Drug Approval Process
My tests had several questions that referenced to the drug approval process. I suggest that anyone planning to take the MPJE for any state be familiar with the drug approval processes
Investigational New Drug Application
•1stapplication before drug is given to humans
•Federal Drug Administration (FDA) has 30 days to decide if suitable for testing
•Must provide clinical protocols to be used in human testing
Clinical Trials
Initiated after FDA approves the investigational new drug application
3 phases before marketing and 1 phase after marketing
Phase 1: Small group of healthy individuals to evaluate toxicity, kinetics, safety
Phase 2: Large group (100+) with the disease being treated to evaluate effectiveness, safety, and adverse drug events (ADEs)
Phase 3: Large group (1000+) to evaluate effectiveness, double-blinded with placebo
Phase 4: Post-marketing surveillance to determine if drug should stay on the market
New Drug Application (NDA)
Can apply once data on safety, efficacy, toxicity, stability, production methods, packaging and clinical trial data exists
Typically takes 6 months for review
Abbreviated New Drug Application (ANDA)
For introducing a generic of an already approved drug
Requires proof of kinetics, bioequivalence/bioavailability
Supplemental New Drug Application (SNDA)
For changes to synthesis, production, manufacturer location, packaging and/or labeling
For new dose form, strength or therapeutic use

Epidiolex – What is it? Is it a controlled substance?
What is it?
First and only FDA-approved prescription cannabidiol (CBD)
What is it used for?
Seizures associated with Lennox-Gastaut syndrome (LGS), Dravet syndrome or tuberous sclerosis complex (TSC)
Mechanism of action for the reduction of seizures is unknown.
How is it dosed and taken?
Titrated dosing given orally or via feeding tube (non PVC) twice daily, administered consistently with or without food.
LGS or Dravet syndrome:
Initial dose: 5mg/kg/day (2.5mg/kg twice daily)
Recommended dosing: 10 to 15mg/kg/day (5 to 7.5mg/kg twice daily) increased in weekly increments of 5mg/kg/day (2.5mg/kg twice daily)
Maximum dosing: 20mg/kg/day (10mg/kg twice daily)
TSC:
Initial dose: 5mg/kg/day (2.5mg/kg twice daily)
Recommended dosing: 10 to 20mg/kg/day (5 to 10mg/kg twice daily) increased in weekly increments of 5mg/kg/day (2.5mg/kg twice daily)
Maximum dosing: 25mg/kg/day (12.5mg/kg twice daily)
If rapid titration is necessary, dose may be increased no more frequently than every other day.
Dose adjustment and a slower titration is recommended in patients with moderate to severe hepatic impairment.
Should not be stopped suddenly due to the risk of increased frequency of seizures and status epilepticus.
Recommended lab work:
Transaminase and bilirubin levels prior to starting treatment, at month 1, month 3 and month 6 then periodically thereafter.
Patients on valproate or are at increased risk of elevated transaminase levels and/or hepatocellular injury.
If levels are elevated, consider a dose reduction or discontinuation of Epidiolex or other medications known to increase transaminase levels such as valproate and/or clobazam.
Common side effects (> 10% and greater than placebo): transaminase elevations, somnolence, fatigue, malaise, asthenia, decreased appetite, diarrhea, vomiting, pyrexia, rash, insomnia and infections.
Other important side effects to be aware of: suicidal behavior and ideation
Potential interactions to consider:
Several potential drug-drug interactions to consider, most commonly run into potential drug-drug interactions with other anticonvulsant medications:
Clobazam, diazepam, & valproate
Recommended to counsel patient or caregiver on signs/symptoms to watch for and recommend lab work as appropriate.
Strawberry flavored but does not contain strawberry.
Compatible with a ketogenic diet.
Federal law no longer considers Epidiolex to be a controlled substance. It had originally been federally scheduled as a CV. Now it is federally non-controlled. There are a handful of states that have it scheduled as a controlled substance.
https://www.drugtopics.com/view/dea-deschedules-antiepileptic-cbd-oral-solution-epidiolex
| Controlled Status | State |
| CIV | Louisiana |
| CV | Florida |
| CV | Georgia |
| CV | Idaho |
| CV | Maryland |
| CV | Montana |
| CV | Nebraska |
| CV | North Dakota |
| CV | Puerto Rico |
