Midterm 2 Development Flashcards
What is the primary objective of drug development?
High number of approved drugs with competitive ‘quality’ drug label claims
True or False: CMC is unlikely to be critical path to First Patient Dosed in any clinical study
True
What is the objective of Registration stage in Drug Development?
Gain regulatory approval of drug label claims
What is critical path in the preclinical development stage?
Guideline safety & tolerability studies supporting safety for IND submission
What general criterion does not define a project
No defined outcome or outcome specifications
True or False: BLA is submitted for regulatory review & approval of a biological drug
True
What clinical study milestone best represents the actual treatment start?
First Patient Dosed
True or False: The global pharmeceutical industry is highly regulated
True
What is the cycle time for regulatory review under ‘standard’ review conditions
12-18 Months
In the US, what regulatory action occurs before regulatory approval, or any other regulatory action?
FDA Advisory Board Meeting
How is drug development defined (start->finish)?
Drug candidate identified -> approved drug
What is a key event (milestone) in preclinical development?
IND submission
What stage is NOT considered a drug development stage?
a) Phase 2 b) Phase 3 c) Preclinical Development d) Commercialization e) Registration
Commercialization
Scientific & Technical Analysis, Commercial Analysis and Valuation are the 3 major parts determining risk & value of an R&D program
True
During what stage is the drug candidate produced at laboratory scale?
Lead Optimization
What is the definition of a pipeline in the pharmeceutical industry?
Totality of all R&D programs operated by a pharmeceutical company
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
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
What is made first in the manufacturing process of small (organic) molecule drug e.g. NEXAVAR?
Drug Substance (= Active Pharmeceutical Ingredient, API)
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
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
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
The CMC Manufacturing concept of “Product=Process” applies only to NCE’s
False
Which US regulatory pathway to approval did NEXAVAR NOT use?
Standard BLA submission
RITUXAN (RITUXIMAB) selectively binds the CD20 receptor of cancerous and non-cancerous B-cells
True
The overall global development time of NEXAVAR was reported as
62 months
RITUXIMAB is currently standard-of-care treatment for several hematological (blood) cancers
True
NEXAVAR is currently marketed as member of which cancer drug class?
Potent Multi-Kinase Inhibitor incl. RAF-1 Kinase
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
What is the starting point in Drug Development?
‘Drug-Like’ Clinical drug candidate
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
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
Drug Development stages
Preclinical –> Phase 1, 2, 3 –> Registration
Key milestone in Preclinical development
IND submission (Investigational New Drug Application)
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
Key milestones of Phase 2 (I)
First Patient Enrolled
Top Line Results (safety, efficacy: PE, biomarkers)
Key milestones Phase 2 (II)
FDA EOP2 Meeting
Phase 3 objective
to establish clinical safety & efficacy for registration
Key Milestones Phase 3 (I)
First Patient Enrolled (protocol Z)
Top Line Results
Key Milestones Phase 3 (II)
FDA Pre-NDA Meeting
Objective of Registration Phase
gain regulatory approval of grug label claims
Key Milestones of Registration
New Drug Application (NDA) Submission (FDA)
Decision: Commitment-To-Launch: 1st Geography
NDA Approval (US)
Launch in 1st Geography
major parts determine risk & value of an R&D program
- Scientific & technical analysis
- Commercial analysis
- Valuation
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?
Project Management is about managing the 4 P’s
Product
People
Process
Playground
Guideline safety & toxicology is critical path to….
IND
IND includes…
specific data to understand long-term safety
True or false: Guideline PK program is NOT critical path to IND
true
Primary goal of Preclinical Development is
to establish safety for First-In-Human (FIH) administration
What is the objective of Phase 2 in drug development?
Establish safety & efficacy in patients and demonstrate clinical proof-of-biological activity
What’s an IND?
Investigational new drug application
Which event (milestone) in phase 2 of clinical development marks the start of actual patient treatment?
First Patient Dosed
CMC is not critical path to IND submission?
False
What is the objective of preclinical development?
Establish safety and tolerability in animals for first in humans
CMC is unlikely to be critical path in First Patient dosed in any clinical study?
True
Demonstration of Phase 2 Proof-of-biological concept is a major inflection point for risk/value analysis
True
What stage is not considered a drug development stage?
Commercialization
What is the objective of Phase 3 in Drug Development?
Establish safetfy and efficacy in patients for registration
Demonstration of an approved, commercially competitive drug label is not a major inflection point for risk/value analysis
False
What is the objective of Registration stage in drug development?
Gain regulatory approval of drug label claims
Scientific & technical analysis, Commercial analysis and valuation are the 3 major parts determining risk & value of an R&D program
true
What set of key regulatory milestones represent the US?
IND submission, EOP2 FDA, NDA submission
During what stage is the drug candidate produced at laboratory scale?
Lead Optimization
NDA stands for what?
New Drug Application
What is critical path in the preclinical development stage?
Guideline safety & tolerability studies supporting safety for IND submission
What does not describe project management in the Pharmaceutical industry
Make decisions which R&D programs to move forward or not
What combination best describes pharmaceutical R&D?
>$800M and <10% success and 10-15 years cycle time
Which kg range best reflects clinical scale manufacturing, assuming early clinical stages (FIH -> Phase 2B) ?
10-100kg
What general criterion does NOT define a project
No defined outcome or outcome specifications?
What final drug product quality is required to enter first in human, and other phase 1, 2 and 3 clinical studies?
GMP
How is successful outcome of a phase 3 study defined?
Meeting the primary clinical endpoint in a statistically significant manner (p<0.05)
BLA is submitted is submitted for regulatory review & approval of a biological drug
True
GLP grade Final Drug Product is Not required to conduct safety & toxicology studies required for IND submission
False
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?
What is the ‘End-Product’ of Preclinical Development?
IND submission
Is achieving statistical significance in meeting the phase 3 primary clinical endpoint necessary for gaining regulatory acceptance & approval?
Yes
During what phase of clinical development is clinical proof-of-concept, of clinical Proof-of-Biologcial Activity established?
Phase 2B
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
Which functional area (area of specific expertise) is not a CMC functional area?
clinical R&D
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
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
What is the cycle time for regulatory review under ‘standard’ review conditions
12-18 months
Which US regulatory meeting will review phase 3 clinical efficacy and safety data?
Pre-NDA, or Pre-BLA meeting with FDA
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
Which scale is mostly used in the Preclinical
pilot scale
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
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
Which parameters are key drivers of clinical study size (patient N), costs and duration?
- Primary clinical endpoint
- Study power
- Statistical significance (p-value)
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
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
