Ich Fda Socra 09 2007

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Ich Fda Socra 09 2007

  1. 1. Where the FDA Regulations End and ICH GCP Begins The Differences & Similarities Between the Two Paul Below, CCRA GCP Trainer Medical Research Management, Inc. SoCRA 16 th Annual Conference Adams Mark Hotel, Denver, CO September 29, 2007
  2. 2. <ul><li>This presentation was inspired by Norman Goldfarb, Managing Director of First Clinical Research. </li></ul><ul><li>At the 2006 SoCRA Annual Meeting, he asked the question during a session on monitoring, “How many in the audience know at least three differences between the FDA regulations and the ICH GCP Guidelines?” </li></ul>
  3. 3. <ul><li>Define what ICH is and what role the ICH guidelines play in clinical research </li></ul><ul><li>Review the ICH Guidelines for Good Clinical Practice (GCP) and how they differ from the FDA regulations </li></ul><ul><li>Discuss the impact of ICH GCPs on Investigator sites </li></ul>Learning Objectives
  4. 4. <ul><li>International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use </li></ul><ul><li>Working group of pharmaceutical industry experts and regulatory authorities from the European Union, Japan, and the United States </li></ul>What is ICH?
  5. 5. <ul><li>Aim to produce a single set of technical requirements for the registration of new drug drug products to streamline development </li></ul><ul><li>Reduce or obviate duplicate testing </li></ul><ul><li>More economical use of human, animal and material resources </li></ul><ul><li>Eliminate unnecessary delays in the availability of new medicines </li></ul>ICH Purpose
  6. 6. <ul><li>Reduced development time and cost </li></ul><ul><li>Easier simultaneous new drug submission in many countries </li></ul><ul><li>Facilitates intra-company globalization </li></ul>Importance of ICH to Industry
  7. 7. <ul><li>European Union began to successfully harmonize member country regulatory requirements in the 1980's </li></ul><ul><li>WHO Conference of Drug Regulatory Authorities (Paris, 1989) was start of the harmonization process between Europe, U.S. and Japan </li></ul><ul><li>First meeting held in 1990 (Brussels) with biennial meetings held since </li></ul><ul><li>37 guidelines produced to date </li></ul>ICH History
  8. 8. <ul><li>Quality (24 guidelines) - related to chemical and pharmaceutical quality assurance </li></ul><ul><li>Safety (15 guidelines) - related to pre-clinical studies </li></ul><ul><li>Efficacy (18 guidelines) - related to clinical research in human subjects </li></ul><ul><li>Multidisciplinary (5 guidelines) – i.e., Medical Terminology (MedDRA) </li></ul>ICH Categories
  9. 9. <ul><li>E2 - Clinical Safety Data Management </li></ul><ul><li>E3 - Structure and Content of Clinical Study Reports </li></ul><ul><li>E6 - Good Clinical Practice </li></ul><ul><li>E7 - Studies in Support of Special Populations/Geriatrics </li></ul><ul><li>E8 - General Consideration of Clinical Trials </li></ul><ul><li>E9 - Statistical Principles for Clinical Trials </li></ul><ul><li>E11 - Clinical Investigation in the Pediatric Population </li></ul><ul><li>E12 - Clinical Evaluation of New Antihypertensive Drugs </li></ul>Efficacy Guidelines
  10. 10. <ul><li>International ethical and scientific quality standard for designing, conducting, recording, and reporting trials that involve participation of human subjects </li></ul><ul><li>Compliance assures rights, safety and well-being of trial subjects are protected (consistent with Declaration of Helsinki) </li></ul>ICH Guideline for GCP (E6)
  11. 11. <ul><li>Facilitate the mutual acceptance of clinical data by the regulatory authorities of the EU, Japan, and the U.S. </li></ul><ul><li>Prior to ICH, criteria for acceptance by FDA of foreign clinical studies outlined in 21 CFR 312.120 (required to conduct trials in accordance with Declaration of Helsinki) </li></ul>ICH GCP Objective
  12. 12. <ul><li>Published as “guidance document” in the Federal Register , Vol. 62, May 9, 1997 </li></ul>ICH GCP Implementation in US
  13. 13. <ul><li>Represents FDA's “current thinking” on ways to comply with regulations </li></ul><ul><li>Not legally binding </li></ul><ul><li>Non-compliance should not be cited in a FDA Form 483 </li></ul>FDA Guidance Documents
  14. 14. <ul><li>E2A Guideline - Requirements and procedures for expedited pre- and post-marketing safety reporting. </li></ul><ul><li>“ Expedited Safety Reporting Requirements for Human Drug and Biological Products” published Federal Register , October 7, 1997. </li></ul><ul><li>Incorporated into CFR 21 part 312.32 on April 6, 1998. </li></ul>ICH as FDA Regulation
