Biopharmaceutics Classification System (BCS) Based Biowaiver Studies of Lenalidomide Capsules (25 mg) – An Alternative to In vivo Bioequivalence Studies for Generic Oncology Drug Products

Abstract

Lenalidomide, commercialized as Revlimid®, is an immunomodulatory drug, approved as a therapy for Multiple Myeloma and deletion 5q Myelodysplastic syndromes. This molecule shows a promising therapeutic potential in other hematologic malignancies. According to the European Medicines Agency (EMA), lenalidomide is considered as a fully absorbed drug substance, however, there is no sufficient data on solubility that enables its BCS classification. Therefore, as per the International Council for Harmonization (ICH) guideline, a solubility study has been done by Les Laboratoires Medis to prove that lenalidomide is a highly soluble compound. This demonstration requires the investigation in different buffer solutions within the range of pH 1- 6.8 (including pKa) at 37 ± 1°C and we have proceeded with a nominal concentration (1.0 mg/ml) which represent ten times the target concentration (0.1 mg/ml). The main reason of conducting this study is to evaluate the possibility of a BCS-based biowaiver for the consent of a generic oncology drug product unescorted by any further in vivo bioequivalence (BE) studies, also, to prove that Lenalidomide can be classified as highly soluble and highly permeable, i.e., BCS class I. The objective of establishing the BCS-based biowaiver procedure is to minimize the need for in vivo BE studies, that would reduce the exposure of healthy volunteers to oncology drugs such as lenalidomide, to prove BE. The test product and Revlimid were evaluated by in vitro methods as stated by ICH guidelines in three dissolution buffers: pH 1.2, 4.5, and 6.8, and QC release medium. The obtained results revealed that both, the test product and Revlimid have exhibited a very rapid dissolution rate (i.e. >85% in 15 min) in all dissolution buffers which infers that the test product complies with the similarity requirements for comparative dissolution testing versus the reference product. It is concluded that lenalidomide 25 mg capsules test product is bioequivalent to reference product using BCS biowaiver.