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FDA Medical Device Quality Systems Compliance

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Presentation on theme: "FDA Medical Device Quality Systems Compliance"— Presentation transcript:

1 FDA Medical Device Quality Systems Compliance
CCAC Quality System Basic Course FDA Medical Device Quality Systems Compliance Quality Systems Compliance

2 CCAC Quality System Basic Course
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
CCAC Quality System Basic Course US and European Regulatory Systems US European System Congress Passes Laws European Commission Issues Directives FDA Writes Regulations Harmonized Standards adopted by the Member Countries Companies Develop Quality Systems Procedures Member Countries identify independent Notified Bodies Notified Bodies Audit for Compliance to the Directive and Harmonized Standards FDA Audits for Compliance to Regulations Quality Systems Compliance

4 CCAC Quality System Basic Course
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
CCAC Quality System Basic Course 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 CCAC Quality System Basic Course
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 Around the turn of the last century, diphtheria patients were routinely treated with antitoxin derived from the blood of horses. There were no central or uniform controls in place and the antitoxin was often manufactured in local plants. In St. Louis, that combination had tragic consequences. Thirteen children died of tetanus in 1901 after being treated with diphtheria antitoxin made from the blood of a tetanus-infected milk wagon horse named Jim. Soon after this and a similar tragedy in Camden, N.J., involving deaths and injuries related to a tainted biological product, Congress enacted the Biologics Control Act. July 1, This regulation gives the Food and Drug Administration's Center for Biologics Evaluation and Research (CBER) authority to regulate biological products and ensure their safety. Biologics are medical products derived from living sources. They include vaccines, blood and blood derivatives, allergenic patch tests and extracts, tests to detect HIV and hepatitis, gene therapy products, cells and tissues for transplantation, and new treatments for cancers, arthritis, and other serious diseases. Beginning as the Division of Chemistry and then (after July 1901) the Bureau of Chemistry, the modern era of the FDA dates to 1906 with the passage of the Pure Food and Drugs Act; this added regulatory functions to the agency's scientific mission. The Bureau of Chemistry's name changed to the Food, Drug, and Insecticide Administration in July 1927, when the nonregulatory research functions of the bureau were transferred elsewhere in the department. In July 1930 the name was shortened to the present version. FDA remained under the Department of Agriculture until June 1940, when the agency was moved to the new Federal Security Agency. In April 1953 the agency again was transferred, to the Department of Health, Education, and Welfare (HEW). Fifteen years later FDA became part of the Public Health Service within HEW, and in May 1980 the education function was removed from HEW to create the Department of Health and Human Services, FDA's current home Quality Systems Compliance

7 CCAC Quality System Basic Course
Offices of Medical Product Regulation within the U.S. Food and Drug Administration (FDA) CBER Center for Biologics Evaluation and Research CDRH Center for Devices and Radiological Health CDER Center for Drug Evaluation and Research Quality Systems Compliance

8 CCAC Quality System Basic Course
Definitions 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) Quality Systems Compliance

9 FDA Center Responsibilities
CCAC Quality System Basic Course FDA Center Responsibilities CDRH CDER CBER Zocor Viagra Tylenol Celebrex Penicillin Stethoscopes MRI Scanners Hemodialysis Machines Surgical Instruments Microwave ovens Blood Products Vaccines Gene/Cell Therapy Stem Cell Research Quality Systems Compliance

10 CCAC Quality System Basic Course
Regulations CDRH CDER CBER Drugs 21 CFR 56 (IRB’s) 21 CFR 58 (GLP) 21CFR 11 (Electronic records) 21 CFR 210, 211 (Drug GMP’s) 21 CFR 312 (IND) 21 CFR 314 (NDA) Devices 21 CFR 21 CFR 820 QSR (GMP) 21 CFR 56 (IRB’s) 21 CFR 58 (GLP) 21CFR 11 (Electronic records) 21 CFRR (devices) 21 CFR 807 (510(k)) 21 CFR 812 (IDE) Biologics 21 CFR 600/601/610 Blood 21CFR 606 CLIA 21CFR 1270, 1271 (tissue) 21 CFR 58 (GLP) 21CFR 11 (electronic records) Quality Systems Compliance

11 Class Exercise - FDA Organization
CCAC Quality System Basic Course 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 CCAC Quality System Basic Course
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