  15. 15. Specific Differences Between ICH GCP and the FDA Regulations
  16. 16. <ul><li>Chapter 1 - Glossary </li></ul><ul><li>Chapter 2 - Principles of ICH GCP </li></ul><ul><li>Chapter 3 - Institutional Review Board </li></ul><ul><li>Chapter 4 - Investigator </li></ul><ul><li>Chapter 5 - Sponsor </li></ul><ul><li>Chapter 6 - Protocol and Amendments </li></ul><ul><li>Chapter 7 - Investigator’s Brochure </li></ul><ul><li>Chapter 8 - Essential Documents </li></ul>ICH GCP Sections
  17. 17. <ul><li>FDA and ICH both require the IRB to review informed consent, protocol, advertisements, and the Investigator's Brochure. </li></ul><ul><li>ICH also requires IRB submission of: </li></ul><ul><ul><li>Subject recruitment procedures </li></ul></ul><ul><ul><li>Written information provided to subjects </li></ul></ul><ul><ul><li>Information about subject compensation </li></ul></ul><ul><ul><li>Investigator's current CV and/or other documents evidencing qualifications </li></ul></ul>IRB Responsibilities (ICH 3.1)
  18. 18. <ul><li>Both FDA and ICH require IRBs to be composed of the following members: </li></ul><ul><ul><li>At least five members </li></ul></ul><ul><ul><li>One non-scientific member </li></ul></ul><ul><ul><li>One member not affiliated with the institution </li></ul></ul><ul><ul><li>Members involved in the protocol not have a voting role </li></ul></ul>IRB Composition (ICH 3.2)
  19. 19. <ul><li>FDA also requires the following ( 56.107a-f ): </li></ul><ul><ul><li>One scientific member </li></ul></ul><ul><ul><li>Diversity in race, gender, cultural backgrounds </li></ul></ul><ul><ul><li>Varying backgrounds - not composed of only one profession </li></ul></ul><ul><ul><li>Members qualified to assess the acceptability of the protocol with institutional SOPs & professional practice standards </li></ul></ul><ul><ul><li>Members with a conflicting interest cannot vote for protocol approval </li></ul></ul>IRB Composition cont.
  20. 20. <ul><li>ICH requires Investigators to maintain a list of appropriately qualified persons to whom significant trial-related duties have been delegated. </li></ul>Investigator Agreements (ICH 4.1)
  21. 21. <ul><li>ICH requires Investigators to demonstrate potential for recruiting the required number of patients within the agreed recruitment period. </li></ul><ul><ul><li>Retrospective data </li></ul></ul><ul><ul><li>Patient database analysis </li></ul></ul>Investigator Resources (ICH 4.2)
  22. 22. <ul><li>ICH requires Investigators to inform subjects when medical care is needed for an intercurrent illness. </li></ul><ul><li>ICH recommends that Investigators inform the subject’s primary physician of trial participation (with the subject’s permission). </li></ul><ul><li>ICH requires Investigators to make every reasonable effort to ascertain the reason(s) for subject early withdrawal (although the subject is not obliged to give a reason). </li></ul>Subject Medical Care (ICH 4.3)
  23. 23. <ul><li>ICH requires Investigators (or their designees) to document and explain any deviation from the approved protocol. </li></ul>Protocol Compliance (ICH 4.5)
  24. 24. <ul><li>ICH allows the delegation of study drug dispensing, patient counselling, and drug accountability to a designee. </li></ul><ul><li>FDA has no regulations or guidance concerning delegation of these duties. </li></ul>Investigational Product (ICH 4.6)
  25. 25. <ul><li>ICH allows the delegation of the informed consent process to a designee. </li></ul><ul><li>FDA has no regulations concerning delegation of this duty although it is discussed in the FDA Information Sheets. </li></ul>Informed Consent (ICH 4.8)
  26. 26. <ul><li>ICH requires the person conducting the informed consent process to sign and date the consent form. </li></ul><ul><li>ICH requires that the subject receive a signed and dated copy of the consent form. FDA only requires that a copy be provided. </li></ul>Informed Consent cont.
  27. 27. <ul><li>ICH requires the following informed consent elements not required by the FDA: </li></ul><ul><ul><li>Discussion of trial treatments and probability of random assignment </li></ul></ul><ul><ul><li>Subject responsibilities </li></ul></ul><ul><ul><li>Anticipated payment, if any, to the subject </li></ul></ul><ul><ul><li>Important potential risks and benefits of alternative treatment </li></ul></ul><ul><ul><li>Authorization to access medical records by regulatory authorities (FDA and foreign) </li></ul></ul>Informed Consent cont.
