Presentation on theme: "Quality Systems Compliance 1 FDA Medical Device Quality Systems Compliance."— Presentation transcript:
Quality Systems Compliance 1 FDA Medical Device Quality Systems Compliance
Quality Systems Compliance 2 Agenda Introductions, Attendance Sign in Domestic and International Quality Systems Food and Drug Law Organization of the FDA Break ( 15 min) Procedures FDA Quality Systems Regulations ( 21 CFR 820) Lunch Labeling Complaint Handling Record Keeping Break (15 Min) FDA Quality Systems Audits Exam Course Evaluations
Quality Systems Compliance 3 US and European Regulatory Systems Congress Passes Laws US FDA Writes Regulations Companies Develop Quality Systems Procedures FDA Audits for Compliance to Regulations European System European Commission Issues Directives Member Countries identify independent Notified Bodies Harmonized Standards adopted by the Member Countries Notified Bodies Audit for Compliance to the Directive and Harmonized Standards
Quality Systems Compliance 4 US vs European Laws US Food, Drug and Cosmetics Act Medical Device Amendments (1976) Safe Medical Devices Amendments (1990) FDAMA (1997) Europe Medical Device Directive (MDD) 1993 Active Implantable Medical Device Directive (AIMD) 1990
Quality Systems Compliance 5 US vs. European Quality System Requirements US 21 CFR 820 (Also known as the QSR) Guidance Documents Europe Essential Requirements Harmonized Standards ISO 13485
Quality Systems Compliance 6 Background of the FDA Biologics Control Act. 1902 The Pure Food and Drug Act-1906 Food Drugs and Cosmetics Act -1938 –Medical Device Amendments to the FDCA – 1976 –Safe Medical Devices Act- 1990 –FDAMA- 1997
Quality Systems Compliance 7 CBER Center for Biologics Evaluation and Research CDRH Center for Devices and Radiological Health CDER Center for Drug Evaluation and Research Offices of Medical Product Regulation within the U.S. Food and Drug Administration (FDA)
Quality Systems Compliance 8 Drugs “[an article] intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease... [or]... intended to affect the structure or any function of the body” FD&C Act, §201(g)(1) Devices “... An instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar related article... intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment or prevention of disease... or intended to affect the structure or any function of the body... and which does not achieve any of its primary intended purposes through chemical action within or on the body... and which is not dependent upon being metabolized for the achievement of any of its primary intended purposes” FD&C Act, §201(h) (emphasis added) Biologics “...any virus, therapeutic serum, toxin, anti-toxin, vaccine, blood, blood component or derivative, allergenic product, or analogous product applicable to the prevention, treatment or cure of diseases or injuries” PHS Act, §351(a)Definitions
Quality Systems Compliance 9 FDA Center Responsibilities Blood Products Vaccines Gene/Cell Therapy Stem Cell Research Stethoscopes MRI Scanners Hemodialysis Machines Surgical Instruments Microwave ovens Zocor Viagra Tylenol Celebrex Penicillin CBER CDRHCDER
Quality Systems Compliance 11 Class Exercise - FDA Organization Which division of the FDA has authority over the following products? Blood banks Bandages Computer terminals Bone graft material Pre-filled antibiotic syringes Lasers for eye surgery Artificial skin graft materials Contact Lenses Dog and Cat Food
Quality Systems Compliance 12 Quality System A Medical Device Quality System is designed to assure that products are Safe and Effective for their Intended Use and Consistently meet the specifications as defined by results of clinical and/or detailed technical design and validation
Quality Systems Compliance 15 Quality System Basics (ctd) Quality is everyone’s responsibility Quality has measurable attributes Specifications are the of a Quality System Documented policy and procedures contribute to consistency Quality planning is essential
Quality Systems Compliance 16 Quality Systems Basics (ctd) Clinical evaluation is the basis for safety and effectiveness Design Controls and validation assure that designs meet clinical expectations and specifications Process validation assures consistency Identification, segregation and control of materials and products prevents mix-ups Documentation control is essential
