HPE HPE Fresenius Kabi handbook - Page 18

LANDSCAPE Evolving landscape of biosimilars current and future Since 2006, approximately 50 biosimilars have been authorised by the European Medicines Agency and continuing pressure on healthcare budgets is expected to force a change in attitude towards these drugs Irene Krämer PhD Pharmacy Department, University Medical Center, Johannes Gutenberg- University, Mainz, Germany The European biosimilar market is the most mature in the world. The first guidance on biosimilars was issued by a European authority, the European Medicines Agency (EMA), and subsequently, many health authorities, including the World Health Organization, implemented specific regulations for the approval of biosimilars. Today most countries have specific regulations for the approval procedure of the follow-on products of recombinant biologics when the reference products come off patent. Expiry of the patent protection and competition by biosimilars usually favours the reduction of prices for the reference product and biosimilars. The economic benefit of biosimilars depends on the specifics of the individual healthcare system, especially regarding the pricing and reimbursement structures. While the rates of discount generally amount to 90% for generics, they are expected to amount to less than 50% for biosimilars. The development process for biosimilars is expensive and takes a long time because of the mandatory clinical programme required by the regulatory authorities. In addition, the contribution of analytical studies to cost and time must not be underestimated. It takes up to eight years to bring a biosimilar to market, and development costs range from US$100–250 million (about 50-times that to launch a conventional generic). 1 Since the very beginning of the biosimilar era, European hospital pharmacists engaged in the field of biosimilars. At first, we had to learn that biosimilars represent a new entity of medicinal products according to the licensing procedure of the EMA. Very soon, hospital pharmacists embraced the topic and set guidelines and conditions for the use of biosimilars in hospital patients. In 2005, a special interest group of pharmacists published a checklist to aid hospital pharmacists in the evaluation of biosimilars. 2 At that time, most of the biosimilars coming to the market were hormones and cytokines. While this so-called first generation of biosimilars was established, another, and much more complex, class of biologics – monoclonal antibodies (mAbs) and their derivatives (for example, fusion proteins, receptors, incomplete antibodies) – continued to revolutionise the treatment of patients with oncological diseases, autoimmune diseases, asthma, wet macular degeneration, and others. Of note, hospital pharmacists gradually became more familiar with the subject and a panel of experts (authors) reviewed the 31 previously drawn evaluation criteria for biosmilars 2 and produced a shortlist of ten criteria relevant for clinicians, pharmacists and clinical practice. 3 These included: how long the drug had been on the market; 18 | 2019 | hospitalpharmacyeurope.com number of registered indications; serious and mild adverse events and their frequency; differing contraindications; and precautions or warnings compared with the reference compound, among others. The publication also suggested a decision matrix system to enable physicians and pharmacists to give their own weight to these criteria. This decision matrix system was designed to support objective decision-making and rational selection of biosimilars by Pharmacy and Therapeutics committees in hospitals. While a general selection matrix can be regarded as an important step forward, additional, more refined selection matrices for specific groups of biosimilars are necessary and their implementation requires expert knowledge. Various parameters of biosimilars should be assessed specifically at product level and on a case-by-case basis. Moreover, additional efforts for registries/ Phase IV studies and potential additional costs arising for stock keeping and administration should be considered. The varying consequences deriving from initiating treatment with a biosimilar for naïve patients or switching experienced patients from the reference to a biosimilar, as well as multiple switches between the reference and one or more biosimilars, are not described in the current decision matrix system. Additional studies and more experience will make us more confident about the therapeutic equivalence in extrapolated indications, potential safety issues, multiple switching, naming and traceability, as well as the economic impact of biosimilars. Meanwhile formulary management of biosimilars and the good prescribing, distribution and administration practices will remain a challenge. In the hospital, local guidelines for prescribing, substitution, switching and pharmacovigilance have to be developed in an appropriate and pragmatic manner. Useful information can be found in the European Public Assessment Reports (EPARs) and various position statements of associations of healthcare professionals. Post-marketing pharmacovigilance is mandatory to determine the benefit–risk profile of biologics and biosimilars throughout their life cycle. Different post-marketing commitments for different biosimilars of the same reference product can be required. Especially in the case of switching, patients should be monitored closely for adverse drug reactions, and reporting by hospital pharmacists should be encouraged. Approved biosimilars Since 2006, about 50 biosimilar products across 15 different biological classes have been approved by the EMA (Table 1). 4 In 2017 and 2018, biosimilar products