13 CCAC Quality System Basic Course
Quality Control Quality Systems Compliance

14 CCAC Quality System Basic Course
Quality Assurance Quality Systems Compliance

15 Quality System Basics (ctd)
CCAC Quality System Basic Course 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)
CCAC Quality System Basic Course 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)
CCAC Quality System Basic Course 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
CCAC Quality System Basic Course The Documentation Pyramid Quality Manual Procedures Work Instructions Records (forms, notebooks, travelers) Quality Systems Compliance

19 CCAC Quality System Basic Course
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 CCAC Quality System Basic Course
Procedures FDA 21 CFR 820 requires following written procedures Quality Systems Compliance

21 Group Exercise: Draw a House
CCAC Quality System Basic Course Group Exercise: Draw a House Quality Systems Compliance

22 CCAC Quality System Basic Course
Draw A House Read all instructions before beginning to draw the house Draw your house in the lower ½ of the page 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. Locate the center of the top edge of the rectangle. Put a small dot at that point. Put a small dot 1 ½ inches above the dot you just made. This dot will be above the rectangle. Draw a line from the new dot to each edge of the top of the rectangle. 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. 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. Draw 4 panes of glass in each window by making a cross in each window. Each pane should be the same size. 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. Draw some smoke coming from the chimney. A squiggly line will represent smoke. Put your pencil down when you are finished. Quality Systems Compliance

23 Quality System Processes
CCAC Quality System Basic Course 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 CCAC Quality System Basic Course
Management Controls Possible careers Internal Auditor External Auditor Quality Specialist Quality Systems Trainer Quality Systems Compliance

25 CCAC Quality System Basic Course
Who is an 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
CCAC Quality System Basic Course 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 CCAC Quality System Basic Course
Design Controls Possible Careers Design Engineer or Technicians Quality Test Technicians Clinical Specialists Documentation Specialists Quality Systems Compliance

28 CCAC Quality System Basic Course
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 CCAC Quality System Basic Course
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
CCAC Quality System Basic Course 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 CCAC Quality System Basic Course
Design Planning Feasibility Studies Risk Assessments Project Plan Defines Interfaces with Others Stage-Gate Methodology Constantly Changing Quality Systems Compliance

32 CCAC Quality System Basic Course
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 CCAC Quality System Basic Course
Design Output Final Design Specifications Quantitative Documented Approved Final Risk Assessments Clinical Testing May Be Needed Quality Systems Compliance

34 CCAC Quality System Basic Course
Design Reviews Planned Formal Technical Reviews Independent Member of Review Team Documented Quality Systems Compliance

35 Design Verification And Validation
CCAC Quality System Basic Course 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 CCAC Quality System Basic Course
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( 1st ones meet specs) PQ - Performance Qualification (Consistently repeatable) Quality Systems Compliance

37 CCAC Quality System Basic Course
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 CCAC Quality System Basic Course
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
CCAC Quality System Basic Course 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. Is the machine a medical device? What steps should Dr. Bright and Dr. Idea take before they can begin marketing the machine? What documents do they need to have on file? Quality Systems Compliance

40 Manufacturing and Servicing the Product
CCAC Quality System Basic Course Manufacturing and Servicing the Product Quality Systems Compliance

41 Manufacturing and Service
CCAC Quality System Basic Course 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 CCAC Quality System Basic Course
Documents Controls Career Opportunities Documentation Control Specialist Change Order Coordinator Drafter Quality Systems Compliance

43 CCAC Quality System Basic Course
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 CCAC Quality System Basic Course
Purchasing Controls Career Opportunities Purchasing Agent Buyer Supplier Auditor Quality Systems Compliance

45 CCAC Quality System Basic Course
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
CCAC Quality System Basic Course Identification and Traceability Career Opportunities Receiving and Inspection Coordinators Shipping Coordinators Quality Technicians Quality Systems Compliance

47 Identification and Traceability
CCAC Quality System Basic Course 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
CCAC Quality System Basic Course Production and Process Controls Career Opportunities Calibration Technician Maintenance Technicians Change Coordinators Trainers Process Validation Technicians Quality Systems Compliance

49 Production and Process Controls
CCAC Quality System Basic Course 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
CCAC Quality System Basic Course 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
CCAC Quality System Basic Course Acceptance Activities Career Opportunities Inspection Technician Test Technicians Non-conforming product coordinator Quality Systems Compliance

