Update of the recommendations on biosimilar low‐molecular‐weight heparins from the Scientific Subcommittee on Control of Anticoagulation of the International Society on Thrombosis and Haemostasis

The introduction of biosimilars of low molecular weight heparins in Europe: a critical review and reappraisal endorsed by the Italian Society for Haemostasis and Thrombosis (SISET) and the Italian Society for Angiology and Vascular Medicine (SIAPAV)

“…The Food and Drug Administration (FDA) considers LMWH semi-synthetic drugs while the European Medicines Agency (EMA) define them as biological products. Debates and controversies arising from these different positions determined the publication of several guidelines and position statements [2, 5–9]. Recommendations regarding the requirements that copies of LMWH must fulfill to be produced and marketed have been issued by the EMA [5]and the FDA [8, 9].…”

“…In 2013, the Scientific Subcommittee (SSC) on Control of Anticoagulation of the Scientific and Standardization Committee of the ISTH published an update summarizing the recommendations for the development of a biosimilar version of a branded LMWH [2]. The SSC of the ISTH recommends that the lack of significant differences between the biosimilar and originator LMWH should be demonstrated using an adequate study design, and that all results obtained in vitro, ex vivo and in clinical settings should adequately demonstrate the similarity or non-inferiority of the biosimilar LMWH relative to the originator LMWH and the confidence intervals should be defined using adequate statistical methods.…”

“…Furthermore, the SSC of the ISTH clearly states that the efficacy and safety of a biosimilar LMWH should be demonstrated in comparison to the originator LMWH in clinical trials for every indication for which regulatory approval is sought. If biosimilar LMWHs claim to be as effective and safe as the originator products, a head to head comparison of the two LMWH preparations should be performed also in prospective, randomized, double blind clinical trials performed to show the non-inferiority of a biosimilar LMWH compared to the originator LMWH, in the most relevant clinical settings where LMWHs are indicated, like prophylaxis of postoperative venous thromboembolism, prophylaxis of venous thromboembolism in hospitalized patients with acute medical illness, treatment of acute deep vein thrombosis and pulmonary embolism, prevention of acute coronary events in patients with unstable or stable angina, prevention of acute coronary syndrome during and after percutaneous coronary intervention, extracorporeal circulation, and chronic haemodialysis [2]. …”

“…The efficacy and safety of LMWHs have been demonstrated in large randomized clinical trials and evidence based guidelines recommend their use for the prevention and treatment of venous and arterial thromboembolic events [1, 2]. …”

“…Biological drugs are pharmaceutical products obtained by extraction from biological tissues or from biotechnological processes, constituted of larger molecules with a complex structure, thus differing from conventional small molecule medications [2]. The term “biosimilars” is used to qualify products developed to be similar to an original biological drug.…”