china drug registration – Accestra Consulting

2020 China Drug Evaluation Report – Part 2

Samantha Beneke — Wed, 04 Aug 2021 22:40:14 +0000

Part 2. Chemical Drugs, Biological Products and Traditional Chinese Medicines

1. Chemical Drugs.
1.1. Application Overview.
1.2. Approval.
2. Biological Products.
2.1. Application Overview.
1.2. Approval.
3. Traditional Chinese Medicine.
3.1. Application Overview.
3.2. Approval.

Despite severe challenges from the COVID-19 pandemic, the Center for Drug Evaluation (CDE) of China reviewed 8,606 drug applications in 2020 and approved many new drugs to help patients suffering from different diseases.

As a follow-up on part 1 of the Drug Evaluation Report 2020, part 2 gives an overview of drug applications and approvals respectively for chemical drugs, biological products, and traditional Chinese medicines.

1. Chemical Drugs

1.1 Application Overview

In 2020, CDE reviewed 6,778 chemical drug applications, including:

1,086 Clinical Trial Applications (CTAs) for Investigational New Drugs (INDs) and confirmatory trials,
163 New Drug Applications (NDAs),
1,697 Abbreviated New Drug Applications (ANDA),
1,136 consistency evaluations,
2,248 supplementary applications.

Comparing to the previous year, the number of consistency evaluations has increased 103.22%

This is followed by CTAs (45.58%) and supplementary applications (23.72%).

View an overview of the chemical drug applications reviewed in 2020 below (Fig. 1).

Fig. 1 Number of Chemical Drug Applications Reviewed in 2020

1.2. Approval

907 INDs, 115 NDAs, and 918 ANDAs were approved with an increase of 51.42%, 30.68%, and 15.33% respectively compared to the previous year.

The table below (Table. 1) gives an overview of the chemical drug applications approved in 2020.

Table 1. Overview of Chemical Drug Application Approvals in 2020

APPLICATION TYPE	NUMBER OF APPLICATIONS
	APPROVAL (INCL. AFTER MATERIAL SUPPLEMENT)	NO APPROVAL SUGGESTED/NOT APPROVED	OTHERS*	TOTAL NUMBER
IND	907	39	14	960
Confirmatory Clinical Trial	108	11	7	126
NDA	115	3	45	163
ANDA	918	32	747	1,697
Supplementary Application	1,732	126	390	2,248
License Renewal of Imported Drugs	380	17	25	422
Consistency Evaluation	577	12	547	1,136
Re-Review	N/A			26
Total	4,737	240	1,775	6,778

Others*: herein refers to the applications which were withdrawn by the applicants or pending for material supplement after technical review, similarly hereinafter.

1.2.1. IND Approval

Under the classification of IND application, the approval rate of 694 Class 1 Innovative New Drugs increased by 40.77% compared to 2019.

Based on the Active Pharmaceutical Ingredients (APIs) of these drugs, 298 categories were approved for Class 1 Drugs with an increase of 57.67% comparing to the previous year.

View the following diagram for a comparison of IND and Class 1 drug IND approvals between the last five years (Fig. 2).

Fig. 2 Number of IND and Class 1 Innovative New Drug IND Approvals from 2016 to 2020

Among the IND approvals of Class 1 drugs, the following shared a large proportion of 80.69%:

Anti-neoplastic,
anti-infective,
circulatory system,
endocrine system,
gastrointestinal,
autoimmune disease,
immunosuppressant drugs.

The diagram below (Fig. 3) shows the number of Class 1 drug IND approvals for each therapeutic field in 2020.

Fig. 3 Number of Class 1 Innovative New Drug IND Approvals for Each Therapeutic Field in 2020

1.2.2. NDA Approval

CDE approved 115 chemical drug NDAs in 2020, among which Class 1 Innovative New Drugs covered 14 drug categories.

View a comparison of NDA approvals between the last five years below (Fig. 4).

Fig. 4 Number of NDA Approvals from 2016 to 2020

2. Biological Products

2.1 Application Overview

CDE reviewed a total of 1,410 Biologics License Applications (BLA) in 2020.

The number of reviewed IND applications and NDAs is given in the below table (Table 2) respectively for preventive and therapeutic biological products and in vitro diagnostics.

Table 2. Number of INDs and NDAs Reviewed for Biological Products in 2020

CLASSIFICATION	NUMBER OF INDs	NUMBER OF NDAs
Preventive Biological Product	27	9
Therapeutic Biological Product	537	108
In-vitro Diagnostics	0	1

The diagram below (Fig. 5) shows the number of BLAs reviewed for every application type.

Fig. 5 Number of BLAs Reviewed in 2020

2.2 Approval

Among the reviewed BLAs, 500 INDs and 89 NDAs were approved with an increase of 60.26% and 20.27% respectively compared to the previous year.

