National mining press the accelerator key, where does generic drugs go from here?

Before the New Year, the National Health Insurance Administration sent an annual gift to the people of the whole country.
La Moon 28 (February 8), the fourth batch of national drug centralized procurement results in Shanghai Sunshine Pharmaceutical Procurement Network officially announced: a total of 152 enterprises of 215 varieties were quoted, the final 118 enterprises of 158 varieties selected, the average price fell by 52%, the highest decline of 96%.
results out, pharmaceutical companies a few happy a few sorrows, each with the thoughts spent the New Year of the Ox Spring Festival.
To date, the National Health Insurance Administration has carried out four batches (five rounds) of centralized procurement of drugs organized by the State (referred to as "national harvesting", which facilitates and "provincial collection" distinction), of which the target of 4 plus 7 collection and 4 plus 7 national expansion of the same 25 common name varieties, as the first and second round of the first batch of national mining.
The first four (five rounds) countries adopted 157 generic varieties with higher sales in public medical institutions, with an annual purchase value of more than 72.2 billion yuan based on the pre-bid price and the agreed purchase volume after winning the bid.
Chart 1. Overview of centralized drug procurement by the first four batches (five rounds) of the State Organization (2021.2) Source: Public Information, China-Kang Industrial Capital Research Center, January 28, 2021, The General Office of the State Council issued the Opinions on Promoting the Normalization and Institutionalization of drug Concentration And Volume Procurement (State Office Issued No.
document states: (1) All varieties with large quantities and high procurement volume will be purchased with volume;
subsequent policy briefing revealed that the first three batches of state mining a total of more than 100 billion yuan, provincial collection savings of 24 billion yuan per year.
, biosynthics and Chinese medicines will also be included in the collection.
has pressed the accelerator button, patent expired original research drugs and their generic drugs high-priced, high gross margin "golden age" line is about to end.
under the NATIONAL Health Insurance Administration's plan, large varieties of state-owned development will begin at the end of 2018 and end in 2022, then the beginning of 2021 will be just over half the schedule.
face the "midfield war", the domestic generics business-oriented enterprises and where to go? The essence of timely stop-loss national extraction is to accelerate the formation of the reasonable market price of patent-expired original research drugs and generic drugs by administrative means, so as to bring them back to a reasonable profit level.
these two types of drugs no longer have a patent-protected premium, in the United States and Europe and other mature pharmaceutical markets can only obtain less profit, which put forward higher requirements for the control of production costs.
tickets are evaluated through the consistency of generic quality and efficacy, and the important premise of "price-for-volume" is to ensure quality and supply.
levels, backward technology, fragmented scale, weak production capacity of generic drug companies are unsustainable.
"tens of millions of roads, not another", some generic drug companies should follow this article.
aim is to promote supply-side structural reform of the pharmaceutical industry and change the situation of China's pharmaceutical industry, which is large but not strong, by increasing quality control fees.
important aspect of structural reform is to improve industrial concentration and abandon "how small and scattered".
therefore, under the pressure of National Mining, some smaller generic drug companies follow the policy direction, transfer at a reasonable price, timely stop loss is a wise move.
not only some domestic generic drug companies to stop loss in due course, some large multinational pharmaceutical companies are more physical.
before the start of national mining, the "patent cliff" of the mature pharmaceutical market did not appear in China, and many of the original research drugs whose patents expired in China were abnormally expensive and enjoyed "super-national status".
state-owned pharmaceutical industry to force these patents expired original research drugs back to a reasonable price level, greatly compressing the multinational pharmaceutical companies generic business profit margins.
faced with a thin cake, some multinational drug companies have decided to spin off generics and generics.
Chart 2. Some multinational pharmaceutical companies in China divest non-patented drugs and generic drugs business (click on the picture to enlarge) Source: Public information, China Kang Industrial Capital Research Center innovation and transformation of the country to raise quality control fees at the same time, with the national medical insurance drug negotiations ("national talks"), the savings of the health insurance fund for the treatment of high-value, clinical needs of innovative drugs, to achieve "cage for birds."
, China talked about many innovative drug support policies, promoting the prosperity and development of China's innovative drug research and development.
"innovation transformation" is a viable option for generic drug companies with a certain strength.
However, most generic drug companies in China's "golden age" of generic drugs will focus most of their efforts on marketing, has not established a sufficient capacity for generic drug research and development, let alone difficult to say the same as the innovative drug research and development capabilities.
in a rush for success and an urgent transformation, some generic drug companies are relying too heavily on licensing to introduce the (license-in) model.
the license-in model of innovative drugs, although it can save some research and development time, so that generic drug companies quickly cut into the innovation drug circuit, but there are many hidden dangers.
