Download Exports & Clinical Trials

Exports & Clinical Trials for
Medical Devices
Dr. Subodh P. Adeshara
Executive Director
Sahajanand Medical Technologies Pvt. Ltd.
&
Coordinator – Medical Devices Panel - Pharmexcil
Industry Segments
Global Clinical Trials
Permission is required from CDSCO for
conducting global clinical trials in the
country
 Phase I for New Drug substance
developed outside India is not permitted
 So far, approx. 500 permissions have been
granted since 2003
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Costs
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Costs – Macro View
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Pre-Clinical (estimates)
 Chemistry – 30% to 60% of the cost of West
 Other Pre-clinical
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Toxicology – 30% of the cost of the West
Animal Testing – 30% of the Cost of the West
Clinical (estimates)
 Phase I – 25% of the cost of the West
 Phase II/III – 30% of the cost of the West
Time Equals Money
 Patient Recruitment
 Pre-clinical Regulations
Costs Cont..
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Costs – Micro View
Item
US Cost
India Cost
Conducting Clinical trials With
Medical Devices in India
Regulatory Aspects
(Regulated by the DCGI office under
Gazette Notification No.
S.O. 1468(E) dated 6th October 2005 and
G.S.R. 627(E) dated 7th October 2005)
Indian Regulatory Environment –
Regulatory Bodies Governing &
Controlling Clinical Trials
Drugs Controller General India
(DCGI) –Role
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Permission to conduct clinical trials with
New Drugs/Existing Drugs/Medical devices
under drugs category
Import license / Test License for clinical trial
drug supplies – concurrent with main
submission
Approval for conducting clinical trials with
Medical Devices under Drug Category
Permission/N.O.C./Notification for Protocol
Amendments/ICF amendments/Safety
reports
Notification for SAEs observed in ongoing
clinical trials
Following Medical Devices have been considered as
Drug by DCGI as per Gazette notification no. S.O.
1468(E) dated 6th October 2005 and G.S.R. 627(E)
dated 7th October 2005
1.Cardiac Stents
2.Drug Eluting Stents
3.Catheters
4.Intra Ocular Lenses
5.I.V. Cannulae
6.Bone Cements
7.Heart Valves
8.Scalp Vein Set
9.Orthopedic Implants
10. Internal Prosthetic Replacements
Medical Devices Contd…
A. All devices falling under the category of devices specified
by DCGI and containing the drug components will:
1.Be reviewed and approved by the NEW
DRUG DIVISION of the DCGI.
2.Approval timelines are 4-6 weeks for Category A and
8-12 weeks for Category B applications.
a. CATEGORY A: Those Protocols which are approved
by recognized and developed countries viz. USA,
UK, Switzerland, Australia, Canada, Germany, South
Africa, Japan, EMEA.
b. CATEGORY B: All other applications not falling
under Category A.
Medical Devices Contd…
B. All devices falling under the category of
devices specified by DCGI and not containing
the drug component will:
1.Be reviewed and approved by the
MEDICAL DEVICE SECTION of DCGI.
2.Approval timelines are between 6-8
weeks.
Medical Devices Contd…
C. All those devices which do not fall under the
category of devices specified by DCGI will :
1.Be submitted ONLY FOR NOTIFICATION at DCGI
for conduct of clinical trial.
2.No written approval / NOC is issued / required
from DCGI to conduct clinical trial in India.
3.Ethics Committee approvals are required to
initiate the clinical trial at the sites.
Timelines
Approval
Time Frame
• Export NOC
• Dual use, Rule 37 &
Neutral code
• Additional indication etc.
