ATELIER R DM - CAP'Tronic · Abbreviated 510(k) 29 • Modified versions of a sponsor’s cleared marketed device (via 510(k)) • No alteration to intended use or fundamental technology

February 19, 2014

ATELIER RÈGLEMENTAIRE DM US/CANADA

Atlanpole Biotherapies 20 février 2014, Angers

2 Overview VCLS

A team of seasoned healthcare product developers who advise on product development, and help you design regulatory strategies, interact with regulators & support product registration

• 15 years of assistance to biotech, medtech & healthcare industry

• 70 employees working as a single scientific & regulatory team

• We create innovative approaches to expedite programs based on experience

• Our expertise & operational capabilities complement your own resources

• We actively contribute to forthcoming regulation & guidance documents

3 Inter-connected Locations

4

USA • Definitions • Roles and responsibilities of stakeholders, regulations and guidance documents • Product classification and market clearance/approval procedures • Regulatory Path to Submissions • Non clinical and clinical evaluation • Medical image management devices and software • Post market requirements

Canada • Regulations and guidance documents • Medical device license requirements • Approval process • Post-approval requirements

Presentation overview

USA

Definitions

6

Any instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, including any component, part or accessory, which is – (1) Intended for use in diagnosis, cure, mitigation, treatment or prevention

of disease (2) Intended to affect the structure or any function of the body which does

not achieve its primary intended purpose through chemical action within or on the body and which is not dependent upon being metabolized for the achievement of any of its principle intended purposes.

Source: Medical Device Amendments of 1976

Medical Device Definition

USA

Stakeholders, regulations and guidance documents

8

Center for Devices and Radiological Health (CDRH)

9

Medical Devices Legislation

• Investigational Device Exemption (IDE) – 21 CFR Part 812

• Premarket Notification Procedures [510(k)] – 21 CFR Part 807 Subpart E

• Premarket Approval (PMA) – 21 CFR Part 814

• Quality System Regulation (QSR) – 21 CFR Part 820

• Labeling – 21 CFR Part 801

• Establishment Registration and Medical device Listing – 21 CFR Part 807

• Medical Device Reporting – 21 CFR Part 803

http://www.fda.gov/

10

Cross-Center Guidance Documents • The New 510(k) Paradigm • Interactive Review for Medical Device Submissions: 510(k)s, Original PMAs,

PMA Supplements www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm081752.htm

Draft Guidance for Industry and FDA Staff: ex.: • General principles of software validation

http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ ucm081752.htm

• Class II Special Controls Guidance Document: Transcutaneous Electrical Nerve Stimulator with Limited Output for Pain Relief - April 5, 2010

www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm198585.htm

Medical Device Guidelines

USA

Product classification and market clearance process

12

Classification is assigned based upon:

• level of risk posed to patient

• subsequent need of regulatory control needed to safely market the device

Medical Device Classification

13

Device classification factors: Product intended use Product indications for use Product risk profile

Classification procedure Search in FDA classification database (by device name, device panel – Ear,

Nose & Throat) Identify corresponding CFR to obtain:

Device class Applicable controls (Specials) Exemption confirmation (as applicable)

Qualification & Classification

14 Medical Device Classification

15

General Controls Good Manufacturing Practices/Quality System Requirements* Labeling Medical Device Reporting FDA Registration and Listing

Most Class I devices are exempt from pre-market review by FDA (21 CFR 862-892) no pre-market clearance by FDA required before distribution (listing) *Except those specifically exempted

Class I Requirements

16

Applies to all device classes

• Devices must not be adulterated or misbranded

• Establishment registration and listing by manufacturer and distributer

• Manufacturing according to Quality System Regulations

• Device labeling requirements

• Report adverse events (AE) identified by user, manufacturer and/or distributor

www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Overview/GeneralandSpecialControls/ucm055910.htm

General Controls

17

All requirements applicable to Class I Devices

Special Controls (product specific guidelines and guidances)

