1. Quality In Investigational Drugs Presented by: Larry Parker, BSMT (ASCP), MHSA, ASQ CQA American Society for Quality Central Arkansas Section 1407

2. What do you expect from the medicines that you take?

3. Expect them to work.

4. What do you expect from the medicines that you take? Expect them to work. Expect them to be safe.

5. How does FDA make sure that medicines used in the United States are safe and effective?

6. Regulations based on scientific quality.

7. How does FDA make sure that medicines used in the United States are safe and effective? Regulations based on scientific quality. Inspections based on the regulations.

8. How does FDA make sure that medicines used in the United States are safe and effective? Regulations based on scientific quality. Inspections based on the regulations. Enforcement actions for companies and individuals based on public health law.

9. Safety First The first thing FDA requires is that you show a drug product is safe.

10. Safety First The first thing FDA requires is that you show a drug product is safe. FDA will almost always require that there are animal safety studies done before a new drug can be given to a human.

11. Safety First The first thing FDA requires is that you show a drug product is safe. FDA will almost always require that there are animal safety studies done before a new drug can be given to a human. Animal studies are regulated under the Good Laboratory Practices (GLPs) found in 21 CFR 58

12. Safety First Quality in the GLPs is insured in the following ways:

13. Safety First Quality in the GLPs is insured in the following ways: 1.Facilities that conduct GLP studies must allow FDA to inspect them.

14. Safety First Quality in the GLPs is insured in the following ways: 1.Facilities that conduct GLP studies must allow FDA to inspect them. 2.Each animal facility must have a quality assurance unit that inspects all it studies

15. Safety First Quality in the GLPs is insured in the following ways: 1.Facilities that conduct GLP studies must allow FDA to inspect them. 2.Each animal facility must have a quality assurance unit that inspects all it studies 3.Written protocols are followed by the facility for the conduct of each study

16. Safety First Quality in the GLPs is insured in the following ways: 1.Facilities that conduct GLP studies must allow FDA to inspect them. 2.Each animal facility must have a quality assurance unit that inspects all it studies 3.Written protocols are followed by the facility for the conduct of each study 4.Equipment used in each study is validated for use in the study prior to the start of the study

17. Safety First: On to humans Before FDA will allow use of a new drug in human studies you must file an Investigational New Drug (IND) application for their review.

18. Safety First: On to humans Before FDA will allow use of a new drug in human studies you must file an Investigational New Drug (IND) application for their review. INDs contain: The clinical protocol that is intend for use in humans

19. Safety First: On to humans Before FDA will allow use of a new drug in human studies you must file an Investigational New Drug (IND) application for their review. INDs contain: The clinical protocol that is intend for use in humans Animal Safety Data

20. Safety First: On to humans Before FDA will allow use of a new drug in human studies you must file an Investigational New Drug (IND) application for their review. INDs contain: The clinical protocol that is intend for use in humans Animal Safety Data Drug product manufacturing information

21. Safety First: On to humans Before FDA will allow use of a new drug in human studies you must file an Investigational New Drug (IND) application for their review. INDs contain: The clinical protocol that is intend for use in humans Animal Safety Data Drug product manufacturing information All references intended to support the application

22. INDs What does FDA expect you to know about a new drug that is going to be used in Humans?

23. INDs What does FDA expect you to know about a new drug that is going to be used in Humans? Identity

24. INDs What does FDA expect you to know about a new drug that is going to be used in Humans? Identity Strength

25. INDs What does FDA expect you to know about a new drug that is going to be used in Humans? Identity Strength Potency

26. INDs What does FDA expect you to know about a new drug that is going to be used in Humans? Identity Strength Potency Purity

27. INDs What does FDA expect you to know about a new drug that is going to be used in Humans? Identity Strength Potency Purity Quality

28. INDs What does FDA expect you to know about a new drug that is going to be used in Humans? Identity Strength Potency Purity Quality Everything!

29. GMPs You know everything about a investigational drug product based on the Good Manufacturing Practice Regulations (cGMPs) found in 21 CFR 210 & 211

30. GMPs The GMPs: Define the responsibilities of a companies Quality Control Unit

31. GMPs The GMPs: Define the responsibilities of a companies Quality Control Unit Define the minimum qualifications for QA personnel

32. GMPs The GMPs: Define the responsibilities of a companies Quality Control Unit Define the minimum qualifications for QA personnel Define the minimum specifications for facilities and equipment

33. GMPs The GMPs: Define the responsibilities of a companies Quality Control Unit Define the minimum qualifications for QA personnel Define the minimum specifications for facilities and equipment Provide requirements for control of components and products

34. GMPs The GMPs: Define the responsibilities of a companies Quality Control Unit Define the minimum qualifications for QA personnel Define the minimum specifications for facilities and equipment Provide requirements for control of components and products Provide for controls on processing, production, packaging, labeling, holding, and distribution of drug product

35. GMPs The GMPs: Define the responsibilities of a companies Quality Control Unit Define the minimum qualifications for QA personnel Define the minimum specifications for facilities and equipment Provide requirements for control of components and products Provide for controls on processing, production, packaging, labeling, holding, and distribution of drug product Also provides minimum requirements for laboratory controls, records and reports

36. But does it work?

37. Phase II clinical trials involve drugs that have successfully completed safety testing and start to look and see if a drug is effective and why it is effective.

38. But does it work? Phase II clinical trials involve drugs that have successfully completed safety testing and start to look and see if a drug is effective and why it is effective. Phase III clinical trials use all the information found in the earlier phases and expand it to large numbers of subjects in different locations to verify that the data is still the same.

39. Marketing a drug After you have completed the Phase III trials you can file for marketing clearance with FDA in order to be able to sell the drug.

40. Marketing a drug After you have completed the Phase III trials you can file for marketing clearance with FDA in order to be able to sell the drug. Quality doesn’t stop there! FDA requires “post-marketing” studies usually called Phase IV studies that are on going as long as the drug is on the market.

41. Questions:

42. Quality Workshop Quality By Design:

43. What is QbD?

44. FDA push to improve the drug development process

45. What is QbD? FDA push to improve the drug development process Seeks to reduce the cost of product development due to low efficiencies, waste, and manufacturing time requirements due to testing

46. What is QbD? FDA push to improve the drug development process Seeks to reduce the cost of product development due to low efficiencies, waste, and manufacturing time requirements due to testing FDA states that you can’t test quality into a product, it must be designed there

47. What is QbD? A scientific, risk-based, holistic and proactive approach to pharmaceutical development.

48. What is QbD? A scientific, risk-based, holistic and proactive approach to pharmaceutical development. A deliberate design effort from product conception through commercialization.

49. What is QbD? A scientific, risk-based, holistic and proactive approach to pharmaceutical development. A deliberate design effort from product conception through commercialization. Manufacturer’s should have a full understanding of how product attributes and process relate to product performance

50. QbD System

51. Better View

52. Another Flow Chart