• Form 10
• Test License
• First response to New Drug
• FDC first response
• Endorsement of additional
products on registration
• Registration
2 Weeks
3
4
4
4
6
6
8
Weeks
Weeks
Weeks
Weeks
Weeks
Weeks
Weeks
12 weeks
Checklist of documents for seeking permission
to conduct Clinical Trial with Medical Devices
under Drug category (With Drug / Without Drug)
and Device category
1.Name of the Applicant
2.Transfer of Responsibility letter from the sponsor
3.Name of the Device
4.Regulatory status of the device in other countries (US
FDA clearance/approval)
5.Objective of the Study
6.Phase of study
7.Names of the Participating Countries/Investigator sites
8.No. of patients to be included in India
9.Country / IRB approvals from participating countries
10.ISO/CN/CE certification for the manufacturing facility
and the list of countries where the device is being
marketed.
Checklist of documents contd….
11. Status of the study in other countries
12. Affidavit from the sponsor regarding nondiscontinuation of the study
13. CE certificate from European authority & approval
from Australia / Canada / Japan, if available
14. Undertaking of conformity w.r.t product standards,
safety & effectiveness requirements and quality
systems in the country of origin.
15. Clinical data and published literature on the safety,
quality & usefulness of the medical substance used
in the medical device (Only for devices containing
drug component).
Checklist of documents contd….
16.Data submitted
I.
Chemical & Pharmaceutical data

Generic name and chemical name
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Dosage Form
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Composition
II.
Animal Pharmacology Data
III.
Animal Toxicology data
IV.
Clinical data
17.Documents submitted
I.
Form 44 & Fee Receipt
II.
Form 12 and Fee Receipt
III.
Details of Biological specimens to be exported
IV.
Protocol
V.
Informed Consent Form
VI.
Case Report Form
VII.
Investigator’s Brochure
VIII. Undertakings & CVs by Investigators
IX.
Ethics Committee approvals (For Category B)
Directorate General of Foreign Trade
–Role
1.Issuing Export Permission for
exporting Human biological samples
for study related analysis to Central
Lab
• Export Permission valid for a period of 1
year
2.Revalidation of Export Permission
Approval Timelines -Export
Permission
1.Devices Containing Drug component
4-6 Weeks
2.Devices not containing Drug
Component
4-6 Weeks
3.Devices Under notification category
Export Permission not issued by DGFT
Joint Directorate General of Foreign
Trade –Role
1.Issuing Export License for exporting
Human biological samples for study
related analysis to central lab
• The export license is valid for a period of
2 years
2.Revalidation of Export License
Checklist of documents to be
submitted for Export License
1.Cover letter
2.Copy of DCGI approval letter
3.Letters from the Labs
4.Aayat Niryaat Form
5.Copy of IEC Certificate
6.Copy of PAN Number
7.Copy of Registration cum Membership certificate
8.List of Directors
9.Copy of Certificate of Incorporation
10.Copy of Study Protocol
11.Copy of Export Permission
Approval Timelines -Export Licence
1.Devices Containing Drug Component
2 Weeks
2.Devices Not Containing Drug
Component
2 Weeks
3.Devices Under Notification Category
Export Licence not issued by Jt. DGFT
Role of Pharmaceutical Export
Promotion Council - PHARMEXCIL
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Promote Activity related to export of
Medical Devices
Conduit for financial assistance by
GOI
Up gradation of medical Device
Industry in the country
Vital link between India & Buyer
Countries
Conducts buyer seller meets
Activity by Pharmexcil
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50% of expense on Registration of Medical Device in
any country for the purpose of Export is Reimbursed by
GOI thro’ Pharmexcil upto Rs 50 lacs pa per company.
Such registration costs several thousands of USD
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Helps exporters to get exposed to buyer’s marke
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Promotes export by helping industry to fulfill export
procedures
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Provides Technical support wherever possible
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Activities like seminars, training, cluster development
for modernization
Current Trials being Conducted in
India – NIH Registered
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Overall Clinical Trials
Device based Trials
Biotechnology based Trials
Stent based Trials
870/68811
25/3544
3/140
13/409
1.3%
0.7%
2.1%
3.2%
ClinicalTrials.gov
Global Trials in India
Based on The Boston Consulting Group and Business Communications Co.
