Latest update USA Regulations By P.Trisler Qserve Group (Qserve Conference 2013)

Page 1 | 2011 |Copyright Qserve Group B.V.

The regulatory road to market The regulatory road to market

US FDA Regulations - Overview & Update Q s e r v e C o n f e r e n c e 1 8 - 1 9 N o v e m b e r 2 0 1 3

P u r m e r e n d – G r e a t e r A m s t e r d a m


Topics

• Overview of FDA, Medical Device Classification System & Regulatory Processes

• New Processes Impacting Many Programs

Refuse to Accept (RTA)

Electronic Copy (eCopy)

• Changes related to Submissions

De Novo Application

Pre-De Novo Submission (PDS)

Pre-Submission (Pre-Sub)

• Miscellaneous

Unique Device Identification (ID)

International Symbols

Medical Device Single Audit Program Pilot (MDSAP)


Topics

Additional New FDA Guidances – Clinical

• Design Considerations for Pivotal Clinical Investigations for Medical Devices

-Guidance for Industry, Clinical Investigators, IRBs & FDA Staff (Nov, 2013)

• Investigational Device Exemptions (IDEs) for Early Feasibility Medical Device Clinical

Studies, Including Certain First in Human Studies (Oct 2013)

• Oversight of Clinical Investigations – a Risk-Based Approach to Monitoring (Aug 2013)

• (Draft) FDA Decisions for IDE Investigations (June 2013)

• Financial Disclosure by Clinical Investigators (Feb 2013)


Overview FDA ….some facts…

Headed by a Commissioner (Margaret Hamburg, MD) appointed by US President

Headquartered in Washington, D.C – CDRH, CDER, CBER, CVM, etc

21 District Offices around the U.S.

Regulates > $1 trillion of products

Has regulatory authority over >65,000 establishments (not including entities under

BIMO – labs & clinical research sites)

Employs > 9,000 staff


US President

Health & Human Services

Food and Drug Administration

CDRH

ODE

CDER CBER

OC

ORA

Div of BIMO


Overview – FDA’s Authority & Governance

US Congress: Federal Food, Drug & Cosmetic Act (1938), as amended…

The ‘device law’ (1976) -- Medical Device Amendments

Several amendments passed since that time

US Federal Agencies/FDA: Regulations

FDA Centers/Offices: Guidances/Guidelines/Points to Consider


Overview – US Federal Regulations

Title 21 Code of Federal Regulations (CFR)

Parts 1 – 99 General – for enforcement

of the FD&C Act

Parts 800 – 1299

Medical Devices & Radiological Health


Part 3 – Combination Products

Part 11 – Electronic Records

Part 50 – Subject Protections

Part 54 – Financial Disclosure

Part 56 – IRB

Part 801, 809 – Labeling

Part 803 – Medical Device Reporting

Part 807 – Premarket Notification/510(k),

Establishment Registration & Listing

Part 812 – IDE

Part 814 – HDE, PMA

Part 820 - QSR (GMP)

Overview – Regulations (21 CFR…)


General – http://www.fda.gov/MedicalDevices/default.htm

Database Search page -

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm

Overview – CDRH search engines

http://www.fda.gov/MedicalDevices/default.htm

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm


Overview

• Classification System

Class I, II & III (1700 devices pre-assigned in 1976)

782

799

119

Class I

Class II

Class III


Overview

• Classified by perceived/known risk & regulated accordingly

General Controls

Special Controls

Premarket Approval

Class I

✔

Class II

✔

✔

Class III ✔

✔


Overview – General Controls

1. Establishment Registration with FDA

2. Medical Device Listing with FDA

3. Manufacture devices according to QSR/GMP in 21 CFR Part 820.

4. Label devices in accordance with labeling regulations in 21 CFR Part

801 or 809.

5. Submit a Premarket Notification [510(k)] before marketing a device.


Overview – Special Controls

Examples

Special labeling requirements

Mandatory performance standards

Postmarket surveillance

Special Controls Guidance Document


Overview – Paths to the Market Application

Type Comments Regulatory

Review

Product Classes

510(k) = Premarket Notification

Substantially equivalent (“at least as safe & effective as a legally marketed/predicate device”)

90 days Class II generally

510(k)/de novo Petition

Low to moderate risk; novel device. 510(k) must conclude NSE bec no predicate device. Product has to be shown to be safe & effective.

?? Class I/II

PMA = Premarket Approval

Reasonable assurance of safety & effectiveness based on valid scientific evidence

180 days

Class III

HDE = Humanitarian Device Exemption

For humanitarian use device (<4000 persons in US/year). Evidence of safety and probable benefit. Requires IRB approval for each use. ~75 HDEs approved by FDA

75 days

Class III


Overview – Device User Fees (2013-14)

Application Type

Standard

US $

*Small Business

Premarket Approval Application (PMA/PDP/BLA)

$258,520 $64,630

1st PMA from firm w/ sales/gross

receipts < $30 mil

n/a $0

513(g) Classification Request $3,490 $1,745

510(k) Premarket Notification $5,170 $2,585

Annual Registration $3,313 $3,313

*Small business = <$100M in gross receipts/

sales


New Processes

• Refuse to Accept Policy for 510(k)s – RTA

31 Dec 2012

• eCopy Program for Medical Device Submissions

10 Oct 2013


New – RTA Key Points

Purpose: Administrative Review

To assure complete submissions - question of ‘completeness’ (administrative)

and not ‘quality of data’ (substantive).