Quality Systems Compliance 17 Quality System Basics (ctd) Corrective and preventative action systems foster continual improvement Labeling is important Internal and external (FDA) auditing keeps quality systems up to date
Quality Systems Compliance 18 The Documentation Pyramid Quality Manual Procedures Work Instructions Records (forms, notebooks, travelers)
Quality Systems Compliance 19 Important Terms Device Master Record (DMR)- Device History Record (DHR) Design History File (DHF) Technical File Complaint Corrective Action Controlled Document Engineering Change Order (ECO) Labeling Verification Validation Traceability Medical Device Directive (MDD) Essential Requirements Notified Body
Quality Systems Compliance 20 Procedures FDA 21 CFR 820 requires following written procedures
Quality Systems Compliance 21 Group Exercise: Draw a House
Quality Systems Compliance 22 Draw A House 1.Read all instructions before beginning to draw the house 2.Draw your house in the lower ½ of the page 3.Begin by drawing a rectangle approximately 4 inches wide by 3 inches tall, with the long side parallel to the bottom edge of the paper. The bottom of the rectangle should be 1 inch from the bottom of the paper. 4.Locate the center of the top edge of the rectangle. Put a small dot at that point. 5.Put a small dot 1 ½ inches above the dot you just made. This dot will be above the rectangle. 6.Draw a line from the new dot to each edge of the top of the rectangle. 7.Draw a door in the center of the rectangle. The door should be 3/4 inch wide by 2 inches tall. The bottom of the door should touch the bottom of the rectangle. 8.Draw a window, approximately 1 inch square on each side of the door, 1 inch from the bottom of the rectangle. Hint: A average thumb is about 1 inch wide at the knuckle. The edge of each window should be ¼ inch from the nearest edge of the door. 9.Draw 4 panes of glass in each window by making a cross in each window. Each pane should be the same size. 10.Draw a chimney on the left side of the roof of the house. The chimney should be parallel to the left wall of the rectangle, touching the roof. The chimney should be ½ inch wide by 1 inch tall and go straight up. 11.Draw some smoke coming from the chimney. A squiggly line will represent smoke. 12.Put your pencil down when you are finished.
Quality Systems Compliance 23 Quality System Processes Management Controls Design Controls Materials Controls Document Controls Purchasing Controls Production and Process Controls Facilities and Equipment Controls Document, Record and Change Controls Corrective and Preventative Action Labeling Controls Handling, Storage, and Distribution controls Servicing Controls Statistical Techniques
Quality Systems Compliance 24 Management Controls Possible careers –Internal Auditor –External Auditor –Quality Specialist –Quality Systems Trainer
Quality Systems Compliance 25 Who is an Auditor? Auditor An Auditor is someone who comes in after the war is lost to bayonet the wounded… Anon.
Quality Systems Compliance 26 Management Controls 21CFR 820 Subpart B Quality Policy Defined Management Representative Management Review Quality Systems Procedures Quality Systems Audits Trained Personnel
Quality Systems Compliance 27 Design Controls Possible Careers –Design Engineer or Technicians –Quality Test Technicians –Clinical Specialists –Documentation Specialists
Quality Systems Compliance 28 Design Controls A Medical Device Quality System is designed to assure that products are Safe and Effective for their Intended Use and Consistently meet the specifications as defined by results of clinical and/or detailed technical design and validation
Quality Systems Compliance 29 Design Controls A Design Control System is intended to design products which provide safe and effective medical devices, meet the clinical needs of the intended patient population, provide outstanding value to the user, satisfy the needs and expectations of our customers. Phased approach to product development Each phase has deliverables Design reviews are the checkpoints
Quality Systems Compliance 30 Design Control Elements Design Planning Design Input (Requirements) Design Output (Specifications) Design Reviews (Technical) Design Verification (Meets Specifications Design Validation (Meets clinical needs) Design Transfer- (Moves from Design to Manufacturing) Design Changes (Formal Process) Design History File (DHF)
