The European Medicines Agency has launched a six-month public consultation on the revised . LMWHs, which are fragments of the protein heparin, display anticoagulant activity and are indicated for various conditions, including the treatment and prophylaxis of deep venous thrombosis and the prevention of complications of acute coronary syndromes. Prepared from animal tissues, LMWHs have a high level of heterogeneity and the structure-effect relationship is still not fully elucidated.


This guideline describes the non-clinical and clinical requirements for a LMWH-containing medicinal product claiming to be similar to another one already on the market. The non-clinical section addresses the pharmacotoxicological requirements and the clinical section describes the requirements for pharmacokinetic, pharmacodynamic, efficacy and safety studies as well as pharmacovigilance aspects. The non-clinical section of the guideline has been revised to reflect that a risk-based approach can be followed. In vivo studies are not required as part of the comparability exercise if physicochemical and biological characterisation of the biosimilar and the reference LMWH has been performed with a high level of resolution and have demonstrated close similarity convincingly. Separate repeated-dose toxicity studies may be required in specific cases, for example when novel or less-well-studied excipients are introduced. Regarding the clinical aspects, a comparative clinical efficacy trial is usually required as part of the comparability exercise. However, the guideline has been revised to reflect that a dedicated efficacy study may be waived in exceptional situations, i.e. if similar efficacy of the biosimilar and the reference product can be convincingly deduced from the comparison of their physicochemical characteristics, biological activity / potency and pharmacodynamic fingerprint profiles, based on the use of highly sensitive and specific methods.


Comments on the guideline should be submitted by 31 July 2013.


Posted on the EMA website on 31 January 2013