The path to the market for biosimilars in China has finally opened.

Introduction: With more and more biosimilars on the market, whether biosimilars can replace primary research products like chemical generics has become a hot topic in the industry!---- 2019 is the "first year" of Biological-like medicine in ChinaOn February 22nd, Fuhong Hanlikang was approved for listing, becoming the first biosimilar drug approved in ChinaWith more and more biosimilars on the market, whether biosimilars can replace original research products like chemical generics has become a hot topic in the industrybiosimilars cannot directly replace biosimilars of primary drugs like chemical generics, which are therapeutic biological products that are similar in quality, safety, effectiveness and have been approved for registrationand chemical generics require raw materials, accessories and reference to the original research drug is completely consistent, biosimilars are by recombinant DNA expression in biological living cells produced by macromolecule proteins, its biosynthesis process is very susceptible to internal biovariability and inevitable production environmental factors, biosimilars have a large molecular weight, complex structure, not easy to characterize characteristics, structural characteristics are difficult to characterizeso it is almost impossible for biosimilars to "replicate" the exact same molecular structure, only to ensure "similarity" to the original drugbecause of the essential differencebetween between small-molecule drugs and macromolecular drugs, the traditional method of evaluating the bioequivalence of chemical generics is not suitable for biosimilarsbiosimilars are not imitation innovation (me-too) drugs, their safety and efficacy is based on a high degree of similarity with reference biological products, once the similarity is established, then scientific reasoning holds that the biological-similar drug and the original drug have the same safety and efficacycompared with the original biological drugs, biosimilar drugs because of the difficulty and risk of research and development is relatively small, so the price is generally lower than the original research drug, can effectively reduce the burden of patients, improve the availability of drugspolicy supervision: the listing policy is basically opened to the development of biosimilar drugs will inevitably have an impact on the interests of the original research and drug companies, even in the United States, also because the original research and drug companies and their support politicians on the implementation of biosimilar drug research and development incentive policies expressed strong opposition, and under the influence of intellectual property protection policy, since 1986 the first therapeutic monoclonal antibody drugs were allowed to market until 2006, the United States in the field of biological-similar drugs regulatory policies basically maintain a "vacuum" in the healthy development of the industrythe United States to liberalize regulation of biosimilars, mainly by the European Unionthe European Union is the first region in the world to have guidelines for biosimilarsthe first edition of the Biosimilar MedicineS Guide (Draft) was issued by the European Union in 2004 and entered into force in 2005this is the world's first guideline for the development and evaluation of biosimilars, and the issuance of the guidelines has greatly contributed to the launch of the first biosimilar drugon April 12, 2006, omnitrope, the world's first biosimilar drug, was developed by Sanders, and omnitrope was born in Europeit can be seen that the current liberalization of biological-similar drugs is mainly a registered listing policyAlthough European and American policies liberalize the threshold for the listing of biosimilars, it does not mean that biosimilars can be exchanged directly with the original drug, as chemical generics domarket substitution of biosimilars is still controversial, and global consensus is still not consistentin the EU, swappability policies are developed by each member statethree terms related to biosimilar drug interchangeability include interchangeability, converterability, and alternative (alternative)achieve sbinoic drug interchangeability, usually in two forms of conversion and substitutioninterchangeability is the possibility of replacing one drug with another drug that is expected to have the same clinical effectthis means replacing primary drug (and vice versa) with biosimilars or replacing another biosimilar drug with one biosimilarconvertability refers to the prescription doctor's decision to replace another drug with one drug with the same therapeutic purposeconvertability involves medical and non-medical conversionnon-medical conversion usually refers to the transition that occurs due to the management restriction of clinician's prescription freedom for objective reasons such as the binding policy of the payer, such as centralized procurement or the availability of clinical supply2015, Finland and the Netherlands became the first EU countries to adopt a switch between primary biologics and biosimilarsthe Hungarian National Institute of Pharmacy and Nutrition, the first biological therapy is not recommended for treatment after the termination of the first one biological therapy for more than one yearthe Portuguese Prescription Drug Commission has made it clear that the conversion of biosimilardrugs should be aimed at promoting clinical stability in all patients and that drugs cannot be converted for less than six months of treatmentthe Hellenic Medicines Agency considers that the current experience of interchangeability of biosimilars is inadequate and recommends that automatic substitution/interchangeability of generic drugs and their biosimilars be prohibitedalternative means the possibility of assigning one drug at the pharmacy level instead of another equivalent and interchangeable drug without consulting a prescribing physician automatic substitution is common in chemical generics, but biosimilars can only be "highly similar" to their reference drugs, and there is not enough evidence to support the replacement of biosimilars as a result, most European countries have taken steps to prevent alternatives to biosimilars but there are also countries that make automatic substitution of biosimilars possible for economic reasons July 2018, the FDA released the Biolikes ActionPlan, BAP, which lists 11 action plans, including a final or revised guide for biosimilar labels and proof of "alternativeness," improving the Purple Book, and future FTC collaboration against anticompetitive behavior , however, the FDA has not yet issued final guidelines on how to