1 / 59

Food and Drug Administration (FDA): FDA overview and Bioresearch Monitoring

Food and Drug Administration (FDA): FDA overview and Bioresearch Monitoring. CDR Tejashri Purohit-Sheth, M.D. Branch Chief, Good Clinical Practice II Division of Scientific Investigations Center for Drug Evaluation and Research Food and Drug Administration. Outline. FDA Overview History

Download Presentation

Food and Drug Administration (FDA): FDA overview and Bioresearch Monitoring

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Food and Drug Administration (FDA): FDA overview andBioresearch Monitoring CDR Tejashri Purohit-Sheth, M.D. Branch Chief, Good Clinical Practice II Division of Scientific Investigations Center for Drug Evaluation and Research Food and Drug Administration

  2. Outline • FDA Overview • History • Product Development Process • Bioresearch Monitoring

  3. FDA Mission • “The FDA's mission is to promote and protect the public health by helping safe and effective products reach the market in a timely way, and monitoring products for continued safety after they are in use. Our work is a blending of law and science aimed at protecting consumers.”

  4. FDA Responsibilities • protecting the public health by assuring the safety, effectiveness, and security of • human and veterinary drugs, vaccines and other biological products, medical devices, our nation’s food supply, cosmetics, dietary supplements, and products that give off radiation • advancing the public health by helping to speed product innovations • helping the public get the accurate, science-based information they need to use medicines and foods to improve their health

  5. FDA Regulates • foods, except for most meat and poultry products, which are regulated by the U.S. Department of Agriculture • food additives • infant formulas • dietary supplements • human drugs • vaccines, blood products, and other biologics • medical devices, from simple items like tongue depressors, to complex technologies such as heart pacemakers • electronic products that give off radiation, such as microwave ovens and X-ray equipment • cosmetics • animal feeds and drugs, and devices used in pets, farm animals, and other animals • tobacco products

  6. History

  7. History • Harvey Wiley – chief chemist in Division of Chemistry in Department of Agriculture Bureau of Chemistry (1901) • Bureau examined chemicals with the aim of standardizing analyses for quality and consistency *FDA: A Century of Consumer Protection – FDLI publication for the FDA Centennial + FDA’s Centennial History sites

  8. History • 1902 Biologics Control Act (later called Public Health Service – PHS – Act) • 1901 = death of 10 children after contracting tetanus from horse anti-diphtheria antitoxin • Regulated sale of viruses, serums, toxins, and analogous products • Authorized biologics regulations • Required licensing of manufacturers and establishments • Provided inspection authority

  9. History • Pure Food and Drugs Act of 1906 • Passed due to shocking disclosures of insanitary conditions in meat packing plants, use of toxic preservatives in dyes and foods, and cure-all claims for dangerous patent meds • Act prohibits interstate commerce of misbranded and adulterated foods, drinks, and drugs • Manufacturer not required to submit evidence of drug safety or efficacy

  10. History • Pure Food and Drugs Act of 1906 (cont.) • Permitted government to take action if a drug proved too dangerous or misbranded • 1911 Supreme Court judgment = Act did not prohibit false therapeutic claims, only false and misleading statements about the ingredients or identity of a drug

  11. History • 1912 – Sherley Amendment prohibits labeling medicines with false therapeutic claims intended to defraud the consumer • 1927 – Bureau of Chemistry reorganized • Bureau of Chemistry and Soils • Food, Drug, and Insecticide Administration • 1931 – Agricultural appropriations act changed name to Food and Drug Administration

  12. History • 1933-1937- several bills introduced into the Senate to modify the Pure Food and Drugs Act, but to no avail • 1937 – elixir of sulfanilamide tragedy • Sulfanilamide = limited solubility in common solvents • Diethylene glycol (antifreeze) proved an excellent solvent • Pleasing fragrance and sweet flavor – but toxic! • 107 died

  13. Food, Drug and Cosmetic Act of 1938 • Required new drugs to be shown safe before marketing (new drug application – NDA) • Authorized factory inspections • Extended controls to cosmetics and therapeutic devices • Authorized standards for foods • Added court injunctions to previous penalties of seizure and prosecution