510(k) Premarket Notification • Some class II devices are exempt from this requirement no pre-

market clearance by FDA prior distribution (listing) http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpcd/315.cfm

Class II Device Requirements

18

Apply to special device classes only (i.e. class II and III) and can include: • Additional labeling requirements

• Mandatory performance standards

• Quality System Regulations (QSR) Compliance – QSR inspection

• Post-market safety surveillance requirements

• Additional controls may be determined on a case by case basis

http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Overview/GeneralandSpecialControls/default.htm

Special Controls

19

All requirements applicable to Class I Devices

Special Controls (product specific guidelines and guidances)

FDA Inspection

Premarket approval (PMA)

Class III Requirements

20

Initial importers to register with FDA (annual update)

Registration and Listing can be done by FDA’s Unified Registration and Listing System (FURLS)/ Device Registration and Listing Module (DRLM)

Miscellaneous Items

21

Quality System Regulation (QSR) Compliant system to be established (21 CFR 820)

• Change Control processes • CAPA (corrective and preventive actions) • Design Controls • Manufacturing validation and controls • Management Review • Internal Audit • Additional elements as defined in QSR

Quality management system

USA

Regulatory Paths to Submission

23

Informal and non-binding Purpose is to obtain early feedback on specific questions from FDA. Situations include: • Before conducting clinical, nonclinical, or analytical studies, or

submitting an IDE, or marketing application • Before submitting a marketing application

Feedback from FDA provided as in-person meeting, teleconference or written response (~60 days) Previously referred to as pre-IDE meetings

Pre-Submission Meeting

24

Recommended Information include: • Cover Letter • Table of Contents • Device Description • Proposed Intended Use/Indications for Use • Previous Discussions or Submissions • Overview of Product Development • Specific Questions • Mechanism for Feedback • Other Logistical Information

Pre-Submission Meeting

25

Marketing clearance - 510 (k)

• Premarket Notification specified in: o Section 510(k) of The Food Drug and Cosmetic Act (FD&C Act) o Regulations 21 CFR 807 Subpart E

• Aiming at: o Introducing a device to the market for the first time o Change in intended use for a marketed device o Making significant modification to a marketed device

• 90-day Review Process

• User Fees (2013) for Traditional 510(k) is $4,960 If qualify as a Small Business: $2,480

• Determination based upon Substantial Equivalence (SE) to an approved device (predicate) http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/510kClearances/default.htm

26

• Based upon Substantial Equivalence (SE) to a predicate device o Demonstrate device is at least as safe and effective to a legally marketed

device that is not subject to PMA. o Based on similarity of

o intended use, o features : design, energy used or delivered, materials, chemical composition

manufacturing process, performance, safety, effectiveness, labeling, biocompatibility, standards, etc.

Or at least difference(s) do not raise safety or effectiveness questions o FDA letter of SE allows market distribution

• 90 day FDA Review o Request for additional data may extend the clock

Traditional 510(k)

27 510(K) - Comparison to Predicate Device

28

• Simplified procedure for clearance when: ο A guidance documents exists ο A special control has been established, or ο FDA has recognized a relevant consensus standard (approx. 400

standards) • Test reports are not required • Declaration of Conformance to the specifications in the

reference standards • 90 day review http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/PremarketSubmissions/PremarketNotifi

cation510k/ucm134574.htm

Abbreviated 510(k)

29

• Modified versions of a sponsor’s cleared marketed device (via 510(k))

• No alteration to intended use or fundamental technology

• Design controls and risk analysis are required

• Processed in 30 days by the FDA

http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/PremarketSubmissions/PremarketNotification510k/ucm134573.htm

Special 510(k)

30

510(k) - FDA Recommended Decision Tree

31

Class I or II devices without a predicate are automatically classified as class III De novo 510(k) process allows these low risk devices to be re-classified as class II:

• Requires an NSE letter from FDA after 510(k) is submitted • Currently not widely used procedure (need clear justification) however utilized

increasingly Request a risk-based classification from FDA into Class I or II (within 30 days from NSE letter) Similar level of product information as a 510 (k) Clearance 60 day Review Process by FDA