prove "alternative" and has not yet been listed as "alternative" biosimilars whether biosimilars can replace primary biological drugs, the United States requires state-level regulation, and can refer to the United States "biological products price competition and innovation" act, pharmacies have a certain replacement right, but ultimately doctors have the final treatment decision this is in deed the same as the EU: all EU countries have officially affirmed the role of prescription doctors as initiators and supervisors of the conversion of biosimilars and primary drugs it follows that interchangeable biosimilars include the following properties: 1) biosimilars are analogues of primary biological drugs; 2) biosimilars are expected to produce the same clinical effects in any patient as the original drug; and 3) the risk of decreasing effectiveness in the same patient is no higher than that of the original drug 4) Interchangeable biosimilars can be exchanged with the original drug without the intervention of a doctor in addition to the listed Phase 3 randomized double-blind "head-to-head" clinical trials demonstrating the effectiveness and safety of biosimilars, the United States believes that the interchangeability of biosimilars may require complementary trials: whether two or more replacements between biosimilars and primary biological drugs affect the safety or efficacy of the treatment process how clinical trials are designed, whether real-world data studies can be used as evidence, everything is still being explored the cost of phase 3 clinical research required to market biosimilar drugs is very high, if there is also a need to do interchangeable tests to demonstrate feasibility, there is no doubt for the use of biosimilar drugs to add a additional threshold the main concern about the current interchangeability of biosimilars in clinical use comes from safety: many stakeholders believe that the interchange of biosimilars may increase different immunogenic reactions and adverse reactions, affecting patient stake safety at the same time, there is growing evidence that adverse biosimilar reactions are due to differences in drug formulations and inappropriate storage and transport conditions, and that interchangeability does not increase the immunogenic response the Eu, in the guidelines, noted that 10 years of clinical evidence showed that EMA-approved biosimilars could be used safely and effectively as other biological agents in all of their approved certificates of adaptation China's market access: The introduction of new guidelines for prescriptions in 2020 can be seen from the table below, the market access policies of biosimilar drugs mainly include pricing policies, drug substitution policies, doctors' patient education and financial incentives or restrictions in Our country, whether biosimilar drugs can replace the original research biopharmaceuticalin in china's clinical market, through administrative means can break through the main two aspects, on the one hand, is the general name to determine the medical insurance catalog and the corresponding standard of payment of medical insurance drugs, biosimilar drugs and primary drugs belong to the same generic name, theoretically can replace each other, which belongs to the pricing policy once the medicare payment price is determined, patients who choose the original drug will have to pay the difference between the drug at their own expense and the biosimilar, and the patient may voluntarily accept the automatic switch on the other hand, China's unique band procurement policy, biosimilar drugs and original research drugs to compete with the generic name, which is related to the pricing policy, but also with the drug substitution policy recent health care sector on whether biological drugs into the volume of procurement of the seminar is caused by the industry's strong concern whether biosimilars in China are interchangeable, whether it is the drug review department or the health management department, have not been clearly defined at the same time, in addition to prescription doctors, whether pharmacists in China's health insurance fixed-point retail pharmacies have the right to exchange biosimilars with their original drugs remains to be considered April 28, 2020, sponsored by the Chinese Society of Pharmacology and the Sino-Japanese Friendship Hospital, the CTDM-GP Project Group of the Chinese Society of Pharmacology, the Professional Committee of Therapeutic Drug Monitoring research of the Chinese Society of Pharmacology, and the "Consensus Line Conference of Experts on Anti-Tumor Biosimilar Drug Monitoring" sponsored by the Chinese Society of Pharmacology provides technical guidance to a wide range of clinical pharmacists and physicians on how to conduct anti-tumor biosimilar drug therapy drug monitoring (TDM) in the clinical real world to strengthen the individualized drug use strategy of anti-tumor biosimilars in clinical practice and promote safe and effective use consensus has led pharmacists to become more involved in the exchange of biosimilars On May 15, , the consensus conference of Chinese biosimilar experts sponsored by the Chinese Society of Clinical Oncology (CSCO) was successfully held, with Professor Zhu Jun of Peking University Cancer Hospital, Professor Shen Zhixiang of Ruijin Hospital affiliated with Shanghai Jiaotong University, Professor Ma Jun, Director of Harbin Hema Cancer Research Institute, and Professor Shi Yuankai of the Chinese Academy of Medical Sciences Oncology Hospital the first "Consensus of Experts in Biological Similar Medicinein in China" was officially released at the meeting from the consensus, at present mainly by prescription doctors to determine whether patients can convert biosimilar drugs, due to the lack of experience in the use of biosimilar drugs, it is expected that the early stage is still personalized drug treatment " China is in a relatively clear market regulations for biosimilars, but the market regulator's conversion policy is not yet clear, prescription doctors' organizations and pharmacists' organizations have issued an exchangeable consensus stage at a stage where clinical data are not clear, the individual believes that biosimilars do not need to replace the original study at once, and let the backtracking system data and real-world trials look at which biosimilars are really available as replaceable should start in the short term is health-care negotiations rather than volume procurement, as long as the willing to sell at a certain price of biologically similar drugs have the possibility of survival, rather than take a band procurement to push the price to the floor price let the bullets of biosimilars fly first .