52 Acceptance Activities
CCAC Quality System Basic Course 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
CCAC Quality System Basic Course 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 CCAC Quality System Basic Course
Typical Inspection, NCMR, and Rework Process (The Happy Path) Quality Systems Compliance

55 Corrective and Preventative Actions (CAPA)
CCAC Quality System Basic Course Corrective and Preventative Actions (CAPA) Career Opportunities Quality Analyst Quality Engineer Complaint Coordinator Quality Systems Compliance

56 Corrective and Preventative Actions (CAPA)
CCAC Quality System Basic Course 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)
CCAC Quality System Basic Course 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)
CCAC Quality System Basic Course 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)
CCAC Quality System Basic Course 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
CCAC Quality System Basic Course 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
CCAC Quality System Basic Course 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
CCAC Quality System Basic Course 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
CCAC Quality System Basic Course 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
CCAC Quality System Basic Course 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
CCAC Quality System Basic Course 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 CCAC Quality System Basic Course
Records General Records Must be Legible Security maintained Available for Life of Product (min) 2 years past shipping date Quality Systems Compliance

67 CCAC Quality System Basic Course
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 CCAC Quality System Basic Course
Service Career Opportunities Service Technicians Quality Systems Compliance

69 CCAC Quality System Basic Course
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
CCAC Quality System Basic Course 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
CCAC Quality System Basic Course 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 CCAC Quality System Basic Course
Labeling Career Opportunities Label Designer Graphic Artist Technical Writer Quality Systems Compliance

73 CCAC Quality System Basic Course
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. The term "accompanying" is interpreted liberally to mean more than physical association with the product. It extends to posters, tags, pamphlets, circulars, booklets, brochures, instruction books, direction sheets, fillers, etc. "Accompanying" also includes labeling that is brought together with the device after shipment or delivery for shipment in interstate commerce. Advertising According to an appellate court decision: "Most, if not all advertising, is labeling. The term 'labeling' is defined in the FFDCA as including all printed matter accompanying any article. Congress did not, and we cannot, exclude from the definition printed matter which constitutes advertising.“ Medical device manufacturers must incorporate in their quality assurance (QA) program several elements that relate to labeling in order to meet the Good Manufacturing Practice (GMP) requirements of the Quality System regulation. The QA program must be adequate to ensure that labeling meets the GMP device master record requirements with respect to legibility, adhesion, etc., and ensure that labeling operations are controlled so that correct labeling is always issued and used. Labeling includes equipment labels, control labels, package labels, directions for use, maintenance manuals, etc. The displays on CRT's and other electronic message panels are considered labeling if instructions, prompts, cautions, and parameter identification information are given. Various sections of the QS regulation have an impact on labeling: Section 21 CFR (b) requires the inspection and testing of incoming materials including labeling; and 21 CFR (f) requires buildings to be of suitable design and have sufficient space for packaging and labeling operations. 21 CFR deals with specific requirements for the control of labeling. It applies to the application of labeling to ensure legibility under normal conditions of use over the expected life of the device; and also applies to inspection, handling, storage, and distribution of labeling. FDA considers a device to be adulterated if these requirements are not met. These requirements do not apply to the adequacy of labeling content, except to make sure the content meets labeling specifications contained in the device master record. However, failure to comply with GMP requirements, such as proofreading and change control, could result in labeling content errors. In such cases, the device is misbranded and adulterated. Specifications are required in the design history file (DHF) 21 CFR for the content and physical design parameters of labels. Labeling specifications are: engineering drawing and/or artwork for each label, appropriate inspection or control procedures, and appropriate procedures for attaching the labels. All procedures, drawings, and artwork must have the name of the preparer, an approval signature, and a date. The approval signature, date, etc., may be on the backside of artwork or on a label approval form. Further, artwork may contain only an identification code or title if the "content" of the artwork is duplicated on approved engineering drawings or adequately identified (cross-referenced) with respect to the label approval form. Hard copy labels, package inserts, and similar labeling are specified and purchased as components. For correct purchase and use of labeling, specifications are usually stated on engineering drawings and/or purchase specifications. Thus, artwork or "copy" alone will not fulfill the device master record requirements for labeling except for the most simplistic labeling such as brief errata sheets. The engineering drawings or purchase specifications and mounting procedure must specify, as appropriate, the label substrate, dimensions, ink, finish, mounting method, etc., so that the purchased label will remain attached and legible during the customary conditions of processing, storage, handling, distribution, and use. Front panels, other instrument panels, meters, fuses, pushbuttons, and the like often are labels or contain labels and must, as appropriate, meet device master record and control requirements. Component specifications, assembly drawings, and test/inspection procedures may be appropriate controls to prevent mixup of meters, pushbuttons, and other labeled instrument controls. Controls to prevent mixups are generally not needed for front and other instrument panels. Whether a firm considers a software driven display to be labeling or data makes little difference under the Quality System regulation, because either way, the finished device labeling or data must meet the device master record specifications. When firms develop and validate software, they should also review these electronic displays to see that the "labeling" meets all applicable requirements, such as adherence to specifications in the device master record, correct parameter identification, agreement with the instruction manual, and of course, correct display of performance data. When reviewing or auditing labeling operations, it is wise to keep in mind that the Quality System regulation contains flexible requirements and thus allows flexibility in a quality assurance program. The degree of labeling control needed to satisfy the Quality System regulation varies considerably for different devices and operations. In order to avoid wasting money and increasing the cost of health care, manufacturers need to give considerable and prudent thought to the appropriate level of control needed for their operations. Information and guidelines presented in this chapter should aid manufacturers in making these decisions. The level of control needed should be reconsidered when products are added or changed. Likewise, the controls needed and success of the existing control program must be reviewed during QA system audits. Quality Systems Compliance