The number of approvals for each application type is summarized in the table below (Table 3).

Table 3. Overview of BLA Approvals in 2020

APPLICATION TYPE	NUMBER OF APPLICATIONS
	APPROVAL (INCL. AFTER MATERIAL SUPPLEMENT)	NO APPROVAL SUGGESTED/NOT APPROVED	OTHERS*	TOTAL NUMBER
Preventive IND	19	4	4	27
Therapeutic IND	481	45	11	537
Preventive NDA	7	0	2	9
Therapeutic NDA	81	1	26	108
In vitro Diagnostic NDA	1	0	0	1
Supplementary Application	551	22	102	675
License Renewal of Imported Drugs	45	0	4	49
Re-Review	N/A	N/A	N/A	4
In Total	1,185	72	149	1,410

For a comparison of biologics IND and NDA approvals between the last five years, please see the diagram below (Fig. 6).

Fig. 6 Number of Biologics IND and NDA Approvals from 2016 to 2020

2.2.1. IND Approval

Under the classification of biologics IND application, 294 cancer drugs were approved in 2020 which covered 58.8% of the total amount. The diagram below (Fig. 7) shows the number of IND approvals for each therapeutic field of biological products in this year.

Fig. 7 Number of Biologics IND Approvals for Each Therapeutic Field in 2020

2.2.2. NDA Approval

Under the classification of biologics NDA, cancer, endocrine, and cardiovascular drugs shared a large proportion of 65.17% of the total amount approved in 2020. The diagram below (Fig. 8) shows the number of NDA approvals for each therapeutic field of biological products this year.

Fig. 8 Number of Biologics NDA Approvals for Each Therapeutic Field in 2020

3. Traditional Chinese Medicines

3.1 Application Overview

CDE reviewed a total of 418 Traditional Chinese Medicine (TCM) applications in 2020, including 37 IND applications, 8 NDAs and 3 ANDAs. The diagram below (Fig. 9) shows the number of TCMs reviewed for each application type.

Fig. 9 Number of TCM Applications Reviewed in 2020

3.2 Approval

Among the reviewed TCM applications, 28 INDs and 4 NDAs were approved by CDE. The number of approvals for each application type is summarized in the table below (Table 4).

Table 4. Overview of TCM Approvals in 2020

APPLICATION TYPE	NUMBER OF APPLICATIONS
	Approval (incl. approval after material supplement)	No Approval Suggested / Not Approved	Others*	Total Number
IND	28	5	4	37
NDA	4	0	4	8
ANDA	0	2	1	3
Supplementary Application	220	42	65	327
License Renewal of Imported Drugs	17	6	4	27
Re-Review	N/A			16
In Total	269	55	78	418

For a comparison of TCM IND and NDA approvals between the last five years, please see the diagram below (Fig. 10).

Fig. 10 Number of TCM IND and NDA Approvals from 2016 to 2020

3.2.1. IND Approval

Under the classification of IND applications, 28 TCMs of 10 therapeutic fields were approved in 2020.

Respiratory, orthopedic, and gastrointestinal drugs shared a large proportion of 53.57%.

The diagram below (Fig. 11) shows the number of IND approvals for each therapeutic field of TCMs this year.

Fig. 11 Number of TCM IND Approvals for Each Therapeutic Field in 2020

Accestra Consulting Provides China Regulatory Affairs Outsourcing for:

Drugs/Pharmaceutical,
Food and Feed products for China NMPA (Formerly CFDA).
Regulatory approval including product registration for China Investigational New Drug (IND),
China New Drug Application (NDA),
China Drug Master File (DMF) for APIs,
Excipients and Packaging Materials,
ANDA,
eCTD submission and others.

Read part 1 of the 2020 Drug Evaluation Report.

Contact Accestra Consulting Group

2020 China Drug Evaluation Report – Part 1

Samantha Beneke — Wed, 28 Jul 2021 22:32:40 +0000

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

Under the impact of COVID-19 in 2020, the Center for Drug Evaluation (CDE) accelerated the drug review and approval process.

More drugs (incl. drug-device combinations) were reviewed and/or approved in 2020 than the previous year.

There were a total of 11,582 registrations (32.67% increase), among which 8,606 registrations required technical review and approval.

The others required only administrative approval. 4,882 registrations were also pending technical review.

For an overview of the registrations reviewed and/or approved (incl. rejections after technical review) in 2020, please see the table below (Table 1).

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

Among 8,606 registrations technically reviewed by CDE, there are:

6,778 chemical drugs (25.33% increase year on year)
418 traditional Chinese medicines (39.33% increase year on year),
1,410 biological products (27.72% year on year).

