A review of the development of the biopharmaceutical field in 2021

In 2021, China will achieve a number of important breakthroughs in the development and production of biological products
.

The popularity of biomacromolecule drugs continued to increase, and the number of newly launched products for recombinant protein drugs and blood products was 6 times that of 2020; 2 new CAR-T products for cell and gene therapy drugs were launched, achieving zero breakthrough compared with 2020; A breakthrough was made in the development of the first inhaled vaccine

01Product Analysis

In 2021, according to the "Administrative Measures for Drug Registration", "Requirements for Registration Classification and Application Materials of Biological Products" and related supporting documents, the Center for Drug Evaluation (CDE) will accept a total of 1988 applications for biological drug registration (1137 domestically produced, 851 imports), including 817 clinical research (IND) applications, 226 supplementary applications, 667 generic drug supplementary applications, 162 applications for production and sales, and 116 other applications
.

The National Medical Products Administration (NMPA) has approved 124 biological drugs (51 domestically produced and 73 imported), mainly covering sub-fields such as antibody drugs, recombinant proteins, and vaccines

Figure 1: Acceptance and approval of biological drugs in 2021 Source: Flint Creation based on public information

In 2021, CDE will accept a total of 1,053 antibody drug applications, an increase of 99.
8% over 2020; 414 recombinant protein applications, an increase of 376% over 2020; 191 vaccine applications, an increase of 20.
1% over 2020; 186 applications for blood products, an increase of 20.
1% over 2020 238% increase in 2020; 59 cell and gene therapy drug applications, an increase of 195% over 2020
.

Figure 2: Layout of biopharmaceutical segments accepted by CDE in 2021 Source: Firestone Creation based on public information

In 2021, the NPMA approved 37 antibody drugs, an increase of 60.
9% over 2020; 38 recombinant protein drugs, an increase of 660% over 2020; 22 vaccines, an increase of 83.
3% over 2020; 18 blood products, an increase of 2020 125%; 2 cell and gene therapy drugs, achieving zero breakthrough compared to 2020
.

Figure 3: Layout of biopharmaceutical segments approved by NMPA in 2021

Source: Flint Creation Arranged based on public information

(1) Vaccines In 2021, China's CDE will accept a total of 191 vaccine applications (104 domestic and 87 imported), including 28 IND applications, 8 supplementary applications, 124 generic drug supplementary applications, 8 applications for production and sales and other applications 23; involving 69 subunit vaccines, 59 toxoid vaccines, 37 inactivated vaccines, 18 attenuated vaccines, 4 nucleic acid vaccines, 1 vector vaccine and 3 others, mainly covering influenza, human papillomavirus , hepatitis, pneumonia and other diseases
.

(1) Vaccines

Figure 4: Vaccine acceptance and approval in 2021

Source: Flint Creation Arranged based on public information

From the perspective of clinical trial applications, in 2021, China's CDE will accept a total of 28 vaccine clinical trial applications (24 domestically produced and 4 imported)
.

Among them, subunit vaccines and toxoid vaccines are the main ones (12 and 9 respectively), 3 inactivated vaccines, 3 attenuated vaccines and 1 other

In terms of product listing, in 2021, NMPA has approved 22 vaccines (16 domestically produced and 6 imported), including 12 inactivated vaccines
.

Among them, the new coronavirus inactivated vaccine developed by Kexing Zhongwei has been approved for emergency use in Turkey and other countries.

Table 1: Domestic marketed vaccines in 2021

Source: Flint Creation Arranged based on public information

(2) Antibody Drugs In 2021, China's CDE will accept a total of 1,053 antibody drug applications (577 domestically produced and 476 imported), including 592 IND applications, 195 supplementary applications, 147 supplementary applications for generic drugs, and 88 applications for production and sales.
31 other applications; involving 745 monoclonal antibodies, 155 bi/polyclonal antibodies, 72 antibody conjugated drugs, 74 antibody fusion proteins, 6 antibody fragments and 1 other
.

(2) Antibody drugs

Figure 5: Antibody drug acceptance and approval in 2021

Source: Flint Creation Arranged based on public information

From the perspective of clinical trial applications, in 2021, China's CDE will accept a total of 592 clinical trial applications for antibody drugs (434 domestically produced and 158 imported), of which 353 are monoclonal antibodies (accounting for 59.
6%), which are clinical trial applications.
The most subdivided tracks include 128 polyclonal antibody drugs, 51 antibody conjugated drugs, 54 antibody fusion proteins and 6 antibody fragments
.

In terms of product listing, in 2021, NMPA will approve 37 antibody drugs (14 domestically produced and 23 imported), including 36 monoclonal antibodies
.