Quality Systems Compliance 31 Design Planning Feasibility Studies Risk Assessments Project Plan Defines Interfaces with Others Stage-Gate Methodology Constantly Changing
Quality Systems Compliance 32 Design Input Where –Customers –Technical Papers –Medical experts –Service people What –Intended Use –Technical Requirements –Safety Issues How –Documented –Approved –Filed –Formal Change Control System
Quality Systems Compliance 33 Design Output Final Design Specifications –Quantitative –Documented –Approved Final Risk Assessments Clinical Testing May Be Needed
Quality Systems Compliance 34 Design Reviews Planned Formal Technical Reviews Independent Member of Review Team Documented
Quality Systems Compliance 35 Design Verification And Validation Verification - Meets Specification Validations - Meets Intended Clinical Use Written Procedure Required Testing Must be Documented, Reviewed and Approved Software Must be Validated Manufacturing Processes Must be Validated
Quality Systems Compliance 36 Design Transfer Design moves from R&D to Manufacturing Manufacturing and Production Specifications are Documented Manufacturing IQ, OQ, PQ –IQ - Installation Qualification (Equipment) –OQ - Operational Qualification( 1 st ones meet specs) –PQ - Performance Qualification (Consistently repeatable)
Quality Systems Compliance 37 Design Changes All changes to the design after release must be controlled (Engineering Change Control) –Re-validation may be needed Continues for the Life of Product
Quality Systems Compliance 38 Design History File Record of the Development Process –Plans –Specifications –V&V Test Results –Design Reviews –Changes to the Design
Quality Systems Compliance 39 Class Exercise-Design Controls Dr. Bright and Dr. Idea have found a novel way to produce a machine to determine if a heart attack patient has additional blockage in the coronary arteries that may be caused by the surgical bypass procedure (CABG). The machine non-invasively measures arterial flow by using Doppler sonar to determine if the arteries are blocked. It can be used in a patient’s home, by itself, on post heart attack patients who may be at risk for additional heart attacks. It transfers the data to a monitoring station at a EMS facility for 24/7 monitoring. They have formed a company (The Bright-Idea Company), built a prototype and tested it in the lab on sheep and pigs. It worked great. Now they want to begin marketing it for use on humans. 1.Is the machine a medical device? 2.What steps should Dr. Bright and Dr. Idea take before they can begin marketing the machine? 3.What documents do they need to have on file?
Quality Systems Compliance 40 Manufacturing and Servicing the Product
Quality Systems Compliance 41 Manufacturing and Service A Medical Device Quality System is designed to assure that products are Safe and Effective for their Intended Use and Consistently meet the specifications as defined by results of clinical and/or detailed technical design and validation
Quality Systems Compliance 42 Documents Controls Career Opportunities –Documentation Control Specialist –Change Order Coordinator –Drafter
Quality Systems Compliance 43 Documents Controls Controlled System Review and Approval Required – Signature, Date – Authorized Personnel Listed in a Procedure Engineering Change Order Process (ECO) Electronic Records Require Special Security
Quality Systems Compliance 44 Purchasing Controls Career Opportunities –Purchasing Agent –Buyer –Supplier Auditor
Quality Systems Compliance 45 Purchasing Controls Written Procedures Required Supplier Selection Process –Approved Supplier List Purchase Orders –Detailed Specifications Needed –Supplier is Required to Have Current Specifications Supplier Auditing
Quality Systems Compliance 46 Identification and Traceability Career Opportunities –Receiving and Inspection Coordinators –Shipping Coordinators –Quality Technicians
Quality Systems Compliance 47 Identification and Traceability Unique Identification of Product Through All stages of Receiving, Production, Installation, and Service Separate Accepted (Good) from Non- Conforming (Bad) Implants or Life Sustaining Product Requires Traceability to the User
