1. Introduction to Pharmacology: Drug Regulation and Approval1
Introduction to Pharmacology: Drug Regulation and Approval

2. Directory
Classroom Response System
Lecture Note Presentation

3. NCLEX-RN Review Question 1
A client tells the nurse, “I have been reading about research trials, and would like to be involved in one.” The nurse asks the client if she has any documented diseases, knowing the client might be eligible to participate in which clinical trial phase? 3

4. NCLEX-RN Review Question 1 – Choices
Preclinical investigation
Phase I
Phase II
Postmarketing surveillance 4

5. NCLEX-RN Review Question 1 – Answer
Preclinical investigation
Phase I
Phase II
Postmarketing surveillance 5

6. NCLEX-RN Review Question 1 – Rationale
Objective: Explain the four stages of approval for therapeutic and biologic drugs. Rationale: Phase II trials involve volunteer patients with the disease. Preclinical investigations do laboratory research; Phase I trials involve normal, healthy volunteers; and postmarketing surveillance is done after the drug is in use. 6

7. NCLEX-RN Review Question 1 – Rationale (cont)
Cognitive Level: Comprehension Client Need: Physiological Integrity: Pharmacological and Parenteral Therapies Nursing Process: Implementation 7

8. NCLEX-RN Review Question 2
A client who plans to purchase drugs from Canada expresses concern that the drugs will be substandard. The nurse explains: 8

9. NCLEX-RN Review Question 2 – Choices
“You should have reservations about obtaining drugs from Canada.”
“Drugs from Canada must comply with standards established by recognized formularies in the United States and are safe.”
“The Canadian Food and Drug Act has a much different approval process, and is not as stringent as ours in the United States.”
“I can understand you want to save money, but it would be better to purchase your drugs in the United States.” 9

10. NCLEX-RN Review Question 2 – Answer
“You should have reservations about obtaining drugs from Canada.”
“Drugs from Canada must comply with standards established by recognized formularies in the United States and are safe.”
“The Canadian Food and Drug Act has a much different approval process, and is not as stringent as ours in the United States.”
“I can understand you want to save money, but it would be better to purchase your drugs in the United States.” 10

11. NCLEX-RN Review Question 2 – Rationale
Objective: Describe the Canadian drug approval process, and identify similarities between how drugs are approved in the United States. Rationale: Drug standards set by the Canadian Food and Drug Act ensure effectiveness and safety of Canadian drugs. “You should have reservations about obtaining drugs from Canada” and 11

12. NCLEX-RN Review Question 2 – Rationale (cont)
“I can understand you want to save money, but it would be better to purchase your drugs in the United States” do not address the client’s questions of drug standards, and “The Canadian Food and Drug Act has a much different approval process and is not as stringent as ours in the United States” is incorrect.

13. NCLEX-RN Review Question 2 – Rationale (cont)
Cognitive Level: Comprehension Client Need: Physiological Integrity: Pharmacological and Parenteral Therapies Nursing Process: Implementation 13

14. NCLEX-RN Review Question 3
A client prefers to purchase over-the-counter medications rather than prescription medications whenever possible. The nurse informs the client that advantages to using over the counter (OTC) meds include: 14

15. NCLEX-RN Review Question 3 – Choices
They are less expensive than prescription medications.
Fewer side effects can be expected.
Access to them is easier.
They do not interact with food and beverages. 15

16. NCLEX-RN Review Question 3 – Answer
They are less expensive than prescription medications.
Fewer side effects can be expected.
Access to them is easier.
They do not interact with food and beverages. 16

17. NCLEX-RN Review Question 3 – Rationale
Objective: Identify the advantages and disadvantages of prescription and over-the-counter (OTC) drugs. Rationale: Over-the-counter meds are available in a wide variety of stores, not just pharmacies. They might not always be less expensive, and can have many side effects and interactions with food and beverages. 17

