FDA Case Study

Getting a Drug to market

Drug Funnel

Development Steps for NME

  • New molecular entity (NME)

Submitting an IND (investigational New Drug)

  • Allows drugs to be moved across state lines for testing

  • Must provide information about:

    • Animal studies
    • Chemistry, Manufacturing and controls (CMC)
    • Clinical protocols and investigator information
    • Informed consent (reporting of potential adverse effects)

The IND application is submitted to the office of new drugs (OND) which is a subsidiary of the center for Drug evaluation and research (CDER).

In addition, the IND is submitted to an institutional review board (IRB) which reviews the informed consent documents. It is a panel of scientists and non-scientists.

  • IND will be responded to by the FDA within 30 days
    • Safe to proceed
    • Clinical hold (not safe to proceed)
    • Partial hold (safe to proceed with limitations)

Informed consent

  • ongoing and interactive
  • needs to be easy to understand for the lay-person
informed consent form

Phase 1 Trial

  • required to report suspected fatal reaction no later than 7 days to FDA
  • report any other significant adverse effect within 15 days
  • Annual progress reports within 60 days of anniversary of the study
  • need to submit study report summarizing results at the end of the study

Phase 2 trial

  • Submit phase 2 protocol
  • End of phase 2-A meeting allows one to receive input about the study from the FDA
  • End of phase 2 meeting before the beginning of phase 3
  • within 60 days of EOP2 meeting, pediatric study plan
  • prior to the meeting submit a meeting package

Phase 3 trial

  • once agreed upon, it is a binding agreement with the FDA
  • pivotal
  • adequate and well-controlled investigations
  • multiple controlled trials are required
  • same reports as phase 1 and 2 are required

Submission of the New Drug application (NDA)

  • pre-NDA meeting allows one to resolve any remaining issues, reducing delays with FDA reviews

  • Need to pay a user fee with the NDA to support timely reviews, though you can get a fee waiver sometimes

  • is the drug safe and effective?

  • is the drug of adequate quality

Risk evaluation and mitigation strategy (REMS)

  • Needed when risks are high
    • large population
    • serious disease
    • duration
    • expected benefit
    • potential effects
    • type of drug

FDA 60 day notification

  • FDA will tell you if the application is complete within 60 days
  • FDA will halt a review and take a “refuse to file” action if there is a problem requiring a resubmission
  • FDA may ask for information during the review
  • FDA will conduct investigations if they deem the potential drug to be out of the ordinary or potentially unsafe
  • FDA may use an advisory committee

FDA letters

  • Approval letter allows one to market and sell a new drug
  • Complete response letter details why a drug was not approved and what issues need to be resolved before it can be approved

Speeding up the review process

  • Unmet medical need
  • Serious condition expedited programs

Recap (meetings)

  • type A meetings are used to restart a stalled development program
  • type B meetings are milestone advice meetings
  • type C meetings are any meeting other than type A or B

Post-Approval Activities

  • Continuing obligation to report any new safety information that comes to light