• If class I or II agreed market approval granted immediately • If class III required PMA to be submitted

*FDA Guidance Document: New Section 513(f)(2) - Evaluation of Automatic Class III Designation, Guidance for Industry and CDRH Staff, 1998 *Draft Guidance for Industry and Food and Drug Administration Staff - De Novo Classification Process (Evaluation of Automatic Class III Designation) from Oct 2011 no longer available * Due to the FDASIA Until the new draft de novo guidance is published, please contact 510(k) Staff

De Novo 510(k) process

32

The manufacturer should check for the: • logical presentation of the data; • scientific soundness of the test and data analysis; • relevance of the test program to the device and the intended use; and • completeness of the summary report of the tests or studies.

To obtain prior to proceed: • Classification of device • Predicate device(s) • Final draft labeling • Specifications including engineering drawings, photos, etc. • Performance data such as bench, animal, or clinical testing (if applicable) • Sterilization information (if applicable) • Guidance document(s) specific to your device type, if it exists

510(k) content

33

Sections in a Traditional or Abbreviated 510(k) :

• Medical Device User Fee Cover Sheet (Form FDA 3601) • CDRH Premarket Review Submission Cover Sheet • 510(k) Cover Letter • Indications for Use Statement • 510(k) Summary or 510(k) Statement • Truthful and Accuracy Statement • Class III Summary and Certification • Financial Certification or Disclosure Statement • Declarations of Conformity and Summary Reports • Executive Summary • Device Description • Substantial Equivalence Discussion • Proposed Labeling • Sterilization and Shelf Life • Biocompatibility • Software • Electromagnetic Compatibility and Electrical Safety • Performance Testing – Bench • Performance Testing – Animal • Performance Testing – Clinical • Other

510(k) content

Screening Checklist for Traditional/Abbreviated Premarket Notification [510(k)] Submissions based on Guidance for Industry and FDA Staff

34

Pre-Market Approval (PMA) – for high risk MD

35

Generally for Class III devices Regulations found in 21 CFR 814 Requires a 180-day FDA Review Period User Fee (2013) for an Original PMA is $248,000

(If qualify as a Small Business: $62,000)

No single FDA Guideline is available Multiple guidelines available on FDA website

http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/PremarketSubmissions/PremarketApprovalPMA/ucm050289.htm#req

Pre-Market Approval (PMA)

36

PMA Process • Only applies to Class III devices • Classification requires PMA • Device found Not Substantially Equivalent (NSE) • "New" - no basis for "SE" • Needs proof of reasonable assurance of safety and effectiveness

(preclinical and/or clinical trials) • PMA Application methods

ο Traditional PMA ο Modular PMA

Pre-Market Approval (PMA)

37

Traditional PMA • Complete application is submitted to FDA all at once. • Includes all required contents:

ο device description, ο intended use, ο clinical studies, ο manufacturing methods, ο etc.

• Requires a Pre-Approval Inspection • 180 day FDA review time.

Pre-Market Approval (PMA)

38 Modular PMA • The application is broken down into well-delineated components (modules)

and each one is submitted when completed.

• A “PMA Shell” or plan is developed and submitted. (It outlines the modules and their schedule)

• Each module is stand alone. (General review is 90 days for each module) • The PMA is viewed as a compilation of all modules, such as manufacturing and

clinical. • This method is recommended for products that are in the early stages of

clinical study but not for those when the design is likely to change.

