Cook Medical

Cook Medical
April Lavender, RAC
Senior Vice President
Regulatory Affairs
18 January 2014
Participants in this Workshop
•  Gain an understanding of regulatory
requirements during the medical device
development process
•  Develop an appreciation of Design History
documentation
•  Examine regulatory submission
requirements for clearance/approval in the
United States
Agenda
•  Introduction to Cook Medical
•  Total Product Life Cycle
•  Device Development Prerequisites
•  Elements of Design Controls
•  Pathways to FDA clearance/approval
Cook is dedicated to
bold leadership in
pioneering innovative
medical solutions
to enhance patient care
worldwide.
– Cook mission statement Cook World Headquarters
Background on Cook Companies
•  Founded in 1963 by Bill and Gayle Cook
•  11,000 employees worldwide (3,400 in
Indiana)
•  Manufacturing on 3 continents
•  10 Strategic Business Units addressing
multiple medical specialties
•  Distribution into more than 110 countries
Company Diversification
TECHNOLOGY
Medical Devices
Tissue Based Products
COOK COMPANY/LOCATION
Cook Incorporated, Bloomington IN
Cook Endoscopy, Winston Salem NC
Cook Vascular, Vandergrift PA
Cook Biotech, West Lafayette IN
Cook General Biotechnology,
Indianapolis IN
Cellular Products
Cook Myosite, Pittsburgh PA
Contract Pharmaceuticals
Cook Pharmica, Bloomington IN
Medical Polymer Manufacturing
Cook Polymer Technology,
Bloomington IN
Contract Research, GLP Testing
and Clinical Trial Management
Med Institute, West Lafayette IN
Example Technologies
Endovascular Graft Technology
For Aneurysm Repair
Approved via PMA
Drug-Eluting Stent Technology
Zilver PTX®
Peripheral (SFA)
Drug-eluting Stent
Approved via PMA
Peripheral Antibiotic Impregnated Central
Venous Catheter Technology
Spectrum Technology Cleared via 510k SIS Biotechnology
Collagen matrix Urethral Sling Cleared via 510k Collagen matrix Dural Subs3tute Cleared via 510k Collagen matrix Anal Fistula Plug Cleared via 510k Total Product Life Cycle (TPLC)
• Concept (Idea)
• Preclinical Prototype Development
• Clinical
• Commercial
• Post-market
Total Product Life Cycle – TPLC
TPLC Concept Phase
A New Idea is sometimes pursued to:
•  Iterate or evolve an existing
technology
•  Improve the quality of care by
changing its point of delivery
•  Brand new idea to enhance patient
care
During Idea / Research Phase
There are no constraints associated with
21 CFR §820.30 Design Controls
Time for Some Strategic Planning
–  Are there any patent issues?
–  How long will it take to develop?
–  How much time and cost will it take for
regulatory approval?
–  Is this idea manufacturable?
–  Will the new product be reimbursed
under CMS coverage?
The Conflict We Manage
•  Innovations in medical technology are
cited frequently as one of the drivers of
increased healthcare costs
•  From 1980 to 2000, new diagnostic and
treatment paradigms helped drive a 4%
increase in life expectancy in the US, a
16% decrease in annual mortality rates
and a 25% decline in disability for the
elderly.
• 
______________________
Gottlieb and Makower, A Role for Entrepreneurs, Am J Prev Med 2013;
44(1S1):S43-S47.
Total Product Life Cycle (TPLC)
Design Controls (21 CFR 820.30)
–  Design and development plans
–  Design inputs
•  intended use, needs of the user and patient
–  Design outputs
–  Design reviews
–  Design verification testing
–  Design validation testing
–  Design transfer
–  Design changes
–  Design history file
Investigational Device
Exemption (21 CFR 812)
•  Investigational Device Exemption (IDE)
Studies include both significant and nonsignificant risk studies
•  Regulatory requirements of 21 CFR § 812
are submitted to get FDA permission to
perform clinical trials with devices in
humans
•  Clinical work is initiated upon approval
from FDA (SR) or an IRB for (NSR)
studies
Steps to Obtain Market Approval
• 
Classify the medical device
• 
Determine the regulatory pathway
• 
Compile required data and information
• 
Submit the marketing application
• 
Work to answer queries or questions
Risk Based Classification System
Low Risk
Class I
Moderate Risk
Class II
High Risk
Class III
FDA Classifications of Devices
•  Class I devices are those
–  That present the lowest risk to health for
which General Controls are sufficient to
assure reasonable safety and effectiveness
–  Examples include:
•  Manual surgical instruments
•  Aspiration and injection needles
•  Introduction and drainage catheters
•  Examination gowns, tongue depressors
–  Majority are exempt from premarket
notification
FDA Classifications of Devices
•  Class II devices are those
–  That cannot be classified into Class I
because there is insufficient information to
show that General Controls alone are
adequate to assure safety and effectiveness
–  Examples include:
•  Percutaneous catheters
•  Vascular access sheaths
•  Tracheostomy tubes
•  Airway pressure monitors
•  Emergency airway needles
FDA Classifications of Devices
•  Class III represents devices
–  That are used to support or sustain human
life
–  Present an unreasonable risk of injury
–  Or cannot be class I or II because General
Controls or Class II Special Controls do not
provide reasonable assurance of safety or
effectiveness
–  Examples include:
•  Cranial electrotherapy stimulators
•  Drug eluting Peripheral Stents
•  Endovascular Grafts
What are General Controls of the
Food, Drug and Cosmetic Act
•  Registering the manufacturing establishment
•  Listing the medical device
•  Compliance with Quality System requirements (21
CFR 820)
•  Labeling in accordance with requirements (21
CFR Part 801)
•  All devices are subject to General Controls
What are Special Controls?
