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Fda Acceptance Of Foreign Clinical Trial Data Feb 2009

Webinar_Feb 24, 2009

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Fda Acceptance Of Foreign Clinical Trial Data Feb 2009

  1. 1. <ul><li>A Product Development Services Company </li></ul><ul><li>From Lab to Market Approval </li></ul><ul><li>Regulatory Strategy </li></ul><ul><li>Strategy Implementation </li></ul><ul><li>Pre-Clinical Assays </li></ul><ul><li>Global Clinical Trials </li></ul><ul><li>Global Regulatory Submissions </li></ul><ul><li>Contact: Patrick Burke at [email_address] </li></ul><ul><li>301-528-7000 </li></ul>Amarex Clinical Research Washington DC metro area
  2. 2. <ul><li>Thank you! </li></ul><ul><li>Goal of these Seminars </li></ul><ul><li>Information sharing </li></ul><ul><li>Professional Development </li></ul><ul><li>Networking </li></ul>
  3. 3. FDA Acceptance of Foreign Clinical Trial Data in INDs and NDA/BLA Mukesh Kumar, PhD, RAC Senior Director, Regulatory Affairs Amarex Clinical Research Germantown, MD 20874, USA Tel: 001-240-750-4893 Email: [email_address]
  4. 4. Agenda for this Seminar <ul><li>Legal Aspects </li></ul><ul><ul><li>Current regulations </li></ul></ul><ul><ul><li>History of acceptance </li></ul></ul><ul><li>Practical Aspects </li></ul><ul><ul><li>Regulatory issues </li></ul></ul><ul><ul><li>Logistical issues </li></ul></ul><ul><ul><li>Scientific issues </li></ul></ul><ul><ul><li>Business issues </li></ul></ul>
  5. 5. Kinds of Foreign Clinical Trails <ul><li>IND studies: Studies partially or completed conducted at foreign sites under a US IND </li></ul><ul><ul><li>All US IND rules apply </li></ul></ul><ul><ul><li>Percent split of foreign verses US subjects </li></ul></ul><ul><li>Non-IND Studies: Studies conducted at foreign sites </li></ul><ul><ul><li>Foreign sponsors </li></ul></ul><ul><ul><li>Conditions apply for acceptance </li></ul></ul>
  6. 6. IND Studies <ul><li>Foreign sites for speed and reduced cost </li></ul><ul><ul><li>All non-US sites treated same (?) </li></ul></ul><ul><ul><li>More than 50% of all IND trials have non-US sites </li></ul></ul><ul><ul><li>More than 40% investigators are non-US </li></ul></ul><ul><li>Involve FDA supervision and discussions </li></ul><ul><li>Percent split in study subjects between US and non-US sites </li></ul><ul><ul><li>Early studies: up to 100% at foreign sites </li></ul></ul><ul><ul><li>Pivotal studies: statistically justifiable subject split between US and foreign sites </li></ul></ul><ul><ul><li>Bridging study for extrapolation of results might be needed </li></ul></ul>
  7. 7. Non-IND Studies <ul><li>Foreign manufacturers </li></ul><ul><ul><li>US market not initially intended </li></ul></ul><ul><ul><li>Product invented/discovered outside the US </li></ul></ul><ul><li>Used in support of an IND or NDA/BLA </li></ul><ul><ul><li>Up to 15% of non-IND data </li></ul></ul>
  8. 8. FDA Acceptance of Foreign Clinical Data <ul><li>Legally acceptable so long as the clinical trials meet the following criteria </li></ul><ul><ul><ul><li>Good Clinical Practices (ICH E6) </li></ul></ul></ul><ul><ul><ul><li>Clinical Investigators of recognized Competence </li></ul></ul></ul><ul><ul><ul><li>Valid Scientific Evidence </li></ul></ul></ul><ul><ul><ul><li>Applicable to U.S. Population/Medical Practice </li></ul></ul></ul>21 CFR §312.120 21 CFR § 860.7
  9. 9. Global Clinical Trials Source: Clinicaltrials.gov
  10. 10. Most of FDA-Registered Investigators Are From the Developed Countries Source: Parexel's Bio/Pharmaceutical R&D Statistical Sourcebook 2006/2007 Total No. of Investigators (~23000) Non-US Investigators 9.6% 3.9% 1.3% 1.5% 1.9%
  11. 11. FDA Guidance Documents <ul><li>June 1998: ICH E5 – Ethnic factors in the acceptability of foreign clinical data </li></ul><ul><ul><li>Sep. 2006: Clarifications and Q&A </li></ul></ul><ul><li>April 2008: Foreign clinical studies not conducted under an IND application </li></ul>
  12. 12. ICH E5: Ethnic Factors <ul><li>Ethnic factors </li></ul><ul><ul><li>Intrinsic: genetic and physiologic </li></ul></ul><ul><ul><li>Extrinsic: cultural and environmental </li></ul></ul><ul><li>An ICH guidance for acceptance of data generated in one region in another </li></ul><ul><ul><li>Avoid duplication of clinical data </li></ul></ul><ul><ul><li>Characterize effect of ethnic factors on safety, efficacy, dosage and dose regimen </li></ul></ul><ul><ul><li>Bridging studies for extrapolation of results </li></ul></ul>
