The new modified drug 505 (b) (2) offers great opportunities in China.

The competition of generic drugs is becoming more and more intense, and the high investment and high risk of innovative drug research and development always exist, and it is a good direction to carry out drug development and application in 505 (b) (2) wayIn recent years, the FDA has approved more than 505 (b) (1) drugs through 505(b), and local Chinese companies have entered the harvest period by testing water in the U.Sinnovative drug market by 505 (b) (2)At present, the domestic pharmaceutical industry policy environment encourages the development of new modified drugs, to achieve improvement and innovation, to meet clinical needsOn June 24, CDE published the Technical Guidelines for Clinical Trials of Chemical Lycing New Drugs (Draft for Comments), which provides the basis for guiding guidelines for the implementation of the new drug policy for improved drugs and for encouraging the clinical development of improved new drugs in ChinaThe new modified drug 505 (b) (2) offers great opportunities in China505 (b) (2) Introduction 1984, the United States Drug Price Competition and Patent Period Amendment (Hatch-Waxman Amendment) formally established 505 (b) (2) as a new way of filing new drugs, with a view to avoiding duplication of relevant studies already undertakenFDA applications for chemical drugs include the following three methods: 505 (b) (1), 505 (b) (2) and 505 (j)505 (b) (1) and 505 (b) (2) are new drug applications (New Drug Application, NDA) and 505 (j) are brief new drug applications (Abbreviated New Drug Application, ANDA)505 (b) (1) is a new application for innovative drugs, characterized by the inclusion of complete safety and efficacy studies in its application materials, including CMC studies, preclinical pharmacological toxicology studies, pharmacokinetics and bioavailability studies, clinical studies, etc., all of which are derived from the applicant or applicant's right to use itDrugs approved by 505 (b) (1) are granted a longer patent protection and market exclusivity period505 (b) (2) is an application for a new drug based on improvements and discoveries of approved drugs, and applicants are required to submit a complete safety and efficacy study, but some of the information in the report is not derived from studies conducted by the applicantExternal resources include the following two forms: 1) published literatureIt is generally publicly available and the public has access to conclusions, analysis results, and aggregated dataHowever, the applicant does not have the right to refer to the original data, nor can he copy or supplement the analysis process2) THE FDA STUDY FOUNDThat is, the FDA's conclusions on the safety and effectiveness of listed drugs usually come from the conclusions of the drug reviews 505 (b) (2) Application avoids the time and cost risk of 505 (b) (1) the need for long-term preclinical studies and clinical trials, while avoiding 505 (j) the vicious competition in the generic drug market Approved new modified drugs can obtain a certain market exclusive period (e.g 5 years for new chemical entities and 3 years for new dosage forms) Improved new drugs have high technical and patent barriers, with its clinical advantages, or can quickly achieve the replacement of ordinary dosage forms Differences between the three pathways of U.S drug declaration 505(b) (2) pathways have been approved for drugs 1 2011-2018 505 (b) (2) the number of new drug applications approved In recent years, FDA505 (b) (2) declaration has been more and more attention and favor edited by the industry, the number of declarations significantly increased In 2011-2018, the FDA approved a total of 420 505(b) (2) new drug applications, with the number of approvals remaining largely constant each year; 2011-2018 505(b) (2) Application approval quantity 505(b) (2) path is not limited to a particular product, but focuses on the source of access to new drug application information, applicable to a variety of products, can generally be summarized as follows: 1) dose specifications, i.e changes in drug dosage 2) Component changes, i.e for the strength and weakness of pharmaceutical compounds, combination 3) The route of administration and the scheme of administration 4) Structural changes in active ingredients, such as different salts of active ingredients, chelates, etc 5) New chemical entities 6) New indications 7) Rx/OTC conversion 8) Compound products According to 420 505(b) (2) NDA application data from 2011 to 2018, the new formula (Type 5) accounted for 45% of the main method, followed by the new dose specification (Type 3), for a total of 110 2011-2018 FDA received 505(b) (2) applications for the submission type FDA submission classification 2 2011-2018 each active ingredient 505(b) (2) approved 2011-2018 a total of 287 active ingredients (including compounds) through 505 (b) (2) access to NDA approval Dorsey had the most applicationnumbers, with