Pre-Market Approval (PMA)

39

PMA review process:

1. Administrative and limited scientific review by FDA to determine completeness (filing review)

2. In-depth scientific, regulatory, and Quality System review by FDA personnel

3. Review and recommendation by advisory committee (panel review if appropriate)

4. Final deliberations, documentation, and notification of FDA decision.

Pre-Market Approval (PMA)

40

• PMA Approval Criteria: ο Evidence of safety and efficacy which includes adequate and well

controlled trials

ο FDA Advisory Panel acceptance

ο Successful Bioresearch Monitoring Inspection (BIMO) and Quality System Inspection

Pre-Market Approval (PMA)

41

PMA Approval timing: • 45 day administrative review preliminary to “filing” of PMA • 180 day initial review after filing (Traditional PMA) • Overall approx 1-2 years (FDA review + company response time)

Post-approval studies possible

Pre-Market Approval (PMA)

42

Complete description of the device Complete description of the components • Photographs • Engineering drawings of the device

Description of the principles of operation of the device (including components) and properties relevant to clinical function Detailed description of the methods, facilities and controls used to manufacture Prepared labeling, advertising literature, any training material

Software documentation Statistical analyses Sterility information Biocompatibility information Extensive clinical studies Reports of key nonclinical studies Bench tests Published and unpublished literature Bibliography of all published reports known concerning the device’s safety or effectiveness

Pre-Market Approval (PMA) content

43

PMA Dossier – Key elements • Summary of Data and Information

• General Information

• [Product] – Claims

• Device Description – Functional Components and Their Purpose

• Description of Device Properties Relevant to [Treatment]

• Principles of Operation

• Alternative Practices and Procedures

Pre-Market Approval (PMA) content

44

PMA Dossier – Key elements • Summary of Data and Information

• Marketing History

• Potential Adverse Effect of the Device on Health

• Summary of Studies

• Conclusions Drawn from Studies

• References

• Description of Methods Used In, and Facilities and Controls Used For, the Manufacture, Processing, Packaging, Sterilization, and Storage of the Device

Pre-Market Approval (PMA) content

45

PMA Dossier – Key elements • Technical section

• Nonclinical Supporting Studies

• Clinical Investigation

• Summaries of Studies

Pre-Market Approval (PMA) content

USA

Non clinical and clinical data

47

Non clinical Evaluation

Same as for Europe Pre-Clinical Studies • Objective: Product safety/performance verification • Types: bench testing, animal testing: proof of principle, biocompatibility • Regulatory framework: GLP highly recommended and mandatory for

toxicological studies Standards (ISO, EN….), “transversal” or « technical » per type of product • Serie ISO 5841: Implants for surgery : Cardiac pacemakers

Series EN ISO 10993: Biological evaluation of medical devices. • EN ISO 10993-1:‘Guidance on Selection of Tests’

48

48 of 68

Durations: Limited: < 60 min. Prolonged: <= 30 days Permanent: > 30 days

49

Clinical Evaluation Non-Significant Risk (NSR) vs. Significant Risk Studies (SR) IDE- Investigational Device Exemption, 21 CFR 812 IRB- Institutional Review Board, 21 CFR 56 ISO 14155: Clinical Investigation of Medical Devices for Human Subjects

• Part 1: General Requirements • Part 2: Clinical Investigation Plans

50

NSR studies: • Approved devices studied within claimed indications • No FDA approval required, but IRB shall review protocols

o Allows a clinical study to proceed without an IDE approved by FDA o Provides intermediate controls without FDA oversight o IRB must concur with determination, approve protocol/consent form to proceed

SR studies: • Involve highly invasive devices, risky procedures and/or

frail patients • Require IDE approved by FDA before initiation

o Generally not applicable to Class II / III devices o 30- day review period by CDRH

http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/InvestigationalDeviceExemptionIDE/ucm046706.htm

Clinical evaluation

51

• To determine if study approval is required sponsor must judge if the study is a NSR or a SR to the patients

o Consult FDA if determination is not straight-forward

• IRB must agree with sponsor determination

Clinical evaluation

52

Investigational Device Exemption (IDE) • Required for Significant risk studies with medical devices

• Comparable to the Investigational New Drug Application (IND) for

drugs or biologics

• 30-day review period by the CDRH

http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/InvestigationalDeviceExemptionIDE/

ucm046706.htm

Clinical evaluation

USA

Medical image management devices and softwares

54

Sec 892.2050, Class II (LLZ)

Picture archiving & com. systems

Sec 892.2040, Class II (LMC)

Medical image hardcopy device

Sec 892.2030, Class II (LMA)

Medical image digitizer

Sec 892.2020, Class I (LMD)

Medical image communication device

Sec 892.2010, Class I (LMB)

Medical image storage device

Electronic storage and retrieval functions for

medical images (devices with magnetic

& optical discs, magnetic tape….)

