How can biopharmaceons innovate and purchase more for the good of the country and the people in the new era?

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Drug quality is the cornerstone of the high-quality development of the pharmaceutical industry.

During the two sessions, Wang Weidong, representative of the National People’s Congress and chairman of Rongchang Biotechnology, pointed out, “We must attach great importance to and pay attention to the transformation and industrialization of biomedical science and technology innovations, realize the implementation of industrialization, and support high-quality development.

Li Yan, a representative of the National People's Congress and President of Qilu Pharmaceuticals, also suggested that biotechnology, as a new economic growth point leading the next round of industrial revolution, must persist in innovation and vigorously promote the high-quality development of the biopharmaceutical industry in the future.

So, how should biopharmaceuticals be innovatively purchased?

01 Ensure the safety of patients' medication

Biological products cannot be evaluated for quality consistency.

Biosimilar does not have a unified, standard definition and opinion in various countries.

In March 2015, the State Food and Drug Administration in its "Biosimilar Drug Development and Evaluation Technical Guidelines (Trial)" document for the first time called biosimilar "biosimilar".

The European Union EMA, which has the most mature development of biosimilars, emphasizes that when biosimilars are approved, their own variability and any differences with reference drugs should be proven not to affect their safety and effectiveness.

The above three clearly defined indicators are all determined by the product characteristics of biological drugs.

As a result, biosimilar drugs cannot completely replicate the reference preparations, but can only be approximated as imitations.

In December 2015, the "Technical Guidelines for the Development and Evaluation of Biosimilar Drugs" was issued.

In July 2017, the Center for Drug Evaluation issued the "Questions and Answers about the Research and Development of Biosimilar Drugs", marking the establishment of my country's biosimilar drug similarity review standards.

In March 2020, the "Administrative Measures for Drug Registration" was issued to confirm the classification of biosimilar drugs.

In February 2021, the Center for Drug Evaluation issued the "Technical Guidelines for the Evaluation of the Similarity of Biosimilars and the Extrapolation of Indications", which means that the "consistency evaluation" policy for biosimilars is officially released.

The lack of guidelines for the substitution of biological products and the inadequacy of real-world research have a considerable impact on the standardization of clinical treatment and the safety of patients' medication.

13 statistical studies carried out by large medical centers reported that changing dressings for non-medical reasons has increased the occupation of medical resources and increased costs, including the increase in the number of outpatient and emergency visits, the increase in consultation time for doctors and patients, the increase in hormone use, and the Increased doses of similar drugs, etc.

In addition, the establishment of a warning system for pharmaceutical companies is still incomplete, especially for domestic pharmaceutical companies.

Biosimilars are similar to but not the same as the original biologics, and the risk of clinical substitution is high.
Patient-centered, full consideration should be given to the three characteristics of specific biological products (similarity of biosimilars, stability of production capacity and supply, and clinical substitutability) ), as well as the burden of passive dressing changes on patient safety and the medical system, exploring a procurement mechanism suitable for specific biological products to ensure the safety of patients’ medication.
It is recommended that relevant national departments learn from international experience, carry out comprehensive similarity assessments, clarify and refine specific requirements, clarify the concept of clinical substitution of biological agents, strengthen pharmacovigilance management, improve post-marketing regulatory systems, and allow sufficient time to accumulate clinical experience and great Data, promote the clinical rational use of drugs, ensure patient safety, and promote the rapid development of industry norms.

02 Promote the healthy and sustainable development of the industry

How to conduct innovative centralized procurement of biopharmaceuticals? From the perspective of the stage of industrial development, the industry agrees that "China's biopharmaceuticals are now in the initial stage of growth and development, and production capacity and core technologies need to be improved.
" The overall production capacity of biological products is limited, and at the same time limited by the particularity of production, short-term large-scale production expansion is difficult, and long-term supply capacity and stability need to be cultivated.
Innovative procurement policies need to pay attention to the particularity of biological products, and fully consider the "three characteristics" of specific products (similarity of biosimilars, stability of production and supply, and clinical substitutability) to formulate appropriate policies to ensure the safety of patients' medications and promote The healthy development of the industry.

The pharmaceutical policy reform initiated in 2015 is considered a "watershed" year for the pharmaceutical industry, and the approval environment for pharmaceutical innovation has been greatly improved.
For example, in terms of the new drug review and approval mechanism, NMPA is almost exactly the same as the FDA in terms of rules.
In terms of time, China has been fully in line with international standards, even faster than the United States.
For example, it takes 10 months for new drug approval in the United States and 200 working days for China; rapid review (including breakthrough therapy) in the United States takes about 6 months, and 120 days to 130 days in China.

Benefiting from this, medical innovation has also yielded small results.
A report released by McKinsey in 2019 believes that by 2018, China's contribution to global pharmaceutical research and development has risen to 4% to 8%, entering the second echelon, second only to the United States and Japan.
In the 2016 report, China was in the third echelon.

The industry has interpreted this view, and they have always believed that China's pharmaceutical innovation has not entered the second echelon.
To be more precise, as an ecological system, China's pharmaceutical innovation has entered the second echelon at certain links or subdivided technical levels, but as a complete ecosystem, there are still many lessons to be supplemented.

Specific to biosimilar drugs, China's first biosimilar drug Han Likang (generic name: rituximab) was approved on February 22, 2019, and it has only been two years since then, that is, the biosimilar in these two years The drug has only begun to enter the fast track for approval, but due to the late development, there are still only 9 biosimilar drugs approved.
Among them, 7 biosimilar drugs come from Biotech, which has no revenue, and only 2 are from traditional and established pharmaceutical companies in the stage of innovation and transformation.
The approved drugs are mainly rituximab, adalimumab and bevacizumab.
Monoclonal antibody.

