Characterisation of the rat lung lavage model as biological assay for testing the activity of surfactant preparations.
The present report describes how pharmacological assays may be validated and sets a basis for a discussion on the validation of biological test systems. The note for guidance on the validation of analytical procedures published by the European agency for the evaluation of medicinal products was adapted to the validation of a pharmacological test system. The presently described rat lung lavage test (RLL-test) is an animal model that has great similarities to the pathophysiology of the acute respiratory distress syndrome of humans. In this RLL-test, the activity of surfactants can be tested in a standardised fashion. The usefulness of the point estimator and the corresponding confidence intervals (CI) as a statistical test procedure for equivalence was demonstrated. A validation can be based on the above mentioned guidance but should be adjusted to pharmacological needs. Based on the presented experiences, it can be concluded that a specific guideline for validation of pharmacological or biological tests is desirable.
Häfner
D
D
Department of Respiratory Pharmacology, Byk Gulden, Konstanz, Germany. dietrich.haefner@byk.de
Burke
M
M
Schick
K
K
Hauschke
D
D
D000758:Anesthesia; D000818:Animals; D001681:Biological Assay; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D010100:Oxygen / Q000097:blood; D011663:Pulmonary Surfactants / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012015:Reference Standards; D015203:Reproducibility of Results; D007507:Therapeutic Irrigation
D011663:Pulmonary Surfactants; D011994:Recombinant Proteins; D010100:Oxygen