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

Competition for aspirin generics is intensifying, and the high investment and high risk of innovative drug research and development is always there, and drug development and application in 505(b) (2) is a good direction.
in recent years, the FDA has approved more than 505 (b) (1) drugs through 505 (b) and the U.S. innovative drug market has entered the harvest period by 505 (b) (2) Chinese companies.
at present, the domestic pharmaceutical industry policy environment encourages the development of new modified drugs, to achieve improvement and innovation, to meet clinical needs. On June 24,
, CDE issued the Technical Guidelines for Clinical Trials of Chemical Drug Improvement New Drugs (Draft for Comments), which provide guidelines for the implementation of the New Drug Policy for Improved Drugs and the encouragement of clinical development of improved new drugs in China.
improved new drug 505 (b) (2) ushers in great opportunities in China.
505 (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 undertaken.
FDA applications 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 applications for simplified new drugs (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 it.
drugs approved by 505(b) (1) can obtain a longer patent protection and market exclusivity period.
505(b) (2) is a new drug application 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 applicant.
external resources include the following two forms: 1) published literature.
are generally public and the public has access to conclusions, analysis results, and aggregated data.
but the applicant does not have the right to refer to the original data, nor can it copy or supplement the analysis process.
2) THE FDA STUDY FOUND THAT.
, 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 the vicious competition in the 505 (j) application generic drug market.
approved new, improved new drugs can be given 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.
the difference of 505(b) (2) the number of approved drugs between the three routes of drug declaration in the United States 1. 2011-2018 505(b) (2) the number of new drug applications approved in recent years, FDA 505 (b) (2) declaration has been more and more attention and favor editing by the industry, the number of declarations has increased significantly.
2011-2018, the FDA approved a total of 420 applications for new 505(b) (2) new drugs, with the number of approvals remaining largely constant each year;
2011-2018 505 (b) (2) application approval quantity 505 (b) (2) path is not only applicable 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, chelates, etc.
5) New chemical entities.
6) New indications.
7) Rx/OTC conversion.
8) compound products.
from 420 505(b) (2) NDA applicationdata 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 applications, with eight, followed by Adrenaline, with seven applicationnumbers.
, a total of 71 active compound formulations were represented by ramivudine.
dosage form is most common in tablets and injections.
in cases where an active ingredient (including a compound) has been modified multiple times, 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.
505(b) (2) Approved for Active Ingredients 2011-2018 Rank3. Active Ingredients 505(b) (2) Direction tracking of 505 (b) (2) approvals published by the FDA in 2015-2018 It was found that injection and oral administration accounted for a larger proportion of 505(b) (2), for the improvement of injection formulation and production, oral drugs to injection drugs, nanocrystals or microspheres such as long-acting drug administration, liposomes or other methods of targeted administration, and oral as the two mainstream improvement direction, local 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 to 4. 2011-2018 505(b) (2) approved quantity 2011-2018 A total of more than 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.
has not yet been approved by a Chinese-owned company by 505 (b) (2).
2011-2018, The Number 505 (b) (2) approved by The Fessenyus Group is a medical company providing dialysis, infusion and clinical nutritional treatment products, hospital and home medical care and ancillary services, headquartered in Baden-Homburg, Germany.
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 operations 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.
is the European market, which is the leading market, and has a significant position in the Asia-Pacific and Latin American markets.
in recent years, Fresenius Kabi approved 505 (b) (2) are injections, including methioxins injections, Agaquban injections, hydroxisis injections, hydrochloric acid hyperglycerides, Acetaminophen injection, injection of boratizomi, injection of acetate capofen net, injection with ticycline, hydrochloric acid Palonosjun injection, calcium gluconate injection, fluorovestr group injection, etc.
Cipla, an Indian multinational pharmaceutical and biotechnology company, was 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.
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 recent years, with 505 (b) (2) approved by CIPLA being oral, including Litonavi tablets, Lopinavelitonavpills, and abaseakamivtablet sulphate.
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 does business around the world, 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, 505 (b) (2) approved by HOSPIRA INC are injections, and varieties include doooster injections, boronatizomi for injections, epinephrine injections, etc.
Global small molecule-modified new drugs in recent years, in the field of adaptation of new modified drugs has undergone great changes.
in the past in the study of improved new drugs in the field of adaptation is usually in pain, schizophrenia, ADHD, Parkinson's, epilepsy and other psychonerved areas as well as eye medication, while hypertension, cardiovascular and other chronic indications have also improved new drugs on the market.
the global distribution of adaptations of improved new drugs (Source: NextPharma) In recent years, improved new drugs have evolved towards cancer and orphan-based drug indications, far outpacing other areas of indications.
the number of new drugs for diabetes improvement also outnumbered the number of psychoneural fields.
ophthalmology indications development is in full swing, is in the ascendant.
recent development of antibiotics and antifungal drugs is also on the rise.
while the field of psychonerves is still a hot spot in the development of innovative drugs for improved types.
these improved new drugs will be introduced in the future to give clinicians better choices for the benefit of patients.
excellent breakthrough improvements, once approved, will also bring developers a rich market returns.
the global definition of the global adaptation distribution of improved new drugs (Source: NextPharma) domestic improved new drug research and development related enterprises 505 (b) (2) and 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 approaches, china-U.S. double reporting.
the fourth quarter of 2019, Baiji Shenzhou's original new drug Zebutinib and stone drug Ouyi's improved new drug Malay acid zoamine chloramine flat tablets were approved by the FDA to market, to achieve a "zero breakthrough" of the local new drug out to sea.
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 acetic goschererin to relieve microspheres (treatment of prostate cancer) and palicodone slow-release mixed muscle 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 fda have had many discussions and communication.
September 2015, the FDA officially confirmed that the Lypone 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 focus on 505 (b)(2) aspects, clinical drug new adaptation development as an important direction.
in the improvement of dosage form, Shanghai Bozhi Research new for the improvement of complex injections has a wealth of experience, can break through high-tech barriers, with an efficient research and development team, focusing on slow-controlled release agents, dissolved platform drugs and long-acting mixed suspension injection research and development.
can also make complex innovations, leveraging a portfolio of listed AND improved APIs.
also Shanghai Bozhi Research new clinical team, can quickly achieve the clinical verification of new indications.
the author thinks that if only the drug transmission system (DDS) improvement, but does not have the advantages of new active ingredients (API) synthesis and improvement, the space is relatively limited, it is difficult to reach the expected market size.
ideal new drug research and development platform, should have the new drug clinical research capability, the synthesis and improvement ability of the new API, there are a variety of DDS technical means of the integrated platform, multi-channel improvement, in order 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 direction, the introduction of priority approval, consistency evaluation, listing licensor system and other policies, so that the pharmaceutical industry has a new vitality.
of high-quality drugs with high clinical value stand out from the crowd due to preferential policies, and inferior drugs are being eliminated.
China's pharmaceutical enterprises will welcome.