18. NCLEX-RN Review Question 3 – Rationale (cont)
Cognitive Level: Application Client Need: Physiological Integrity: Pharmacological and Parenteral Therapies Nursing Process: Implementation 18

19. NCLEX-RN Review Question 4
The nurse explains to a client that the phase postmarketing surveillance is best described as: 19

20. NCLEX-RN Review Question 4 – Choices
Trials and animal drug testing
The longest part of the approval process
The final stage of the approval process
Extensive laboratory research 20

21. NCLEX-RN Review Question 4 – Answer
Trials and animal drug testing
The longest part of the approval process
The final stage of the approval process
Extensive laboratory research 21

22. NCLEX-RN Review Question 4 – Rationale
Objective: Discuss the role of the U.S. Food and Drug Administration (FDA) in the drug approval process. Rationale: Postmarketing surveillance is best described as the final stage of the approval process. Laboratory research and testing are done before the drug is marketed, and involve the longest part of the application process. 22

23. NCLEX-RN Review Question 4 – Rationale (cont)
Cognitive Level: Comprehension Client Need: Physiological Integrity: Pharmacological and Parenteral Therapies Nursing Process: Implementation 23

24. NCLEX-RN Review Question 5
The nurse explains to a client that during the FDA drug approval process, clinical investigators from many different medical specialties address concerns such as: 24

25. NCLEX-RN Review Question 5 – Choices
Whether the drug is effective
Whether a New Drug Application (NDA) must be filed
Placing the application for review for six months
Determining the marketability of the drug 25

26. NCLEX-RN Review Question 5 – Answer
Whether the drug is effective
Whether a New Drug Application (NDA) must be filed
Placing the application for review for six months
Determining the marketability of the drug 26

27. NCLEX-RN Review Question 5 – Rationale
Objective: Discuss the role of the U.S. Food and Drug Administration (FDA) in the drug approval process. Rationale: In this phase, the clinical investigators address concerns such as whether the drug is effective, and whether it worsens other medical conditions. 27

28. NCLEX-RN Review Question 5 – Rationale (cont)
Cognitive Level: Knowledge Client Need: Physiological Integrity: Pharmacological and Parenteral Therapies Nursing Process: Implementation 28

29. NCLEX-RN Review Question 6
A client asks the nurse, “I read that the pill I am taking is a biologic. Is this some kind of special drug?” The nurse’s explanation is based on the knowledge that biologics: 29

30. NCLEX-RN Review Question 6 – Choices
Include medications as well as all types of complementary alternative therapies
Are strictly derived from natural plant products
Are drugs that are similar to natural products but are artificially created in a laboratory
Are agents naturally produced by animals, microorganisms, or the human body 30

31. NCLEX-RN Review Question 6 – Answer
Include medications as well as all types of complementary alternative therapies
Are strictly derived from natural plant products
Are drugs that are similar to natural products but are artificially created in a laboratory
Are agents naturally produced by animals, microorganisms, or the human body 31

32. NCLEX-RN Review Question 6 – Rationale
Objective: Compare and contrast traditional drugs, biologics, and alternative therapies. Rationale: Biologics are agents that are naturally produced in animal cells, microorganisms, and the human body. 32

33. NCLEX-RN Review Question 6 – Rationale (cont)
Cognitive Level: Comprehension Client Need: Physiological Integrity: Pharmacological and Parenteral Therapies Nursing Process: Implementation 33

34. NCLEX-RN Review Question 7
A healthy, young client informs the nurse that she has enrolled in a clinical drug research study. The nurse recognizes the client is involved in which phase of trials? 34

35. NCLEX-RN Review Question 7 – Choices
Preclinical investigation
Clinical investigation
Review of the New Drug Application (NDA)
Postmarketing surveillance 35

36. NCLEX-RN Review Question 7 – Answer
Preclinical investigation
Clinical investigation
Review of the New Drug Application (NDA)
Postmarketing surveillance 36

