Biosimilars Present Opportunity, Challenge For Developing Countries, UNCTAD Group Says 23/01/2015 by Catherine Saez, Intellectual Property Watch 3 Comments Share this:Click to share on Twitter (Opens in new window)Click to share on LinkedIn (Opens in new window)Click to share on Facebook (Opens in new window)Click to email this to a friend (Opens in new window)Click to print (Opens in new window)Biosimilars are a hot topic. Beyond the colossal profits foreseen by some, drawing a lot of interested parties into the game, developing countries mean to play a role in this new frontier. However, biosimilars – close copies of biopharmaceutical products – are difficult and very costly to produce and come as a challenge to the generic industry used to duplicating small molecules. And some warn about differences in regulatory requirements, which could effectively boot developing countries out of the global market. The Intellectual Property Division of the United Nations Conference on Trade and Development (UNCTAD) held an ad hoc expert group meeting on “The production of biosimilars in developing countries: The Next Frontier?” on 21 January, aimed at examining the issues faced by developing countries in biosimilars manufacture. According to Kiyoshi Adachi, chief, Intellectual Property Unit, Division on Investment and Enterprise at UNCTAD, the purpose of expert group meetings at UNCTAD is to probe new potential interesting areas for work programmes of United Nations agencies within their mandate. UNCTAD has developed an interest in local production of drugs in developing countries since 2005, he said, and in 2008, UNCTAD was named as a stakeholder in the World Health Organization Global Strategy [pdf] and Plan of Action on Public Health, Innovation and Intellectual Property. Biosimilars, What They Are Vanya Loroch, CEO and principal at Loroch CTLS, a life science communication and training company, presented key distinctions between chemical and biopharmaceutical drugs, and consequent challenges for biosimilar production. Biosimilar products, also called follow-on biological products, or similar biotherapeutic products, are defined by the WHO as: “a biotherapeutic product which is similar in terms of quality, safety and efficacy to an already licensed reference biotherapeutic product.” Loroch, taking aspirin (acetylsalicylic acid), as an example, said it is a molecule with 21 atoms. Comparatively, a biopharmaceutical drug such as Tysabri, used to prevent episodes of multiple sclerosis, is a huge molecule, which is a thousand times more complex than aspirin, too complex in fact to be synthesised, he said. Biopharmaceutical products start with a living cell, which is asked “to become a factory” and produce a drug. That living cell will produce a very large quantity of different products and only one of them is a drug, he said. The production of biopharmaceuticals is difficult to standardise, he added. The particular cell line which is used by a company to manufacture a biopharmaceutical is unique and is kept as a trade secret, he said, never to be released into the public domain. Safety is a major issue, he said, as assuming there is efficacy, biopharmaceuticals can lead to severe immune reactions as they interact with the immune system of patients. Regulation of Biosimilars: Double Standard A WHO representative attending the expert group said that for the time being the harmonisation level for the regulation of similar biotherapeutic products “is not very high”. There is an initiative under the International Pharmaceutical Regulators Forum to try to have a bigger convergence and harmonisation of the regulators’ view and approach to this particular group of products, he said. Fernando de Mora, director of the Pharmacology of Therapeutics and Toxicology Department at the Universitat Autònoma de Barcelona, said different regulatory authorities have different views on how the equivalence of biosimilars with the original product should be demonstrated. The United States, the European Union, Canada, Japan, and Australia have a closely similar framework on how similarity should be shown, he said. A small manufacturing change in a biotherapeutic product or a biosimilar can bring severe adverse reactions, he said, marking the importance of equivalence. At the moment, there are two regulatory zones, he said, one in which countries recognise the need for highly and extensive comparability studies that take years and cost hundreds of millions of dollars, and one in which some think it may be enough to just do a “breached relatively customised pathway.” They are two parallel markets, he stated, and some products should not be called strictly speaking “biosimilar”. Many products being launched in countries without stringent requirements for equivalence would not make it to the US, EU, Japan or Australia, he asserted. There is a need for regulatory convergence and stringent regulatory rules, he said. The lack of strict regulation of biosimilar products comes at a disadvantage of developing countries producers, which will be unable to penetrate the global market. Biotherapeutic Drugs, Biosimilars to take over Industry According to Brian Tempest, editor, Journal of Generic Medicines, in the near coming years, biotherapeutic drugs and biosimilars are going to take over the whole pharmaceutical industry. By 2016, he said, 11 out