标题: What Are Biosimilars? [打印本页] 作者: choi 时间: 6-9-2016 14:51 标题: What Are Biosimilars? (1) Established in 2012, Samsung Bioepis is a joint venture between Samsung and US biotech Biogen (headquarters: Cambridge, Massachusetts). The Samsung subsidiary aims to produce biosimilars -- both for itself and as a contractor (for pharmaceuticals).
(2) On June 3, 2016 Mylan and Biocon Ltd (based in Bangalore, India) presented Phase 3 Trastuzumab biosimilar data at the American Society of Clinical Oncology (ASCO) annual meeting held in Chicago June 3 to 7. The presentation shows its version of Trastuzumab is similar to the "reference product": Herceptin of Roche Group.
Note:
(a) About Us: History. Mylan, undated http://www.mylan.com/en/company/about-us
("1961[:] Day 1 First known as Milan, the company starts doing business in White Sulphur Springs, West Virginia. US Army buddies, Milan 'Mike' Puskar and Don Panoz flip a coin to see who will name the business and who will be the company's first president. They start distributing products to doctors and pharmacists from an old Pontiac Bonneville")
(b) The patent on Herceptin expires in 2014 in Europe and in 2019 in US.
(c) Roche sells Trastuzumab under the brandname Herceptin.
(d) Trastuzumab is a monoclonal antibody (immunoglobulin G subclass 1 (IgG1, for short) with kappa light chain (lambda is the other type of light chain). Because Herceptin was first generated as mouse antibody (see (f)), it has to be humanized -- to reduce the chance of rejection by (human) patients -- by retaining the part (academically called "complementarity determining regions (CDR)") of the antibody that recognizes the antigen but replaces the rest of the antibody as much as possible.
(e) Trastuzumab is directed at (extracellular part of) human epidermal growth factor receptor 2 ("HER2" for short), which a subset of breast cancer overexpressed (on cancer cell surface). Subsequently (after the monoclonal antibody attaches to HER2), antibody-dependent cellular cytotoxicity (ADCC) follows (and cancer cells are killed).
(f) Herceptin® (Trastuzumab) Development Timeline. Genentech, undated http://www.gene.com/media/produc ... evelopment-timeline
(i) Please read events of 1987 and 1990.
(ii) Roche group (based in Basel, Switzerland) acquired Genetech in 2009.
(g) "Conventional drugs are made of pure chemical substances," says US Food and Drug Administration (FDA); its copy is a generic. But a monoclonal antibody is a huge molecule (protein) that must be produced by a cell line. its copy is therefore called a biosimilar (the original is identified as the reference product). The chemical composition (ie amino acids) of a biosimilar is different from that of the reference product.
(h) How to make a biosimilar?
Clone Identification; Selecting a clone from thousands of cells to produce a high-quality biosimilar requires thorough understanding of the reference product and deep scientific capabilities. Amgen Biosimilars. undated http://www.amgenbiosimilars.com/the-science/clone-identification/
Quote: "In order to select the best clone to produce a biosimilar, scientists must match, as closely as possible, the critical quality attributes and, most importantly, the biological function of the reference product. The match of critical quality attributes and biological function gives confidence that the biosimilar will have similar efficacy and safety to the reference product. To best match these attributes, hundreds to thousands of cells are evaluated using an extensive screening process to identify the one that will produce a biosimilar of the highest functional similarity. This screening process demands constant comparison to the reference product and follows four basic steps: candidate clone evaluation, transfection and amplification, clone selection, and product and process optimization. When each of these steps is completed, the end result can lead to a high-quality biosimilar.