Bioequivalence Considerations for Locally Acting Nasal Drugs

1
Bioequivalence Considerationsfor Locally Acting
Nasal Drugs

• Dale P. Conner, Pharm.D.
• Division of Bioequivalence
• Office of Generic Drugs, CDER, FDA

2
Definition of Bioequivalence

• Pharmaceutical equivalents whose rate and extent
  of absorption are not statistically different
  when administered to patients or subjects at the
  same molar dose under similar experimental
  conditions

3
Purpose of BE

• Therapeutic equivalence (TE)
• Bioequivalent products can be substituted for
  each other without any adjustment in dose or
  other additional therapeutic monitoring.
• The most efficient method of assuring TE is to
  assure that the formulations perform in an
  equivalent manner.

4
What are the questions?

• Bioavailability (BA)
• How is the drug absorbed?
• How much gets to the site(s) of activity?
• Bioequivalence (BE)
• Are the two pharmaceutically equivalent
  formulations equivalent in their in vivo
  performance, leading to therapeutic equivalence?
• Performance is release of the drug substance from
  the drug product

5
Model of Oral Dosage Form Performance
Dosage Form Performance (Formulation)
Pharmacokinetic Measurement
Clinical/PD Measurement
Therapeutic Effect
Gut Wall
Drug in Solution
Blood
Site of Activity
Dosage Form
ln Dose
Dose
6
Model of Nasal Spray Dosage Form Performance
Clinical/PD Measurements
Dosage Form Performance (Device and Formulation)
Membrane (Nasal)
Site of Activity
Therapeutic Effect
Drug in Solution
Dosage Form
Blood
GI Tract, Lung
Toxic/Ther. Effect
Pharmacokinetic Measurement
7
Clinical/PD Dose-Response
Clinical/PD Response
Log Dose
8
Plasma Concentration-Dose
Plasma Conc.
Dose