Read by QxMD icon Read

biosimilar LMWH

Rohitesh Gupta, Moorthy P Ponnusamy
Structural characterization of Low Molecular Weight Heparin (LMWH) is critical to meet biosimilarity standards. In this context, the review focuses on structural analysis of labile sulfates attached to the side-groups of LMWH using mass spectrometry. A comprehensive review of this topic will help readers to identify key strategies for tackling the problem related to sulfate loss. At the same time, various mass spectrometry techniques are presented to facilitate compositional analysis of LMWH, mainly Enoxaparin...
May 21, 2018: Expert Review of Proteomics
Radosław Sadowski, Renata Gadzała-Kopciuch, Tomasz Kowalkowski, Paweł Widomski, Ludwik Jujeczka, Bogusław Buszewski
Currently, detailed structural characterization of low-molecular-weight heparin (LMWH) products is an analytical subject of great interest. In this work, we carried out a comprehensive structural analysis of LMWHs and applied a modified pharmacopeial method, as well as methods developed by other researchers, to the analysis of novel biosimilar LMWH products; and, for the first time, compared the qualitative and quantitative composition of commercially available drugs (enoxaparin, nadroparin, and dalteparin)...
July 13, 2017: Journal of AOAC International
Antonella Bisio, Elena Urso, Marco Guerrini, Pauline de Wit, Giangiacomo Torri, Annamaria Naggi
A number of low molecular weight heparin (LMWH) products are available for clinical use and although all share a similar mechanism of action, they are classified as distinct drugs because of the different depolymerisation processes of the native heparin resulting in substantial pharmacokinetic and pharmacodynamics differences. While enoxaparin has been extensively investigated, little information is available regarding the LMWH dalteparin. The present study is focused on the detailed structural characterization of Fragmin® by LC-MS and NMR applied both to the whole drug and to its enzymatic products...
June 24, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Davide Imberti, Marco Marietta, Hernan Polo Friz, Claudio Cimminiello
Recently, the European Medicines Agency (EMA) authorized the introduction and marketing of Thorinane® and Inhixa®, biosimilars of the Low Molecular Weight Heparin (LMWH) enoxaparin. The authorization path is considerably different from the guidelines published by the EMA in 2009, as well as from the recommendations from the International Society on Thrombosis and Haemostasis published in 2013. Indeed, both of them recommended that LMWHs biosimilars therapeutic equivalence should be demonstrated in at least one adequately designed clinical trial...
2017: Thrombosis Journal
Joseph Zaia, Kshitij Khatri, Joshua Klein, Chun Shao, Yuewei Sheng, Rosa Viner
Low-molecular weight heparins (LMWH) prepared by partial depolymerization of unfractionated heparin are used globally to treat coagulation disorders on an outpatient basis. Patent protection for several LMWH has expired and abbreviated new drug applications have been approved by the Food and Drug Administration. As a result, reverse engineering of LMWH for biosimilar LMWH has become an active global endeavor. Traditionally, the molecular weight distributions of LMWH preparations have been determined using size exclusion chromatography (SEC) with optical detection...
November 1, 2016: Analytical Chemistry
H Nandurkar, B Chong, H Salem, A Gallus, V Ferro, R McKinnon
A working group of clinicians and scientists was formed to review the clinical considerations for use of low-molecular-weight heparin (LMWH) biosimilars. LMWH are biological molecules of significant complexity; the full complexity of chemical structure is still to be elucidated. LMWH biosimilars are products that are biologically similar to their reference product and rely on clinical data from a reference product to establish safety and efficacy. The complex nature of LMWH molecules means that it is uncertain whether a LMWH biosimilar is chemically identical to its reference product; this introduces the possibility of differences in activity and immunogenicity...
May 2014: Internal Medicine Journal
Pierre A J Mourier, Olivier Y Guichard, Frédéric Herman, Christian Viskov
Heparin and low-molecular-weight heparins (LMWHs) are anticoagulant drugs that mainly inhibit the coagulation cascade by indirectly interacting with factor Xa and factor IIa (thrombin). Inhibition of factor Xa by antithrombin (AT) requires the activation of AT by specific pentasaccharide sequences containing 3-O-sulfated glucosamine. Activated AT also inhibits thrombin by forming a stable ternary complex of AT, thrombin, and a polysaccharide (requires at least an 18-mer/octadeca-mer polysaccharide). The full structure of any naturally occurring octadecasaccharide sequence has yet to be determined...
May 15, 2014: Analytical Biochemistry
Paola Minghetti, Francesco Cilurzo, Silvia Franzé, Umberto M Musazzi, Manuela Itri
The protection rights of low molecular weight heparins (LMWHs) are expired or are expiring, so the extent and nature of the studies required to obtain a market authorization for LMWH copies represents a hot topic. FDA classifies LMWHs as semisynthetic drugs and their copies as generics whereas the EMA views them as biological medicines and consequently their copies as biosimilars. Consequently, FDA requires only in vivo pharmacodynamic studies, while EMA requires also clinical trials. The current work reviews the chemical composition and therapeutic indications of LMWHs available in the EU and USA markets to discuss the two different approaches...