37. NCLEX-RN Review Question 7 – Rationale
Objective: Explain the four stages of approval for therapeutic and biologic drugs. Rationale: Phase 2 is the clinical investigation phase. It is in this phase that individuals are given drugs in the review process to appraise for adverse drug effects. 37

38. NCLEX-RN Review Question 7 – Rationale (cont)
Cognitive Level: Comprehension Client Need: Physiological Integrity: Pharmacological and Parenteral Therapies Nursing Process: Assessment 38

39. NCLEX-RN Review Question 10
The nurse can check the U.S. Pharmacopoeia: National Formulary to find which information about a drug that a client is receiving? 39

40. NCLEX-RN Review Question 10 – Choices
Exact ingredients and strength of purity
Common side effects
Reports of death attributed to the drugs’ use
Off-label uses for the drug 40

41. NCLEX-RN Review Question 10 – Answer
Exact ingredients and strength of purity
Common side effects
Reports of death attributed to the drugs’ use
Off-label uses for the drug 41

42. NCLEX-RN Review Question 10 – Rationale
Objective: Identify key U.S. drug regulations that have ensured the safety and efficacy of medications. Rationale: This reference includes drug monographs that summarize the standards of purity, strength, and directions for synthesis. 42

43. NCLEX-RN Review Question 10 – Rationale (cont)
Cognitive Level: Application Client Need: Physiological Integrity: Pharmacological and Parenteral Therapies Nursing Process: Assessment 43

44. History of Pharmacology
Records exist in every culture dating to antiquity
Records describe use of plants (herbs) to relieve symptoms.
Dark Ages show few records; still using herbs

45. Pharmacologia sen Manuducto and Materiam Medicum
Written by Samuel Dale in 1693
First recorded reference to pharmacology

46. Modern Pharmacology Began in Early 1800s
Chemists isolated pharmacological substances from natural substances
Effects on animals studied
Early researchers used themselves as test subjects

47. Pharmacology Recognized as Distinct Discipline
First department of pharmacology established at Estonia in 1847

48. John Jacob Abel Father of American pharmacology
Founded first pharmacology department in United States at University of Michigan in 1890

49. Twentieth Century to Present
Drugs synthesized in laboratory
Drugs tested for relatively short time
Understanding increased of how drugs produce their effects
Focus is on improvements in quality of life

50. Pharmacology Simply defined, from the Greek, as the study of medicine
Pharmacology is an expansive subject encompassing:
How drugs are administered
Where drugs travel in the body
Responses drugs produce

51. Interrelated Subject Areas
Anatomy and physiology
Chemistry
Microbiology
Pathophysiology

52. Pharmacology Is Challenging and Always Changing
10,000 drugs currently available
Each drug has its own characteristics
Therapeutic applications
Interactions
Side effects
Mechanisms of action

53. Pharmacology Is Challenging and Always Changing (cont'd)
Many drugs prescribed for more than one disease
Drugs elicit different responses depending on individual factors
Age
Sex
Body mass
Health status
Genetics

54. Nursing and Pharmocology
Knowledge of pharmacology is essential to the nursing profession
Nurses are health care providers most often directly involved in patient care
Applies to nurses in all settings, from hospital to home care
Study of pharmacology is a long, challenging, and continual process

55. Therapeutics and Pharmacology Are Closely Connected
Therapeutics is concerned with
Prevention of disease
Treatment of suffering
Pharmacotherapy is the application of drugs for
Disease prevention

56. Traditional Drugs Are Chemical Agents
Synthesized in a laboratory
Produce biological responses in the body
If desirable response—therapeutic
If undesirable response—adverse
After a drug is administered, it is called a medication

57. Biologics
Biologics are agents naturally produced in animal cells, by microorganisms, or by the body itself

58. Examples of Biologics Hormones Monoclonal antibodies
Natural blood products and components
Interferon
Vaccines

59. Complementary and Alternative Therapies
Natural plant extracts, herbs, vitamins, minerals, dietary supplements
Acupuncture, hypnosis, biofeedback, massage

60. Prescription Drugs and Over the Counter (OTC) Drugs
Prescription drugs require that the recipient obtain a written order from a person with the legal authority to write such a prescription.

