1. Calcified Lesion and Device Intervention Across the Pacific: PMDA View
Tomohito Suzuki, Ph.D.
Office of Medical Devices I,
PMDA, Japan

2. Calcified Lesion and Device Intervention
Review Points
Points to Consider in review process –non clinical part
Clinical evaluation
Points to Consider in review process –Clinical part
Summary

3. Calcified Lesion and Device Intervention
Rotational atherectomy device
Rotablator™ / RotaLink™ System (Approval：1997)
Directional coronary atherectomy device
Simpson’s coronary atherectomy catheter system (Approval：1992) : now not available in Japan
Approved only for Coronary artery
In Japan rotational atherectomy device such as rotablator and directional coronary atheretomy device such as sinmpsons coronary athrectomy catheter are use in calcified lesion
And thse devices use only fore voronary artery in Japan, so today I talk about coronary calcified lesion.

4. What is the development purpose?
Review points
What is the development purpose?
What is intended for additional materials?
What character/performance is expected in the design of additional materials?
What will appropriately evaluate the additional materials for the intended purpose?
In our pre-marketing review process, these items should be clarified;
What is the purpose of development?
And what kind of materials is utilized to achieve the concept?
What character/performance are expected in the design for the behavior of additional materials?
What are the appropriate evaluation that additional material could achieve the purpose?

5. Points to Consider in review process –non clinical part for devices
Characterization of Novel products
Efficacy: mode of action
Safety
Vessel perforation
Heat production
General requirements for electric device
Refer to the MHLW notification for electric device
Rotablator
Size of debris （smaller than RBC?)
DCA
Vessels involved in the rotation
In this slide, we would like to briefly introduce the point to consider in non-clinical data review for the devices use in calcified lision.
These devices needs to be clarified in following points;
The additional characteristics of novel products.
The mechanism of its efficacy
And the Safety, for example Vessel perforation and Heat production
In addition to these　rotablator need evaluate a size of debris
And DCA needs evaluate Vessels involved with the rotation
When you develop electric devices in Japan, please refer to a MHLW notification regarding electric products.

6. Other related requirements
Data for device stability and durability
Data for biocompatibility
Animal study
Insertion test in swine (pig) coronary arteries
Nonclinical evaluation to determine if the device perform its intended purpose
Off course following items that are general requirements for medical devices are required too:
Device stability and durability, biocompatibility, and it is not always requires, if needed performance evaluation in animal study. And device concept validation by bench testing.

7. Review points –clinical evaluation
What is clinical positioning of Rotablator ＆ DCA?
Mainly complementary devices
Mainstay of therapy is POBA or stent
Next, we briefly introduce point to consider in clinical review of devices foe calcified lesion.
Rotablator and DCA, these devices are mainly complementary devices
And Mainstay therapy is POBA or stent

8. Clinical evaluation Complementary devices Confirm that it works safely
The validity of complementary use
Increase the benefit, but not increase the risk
Confirm that it works safely
without cutting too much
without having negative impact
with evaluation of the treated vessel
Thus these devices are Complementary devices,
Need to evaluate the validity　of complementary use
And Need to shown increase the benefit, but not increase the risk
Confirm that it works safely
without cutting too much, without having negative impact, ant with evaluation of the treated vessel

9. Points to Consider in review process –Clinical part
Purpose of the clinical trial
It works safely?
Patient population
With strong calcified lesion which can’t be expanded enough with balloon or stent?
Control arm
With existing comparable devices or no complementary device
Primary endpoints
Acute success ? (complementary use)
Rotabretor and DCA are supportive devices, so we should evaluate its works safty.

10. Points to Consider in review process –clinical part
Important items
Necessary secondary endpoints?
Items to be evaluated?
Additional topics, e.g. easiness of reintervention
Side branch occlusion, slow flow
Properties of the treated vessel, vessel dissection
might have undetected risk, so we should evaluate its clinical benefit.
So following items are important in the review of clinical trial;
Secondary endpoints
Clinical items to be observed
Facility in case of retreatment
And risk of said branch occlusion and slow flow.
Properties of the vessel, vessel dissociation
The necessity of innovative device development is understandable.
The device may be an option to solve various remaining problems in calcified region.
On the other hand, its clinical efficacy and safety are not yet to be clarified in many aspects

11. Review points What is the development concept? Clinical positioning
Risk
Benefit
Clinical positioning
Alternative? or Complementary?
Follow-on? or Brand new?
Non-clinical test
Clinical trial
Purpose
Patient population
Control
endpoint
Safety
duration
Novel materials
Efficacy
Safety
Device performance
Appropriate study design and evaluation based on its clinical positioning
Appropriate evaluation based on its concept
As a summary, it is necessary to make clear what is the purpose of development.
Should it increase the benefit or decrease the risk?
If it would be clear , we could understand its clinical positioning.
Regarding its clinical positioning, we could make clear patients population, suitable control, efficacy and safety measures.
Off course, pre-clinical test and bench test are required.

12. PMDA’s Consultation Menu
Very early stage
Non-Clinical
CT required? CT
Pre-application
Market and Literature Surveys
Stability Test
Biological Safety Test
Performance Test
Exploratory Clinical Test
Clinical Test for Verification
Development of Application Dossier
Electrical Safety Test
Pre-development consultation
Safety Confirmation Consultation
Consultation on Clinical Evaluation
Clinical Trial Consultation
Pre-application　Consultation
And this slide shows PMDA’s consultation menu. From very early stage to pre-application stage, we have offered various menu.
[click] And these are new categories of consultations, prior assessment consultation and pharmaceutical affairs consultation on R&D strategy.
Quality Consultation
Consultation on Performance Test
Exploratory Clinical Trial Consultation
Application Procedural Consultation
Pharmaceutical Affairs Consultation on R&D Strategy
Prior Assessment Consultation

13. PMDA, Japan Tomohito Suzuki, Ph.D. Office of Medical Devices I
For more information, please visit our website:
URL :
PMDA/we suggest consultation meetings in an early stage of development for clinical trial designing.
You can find that information via PMDA’s web site and it’ll also be welcomed to me.
Thank you so much for your kind attention!
Thank you! 13