Learning Objectives

3. Learning Objectives • Explain the new drug development and review process in the United States. • State how to obtain current drug information from the FDA.

5. Food and Drug Administration CBER CDRH NCTR Center for Drug Evaluation and Research ORA CFSAN CVM CDER

6. OFFICE OF REGULATORY AFFAIRS OVER 160 OFFICES NATIONWIDE NORTHEAST AL PACIFIC CENTRAL NH ME VT ND MN WA MA NY WI SD MT RI MI CT OR NJ PA ID OH MD IN DE IL WV VA KY NV CA WY IA NE TN NC AZ SC UT GA AL CO KS MS PR MO HI LA OK AR NM REGIONAL OFFICES - 5 DISTRICT OFFICES - 20 RESIDENT INSPECTION POSTS –100+ OCI FIELD OFFICES - 6 OCI RESIDENT OFFICES - 4 OCI DOMICILES - 4 FL TX SOUTHEAST SOUTHWEST

7. Office of the Center Director Office of New Drugs Office of Pharmaceutical Science Office of Management Office of New Drug Chemistry Office of Medical Policy Office of Drug Evaluation I Office of Information Technology Office of Generic Drugs Office of Drug Evaluation II Office Training and Communications Office of Drug Evaluation III Office of Clinical Pharmacology and Biopharmaceutics Office of Drug Evaluation IV Office of Compliance Office of Testing and Research Office of Drug Evaluation V Office of Regulatory Policy Office of Biotechnology Products Office of Drugs Evaluation VI Office of Executive Programs Office of Counter Terrorism and Pediatric Drug Development Office of Pharmacoepidemiology and Statistical Science Office of Information Management

8. A drug is defined as: (A)articles recognized in the official USP, HPUS or NF or any supplement to any of them, (B)articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals, (C)articles (other than food) intended to affect the structure or any function of the body of man or other function of the body of man or other animals…..

9. What is a Biologic? Any virus, therapeutic serum, toxic, antitoxin, vaccine, blood, blood component or derivative, allergenic product, or analogous product, or arsphenamine or its derivatives, applicable to the prevention treatment or cure of diseases or injuries of man.

10. Industry Guidance http://www.access.gpo.gov/nara/cfr/

11. SYNTHESIS AND PURIFICATION DISCOVERY/SCREENING PRE-CLINICAL RESEARCH INDUSTRY TIME FDA TIME FDA & INDUSTRY TIME SPONSOR/FDA MEETINGS ENCOURAGED

12. PRE-CLINICAL RESEARCH CLINICAL STUDIES SYNTHESIS AND PURIFICATION DISCOVERY/SCREENING ANIMAL TESTING SHORT-TERM LONG-TERM INDUSTRY TIME IND NDA FDA TIME FDA & INDUSTRY TIME SPONSOR/FDA MEETINGS ENCOURAGED

13. PRE-CLINICAL RESEARCH CLINICAL STUDIES FDA REVIEW PHASE 1 SYNTHESIS AND PURIFICATION PHASE 2 PHASE 3 DISCOVERY/SCREENING ANIMAL TESTING SHORT-TERM LONG-TERM INDUSTRY TIME IND NDA/ BLA FDA ACTION FDA TIME FDA & INDUSTRY TIME SPONSOR/FDA MEETINGS ENCOURAGED

14. PHASE 1 PHASE 2 PHASE 3

15. PRE-CLINICAL RESEARCH CLINICAL STUDIES FDA REVIEW PHASE 1 SYNTHESIS AND PURIFICATION PHASE 2 PHASE 3 DISCOVERY/SCREENING ANIMAL TESTING SHORT-TERM LONG-TERM INDUSTRY TIME IND NDA/ BLA FDA ACTION FDA TIME FDA & INDUSTRY TIME SPONSOR/FDA MEETINGS ENCOURAGED

16. PRE-CLINICAL RESEARCH POST MARKETING CLINICAL STUDIES FDA REVIEW ADVERSE REACTION SURVEILLANCE PRODUCT DEFECT REPORTING PHASE 1 SYNTHESIS AND PURIFICATION PHASE 2 PHASE 3 PHASE 4 DISCOVERY/SCREENING SURVEYS/ SAMPLING TESTING ANIMAL TESTING ACCELERATED APPROVAL TREATMENT USE SHORT-TERM PARALLEL TRACK POST APPROVAL INSPECTIONS LONG-TERM INDUSTRY TIME NDA/BLA IND FDA ACTION FDA TIME FDA & INDUSTRY TIME ACCELERATED REVIEW: SUBPART E ACCELERATED REVIEW EXPANDED ACCESS: E PARALLEL TRACK SPONSOR/FDA MEETINGS ENCOURAGED TREATMENT USE

17. New Drug Application (NDA) or Biologic License Application (BLA) contains the following: • Pre-clinical studies • Human clinical studies • Manufacturing details • Labeling • Additional information

19. A Better Way The equivalent of 50,000 paper pages of data..

20. DRUG PRODUCT DIVISIONS ODE I ODE II ODE III ODE IV ODE V ODEVI Anti-Inflammatory, Analgesic and Ophthalmologic Anesthetic, Critical Care, and Addiction Neuro-pharmacological Gastrointestinal and Coagulation Therapeutic Biological Oncology Anti-Viral Therapeutic Biological Internal Medicine Medical Imaging and Radiopharmaceuticals Anti-Infective Oncology Pulmonary Dermatologic and Dental Metabolic and Endocrine Special Pathogen and Immunologic Reproductive and Urologic Over-the- Counter Review Management & Policy Cardio-Renal