Quality Systems Compliance 48 Production and Process Controls Career Opportunities –Calibration Technician –Maintenance Technicians –Change Coordinators –Trainers –Process Validation Technicians
Quality Systems Compliance 49 Production and Process Controls Written Instructions (SOP’s) Required Environmental Controls –Clean Rooms Personnel –Health, Cleanliness, etc. Contamination Control Equipment –Maintenance Schedules –Software Validation Required in Process Equipment
Quality Systems Compliance 50 Inspection, Measurement and Test Equipment Routine Calibration of Measurement Equipment Reference Standards Must Be Maintained Records Must Be Kept In Secure Areas
Quality Systems Compliance 51 Acceptance Activities Career Opportunities –Inspection Technician –Test Technicians –Non-conforming product coordinator
Quality Systems Compliance 52 Acceptance Activities Written Procedures are Required for all Inspection and Test Activities Receiving Inspection In-Process Inspection and Test Final Inspection and Test Records
Quality Systems Compliance 53 Non-Conforming Product Non-conforming- Def: Does not meet Specifications Segregation, Identification and Status of Nonconforming Product is Required Material Review Board (MRB) Rework, Retest and Disposition
Quality Systems Compliance 54 Typical Inspection, NCMR, and Rework Process (The Happy Path)
Quality Systems Compliance 55 Corrective and Preventative Actions (CAPA) Career Opportunities –Quality Analyst –Quality Engineer –Complaint Coordinator
Quality Systems Compliance 56 Corrective and Preventative Actions (CAPA) Includes Internal and External Actions (Complaints to be covered after lunch) Corrective Actions- Actions Taken After Occurrence of the Event to Prevent Reoccurrence –Process Analysis –Failure Analysis –Procedure Review
Quality Systems Compliance 57 Corrective and Preventative Actions (CAPA) Examples of Corrective Actions –Review of Field Failures –Review of NCMR –Procedure Reviews Corrective Actions Should be Validated to Assure They Work
Quality Systems Compliance 58 Corrective and Preventative Actions (CAPA) Preventative Action- Actions Taken to Prevent a Problem from Occurring – Process Validations (IQ,OQ,PQ) –Trend Analysis of Complaints, Repairs –Internal Production Rework Trend Analysis (NCMR DATA) –Supplier Audits and Reviews –Highly Accelerated Stress Screening Testing (HASS) –Highly Accelerated Life Testing (HALT) –Market Information Review from Competitors
Quality Systems Compliance 59 Corrective and Preventative Actions (CAPA) Communicate the Results of Analysis Management Reviews must Include CAPA Information Documentation of Actions is REQUIRED –Indication of the effectiveness of the Quality System
Quality Systems Compliance 60 Labeling and Packaging Written Procedures Required Label Integrity- –Does the label remain legible for product life Label Inspection –Control of labels required Label Storage –Secure area –QA release Labeling Operations –Assure that labels are not mixed up –Recalls of FDA regulated product can be initiated by mis- labeling Serial Numbers
Quality Systems Compliance 61 Labeling and Packaging Packaging must be Designed to Assure That Products Are Protected During Transit and Storage –Shipping testing –Environmental testing ( Temperature, Humidity ) –Specialized labeling of the package may be needed Sterile Packaging has Special Considerations
Quality Systems Compliance 62 Handling, Storage, Distribution and Installation Career Opportunities –Material Handlers –Stockroom Personnel –Shipping Personnel –Field Installation –Traffic Managers
Quality Systems Compliance 63 Handling, Storage, Distribution and Installation Official Release (QA) from Production to Storage (Stockroom) Required Mix-Ups Must be Prevented Prevention from Damage or Deterioration –Shelf Life –Stock Control-FIFO
Quality Systems Compliance 64 Handling, Storage, Distribution and Installation Procedures Required to Assure that Only “GOOD” Product is Released for Distribution Records of Following must be Kept by Manufacturer –Name and Address of Consignee (Company or Person who Receives Product) –Quantity shipped –Date Shipped –Serial, Lot Numbers Shipped
Quality Systems Compliance 65 Handling, Storage, Distribution and Installation Installation Instructions Required (IQ) Installation of Equipment Must Be Verified Records Kept (if done by Mfgr.)