Among them, Vidicitumumab of Rongchang Bio is the first original antibody-conjugated (ADC) drug in China that has obtained both the U.

Table 2: Domestic marketed antibodies in 2021

Source: Flint Creation Arranged based on public information

(3) Recombinant protein In 2021, China's CDE will accept a total of 414 recombinant protein applications (231 domestic applications and 183 imported applications), including 80 IND applications, 16 supplementary applications, 224 generic drug supplementary applications, and 45 applications for production and sales.
and 49 other applications; involving 270 polypeptide hormones, 106 cytokines, 20 recombinant enzymes and 18 others
.

(3) Recombinant protein

Figure 6: Recombinant protein acceptance and approval in 2021 Source: Flint Creation based on public information

From the perspective of clinical trial applications, in 2021, China's CDE will accept a total of 80 clinical trial applications (52 domestically produced and 28 imported)
.

Among them, the largest number of applications for clinical trials (44) were subdivided into polypeptide hormones, including 16 cytokines, 8 recombinant enzymes and 12 others

In terms of product listing, in 2021, NMPA has approved 38 recombinant proteins (11 domestically produced and 27 imported), including 34 polypeptide hormones.
Among them, Livzon Bio's recombinant human chorionic gonadotropin is the first in China and the world's first in the world.
The second listed product; 1 cytokine, which is the PEGylated human granulocyte stimulating factor injection of New Era Pharmaceuticals; 3 recombinant enzymes, which are altepl for injection by Boehringer Ingelheim Pharma GmbH & Co.
KG Enzyme and velaglucerase alfa for injection from Shire Pharmaceuticals Ireland Limited
.

Table 3: The newly approved recombinant protein drugs in my country in 2021

Source: Flint Creation Arranged based on public information

(IV) Blood Products In 2021, CDE will accept a total of 186 blood products (108 domestic and 78 imported), including 10 IND applications, 4 supplementary applications, 149 generic drug supplementary applications, 16 applications for production and sales and other applications 7 cases; 90 cases involving coagulation factors, 39 cases of albumin and 57 cases of immunoglobulin
.

(4) Blood products

Figure 7: Acceptance and approval of blood products in 2021 Source: Flint Creation based on public information

From the perspective of clinical trial applications, a total of 10 clinical trial applications for blood products have been accepted in 2021 (7 domestically produced and 3 imported)
.

Among them, there are 7 clinical trial applications in the coagulation factor field, which is the sub-track with the most clinical trial applications, and there are 2 clinical trial applications in the albumin field and 1 clinical trial application in the immunoglobulin field

In terms of product listing, 6 new blood products (involving 7 approvals) will be added to the market in 2021, namely the coagulation factor products of Tonglu Bio, Nanyue Bio, Kangbao Bio, Yuanda Shuyang, Likangrui Bio and Shenzhou Cell.
;6 kinds of imported blood products (involving 11 approvals), including coagulation factor products of Vetter Pharma-Fertigung GmbH & Co.
KG, Green Cross Corporation and Green Cross Corporation, SK Plasma Co.
, Ltd.
, CSL Behring AG, Bio Products Laboratory Limited's human albumin product
.

Table 4.
Domestic marketed blood products in 2021

Source: Flint Creation Arranged based on public information

(5) Cell and gene therapy In 2021, CDE will accept a total of 59 cell and gene therapy products (54 domestic and 5 imported), including 52 IND applications, 3 supplementary applications and 4 supplementary applications for generic drugs; involving immune cells 28 cases, 17 cases of stem cells, 11 cases of viruses and 3 cases of gene therapy
.

(5) Cell and gene therapy

Figure 8: Acceptance and approval of cell and gene therapy products in 2021 Source: Flint Creation based on public information

From the perspective of clinical trial applications, in 2021, China's CDE will accept a total of 59 cell and gene therapy products (54 domestic products and 5 imported products)
.

Among them, there are 28 clinical trial applications in the field of immune cells, which is the sub-track with the most clinical trial applications.

In terms of product listing, 2 new cell and gene therapy products will be approved for marketing in 2021, both of which are CAR-T products, respectively from Fosun Kite (Aquilence Injection) and WuXi Junuo (Ricchio).
Lunsai injection)
.
The two products are both CD19-targeting CAR-T cell therapy for the treatment of large B-cell lymphoma, and are the only two CAR-T products currently on the market in China
.

