Regulatory Class - Oct 10

Question 1

Parts of a 510(k)

Answer 1

Cover Sheet (FDA Form 3514)
Cover Letter
Table of Contents
User Fee Information
Certification of Compliance with ClinicalTrials.gov (FDA Form 3674)
Statement of Substantial Equivalence
Labeling
Advertising and Promotional Material
Comparative Information
Biocompatability Assessment
Truthful and Accurate Statement
Clinical Data
Shelf Life (and Sterilization)
Indication for Use Form
Financial Certification and/or Disclosure
Device Description
Executive Summary
Performance Testing
Software
Electromagnetic Compatibility (EMC) and Electrical Safety

Question 2

Parts of a PMA

Answer 2

Premarket Review Submission Cover Sheet (FDA Form 3514)
Medical Device User Fee Cover Sheet
Certification of Compliance with ClinicalTrials.gov (FDA Form 3674)
Applicant name and addresss
Table of Content
Summary Section
Description of Device
Performance Standards
Nonclinical Technical Data
Clinical Technical Data
Justification for Single Investigator (if applicable)
Bibliography
Device Sample
Proposed Labeling
Environmental Assessment or Exclusion
Financial Certification and/or Disclosure

Question 3

Parts of PMA section: Summary Section

Answer 3

Indications for Use
Device description
Alternative practices and procedures
Marketing history
Summary of studies

Question 4

Parts of PMA section: Description of device

Answer 4

Device
Functional Components
Properties relevant to diagnosis, treatment, cure or mitigation of disease
Methods, facilities, and controls

Question 5

Quality System Regulations (QSR)

Answer 5

Device GMPs
Apply to device development and manufacturing process (Class II and III)
Apply to manufacturing (Class I)
Does not apply to research devices

Goal is to create a self-correcting system that reliably produces robust device designs and production methods, ensuring they perform consistent with their intended use

Question 6

QSR: Management Responsibility

Answer 6

Establish quality policy (ensure it’s understood, implemented, and maintained)
Ensure adequate organizational structure
Appoint management representative to ensure quality system maintained and report to executive management (quality system audits)
Establish quality plan and quality system procedures

Management review QSR and oversee SOPs

Question 7

QSR: Personnel Requirements

Answer 7

Sufficient personnel (education, background, training and experience)
Identify training needs
Personnel trained to adequately perform their assigned responsibilities
Training should be documented

SOPs should identify training methods and policies

Question 8

QSR: Design Controls

Answer 8

Establish plan describing design and development activities and define responsibility for implementation (review, update, and approve as design/development progress)
Procedures required to ensure specified design requirements are met
Applies to Class II and III devices and some Class I

Question 9

QSR: Document Controls

Answer 9

Procedures required to control documents (New procedures and/or documents must be reviewed/approved
Approval must be documented
Documents available at all relevant locations
Changes to documents must be reviewed/approved
Obsolete documents removed to prevent unintended use

New documents or SOPs need way to determine which is the official document (usually special ink or signature)

Question 10

QSR: Document Controls: Change records must include:

Answer 10

Description of change
Identification of affected documents
Signature/date of approval
Effective date (When document is released to personnel)

Question 11

QSR: Purchasing Controls

Answer 11

All received products and services meet requirements

Applies to suppliers, contractors and consultants (make sure they are qualified)
Must evaluate suppliers; Define control over product, services, suppliers; Maintain records of acceptable suppliers

Maintain purchasing documents, including agreement that suppliers notify manufacturer of product/service changes

Question 12

QSR: Identification and Traceability

Answer 12

Procedures for identifying product at all stages: receipt, production, distribution, installation (to prevent mix-ups)

Procedures for identifying finished devices or appropriate components by control number of unit, lot or batch (to facilitate corrective action; ex. surgical implants)

