Amarex Clinical Research Washington DC metro area A Product Development Services Company. From Lab to Market Approval

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1 Amarex Clinical Research Washington DC metro area A Product Development Services Company Regulatory Strategy From Lab to Market Approval Strategy Implementation Pre-Clinical Assays Global Clinical Trials Global Regulatory Submissions Contact: Patrick Burke at patrickb@amarexcro.com Thank you! Goal of these Seminars Information sharing Professional Development Networking 2 1

2 Applicable Clinical Trials for Clinical Trial Registration Mukesh Kumar, PhD, RAC Senior Director, Regulatory Affairs Amarex Clinical Research Germantown, MD 20874, USA Tel: Applicability of the Law Confusion about certain(!) trials Registration before trial initiation Bioequivalence studies (ANDA) IND/IDE studies 505(b)(2) applications Amendments to applications Protocol amendments Information amendments (CMC, Pharm-tox, etc) Foreign clinical trials Enforcement 4 2

3 History of Clinical Trial Registration FDA Modernization Act 1997 Section 113 instructed the NIH to establish a clinical trial database Serious and life-threatening conditions Only drugs and biologics (not devices) Purpose, eligibility, location and contact First version in Feb 2000 Final Guidance in March 2002 Not mandatory, no penalties for noncompliance Within 21 days of first subject enrollment 5 The Process for Registration Set up an account on Protocol Registration System Organization account: Many trials Individual account: individual investigator Enter Trial information Within 21 days of first subject enrollment Update information as applicable 6 3

4 International Committee of Medical Journal Editors (ICMJE) Declared in 2004 that it will not accept publications for non-registered clinical trials Based on discussions with WHO To increase patient access of clinical trial information Establish a world-wide standard for trial registration Lead to Fair Access to Clinical Trials (FACT) Act proposed in the US Congress in June International Committee of Medical Journal Editors (ICMJE) Minimal Registration Dataset Item Comment 1. Unique trial number 2. Trial registration date 3. Secondary IDs 4. Funding source(s) Name of the organization(s) that provided funding for the study. 5. Primary sponsor 6. Secondary sponsor(s) 7. Responsible contact person Public contact person for the trial, for patients interested in participating. 8. Research contact person Person to contact for scientific inquiries about the trial. 9. Title of the study Brief title chosen by the research group (can be omitted if the researchers wish). 10. Official scientific title of the study This title must include the name of the intervention, the condition being studied, and the outcome 11. Research ethics review Has the study at the time of registration received appropriate ethics committee approval (yes/no)? 8 4

5 International Committee of Medical Journal Editors (ICMJE) Minimal Registration Dataset Item Comment 12. Condition The medical condition being studied 13. Intervention(s) A description of the study and comparison/control intervention(s) 14. Key inclusion and exclusion criteria Key patient characteristics that determine eligibility for participation in the study. 15. Study type Randomized vs. non-randomized, type of masking (e.g., double-blind, single-blind), type of controls (e.g., placebo, active), and group assignment, (e.g., parallel, crossover, factorial). 16. Anticipated trial start date Estimated enrollment date of the first participant. 17. Target sample size The total number of subjects the investigators plan to enroll before closing the trial to new participants. 18. Recruitment status Is this information available (yes/no) (If yes, link to information). 19. Primary outcome The primary outcome that the study was designed to evaluate Description should include the time at which the outcome is measured (e.g., blood pressure at 12 months) 20. Key secondary outcomes The secondary outcomes specified in the protocol. Description should include time of measurement (e.g., creatinine clearance at 6 months). 9 FDA Amendment Act (FDAAA) 2007 All Applicable Clinical trials must be registered by sponsors (responsible party) Expanded data elements Must be done by 26 Dec 2007 Certification of compliance to accompany Applicable trial submissions to FDA Submit trial results upon study completion Severe penalties for non-compliance $10,000 plus $10,000/day till the violation is corrected 10 5

6 The Process for Registration Set up an account on Protocol Registration System Organization account: Many trials Individual account: individual investigator Enter Trial information (Aug 20, 2008) Before IND submission Update information as applicable Enter trial results (Jan 9, 2009) Within 1 year of completion of trial Extension provided on a case-by-case basis with written request and certification 11 Compliance Certification Form FDA 3674 Certify that either not applicable due to No clinical trials No applicable clinical trials Applicable Provide Registration Number obtained from Clinicaltrials.gov Declare that the sponsor is Aware of the law the information is accurate there are no false statements 12 6

7 Initial Developments and Confusion Dec 12, 2007: Emergency release of Form FDA 3674 Compliance should take about 45 min March 5, 2008: First draft guidance May 21, 2008 Guidance on reporting results (Basic Results) August 25, 2008: FDA published response to its March notice (IND trials) December 8, 2008: Draft description of Applicable clinical trials: Bioequivalence studies Jan 21, 2009: Final Guidance 13 Applicable Clinical Trials A clinical trial meeting the following four criteria 1. Using a drug, biologic or device requiring FDA approval for investigation and sale 2. Clinical investigation according to a study protocol 3. Controlled clinical trial 1. Placebo-controlled 2. Dose-comparison 3. Blinded 4. No intervention or active intervention 5. Historical control 4. Other than Phase 1, feasibility, pilot or prototype-testing trial 14 7

8 Current Understanding Covered trials: INDs and new protocol submissions to existing INDs NDAs and efficacy supplements to approved NDAs BLAs and efficacy supplements to approved BLAs Abbreviated new drug applications (ANDAs) Premarket approval applications (PMAs) PMA panel track supplements Humanitarian device exemptions (HDEs) 510(k)s that refer to or include information on a clinical trial 15 Current Understanding Exempt applications: CMC amendments to INDs, NDAs and BLAs Non-clinical pharmacology/toxicology amendments to INDs, NDAs and BLAs Single Patient INDs ANDA amendments and supplements that contain no in-vivo bioequivalence information ANDA, BLA, and NDA promotional materials IND, BLA and NDA Safety Reports ANDA, BLA, NDA, HDE, and PMA mandatory and voluntary adverse event or medical device reports FDA Meeting requests 510(k)s that contain no clinical data 16 8

9 Foreign Clinical Trials Covered only if: Done under a US IND Drug/device manufactured in the US Have US sites (will have a US IND) Used to support a US marketing approval application Completed after Dec 26, Foreign Clinical Trials Three options in FDA 3674 A. I certify that the requirements do not apply because the application/submission which this certification accompanies does not reference any clinical trial. B. I certify that the requirements do not apply to any clinical trial referenced in the application/submission which this certification accompanies. C. I certify that the requirements apply to one or more of the clinical trials referenced in the application/submission which this certification accompanies and that those requirements have been met. 18 9

10 Applicability of the Law Registration before trial initiation Bioequivalence studies (ANDA) IND/IDE studies Foreign clinical trials 505(b)(2) applications Amendments to applications Protocol amendments Information amendments (CMC, Pharm-tox, etc) Enforcement Case by case, for now Avoid by discussing at the meetings 19 Best Practices Register trials on Clinicaltrials.gov Easy process: less than an hour to comply Simple one page certification form, easy account set-up Does not need IRB/FDA pre-approval Easy to update, single user, non-technical Similar processes world-wide Free Foreign trials: If you ever want to think about US market register now 20 10

11 Thank You! Questions and Comments Mukesh Kumar, PhD, RAC Senior Director, Regulatory Affairs Amarex Clinical Research Germantown, MD 20874, USA Tel: