2. “Journey of a Drug” From Test Tube TO Prescribing Physician

3. 1-How Modern Drugs are Developed? 2-Naming of Drugs. 3-Drug Advertisement.

4. 1-History. 2-Physical Examination. 3-Diffrential diagnosis. 4-Investigations. 5-Diagnosis. 6-Treatment. 7-Prognosis.

5. Treatment is the aim of Physician and whether this was: Medical Surgical Psychological “Drugs are almost always used”

6. Whenever a drug is prescribed: The Skill & knowledge of Pharmacology is Exercised and Used !

7. Three Basic Principles! 1-The drug is safe. 2-It is effective for the disease on which it was developed to treat. 3-It can be manufactured correctly and reproducibly each time.

8. “Innovator product” passes in the following process: 1-Prediscovery stage. 2-Preclinical stage. 3-Human trials. A process of 10-15 years.

9. In Summary! Starting 5000-10,000 compounds in Prediscovery. 250 reach Preclinical stage. 5 involved in Clinical trials. 1 drug reach the Market !

10. Drug development is a long and risky process 1.1-1.7 billion dollars Clinical trials cost most !

11. 1-Prediscovery Stage 10,000 compounds

12. Preclinical goal: 1-Understand the disease what is wrong with the gene or protein. 2-Biological target identification. 3-Discovering molecules which could interact with the target.

13. From where we get the test compounds? 1- Natural sources. 2-High Throughput Screening.(most common). 3-Computarized methods and biotechnology matching from electronic libraries.

14. The Aim is to find out the compound which fits the target protein ex. Enzyme

15. (High Throughput Robot Unit)

16. 2-Preclinical Stage 250 compounds

17. Early safety evaluation Animals rodents In Absorption. Through Distribution. Out Metabolism and excretion.

18. Final Animal Testing: 1-Acute Toxicology Studies = 2 Weeks. “Dose of No Adverse Effect” 2-Determination of Maximum Tolerated Dose MTD = 2 Weeks 3-Long Term Toxicology = 6 Months (or more)

19. IND application: Investigational New Drug

20. IND application: 1-Animal Pharmacology & Toxicology. 2-Manufacturing Data. Safety is a key aspect!

21. 3-Clinical Trials 5 Compounds!

22. Clinical trials: Out of 250 compounds of preclinical stage. 5 reach clinical trials. 70 % of the cost of development.

23. Basic Principles of Clinical Trials: 1-Placebo controlled trials. 2-Randomized trials. 3-Double blind trials.

24. Basic Principle of Clinical Trials: 1-Phase one clinical trial. 2-Phase two clinical trial. 3-Phase three clinical trial.

25. Phase One Clinical Trial

26. Phase one: “Healthy volunteers” Evaluation of safety. One dose. “20-100 Subjects” 6-18 months.

27. Single dose maximum tolerable dose 40 % of tested drugs FAIL the study!

28. Phase Two Clinical Trial

29. Phase 2 : “100 – 200 patients with the disease” To assess the efficacy of the drug Side effects Risks Phase two 6 months – 3 years “60 % of drugs fail phase 2”

30. Phase Three Clinical Trial

31. Phase 3 : “Largest 1,000-5,000 Patients” Statistically significant data on risk & benefit 2- 4 years 40 % will fail the study!

32. NDA Application is issued (New Drug Application)

33. At this stage a: “NEW DRUG APPLICATION IS ISSUED” NDA Summary of all tests 100,000 pages!

34. NDA is reviewed within 18 months 6 different teams review the tests THEN: Approval is Granted Then it can be marketed immediately!

35. Phase 4 stage: Post marketing Surveillance 1000 s of patients Long term risks When severe reaction is reported the drug will be withdrawn from the market!

36. Only two out of 10 approvals recoup the cost of development!

37. After approval a Patent is issued: Its average time is 11 years where the Pharmaceutical company has exclusive rights to manufacture the drug. Patent include composition and methods and synthesis.

38. Generic drug approval After the patent has expired any pharmaceutical company can apply for generic drug approval. Needs Bioequivalence to the innovative drug. Approved drug with therapeutic equivalence evaluation.

39. Approved Generic drug is registered in the Orange book www.fda.gov/cder/ob

41. 1-Full Chemical name. IUPAC. International Union of Pure and Applied Chemistry. 2-rINN Recommended International non proprietary name. (Generic Name, Official Name) 3-Properietary name (Brand Name).

42. Old Names: British Approved Name(BAN) not used after 2003. Amoxycillin = BAN Amoxicillin = rINN

43. Stands for = “Drug Making” BP = British Pharmacopeia. USP = United States Pharmacopeia. Ph. Eur. = European Pharmacopoeia.