of the top 20 pharmaceutical products will be biologics. He mentioned a story published in PharmaTimes in the fall, saying that over 700 biosimilars are now in development worldwide. The story says that those biologic therapies “are expected to account for around a quarter of the US$100 billion-worth of sales stemming from off-patent biologic drugs” by the end of the decade. However biologic products are made of very complex molecules which come at a very high price. This shift from traditional medicines represents great business opportunities, Tempest said, but it also represents a challenge for the generics industry. A number of patents on biologics will expire in the next 3 or 4 years, opening a market for follow-on products, but the question remains as to who will be producing them, he said, as producing costs are extremely high. There is a lack of clarity on who does what, Tempest added. Certain products are in the public domain, others not, and many companies “are hiding what they are doing,” clouding a clear view of the engagement of pharmaceutical companies in the production of biosimilars, he said. The prospect of profit is attracting companies outside of the realm of pharmaceutical companies, he noted. Fuji Film or Samsung are among non-pharmaceutical companies entering the game, he said. Originator companies also have a high interest in developing biosimilars. Numerous challenges need to be met by developing countries so they can develop biosimilars. In particular, the up-front investment, between US$100 and US$200 million, with a 12-year rate of return, which will be hard to meet, as generics companies usually work with a 2 year return, he said. Those companies could also be asked to spend millions to get the innovator samples to start clinical trials, he said. Also of concern, he said, is the length of the process to develop biosimilars, and the fact that existing pharmaceutical manufacturing assets are unlikely to be relevant. However, biosimilars could provide developing countries with independence from other countries for their complex medicines. The development process of biosimilars is so long that most patents will have expired by the time the process is over, he said. Brazil Producing Biopharmaceuticals Antonio de Padua Barbosa of BioManguinos, Brazil, described how BioManguinos, which is part of Fiocruz, a publicly-owned company, moved from vaccines production in 1976, to HIV diagnostic kits in 1986, to the beginning of biopharmaceutical drugs supply in 2006. BioManguinos currently produces 10 vaccines and 4 biopharmaceuticals, Barbosa explained. He further said that by law Brazil must supply biological products to its population and does it through specific health programmes, despite high costs. Brazil has set up product development partnership (PDPs) to address high prices in several sectors, including nanotechnology, fine chemistry, medical devices and biotechnology, he said. Barbosa said the Brazilian regulatory requirements demand high quality standards for safety and efficacy of biological products. Brazil is aiming to: increase the number of biotherapeutics produced, expand access for the population, reduce imports, increase its technological capacities, guarantee the supply and lower the costs, he said. Bangladesh, Strongest Pharma Sector in LDCs Iqbal Hassan Khan, senior manager and head of the Biotech Division for Incepta Pharmaceuticals, Bangladesh, said the country “has made considerable progress” in medicine supply for local population. Bangladesh has the most robust pharmaceutical sector of least-developed countries (LDCs), he said. Some 97 percent of the domestic demand in pharmaceutical products is met, he added, with 86 percent of the market share going to nearly 200 local companies. In 2013-2014, Bangladesh exported pharmaceuticals to 88 countries in Europe, Asia, Africa and Latin America, he said, adding that the pharmaceutical sector is the most promising industrial sector in the country. Among the strengths of the sector are the large demand in the domestic market, a favourable regulatory authority for domestic producers, and increasing health expenditures, he said in his presentation. However, the sector still suffers from lack of investment and knowledge-based work force, which hinders research and development, and from a dependence on imports of active pharmaceutical ingredients and intermediate drug products. The patent protection for most of the first generation of biopharmaceuticals began to expire in 2004, opening the door to biosimilars, he said, and added that Bangladesh “must adopt an innovative approach of manufacturing biosimilars.” In the world, very few biosimilars are currently commercialised. A large number of them are going through the approval process in several countries, such as the United States, according to some sources. Image Credits: Flickr – net_efekt Share this:Click to share on Twitter (Opens in new window)Click to share on LinkedIn (Opens in new window)Click to share on Facebook (Opens in new window)Click to email this to a friend (Opens in new window)Click to print (Opens in new window) Related Catherine Saez may be reached at firstname.lastname@example.org."Biosimilars Present Opportunity, Challenge For Developing Countries, UNCTAD Group Says" by Intellectual Property Watch is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.