Question 13

QSR: Production and Process Controls

Answer 13

Ensure that devices conform to specification
Procedures for changes to specification, methods, processes or procedures (Changes approved, verified, validated prior to implementation and documented)
Environmental control (temperature, humidity)
Personnel (health, cleanliness, clothing)
Contamination control (equipment and product)
Buildings (suitable design and sufficient space)
Equipment (specified requirements, appropriate for use, maintained, inspected, adjusted)
Automated Processes (validate computer software for its intended use)

Question 14

QSR: Inspection, measuring and test equipment

Answer 14

Suitable for intended purposes and capable of producing valid results
Need procedures for: calibration, inspection, maintenance

Question 15

QSR: Process Validation

Answer 15

Establishing by objective evidence that a process consistently produces a result meeting predetermined specification
DOne if process cannot be fully verified by inspection and testing (ex, if testing would destroy product)
Performed by qualified personnel
All procedures and validation records maintained

Question 16

QSR: Acceptance activities

Answer 16

Need procedures and records for:
Receiving - acceptance (inspection, testing, verification) of incoming product
In-process - ensure in-process product controlled until inspection, test, or verification activities are completed
Final acceptance - ensure each production lot or batch meets acceptance criteria

Finished devices quarantined and controlled until released

Question 17

QSR: Acceptance records

Answer 17

Activities performed, dates, results
Signature of person(s) conduction acceptance activities
Equipment used

Question 18

QSR: Acceptance Status

Answer 18

Conformance or nonconformance with acceptance criteria
Maintained throughout manufacturing, packaging, labeling, installation, and servicing
Ensure only product that has passed is distributed, used, or installed

Question 19

QSR: Nonconforming Product

Answer 19

Establish procedures to control product that does not meet specifications; document evaluation and investigation of nonconforming product
Review and disposition of nonconforming product
Rework - including retesting and re-evaluation

Question 20

QSR: Labeling and Packaging

Answer 20

Maintain procedures to ensure labeling integrity; document labeling inspection and release; Control labeling storage and operations to prevent mix-ups; Ensure packaging protects device from damage during processing, shipping, storage, and handling

Question 21

QSR: Handling and Storage

Answer 21

Procedures to prevent mix-ups, damage, deterioration, contamination during handling

Procedures to control storage areas and stock rooms:
Prevent mix-ups, damage, deterioration, contamination
Ensure obsolete, rejected, deteriorated product is not used or distributed
Authorize product movement to/from storage areas and stock rooms

Question 22

QSR Controls: Distribution and Installation

Answer 22

Procedures to ensure only devices approved for release are distributed; prevent expired or deteriorated devices from distribution; maintain records of initial consignee

Maintain installation instructions and test procedures; installer document inspection and test results that demonstrate proper installation

Question 23

Device Master Record (DMR)

Answer 23

For each type of device

Procedures and specification for finished device: device, production process, packaging and labeling, installation, maintenance specification

Question 24

Device History Record (DHR)

Answer 24

Production history of a finished device or production-run of devices

Manufacturing documentation, testing results, labeling documentation, release/approval documentation

Question 25

Corrective and Preventative Action (CAPA)

Answer 25

Corrective action - correct product problem that has been identified Preventative action - prevent a potential problem that could occur in the future Data from: internal audits; incoming, in-process, and final QC testing; service and repair records; customer feedback Verify and validate effectiveness of CAPA; need to complete testing periodically to confirm that preventative actions are successful

Question 26

QSR: Complaint Files

Answer 26

Complaint - any written, electronic, or oral communication that alleges deficiencies in a device after it is released for distribution; deficiencies in: identity, quality, durability, reliability, safety, effectiveness, performance Maintain procedures for receiving, reviewing, evaluating complaints; records of investigations, determine if reportable to FDA

Question 27

QSR: Servicing

Answer 27

Procedures required Service reports must be reviewed to determine whether event represents adverse event reportable to FDA

