The safety of Filmix has been tested in animals, in compliance with the Principles of Good Laboratory Practices (GLP). Specifically, the Filmix preparation was first filtered through "Biosafe" sterile membrane filters (that pass USP class IV tests) into sterile 10-mL glass vials under aseptic conditions. These Filmix product vials (lot no. 12-29-89) were then tested at an independent GLP contractor, Leberco Testing Inc., and passed USP sterility and LAL pyrogen tests. Thereafter, this specific lot of Filmix product was employed in GLP acute intravenous (I.V.) toxicity studies in rabbits ( abstract; full report) and dogs ( abstract;full report ) at another independent GLP contractor, Pharmakon Research International Inc. No significant signs of gross toxicity or mortality were observed at a dosage of 4.8 mL/kg, which is 15 to 30 times those dosages to be employed in a Phase I human clinical trial. Similarly, efficacy testing of Filmix at Colorado State University in 53 dogs (abstract; full report), at a dose of 0.3 mL/kg, has never resulted in any post-injection clinical effects in these dog patients.
Besides the acute studies conducted with the Filmix lipid formulation in the rabbit and dog, subchronic toxicological studies also were conducted with Filmix in rats and rabbits. In the case of the rats (abstract; full report [see pp. 1, & 8-14]), the average dosage was 0.14 mL/kg I.V., 3 times weekly for 6 weeks, and for the rabbits (abstract; full report [see pp. 1-7]) 3 times weekly I.V. for 2.5 weeks at a dosage of 0.48 mL/kg. An extension of the rabbit studies in which Filmix was administered with added Gadolinium-DTPA derivative (related to Magnevist®) was continued at the same dosage and frequency for 2.5 months. The microscopic pathology for both species did not reveal any findings that could be related to the administration of Filmix. The tissues were read by Stuart Wyand, D.V.M., Professor of Pathobiology, University of Connecticut.
Finally, the lipids present in Filmix are similar to those found in
intravenous 20%-soybean-oil emulsion products, Intralipid (NDA 18-449,
KABI) and Liposyn-III (NDA 18-203, Abbott), except at far lower
concentrations, dosages, and frequency than employed with these two
approved products. These differences provide enormous margins of safety
for Filmix in its intended diagnostic and therapeutic applications in
humans. Moreover, Filmix product vials (lot no. 06-912) were also tested
for pyrogenicity by another independent GLP contractor, Toxikon Corporation,
using the USP XXII Rabbit Pyrogen Test.
The Filmix test article did not produce a pyrogenic response when tested in albino rabbits,
and was therefore considered non-pyrogenic.
RETURN TO MAIN PAGE