Trials in India
Based on The Boston Consulting Group and Business Communications Co.
Why India ?
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Genetically diverse population : Western
disease distribution
Low Cost : 40-60% reduction
Large and quick pt. recruitment
Over 600 ICH/GCP compatible sites
Large number of medical specialists
Well developed IT and other infrastructure
available
English as spoken and technical language
Increase in number of CROs [National and
International]
On-going Device Based Trials in
India
Interventional Cardiology Device
based Trials
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Indian Trials
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Multi-national Trials
Indian Stent Trials - Completed
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SIMPLE I : Infinnium stent, FIM, completed (SMT)
NOVA FIM : Pronova stent, FIM, completed (Vascular
Concepts)
RELEASE T : Relisys stent, FIM, completed (Relisys Medical
Devices)
SIMPLE II & III : Infinnium stent, Pre-market, completed
(SMT)
EMPIRE : Propass stent, Pre-market, completed (Vascular
Concepts)
PROSES & INNOVA : Propass stent, Post-market,
completed (Vascular Concepts)
SERIES I : Supralimus stent, FIM, Completed (SMT)
MAXIMUS : Supralimus-Core stent, FIM, Completed (SMT)
Multinational Device based Trials Completed
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COSTAR I : Costar stent, FIM (Conor Medsystems)
WISDOM : Taxus stent, Pre-market (Boston Scientific)
SPIRIT II : Xience V vs. Taxus stent, Pre-market (Abbott
Vascular)
TAXUS OLYMPIA : Taxus stent, Post-market (Boston
Scientific)
E – Cypher : Cypher stent, Post-market (Cordis, J & J)
VIVE : Vision stent, Post-market (Abbott Vascular)
REALITY : Cypher vs. Taxus stent, Post-market (Cordis, J
& J)
DECODE : Cypher vs. Bx Velocity stent, Post-market
(Cordis, J & J)
SPIRIT V : Xience V stent, Post-market (Abbott Vascular)
Multinational Device based Trials On-going
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FRONTIER : Frontier Bifurcation stent, Post-market
(Abbott Vascular)
PROTECT : Endeavor vs. Cypher stent, Post-market
(Medtronic)
E – SELECT : Cypher stent, Post-market (Cordis, J &
J)
CC Flex : CC Flex stent, Post-market (eucatech )
FREEDOM : Cypher vs. CABG, Post-market (Boston)
ENDEAVOR 5 : Endeavor stent, Post-market
(Medtronic)
EXPORT : Export Aspiration Catheter, Post-market
(Medtronic)
PANORAMA : CRDM Device, Post-market (Medtronic)
Bone Marrow aspiration for CLI, Post-market
CiTopTM Guidewire for CTO, Post-market (Ovalum)
Issues in India
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Informed Consent Issues
Truly Independent IRBs
Proper documentation
Under-reporting by pts., physicians etc.
Proper Follow-up
Change in study co-coordinators
Regulatory Apparatus
Market Implications
Devices
Drugs
Engineering, materials
Local effects
Technology development
Systematic & rapid product development
Engineers
Product lifetime usually short
Biology, chemistry
Systemic effects
Research
Slow, trial & error product development
Scientists
Product lifetime usually long
[adapted from Sumner K. Attitude Adjustment. Available
on www.devicelink.com]
WW Combination Product Market
2009 (est)
$10 billion
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88% all Cardiovascular applications
12% Wound Care, Orthopedics and all other
applications
DES will account for 70% of total market
[Combination Products: An Impact Analysis on the
Convergence of Medical Devices and Therapeutics.
Navigant Consulting/Front Line Strategic Market Reports]
Conclusions
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Clinical trial industry in India accounts for ~
1% of global trials but is likely to increase
up to 15%
Lower cost and faster recruitment potential
is most important reason for it
Several Indian and prestigious Multinational device based trials have already
been conducted and many more are in
pipeline
Some regulatory and local IRB
Accreditation issues need still to be
addressed