  28. 28. <ul><li>ICH requires Investigators (or designees) to: </li></ul><ul><ul><li>Document explanations for discrepancies between data in the CRFs and the source documents. </li></ul></ul><ul><ul><li>Initial, date and explain (if necessary) all CRF changes/corrections. CRF designees must be documented. </li></ul></ul><ul><ul><li>Endorse & retain records of all CRF changes made by the Sponsor. </li></ul></ul>Records and Reports (ICH 4.9)
  29. 29. <ul><li>ICH requires the retention of “essential documents” for at least two years after the approval of a marketing application in an ICH region or until there is no pending or contemplated applications in an ICH region or development is formally discontinued. </li></ul><ul><li>ICH compliance generally requires a longer retention time than FDA regulations. </li></ul>Records and Reports (ICH 4.9)
  30. 30. <ul><li>ICH requires Sponsors to secure agreement from all involved parties to ensure direct access of study records to foreign regulatory authorities. </li></ul>Sponsor QA/QC (ICH 5.1)
  31. 31. <ul><li>ICH requires Sponsors to inform Investigators in writing of: </li></ul><ul><ul><li>Study record retention requirements </li></ul></ul><ul><ul><li>Notification of when records are no longer needed </li></ul></ul>Record Keeping (ICH 5.5)
  32. 32. <ul><li>ICH requires Sponsors to provide insurance or indemnify the investigator against claims arising from the trial. </li></ul>Compensation (ICH 5.8)
  33. 33. <ul><li>FDA requires extensive disclosure of the Investigator’s financial relationship with the Sponsor (21 CFR 54). </li></ul><ul><li>ICH has no comparable guideline and only requires that financial aspects of the trial be documented in an agreement between the Sponsor and Investigator. </li></ul>Financing (ICH 5.9)
  34. 34. <ul><li>ICH requires Sponsors to obtain a statement from Investigators that their local IRB is organized and operates according to GCP and applicable laws and regulations. </li></ul>IRB Review (ICH 5.11)
  35. 35. <ul><li>ICH requires Sponsors to obtain documentation of IRB approval prior to shipping investigational product to an Investigator. </li></ul>Supplying IP (ICH 5.14)
  36. 36. <ul><li>FDA specifies that Sponsors shall monitor the progress of all clinical investigations (21 CFR 312.56) and that monitors be qualified by training and experience (21 CFR 312.53). </li></ul><ul><li>FDA has a guidance document on the topic, “Guideline for the Monitoring Clinical Investigations” (January 1988). </li></ul>Monitoring (ICH 5.18)
  37. 37. <ul><li>ICH includes the following items not addressed in the FDA guidance: </li></ul><ul><ul><li>Monitor qualifications must be documented </li></ul></ul><ul><ul><li>Monitors must verify that trial functions have not been delegated to unauthorized individuals </li></ul></ul><ul><ul><li>Sponsors must document review and follow-up of the monitoring report </li></ul></ul>Monitoring cont.
  38. 38. <ul><li>ICH has more detailed outline of contents of the protocol and Investigator Brochure than the FDA regulations [21 CFR 312.23(a)(5-6)] </li></ul><ul><li>ICH requires that the protocol identify any data to be recorded directly on the CRFs and to be considered source data (ICH 6.4.9) </li></ul>Protocol and IB (ICH 6 & 7)
  39. 39. <ul><li>ICH requires the following documents not specified by the FDA: </li></ul><ul><ul><li>Subject Screening Log (to document subjects who enter trial screening) </li></ul></ul><ul><ul><li>Subject Identification Code List (confidential list of subject names in case identity must be revealed for follow-up) </li></ul></ul><ul><ul><li>Signature Sheet (to document signatures/initials of persons authorized to make CRF entries and corrections) </li></ul></ul>Essential Documents (ICH 8)
  40. 40. <ul><li>ICH requires the following documents be filed at the site: </li></ul><ul><ul><li>Trial Initiation Monitoring Report (to document that trial procedures were reviewed with the Investigator and staff) </li></ul></ul><ul><ul><li>Relevant Communications (letters, meeting notes, notes of telephone calls) </li></ul></ul>Essential Documents cont.
  41. 41. <ul><li>This presentation and related references are posted on my corporate website at: www.pbelow-consulting.com/ich-fda.html </li></ul>
  42. 42. <ul><li>Office: (952) 882-4083 </li></ul><ul><li>E-mail: [email_address] </li></ul>Contact Information

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