  14. New tragedy reform • 1961 – thalidomide, sedative-hypnotic marketed to pregnant women to combat morning sickness, found to cause birth defects • Safety concerns led FDA’s Dr. Frances Kelsey to keep it off of U.S. market • Distributed in U.S. only as investigational product, though recipients not informed of investigational status

  15. Kefauver-Harris amendments of 1962 • Required • Demonstration of efficacy • Informed consent • Control of investigational drugs • 1963 – implemented via Investigational New Drug (IND) regulations requiring • Submission of protocols • Identification of clinical investigators involved and submission of their qualifications • Identification of facilities involved with the studies

  16. Judicial concurrence • 1970 – Court of Appeals upholds enforcement of 1962 amendments – rules commercial success alone ≠ substantial evidence of safety and efficacy • 1973 – Supreme Court upholds effectiveness law and endorses FDA regulatory actions to control entire classes of products rather than relying on time-consuming litigation

  17. Other additions • 1971 – Bureau of Radiological Health • 1972 • Regulation of biologics, including serums, vaccines, and blood products transferred from NIH • Over-the-Counter (OTC) drug review initiated • 1976 (and 1990) – Medical Device regulations

  18. FDA-Legal Authority • 1902 – Biologics Control Act • 1906 – Pure Food and Drug Act • 1938 – Federal Food, Drug, and Cosmetic Act • 1944 – Public Health Service Act • 1951 – Food, Drug, and Cosmetics Act Amendments • 1962 – Food, Drug, and Cosmetics Act Amendments • 1966 – Fair Packaging and Labeling Act • 1976 – Medical Device Regulation Act • 1987 – Prescription Drug Marketing Act

  19. FDA-Legal Authority • 1988 – Anti–drug Abuse Act • 1990 – Nutrition Labeling and Education Act • 1992 – Prescription Drug User Fee Act • 1994 – Dietary Supplement Health and Education Act • 1997 – Food and Drug Modernization Act • 2002 – Bioterrorism Act • 2002 – Medical Device User Fee and Modernization Act (MDUFMA) • 2003 – Animal Drug User Fee Act • 2007 – Food and Drug Administration Amendments Act of 2007

  20. Product Development Process

  21. Phases of Product DevelopmentCBER and CDER • Preclinical Studies • Phase I • Phase II • Phase III • Approval or Licensing • Phase IV or Post Approval Studies

  22. Drug Development and Review Process Preclinical Testing Phase I Phase II Phase III FDA Approval 1 2 8 9 10 YEARS 3 4 5 6 7 20to80 Healthy Volunteers Test Population 100 to 300 Subject Volunteers 1,000 to 3,000 Subject Volunteers Laboratory and Animal Studies Post-marketing safety monitoring Verify effectiveness, monitor adverse reactions from Cumulative dosing and delayed Toxicity Evaluate effectiveness. Look for Side effects. • Review • usually • takes • about • - 1 year Assess toxicity and biological activity Determine Acute Toxicity and Dosage Distribution FILE IND PURPOSE FILE NDA Expedited Review: Phases II and III combined to shorten approval process on new medicines for serious & life-threatening diseases. Education % of all new drugs that pass • 70% of • INDs • 33% of • INDs • 27% of • INDs • 20% of • INDs

  23. Goals of Product Development • Safety • Efficacy

  24. Preclinical Studies • Animal studies • GLPs = Good Laboratory Practices

  25. Pre-Approval: Phase I, II, III • Phase I, II and III studies are conducted prior to the approval or licensure of a product • Exception: post-approval for new indication • These studies are conducted under IND or IDE • IND = Investigational New Drug Application • IDE= Investigational Device Exemption

  26. Phase I • First time evaluation in humans • Generally small numbers of subjects (20 to 80) • Determine early safety concerns • Determine safe dose range • Identify side effects • Route of administration

  27. Phase II • Larger group of subjects (hundreds) • Further evaluate safety • Evaluation of appropriate dose • Evaluate early effectiveness • Determine common side effects • Usually with comparator product