74 Over The Counter (OTC) Device Labeling
CCAC Quality System Basic Course Over The Counter (OTC) Device Labeling Principal Display Panel 21 CFR 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 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 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. Principal Display Panel 21 CFR 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. The area of the principal display panel is considered to be: In the case of a rectangular package, the height x width of one side; In the case of a cylindrical or nearly cylindrical package, 40% of height x circumference; or In the case of any other shapes, 40% of the total surface area of the container, unless a more prominent site exists. Statement of Identity 21 CFR The statement of identity of the device must be listed on the principal display panel. It must list the common name of the device followed by a statement of its principal intended action(s); Indications for use must be listed in the directions for use; and The statement must be in bold type, reasonably related in size to the most prominent printed matter on the display panel, and must be in lines generally parallel to the base of the package on which it rests. Net Quantity of Contents Statement 21 CFR 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, or size, which are described below: Count - If the declaration by count does not give accurate information as to the quantity, it shall be augmented by statements of weight, measure, or size; Measure - In cases of established customer usage and trade custom where units of linear measure or measure of area are used, they shall be augmented when necessary with statements of weight measure or size. Liquid measure is to be expressed in terms of the U.S. gallon of 231 cu. In. And quart, ping, and fluid ounce subdivisions, and shall express the volume at 68 degrees Fahrenheit; and Weight - Terms of weight are to be expressed in avoirdupois pound and ounce. Units of metric weight or measure are considered supplemental. The declaration may contain common or decimal fractions. Common fractions shall be reduced to their lowest terms. Placement - The declaration shall appear as a separate item on each principal display panel; and be separated by at least a space equal to the height of the lettering used in the declaration, from other information appearing above and below, and separated by at least twice the width of the letter "N" from labeling to the left or right. Quality Systems Compliance

