Zina Kobbi a pharmacist and PhD student, with a broad and acute interest in drug development, regulation and researches. Her long experience in pharmaceutical industry and researches on biosimilars, lead her to be an expert in the field. After pharmaceutical studies she followed a master degree in drug development and worked on therapeutic equivalence of generic products and BCS classification. Passionate by researches she continued a PhD on biosimilar evaluation, while working in an industry developing generics and biosimilars. She has built the first model and platform of preclinical toxicity studies in Tunisia and built a bridge between the academy and the industry.
During last decades we observed explosion of biosimilars, which require biosimilarity study including comparative safety evaluation conducted on animals.
Enoxaparin is a low molecular weight heparin widely used for the prevention and treatment of thromboembolism and is considered as a biological product. With the development of several Enoxparin biosimilars, real medical concerns about their safety and efficacy were raised.
This repeated dose toxicity study part of the biosimilarity study consists of preclinical toxicological evaluation of a similar biological version of enoxaparin drug product “Enoxa” manufactured by “les Laboratoires Médis” (Tunisia), compared to the enoxaparin reference drug product “Lovenox” manufactured by Sanofi-Aventis (France). Eighty (80) white Wistar rats were treated with enoxaparin biosimilar, versus the reference product, using subcutaneous therapeutic dose and toxic doses, varying from 3.5 to 100 mg/kg/day. Dose levels were adjusted and ultimately fixed at 3.5 mg/kg/day for a therapeutic dose and 20 mg/kg/day for a toxic dose. A 0.9% sodium chloride solution was used for the control group and the comparative study was conducted over a period of 14 days and 28 days.
Animals were observed before and during study, all animal were euthanized at the end of the study design then necropsy, organs sampling and anatomo-histopathology were then performed. Hematology and biochimestry evaluation of relevant parameters was performed on all animals.
Comparable effects were observed at all doses and all products with few adverse effects observed at doses 20 mg/kg/day for both enoxaparin biosimilar and reference products. Mortality started at a dose of 40mg/kg/day and reached 25%, at 100 mg/kg/day for both products. Since results from the similar biological version of enoxaparin drug product “Enoxa” and reference drug product “Lovenox”, have comparable toxicity profile in rats, continuing investigation of biosimilarity on humans to confirm safety and efficacy is suggested.
Audience will learn:
•Biologics and biosimilar medicines development challenges
•Safety evaluation approach, for a new drug product as well as for a biosimilar product.
•Biosimilar development requirements (general and specific preclinical requirements)
•How to set up a preclinical toxicological protocol. Actually, few publications were issued about toxicity studies during biosimilar development, as they were usually performed by pharmaceutical companies and commercial facilities that provide animal-testing services to the industry, with no official published results
•Different tests used during preclinical study to evaluate biosimilar safety, this also could be applicable for other medicines and could help researchers to improve preclinical study design.