Research and development of mAb drugs in China: a look from policy perspectives

Figures & data

Figure 1. Application situation on mAb drugs clinical trials in China. Data source: www.yaozh.com.

Figure 2. Registration situation on mAbs drugs clinical trials in China. Data source: Registration of drug clinical trials and information publicity platform.

Figure 3. Research fields of mAb drugs clinical trials in China. Data source: Registration of drug clinical trials and information publicity platform.

Table 1. Domestically approved mAb drugs by 2017.

Type	Brand name	Generic name	Manufacturing enterprise	Technology	Approval dated	Indication
Domestic	Anti-human T cell CD3 mouse mAbs for injection	Anti-human T cell CD3 mouse mAbsfor injection	Wuhan Institute of Biological Products Co., Ltd.	Mouse	1999	Organ Transplant Rejection
	Abcream	Anti Human Interleukin-8 Monnoclonal Antibody Cream	Dongguan Hongyishi Biotechnological Pharmaceutics Co., Ltd.&Asia Space Pharmaceutical [Dalian]. INC	Mouse	2003	Psoriasis
	Etanercept	Recombinant Human Tumor Necrosis Factor ReceptorⅡ:Ig Fc Fusion Protein for Injection	Shanghai CP Guojian Pharmaceutical Co., Ltd.	Fusion Protein	2005	Rheumatoid Arthritis, Ankylosing Spondylitis, Psoriasis
	Vivatuxin	Iodine[131I] Tumor Necrosis Therapy Monoclonal Antibody Injection	Medipharm Biotech Pharmaceutical Co., Ltd. (Shanghai)	Chimeric	2006	Liver Cancer
	Licartin	Iodine[131I] Metuximab Injection	ChenduHuasun Biotechnology Co. Ltd.	Mouse	2006	Primary Liver Cancer
	Nimotuzumab	Nimotuzumab Injection	Biotech Pharmaceutical Co., Ltd.	Humanized	2008	NasopharyngealCarcinoma
	Jiannipai	Recombinant Humanized Anti-CD25 mAbs Injection	Shanghai CP Guojian Pharmaceutical Co., Ltd.	Humanzied	2011	Transplant Rejection
	Qiangke	Recombinant Human Tumor Necrosis Factor ReceptorⅡ:Ig Fc Fusion Protein for Injection	Shanghai Celgen Biopharma Co., Ltd.	Fusion Protein	2011	Ankylosing Sopudylity
	Conbercept Ophthalmic Injection	Conbercept	Chengdu Kanghong Biotechnologies Co. Ltd	Fusion Protein	2013	Age-related Macular Degeneration
	Anbainuo	Recombinant Human Tumor Necrosis Factor ReceptorⅡ:Ig Fc Fusion Protein for Injection	Zhejiang Hisun Pharmaceutical Co., Ltd.	Fusion Protein	2015	Rheumatoid Arthritis, Ankylosing Spondylitis, Psoriasis
Imported	Mabthera	Rituximab Injection	Roche	Chimeric	2008	Non – Hodgkin‘s Lymphoma
	Herceptin	Trastuzumab	Roche	Humanized	2002	Breast Cancer, Stomach Cancer
	Simulect	Basiliximab for Injection	Novartis	Chimeric	2002	Preventing early acute rejection after kidney transplant
	Remicade	Infliximab	Xian Janssen Pharmaceutical Ltd.	Chimeric	2007	Rheumatoid Arthritis, Ankylosing Spondylitis
	Erbitux	Cetuximab	Merck & Co., Inc.	Chimeric	2005	Colorectal Cancer
	Avastin	Bevacizumab	Roche	Humanized	2010	Colorectal Cancer
	Humira	Adalimumab	AbbVie	Humanized	2010	Rheumatoid Arthritis, Ankylosing Spondylitis, Psoriasis
	Enbrel	Etanercept	Amgen	Fusion Protein	2010	Rheumatoid Arthritis, Ankylosing Spondylitis,
	Lucentis	Ranibizumab	Novartis	Humanized	2011	Age-related Macular Degeneration
	Actemra	Tocilizumab	Roche	Humanized	2013	Rheumatoid Arthritis
	Xolair	Omalizumab	Roche	Humanized	2017	Asthma

Figure 4. Drug lag of mAb drugs approved by China compared with the countries that granted the first approval (by 2017).