Electronic transfer of medical image data

between medical devices

(modem,interfaces, …)

Conversion of analog medical image to digital

format (frame grabbers,

scanners-lasers, …)

Production of printed record of medical image, including

associated identification information

(cameras, printers…)

One or more capabilities relating to

the acceptance, transfer, display,

storage and digital processing of medical

images (complex structure + image manipulation,

compression….)

yes yes yes yes yes

No or not only

US Classifications for Medical Image Management

55 Class I products

Current classification, product code Class I – Medical image storage device - LMB

Regulation number Sec. 892,2010 Medical image storage device (a)Identification. A medical image storage device is a device that provides electronic storage and retrieval functions for medical images. Examples include devices employing magnetic and optical discs, magnetic tape, and digital memory. (b)Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to 892.9. [63 FR 23387, Apr. 29, 1998; 63 FR 44998, Aug. 24, 1998, as amended at 65 FR 2323, Jan. 14, 2000]

Applicable harmonized standard and guidance documents

• Guidance for the Submission of Premarket Notifications for Medical Image Management Devices

56 Class II products

Classification, product code Class II - System, image processing, radiological - LLZ

Regulation number Sec. 892.2050 Picture archiving and communications system. (a)Identification. A picture archiving and communications system is a device that provides one or more capabilities relating to the acceptance, transfer, display, storage, and digital processing of medical images. Its hardware components may include workstations, digitizers, communications devices, computers, video monitors, magnetic, optical disk, or other digital data storage devices, and hardcopy devices. The software components may provide functions for performing operations related to image manipulation, enhancement, compression or quantification. (b)Classification. Class II (special controls; voluntary standards--Digital Imaging and Communications in Medicine (DICOM) Std., Joint Photographic Experts Group (JPEG) Std., Society of Motion Picture and Television Engineers (SMPTE) Test Pattern). [63 FR 23387, Apr. 29, 1998]

Applicable harmonized standard and guidance documents

• NEMA PS 3.1 - 3.20 (2011) Digital Imaging and Communications in Medicine (DICOM) Set • IEC/ISO 10918-1:1994 Technical Corrigendum 1:2005 Information technology -- Digital compression and

coding of continuous-tone still images - Part 1: Requirements and guidelines • NEMA XR 22-2006 "Quality Control Manual" Template for Manufacturers of Displays and Workstations

Labeled for Final Interpretation in Full-field Digital Mammography • NEMA XR 23-2006 "Quality Control Manual" Template for Manufacturers of Hardcopy Output Devices Labeled

for Final Interpretation in Full-field Digital Mammography • Guidance for the Submission of Premarket Notifications for Medical Image Management Devices • Guidance for Industry and FDA Staff: Display Accessories for Full-Field Digital Mammography Systems-

Premarket Notification (510(k)) Submissions • Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices

57

FDA Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices Software devices subject to 510(k), PMA, IDE or HDE • Software based control of medical devices • Sand alone software applications • Softwares for installation in general purpose computers • Dedicated hard/software medical devices • Accessories composed of or containing softwares

Level of concern

58 Level of concern (2)

Products Level of concern

Major - if a failure or latent flaw could directly result in death or serious injury to the patient or operator. The level of concern is also Major if a failure or latent flaw could indirectly result in death or serious injury of the patient or operator through incorrect or delayed information or through the action of a care provider. - Blood establishment computer software - Combination to drug / biologic - Accessory to MD with major level of concern - Failure could result in death or serious injury / patient or user (life sustaining, high level of energy, delivery of therapy, diagnostic, vital signs)

Moderate - if a failure or latent design flaw could directly result in minor injury to the patient or operator. The level of concern is also Moderate if a failure or latent flaw could indirectly result in minor injury to the patient or operator through incorrect or delayed information or through the action of a care provider. - Accessory to MD with moderate level of concern - Failure (prior mitigation) could result in minor injury / patient or user - Failure/latent design flaw could lead to erroneous diagnostic or delay in medical care

Minor - if failures or latent design flaws are unlikely to cause any injury to the patient or operator.