61. Advantages and Disadvantages of Prescription Drugs
Health-care provider examines the client and orders proper drug.
Amount and frequency of drug is controlled
Instructions on use and side effects of drug are discussed
Disadvantages
Require a prescription to obtain
Need for health-care-provider appointment

62. Advantages and Disadvantages of OTC Drugs
No health-care provider appointment required
Often less expensive than prescription drugs
Disadvantages
Client may choose wrong drug
Client may not know reactions or interactions
Ineffective treatment may result in progression of disease

63. Prior to 19th Century
Few standards or guidelines to protect the public
Some drugs contained hazardous levels of
Dangerous substances
Addictive substances

64. Early Drug References
The first standard commonly used by pharmacists was the formulary, or list of drugs and drug recipes
A pharmacopoeia is a medical reference summarizing standards of drug purity, strength, and directions for synthesis

65. United States Pharmacopoeia (USP), 1820
First comprehensive publication of drug standards
Summarized standards of drug
Purity
Strength
Directions for synthesis

66. American Pharmaceutical Organization (APhA)
National professional society of pharmacists, established 1852
Maintained the national compendia of drug standards, the National Formulary (NF)
National formulary competed with other compendia, U.S. Pharmacopoeia (USP)

67. USP and NF Merged in 1975
Formed United States Pharmacopoeia–National Formulary (USP-NF)
Official monographs and interim announcements published regularly
Full bound version printed every five years

68. United States Develops and Enforces Tougher Drug Laws, 1900s
Biologics Control Act, 1902
Standardized serum and blood-related products
Pure Food and Drug Act, 1906
Government controls labeling of medicines
Sherley Amendment, 1912
Prohibited drugs labeled with false therapeutic claims

69. United States Develops and Enforces Tougher Drug Laws, 1900s (cont'd)
Food, Drug, and Cosmetic Act (1938) and amendments
Thorough testing of drug
Proof of safety and efficacy of drug
Dietary Supplement Health and Education Act, 1994
Controls misleading industry claims

70. Figure Examples of USP labels Source: Courtesy of Novartis Pharmaceuticals Corporation and Mallinckrodt Pharmaceuticals. 70

71. Figure 1.1 (cont'd) Examples of USP labels Source: Courtesy of Novartis Pharmaceuticals Corporation and Mallinckrodt Pharmaceuticals 71

72. Food and Drug Administration (FDA)
Officially established in 1988
Agency of US Department of Health and Human Services in 1988

73. Figure 1.2 A historical timeline of regulatory acts, standards, and organizations73

74. Center for Drug Evaluation and Research
Branch of FDA
Determines safety and efficacy of drugs
Pharmaceutical laboratories must solicit approval from FDA before marketing a drug

75. Center for Biologics Evaluation and Research (CBER)
Branch of FDA
Regulates use of biologics (serums, vaccines, and blood products)
1986 Childhood Vaccine Act result of CBER work

76. Center for Food Safety and Applied Nutrition (CFSAN)
Branch of FDA
Oversees herbal and dietary products
Enforces 1994 Dietary and Supplemental Health and Education Act
Regulation not as close as Food, Drug, and Cosmetic Act
Herbal and Dietary supplements can be marketed without prior approval from FDA

77. Four Stages of Approval for Therapeutic and Biologic Drugs
Preclinical investigation
Clinical investigation
Review of new drug application (NDA)
Postmarketing surveillance
Amount of time for approval varies

78. Figure 1.3 A new drug development timeline, with the four phases of drug approval78

79. Preclinical Investigation
Involves laboratory research
Tests done on cells and animals
Determines drug-dose range
Examines adverse effects
Results are considered inconclusive

80. FDA Critical Path Initiative
In 1997, FDA restated its concern that a number of innovative and critical medical products had decreased since the 1990s
Critical Path Initiative initiated to modernize the sciences to enhance the use of bioinformation to improve the “safety, effectiveness, and manufacturability of candidate medical products.”

