Global Biosimilar market – Overview and Outlook Introduction According to the “WHO guideline for abbreviated licensing pathways for certain biological therapeutic products” a biosimilar is a new biological medicinal product claimed to be “similar” with regard to quality, safety and efficacy to an already approved reference medicinal product. In EU, the term “biosimilar” is used as a short designation for “similar biological medicinal products”. The global biosimilars market in 2008 was approximately $2 billion.The future biosimilar market is expected to be $19.4 billion by 2014.Currently, the biosimilars market is fragmented and its huge opportunities are attracting new players. Regulatory Scenario EMEA has developed biosimilar approval guidelines in two broad categories. Firstly, there are general guidelines that apply to all categories of biosimilars, and secondly there are specific guidelines that are dependent on the product class in question. EMEA has drafted specific clinical and non-clinical data requirements for four product types’ namely Recombinant insulin, human growth factor, erythropoietin and CSFs. In Europe Comparability studies are required with parent molecule to substantiate evidence for safety, efficacy and quality. The authority for marketing approval of a biosimilar lies with European Commission. In the US, currently there is no clear guidelines and authority for approval of biosimilars. Drugs are generally covered by Federal Drug & Cosmetic Act, and biologics approved under Public Health and Safety Act .Most of the Biologics are approved through Biologic License Application (BLA) and some early biologics, such as human growth hormone (hGH), insulin, and conjugated estrogens, were approved as drugs by FDA under the FD&C Act.The congress and the FDA are considering various scientific and legal issues surrounding follow-on biologics, to define a regulatory process for follow on biologics. In Japan also there is no guideline for approval of biosimilars. Central Pharmaceutical Affairs Council (CPAC) evaluates and makes the recommendation & the Ministry of Health and Family Welfare (MHFWA) makes the decision on approval of drugs and biologics. In Japan Pharmaceutical & Medical Devices Agency (PMDA) has office of biologics for handling biotech medicines including generic biologicals. Use of foreign clinical data is very limited for approval of new medicines in this country. Major Players Current leader is Sandoz (Novartis) which has three follow-on biologics namely Omnitrope, Binocrit and Zarzio in European market. The only follow-on biologic (Omnitrope) in the US market is also of Sandoz. Teva Pharmaceuticals is another major player in biosimilars. It has one product in European market (Tevagrastim) and has improved its biologics capabilities through the
recent acquisitions of Barr Pharmaceuticals and CoGenesys. It has also done strategic partnership with Lonza to develop, manufacture and market biosimilars. Indian manufacturers like Ranbaxy, Dr. Reddy's, Reliance life sciences and Biocon, which has biosimilar manufacturing capabilities are also serious contenders. Biocon has done partnership with Mylan for entrance in western markets. Several Big pharma are also interested in biosimilar market. The most notable is Merck which has established Merck BioVentures (MBV) purchased Insmed for developing portfolio of follow-on biologics. Eli Lilly is another player which after acquiring ImClone Systems has launched an initiative to develop follow-on biologics. AstraZeneca is also considering entering the biosimilars market. Key Challenges Biosimilar development – The approximate cost of bringing a biosimilar to market is $100-$200 million which makes it costly venture to invest. The development period on one biosimilar is from eight to ten years which is equivalent to that for a biopharmaceutical product Therefore Pharma companies are find it difficult to choose between the development of a new product or a biosimilar. Regulatory Hurdles – Although in Europe biosimilar regulatory pathway is fairly clear, the volume of data that manufacturers need to submit for an approval is huge. Clinical trials are required to compare quality, safety, efficacy, pharmacokinetic and pharmacodynamic data between the biosimilar and parent molecule, in addition to a pharmacovigilance trial. Supplementary trials may be required, depending on the complexity and formulation of the product. Where as there is no clear cut regulatory mechanism in the US and Japan. Manufacturing Complexities – Manufacturing of biosimilars is a highly complex and labour-intensive process in which manufacturers will have to replicate the parent molecule as closely as possible, without infringing on any of the patents covering these processes. Key Drivers Biologics Patent Expiries - Biologics worth US$25 billion are going to be off-patent by 2016. hGH and EPO lost patent protection in 2006 and 2007 . In addition, G-CSFs, insulins, and interferons, are amongst those segments that have lost patent protection and offer a multi-billion dollar opportunity to biosimilar manufacturers. Increasing pressure to reduce healthcare expenditure- Cost-containment is the key concern for all the major governments, as most of them are experiencing severe pressure to curb rising pharmaceutical expenditure. This is highly relevant to biopharmaceuticals, most of which are expensive, and are reimbursed fully. One of the key drivers for the uptake of biosimilars will be the attitude of individual country governments in promoting them as an affordable alternative to originator medicines.
Conclusion In long term, it is unlikely that a large number of newcomers will enter the biosimilars marketplace as cost of developing biosimilars is huge and will not be affordable by many players. Prominent challenges include the sizeable investments in time and expertise associated with biosimilars development. Legislative restraints in the US and a recently established regulatory framework in the EU have also contributed to key challenges, but for those developers who persevere, biosimilars are set to offer lucrative returns.