Question 28

QSR: Statistical Techniques

Answer 28

Procedures for identifying valid statistical techniques for control of manufacturing processes and product characteristics Sampling plans based on valid statistical rationale

Question 29

QSR Records

Answer 29

Records must be maintained for time equivalent to design and expected life of device (a minimum of 2 years from date of release for commercial distribution) Internal audit reports (management review, quality audit, supplier audit) are not subject to retention requirement Not required to be provided to the FDA, but must certify that reviews and audits were performed

Question 30

Medical Device Classification

Answer 30

Class I - lowest risk; general controls, may require only listing it with the FDA Class II - moderate risk; general and special controls; most require 510(k) Class III - highest risk; general controls; PMA

Question 31

General Controls

Answer 31

Baseline requirements apply to all medical devices Quality System Regulations: manufacturing (cGMPs) and recordkeeping Establishment registration Device listing Reporting adverse events Labeling, advertising, and promotional materials requirements

Question 32

Special Controls

Answer 32

Performance standards - mandatory or voluntary Specific FDA guidance documents Special labeling requirements Postmarketing surveillance

Question 33

510(k) - Required for:

Answer 33

Significantly changed or modified in design, components, method of manufacture (could significantly affect safety or effectiveness) Major change in intended use Custom devices are exempt: must not be generally available for purchase, not advertised, only for a specific person and named in order by a physician

Question 34

Substantially Equivalent (SE)

Answer 34

Must demonstrate substantial equivalence to predicate device (class I or II device, cleared thru 510(k), legally marketed in US) SE in: Intended use; technological characteristics (not identical but no new questions of safety or effectiveness) Specifically demonstrate SE with: intended use, design, materials in construction, biocompatability, performance, safety, labeling, standards

Question 35

Traditional 510(k)

Answer 35

Most commonly used; device must not be a modification of manufacturer's own cleared device 90 day review

Question 36

513(g) Submission

Answer 36

``` Request for designation of device classification Company writes description of device and makes an argument for the class they think it is ``` Helpful with Class I devices, since they only need to be listed, to make sure not a Class II device requiring a premarket notification 60 Day review

Question 37

Special 510(k)

Answer 37

Modification of manufacturer's own device No new indication for use; No change to fundamental scientific technology (Modification to operating principles or mechanism of action) Requires design controls and risk analysis Cannot file until all design controls are in place 30 Day Review

Question 38

De Novo 510(k)

Answer 38

Low risk Class III products that are NSE to predicate device Within 30 days after receiving a NSE determination, sponsor may request a risk-based classification determination

Question 39

510(k) Cover Letter

Answer 39

Type of submission, device name, submitter, contact person name, title, and phone number, preference for continued confidentiality, class, FDA review panel, product code

Question 40

Indications for Use Statement

Answer 40

Specific indications, clinical settings, target population, anatomical sites Must be consistent with labeling, advertising and instructions for use Will be available on FDA's website within 30 days of SE letter

Question 41

510(k) Summary or Statement

Answer 41

Brief summary of the device and safety and effectiveness information that forms the basis for SE determination If you don't provide the summary, you must submit a statement saying you have 30 days to redact the whole 510(k) submission when a request is made in writing

Question 42

510(k): Truthful and Accurate Statement

Answer 42

Signed and dated by a responsible person at the sponsor (not a consultant) Judicial action can be taken if false or misleading info is submitted Usually, Director or VP of Quality or Regulatory department sign the truthful or accurate statement

Question 43

510(k): Declarations of Conformity and Summary Reports

Answer 43

to standards, quality, or guidance documents For abbreviated 510(k) submission: info regarding conformity to any standards, summary reports recommended in any relevant device-specific guidance For Special 510(k): info regarding design control activities

Question 44

510(k): Executive Summary

Answer 44

Concise description of the device (indications for use and technology) Device comparison table Concise summary of performance testing

Question 45

510(k): Device Description

Answer 45

Operating principles, photos, engineering drawings, diagrams, schematics Performance specifications and device design requirements Identify all models, accessories, or components included in the submission List all patient contacting components and respective materials Very detailed

Question 46

510(k): Substantial Equivalence Discussion

Answer 46

Detailed comparison with the predicate device sufficient to demonstrate substantial equivalence (indications for use, technology, and performance specifications)

Question 47

510(k): Proposed Labeling

Answer 47

Packaging, stickers, operator's manual, instructions for use, patient brochures, promotional materials promotional materials and patient brochures are not likely to be included as they aren't typically made until device is marketed

Question 48

510(k): Sterilization and Shelf-life

Answer 48

Accelerated aging data; real-time studies, validation

Question 49

510(k): Biocompatibility assessment

Answer 49

if device includes patient-contacting materials difference requirements for devices that contact the surface of the body versus invasive contact or implantables Know short-term and long-term or specific toxic effect and effects on reproduction Can pass on the bioavailability assessment, if the exact same materials are used in the predicate device

Question 50

510(k): EMC and Electrical Safety

Answer 50

if the device includes an electric component, evaluate device's EMC Emission (interference with electronic products) Immunity (interference with device performance created by emissions from other electronic products)

Question 51

510(k): Performance Testing (Bench and Animal Studies)

Answer 51

