Skip links

505(b)(2) – Part 2: The Assessment: Pharmacokinetic Review

A comprehensive search of the literature is performed to obtain published pharmacokinetic (PK) data for the proposed product (dependent on selected regulatory pathway). This review compares the PK profiles for all available routes and conditions of administration and dose strengths. This review includes studies assessing:

  • Single- and multiple-dose administration
  • Dose proportionality
  • Bioavailability
  • Dose-ranging studies
  • Drug-drug interaction studies
  • Food effects

PK information is essential in a 505(b)(2) because it tends to drive what clinical studies will be needed.  The safety and efficacy of a drug depend on several factors but a key concept is exposure.  Exposure is both the concentration of drug as well as the total amount of drug a patient will be exposed to over a given time interval.  If the proposed product exceeds the exposure of the RLD then additional safety studies might be needed.  If the exposure is significantly lower, then efficacy trials might be needed.

The following slide illustrates two different PK profiles.  One profile has a maximum concentration in the blood that is in an area associated with adverse events. The other profile does not.