eight, followed by Adrenaline with seven In addition, a total of 71 active compound formulations were represented by lamivudine Dosage form is most common in tablets and injections In the case of multiple improvements in an active ingredient (including a compound), it is usually an improvement in the way the drug is administered Improvements in pre-drugs or neo-indications usually don't repeat so much 2011-2018 Active Ingredient 505 (b) (2) Approved Ranking 3 2015-2018 Active Ingredient 505 (b) (2) Direction of Administration Tracking 505(b) (2) approvals announced by the FDA 2015-2018 Found that injections and oral administrations were at 505 (b) (2) accounted for a larger proportion of the injection formulation and production of improvement, oral drugs to injection drugs, nanocrystals or microspheres and other long-acting drugs, lipids or other ways of targeted administration, etc , has been the same as oral two mainstream improvement direction, local drug administration is also very suitable for the direction of improvement In recent years, the study of inhalation administration has gradually increased, while approval has gradually increased 2015-2018 by 505 (b) (2) to obtain FDA drug access 4 2011-2018 505(b) (2) approved number of enterprises 2011-2018 A total of 220 enterprises through 505 (b) (2) access to NDA approval, 154 enterprises have only one application number Fresenius Kabi had the largest number of applicationnumbers, with a total of 15, followed by Cipla with 12 application numbers No local Chinese company has been approved by 505 (b) (2) approach For 2011-2018, 505 (b) (2) approved quantity Ranking Fesenyus Group is a medical company providing dialysis, infusion and clinical nutritional treatment products, hospital and home medical care and ancillary services, headquartered in Baden-Humboldt, Germany The business consists of five branches, namely Fresenius Medical Care (dialysis equipment and products), Fresenius Kabi (infusion therapy and clinical nutrition), Fresenius Helios (hospital group), Fresenius Vamed (global healthcare project design, construction and operation management), Fresenius Biotech (gene therapy, transplantation and regenerative drug development) Fessenyus Medical is an excellent company in dialysis products and services, as well as a multinational company that provides clinical nutrition and fluid therapy for patients with severe and chronic diseases The European market is the number one market in Asia-Pacific and Latin America In recent years, 505 (b) (2) approved by Fresenius Kabi are injections, and varieties include methilytic injections, Agaquban injections, hydroxide moxisal injections, hyperglycerides for injections, Acetaminophen injection, injection of boronyzomi, injection of acetate capofen net, injection of tipressin, hydrochloric acid Palonosan injection, calcium gluconate injection, fluorovester group injection, etc Cipla is an Indian multinational pharmaceutical and biotechnology company founded in 1935 as a "chemical, industrial and pharmaceutical laboratory" by Khwaja Abdul Hamied, India, and changed its name to Sipra Co., Ltd on July 20, 1984 In 1985, the U.S FDA approved its API production base Cipla is now India's second-largest pharmaceutical company with strong financial and scientific resources, especially in the case of cheap anti-AIDS and anti-cancer drugs, and 505 (b) (2) of CIPLA approved are oral preparations in recent years, including Litonavi tablets, Lopinaveliave pills, and abakacabamiev tablets Hospira is a hospital products company that manufactures drug delivery systems, generic drugs and intensive care drugs Hospira's pharmaceutical products include generic injections for anesthesia, cardiovascular, infectious diseases and pain management Its more complex drug delivery systems include electronic drug pumps and related drug management software In addition, Hospira offers IV nutrition solutions and contract manufacturing services The company operates globally, but 85 percent of its revenue comes from sales to U.S hospital customers Hospira has 15 manufacturing facilities in the United States and abroad Pfizer bought Hospira in 2015 for about $17 billion In recent years, the 505 (b) (2) approved by HOSPIRA INC are injections, including dooobonisol injections, boronyzomi for injection, epinephrine injections, etc Global small molecule-improved new drugs in the study of the situation in recent years, in the field of adaptation of new modified drugs have undergone great changes In the past, the study of improved new drugs in the field of psychopathry, such as pain, schizophrenia, ADHD, Parkinson's, epilepsy and other psychosis, as well as the field of eye medication, while hypertension, cardiovascular and other chronic indications have also been on the market for improved new drugs the global distribution of adaptations of improved new drugs (Source: NextPharma) In recent years, improved new drugs have evolved towards cancer and orphan