  13. 13. ICH E5: Main Elements <ul><li>Complete clinical package </li></ul><ul><ul><li>Adequate PK, PD, dose response, safety and efficacy </li></ul></ul><ul><ul><li>GCP clinical trials </li></ul></ul><ul><ul><li>Population representative of the new region </li></ul></ul><ul><li>Extrapolation of data to new region </li></ul><ul><ul><li>Sensitivity to ethnic factors </li></ul></ul><ul><ul><li>Bridging data: safety and efficacy </li></ul></ul><ul><ul><ul><li>Sub-set of complete data </li></ul></ul></ul><ul><ul><ul><li>Bridging clinical study </li></ul></ul></ul>
  14. 14. Non-IND Clinical Studies <ul><li>Acceptable if: “Well-designed, well-conducted study conducted in accordance with GCP and FDA ability to audit” </li></ul><ul><ul><li>Proof of GCP compliance </li></ul></ul><ul><ul><li>On site audit of complete data </li></ul></ul><ul><li>Specific clarification and final decisions provided in April 2008 guidance </li></ul>
  15. 15. Acceptance Criteria for non-IND studies <ul><li>GCP as defined in ICH E6 </li></ul><ul><ul><li>Complete data </li></ul></ul><ul><ul><ul><li>Source data </li></ul></ul></ul><ul><ul><ul><li>CRFs </li></ul></ul></ul><ul><ul><ul><li>Quality documents </li></ul></ul></ul><ul><li>Under the law of the region where study conducted </li></ul><ul><ul><li>All regions follow GCP </li></ul></ul><ul><ul><li>Stringent human subject protection </li></ul></ul>
  16. 16. Acceptance Criteria for non-IND studies <ul><li>Specific documents required </li></ul><ul><li>Investigator qualifications </li></ul><ul><li>Description of research facilities </li></ul><ul><li>Detailed protocol and results </li></ul><ul><li>Complete CMC information </li></ul><ul><li>Scientific rationale and statistical justification of results </li></ul><ul><li>Name and address of the IEC </li></ul><ul><li>Summary of IEC decisions </li></ul><ul><li>Description of informed consent process </li></ul><ul><li>Incentives to participants </li></ul><ul><li>Clinical and safety monitoring processes followed </li></ul><ul><li>Investigator training </li></ul>
  17. 17. Practical Issues with using non-US sites in clinical trials <ul><li>Regulatory issues </li></ul><ul><ul><li>Variations in regional regulatory processes </li></ul></ul><ul><ul><li>Non-IND studies with limited data </li></ul></ul><ul><ul><li>IRB and IEC requirements </li></ul></ul><ul><ul><li>All studies are need for safety ( even studies that cannot be used in support of IND/NDA ) </li></ul></ul><ul><ul><li>Final decision of acceptability resides with FDA </li></ul></ul><ul><li>Logistical issues </li></ul><ul><ul><li>Documentation required </li></ul></ul><ul><ul><li>Packaging of information </li></ul></ul><ul><ul><li>Management of sites and investigators </li></ul></ul>
  18. 18. Practical Issues with using non-US sites in clinical trials <ul><li>Scientific issues </li></ul><ul><ul><li>Extrapolation of results minus the bridging studies </li></ul></ul><ul><ul><li>Characterization of ethnic factors </li></ul></ul><ul><ul><li>Percent split of the subjects between US and non-US sites </li></ul></ul><ul><li>Business issues </li></ul><ul><ul><li>Risk of rejection by the FDA </li></ul></ul><ul><ul><li>Ethical and public policy issues </li></ul></ul><ul><ul><li>Public opinion and political environment </li></ul></ul>
  19. 19. Best Options <ul><li>File IND as early as possible </li></ul><ul><ul><li>Foreign proof-of-concept under US IND </li></ul></ul><ul><ul><li>Good rationale and statistical strength of data </li></ul></ul><ul><li>Strict enforcement of GCP </li></ul><ul><li>Good documentation </li></ul><ul><ul><li>in English – translate early </li></ul></ul><ul><li>FDA discussions </li></ul><ul><ul><li>FDA Meetings and other communications </li></ul></ul><ul><ul><li>Small business office </li></ul></ul><ul><ul><li>Foreign collaboration office </li></ul></ul>
  20. 20. <ul><li>&quot;It takes 20 years to build a reputation and five minutes to ruin it.&quot; </li></ul><ul><li>Warren Buffett Investor, businessman and philanthropist </li></ul>
  21. 21. Thank You! Questions and Comments Mukesh Kumar, PhD, RAC Senior Director, Regulatory Affairs Amarex Clinical Research Germantown, MD 20874, USA Tel: 001-240-750-4893 Email: [email_address]

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