On July 20th, 2020, China Center for Drug Evaluation (CDE) issued the China Drug Evaluation Report 2019. In this article, BaiPharm collected some key information of the original report to help global pharmaceutical enterprises learn the situation and tendency of drug approval in China in 2019.
1. Drug registration applications
1.1 Innovative new drug and original drug
In 2019, there were 700 applications for Class 1 innovative new drugs accepted by China CDE, which covered 319 drug products (the numbers are calculated based on the statistical analysis of APIs for chemical drugs, and based on drug names for biological products and traditional Chinese medicines), with a year-on-year growth of 20.8%.
Among the 319 drug products, Investigational New Drug (IND) Applications accounted for 302, up by 26.4% from 2018; while only 17 were New Drug Applications (NDAs), reducing by 8 products from the previous year.
If looking at the data of the domestic products, there were 528 applications for 244 domestic innovative drug products under Class 1, which included 503 IND applications for 228 drug products, and 25 marketing approval applications of 16 drug products. In the perspective of drug classifications, the applications include 401 applications for 144 chemical drug products, 127 applications for 100 biological products. The involved indications are mainly tumors, infections and gastrointestinal diseases.
CDE also accepted 157 applications for 92 imported original chemical drug products under the drug registration Class 5.1, and 172 applications for 75 imported innovative drugs under Class 1, which mainly treat tumors, endocrine and nervous system disorders.
Fig. 1: IND applications and NDAs Accepted by CDE in 2019 for Domestic and Imported Chemical Drugs for Each Indication
1.2 Biological product
In 2019, CDE accepted 1,179 biological product applications, including 310 IND applications (7 for prophylactic and 303 for therapeutic) with an increase of 4% compared to 2018, and 124 NDAs (7 for prophylactic and 117 for therapeutic) with an increase of 45.9% over last year.
Fig.2: Biological Product IND Applications and NDAs Accepted by CDE from 2016 to 2019
In 2019, CDE accepted 127 applications for 100 innovative new biological products under the registration Class 1, increasing by 3.3% from 2018. They included 2 for prophylactic and 125 for therapeutic.
Among the applications, there were 121 IND applications (covering 96 products), up by 8% from the previous year, and 6 NDAs (for 4 therapeutic biological products).
119 Class 1 IND applications for 95 therapeutic biological products were accepted by CDE. These products were mainly for the treatment of tumors.
Fig. 3: IND Applications of Class 1 Therapeutic Biological Products Accepted by CDE for Each Indication in 2019
1.3 Traditional Chinese medicine (TCM)
In 2019, CDE accepted 423 traditional Chinese medicine applications, including 17 IND applications, 3 NDAs and 3 Abbreviated New Drug Applications (ANDAs). The rest were mainly supplementary applications. Among the 17 IND applications, 76% were for TCMs which mainly treat gastrointestinal, respiratory and orthopedic disorders.
2. Drug registration review & approval
From 2015 to 2018, CDE were making efforts to expand its review channels, improve internal project management, and increase its staff numbers so that it could complete the review and approval of a backlog of drug applications. After that, the major task for CDE has shifted to improving work efficacy to ensure that the review and approval could be completed in time. In 2019, over 90% of all types of applications were reviewed and approved on schedule. CDE thus basically achieved the goals set forth in the Opinions on Reforming the Review & Approval System for Drug and Medical Device Registrations (State Council [2015] No.44, hereinafter referred to as Document No. 44).
In 2019, CDE reviewed and approved a total of 8,730 applications, 5 of them were drug-device combinations. Among all applications, 6,817 were required for technical review and approval, and 4,075 of them needed both technical review and administrative approval by CDE. Another 1,908 applications were for direct administrative approval.
The number of applications which were under or pending for review and approval has dropped from the peak of nearly 22,000 in Sept. 2015 to 4,423 by the end of 2019 (not including the pending applications due to incomplete or flawed application materials). With regard to the approved 6,817 applications, 300 of them were TCM registrations, 1,104 were biological product registrations, and 5,423 were chemical drug registrations. Chemical drugs accounted for 79% of all finished reviewed and approved applications.
Among all applications, CDE reviewed and approved 926 IND Applications, 164 NDAs, 654 ANDAs, and 260 applications for generic drug consistency evaluation of oral solid dosage form. It also issued marketing approvals to 10 innovative new drug products under registration Class 1 and 58 imported original drug products with new indications.
