Exports & Clinical Trials for Medical Devices

Dr. Subodh P. AdesharaExecutive DirectorSahajanand 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

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

Costs Cont..

Costs – Micro ViewItem 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

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

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 ?

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

Indian Trials

Multi-national Trials

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