Table 2. Approval lag time of mAb drugs in different regions.

	USA	EU	Japan	China
Median（month）	0.0	8.9	43.4	87.1
Average（month）	5.3	14.9	55.4	90.4

Table 3. Supports of R&D and guidance policies for Chinese biological drugs.

Types	Time	Department	File name	Main contents
Plan for Industrial Developments	2012.07.10	Former CFDA	12th Five-Year Plan of Biotechnology Development	National action is recommended to accelerate the development of “new biology”, with a focus on strengthening the applications of life sciences and biotechnology in grain, energy, environment and health.
	2016.12.19	The State Council	13th Five-Year Plan for the Emerging Sectors of Strategic Importance	The Plan requires the acceleration of the development for innovative drugs and biological products with major clinical needs, and developing new types of antibodies and vaccines, gene therapy, cell therapy and other biological products and preparations. It centers on building a sustainable biomedical industry system, especially on emerging drugs such as antibody drugs, recombinant protein drugs, new types of vaccines etc. to promote the development, industrialization and quality upgrade of new drugs for critical diseases, multicentric diseases, rare diseases, and childhood diseases that are in short supply.
	2017.01.10	The State Council	13th Five-Year Plan of Health	The Plan focuses on health issues such as critical diseases like malignant tumors, cardiovascular and cerebrovascular diseases and rare diseases, as well as health industry development needs. It also requires strengthening the frontier basic research of medical science, research and development of key technology, transfer of results, and development of pharmaceutical products and promotion of appropriate technologies.
	2017.02.14	The State Council	13th Five-Year Plan of Country‘s Pharmaceutical Safety	The Plan encourages the development and launch of new drugs with clinical value and clinically needed generic drugs. It also implements priority review and approval for innovative drugs with obvious clinical value, together with clinically urgently needed drugs for the prevention and treatment of diseases such as AIDS, malignant tumors, critical infectious diseases and rare diseases.
	2017.05.19	The Central Committee of CPC, the State Council	Outline of the National Strategy on Innovation-Driven Development	Research and development of innovative drugs, new vaccines, advanced medical equipment and biotherapy technologies
Guidance Documents	2003.03.20	Former CFDA	Guidelines for the Quality Control Technologies of Human mAbs	The Guidelines are applicable to mAbs prepared by hybridoma technology of internal diagnostics for therapeutic use, and quality control for genetically engineered antibodies prepared by repetitive DNA techniques for use in humans.
	2015.02.28	Former CFDA	Technical Guidelines for the Development and Evaluation of Biosimilars (Trial)	The Guidelines standardize the development and evaluation of biosimilars.
	2016.03.11	General Office of the State Council	Guiding Opinions of the General Office of the State Council on Promoting the Healthy Development of the Pharmaceutical Industry (published by General Office of the State Council [2016] No. 11)	The Opinions require accelerating the development and industrialization of new antibodies, proteins and polypeptides.
	2016.07.28	The State Council	13th Five-Year Plan for the Country‘s Scientific and Technological Progress	The Plan focuses on supporting the development of drugs with strong innovation, good curative effect, meeting important needs, and having major industrialization prospects. It requires the basic construction of a national drug innovation system with advanced world level, to achieve the comprehensive capabilities and overall level of new drug research and development which can enter the international advanced ranks. So that we can accelerate China‘s transition from a big pharmaceutical country to a powerful pharmaceutical country.
	2018.02.08	CDE	Basic marketing requirements for data on anti-PD-1/PD-L1 mAbs.	Provide clear policy guidance and support for the development and authorization application of anti-PD-1/PD-L1 mAbs, “Pre-NDA meeting”, “priority review” and “review speed increase.

Table 4. China’s bio-pharmaceutical clinical trial policy.

