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Flashcards in Midterm 2 Development Deck (91):
1

What is the primary objective of drug development?

High number of approved drugs with competitive 'quality' drug label claims

2

True or False: CMC is unlikely to be critical path to First Patient Dosed in any clinical study

True

3

What is the objective of Registration stage in Drug Development?

Gain regulatory approval of drug label claims

4

What is critical path in the preclinical development stage?

Guideline safety & tolerability studies supporting safety for IND submission

5

What general criterion does not define a project

No defined outcome or outcome specifications

6

True or False: BLA is submitted for regulatory review & approval of a biological drug

True

7

What clinical study milestone best represents the actual treatment start?

First Patient Dosed

8

True or False: The global pharmeceutical industry is highly regulated

True

9

What is the cycle time for regulatory review under 'standard' review conditions

12-18 Months

10

In the US, what regulatory action occurs before regulatory approval, or any other regulatory action?

FDA Advisory Board Meeting

11

How is drug development defined (start->finish)?

Drug candidate identified -> approved drug

12

What is a key event (milestone) in preclinical development?

IND submission

13

What stage is NOT considered a drug development stage?

a) Phase 2 b) Phase 3 c) Preclinical Development d) Commercialization e) Registration

Commercialization

14

Scientific & Technical Analysis, Commercial Analysis and Valuation are the 3 major parts determining risk & value of an R&D program

True

15

During what stage is the drug candidate produced at laboratory scale?

Lead Optimization

16

What is the definition of a pipeline in the pharmeceutical industry?

Totality of all R&D programs operated by a pharmeceutical company

17

CMC product development is mainly about answering the following set of key questions?

What's the product and whats the process to make it? What quantities are required & with what grade? When is it needed? Where can the product be manufactured?

All of the above

18

Which Non-US Regulatory milestone (key event) is similar to Pre-IND meeting in the US?

Scientific Advice Meeting with EMA, Scientific Advice Metting with PDMA, Scientific Advice Meeting with Health Canada,

All of the above

19

What is made first in the manufacturing process of small (organic) molecule drug e.g. NEXAVAR?

Drug Substance (= Active Pharmeceutical Ingredient, API)

20

Which disease areas (clinical indications) have increasingly been using expedited regulatory pathways provided in the US?

Cancer indications e.g. kidney, liver, and ovarian cancer

21

The manufacturing process of RITUXAN (Rituximab), a monoclonal antibody, is more complex than the manufacturing process leading to NEXAVAR, true or false

True, because it is an NBE and NBE's take longer than NCE's to manufacture

22

The global development strategy of NEXAVAR (Sorafinib) was mainly determined by which of the following criteria?

Predominantly unmet medical need & expedited regulatory pathways, and clinical cancer indications best-suited to multi-kinase inhibitory drug action

23

The CMC Manufacturing concept of "Product=Process" applies only to NCE's

False

24

Which US regulatory pathway to approval did NEXAVAR NOT use?

Standard BLA submission

25

RITUXAN (RITUXIMAB) selectively binds the CD20 receptor of cancerous and non-cancerous B-cells

True

26

The overall global development time of NEXAVAR was reported as

62 months

27

RITUXIMAB is currently standard-of-care treatment for several hematological (blood) cancers

True

28

NEXAVAR is currently marketed as member of which cancer drug class?

Potent Multi-Kinase Inhibitor incl. RAF-1 Kinase

29

Development value chain objectives

  • New Chemical Entities; New Biological Entities; First-In-Class; Best-In-Class
  • High # of approved drugs
  • Competitive 'quality' of drug label claims

30

What is the starting point in Drug Development?

'Drug-Like' Clinical drug candidate

31

What is bioavailability?

  • The degree to which a drug or other [bioactive] substance becomes available to the target tissue after administration
  • The physiological availability of a given amount of a drug, as distinct from its potency

32

What is PK and PD?

Pharmacokinetics: The process by which a drug is Absorbed, Distributed, Metabolized, and Eliminated (ADME) by the body

Pharmacodynamics: The study of how a drug acts on a living organism (duration and magnitude) of response

33

Drug Development stages

Preclinical --> Phase 1, 2, 3 --> Registration

34

Key milestone in Preclinical development

IND submission (Investigational New Drug Application)

35

Milestones for Phase 1

  • FIH single dose
  • FIH multiple dose
  • Safety parameters
  • PK: Bioavailability
  • What drug levels needed? Biomarkers of efficacy?
  • Low dose --> highest dose

36

Key milestones of Phase 2 (I)

First Patient Enrolled

Top Line Results (safety, efficacy: PE, biomarkers)

37

Key milestones Phase 2 (II)

FDA EOP2 Meeting

38

Phase 3 objective

to establish clinical safety & efficacy for registration

39

Key Milestones Phase 3 (I)

First Patient Enrolled (protocol Z)

Top Line Results

40

Key Milestones Phase 3 (II)

FDA Pre-NDA Meeting

41

Objective of Registration Phase

gain regulatory approval of grug label claims

42

Key Milestones of Registration

New Drug Application (NDA) Submission (FDA)

Decision: Commitment-To-Launch: 1st Geography

NDA Approval (US)

Launch in 1st Geography

43

# major parts determine risk & value of an R&D program

  • Scientific & technical analysis
  • Commercial analysis
  • Valuation

44

Risks in Drug Discovery/Development

 

  • How much risk, how many uncertainties?
  • What price are you willing to pay?
  • For What outcome, and how important is it to you?

