Exports

1
Exports Clinical Trials for Medical Devices

• Dr. Subodh P. Adeshara
• Executive Director
• Sahajanand Medical Technologies Pvt. Ltd.
• Coordinator Medical Devices Panel - Pharmexcil

2
(No Transcript)
3
(No Transcript)
4
(No Transcript)
5
Industry Segments
6
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

7
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

8
Costs Cont..

• Costs Micro View
• Item US Cost India Cost

9
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)

10
Indian Regulatory Environment Regulatory Bodies
Governing Controlling Clinical Trials
11
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

12
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

13
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.

14
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.

15
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.

16
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

17
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/Investigato
  r 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.

18
Checklist of documents contd.

• 11. Status of the study in other countries
• 12. Affidavit from the sponsor regarding non-
• discontinuation 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).

19
Checklist of documents contd.

• 16.Data submitted
• Chemical Pharmaceutical data
• Generic name and chemical name
• Dosage Form
• Composition
• Animal Pharmacology Data
• Animal Toxicology data
• Clinical data
• 17.Documents submitted
• Form 44 Fee Receipt
• Form 12 and Fee Receipt
• Details of Biological specimens to be exported
• Protocol
• Informed Consent Form
• Case Report Form
• Investigators Brochure
• Undertakings CVs by Investigators
• Ethics Committee approvals (For Category B)

20
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

21
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

22
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

23
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

24
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

25
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

26
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 buyers marke
• Promotes export by helping industry to fulfill
  export procedures
• Provides Technical support wherever possible
• Activities like seminars, training, cluster
  development for modernization

27
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

28
Global Trials in India
Based on The Boston Consulting Group and Business
Communications Co.
29
Trials in India
Based on The Boston Consulting Group and Business
Communications Co.
30
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

31
On-going Device Based Trials in India
32
Interventional Cardiology Device based Trials

• Indian Trials
• Multi-national Trials

33
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)

34
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)

35
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)

36
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

37
(No Transcript)
38
(No Transcript)
39
Market Implications

• adapted from Sumner K. Attitude Adjustment.
  Available on www.devicelink.com

40
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

41
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 devi
  ce based trials have already been conducted and
  many more are in pipeline
• Some regulatory and local IRB Accreditation
  issues need still to be addressed

42
Thank You