Date	Department	Document	Content
2005.03.18	CFDA	Technical Guidelines on Bio-statistics in Clinical Trials of Chemical Drugs and Biological Products	Provide drug registration applicants and clinical trial researchers with guidance on the design, implementation, analysis, and evaluation of clinical trials so as to ensure that drug clinical trials are scientific, rigorous, and standardized
2012.05.15	CFDA	Technical Guiding Principles for Clinical Trials of Anti-tumor Drugs	The clinical research of anti-tumor drugs usually focuses on the issues that need to be considered in different clinical research phases, which provide methodological guidance for the design, implementation, and evaluation for the clinical research of anti-tumor drugs.
2012.05.15	CFDA	Technical Guidelines on Endpoints in Clinical Trials for Anti-Tumor Drugs	Provide reference on the clinical trial endpoint criteria of anti-tumor drugs to applicants, so that they meet the requirements for the effectiveness of a certain drug that will be launched, and are applicable to clinical trials of new anti-tumor compounds that are not launched at home and abroad.
2012.05.15	CFDA	Technical Guiding Principles on Clinical Data Collection of Anti-tumor Drugs launch Applications	General principles for data collection and information submission
2012.05.15	CFDA	Technical Guidelines on Adding New Indications to Launched Anti-tumor Drugs	Requirements for clinical studies in terms of new indications to anti-tumor drugs are discussed and illustrated
2017.10.08	General Office of the CPC Central Committee and General Office of the State Council	Opinions on Deepening the Reform of the Examination, Evaluation and Approval System to Encourage the Innovation of Drugs and Medical Equipment	The qualification accreditation of clinical trial institutions shall be subject to recordation administration; the application for clinical trials shall be changed from the examination and approval system to the default licensing system; and overseas clinical trial data shall be accepted.
2017.10.10	CFDA	Decisions on Changes in Terms of the Registration Administration of Imported Drugs	1 Overseas new drugs can enter China and be tested in clinical trials at an earlier stage of R&D: phase I clinical trials in China can take place simultaneously with those in other medical centers across the world and we’ll remove the requirements for drugs used in clinical trials that should have been registered overseas or have entered Phase II or III clinical trial (not include preventive biological products.) 2 Red tape in application will be cut: after the completion of international multi-center drug clinical trials, relevant institutions can directly apply for drug launch registration; when applying for registration, these institutions should meet requirements of the Administrative Measures for Drug Registration and other related documents. 3 Overseas new drugs can be launched first in China: For new imported chemical drugs and innovative therapeutic biological products that should be tested in clinical trials, the requirements for obtaining a market permit for these drugs from the country or region where they are produced shall be cancelled.
2018.07.27	CDA	Announcement on Adjusting the Examination, Evaluation and Approval Procedures for Drug Clinical Trials	Before applying for a clinical trial, a pre-application meeting is required. A 60-day default licensing system for clinical trials will be implemented.

Table 5. China bio-medicine marketing approval policy.

Date	Department	Document	Content
2015.08.18	State Council	Opinions of the State Council on Reforming the Examination, Evaluation and Approval System for Drugs and Medical Equipment (No. 44 [2015], State Council)	Accelerate the review and approval of innovative drugs for the prevention and treatment of diseases such as AIDS, malignant tumors, major infectious diseases, and rare diseases, drugs listed in major national science and technology projects and national key R&D programs, and innovative drugs and children‘s medications made into mass production domestically, as well as the use of advanced preparation technologies, innovative treatments, and innovative drugs with obvious therapeutic advantages
2015.11.11	CFDA	Announcement on Several Policies for the Examination, Evaluation and Approval of Drug Registration(Announcement No. 230)	Optimize the review and approval of clinical trial applications: BE changes from the approval system to the filing system; accelerate the approval of clinically needed drugs
2016.02.26	CFDA	Opinions on Solving the Backlog of Drug Registration Applications through the Establishment of Priority Review, and Approval System	The scope of priority review and approval has been expanded much larger than proposed scope. The expanded categories include: applications for registration of new drugs listed in major national science and technology projects or national key R&D programs; applications for registration of drugs for the prevention and treatment of tuberculosis and viral hepatitis with obvious clinical advantages.
2017.10.08	General Office of the CPC Central Committee and General Office of the State Council	Opinions on Deepening the Reform of the Examination, Evaluation and Approval System to Encourage the Innovation of Drugs and Medical Equipment	Accelerate the review and approval of the marketing of drugs: priority for review should be given to clinically needed drugs and drugs for rare diseases
2017.12.29	CFDA	Regulations for the Approval and Review of Biological Products (Order No. 39 of the State Food and Drug Administration)	Strengthen supervision and management of biological products, standardize the approval procedures of biological products, and ensure the safety and effectiveness of biological products

Figure 5. China mAb drugs innovation supporting system.