Quality Systems Compliance 66 Records General – Records Must be Legible –Security maintained –Available for Life of Product (min) 2 years past shipping date
Quality Systems Compliance 67 Records Device Master Record (DMR)( Recipe) –Design Specifications –Process Specifications –QA Procedures –Packaging Info Records –Labeling Info –Installation and Maintenance Info Device History Record (DHR)(As really Built) –Date of Manufacture –Quantity Manufactured –Quantity Released for Distribution –Acceptance ( Test) Records –Primary Labeling Information Quality System Record (QSR) – Quality Manual, Management Review Procedures, SOP’s, Generic Training Procedures, Other Non-device Specific Quality Procedures
Quality Systems Compliance 68 Service Career Opportunities –Service Technicians
Quality Systems Compliance 69 Service Written Procedure For Service Required Testing Post Servicing Required –Record is part of the DHR Records Must Contain –Name and SN of Device –Date and Person Servicing Device –Service preformed and Test Results Service Information Must Reviewed for Complaints
Quality Systems Compliance 70 Statistical Techniques Valid Statistical Plans must be used for all sampling and testing to verify conformance to specifications
Quality Systems Compliance 71 Class Exercise Manufacturing and Service The Bright-Idea Company received approval to market the machine. They have produced approximately 1000 of the machines, shipped 700 to their customers. One afternoon, the final tester began to notice that the machines did not always work the way they were supposed to at the final test station. He was rejecting about 50% of them. The design engineer in charge found that there was a sticky valve in about 50% of one of the lots of valves they received two months ago. It was hard to tell if the valves would always fail or not, because the problem was intermittent. 350 machines had been made using the lot with the defective valves. You are the Quality Engineer responsible for Corrective Actions. What steps should you take next?
Quality Systems Compliance 72 Labeling Career Opportunities –Label Designer –Graphic Artist –Technical Writer
Quality Systems Compliance 73 Labeling 21 CFR 801 Section 201(k) defines "label" as a: "display of written, printed, or graphic matter upon the immediate container of any article..." The term "immediate container" does not include package liners. Any word, statement, or other information appearing on the immediate container must also appear "on the outside container or wrapper, if any there be, of the retain package of such article, or is easily legible through the outside container of wrapper." Section 201(m) defines "labeling" as: "all labels and other written, printed, or graphic matter (1) upon any article or any of its containers or wrappers, or (2) accompanying such article" at any time while a device is held for sale after shipment or delivery for shipment in interstate commerce.
Quality Systems Compliance 74 Over The Counter (OTC) Device Labeling Principal Display Panel 21 CFR 801.6021 CFR 801.60 The principal display panel is that portion of the label which is intended to be displayed, presented, shown, or examined under customary conditions for retail sales. Statement of Identity 21 CFR 801.6121 CFR 801.61 The statement of identity of the device must be listed on the principal display panel. –It must list the common name –Indications for use –Bold type, –Reasonably sized generally parallel to the base of the package Net Quantity of Contents Statement 21 CFR 801.6221 CFR 801.62 The label of an over-the-counter (OTC) device in package form must contain a statement of net quantity of contents in terms of weight, measure, numerical count; or a combination of numerical count and weight, measure.
Quality Systems Compliance 75 Prescription Device Labeling Prescription Device 21 CFR 801.10921 CFR 801.109 A device which, because of any potentiality for harmful effect, or the supervision of the method of its use, or the collateral measures necessary to its use is not safe unless under a practitioner licensed by law to direct use this device, and hence for which "adequate directions for use" cannot be written, is exempt from such provided: –- It is in the possession of either a licensed practitioner or persons lawfully engaged in the manufacture of distribution of the product; –- Its labeling bears an Rx statement, i.e., "Caution: Federal law restricts this device to sale by or on the order of a (Insert name of physician, dentist or other licensed practitioner;" –- Its labeling bears information for use including, indications, effects, routes, methods, and frequency and duration of administration, and any relevant hazards, contraindications, side effects, and precautions under which the device can safely be used; and –- All labeling other than labels and carton bears the date of issuance or date of the latest revision.