75 Prescription Device Labeling
CCAC Quality System Basic Course Prescription Device Labeling Prescription Device 21 CFR 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
CCAC Quality System Basic Course 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
CCAC Quality System Basic Course FDA Actions for Mislabeling Warning Letters Mandatory Recall Injunctions to Stop Shipment Seizure Fines and Imprisonment Misbranding Section 502 of the FFDCA contains provisions on misbranding and false or misleading labeling. A device is misbranded if: Its labeling is false or misleading in any particular: It is in package form and its label fails to contain the name and place of business of the manufacturer, packer, or distributor; and an accurate statement of the quantity of the contents in terms of weight, measure, or numerical count; Any required wording is not prominently displayed as compared with other wording on the device, or is not clearly stated; Its label does not bear adequate directions for use; including warnings against use in certain pathological conditions; or by children where its use may be dangerous in health; or against unsafe dosage, or methods, or duration of administration or application; It is dangerous to health when used in the dosage or manner or with the frequency or duration prescribed, recommended or suggested in the labeling; or It does not comply with the color additives provisions listed under Section 706 of the Act. If the device's established name (if it has one) its name in an official compendium, or any common or usual name is not prominently printed in type at least half as large as that used for any proprietary name; If the establishment is not registered with FDA as per Section 510, has not device listed as per section 510(j), or obtained applicable premarket notification clearance as per Section 510(k); If the device is subject to a performance standard and it does not bear the labeling prescribed in that standard; If there is a failure or refusal to comply with any requirement prescribed under the FFDCA, Section 518 on notification and other remedies, or failure to furnish any materials or information requested by or under Section 519 on reports and records or under Section 522; or If there is any representation that created an impression of official approval because of the possession by the firm of an FDA registration number. Note: Previously, it was considered misbranding to have or premarket notification number. The Modernization Act repealed the restriction in Section 301(l) of the Federal Food, Drug and Cosmetic (FFD&C) Act, which prohibited reference to FDA approval in the labeling or advertising of medical devices that have an approved PMA or IDE. Quality Systems Compliance

78 CCAC Quality System Basic Course
FDA Legal Actions SEC [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
CCAC Quality System Basic Course Class Exercise- Labeling Review of Respironics REMStar® Heated Humidifier labeling for: Indications for use Contraindications Prescription Statement Description Corrective Actions Quality Systems Compliance

80 CCAC Quality System Basic Course
Complaints Quality Systems Compliance

81 Complaint Definitions
CCAC Quality System Basic Course 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

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Quality Systems Compliance

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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 Complaints from any source shall be equally addressed by and be processed according to the company complaint policy and procedure. The company should make certain that market, sales, engineering, manufacturing, regulatory, installation, and service personnel are trained to properly identify and report complaints. These employees shall be made aware of this requirement according to section (b). Quality Systems Compliance

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What to do Quality Systems Compliance

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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. Manufacturers of medical devices are required to report a device related death, serious injury or malfunction to FDA using FDA Form 3500A, within 30 calendar days after becoming aware of the event. However, if the event necessitates remedial action to prevent an unreasonable risk of substantial harm to public health, then a report shall be submitted within 5 work days. Reports shall also be submitted when FDA notifies a manufacturer that 5-day reports involving a particular type of medical device or type of event are required. The reporting process starts when an MDR reportable event is first recognized. Manufacturers are responsible for making sure their employees know how to recognize what may be reportable. Manufacturers should also emphasize that any employee may learn of an adverse event during a phone call, a sales visit, a professional conference, from correspondence received or from service/warranty orders. Individual Adverse Event Reports There are two types of individual adverse event reports that may be submitted by manufacturers. The 5 work day and 30 calendar day reports. The 5-day report (803.53) is for MDR reportable event(s) that require a remedial action to prevent an unreasonable risk of substantial harm to the public health or where FDA has specified that a 5-day report is needed. This situation may be identified by the manufacturer or FDA: If the manufacturer identifies the event and initiates a remedial action to prevent an unreasonable risk of substantial harm to the public health, a 5-day report is submitted instead of the 30-day report. Information not available within the five days should be provided in a supplemental report. If FDA identifies the event, the manufacturer will receive a written request directing them to file a 5-day report for all subsequent events of the same nature that involve similar devices for a specified time period. The FDA identification may be a result of its review of 30-day reports, inspection reports, user facility reports, etc. The 5-day period of reporting starts the day after any employee, who is a person with management or supervisory responsibilities over persons with regulatory, scientific, or technical responsibilities, or a person whose duties relate to the collection and reporting of adverse events, becomes aware that a reportable MDR event or events, from any information, including any analysis, necessitate remedial action to prevent an unreasonable risk of substantial harm to the public health. Quality Systems Compliance

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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

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FDA Audits Quality Systems Compliance

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FDA Audits Career Opportunities FDA Compliance Officer FDA Consumer Safety Officer Internal Auditor FDA Quality Systems Compliance

89 FDA Audits of a Device Manufacturer
CCAC Quality System Basic Course 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
CCAC Quality System Basic Course 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 Quality Systems Compliance

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Questions Quality Systems Compliance

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Test Quality Systems Compliance


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