper installation FDA QSR Overview and Training

21 CFR Part 820 - The QSR Records All records required by this part shall be maintained at the manufacturing establishment or other location that is reasonably accessible Records must be readily available for review and copying by FDA employees Records shall be legible and stored to minimize deterioration records stored in automated data processing systems shall be backed up FDA QSR Overview and Training

21 CFR Part 820 - The QSR Records Records must be retained for the life of the device but in no case not less than two years from the date of release for distribution FDA QSR Overview and Training

21 CFR Part 820 - The QSR Device Master Record The DMR is set up to contain or reference the procedures and specifications that are current on manufacturing floor for a finished device FDA QSR Overview and Training

21 CFR Part 820 - The QSR Device History Record The DHR is the actual production records for a particular device and should be able to show the processes, tests, rework, and so on that went through from the beginning of manufacture through distribution, and if applicable, installation. FDA QSR Overview and Training

21 CFR Part 820 - The QSR Quality System Record This section separates the procedures and documentation of activities that are not specific to a particular type of device from the device specific records FDA QSR Overview and Training

21 CFR Part 820 - The QSR Complaint Files Establish and maintain procedures for receiving, reviewing, and evaluating complaints by a formally designated unit. The program shall ensure: All complaints are processed in a uniform and timely manner Oral complaints are documented upon receipt Complaints are evaluated to determine whether the complaint represents an event which is required to reported to FDA under part 803 or 804 (Medical Device Reporting) FDA QSR Overview and Training

21 CFR Part 820 - The QSR Complaint Files Review and evaluate all complaints to determine whether an investigation is necessary Determine if the complaint is valid If valid, determine if the complaint needs to be investigated If no investigation is required, document the justification not to investigate justification requires signature of person making decision FDA QSR Overview and Training

21 CFR Part 820 - The QSR Complaint Files Any complaint involving the possible failure of a device, labeling, or packaging to meet any of its specifications shall be reviewed evaluated investigated No investigation is required if a previous investigation has been conducted for a similar complaint FDA QSR Overview and Training

21 CFR Part 820 - The QSR Complaint Files Any complaint that represents and event which must be reported under Part 803 or 804 must be promptly reviewed, evaluated, and investigated by a designated individual(s) Records maintained in a separate portion of the complaint file or is clearly identified Records of these investigations must include a determination of failure to meet device specification device used for treatment or diagnosis relationship, if any, of the device to the reported adverse event FDA QSR Overview and Training

21 CFR Part 820 - The QSR Complaint Files A record of each investigation must be maintained by the formally designated unit Name of device Date complaint was received Device ID and any control number Name, address, and phone no. of complainant Nature and detail of the complaint Dates and results of investigation Any corrective action taken Any reply to the complainant FDA QSR Overview and Training

21 CFR Part 820 - The QSR Complaint Files When the formally designated complaint unit is located at a site separate from the manufacturing establishment, the investigated complaint(s) and the record(s) of the investigation shall be reasonably accessible to the manufacturing establishment FDA QSR Overview and Training

21 CFR Part 820 - The QSR Complaint Files If the formally designated complaint unit is located outside of the US, required records must be reasonably accessible in the US at either a location in the US where the manufacturer’s records are regularly kept the location of the initial distributor FDA QSR Overview and Training

21 CFR Part 820 - The QSR Servicing Where servicing is a specified requirement, establish and maintain procedures for performing and verifying that servicing meets the specified requirements Assure that servicing is correctly performed and verified according to company specified requirements FDA QSR Overview and Training

21 CFR Part 820 - The QSR Servicing Service shall be conducted by appropriately trained and experienced service personnel (820.25) in order to: assure, to the extent feasible, that the process of device handling, diagnosis, and repair will not compromise the determination of the root cause of the device failure; identify and correct the failure; correctly report the service information; and identify and report data related to a serious incident or adverse event. FDA QSR Overview and Training

21 CFR Part 820 - The QSR Servicing The repair diagnosis should also try to determine, and/or provide adequate data to assist analysts in determining, the actual failure mechanism to the objective level necessary to correct or reduce the problem FDA QSR Overview and Training

21 CFR Part 820 - The QSR Servicing Service reports must be analyzed with appropriate statistical methodology in accordance with 820.100 (CAPA) Develop sufficient trend data to make a reasonable determination as to whether corrective/preventive action is warranted Any service report that represents a reportable event under part 803 or 804 shall automatically consider it a complaint and must be processed per 820.198 FDA QSR Overview and Training