59

Manipulation of images, files and films • Define clear requirements and controls for measurements, modifications, data inclusion,

image quality… having an impact on the health professional analysis and decision • Need of validation of tools for decision making process (choice & qualification of photos

and texts, quality of pictures, accuracy and reproducibility of measurements etc…), including clinical trial data comparing diagnostic based on device use versus current State-of-Art diagnostic

Control - Qualification of stakeholders (based on diploma, national registry number for professional health,...?) for:

• Health professionals / users (log in with Professional Organization Number for example, recording of qualification);

• Developers, Advisor / Company’s staff involved • If forum, medical information requirements to be fulfilled • Access and modification controls

Level of concern may be increased (at least moderate, even major if life-threatening therapeutic area)

Limit(s) towards diagnostic purpose

USA

Post market requirements

61

When to Submit a 510(k) for a Change to an Existing Device? • Significantly affect safety and effectiveness of the device, incl.:

ο Labelling (indications, warning and precautions, contra-indication, clarity) ο Technology or performance specifications (control mechanism, operating

principle, energy, environment, performance, ergonomics/user interface, dimensions, software, packaging/expiration, sterilisation)

ο Materials (type, formulation, supplier) • May be due to recall or corrective action

Post Market Requirements – product life cycle

62

PMA Supplements: Any changes to the indications, design and/or manufacturing process of the device after receiving PMA approval must be assessed to determine if a PMA Supplement is necessary. Traditional PMA Supplement

• Used for changes or modifications to a PMA approved device • 180 FDA day review

Special PMA Supplement –Changes Being Effected • Limited supplement changes can be made once FDA has acknowledged the submission is

being processed Alternate PMA Supplement (30 day)

• FDA will indicate that an alternate submission would be permitted Refer to FDA Guidance for more information: ”Guidance for Industry and FDA Staff Modifications to Devices Subject to Premarket Approval (PMA) - The PMA Supplement Decision-Making Process”. http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm089360.pdf

Post Market Requirements – product life cycle

63

Examples of changes to be submitted via PMA supplements • new indications for use of the device; • labeling changes; • the use of a different facility or establishment to manufacture, process, or package

the device; • changes in sterilization procedures; • changes in packaging; • changes in the performance or design specifications, circuits, components,

ingredients, principle of operation, or physical layout of the device; and • extension of the expiration date of the device based on data obtained under a new

or revised shelf life testing protocol that has not been approved by FDA. If FDA has approved the protocol, the change should be reported in a periodic report (21 CFR 814.39(b)).

Post Market Requirements – product life cycle

64

http

://w

ww

.fda.

gov/

dow

nloa

ds/M

edic

alDe

vice

s/De

vice

Regu

latio

nand

Gui

danc

e/G

uida

nceD

ocum

ents

/ucm

0893

60.p

df

65

http

://w

ww

.fda.

gov/

dow

nloa

ds/M

edic

alDe

vice

s/De

vice

Regu

latio

nand

Gui

danc

e/G

uida

nceD

ocum

ents

/ucm

0893

60.p

df

66

PMA Periodic Reports • Annual Report • As requested by FDA • Updates or changes post approval that do not affect safety and

efficiency

Post-Approval Studies • Study and reporting requirements defined by FDA in PMA Conditional

Approval Letter

Post Market Requirements – product life cycle

67

No legal responsibilities for the MD distributor

Initial device importer to US to register with the FDA • FDA on-line registration FURLS (Electronic Registration and Listing System) as per 21CFR 807.20 *