2.1 Chemical drug
In 2019, a total of 156 NDA registration applications for chemical drugs were reviewed, with 88 approved. A total of 621 IND applications for chemical drugs were reviewed and 599 of them got approved, including 493 approved IND applications for 189 Class 1 innovative new chemical drugs.
Table 1: Overview of Approvals for Chemical Drug Applications in 2019
Fig. 4: Number of Approved Chemical Drug NDAs & Approved IND Applications for Class 1 Innovative New Chemical Drugs from 2016 to 2019
Among the approved 189 Class 1 Innovative New Chemical Drugs, 70% are anti-neoplastic, gastrointestinal, anti-infective and nervous system drugs.
Fig. 5: Class 1 Innovative New Drug IND Applications Approved for Each Indication in 2019
2.2 Biological product
In 2019, CDE completed technical reviews for 1,104 biological product applications. Among the applications, there were 24 IND applications for prophylactic products, 338 IND applications for therapeutic products, 13 NDAs for prophylactic products, 95 NDAs for therapeutic products, and 2 NDAs for in vitro diagnostic devices (IVDs).
For all applications, CDE approved 18 INDs for prophylactic products, 294 INDs for therapeutic products, 5 NDAs for prophylactic products, 67 NDAs for therapeutic products, and 2 NDAs for IVDs.
Table 2: Overview of Biological Product Registration Applications Approved in 2019
Fig. 6: Number of Number of Approved Biological Product IND Applications & NDAs from 2016 to 2019
Most of the IND applications were for the treatment of tumors, rheumatism, endocrine system or immune system disorders or gastrointestinal diseases. The approved NDAs are mainly anti-neoplastic drugs, autoimmune disease and immunosuppressant drugs, endocrine system drugs or gastrointestinal drugs.
Fig. 7: Approved Biological Product IND Applications for Each Indication in 2019
Fig. 8: Approved Biological Product NDAs for Each Indication in 2019
2.3 Traditional Chinese medicine
In 2019, CDE completed the reviewing work of 300 TCM applications, including 17 IND applications, 3 NDAs, and 6 ANDAs. Among all these applications, 15 INDs and 2 NDAs were approved.
Table 3: Overview of Approvals for Traditional Chinese Medicine Registrations in 2019
Fig. 9: Number of Approved IND Applications and NDAs for Traditional Chinese Medicines from 2016 to 2019
3. Priority review and approval
In 2019, CDE brought 253 registration applications for 139 drugs products onto the priority review pathway. The most applications accepted for priority review in 2019 were registrations for new drugs with substantial clinical benefit (34%) followed by registration applications parallel to other countries (28.1%). In addition, 52 applications were for pediatric drugs and rare disease drugs. As revealed by the data in Table 4, the number of generic drugs approved for priority review has declined continuously, and the innovative new drugs with substantial clinical benefit or urgent medical need are more focused.
Table 4: Number of Applications Accepted for Priority Review from 2016 to 2019
There were 143 applications (82 if calculated by drug names) approved for priority review and issued with marketing authorizations with acceleration in 2019.
4. Newly approved drug products in key therapeutic areas in 2019
Area | Drug Category | Indication |
Anti-neoplastic Drugs | 1. Flumatinib Mesylate Tablets | Leukemia |
2. Dacomitinib Tablets | Non-small Cell Lung Cancer | |
3. Niraparib Tosylate Capsules | Ovarian Cancer | |
4. Denosumab Injection | Giant Cell Tumor of Bone | |
5. Daratumumab Injection | Multiple Myeloma | |
6. Rituximab Injection | Non-Hodgkin’s Lymphom | |
7. Bevacizumab Injection | Metastatic Colon/Rectal Cancer; Non-small Cell Lung Cancer | |
Anti-infective Drugs | 1. Glecaprevir/Pibrentasvir Tablets | Chronic Hepatitis C |
2. Sofosbuvir/Velpatasvir/Voxilaprevir Tablets | ||
3. Lamuvudine/Tenofovir Disoproxil Fumarate | HIV-1 | |
4. Ceftazidime/Avibactam Injection | Intra-abdominal and Urinary Tract Infections; Bacterial Pneumonia | |
Circulatory System Drugs | 1. Dispersible Bosentan Tablets | Pediatric Pulmonary Arterial Hypertension |
Autoimmune Drugs | 1. Belimumab Injection | Systemic Lupus erythematosus |
2. Adalimumab Injection | Rheumatoid arthritis, Ankylosing spondylitis, Psoriasis | |
Nervous System Drugs | 1. Lacosamide Tablets | Epilepsy |
2. Midazolam Oromucosal Solution | ||
Analgesics and Anesthetics | 1. Chloral Hydrate Enema | Pediatric Sedative, Hypnotic |
Dermatological and Otorhinolaryngological Drugs | 1. Benvitimod Cream | Psoriasis |
2. Secukinumab Injection | ||