First, for the screening of projects to be introduced, such as market prospects, probability of success, etc., enterprises need to have a certain degree of independent research and development capabilities;
and development capabilities, commercialization capabilities require a certain amount of time and process, need to be actively cultivated and laid out early.
side effect of starting the "buy,buy" model for generic drug companies is that the valuation of innovative drug projects is "bubbled".
In fact, in addition to the research and development of new molecular real innovative drugs (i.e., domestic 1 class of innovative drugs), research and development of new drugs (i.e., domestic class 2 chemical drugs, FDA 505b2 declaration channel) is also a feasible direction of innovation transformation.
improved new drugs are based on known active ingredients and are obtained through hand splitting or structural fine-tuning, changing dosage forms, developing drug combination therapies, and expanding new adaptive disorders.
the core of the modified new drug is that it has a "clear clinical advantage" over the reference drug that has been marketed, rather than the early "three-change" varieties (change the dosage form, change the specification, change the salt base).
, the domestic improvement of new drug development mainly concentrated in the modified dosage form, mainly for lipids, microspheres, osmosis pump control release.
, in addition to a few independent research and development, there are generic drug companies to introduce some improved new drug projects.
generic drugs can still be for the general generic drug market has played a huge impact, but does not mean that the entire generic industry is completely not good.
is still possible for companies that are aspiring to the generics business.
summary, the future direction of the generics business includes: expanding the generic product line, developing difficult generic drugs, developing first generic drugs through patent challenges, and developing clinically urgent generic drugs.
the expansion of product lines, capacity and channels, although the profits of individual generic drug varieties are less, but if there are more varieties, and after winning the bid to supply a larger market range, then the accumulation of more can still obtain a more objective profit.
large generic pharmaceutical companies in the mature pharmaceutical market in Europe and the United States have a large number of generic drug varieties, and cover a wide range of countries and regions around the world, such as Teva (Teva) product line including more than 1000 kinds of drugs, covering more than 100 countries around the world.
Access to generic drug varieties and markets can be achieved through self-development or through cooperative mergers and acquisitions, which can include preparation capacity, as well as upstream API and downstream promotion, distribution and distribution.
's major generic pharmaceutical companies such as China Biopharmaceuticals, Fosun Pharmaceuticals, Stone Pharmaceutical Group, Qilu Pharmaceuticals, Yangzijiang Pharmaceuticals, etc. have a wealth of generic drug product lines, in the national harvest also has a number of products selected.
Many domestic pharmaceutical companies continue to actively expand their generic product lines, production capacity and channels, including actively carrying out cooperative mergers and acquisitions at home and abroad, such as Fosun Pharma's acquisition of Gland Pharma, Shi Pharmaceutical Group's acquisition of Wuhan Youzhiyou, Manfu Pharmaceutical's acquisition of Epic Pharma, Huahai Pharmaceutical's acquisition of Solco, etc.
difficulty of developing generic drugs, the original drug will soon have the corresponding generic products on the market after the expiration of the patent, the price will go through the "patent cliff."
, however, a small number of original drugs due to inherent technical difficulties still maintain high barriers, for a period of time only a few generic drugs, can still maintain a high level of pricing.
these generics are known as difficult generics.
difficult generics include some fermented semi-synthetic drugs, typically such as carpentry acetate, first developed by Mercadon through fermentation semi-synthetic technology, and approved by the FDA in 2001, becoming the world's first marketed echinobacterial antifungal agent.
is the ace drug in the whole body antifillant market, is recommended by many national clinical guidelines for antifellar infection medication.
preparation process needs to obtain the main ring rough through fermentation technology, then through separation and purification to obtain intermediate products, and then take the middle product as the starting material, using synthetic technology to complete side chain stitching, and finally obtain the target compound.
fermented semi-synthetic drugs require multiple technical processes, and the control of technical routes and process parameters is very complex.
Chart 3. Source: Public Information: China Kang Industrial Capital Research Center 2014, Capofen Net Patent Expires.
January 2017, Hengrui Pharmaceuticals announced that the domestic first imitation injection with acetic acid capofen was approved for the market, the announcement revealed that the research and development investment of up to 30.54 million yuan.
in June 2019, Zhengda Qing's two imitations were approved for listing.