FDA checklist

Provides specific information point-by-point of the elements/contents that are

considered ‘incomplete’.

15 calendar day post-submission review period

90-day substantive review clock starts on a determination of ‘completeness’.

Date will be the log-in date if no issues.

If there are issues & the RTA checklist is sent to applicant, the 90-day review

clock will not start until those have been resolved.


New – eCopy (1)

• Definition: Exact duplicate of paper copy, created and submitted on a CD, DVD or

flash drive. It is not a submission transmitted electronically.

Some exceptions regarding ‘exact duplicate’

• Required for:

510(k)

PMA, traditional and modular

De Novo

PDP

IDE, with certain exceptions (compassionate use & emergency use)


New – eCopy (2)

• Requirements:

Technical standards for loading the file must be met (no exceptions) Particularly

important:

Naming convention (‘correct’ prefix: “001_”)

» Follow instructions closely with more than 1 volume

Files must be 50MB or smaller

Adobe Acrobat PDF Ver 11 or below

No embedded attachments

No security settings

Beware of special characters


New – eCopy (3)

Consequences of incorrectly prepared eCopy: Submission will not be accepted

and the date of receipt will not be the ‘log-in’ date.

However, FDA will hold the paper copy until a correctly-created

replacement eCopy has been received & loaded.


Submission Changes/Updates

• De Novo Classification Process (Evaluation of Automatic Class III

Designation): Draft Guidance, 3 Oct 2011 (to replace a 1998 guidance)

• Medical Devices: The Pre-Submission Program and Meetings with FDA

Staff: Draft Guidance 13 July 2012 (includes Pre-IDE Program)


Changes – De Novo Process (1)

• Authorization: 513(f)(2) of US Federal Food, Drug & Cosmetic Act (FD&C Act) –

passed in 1997, FDA Modernization Act (FDAMA)

• Prior to 1997 all new devices, regardless of risk level, would have been

classified in Class III and require PMA.

• De Novo = “Evaluation of Automatic Class III Designation”

• Requirements for qualifying for de novo:

Low to moderate risk medical device

Novel (no predicate device/not previously classified)

NSE (not substantially equivalent) determination by FDA via 510(k), e.g ‘auto

classification into Class III’

File De Novo Petition


Changes – De Novo Process (2)

• Additional requirements to a successful petition

Risks & benefits need to be understood

‘Controls’ need to be possible to provide reasonable assurance of safety & effectiveness of the

device ‘type’

Those controls often include the conduct of clinical studies.

• Good news if the new guidance is fully implemented: It provides for greater clarity &

transparency, in particular:

Pre de novo submission (PDS) >> 510(k)/De Novo Petition,

vs the ‘standard’:

510(k) >> De Novo Petition

90 de novo petitions granted to date.


Changes – Pre-Sub (Encompasses Pre-IDE)

• Process that formalizes obtaining FDA’s pre-review for:

Non-clinical (laboratory & animal) protocol

Clinical protocol/design issues, prior to submitting an IDE

Pre-marketing submission interactions on a variety of topics (such as

uncertainty in method of presenting data, changes in device during IDE

study, discussion of problems encountered during conduct of clin study)

• Specified format & content requirements

• Timeline = 75-90 days

• Feedback via teleconference, face-to-face meeting or written

(always receive written comments)


New – Unique Device Identifier (UDI) System

Implementation of US FD&C Act §519(f) (Sept, 2013).

Two key elements:

(1) Requires a UDI on devices & device packages (w/ some exceptions)

Must be marked on the device itself if the device is intended for use more than

once & intended for reprocessing before each use.

(2) Device labelers – info for each device labeled with UDI to FDA’s Global UDI

Database (GUDID).

Plain-text version & in a form that uses automatic ID & data capture tech.

All required device records must include the UDI.

7-year phase-in period (depending on risk level).


New – International Symbols

• Currently – Medical Device Labeling (except for IVD) must accompany

international symbols with ‘words’.

• Under consideration (proposed Rule) – Option on part of medical device

manufacturers to use standardized international symbols (recognized by FDA)

on labeling.


• Mission: Single audit program for medical device manufacturers

• Sponsored by International Medical Device Regulators Forum (IMDRF)

• January 2014 - FDA will begin participating in a MDSAP Pilot alongside other

international partner agencies:

• Partners: Australia, Brazil, Canada

• Observer: Japan

• Pilot (Jan 2014 – Dec 2016) – auditing organizations: only those utilized by

Health Canada’s CMDCAS Program.

• MDSAP for FDA:

• routine inspections only

• no ‘for cause’, no PMA (pre- or post-approval)

New – Medical Device Single Audit Program Pilot


Thank you!

P a t s y Tr i s l e r Q s e r v e G r o u p U S I n c . P a t s y. t r i s l e r @ q s e r v e g r o u p . c o m

www.qservegroup.com Qserve Group B.V.

Asterweg 19 D12 1031 DL Amsterdam

The Netherlands T +31 (0)20 78 82 630

E [email protected]

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