This study implies that state-of-the-art liquid chromatography (LC) and mass spectrometry (MS) can be used for rapid verification of identity and characterization of sequence variants and posttranslational modifications (PTMs) for antibody products. number and identity of glycans were the same. These results demonstrate that this combination of accurate intact mass measurement, released glycan profiling and LC-MSE peptide mapping provides a set of routine tools that can be used to comprehensively compare a candidate biosimilar and an innovator mAb. Key words: biosimilar mAb, innovator mAb, molecular similarity, sequence variants, posttranslational modifications, N-linked glycosylation, chemical degradations, micro-heterogeneities, characterization, intact protein mass measurement, peptide mapping, glycan profiling, LC-MS, LC-fluorescence, MALDI MS Introduction Recombinant monoclonal antibodies (mAbs) are large, heterogeneous proteins that have emerged as therapeutics due to their predictable properties, controlled functions and long circulating life. MAbs represent a class of advanced, but expensive, medicines. With healthcare costs increasing to more than 16% of total GW 501516 gross domestic product in the US, lowering the cost of medicine is an economic and public health priority.1 There has recently been increasing interest Rabbit Polyclonal to TAF15. in developing less expensive biosimilar mAbs by both innovator and universal drug businesses.2 Another traveling force for the eye in biosimilars may be the upcoming patent expiration for marketed proteins products. In a recently available workshop, the feasibility from the advancement and authorization of mAbs using Western european Medications Agency’s (EMA) biosimilar regulatory pathways GW 501516 was talked about.3 In European countries, EMA has generated suggestions and defines a biosimilar being a medication which is comparable to a biological medication that has recently been authorized.4 Several biosimilar products are marketed in European countries already, although non-e are mAbs5 and developing biosimilar products is complicated.6 Few biosimilar items have been accepted in america, where they are referred to as follow-on protein products GW 501516 or follow-on biologics (this short article uses the term biosimilars throughout), due to restrictions in the legislative pathways used by the Food and Drug Administration to approve therapeutic agents. This situation may change as a consequence of healthcare legislation exceeded in March 2010 that contains specific provisions for biosimilars.7 The stated intention was to produce an approval GW 501516 pathway similar to that used for small molecule generic drugs to potentially reduce healthcare costs and expand competition. Nonetheless, the bill was severely criticized by proponents of biosimilars because of the 12-12 months data exclusivity protection afforded biotherapeutics.8 Under these circumstances, innovators have an interest in ensuring that their products are well-characterized so that biosimilars undergo similar rigorous characterization. Conversely, biosimilar manufacturers must ensure that their product conforms as closely as you possibly can to the existing product, reducing the need for expensive clinical trials and velocity time to market. Therefore, all parties have an interest in performing comprehensive analysis of their products. For innovative products as well as biosimilars, criteria for approval include quality, efficacy and safety. The objective of the biosimilar industry is to develop a product GW 501516 that is, as much as possible, much like a marketed innovator product. Therefore, the quality, non-clinical and clinical development programs are designed to demonstrate similarity of a biosimilar to its innovator product in every aspect. A number of physicochemical and biological methods are required by regulatory government bodies for characterization of mAbs.3,9 Individuals in EMA’s 2009 workshop questioned precisely how similar a biosimilar should be and commented on the issue of obtaining information on every atom in something and the necessity for the biosimilar mAb to really have the same distribution of antibody variants as the innovator product.3 It had been emphasized.