Latest update USA Regulations By P.Trisler Qserve Group (Qserve Conference 2013)
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.
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)
Unique Device Identification (ID)
Medical Device Single Audit Program Pilot (MDSAP)
Page 2 | 2013 |Copyright Qserve Group B.V.
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.
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.
Health & Human Services
Food and Drug Administration
Div of BIMO
Page 5 | 2013 |Copyright Qserve Group B.V.
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.
Overview – US Federal Regulations
Code of Federal Regulations (CFR)
Parts 1 – 99
General – for enforcement
of the FD&C Act
Parts 800 – 1299
Medical Devices &
Page 7 | 2013 |Copyright Qserve Group B.V.
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
- QSR (GMP)
Page 8 | 2013 |Copyright Qserve Group B.V.
Class I, II & III (1700 devices pre-assigned in 1976)
Page 10 | 2013 |Copyright Qserve Group B.V.
Classified by perceived/known risk & regulated accordingly
Page 11 | 2013 |Copyright Qserve Group B.V.
Overview – General Controls
Establishment Registration with FDA
Medical Device Listing with FDA
Manufacture devices according to QSR/GMP in 21 CFR Part 820.
Label devices in accordance with labeling regulations in 21 CFR Part
801 or 809.
Submit a Premarket Notification [510(k)] before marketing a device.
Page 12 | 2013 |Copyright Qserve Group B.V.
Overview – Special Controls
Special labeling requirements
Mandatory performance standards
Special Controls Guidance Document
Page 13 | 2013 |Copyright Qserve Group B.V.
Overview – Paths to the Market
Substantially equivalent (“at least as safe &
effective as a legally marketed/predicate
Low to moderate risk; novel device. 510(k) must
conclude NSE bec no predicate device. Product
has to be shown to be safe & effective.
Reasonable assurance of safety & effectiveness
based on valid scientific evidence
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
Page 14 | 2013 |Copyright Qserve Group B.V.
Overview – Device User Fees (2013-14)
Premarket Approval Application
1st PMA from firm w/ sales/gross
receipts < $30 mil
513(g) Classification Request
510(k) Premarket Notification
*Small business = <$100M in gross receipts/
Page 15 | 2013 |Copyright Qserve Group B.V.
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.
New – RTA
Purpose: Administrative Review
To assure complete submissions - question of ‘completeness’ (administrative)
and not ‘quality of data’ (substantive).
Provides specific information point-by-point of the elements/contents that are
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.
New – eCopy
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’
PMA, traditional and modular
IDE, with certain exceptions (compassionate use & emergency use)
Page 18 | 2013 |Copyright Qserve Group B.V.
New – eCopy
Technical standards for loading the file must be met (no exceptions) Particularly
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.
New – eCopy
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.
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.
Changes – De Novo Process
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.
Changes – De Novo Process
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
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.
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.
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
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.
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)
Page 26 | 2013 |Copyright Qserve Group B.V.
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
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.
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
Qserve Group B.V.
Asterweg 19 D12
1031 DL Amsterdam
T +31 (0)20 78 82 630
Page 28 | 2013 |Copyright Qserve Group B.V.