``` List specific tests conducted Describe each test protocol-objective, test articles used, test methods and procedures, study endpoint and criteria for assessment Summarize the results Describe analysis Discuss conclusions ``` Can be extensive if no clinical trial data; should compare to predicate device, standards, or guidelines if possible

Question 52

510(k): Performance Testing (Clinical)

Answer 52

FDA considers alternatives to clinical studies if supported by adequate scientific rationale Provide the clinical protocol - objective of the test, test methods and procedures, study endpoints (safety and effectiveness), statistical methodology Discuss study results, analyses performed and conclusions IRB and informed consent apply. If study is significan risk, must use an IDE

Question 53

Abbreviated 510(k)

Answer 53

Relies on guidance documents, performance standards to demonstrate substantial equivalence Submission must include Declaration of Conformance to FDA-recognized performance standards Typically less info, specific data not required if providing summary of conformance to special controls (guidance, standards) 90 Day Review

Question 54

FDA Review of 510(k)

Answer 54

FDA acknowledges receipt of 510(k) and assigns a 'k number' to use for all future correspondence 'K number' - first 2 digits are year submitted May request additional info, which can reset the review clock, sponsor must respond in 30 days or the FDA considers the 510(k) withdrawn (can ask the FDA for an extensions, up to 2) Does not approve, but clears device for marketing FDA acknowledges that devices are or are not substantially equivalent to legally marketed product; does not determine if devices are safe or effective

Question 55

PMAs: Used for

Answer 55

Devices that are not substantially equivalent o any advice cleared through 510(k) Also, Class III devices that support or sustain human life; substantial importance in preventing impairment of human health; present potential unreasonable risk of illness or injury Must demonstrate safety and effectiveness

Question 56

PMA: Summary Section

Answer 56

Indications for use Device description: function, scientific concepts that form the basis for the devices, and significant physical and performance characteristics Alternative practices and procedures: for diagnosing, treating, preventing, curing, or mitigating the disease or condition Marketing history (foreign and US): lit all countries where device has been marketed or withdrawn because of safety or effectiveness; Most are first marketed in Europe Summary of studies: results of technical data (nonclinical and clinical studies); Objective of each study, experimental design, how data were collected and analyzed, brief description of findings and conclusions Discuss how the data constitutes valid scientific evidence and a determination of safety and effectiveness for its intended use

Question 57

PMA: Description of Device

Answer 57

Device (including pictorial representations) Functional components or ingredients Properties of the device relevant to the diagnosis, treatment, prevention, cure, or mitigation of a disease or condition Principles of operation of the device Methods, facilities, and controls used in manufacture, processing, packaging, storage, and installation of the device (consistent with cGMPs)