Form FDA 2892, "Device Listing” Form FDA 2891, "Initial Registration of Device Establishment”

• Annual update submissions

US agent appointment (optional) Contractual aspects:

o Products reception & verification - Origin, serial/batch numbers, etc.

o Storage conditions o Vigilance delegations

- Product recall, communication with the FDA, etc. - Training requirements (up to date & documented)

* http://www.fda.gov/cdrh/registration/furls.html

Post Market Requirements - MD Distribution

68

Type of Reportable Incidents • Device malfunctions, serious injuries or deaths associated with medical devices

Reporting Modalities • Medical Device Reporting (MDR)

o FDA form 3500A (electronic Medical Device Reporting eMDR)

Declaration Responsibilities • Medical device manufacturers as well as other firms involved in the distribution of

devices o Domestic distributors: not required to file MDR reports, but must continue to maintain complaint files. o Initial distributors (devices manufactured overseas and imported into the USA): must file MDR reports

Reporting Timelines • 30 day reports for deaths, serious injuries and malfunctions • 5-day reports for events that require remedial action to prevent an unreasonable risk of

substantial harm to the public health

* FDA Medical Device Reporting (MDR) regulations – (21 CFR 803)

Post Market Requirements - Vigilance

69

To comply with FDA regulation on advertisement for prescribed MD, promotional pieces :

• Cannot be false or misleading; • Must reveal material facts the consequences that can result from use of

the product as suggested in the promotional piece • Should present information about effectiveness and information about risk

in a balanced manner. No specific FDA guidance so far on advertising on the Internet • In practice, existing US regulation on prescribed MD should extend to Internet

medium

Guidance for Industry: Presenting risk information in Prescription Drug and Medical Device Promotion http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm064956.htm.

Post Market Requirements - Advertising & Sales

70

• Creation of new device subset (class “IIb”): Clinical, manufacturing & postmarket information necessary to support a substantial equivalence determination

• Postmarket surveillance studies: FDA to increase requirements on postmarket surveillance studies as condition of clearance of certain types of devices (i.e. class “Iib” devices)

• De Novo process: Initiated with “pre de novo submission” (PDS) Versus traditional 510(k)

Foreseable changes in USA

Canada

72

Major Regulations • Canadian Medical Devices Regulations - SOR 98-282 • Medical Devices Active Licence Listing (MDALL) • Quality Systems ISO 13485 • Officially Recognized CMDCAS Registrars

Canada - Regulations and guidance documents

73

General Guidance Documents • Health Canada - Guidance on the Content of Quality Management System Audit

Reports - GD211 • Information to be Provided by Manufacturers for the Reprocessing and

Sterilization of Reusable Medical Devices - DRAFT • Recognition and Use Of Standards under the Medical Devices Regulations • Private Label Medical Devices • Licensing Requirements for Inter-dependent Medical Devices - Notice • The Risk-based Classification System - DRAFT • The Risk Based Classification System of In Vitro Diagnostic Devices - DRAFT • Health Canada Licensing Fees …

Canada - Regulations and guidance documents

74

Specific Guidance Documents • Health Canada Guidance on Transition to IEC 60601, 3rd Ed • Health Canada - Guide to Recall of Medical Devices - GUI-0054 • Health Canada - Guidance Document for Mandatory Problem Reporting for

Medical Devices • Health Canada - Guidance on Investigation of Reported Medical Device

Problems - GUI-0065 • Preparation of an Application for Investigational Testing - Medical Devices • Medical Device Licence Renewal - revised 1 April 2012 …

Canada - Regulations and guidance documents

75

Classified according rules on invasive, non-invasive, active devices and also special rules Class I devices:

• not subject to any regulatory review. • Manufacturers establishment licence required • documented procedures for the distribution of records, as well as the handling of complaints and product recalls. • Examples of class I devices : some surgical instruments.

Class II devices: • Medical device license required • Request objective evidence that the device meets safety and effectiveness requirements. • Examples of class II devices : surgically invasive devices, less than 30 days.

