Bio generic PK chemical generic: complexity in "biology"

Source: Bio exploration 2013-9-12 is the same as the treatment of disease and saving people, and they are all generic drugs, but bio generic drugs and chemical generic drugs are significantly different Compared with chemical generic drugs, biological generic drugs have two characteristics: high technology threshold and high investment threshold It is generally believed that the research and development of biological generic drugs usually takes 8-10 years, while that of chemical generic drugs takes 3-5 years According to Sanders of Novartis, one of the world's largest generics companies and a famous multinational pharmaceutical company, the cost of a typical chemical generics is 23 million US dollars, while for biological generics, the cost is as high as 75 million to 250 million US dollars, a difference of about 100 times As a result, the difference between the two lies in the time and money cost of R & D The reason of the difference between the two kinds of drugs is worth exploring In order to understand the difference between the original biological medicine and the chemical medicine, we need to know the difference between the original biological medicine and the chemical medicine Small molecule chemical drugs are usually synthesized, while large molecule biological drugs are usually synthesized The difference in source directly results in the difference in structure, composition, production method and equipment, intellectual property rights, formula, preservation method, dosage, supervision mode and sales mode Compared with synthetic small molecule chemical drugs, biological drugs are 100 to 1000 times larger in molecular size For example, the molecular weight of antibody drugs is up to 150000 daltons, while that of chemical drugs is usually less than 1000 daltons It has been reported that the size of small molecular chemicals is compared to that of a bicycle, while the size of biological drugs is equivalent to that of an airplane In fact, the difference between the two is not only the molecular size More importantly, the molecular structure of biological drugs is far more complex than that of chemical drugs Similar or imitated? Due to the higher molecular weight and complex structure of biopharmaceuticals, the characterization of biopharmaceuticals is facing great challenges However, due to the above characteristics, even if the most advanced instruments and equipment in the world are fully used, it is impossible to fully characterize the structure and other characteristics of biological drugs As like as two peas, the same biological drugs are produced by the same company Even in the same batch, in the process of storage and circulation, the structure and activity of biological drugs (especially protein drugs) will inevitably change For bio generic manufacturers, due to various reasons such as intellectual property protection, the production process and even the cell lines used by the original research drug companies will not be clear, which leads to the difference between bio generic drugs and the original research drugs In addition, for biological drugs, the production and circulation process is more complex and demanding There are many steps Cell culture conditions (temperature and Nutrition), product processing, purification, storage and packaging and other aspects will affect the production of products Small differences in the whole process may affect the quality, purity, biological characteristics and clinical effect of the final product It has a great impact For all these reasons, although the English of chemical generics is generic drug, biological generics is not biogenic, but biosimilar, because biological generics can only be "similar" to the original research drug, and can never be the same It is for this reason that some people in China think biosimilar should be translated into bio similar drugs rather than bio generic drugs However, for the traditional small molecule chemical drugs, there are generally very definite and stable chemical structures The existing analytical methods (such as infrared, nuclear magnetic resonance, X-ray diffraction, mass spectrometry, etc.) are enough to fully understand their chemical structures In general, the production of Biopharmaceutics requires much more stringent production conditions than chemical drugs Of course, the production cost is also higher, and the research and development cost of Biopharmaceutics in preclinical and clinical stages is also higher Regulatory differences based on this, regulatory agencies (especially in Europe and the United States) require biosimilars manufacturers to provide sufficient clinical data, which also leads to the cost of biosimilars before being approved for marketing is often hundreds of times higher than that of chemical drugs Because of the high cost of imitation and production, the cost of generic drugs can only be reduced by 10% - 30% compared with the original drugs, while the cost of chemical generic drugs can be as high as 80% or even higher Therefore, once the patent expires, the original chemical drugs will be severely impacted by the generic drugs, and the chemical generic drugs will soon occupy the market; after the patent expires, the sales volume of the original biological drugs will be less affected by the generic drugs Another important difference between biological medicine and chemical medicine is their immunogenicity Almost all therapeutic proteins produce antibodies in human body They can reduce the activity and even induce serious side effects by neutralizing endogenous factors There are also differences in post IPO regulation Due to the same structure and simple structure as the original research drug, European and American regulatory authorities allow automatic replacement policy (that is, pharmacists can replace the original research drug with chemical generic drugs on their own), without requiring the doctor who prescribes the prescription For bio generic drugs, EU regulations explicitly require that automatic replacement is not allowed Although the United States does not have a clear requirement at present, at present, it is likely that the future policy will be closer to the EU This is also a potential risk for companies interested in entering bio generic drugs As a result, more complex and often more expensive biopharmaceuticals face greater challenges to market than chemical ones, especially for low-income developing countries Although at present in China, the proportion of local biological drugs (such as interferon, growth factor, etc.) in the total drug market is relatively small, and the number of innovative biological drugs approved in Europe and the United States basically accounts for more than 30% of the total number of approved new drugs in recent years Because the price of biological drugs is generally higher, the market share of biological drugs is rising rapidly in the world (about 16% in 2011) As far as the world is concerned, bio generic drugs are still in its infancy However, the industry generally believes that the next 10-15 years will be the golden development period of bio generic drugs According to IMS Health, the world's top consulting company in the field of medicine, the annual sales volume of bio generic drugs is expected to reach 25 billion US dollars by 2020, accounting for about 10% of the market share of bio generic drugs.