21. Review Team Project Manager Medical Officer Chemist Microbiologist Statistician Pharmacologist Establishment/Facility Reviewer Support Personnel

22. ADVISORY COMMITTEE • http://www.fda.gov/oc/advisory/default • Panel of OUTSIDE experts • Provide advice and opinions • to the FDA drug review team • FDA advisory committee • information, 1-800-741-8138 or 301-443-0572

23. Prescription DrugUser Fee Act (PDUFA) http://www.fda.gov/oc/pdufa/default.htm • Permits CDER/CBER to charge pharmaceutical manufacturers a fee to review drug applications • These fees provide appropriate resources to accelerate the review of applications • Not the only source of funds for CDER/CBER • Funds go directly to CDER/CBER, not individuals

24. PRE-CLINICAL RESEARCH POST MARKETING CLINICAL STUDIES FDA REVIEW ADVERSE REACTION SURVEILLANCE PRODUCT DEFECT REPORTING PHASE 1 SYNTHESIS AND PURIFICATION PHASE 2 DISCOVERY/SCREENING PHASE 3 PHASE 4 SURVEYS/ SAMPLING TESTING ANIMAL TESTING ACCELERATED APPROVAL TREATMENT USE SHORT-TERM PARALLEL TRACK POST APPROVAL INSPECTIONS LONG-TERM INDUSTRY TIME NDA BLA IND ACTION FDA TIME FDA & INDUSTRY TIME SPONSOR/FDA MEETINGS ENCOURAGED

25. Post-market Surveillance

26. Office of Drug Safety • Division of Drug Risk Evaluation • Division of Medication Errors and Technical Support, • Division of Surveillance, Research, and Communication Support

27. MedWatch Website • Safety Information Retrieval • Adverse Event Reporting for Drugs,Devices, Biologics and Dietary Supplements www.fda.gov/medwatch

28. Adverse Event Reporting System (AERS) • Database • Internationally compatible Office of Drug Safety (ODS) uses AERS to: • triage • review • assess risk

29. Potential Regulatory Action for Postmarketing Safety Issues • Labeling Change • Scientific publication • "Dear Doctor" letter (for specific warnings) • Restricted use • Restricted distribution • Patient Medication guide • Product withdrawal

30. Benefits Risks Risks Benefits FDA evaluates benefits/risks for the population Provider evaluates benefits/risks for a patient Patient evaluates benefits/risks in terms of personal values

31. DDMAC (Division of Drug Marketing Advertising and Communications) • Promotional Materials ReviewGuidances and policy development • Research • Surveillance and enforcement

32. CDER’s Office of Compliance • Sets labeling, manufacturing, and testing standards • Monitors the quality of marketed drugs • Evaluates, classifies, and recommends human drug recalls

33. Bioequivalence Review Plant Inspection Chemistry/Micro Review Labeling Review Generic Drug Review Process Determine if application is acceptable FDA reviews and decides if product is approved or not approvable Application submitted to Office of Generic Drugs

34. Definition of Bioequivalence A generic drug is considered to be bioequivalent if: • The rate and extent of absorption do not show a significant difference from listed drug, or • The extent of absorption does not show a significant difference and any difference in rate is intentional or not medically significant

35. APPROVED DRUG PRODUCTS WITH THERAPEUTIC EQUIVALENCE EVALUATIONS “Orange Book” http://cdsmlweb1/ob/index.htm

36. Orphan Drug Products www.fda.gov/orphan • Rare diseases or conditions affecting fewer • than 200,000 people in the U.S. • 7 years exclusively after approval • Special financial incentives • Grants • Protocol Assistance

37. Three Regions, Six Parties • Europe • EU EFPIA • Japan • MHLW JPMA • United States of America • FDA PhRMA • Observers: WHO, Canada, EFTA

38. New OTC drug The sponsor/manufacturer submits a new drug application (NDA) as an OTC drug. Prescription to OTC Switch The drug company submits a supplement to the new drug application NDA to “switch” to OTC. OTC Drug Review Process FDA reviews active ingredients and finds they are safe and effective. http://www.fda.gov/cder/Offices/OTC/industry.htm.

39. Panel reviews all known data or any submitted by company Advisory Panel Review Agency input ingredients amounts combinations labeling claims cat. I cat. II cat. III ANPR FR (Panel Report) OTC DRUGREVIEW Change in category could occur -Public Comment- Agency addresses comments Agency review

40. PR (Tentative Final Monograph) -Public Comment- Agency review/ address comments OTC DRUG REVIEW cat. I monograph cat. II nonmonograph FR (Final Monograph) Codified in CFR [April]

41. The New OTC Label

42. Customize and Expand Enforcement Efforts • Partner with Federal, State and other Organizations • Engage in Public Outreach • http://www.fda.gov/oc/buyonline/default.htm • Cooperate Internationally • E-mail webcomplaints@ora.fda.gov

43. Counterterrorism • Help prevent or alleviate shortages of medically necessary drug products • Public Health Security and Bioterrorism Preparedness and Response Act of 2002 • Counterterrorism Drug Development • Radiation emergencies • Anthrax • Chemical agents

44. Working with Partners to Meet the Challenge

45. www.fda.gov/cder

46. www.fda.gov/cder /http://www.fda.gov/cder/handbook/

47. CDER’s Internet Home Page http://www.fda.gov/cder • Drug Information • 888-INFO-FDA or 301- 827-4573 • druginfo@cder.fda.gov