Transcript Nariko Koto - French American Chamber of Commerce, Minneapolis

Global Regulatory Affairs
US vs. EU
Nariko Koto, MBA
Global Regulatory/Business Consultants, LLC
January 13, 2014
For French Chamber of Commerce
Nariko Koto Bio
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15 years experience in the medical device, biologics and pharmaceutical industries
•
Worked at Medtronic, Johnson & Johnson, 3M and AGA Medical (now part of St. Jude Medical)
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Formed Global Regulatory/Business Consultants LLC
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Responsibilities: Global Regulatory, Quality, Clinical and Business Development including CRO
and clinical site management to perform quality of clinical studies and distributor/supplier
management to receive approvals/clearances and deliver quality products throughout the
world
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Developing global QA, RA and clinical strategies and dealing directly with global government
authorities including US FDA, EU, Middle East, Africa (EMEA), Health Canada, Japanese PMDA,
China, India, Korea, Singapore, Thailand and other international locations in numerous devices,
biologics and combination devices for various therapeutic areas
•
Ensuring regulatory/clinical/quality compliance with FDA, Health Canada, MDD, 93/42/EEC,
MEDDEV, JPAL, ISO 9001, ISO 13485/EN 46001, ISO14155, ISO14971 Risk Management, and
applicable standards to determine filing or notification requirements
•
Provided presentations at RAPS, Infection Control, NASPE, etc.
•
Living and working in the US, the Netherlands, the UK and Japan. Traveled to over 40 countries.
Speaks several languages including English, Japanese, French, some German, Chinese and
Russian.
Why do you need FDA approvals to
market products?
• “The Food and Drug Administration (FDA or USFDA) is
an agency of the United States Department of Health and
Human Services, one of the United States federal
executive departments. The FDA is responsible for
protecting and promoting public health through the
regulation and supervision of food safety, tobacco
products, dietary supplements, prescription and over-the
counter pharmaceutical drugs (medications), vaccines,
biopharmaceuticals, blood transfusions, medical devices,
electromagnetic radiation, cosmetics, emitting devices
(ERED), and veterinary products.”
• http://en.wikipedia.org/wiki/Food_and_Drug_Administration
FDA Medical Device
Submission and Approval System
Medical Device Classifications
i.
CLASS I
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ii.
CLASS II
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iii.
More complex, higher risk
Premarket Notification [510(k)] - Substantial Equivalence (SE) to a predicate device
(currently on U.S. market)
CLASS III

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iv.
Simple design, low risk
Most exempt from premarket submission exempt from premarket submission
Most complex, highest risk
Premarket Application [PMA] - Device is reasonably safe and effective for its
intended use; Contain valid scientific evidence and provide reasonable assurance
HDE - Additional Classification