45

Project Management is about managing the 4 P's

Product

People

Process

Playground

46

Guideline safety & toxicology is critical path to....

IND

47

IND includes...

specific data to understand long-term safety

48

True or false: Guideline PK program is NOT critical path to IND

true

49

Primary goal of Preclinical Development is

to establish safety for First-In-Human (FIH) administration

50

What is the objective of Phase 2 in drug development?

Establish safety & efficacy in patients and demonstrate clinical proof-of-biological activity

51

What's an IND?

 

Investigational new drug application

52

Which event (milestone) in phase 2 of clinical development marks the start of actual patient treatment?

First Patient Dosed

53

CMC is not critical path to IND submission?

False

54

What is the objective of preclinical development?

Establish safety and tolerability in animals for first in humans

55

CMC is unlikely to be critical path in First Patient dosed in any clinical study?

 

True

56

Demonstration of Phase 2 Proof-of-biological concept is a major inflection point for risk/value analysis

True

57

What stage is not considered a drug development stage?

Commercialization

58

What is the objective of Phase 3 in Drug Development?

Establish safetfy and efficacy in patients for registration

59

Demonstration of an approved, commercially competitive drug label is not a major inflection point for risk/value analysis

False

60

What is the objective of Registration stage in drug development?

Gain regulatory approval of drug label claims

61

Scientific & technical analysis, Commercial analysis and valuation are the 3 major parts determining risk & value of an R&D program

true

62

What set of key regulatory milestones represent the US?

IND submission, EOP2 FDA, NDA submission

63

During what stage is the drug candidate produced at laboratory scale?

Lead Optimization

64

NDA stands for what?

New Drug Application

65

What is critical path in the preclinical development stage?

Guideline safety & tolerability studies supporting safety for IND submission

66

What does not describe project management in the Pharmaceutical industry 

Make decisions which R&D programs to move forward or not

67

What combination best describes pharmaceutical R&D?

>$800M and <10% success and 10-15 years cycle time

68

Which kg range best reflects clinical scale manufacturing, assuming early clinical stages (FIH -> Phase 2B) ?

10-100kg

69

What general criterion does NOT define a project

No defined outcome or outcome specifications?

70

What final drug product quality is required to enter first in human, and other phase 1, 2 and 3 clinical studies?

GMP

71

How is successful outcome of a phase 3 study defined?

Meeting the primary clinical endpoint in a statistically significant manner (p<0.05)

72

BLA is submitted is submitted for regulatory review & approval of a biological drug

True

73

GLP grade Final Drug Product is Not required to conduct safety & toxicology studies required for IND submission

False

74

CMC product development is mainly about answering the following set of key questions

  • What's the product and whats the process to make it?
  • What Quantities are required & with what grade?
  • When is it needed?
  • Where can the product be manufactured?

75

What is the 'End-Product' of Preclinical Development?

IND submission

76

Is achieving statistical significance in meeting the phase 3 primary clinical endpoint necessary for gaining regulatory acceptance & approval?

Yes

77

During what phase of clinical development is clinical proof-of-concept, of clinical Proof-of-Biologcial Activity established?

Phase 2B

78

What is included in the Clinical Trial Protocol, a key document in Clinical Drug Development?

Clinical objective, clinical success criteria & primary clinical endpoint, patient inclusion & exclusion criteria, safety & efficacy criteria

79

Which functional area (area of specific expertise) is not a CMC functional area?

clinical R&D

80

What is the key objective of regulatory authorities worldwide?

Ensure sufficient evidence is provided demonstrating efficacy, safety, therapeutic benefit and risk/benefit in the studied patient population

81

What are the objectives in the Registration stage of development?

Approval of drug label claims re: clinical safety; approval of drug label claims re: clinical efficacy; approval of drug label claims re: disease (therapeutic) area and indication; approval of drug label claims re: studied patient population

82

What is the cycle time for regulatory review under 'standard' review conditions

12-18 months

83

Which US regulatory meeting will review phase 3 clinical efficacy and safety data?

Pre-NDA, or Pre-BLA meeting with FDA

84

Which Non-US regulatory milestone (key event) is similar to the Pre-IND Meeting in the US?

  • Scientific Advice meeting with EMA
  • Scientific Advice Meeting with PMDA
  • Scientific Advice Meeting with Health Canada

85

Which scale is mostly used in the Preclinical

pilot scale

86

Assuming successful Phase 3 and Pre-NDA Meeting outcome, which regulatory action is the most likely to occur?

Conditional approval, including defined post-approval commitments to be fulfilled by the company

87

Which expedited regulatory pathway provides 1) additional 7-year market exclusivity post approval, and 2) tax deductions for R&D expenses incurred in the US?

Orphan Drug Status

88

Which parameters are key drivers of clinical study size (patient N), costs and duration?

  • Primary clinical endpoint
  • Study power
  • Statistical significance (p-value)

89

In general, major manufacturing process optimization occurs during preclinical development, and minor process improvements occur until the manufacturing process is locked-in prior to phase 3 start


True

90

Which disease areas (clinical indications) have increasingly been using expedited regulatory pathways provided in the US?

Cancer indications e.g. kidney, liver, and ovarian cancer

91