Despite farmacological equivalence, generic vancomycin preparations exhibited inferior antimicrobial activity compared with the brand product in an infection model.
According to WHO regulations, generic versions of intravenous antibiotics are not required to demonstrate therapeutic equivalence with the brand product because therapeutic equivalence is assumed from pharmaceutical equivalence. Such practice is generally accepted worldwide. To test whether this assumption is justified for vancomycin, researchers compared the pharmacokinetic characteristics and antibacterial activity of the original Eli Lilly vancomycin (VAN-Lilly) with those of the competitor generic preparations marketed in Colombia between November 2002 and November 2009.
In vitro antibacterial effects, protein binding, and pharmacokinetic properties were similar between the generic vancomycin preparations and VAN-Lilly. However, in a Staphylococcus aureus neutropenic mouse thigh infection model, the antibacterial activity of the generic vancomycin preparations marketed between 2002 and November 2004 (when Eli Lilly sold its brand name and production secrets to several manufacturers worldwide) proved to be significantly inferior to that of VAN-Lilly. One generic could not even achieve bacteriostasis, and others showed a pronounced Eagle effect, with paradoxical bacterial growth at high antibiotic concentrations; VAN-Lilly exhibited bactericidal activity over a broad concentration range.
After November 2004, the production process of some generic vancomycin preparations was changed. Those produced according to the original Eli Lilly protocol showed in vivo antibacterial potency similar to that of VAN-Lilly; however, one other generic continued to have significantly poorer efficacy.
The major variations in in vivo antibacterial activity among the vancomycin preparations despite pharmacological and in vitro microbiological equivalency are astonishing. The authors noted that high concentrations of fermentation impurities in the generic products probably explain their impaired antibacterial activity and the Eagle effect.
At least for vancomycin, with its delicate production process, identical pharmacological profiles apparently do not predict similar antimicrobial activity. Whether this is true for other generic antibiotics is unclear. Given the broad use of generic antibiotics and the paramount importance of appropriate antimicrobial treatment in patients with life-threatening infections, more research on the efficacy of generic antibiotics is urgently needed.