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. NCTR CBER CDRH CFSANCVM Food and Drug Administration Center for Drug Evaluation and Research CDER ORA

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

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

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

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

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

14. PHASE 1PHASE 2PHASE 3

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

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

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

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

22. 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 ADVISORY COMMITTEE http://www.fda.gov/oc/advisory/default

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

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. Database Internationally compatible Adverse Event Reporting System (AERS) 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. FDA evaluates benefits/risks for the population Provider evaluates benefits/risks for a patient Patient evaluates benefits/risks in terms of personal values Benefits Risks

31. DDMAC (Division of Drug Marketing Advertising and Communications) Promotional Materials Review Guidances 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. Generic Drug Review Process Application submitted to Office of Generic Drugs Bioequivalence Review Plant Inspection Chemistry/Micro Review Labeling Review FDA reviews and decides if product is approved or not approvable Determine if application is acceptable

34. Definition of Bioequivalence 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 A generic drug is considered to be bioequivalent if:

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 EUEFPIA Japan MHLWJPMA United States of America FDAPhRMA Observers: WHO, Canada, EFTA

38. OTC Drug Review Process FDA reviews active ingredients and finds they are safe and effective. http://www.fda.gov/cder/Offices/OTC/industry.htm. 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.

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

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

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

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