  28. Phase III • Large group of subjects (thousands) • Confirm effectiveness • Continue to evaluate safety • Evaluate risk/benefit relationship • Provide adequate basis for labeling • Randomization

  29. Randomization • Subjects are assigned by chance to receive the study product or placebo/standard treatment • Intervention group – those subjects receiving the investigational product • Control group – those subjects receiving placebo or standard care

  30. Blinding • Prevents bias • Single blind – subject does not know if they receive investigational product or placebo • Double blind – neither subject or investigator know if the subject receives investigational product or placebo

  31. Approval or Licensing • NDA = New Drug Application (drugs) • BLA = Biologics Licensing Application (biologics) • ANDA=Abbreviated New Drug Application (generics) • PMA = Pre-market approval (devices) • NADA = New Animal Drug Application

  32. Terminology • Drugs and devices are approved • Biologics are licensed

  33. Phase IV • Post approval or post licensure • Safety Monitoring • AERS = Adverse Event Reporting System (Med Watch); CDER & CBER • VAERS = Vaccine Adverse Event Reporting System; CDC & CBER • Lot Release

  34. Drug Approval • FDA’s determinations on drug approval depend on the submission of reliable data from clinical trials • Regulatory review of the data is a multidisciplinary approach • Clinical, pharmacology/toxicology, clinical pharmacology, drug quality (chemistry), and statistics • FDA’s assessment on the validity/reliability of the data is often based on inspections at the time of marketing application submission • Clinical investigators • Sponsors • Contract Research Organizations (CROs)

  35. Bioresearch Monitoring

  36. How Does FDA Ensure Data Integrity and Human Subject Protection? BIORESEARCH MONITORING PROGRAM (BIMO)

  37. BIMO Program Comprehensive program of on-site inspections and data audits designed to monitor all aspects of the conduct and reporting of FDA-regulated research

  38. BIMO Program Objectives • Protect the rights, safety, and welfare of subjects in FDA-regulated trials • Determine the accuracy and reliability of clinical trial data submitted to FDA in support of research or marketing applications; and • Assess compliance with FDA’s regulations governing the conduct of clinical trials, including those for informed consent and ethical review

  39. BIMO Inspections • Each FDA Center has oversight of inspections of research related to the product(s) it regulates • Inspections are usually conducted by ORA field investigators • Field inspectors are NOT specifically assigned to CDER • All Field inspectors are responsible for conducting inspections for all centers (CBER, CDER, CDRH, CFSAN, etc.)

  40. BIMO Inspections Completed FY09 CenterCIIRBSpon/MonGLPTotal CBER 83 15 11 6 115 CDER*458 102 73 36 674 CDRH163 79 59 4 305 CFSAN0 0 0 1 1 CVM26 na 4 15 45 All Centers730 196 147 53 1135

  41. FDA/CDER GCP Regulations These are legally enforceable requirements

  42. Clinical Investigators • Compliance Program • Inspections of CIs (physicians, researchers) conducting clinical trials on drug and biologic products • Inspection • Usually preannounced • Inspection includes • an interview with the clinical investigator and pertinent study staff • an in-depth study/data audit – to validate study findings and verify compliance with regulations

  43. FDA Expectations of Clinical Investigators • Adherence to Code of Federal Regulations • Knowledge of Clinical Investigator regulations • Understanding Clinical Investigator responsibilities

  44. General Clinical Investigator Responsibilities • Ensuring that an investigation is conducted according to the • Signed investigator statement (Form 1572) • Investigational plan • Applicable regulations • Control of drugs under investigation • Adequate Recordkeeping • Ensuring that informed consent is adequately obtained according to 21 CFR 50 • Ensuring IRB review, approval and reporting requirements are met IAW 21 CFR 56

  45. Most Common CI Deficiencies • Failure to follow the investigational plan • Protocol deviations • Inadequate recordkeeping • Inadequate accountability for the investigational product • Inadequate subject protection – including informed consent issues

  46. Administrative/regulatory options • Untitled or Warning letter • Initiation of disqualification procedures • Sharing information with Office of Criminal Investigations (OCI) for pursuit of prosecution • Recommendation for rejection of site/study data

More Related