January and August 2020, Borry Pharmaceuticals and Hesco's generic products were approved for the market, respectively.
as of February 2021, injectable acetate capofen net in the domestic generic products are still only above 4 models, the competitive landscape is relatively relaxed.
figure 4. Injection acetate capofen net domestic grade hospital market pattern (millions of yuan) Source: Zhongkang CMH data, Zhongkang Industrial Capital Research Center difficult generic drugs also include some respiratory inhalation agents, such drugs through mouth and nose inhalation to relieve and treat asthma and chronic obstructive pulmonary disease (COPD), characterized by the combination of drugs, need to be used with inhalation devices, commonly including quantitative pressure gas mist inhalers, dry powder inhalers and fog inhalers.
pharmaceutical packages account for the highest proportion of the cost of certain respiratory inhalation preparations because inhalation devices often have technical and patent barriers, which give upstream package suppliers pricing power and high bargaining power.
April 2019, health yuan's first imitation compound isopropyl bromide solution was approved for market, becoming the first respiratory inhaler generic drug in China to pass a consistent evaluation.
September 2019, Health Yuan's domestic first imitation hydrochloric acid zusaldamine alcohol atomized inhalation solution was approved for listing.
February 2020, the country's first imitation inhalation of Budinaid mixed suspension was approved for sale, breaking AstraZeneta's monopoly on the 6 billion-year-old.
through the patent challenge to develop the first generic drug because the first to establish a sound patent link system and supporting regulations, patent challenge in the United States, is a common strategy of generic drug research and development enterprises.
Generic drug companies first discover patent loopholes or non-compliance in the original drug during the patent period, quickly develop generic drugs, and then generally after legal proceedings and invalidation of the patent to market the first generic drug, and obtain the U.S. law of the six-month market exclusive period.
In September 2020, the State Drug Administration issued a draft of the Measures for the Implementation of the Early Settlement Mechanism for Drug Patent Disputes (Trial), which for the first time raised the patent challenge successfully and was approved for listing in the domestic market for up to 12 months.
this has undoubtedly encouraged pharmaceutical companies to market their first generic drugs through patent challenges in the future.
, however, it should be noted that patent challenges require not only strong research and development capabilities, the discovery of patent loopholes in the original drug, but also strong legal capabilities, and close cooperation between the two.
after the first imitation was approved for listing, it needed strong marketing capabilities to quickly seize the market and push up sales during the exclusive market period.
is that before China's patent system was perfected, a small number of drug companies had benefited from patent challenges.
2010, ZhengDaTianQing in China was approved to list the first generic drug Entecave dispersal tablets.
2011, Entecawe original research company BMS filed a patent lawsuit, in 2012 by the State Information Administration declared the patent part invalid.
2013, BMS filed an appeal with the Beijing Municipal High Court and was eventually declared invalid in 2020.
Zhengda Tianqing successfully designed a new synthetic process and preparation with independent intellectual property rights by fully analyzing the patents involved in the case at the time of initiation of research and development.
the patent litigation period, zhengtian qingrun crowd (Entikave dispersal film) successfully grew into an annual sales of more than 3 billion yuan of large single products.
In 2018, Zheng Tianqing submitted the first generic listing application for the "hepatitis B drug" phosphate nofowe (TAF), while Gilead's original drug Vemlidy has not yet been listed in China, and the patent game between the two sides is expected to be inevitable.
development of pediatric generic drugs in China's children drug safety, special drug shortage has not been resolved.
government has issued a series of relevant incentives, including encouraging research and development, priority review and approval, strengthening hospital staffing, recruitment and direct networking.
The former State Health and Planning Commission has issued two batches to encourage the development of children's drug catalog, to encourage pharmaceutical companies and research and development institutions to develop clinically urgently needed children suitable varieties, dosage forms and specifications.
Taking into account the limitations of conducting clinical trials in children, in May 2020, the Center for Drug Review issued the Technical Guidelines for Real-World Evidence to Support Research and Review of Children's Drugs (Draft for Comments), which use real-world data as additional post-market data to drive more children's medicines to market more quickly.
, the domestic children's medicine less difficult research and development direction may be two: imitation of foreign listed and domestic unlisted children's drugs, improved dosage form.
the former is the issue of human differences in overseas data, which may be approved first in China for adult adaptation and then with extraterressional doses for reasonable approval of childhood adaptive disorders.
improved dosage form is to change the current oral solid preparation of children's medicine to oral solution, the main difficulty lies in the orthopaedic.
the conclusion