1. The regulatory road to market
US FDA Regulations - Overview & Update
Qserve Conference 18-19 November 2013
Purmerend – Greater Amsterdam
Page 1 | 2011 |Copyright Qserve Group B.V.

2. 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)
Page 2 | 2013 |Copyright Qserve Group B.V.

3. 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)
Page 3 | 2013 |Copyright Qserve Group B.V.

4. 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
Page 4 | 2013 |Copyright Qserve Group B.V.

5. US President
Health & Human Services
Food and Drug Administration
CDRH
ODE
CDER
CBER
ORA
OC
Div of BIMO
Page 5 | 2013 |Copyright Qserve Group B.V.

6. 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
Page 6 | 2013 |Copyright Qserve Group B.V.

7. 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
Page 7 | 2013 |Copyright Qserve Group B.V.

8. Overview – Regulations (21 CFR…)
 Part 3 – Combination Products
 Part 803 – Medical Device Reporting
 Part 11 – Electronic Records
 Part 807 – Premarket Notification/510(k),
 Part 50 – Subject Protections
 Part 54 – Financial Disclosure
 Part 56 – IRB
 Part 801, 809 – Labeling
Establishment Registration & Listing
 Part 812 – IDE
 Part 814 – HDE, PMA
 Part 820
- QSR (GMP)
Page 8 | 2013 |Copyright Qserve Group B.V.

9. Overview – CDRH search engines
General – http://www.fda.gov/MedicalDevices/default.htm
Database Search page http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm
Page 9 | 2013 |Copyright Qserve Group B.V.

10. Overview
•
Classification System

Class I, II & III (1700 devices pre-assigned in 1976)
799
Class I
Class II
119
Class III
782
Page 10 | 2013 |Copyright Qserve Group B.V.

11. Overview
•
Classified by perceived/known risk & regulated accordingly
General
Controls
Class I
✔
Class III
✔
Premarket
Approval
✔
Class II
Special
Controls
✔
✔
Page 11 | 2013 |Copyright Qserve Group B.V.

12. 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.
Page 12 | 2013 |Copyright Qserve Group B.V.

13. Overview – Special Controls
Examples
 Special labeling requirements
 Mandatory performance standards
 Postmarket surveillance
 Special Controls Guidance Document
Page 13 | 2013 |Copyright Qserve Group B.V.

14. 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
Page 14 | 2013 |Copyright Qserve Group B.V.

15. 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
Page 15 | 2013 |Copyright Qserve Group B.V.

16. New Processes
•
Refuse to Accept Policy for 510(k)s – RTA

•
31 Dec 2012
eCopy Program for Medical Device Submissions

10 Oct 2013
Page 16 | 2013 |Copyright Qserve Group B.V.

17. 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.
Page 17 | 2013 |Copyright Qserve Group B.V.

18. 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)
Page 18 | 2013 |Copyright Qserve Group B.V.

19. 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
Page 19 | 2013 |Copyright Qserve Group B.V.

20. 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.
Page 20 | 2013 |Copyright Qserve Group B.V.

21. 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)
Page 21 | 2013 |Copyright Qserve Group B.V.

22. 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
Page 22 | 2013 |Copyright Qserve Group B.V.

23. 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.
Page 23 | 2013 |Copyright Qserve Group B.V.

24. 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)
Page 24 | 2013 |Copyright Qserve Group B.V.

25. 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).
Page 25 | 2013 |Copyright Qserve Group B.V.

26. 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.
Page 26 | 2013 |Copyright Qserve Group B.V.

27. New – Medical Device Single Audit Program Pilot
•
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)
Page 27 | 2013 |Copyright Qserve Group B.V.

28. Thank you!
P a t s y Tr i s l e r
Qserve Group US Inc.
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 info@qservegroup.com
Page 28 | 2013 |Copyright Qserve Group B.V.