81. Clinical Investigation
Takes place in takes in three different stages termed clinical phase trials
Longest part of approval process
Evaluates human benefits
Tests on healthy humans first, then on those with the target ailment

82. Review of New Drug Application (NDA)
If results of clinical investigation are positive, even if precautions are noted, a New Drug Application is next step
NDA is third step of drug approval process
Average review time 17–24 months
Drug approved: process continues
Drug rejected: process suspended

83. Investigational New Drug Application (IND)
May be submitted for Phase I clinical trials when it is determined there are significant therapeutic benefits, and the product is reasonably safe for initial use in humans 83

84. Post Marketing Surveillance
New drug placed on market
Surveyed for harmful effects in larger population
Diabetes drug troglitazone (Rezulin) is example of drug that did not exhibit harmful effects until the year after release
FDA holds annual public meetings
Will withdraw a drug if serious problem found

85. The Lengthy FDA Drug-Approval Process
NDAs can be massively long and FDA review can take several years
Pharmaceutical manufacturer expenses for creating and marketing a new drug can be in the millions of dollars
Core FDA goal is to make sure drugs are safe for public

86. The Lengthy FDA Drug-Approval Process (cont'd)
In 1990s, delays in process determined
Outdated guidelines
Insufficient staff
Poor communication

87. Prescription Drug User Fee Act, 1992
Established on five-year trial basis
Drug and biologic manufacturers provide drug-user fee
FDA hired more employees
FDA restructured its organization

88. Results Successful Double the number of drugs approved
Some review times cut by half

89. FDA Modernization Act, 1997
Reauthorized Prescription Drug User Fee Act
FDA Amendments Act expanded the reforms in 2007

90. Research Shows
Researchers recently completed a review of all adverse drug events reported to the FDA since 2006
Clinicians found 10 potentiall fatal drugs
Nurses should constantly review the literature for drugs that have been recalled or reported dangerous 90

91. Drug-Approval Process in Canada: Six Steps
Preclinical studies
Living tissue
Small animals
Then humans

92. Drug-Approval Process in Canada: Six Steps (cont'd)
Complete drug submission to Health Canada
Safety and effectiveness information
Therapeutic benefits
Adverse reactions
Committee of experts reviews drug submission
Benefits
Drug risks

93. Drug-Approval Process in Canada: Six Steps (cont'd)
Health Canada reviews information about drug product
Passes important details to health practitioners and consumers
Health Canada issues permits to market drug product
Issues notice of compliance (NOC)
Issues drug identification number (DIN)

94. Drug-Approval Process in Canada: Six Steps (cont'd)
Health Canada monitors drug postmarketing
Effectiveness
Concerns

95. 95

96. Similarities Between Drug-Approval Processes in United States and in Canada
Preclinical testing of drug
Proving safety and effectiveness of drug
Monitoring drug after placement on the market
Health Canada is the federal department working in partnership with provincial and territorial governments

97. Canadian Drug Standards
Multiple Directorates of the Health Products and Food Branch (HPFB) of Health Canada conduct and supervise the approval process
The Canadian Food and Drugs Act specifies that drugs cannot be marketed without a Notice of Compliance (NOC) and Drug Identification Number (DIN) from Health Canada 97

98. Nurses and the Drug Approval Process
Nurses participate most in the drug approval process during the postmarketing surveillance period of Phase IV
All nurses administering medications monitor for therapeutic effects and adverse reactions from the drugs
Responsible for reporting adverse reactions 98