Both the number of participating companies and the number of varieties show that my country has not yet formed a mature biosimilar drug system.
Moreover, due to the complex development and production of biosimilar drugs, the investment is quite huge.
A set of public data shows that it takes 6.
5 to 8 years for biosimilars to go from IND to market, second only to the time of new drugs; R&D capital investment requires 100 to 300 million US dollars.

A pharmaceutical company that makes biosimilar drugs disclosed that “purchasing the original research drug used in the test process is also a large expense, and the drug produced by itself for the test.
This part depends on the supply of the follow-up product after the market.
For example, if a small-capacity machine is used for production, it can only be produced with a small machine after it is approved for the market, which will face greater supply pressure.
However, if a large-capacity machine is used for production once, only a small batch of samples will be used for testing.
The proportion is used for experiments, most of which need to be destroyed.
"

Affected by the above-mentioned factors, the cost and capacity supply problems of biosimilars are prominent and need to be solved urgently.
Because the cost is still relatively high, the price of biosimilar drugs currently on the market has not opened a significant gap with the original research drug.
For example, the bevacizumab single antigen research drug Avastin has a medical insurance negotiation price of 1500 yuan per bottle in 2019, and the medical insurance contract will be renewed in 2020.
However, the price is unknown.
Compared with the medical insurance in 2019, the prices of the two biosimilar drugs have fallen by 24.
9% and 26.
3%, respectively.
For example, adalimumab was included in the medical insurance at the end of 2019, and the price is 1,290 yuan/bottle, Biotop’s biosimilar is 1,160 yuan/bottle, and Hisun and Cinda’s are 1,150 yuan/bottle, and the difference is not significant.

On the other hand, the problem of capacity supply is also very prominent, and large-scale production expansion is urgently needed.

Data show that in 2018, the total production capacity of global biological products companies exceeded 16.
7 million liters, while the total production capacity of China's biological products was only 860,000 liters, accounting for 5.
2% of the total global production capacity.
Specific to antibody drugs, the latest data from IQVIA shows that the actual domestic production capacity is less than 200,000 liters, which is not even as high as that of any large multinational pharmaceutical company.
For example, Roche’s 670,000 liters and Johnson & Johnson’s 230,000 liters.
As we all know, the rate of increase in the production capacity of biological agents is slow.
Even under the inventory production line, the increase in output is still limited by factors such as complex processes, long production cycles, high equipment requirements, and shortage of production quality inspectors.
For example, the cell culture, harvesting and purification of APIs have established time requirements.
In addition, each step in the aseptic production process requires a certain time.
Under the established plant facilities, it is impossible to increase the production speed in a short time to meet the contracted volume.
It will take 3 to 6 years to achieve.
A foreign company revealed that it took 5 years for its domestic factory to reach production with the efforts of experts and technicians from its headquarters.

Another constraint is that domestic key consumables and equipment for biological products mainly rely on imports, such as culture media, drug analysis equipment, etc.
, including the risk of shortages of raw materials.
If centralized procurement is carried out in a short period of time, it is prone to the risk of insufficient supply and short supply.
This type of situation has previously occurred in the centralized procurement of chemical drugs.
In addition, "It may be difficult for enterprises to balance price and quality, and it is easy to cause quality problems.
However, the quality of medicines is the basis of the people's livelihood that the central government pays great attention to.
" Some insiders said.

The role of biosimilars as a ladder for the transformation and innovation of traditional pharmaceutical companies and small start-up companies to obtain cash flow to water the source of innovation are self-evident for the transformation and upgrading of the biomedical industry.
If it is in the difficult climbing stage, the stage where innovation needs to be encouraged, and the impact of centralized procurement will inevitably be detrimental to innovation and transformation.

03 Encourage innovation and promote high-quality industrial development

Three years after the introduction of centralized procurement, it has gradually entered the stage of normalization, but the "low price theory" still seems to exist.
Many companies have expressed their position, "I would rather not make money to get tickets for centralized procurement, because You can keep the production line if you enter the centralized sourcing.
As long as the production line is still there, new products can be added in the future.
" Some varieties in these rounds of centralized sourcing may have been upside down in price, such as metformin with a reserve price of 1.
5 cents/piece.
In the fourth batch of centralized procurement, two 16-in-10 varieties of parecoxib injection and ambroxol decreased by 96.
8% and 93.
3%.
If the biopharmaceutical collection is carried out in this manner, it will be difficult for companies to achieve sustainable development, especially for the current biosimilar drug field with only 9 varieties.
For those biotechs who are just starting to develop, there is no need to rely on profit.
Capital blood transfusion, if there is no phased product commercialization support, may be kidnapped by capital and further affect the development of original innovation.

Improving the research and development level of innovative drugs and releasing the innovative potential of the biomedical industry are inevitable demands for the sustained and high-quality development of the industry.
Sustainable innovation is based on reasonable profit incentives, and high-quality drug research and development is based on reasonable price guarantees, forming a benign industrial development mechanism.
It is recommended that relevant national departments take overall consideration of biological product innovation procurement policies and systematic planning to promote the formation of a stable, high-quality and sustainable supply system in the industry and promote the high-quality development of the industry.
Balance the relationship between price and quality, take into account the reasonable profits of the enterprise, encourage innovation, and promote the sustainable development of the industry.