Local tolerance testing of parenteral drugs: how to put into practice

Abstract

Notwithstanding that there are national and international guidelines about local tolerance testing of parenteral drugs in animals, in particular to mention CPMP/SWP/2145/00 ( Note for Guidance on Non-Clinical Local Tolerance Testing of Medicinal Products), very heterogeneous study designs have been established in the past. A working group including experts of the leading pharmaceutical industry from German-language countries, named “Arbeitskreis Lokale Verträglichkeit,” has been intensively discussing the experimental procedures in detail for a period of six years and has been considering their pros and cons. This team of experts now feels confident to give some recommendations for study conduct besides describing different materials and methods for this type of toxicological study. Special knowledge from toxicologists as well as pathologists from our working group has been taken into account. This paper deals with choice of species, number of animals used, controls, administration sites, volumes, rate and frequency, length of observation period, termination, clinical, macroscopic and histopathological examinations and, finally, overall assessment criteria and conclusion. Our purpose is that this paper may be of value for: • The study director who is inexperienced in the conduction of local tolerance testing and who may need a standard design as his first step into this new field. • The well-versed study director who would like to know how others have done in the past, who may examine self-critically his own practice and who is open to our team’s recommendations, tips and tricks from practice. • The specialist at a regulatory authority who, finally, reviews study reports, assesses their format and content and, above all, decides on the approval of a drug product.