Class III devices: • Medical device license required • Request a summary of all studies to ensure the device meets safety and effectiveness requirements. • Examples of class III devices : surgically invasive devices that are absorbed by the body or remain in the body for at least 30 days.

Class IV devices: • Medical device license required • Request detailed information on all studies on which it relies to ensure the device meets safety and effectiveness requirements,

including pre-clinical and clinical studies, process validation studies, software validation studies (if appropriate), and literature studies.

• Request a summary of all these studies. • Examples of class IV devices : breast implants, prosthetic heart valves, and HIV test kits

Canada – Medical device classification

76

For Class II, III, and IV medical devices in Canada. = product approval, prior to being imported, sold or advertised for sale should not be confused with the MDEL, = license for the company/distributor/importer itself. comparable to the US FDA 510(k) process, except • faster for Class II devices, • about the same for Class III devices • more complicated for Class IV devices.

ISO 13485:2003 quality system certification required including specific requirements of the Canadian Medical Device Regulations (CMDR), also known as the Canadian Medical Devices Conformity Assessment System (CMDCAS).

Health Canada Medical Device License (MDL) Approvals

77 Canada – Medical device submission requirements 1/2

Class

Submission Requirements I II III IV Name of device X X X X Class of device X X X X Device identifier X X X X Name and address of manufacturer X X X X Name and address of place of manufacture X X X X Description of conditions, purposes and uses for which device is sold X List of standards complied with to satisfy safety and effectiveness requirements X Attestation that manufacturer has objective evidence to establish that device meets safety and effectiveness requirements X Attestation by manufacturer that label meets applicable requirements X For in vitro diagnostics, attestation that investigational testing has been done on human subjects representative of intended users and under conditions similar to conditions of use X Copy of quality management certificate certifying that quality management system satisfies ISO 13485:2003 X X X Description of device and materials used in its manufacture and packaging X X Description of features of device X X List of all countries other than Canada where it has been sold, number of units sold, and summary of any reported problems or recalls X X

78

Class Submission Requirements I II III IV List of standards complied with in design and manufacture to satisfy safety and effectiveness requirements X X For sterile devices, description of sterilization method X Summary of all studies relied on by manufacturer to ensure safety and effectiveness and conclusions drawn by manufacturer X X Copy of device label X X For a near-patient in vitro diagnostic device, summary of investigational testing using human subjects representative of intended users and under conditions similar to conditions of use X X Bibliography of all published reports dealing with use, safety and effectiveness of device X X Risk assessment comprising an analysis and evaluation of risks, and the risk reduction measures adopted to satisfy the safety and effectiveness requirements X Quality plan setting out the specific quality practices, resources and sequence of activities relevant to the device X Specification of materials used in the manufacture and packaging of the device X Manufacturing process X Detailed information on all studies on which manufacturer relies to ensure device meets safety and effectiveness requirements including pre-clinical and clinical studies, process validation studies, software validation studies (if appropriate), and literature studies. X For devices, other than in vitro diagnostic, incorporating animal or human tissue, objective evidence of biological safety X For a near-patient in vitro diagnostic device, detailed information on investigational testing using human subjects representative of intended users and under conditions similar to conditions of use X

Canada – Medical device submission requirements 2/2

79 Canada – Approval process

Administrative process for class II, III or IV device applications

80 Canada – Approval process

Application validation process for class II, III or IV device applications

81 Canada – Approval process Technical review process for

class III or IV device applications

82

Product / QMS changes declaration Distribution agreement and Safety documentation and reporting • Distribution records • Complaint records • Reporting of

ο Failure ο Deterioration of effectiveness ο Inadequacy of labelling or in directions for use

that results in the death or serious health deterioration of a patient, user or other person, or that could do so should the incident recur

Canada - Post-approval requirements

83

Many thanks for your attention

Questions?

Voisin Consulting Life Sciences voisinconsulting.com linkedin.com/company/voisin-consulting [email protected]