EMA Guidance Amended on PK Evaluations, BE Study Requirements

Drugmakers may use pharmacokinetic bioequivalence studies to compare how two orally inhaled drugs with the same active substance disperse in the lungs, the European Medicines Agency says.

The amount of drug reaching the lungs and the pattern that drug particles settle within the lung must be equivalent to determine efficacy, the EMA adds. The advice updates a questions-and-answers guideline on bioequivalence studies.

For inhaled drugs where there is some intestinal absorption but the impact on systemic exposure is negligible, a single-dose PK study without charcoal may be used to compare both efficacy and safety. Drugs such as budesonide, formoterol and salmeterol, which have significant oral bioavailability, require a PK study with active charcoal to assess efficacy as well as one without charcoal to assess safety.

The EMA also clarifies 2005 guidance on the evaluation of PK in patients with impaired liver function, saying subjects selected for studies should cover the range of impairments. PK studies are recommended when the liver problem is likely to significantly alter the way in which the drug or its active metabolites are metabolized and excreted and when a dosage adjustment may be needed as a result of the PK/pharmacodynamic relationship, the guideline says.

Sponsors that choose not to conduct such a study must justify the decision in their submission to the agency.

Read the Q&A at www.fdanews.com/03-15-EMA-QA.pdf. — Jonathon Shacat