2 - Drug Approval Process (Part 1) Flashcards
Describe the “drug discovery to market” portion of drug development process
- Molecule discovery
- Pre-clinical trials
- Clinical trials (phase 1, 2, 3)
- Therapeutic Products Directorate (TPD)
- Notice of Compliance (NOC, NOC/C)
Describe the “drug pricing and access” portion of drug development process
- PMBRB
- CADTH Common Drug Review (CDR)
- Phase 4 trials, ADR Surveillance
- Formulary Decision (provincial, hospital)
What is involved in Pre-Clinical Trials ?
Pharmaceutics:
-physicochemical characterization, impurity analysis, formulation, stability testing
Efficacy screening:
-in vitro, in vivo models
ADME profiling
Toxicology:
-Cytotoxicity, hepatotoxicity, CV safety pharmacology, maximum tolerated dose, etc.
Describe a Phase 1 Clinical Trial
- Primarily to establish safe dosing range in humans
- Pharmacologic profiles
- Normal, healthy volunteers (n = 20-100)
- 1 year
Describe a Phase 2 Clinical Trial
- Pilot efficacy trials in small population with the indicated condition
- Select optimal dose, observe for AEs
- Volunteer patients (n = 100-150)
- 2-3 years
Describe a Phase 3 Clinical Trial
- Extensive clinical trials in large populations with the indicated condition (n = hundreds to thousands)
- Goal to verify efficacy of the drug by comparing the new drug to a control group (placebo or comparator) - demonstrate magnitude of benefit is not due to chance
- 1-5+ years depending on indications
- Also intended to establish safety in target patient population
- Sample size of phase 3 trials are designed to have enough power to detect difference in the clinical outcomes of interest, NOT adverse events
- Severe, life-threatening ADEs (ex. Steven Johnson’s, QT prolongation) occur far more less frequently than the clinical outcomes
Know difference between type 1 and 2 errors man
yo
Just because it’s gone through phase 3 trials doesn’t mean it’s ____. This is where we need phase 4 (surveillance of real-world effectiveness)
safe
Describe phase 4 clinical trials
- Post-marketing trials of effectiveness and safety
- Surveillance of real-world effectiveness and long-term safety
- New indications for use
- Special disease-state and populations (ex. renal impairment, geriatric and paediatric populations, genetic subtypes)
- Drug interaction studies
- Pharmacoeconomic studies
Describe Efficacy vs. Effectiveness
Efficacy:
- the actual therapeutic benefit that a drug has (controlled environment)
- RCTs
- frequency contact with clinicians
- 100% compliance
Effectiveness: In real world (not controlled)
-Each patient has other factors that may contribute
Describe the Therapeutic Products Directorate (TPD)
The national authority in Canada that regulates, evaluates and monitors the safety, efficacy and quality of therapeutic and diagnostic products available to Canadians
In the drug licensing process, TPD has regulatory authority in the following 3 stages:
- Clinical trial authorization
- Drug submission reviews
- Post-market
How is TPD applied to conduct a clinical trial
- informed consent phase 1
- good clinical practices
- primary safety and dosing range in humans
- controlled environment - administration and evaluation monitored
- drug limited to clinical investigators named on trial
NOC
Notice of compliance
Describe NOC (Notice of compliance)
- Permits the sponsor to market drug
- Indicates the drug’s official approval in Canada
DPD
Drug product database