Question 58

PMA: Performance standards

Answer 58

Justify any deviations from performance standards or voluntary standards

Question 59

PMA: Technical Data - nonclinical

Answer 59

Results of the nonclinical laboratory studies Statement that each study was conducted in compliance with GLPs or justification for noncompliance

Question 60

PMA: Technical Data - clinical

Answer 60

Results of human clinical studies including: protocols, number of investigators and subjects, inclusion/exclusion criteria, demographics, safety and effectiveness data, patient discontinuation, device failures and replacements, tabulations of data and copies of CRFs for each subject who died or who did not complete the investigation, statistical analyses Statement that each study was conducted in compliance with IRB, informed consent, and IDE requirements or justification

Question 61

Foreign Clinical Data

Answer 61

Must be conducted in accordance with Declaration of Helsinki and local requirements Applicable to US patient population Standard of care and medical practice similar to US Competent investigators Data and source documentation available for audit by FDA

Question 62

PMA: Justification for Single Investigator

Answer 62

Data sufficient to demonstrate safety and effectiveness and ensure reproducibility of test results

Question 63

PMA: Bibliography

Answer 63

Al published reports (adverse or supportive) that concern safety and effectiveness Other data, info, or reports relevant too safety and effectiveness

Question 64

PMA: Proposed Labeling

Answer 64

Instructions for use, advertising, package labels

Question 65

PMA: Environmental assessment or exclusion

Answer 65

Not usually required if the device is of the same type and for the same use as a previously approved device

Question 66

Modular PMA

Answer 66

Contents broken down into well-delineated components and each module is submitted to FDA as soon as it is completed (manufacturing, software validation, preclinical, clinical, labeling) Recommended for products in early stages of clinical study but when device design is not likely to change Shell-outline of PMA and plan for submission of the modules (developed individually with the manufacturer for a specific device) FDA reviews each module separately - 90 day review When final module is submitted, PMA is filed - 180 day review

Question 67

PMA Amendments

Answer 67

Any new safety and effectiveness information learned about the device From ongoing or completed studies that may affect safety and effectiveness or statements of contraindications, warnings, precautions, and AEs in draft labeling Submitted 3 months after the filing date, or following the receipt of an approvable letter

Question 68

FDA Review of PMA

Answer 68

Filing PMA occurs within 45 days after a PMA is received by the FDA Date of filing starts the 180 Day review period Timeframe not typically extended without major amendment Within 100 days of filing, sponsor can meet with FDA to discuss the PMA

Question 69

Reasons FDA may refuse to file PMA

Answer 69

``` PMA is incomplete Justification for omission of required info is inadequate 510(k) processing for the same device Contains a false statement Financial disclosure is missing ```

Question 70

Advisory Panels

Answer 70

Generally used with all PMAs for the first of a kin device; devices raises questions that FDA has not addressed previously Includes 1 nonvoting industry rep and 1 nonvoting consumer rep Hold public meeting to discuss findings, review parts of the PMA, panel recommendation are not binding

Question 71

Quality System Inspection

Answer 71

Scheduled following FDA determination that PMA design and manufacturing sections demonstrate compliance Assess manufacturer's ability to manufacture device; consistent with PMA; compliance with QSR

Question 72

Bioresearch Monitoring (BIMO) Inspection

Answer 72

Clinical sites, sponsor, CROs, IRBs Site selection based on: contribution to pivotal data, history of compliance, safety issues identified in PMA, concerns raised by reviewers

Question 73

Response to PMA

Answer 73

Approval order - FDA approves the application on the basis of draft final labeling, (copy of final printed labeling must be submitted to FDA before marketing) Approvable letter: specific additional info must be submitted or specific conditions are agreed to by the applicant; letter describes the requirement for approval Not approvable letter: significant deficiencies in the application Denying Approval