Lecture 1

Question 1

Goals for New Drug (8)

Answer 1

1. Cheap to manufacture
2. Pharmaceutically elegant (accepted, recognizable dosage form)
3. Physically and chemically stable
4. Specific Desired Effect
5. Administered by most desired route (usually oral)
6. Optimal onset & duration
7. No side effects
8. Eliminated from the body efficiently, completely, and without residual effect

Question 2

New Drug Definition Components (7)

Answer 2

1. New chemical entity
2. Change in previously approved drug product’s manufacture or formulation
3. New combination of drugs if a question of safety is introduced by the change
4. New use for an approved drug
5. New dosage schedule or regimen
6. New route of administration
7. New dosage form
   * *NOT recognized as being safe & effective under the conditions recommended**

Question 3

Processes of Drug Discovery (5)

Answer 3

1. Random, non-targeted screening
2. Testing large numbers of synthetic organic compounds or natural compounds
3. Bioassays
4. Chemical alterations
5. Mechanism-based drug design

Question 4

2 Types of Bioassays

Answer 4

1. High throughput screenings

2. Molecular/Chemical modifications

Question 5

Chemical Alterations

Answer 5

Changing of an organic compounds to increase its usefulness

Ex: Changing of burimamide (an injection) into Cimetidine (oral tablet with minimal side effects)

Question 6

Mechanism-based Drug Design

Answer 6

Designing a drug with a known or suspected biochemical pathway or disease process in mind for its mechanism

Question 7

Drug Nomenclature Characteristics (3)

Answer 7

1. Short and distinctive
2. Indicate general pharmacologic or therapeutic class
3. Embody the syllable(s) characteristic of a related group of compounds

Question 8

What do Preclinical Studies find?

Answer 8

1. Chemical/physical properties
2. Pharmacology/Toxcology
3. ADME
4. Preformulation

Question 9

How are Preclinical Studies conducted?

Answer 9

• Conducted on animals PRIOR to human administration
• Utilize several animal species
• Certain species are chosen as “best representatives” for particular organ systems or disease states
• At least one rodent and one non-rodent species will be used

Question 10

Pharmacology

Answer 10

• Finds selectivity and efficacy

- Basic information on drug’s effects that can be used to predict the drug’s safe & effective use in humans

Question 11

ADME

Answer 11

Aka Pharmacokinetics

• Finds rate & extent of drug absorption from various routes of administration
• Studies how the drug is metabolized and distributes throughout the body, its pathways of metabolism, identification of its metabolites and their possible activity
• Proportion of drug eliminated by various routes and the time it takes to eliminate the drug from the body
• *Helps guide the selection for ideal doses and dosage forms of drug in humans**

Question 12

Toxicology

Answer 12

Drug Safety Evaluation (DSE)

• Studies its potential toxicity for both short-term (acute) and long-term (chronic) use
• *Human initial dose = 1/10 of the nontoxic dose**
• Potential for specific organ toxicity and its mode, site, and degree of toxicity
• Dose-Response relationships
• Reproductive, gender, teratogenic toxicities and its carcinogenic and genotoxic potentials

Question 13

Preformulation

Answer 13

Evaluation of a drug’s physical and chemical properties that could effect its formulation
Continues into clinical trials

Question 14

INDA

Answer 14

Investigational New Drug Application

• Drug sponsor files INDA with FDA before it can be given to humans
• This protects subject’s safety and insures the drug is scientifically sound and has planned protocols to reach its goals
• Once approved, clinical trials are conducted by the sponsor

Question 15

Clinical Protocol Requirements (8)

Answer 15

1. Purpose/objective of study and a study design
2. Estimate number of patients
3. Basis for subject selection - inclusion/exclusion
4. Dosing plan
5. Patient Monitoring - tests, measurements, observing
6. Contact info & investigators’ credentials
7. Locations & descriptions of research facilities
8. Approval from authorized Institutional Review Board (IRB)

Question 16

Clinical Trial Materials (3)

Answer 16

1. Initial formulation prepared for trials and human administration
2. Capsules containing ONLY active ingredients
3. Blinded studies - indistinguishable capsules between the test drug, placebo, and competitor drug

Question 17

Phase I

Answer 17

• 1st administration of drugs to humans
• Assesses safety and early PK studies
• Conducted in HEALTHY volunteers (~20-100)

Question 18

Phase II

Answer 18

• 1st administration to PATIENTS (~200-400)
• Evaluate effectiveness and assesses side effects/risks
• Determines effective dose
• Additional PK studies
• Final formulation refined

Question 19

Phase III

Answer 19

• Usefulness of drug in an expanded patient base (~2000-4000)
• Overall benefit to risk profile
• Several dosage strengths administered
• Information gathered for marketing

Question 20

Information Gathered for Marketing (5)

Answer 20

1. Labeling
2. Quality of Life
3. Advantages
4. Additional Indications
5. Post-Marketing Studies

Question 21

NDA

Answer 21

New Drug Application

• Submitted to FDA by sponsor after trials I-III are complete
• Sponsor must demonstrate sufficient drug safety & therapeutic effectiveness
• If approved, drug is given permission to enter the U.S. market

Question 22

Additional Drug Aspects Regulated by FDA (6)

Answer 22

1. Labeling Requirements
2. Package Inserts
3. Advertising
4. Promotional Material
5. Direct-to-Customer advertising of script drugs
6. Direct-to-Customer advertising of OTC drugs

Question 23

Phase IV

Answer 23

• Post-NDA approval and drug on the market
• Post-marketing surveillance done by MedWatch
• Administration of drug to more people may surface information not revealed in controlled studies

Question 24

Additional Post-Marketing Info to Report (5)

Answer 24

1. Drug interactions
2. Additional side effects or adverse effects
3. New uses
4. Better understandings of mechanisms of action
5. Need for difference dosage strengths, dosage forms, or routes of administrations

Question 25

TIND

Answer 25

Treatment Investigation New Drug -Allows patients with severe or life-threatening diseases to access investigational drugs in clinical trials that may help their condition

Question 26

SNDA

Answer 26

Supplemental New Drug Application - Sponsor of approved NDA may request approval for changes to that application - Changes in formulation, packaging, or labeling for example

Question 27

ANDA

Answer 27

Abbreviated New Drug Application - filed after patent expired for a marketed product by companies are making or who made generics - Generics: omit clinical/non-clinical studies, must show bioequivalence - Usually uses human PK data - If class 1, a biowaiver may be available

Question 28

BLA

Answer 28

Biologics License Application - Submitted to FDA prior to marketing of vaccines, blood products, toxins, etc. * *How the flu shot can be released so quickly on a yearly basis**

Question 29

505(b)

Answer 29

- NDA application that contains full safety and effectiveness reports, but some information (like safety and efficacy information on the active ingredient) to come from studies not completed by applicant - Includes all 4 clinical trials but trial 1 may be shortened

Question 30

New Route Applications

Answer 30

- Follows the same general process - Some pre-formulation and toxicity may be avoided in respect to the active ingredient ONLY - All studies that involve the new product must be reevaluated - Can be a significant cost!