2020 China Drug Evaluation Report – Part 1

 

Table of contents 1. Summary. 2. Technical Review & Approval. 3. Reason For Application Rejections. 3.1 New Drug Application Rejections. 3.2 ANDA Rejections. 3.3 Supplementary Application Rejections. 3.4 Other Application Rejection.

In 2020, the Center for Drug Evaluation (CDE) of China reviewed and/or approved 11,582 drug registrations. To summarize the accomplishments and failures of drug approvals, CDE released a China Drug Evaluation Report of the year. Part 1 of the report gives an overview of drug approvals for: All application types (incl. INDs, NDAs and ANDAs), New drug approvals for hot topics in 2020, Reasons for rejected applications.

1. China Drug Evaluation Report Summary

CATEGORY	REGISTRATION TYPE	NUMBER OF REGISTRATIONS
Drug Product	Requires Technical Review	8,606
	Only Administrative Approval	2,972
Drug-device Combination		4
Total Number		11,582

Fig. 1 Comparison of Drug Registrations Reviewed from 2016 to 2020.
(Note: There was no registration that required only administrative approval in 2016, i.e., all registrations required technical review & approval. From 2017, specific registrations could be approved without technical review under the new regulatory framework.)

2. Technical Review & Approval

Table 2. Overview of New Drug Approvals for Hot Topics in 2020.

NO.	TOPIC IN DRUG THERAPY	INDICATION	DRUG CATEGORY
1	COVID-19 Vaccines and other treatments	SARS-CoV-2	COVID-19 Vaccine (Vero Cell) Inactivated
2	COVID-19 Vaccines and other treatments	Acute Lung Injury (ALI) / Acute Respiratory Distress Syndrome (ARDS)	Liahnhua Qingwen Tables/Capsules/Jinhua Qinggan Tables / Xuebijing Injection
3	COVID-19 Vaccines and other treatments	Non-small Cell Lung Cancer	Sivelestat Sodium Hydrate for Ijection
4	Anti-neoplastic Drugs	Non-small Cell Lung Cancer	Almonertinib Mesylate Tablets
5	Anti-neoplastic Drugs	Pancreatic and Non-pancreatic Neuroendocrine Tumors	Surufatinib Capsules
6	Anti-neoplastic Drugs	Hodgkin Lymphoma and Anaplastic Large Cell Lymphoma	Bretunximab Vedotin for Injection
7	Anti-neoplastic Drugs	B-precursor Acute Lymphoblastic Leukaemia	Blinatumomab for Injection
8	Anti-neoplastic Drugs	Differentiate Thyroid Cancer	Lenvatinib Mesylate Capsules
9	Anti-infective Drugs	Chronic Hepatitis C	Coblopasvir Hydrochloride Capsules
10	Anti-infective Drugs	HIV-1 Pre-Exposure Prophylaxis	Emtricitabine / Tenofovir Disoproxil Fumarate Tablets
11	Circulatory System Drugs	Hereditary Angioedema	Lanadelumab-flyo Injection
12	Circulatory System Drugs	Transthyretin Amyloidosis	Tafamidis Soft Capsules
13	Respiratory System Drugs	Persistent Allergic Rhinitis	Bencycloquidium Bromide Nasal Spray
14	Respiratory System Drugs	Idiopathic Pulmonary Fibrosis (IPF)/Systemic Sclerosis Associated Interstitial Lung Disease (SSc-ILD)	Nintedanib Esylate Soft Capsules
15	Nervous System Drugs	Huntington’s Disease	Deutetrabenazine Tablets
16	Nervous System Drugs	Stage 1 Symptomatic Polyneuropathy	Tafamidis Meglumine Soft Capsules
17	Analgesics and Anesthetics	Painless Gastroenteroscopy	Ciprofol Injection
18	Dermatological and Otorhinolaryngological Drugs	Neurotrophic Keratitis	Cenegermin Eye Drops
19	Dermatological and Otorhinolaryngological Drugs	Atopic Dermatitis	Dupilumab Injection
20	Gastrointestinal Drug	Ulcerative Colitis/Crohn’s Disease	Vedolizumab for Injection
21	Surgical Drugs	Malignant Hyperthermia	Tacrolimus Granules
22	Surgical Drugs	Pediatric Transplant Rejection	Tacrolimus Granules
23	Rare Disease Drugs	Mucopolysaccharidosis 1	Laronidase Concentrate for Injection
24	Rare Disease Drugs	Mucopolysaccharidosis 2	Idursulfase-beta Injection
25	In Vivo Diagnostics	In-vivo diagnosis of mycobaterium tuberculosis infection	Recombinant ESAT-6:CFP-10 Fusion Protein
26	Preventive Biological Product (Vaccine)	Influenza	Influenza Vaccine, Live, Nasal, Freeze-dried
27	Traditional Chinese Medicine	Type 2 Diabetes	Mulberry Twig Alkaloids Tablets
28	Traditional Chinese Medicine	Knee Osteoarthritis	Jingu Zhitong Gel
29	Traditional Chinese Medicine	Acute Bronchitis and Tracheitis	Lianhua Qingke Tablets