Quality Systems Compliance 76 Rx Medical Device Labeling- General Requirements Intended Use Indications for Use Contraindications for Use Warnings, Cautions Description of the Device User Instructions Specifications Corrective Actions (Troubleshooting)
Quality Systems Compliance 77 FDA Actions for Mislabeling Warning Letters Mandatory Recall Injunctions to Stop Shipment Seizure Fines and Imprisonment
Quality Systems Compliance 78 FDA Legal Actions SEC. 303. [21 U.S.C. 333] (a)(1) Any person who violates a provision of section 301 shall be imprisoned for not more than one year or fined not more than $1,000, or both. Notwithstanding the provisions of paragraph (1) of this section, if any person commits such a violation after a conviction of him under this section has become final, or commits such a violation with the intent to defraud or mislead, such person shall be imprisoned for not more than three years or fined not more than $10,000 or both. Knowingly distributing drugs/devices in violation of section 503(e)(2)(A), shall be imprisoned for not more than 10 years or fined not more than $250,000, or both. Any manufacturer or distributor who distributes drug/device samples by means other than the mail or common carrier whose representative, during the course of the representative’s employment or association with that manufacturer or distributor, violated section 301(t) because of a violation of section 503(c)(1) or violated any State law prohibiting the sale, purchase, or trade of a drug sample subject to section 503(b) or the offer to sell, purchase, or trade such a drug sample shall, upon conviction of the representative for such violation, be subject to the following civil penalties: (A) A civil penalty of not more than $50,000 for each of the first two such violations resulting in a conviction of any representative of the manufacturer or distributor in any 10-year period. (B) A civil penalty of not more than $1,000,000 for each violation resulting in a conviction of any representative after the second conviction in any 10-year period.
Quality Systems Compliance 79 Class Exercise- Labeling Review of Respironics REMStar® Heated Humidifier labeling for: –Indications for use –Contraindications –Prescription Statement –Description –Corrective Actions
Quality Systems Compliance 81 Complaint Definitions Any written, electronic, or oral communication that alleges deficiencies related to the –Identity – quality – durability – reliability – safety – effectiveness – or performance of a device after it is released for distribution."
Quality Systems Compliance 83 Sources of Complaints Complaints that shall be processed according to the GMP requirements may be received from: Customers by letter, credit memo, returned goods form, or phone; A manufacturer's representative, or other employees; The MedWatch voluntary reporting program; A service or repair request; Journal articles; or The FDA
Quality Systems Compliance 85 Complaints-MDR Medical Device Report (MDR)-The MDR regulation requires that all manufacturers of medical devices notify FDA when they become aware of a death or serious injury that may have been caused or contributed to by one of their marketed devices and/or any malfunction of one of their devices which, if it were to recur, would be likely to cause or contribute to a death or serious injury.
Quality Systems Compliance 86 Class Exercise Sandy Bright is Dr. Bright’s daughter. One day she was at a neighbor’s house (Ms. Consumer) when the machine Dr. Bright’s company made stopped working while Ms. Consumer was using it and Ms. Consumer had to go to the hospital. Ms. Consumer told Sandy to tell her Dad about the problem. Sandy told her Dad the next morning. What Should Dr. Bright do and when?
Quality Systems Compliance 88 FDA Audits Career Opportunities –FDA Compliance Officer –FDA Consumer Safety Officer –Internal Auditor FDA
Quality Systems Compliance 89 FDA Audits of a Device Manufacturer Types –QSR-Risk Based Approach –Targeted- Based on a Complaint/Recall Establishment must be registered May Be Unannounced FDA issues a Form 482-Notice of Inspection If problems- FDA issues a form 483-Notice of Observations Possible Warning Letter if not corrected.
Quality Systems Compliance 90 Manufacturer’s Responsibilities Have Written Policy for FDA or other External Audits Have Records Organized Have an Escort at all Times Have a Separate Room for the Auditor Bring Information to Auditor Be Courteous Don’t offer any “bribes” –Lunch –Trips to Hawaii –Baseball Game Tickets –Company Party
Quality Systems Compliance 91 Employee Responsibility Remain Calm Answer Questions Truthfully Don’t Volunteer Information Refer to Procedures If in Doubt, Refer to Supervisor/Escort