Under the froth of the "Great Innovation Era", the "involution" of biological products has become fierce

In order to fully grasp the progress of clinical trials in China's new drug registration and strengthen drug regulatory capacity building, CDE based on the registration information of the drug clinical trial registration and information disclosure platform, on November 10, 2021, the CDE official website released the "China New Drug Registration Clinical Trials Annual Report (" 2020)”, this is the first time that CDE has conducted a comprehensive analysis of the current status of clinical trials of new drug registration in China.
This article focuses on the analysis of the clinical trial information of biological products registered in the "Annual Report on the Status of Clinical Trials of New Drug Registration in China (2020)"
.

PART 0 1.
Definition of biological products

PART 0 1.
Definition of biological products

Before the implementation of the Drug Administration Law in 2019, the "biological products" we often referred to were antibiotics, biochemical drugs, radiopharmaceuticals, serums, vaccines, blood products, and diagnostic drugs.
After December 1, 2019, 2019 The annual "Drug Administration Law" clearly classifies medicines into three categories: Chinese medicine, chemical medicine and biological products.
Regarding the evolution of the definition of biological products, the author has sorted out:

(1) GMP Appendix-"Biological Products" on November 03, 2005 (Draft for Solicitation of Comments ):

(1) GMP Appendix-"Biological Products" on November 03, 2005 (Draft for Solicitation of Comments)

Biological products are microorganisms (bacteria, viruses, bacteriophages, ricks Secondary bodies, parasites, etc.
), cells and various animal and human-derived tissues and body fluids and other biological materials, and used for disease prevention, treatment and diagnosis
.

Human biological products include bacterial vaccines (including toxoids), virus vaccines, antitoxins and immune serum, blood products, cytokines, in vivo and in vitro diagnostic products, and other active agents (including toxins, antigens, allergens, monoclonal Antibodies, recombinant DNA products, antigen-antibody complexes, immunomodulators, probiotics, etc.

(2) The three general rules of the 2020 edition of the Pharmacopoeia on December 30, 2020:

(2) The three general rules of the 2020 edition of the Pharmacopoeia on December 30, 2020:

Biological Products (Biological Products) refer to preparations that use microorganisms, cells, animal or human-derived tissues and body fluids as starting materials and are made with biological technology for the prevention, treatment and diagnosis of human diseases, such as vaccines, blood products, biotech drugs, probiotics, immunomodulators, diagnostic agents and the like
.

PART 0 2.
Significant adjustments to the registration and classification rules for biological products in 2020

PART 0 2.
Significant adjustments to the registration and classification rules for biological products in 2020

The registration classification of biological products has experienced a development process from scratch, from lack to continuous improvement for more than 30 years
.

In 1985, the Ministry of Health promulgated the first "Measures for the Approval of New Biological Products", which divided new biological products into four registration categories for the first time.

PART 0 3.
Clinical trials of new biological products in 2020

PART 0 3.
Clinical trials of new biological products in 2020

The 605 clinical trials of new biological products involved a total of 502 acceptance numbers (one for the same variety, multiple specifications or related supplementary application acceptance numbers).
The number of acceptance numbers for therapeutic biological products was significantly more than that for preventive biological products, 439 and 439 respectively.
63
.

Category 1 registered the largest proportion, with therapeutic biological products accounting for 65.

PART 0 4.
How involved in the great craze of biopharmaceutical innovation?

PART 0 4.
How involved in the great craze of biopharmaceutical innovation?

The "Annual Report on the Current Status of Clinical Trials for New Drug Registration in China (2020)" sorts out and analyzes the outstanding issues in the current status of clinical trials for new drug registration in China.
Most of the bio-innovative drugs under research are antibody drugs, with high target concentration and fierce competition for homogeneity.
PD-1 is the most typical.
This type of drug is an epoch-making anti-tumor drug with good anti-tumor efficacy.
With high safety and a wide range of indications, innovative drugs have become popular in recent years.
However, it can be seen from the report that the research on PD-1 new drugs has been excessively repeated and the homogeneity is serious.
The analysis of the target points is as follows:

(1) The "Annual Report on the Current Status of Clinical Trials of New Drug Registration in China (2020)" shows that there has been an "involution" in the field of bio-innovative drugs.
How popular is PD-1? According to the data analysis of the "Report", the top 10 targets of drugs registered for clinical trials are PD-1, CYP51A1, VEGFR, PD-L1, etc.
, and the number of varieties is as many as 75, 53, 50, 43, respectively.
Item; among the top 10 targets, 9 target drug indications are concentrated in the same indication field, of which 7 target drugs have more than 90 indications, which are concentrated in the anti-tumor field, as shown in the figure below:

(2) The top 10 targets with the largest number of clinical trials are also mainly concentrated in PD-1, etc.
Among them, more than 60 clinical trials have been carried out for PD-1, VEGFR, PD-L1 and other target varieties.
PD- The number of clinical trials for 1 target is nearly 100; in addition, the proportion of phase I in the clinical trials of 6 targets is more than 40%, and the proportion of phase II clinical trials in each target is not high.
There are as many as 20 Phase III clinical trials of PD-1, VEGFR, PD-L1 and other targets, as shown in the figure below:

The PD-1 series of drugs is just a microcosm of the homogenization of R&D by domestic pharmaceutical companies.
Limited clinical resources are wasted in a large number of repetitive R&D projects.
Therefore, CDE first issued the The Guiding Principles for the Clinical Research and Development of Value-Oriented Anti-tumor Drugs (draft for comments), which puts forward the need to focus on the interests of patients, be clinically value-oriented, and target the market, but not the end of the market, and focus on patient life-cycle management , To maximize the benefits of drugs
.

The aim is to let those products that dare not use the best treatment methods as a comparison to retreat, concentrate all effective resources on the best product research and development, and clear the heat of the involved biomedical field

Subsequent CDE will report on new drug registration clinical trials on an annual basis, relying on China's new drug registration clinical trial registration data, focus on regulatory innovation, improve regulatory efficiency, strengthen communication with the industry in the modernization of drug regulatory capabilities, increase information transparency, and promote High-quality and healthy development of clinical trials of new drugs in China

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