•  Some devices are subject to both General
and Special Controls
•  Special Controls may include:
– Specific labeling requirements for a
given device
– Mandatory performance to established
standards
– Required postmarket surveillance
studies
Determine Regulatory Pathway
Device
Classification
I (low risk)
II (moderate risk)
III (high risk)
Typical Type of
Regulatory Submission and
Regulatory Timeline
None—exempt
Premarket Notification
..Special 510k
30 days
..Traditional 510k 90 days
Premarket Approval with
Clinical Data
Original PMA
180 days
Contents of a (510k)
– Indications for Use
– Detailed Device Description Information
– Proposed Labeling
– Biocompatibility Data
– Performance Testing
– Sterilization Information
– Shelf Life/Expiration
– Packaging
– Substantial Equivalence Information
– Standard Certifications
– Truthful & Accurate Statement
– 510(k) Summary or Statement
What is Substantial Equivalence
Each new device is compared to a currently
marketed device that has:
• The same intended use and the same
technological characteristics as the predicate
Or
• The same intended use and different
technological characteristics from the predicate
and the information collected on the new device
raises no new questions of safety or effectiveness
and demonstrates that the device is as safe and
effective as the legally marketed predicate device
When a Device is Found Not
Substantially Equivalent?
•  A Submitter must request reclassification
within 30 days of an NSE determination
•  FDA must respond to the request for
reclassification within 60 days
•  Devices found NSE are placed into Class
III may not be marketed before approval
of a PMA or some other regulatory
submission
Premarket Approval (PMA) Process
(21 CFR 814)
•  Filing review (occurs within 45 days of receipt of
submission at FDA)
–  Consists of administrative review
–  Limited scientific review
•  In-depth review—usually a team approach
•  Panel review by an Advisory Committee
•  Final review after Panel
•  6 month process after submission is complete
and meets FDA requirements
Contents of a PMA
•  Full reports of all information, published or
reasonably known to the applicant,
including investigations which have been
done to show safety and effectiveness
•  Full statement of components, ingredients
and properties and principles of operation
of the device
•  Full description of the methods used in,
and the facilities and controls used for, the
manufacturing and processing of a device
Contents of a PMA
•  Summary of Safety and Effectiveness
•  Labeling
•  Nonclinical Laboratory Studies
–  In Vitro (Bench) GLP Studies
–  In Vivo (Animal) GLP Studies
•  Clinical Investigations
–  Done in accordance with IDE regulations
( 21 CFR 812)
How Long Does This Process Take? Event Date Inves3ga3onal Device Exemp3on (IDE) approved by FDA June 4, 2004 (Condi3onal) April 18, 2007 (Full) Pa3ent enrollment period March 21, 2005 – August 25, 2008 Premarket Approval Applica3on (PMA) May 28, 2010 submiSed to FDA Quality System (QSR) inspec3on at Cook manufacturing facili3es September 22 to October 5, 2010 Bioresearch Monitoring (BIMO) inspec3ons at clinical sites January through October 2010 Bioresearch Monitoring (BIMO) inspec3on at Cook October 25 to November 4, 2010 The most important theme for all
of 2013 is that the entrepreneur
came through with productivity
enhancing innovation in spite of
having a bloated government on
its back
– Economist Brian Westbury Thank you for working today on
tomorrow’s improvements!
http://www.fda.gov/MedicalDevices/default.htm
Medical Device User Fees
Fiscal Year 2014
SUBMISSION TYPE
FEE
Annual Establishment Registration
$3,313
510(K) (traditional, special
abbreviated)
$5,170
Original PMA
$258,520
Panel Track PMA Supplement
$193,890
PMA 180-day supplement
$38,778
Real-Time PMA Supplement
$18,096
PMA 30-day Notice
$4,136
Class III Annual Reports
$9,048