Table 5: Domestic marketed cell and gene therapy products in 2021

Source: Flint Creation Arranged based on public information

02Investment and financing analysis

(1) Listing analysis In 2021, there will be 23 companies in the biopharmaceutical field (excluding the New Third Board), including 3 companies listed on NASDAQ, 9 companies listed on the Science and Technology Innovation Board, and 6 companies listed on the Hong Kong Stock Exchange
.
From the perspective of subdivisions, there are 8 companies and 10 companies in the recombinant protein field and 10 companies in the antibody field (including 4 companies in the two fields of recombinant protein and antibody), 5 companies in the field of vaccines, and 2 companies in the cell.
There are 1 enterprise in the therapeutic field, blood products field and nucleic acid interference drug field
.
In terms of geographical distribution, Beijing (5), Shanghai (5), and Chengdu (4) are the three cities with the largest number of newly listed companies in 2021, three companies are listed in Suzhou, and six cities including Guangzhou and Taizhou are listed 1 company is listed
.

(1) Listing analysis

Table 6: Newly listed biopharmaceutical companies in China in 2021

Source: Flint Creation Arranged based on public information

(2) Financing analysis In 2021, there will be 237 financing events in the biopharmaceutical field nationwide, with a cumulative amount of 45.
5 billion yuan
.
From the perspective of geographical distribution, Shanghai (60 cases), Beijing (45 cases), and Jiangsu (42 cases) are the three provinces and cities with the largest number of financings; Jiangsu (11.
5 billion yuan), Shanghai (9.
1 billion yuan), Guangdong (53 million yuan) RMB 100 million) are the three provinces and cities with the highest financing amount
.

(2) Financing analysis

Figure 9: Major provinces and cities across the country have disclosed financing in the field of biopharmaceuticals (unit: 100 million yuan) Source: Firestone Creation based on public information

From the perspective of subdivisions, the top three subdivisions with the most concentrated financing amount are the field of cell and gene therapy (15.
31 billion yuan), the field of antibodies (14.
48 billion yuan) and the field of vaccines (11.
36 billion yuan)
.
Among them, Aibo Bio (6.
51 billion yuan), Clover Bio (2.
37 billion yuan), Aibo Tech (1.
80 billion yuan), Funuojian Bio (1.
33 billion yuan), Dingkang Bio (1.
24 billion yuan) are the financing amount the five largest companies
.

Figure 10: The financing situation of biopharmaceuticals has been disclosed in each sub-sector (unit: 100 million yuan) Source: Firestone Creation Based on public information

03Further optimization of biological drug policy

Lot release supervision becomes more flexible and efficient
.
On April 27, the "Implementation Opinions of the General Office of the State Council on Comprehensively Strengthening the Construction of Drug Supervision and Administration" was issued.
The testing institution is designated as the national biological product (vaccine) batch issuing institution
.
" This policy further simplifies the access procedures for biological product (vaccine) batch issuing institutions, which will effectively activate the enthusiasm of market players for R&D and production
.

Lot release supervision becomes more flexible and efficient
.

The pharmacovigilance system has gradually achieved international standards
.
On May 13, the State Food and Drug Administration issued the "Quality Management Specification for Pharmacovigilance", which will be officially implemented on December 1, 2021
.
As the first pharmacovigilance supporting document of the newly revised Drug Administration Law, the "Specification" fully draws on international mature experience, fully implements the main responsibility of the holder's pharmacovigilance, and positions pharmacovigilance as a practical activity that runs through the entire life cycle of drugs.
It is of great significance to improve the quality and safety of drugs and promote the healthy development of the industry
.

The pharmacovigilance system has gradually achieved international standards
.

The management of vaccine production and circulation will continue to be standardized
.
On February 26, the General Department of the State Food and Drug Administration once again solicited public comments on the "Regulations on the Administration of Vaccine Production and Circulation".
The new draft for comments further clarified the rights and responsibilities of all relevant subjects in the process of entrusted production and sales of polyvalent and multivalent vaccines.
More emphasis is placed on the process management of all aspects of vaccine production and distribution, which will accelerate the standardized development of the vaccine production and distribution industry
.

The management of vaccine production and circulation will continue to be standardized
.

The review principle system was further improved
.
In 2021, CDE will issue a total of 29 guiding principles closely related to biological drugs (including 18 drafts for comments), among which, "Technical Guidelines for Similarity Evaluation and Indication Extrapolation of Biosimilars", "Research on Pharmacy Changes of Listed Biological Products" General principles such as Technical Guiding Principles (Trial) and Guidelines for Acceptance and Review of Biological Products Changes (Trial), further standardize the development and evaluation of biosimilars for biological drugs, strengthen the management of the whole life cycle of biological drugs, and optimize the review.
Process requirements in approval
.
From the perspective of subdivisions, the field of antibody drugs is the focus of CDE, and a total of 8 principles have been released, covering Pertuzumab, Tocilizumab, Omalizumab and other drugs
.

The review principle system was further improved
.

Table 7: Guidelines for the Center for Drug Evaluation of the State Drug Administration

Source: Flint Creation Arranged based on public information