Exports & Clinical Trials for Medical Devices
Dr. Subodh P. AdesharaExecutive DirectorSahajanand Medical Technologies Pvt. Ltd.
&Coordinator – Medical Devices Panel - Pharmexcil
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
Costs
Costs – Macro View Pre-Clinical (estimates)
Chemistry – 30% to 60% of the cost of West Other Pre-clinical
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
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)
Drugs Controller General India (DCGI) –Role
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 Stents2.Drug Eluting Stents3.Catheters4.Intra Ocular Lenses5.I.V. Cannulae6.Bone Cements7.Heart Valves8.Scalp Vein Set9.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 2 Weeks• Dual use, Rule 37 & Neutral code 3 Weeks• Additional indication etc. 4 Weeks• Form 10 4 Weeks• Test License 4 Weeks• First response to New Drug 6 Weeks• FDC first response 6 Weeks• Endorsement of additional 8 Weeks products on registration• Registration 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 Applicant2.Transfer of Responsibility letter from the sponsor3.Name of the Device4.Regulatory status of the device in other countries (US
FDA clearance/approval)5.Objective of the Study6.Phase of study7.Names of the Participating Countries/Investigator sites 8.No. of patients to be included in India9.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 countries12. Affidavit from the sponsor regarding non- discontinuation of the study13. 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 Dosage Form Composition
II. Animal Pharmacology DataIII. Animal Toxicology dataIV. Clinical data
17.Documents submittedI. Form 44 & Fee ReceiptII. Form 12 and Fee ReceiptIII. Details of Biological specimens to be exportedIV. ProtocolV. Informed Consent FormVI. Case Report FormVII. Investigator’s BrochureVIII. Undertakings & CVs by InvestigatorsIX. 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 component4-6 Weeks
2.Devices not containing Drug Component4-6 Weeks
3.Devices Under notification categoryExport 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 letter2.Copy of DCGI approval letter3.Letters from the Labs4.Aayat Niryaat Form5.Copy of IEC Certificate6.Copy of PAN Number7.Copy of Registration cum Membership certificate8.List of Directors9.Copy of Certificate of Incorporation10.Copy of Study Protocol11.Copy of Export Permission
Approval Timelines -Export Licence
1.Devices Containing Drug Component2 Weeks
2.Devices Not Containing Drug Component2 Weeks
3.Devices Under Notification CategoryExport Licence not issued by Jt. DGFT
Role of Pharmaceutical Export Promotion Council - PHARMEXCIL
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
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
Helps exporters to get exposed to buyer’s marke Promotes export by helping industry to fulfill export
procedures
Provides Technical support wherever possible
Activities like seminars, training, cluster development for modernization
Current Trials being Conducted inIndia – NIH Registered
Overall Clinical Trials 870/68811 1.3%
Device based Trials 25/3544 0.7%
Biotechnology based Trials 3/140 2.1% Stent based Trials 13/409 3.2%
ClinicalTrials.gov
Why India ?
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]
Indian Stent Trials - Completed
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
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
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
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 Biology, chemistryLocal effects Systemic effectsTechnology development ResearchSystematic & rapid product development Slow, trial & error product developmentEngineers ScientistsProduct lifetime usually short Product lifetime usually long
[adapted from Sumner K. Attitude Adjustment. Available on www.devicelink.com]
WW Combination Product Market
2009 (est)$10 billion
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
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 Multi-national 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