 

3. Reasons for Application Rejections

1. Lack of pre-IND meeting
   Major data gaps were identified after IND applications were filed and couldn’t be supplemented in the given timeline.
   

   
   
2. Insufficient data for clinical development justification.
   a. The IND-enabling (incl. pharmaceutical, nonclinical, preclinical) studies demonstrated that the drug efficacy was low and safety risk was high. The risk-benefit ratio was not suitable for first-in-human testing.
   b. The clinical development purpose did not comply with the principles of clinical trials.
   c. The IND-enabling studies were insufficient to start clinical trials.
   

   
   
3. Insufficient data to enable clinical studies or control safety risks in humans.
   a. Major defects in the clinical trial protocol and insufficient risk control measures.
   b. Insufficient nonclinical data for combination therapy drugs.
   c. Insufficient data for each individual vaccine or different immunization procedures between the individual vaccines of a combination vaccine.
   

   
   

3.1.2. NDA Rejections

1. Major defects in the research quality control and management system. Thus the submitted data couldn’t prove the safety, efficacy, and quality of the drug.
   

   
   
2. Lack or regulatory compliance
   a. Inconsistent study drugs were used for different phases of clinical trials.
   b. Authenticity issues were identified in clinical data during on-site inspection/audit.
   

   
   

3.2. ANDA Rejections

1. Unsuitable justification for generic development: The reference listed drug (RLD) which the generic compared to has been withdrawn from the market. A new drug with improved safety has been authorized for marketing in China.
   

   
   
2. Insufficient data for quality consistency
   a. Product specification review and sample inspection did not follow the requirements, or major defects were identified in the analytical methods.
   b. The bioequivalence study demonstrated that the generic and RLD were not bioequivalent.
   c. Lack of compliance with technical requirements for generics (such as stability testing and choose of API starting materials).
   d. The APIs were not from legal sources.
   

   
   

3.3. Supplementary Application Rejections

1. Insufficient data to justify the change to an approved drug.
   a. The submitted change had a major impact on the drug substance and caused substance change.
   b. The submitted change to the drug label/insert did not follow technical requirements for drafting the drug label/insert.
   

   
   
2. The submitted data could not prove that the change to an approved drug had no impact on the drug safety, efficacy, and quality (such as insufficient reference literature and clinical data).
   

   
   

3.4. Other Application Rejection

1. Biosimilars.
   a. Lack of similarity assessment or the choice of reference drug in the comparative study did not follow requirements.
   b. Insufficient nonclinical/preclinical data to enable clinical studies.
   

   
   
2. Natural Medicines: The submitted data did not follow requirements for multi-regional clinical trials or the national guidelines for the review of natural medicines.
   

   
   

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