Devices for orphan diseases intended to benefit patients in diagnosis and/or
treatment of disease or condition affecting or manifested in fewer than 4,000
patients per year in the United States . (Approval based on safety & probable
benefit)
FDA – Clinical Study Phases
Device/Biologics
Device and Biologics
o First in human (FIH) study
A specific indication is evaluated for the first time in human subjects
o Early feasibility study
Initial clinical safety and device functionality in a small number of
subjects (generally fewer than 10 initial subjects)
o Traditional feasibility study
To capture preliminary safety and effectiveness information
o Pivotal study
A clinical investigation designed to collect definitive evidence of the
safety and effectiveness of a device for a specified intended use,
typically in a statistically justified number of subjects
5
FDA – Clinical Study Phases
Drugs
• Phase I: Researchers test a new drug or treatment in a small group of
people for the first time to evaluate its safety, determine a safe dosage
range, and identify side effects. (15 – 30 volunteers)
• Phase II: The drug or treatment is given to a larger group of people to see
if it is effective and to further evaluate its safety. (Fewer than 100
volunteers)
• Phase III: The drug or treatment is given to large groups of people to
confirm its effectiveness, monitor side effects, compare it to commonly
used treatments, and collect information that will allow the drug or
treatment to be used safely. (100s – 1000s of volunteers)
• Phase IV: Studies are done after the drug or treatment has been
marketed to gather information on the drug's effect in various populations
and any side effects associated with long-term use. (After approval)
EU Submission and Approval System
1.
CE Mark for devices vs. Medicines Agency for drugs (Biologics must be decided
based on the historic background)
2.
CE Mark – classifications
i.
Class I - This group covers low-risk devices and the conformity assessment procedures are
carried out by the manufacturer. Examples of this type of classification include devices that
do not penetrate the body such as bandages, hospital beds, sterilization packaging and
dental mirrors. There is no need for a Notified Body for class I devices.
ii.
Class IIa - In most cases, the intervention of a Notified Body is compulsory at the
production stage for class IIa devices. Examples include anesthetic gas masks, acupuncture
needles, oxygen masks and spirometer peak flow meters.
iii.
Class IIb - In this class, inspection by a Notified Body is required with regard to the design
and manufacture of the device. Examples of this type of classification include anesthesia
gas machines, hyperbaric chambers and respiratory monitors.
iv.
Class III - This group covers the most critical devices for which explicit authorization with
regard to conformity is required before commercialization. Examples include artificial
hearts, pacemaker batteries and bone grafts.
US Study vs. European Study
21 CFR 812, 50, 54, 56
ISO 14155:2011
Element
Difference
Element
Difference
Protocol
Concise-no additional verbiage required
Protocol
Must have add’l verbiage to meet ISO
IRB approval
At the center
EC approval
Country, Regional & Local
Advisory
Meeting
Always responsible and same people
attend
Advisory Meeting
Different people each time, may attend
or may not attend
Reports
To FDA/IRB
Reports
CA/ECs (all PI)
Auditing
Required
Auditing
Not required
Clinical
Research
Coordinators
Always exist at each hospital
Clinical Research
Coordinators
No Clinical Research Coordinators
Endpoints
US and EU have different endpoints
Endpoints
US and EU have different endpoints
Translation
0
Translation
$
Interpreter
0
Interpreter
$
Local Representative
For filing to the authorities $
Data Transfer
Legal authorization
Compliance
Poor compliance with protocol -> Many
protocol deviations
CRO
Difficult to manage due to cultural
differences and long holidays
8
Common Clinical/Regulatory Practices
for High Risk Devices and Biologics
US
• Feasibility Study – 10 pts
o Minimum indication
o Preparation for Pivotal Study
- Identify Endpoints
• Pivotal study
• US submission (Modular)
Submit clinical section upon
the Pivotal study
completion
EU
• CE Mark
– Literature approach with
minimum indication
• Bring 10 pts feasibility study
results to various global
conferences
• Share annual report and
interim publications, as well
as the completed study
results
9
New FDA Guidance
• New feasibility IDE guidance and FDA
Teleconferences
• FDA emphasizes early product development
and willingness to work with sponsors in the US
• May recommend small feasibility study if the
assumption (it is a device) is correct
10
New EU Medical Device Reform
Measures
Background: A series of high-profile scandals and device failures, including deficient
breast implants and faulty metal-on-metal hip implants.
Oct 22,2013: The European Parliament approved compromise legislation for medical
devices and in-vitro diagnostics:
– "The proposed legislation seeks to improve transparency of information for
patients and medical staff and to strengthen traceability rules, without
creating additional burdens for innovative small manufacturers,“
• To "reinforce" public access to clinical trials data
• The creation of an "implant card" system to allow patients to know which products
are inside them
• New CE marking requirements to permit only qualified experts to mark devices,
new safety rules for IVDs that will require the approval of an ethics board, and new
liabilities for device reprocessors.
Next step: Parliament to negotiate a package with Europe’s other legislative body, the
Council, but some are questioning whether more progress can be made before 2014
elections.
Resources: Medical Device Today; and Regulatory Focus
Challenges, Opportunities and
Future with France
• Challenges
– Language barriers
– Differences in systems and practices
– Cultural
• Opportunities and Future
to fill the current gap between the US and the EU
Adopt the new EU Medical Device Reform Measures
faster than other EU nations
Merci!