Rare Diseases Drugs | 1. Elosulfase α Injection | Mucopolysaccharidosis Type IVA |
2. Agalsidase β Injection | Fabry Disease | |
3. Nusinersen Sodium Injection | Spinal Muscular Atrophy | |
4. Edaravone and Sodium Chloride Injection | Amyotrophic Lateral Sclerosis | |
Prophylactic Biological Products | 1. 13-Valent Pneumococcal Polysaccharide Conjugate Vaccine | Streptococcos pneumoniae |
2. Recombinant Zoster Vaccine | Herpes Zoster | |
3. HPV Type 15 and 18 Bivalent Vaccine Produced by E.coli | Human Papillomavirus | |
Traditional Chinese Medicine | 1. Pediatric Shaoma Antispasmodic Polypill | Pediatric Tourette Syndrome |
2. Pediatric Jingxing Cough Polypill | Pediatric Acute Bronchitis |
5. Key work progress
5.1 Expediting review for imported new drugs of urgent clinical need
After confirming the first batch of 48 new drug products that had been marketed overseas and were of urgent clinical need, CDE urged experts to continue selecting new drugs clinically needed in China and determined the second batch of 26 drug products. CDE sought to actively communicate with pharmaceutical enterprises about the new policies for expediting the review process of imported new drugs of urgent clinical need. For those enterprises that experienced certain difficulties, CDE provided guidance and helped them initiate the applications. Meanwhile, the procedure and document requirement of application for such products was clarified and available: including accepting foreign clinical trial data, establishing a designated channel and accelerating the review process.
After adopting the above-mentioned mechanism, in 2019, CDE authorized 16 drugs of urgent clinical need or to treat rare diseases. There was a 60% increase from 2018. The review processes for rare disease drugs were completed in three months, and six months for other drugs of urgent clinical need. This has greatly reduced the time needed for such drugs to enter the market in China.
Currently, 26 drug products have been approved for marketing and 14 are undergoing technical review. Holders of 6 drug products are gathering materials and preparing to initiate the application formally. Holders of 11 drug products have no plan to enter the market so far, and CDE cannot establish contact with the holders of another six drugs.
5.2 Advocating consistency of generic drugs
In order to standardize the selection process of Reference Listed Drug (RLD), CDE published the “Procedures of RLD Selection and Determination for Chemical Generics.” Ever since adopting the RLD selection mechanism stipulated in the document, 1,899 RLDs in 22 batches have been issued (402 are injections), including three batches of 748 RLDs in 2019.
In an effort to improve transparency and communication, the CDE established a special column to display information on the quality and efficacy consistency evaluation of generic drugs. By publishing package inserts of drugs, company investigation reports, and also experimental results of bioequivalence study, CDE sought to further enhance its communication with the industry. Other channels of communications include designated consulting days, a gateway for applicants, and also consultation via phone or written documents.
To further define and clarify the general road map and technical requirements for the quality and efficacy consistency evaluation of generic injections, the CDE legislated the following technical guidance: Technical Requirements for Consistency Evaluation of Marketed Injectable Chemical Generics, Application Dossier Requirements for Consistency Evaluation of Marketed Injectable Chemical Generics, and Technical Requirements for Consistency Evaluation of Injectable Chemical Generics with Special Features in 2019.
5.3 Advancing the reform of the review & approval system
CDE has created a risk management system during clinical trials and promoted a simultaneous system of technical review, compliance inspection, and sample testing for active pharmaceutical ingredients, excipients, and packaging materials jointly with finished drugs. Moreover, it also moved forward in establishing a catalog of marketed drugs in China.
5.4 Improving drug registration mechanism
Besides actively participating in the legislation and revision of Drug Administrative Law and the Vaccine Administration Law, CDE is also striving to revise the 35 relevant regulations, e.g., Provisions for Drug Registration. At the same time, CDE is working to transform the ICH Guidelines and proceed with the eCTD system building in China.
Read more of the original report: China Drug Evaluation Report 2019 by Center for Drug Evaluation