March 2013: Drug Discovery Today
Ludovic Drouet
The development of biosimilar versions of low molecular weight heparins (LMWHs) raises real medical concerns. To illustrate this, we have chosen as an example the specific clinical setting of antithrombotic management of acute coronary syndromes (ACS). In this indication, the LMWH enoxaparin has consistently shown its superiority in terms of efficacy when compared to unfractionated heparin (UFH) and in a number of direct or indirect comparisons to other LMWHs. For this reason, enoxaparin has become the gold standard for anticoagulation in cardiology, recommended by practice guidelines and extensively used in everyday practice...
March 2012: Targeted Oncology
Frederick A Ofosu
With the expiry or pending expiry of originator low-molecular-weight heparin (LMWH) patents, pharmaceutical companies have invested in developing non-proprietary versions of LMWHs. LMWHs are manufactured by depolymerising highly purified unfractionated heparin. In contrast to traditional synthetic drugs with well-defined chemical structures, LMWHs contain complex oligosaccharide mixtures and the different manufacturing processes for LMWHs add to the heterogeneity in their physicochemical properties such that the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) consider existing originator LMWHs to be distinct medicinal entities that are not clinically interchangeable...
February 2012: Thrombosis and Haemostasis
Jeanine M Walenga, Craig M Jackson, Craig M Kessler
Generic drugs are an important component for meaningful health-care reform currently being debated in the United States. Aside from defining the period of drug exclusivity, however, there is a critical need to ensure that generics of biologic medicines (biosimilars) are safe and effective. For low molecular weight heparins (LMWHs), the standard of care for management of venous thromboembolism, their complex structure and polypharmacological actions make producing a generic LMWH more challenging than a generic small molecule medicine...
April 2011: Seminars in Thrombosis and Hemostasis
Marise Gomes, Eduardo Ramacciotti, Debra Hoppensteadt, Jeanine M Walenga, Bruce Lewis, Indermohan Thethi, Jawed Fareed
INTRODUCTION: Compositional variations among biosimilar enoxaparin could lead to a differential immunogenic response between these preparations. METHODS: Enoxaparin (Clexane, n = 110) and a biosimilar version (Cutenox, n = 110) were administered to healthy volunteers in Brazil, 40 mg subcutaneous (SQ), daily, for 10 days. Blood was collected at baseline, days 1 and 10, and analyzed for antiheparin/PF4 antibody (AHPF4 antibodies) titers and subtypes by enzyme-linked-immunosorbent serologic assay (ELISA)...
February 2011: Clinical and Applied Thrombosis/hemostasis
Evi Kalodiki, Jawed Fareed
The recent health care changes and approval of a generic low-molecular-weight heparin (LMWH) by the US Food and Drug Administration (FDA) merit a review of the facts regarding the new and generic anticoagulants. Fatal hypotension from anaphylactoid type reactions following heparin administration was responsible for more than 149 deaths all over the world. Researchers detected a heparin-like semisynthetic contaminant, over-sulfated chondroitin sulfate (OSCS), that appeared to be intentional. Low-molecular-weight heparins are produced using unfractionated heparin and OSCS has been found in various batches of LMWHs...
April 2011: Clinical and Applied Thrombosis/hemostasis
Vineeta Sharma, Sirisha Madhu, Parthiban Natarajan, Ganesan Muniyandi, Vijaya Jaiswal, Renu Saxena
INTRODUCTION: India is one of the few countries where biosimilar enoxaparin is available for clinical use. Despite availability since past 4 to 5 years, there is a paucity of published literature regarding their biological activity. The aim of the current study is to compare the biological activity of an endogenously developed formulation of enoxaparin with the branded formulation. MATERIALS AND METHODS: Twelve healthy male volunteers received 1 subcutaneous injection of 2 different formulations of enoxaparin in a randomized, open-label, balanced, 2-treatment, 2-period, 2-sequence, cross-over study...
August 2010: Clinical and Applied Thrombosis/hemostasis
Karina Kuczka, Sebastian Harder, Bettina Picard-Willems, André Warnke, Frank Donath, Pietro Bianchini, Bruna Parma, Henning Blume
Low-molecular-weight heparins (LMWHs) differ considerably in their influence on clotting tests and release of tissue factor pathway inhibitor (TFPI). Biosimilarity therefore becomes an issue when generic forms of LMWHs are developed. So far, no bioequivalence study with a generic LMWH has been reported. A generic enoxaparin (test) was compared with the originator (reference) in 20 volunteers after single-dose subcutaneous administration (40 mg enoxaparin sodium, 4000 IU/mL anti-factor Xa (anti-FXa; activity)...
October 2008: Journal of Clinical Pharmacology
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"