drug indications, far outpacing other areas of indications The number of new drugs for diabetes improvement also exceeds the number of psychoneural fields The development of ophthalmic indications is in full swing and in the ascendant The development of antibiotics and antifungal drugs in recent years has also been on the rise And the field of psychonerves is still the development hot spot of improved innovative drugs These improved new drugs will certainly give clinicians better choices for the benefit of patients when they are introduced in the future Excellent breakthrough improvements, once approved, will also bring rich market returns to developers the global definition of the adaptation distribution of new drugs in research and improvement (Source: NextPharma) Domestic improved new drug research and development related enterprises 505(b) (2) and the definition of China's new registration classification of chemical drugs category 2 (improved new drugs) is basically the same Domestic enterprises are actively trying 505 (b) (2) and improved new drug routes, china-U.S double reporting In the fourth quarter of 2019, The modified new drug Zebutinib and the improved new drug Ofi of Baiji Shenzhou obtained FDA approval for listing, achieving a "zero breakthrough" of the local new drug Green Leaf Pharmaceuticals also has a number of varieties using 505 (b) (2) declaration Such as injections of rotigotin slow release microspheres (treatment of Parkinson's disease), injections of acetate goschererin slow-release microspheres (treatment of prostate cancer) and palicodone slow-release mixed suspension intramuscular injections (treatment of schizophrenia and divisive affective disorder) It is worth mentioning that after the completion of Phase I clinical trials, Green Leaf Pharmaceuticals and the FDA have had many discussions and communication In September 2015, the FDA officially confirmed that the Leperone Slow Release Microsphere Injection (Rykindo) does not require further clinical trials and can submit a new drug NDA application in the United States Non-traditional pharmaceutical companies, taking Shanghai Bozhi Research as an example, it is a small molecule innovative drugs, improved new drugs, high-difficult drug research and development as the core, with DMF, MAH, clinical research capabilities of innovative research and development enterprises, in recent years also focused on 505 (b)(2), clinical drug adaptation development as an important direction In terms of dosage form improvement, Shanghai Bozhi Research has a wealth of experience in the improvement of complex injections, can break through high-tech barriers, has an efficient research and development team, focusing on slow-controlled release agents, dissolving platform drugs and long-acting mixed suspension injections research and development You can also make complex innovations, leveraging a listed API and an improved API portfolio In addition, Shanghai Bozhi Research new has a clinical team, can quickly achieve the clinical verification of the new indications The author thinks that if only the drug transmission system (DDS) improvement is carried out, and does not have the advantages of synthesis and improvement of new active ingredients (APIs), the space is limited and it is difficult to reach the expected market size The ideal platform for the development of new drug research and development should have the ability of clinical research of new drugs, the synthesis and improvement capability of new API, the integration platform of a variety of DDS technical means, and make multi-channel improvement senough to build a cutting-edge innovation research and development system to meet clinical needs At present, the national policy to encourage innovation and attach importance to clinical value as the overall orientation, the introduction of priority approval, consistency evaluation, listing licensor system and other policies, so that the pharmaceutical industry has a new vitality High quality, high clinical value of drugs by the policy concessions and stand out, poor quality drugs face elimination China's pharmaceutical enterprises will usher in great changes, and gradually to high-quality and high-tech direction, but also conducive to China's medicine out of the country, the benefit of all mankind In recent years, the investment risk of new drugs has become more and more serious, the technical requirements have increased significantly, and the time and speed of new drug development has been relatively slowed Global new drug research and development failure rate is getting higher and higher, the development of new targets more and more difficult, drug research and development has entered the era of preparation innovation, enjoy the national policy dividend, new high-end preparations will become the forefront of drug innovation, multi-dose type research and development of 505 (b) (2) innovative drugs will become the future leader in preparation innovation