View the diagram below (Fig. 1) for a comparison between the categories and the total number of registrations reviewed between 2016 and 2020.

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

Among 8,606 registrations technically reviewed by CDE, there are:

1,561 Investigational New Drug (IND) applications (55.94% increase year on year ),
289 New Drug Applications (7.04% increase year on year ),
1,700 Abbreviated New Drug Applications (2.16% increase year on year).

View the diagram below (Fig. 2) for a comparison between the categories and the total number of applications reviewed between 2016 and 2020.

Fig. 2 Number of Applications Reviewed from 2016 to 2020. (Note: CDE has started to conduct quality and efficacy consistency evaluation of generic drugs since August 2017.)

Among these applications, 1,435 INDs, 208 NDAs, and 918 ANDAs were approved after technical review.

These approved NDAs covered a total of 92 drug categories. This includes 20 categories of domestic new drugs and 72 categories of imported new drugs.

The drug category of a chemical drug is referred to as the Active Pharmaceutical Ingredient (API) of the drug, whereas the drug category of a biological product or traditional Chinese medicine is referred to as the International Nonproprietary Name (INN) of the drug.

29 Categories of NDAs were chosen and given below (Table 2). This provides an overview of the new drugs approved for hot topics in 2020, such as COVID-19 vaccines and anti-neoplastic drugs.

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

367 Applications failed to get approved in 2020 because of:

Insufficient proof for drug safety,
Efficacy,
Quality control or delay in submitting the supplementary materials upon CDE’s requests.

The following reasons are identified from different perspectives of drug development and regulatory submission for INDs, NDAs, ANDAs, supplementary applications, and others.

3.1 New Drug Application Rejections

3.1.1. IND Application Rejections.

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

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.
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

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.
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

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.
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

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

Accestra Consulting Provides China Regulatory Affairs Outsourcing for:

Drugs/Pharmaceutical,
Food and Feed products for China NMPA (Formerly CFDA).
Regulatory approval including product registration for China Investigational New Drug (IND),
China New Drug Application (NDA),
China Drug Master File (DMF) for APIs,
Excipients and Packaging Materials,
ANDA,
eCTD submission and others.

Contact Accestra Consulting Group

Chinese Pharmacopoeia 2020 Edition: Key Points

troy — Thu, 23 Jul 2020 12:00:10 +0000

On July 2, 2020, the National Medical Products Administration (NMPA) and the National Health Commission of the People’s Republic of China (NHC) announced the Chinese Pharmacopoeia 2020 Edition.

Read NMPA announces the implementation of the Chinese Pharmacopoeia 2020 edition

This is the 11th edition of Chinese Pharmacopoeia and will be officially implemented from December 30, 2020.

The Chinese Pharmacopoeia is published in 4 volumes:

Volume I:

Traditional Chinese medicines including medicinal materials, cut crude drugs, vegetable oils and extracts, formulation preparation and single flavour preparation;

Volume II:

Chemical drugs, antibiotics, biochemical drugs and radioactive drugs;

Volume III:

Biologics;

Volume IV:

General chapters for finished dosage forms, test methods, guidelines, reference substances, regents, test solutions, and pharmaceutical excipients.

1. Basic Information of Chinese Pharmacopoeia 2020 Edition

The Chinese Pharmacopoeia 2020 edition was compiled under a fixed framework. All goals under the framework have been achieved.

Achievement 1

An appropriate amount of finished pharmaceutical products have been newly listed in the 2020 edition.

This gives a total of 5,911 finished pharmaceutical products listed in the Chinese Pharmacopoeia.

Achievement 2

The 2020 edition deleted several standards of China finished pharmaceutical products to meet the new requirements.

Achievement 3

The 2020 edition comprehensively optimizes the standards of finished pharmaceutical products.

Technical requirements of quality control have been improved for:

Traditional Chinese medicines,
Chemical drugs,
Biological products,
APIs,
Pharmaceutical excipients,
Packaging materials,
Reference substances.

General notices, general chapters of finished dosage forms, test methods and guidelines have been revised.

Achievement 4

The Chinese Pharmacopoeia 2020 edition has established and optimized the general naming conventions for standard drugs, pharmaceutical excipients and packaging materials.

Achievement 5

The Chinese Pharmacopoeia 2020 edition has improved common technical requirements for finished pharmaceutical products.

For example, the standards of traditional Chinese medicines are maintained at international standards, whereas the standards of chemical drugs and pharmaceutical excipients have nearly approached the international level.

Meanwhile, the standards of biological products have reached the international level and are closely related to novel scientific development.

Achievement 6

The international communication and cooperation between pharmacopoeia authorities has been further strengthened.

A variety of national pharmacopoeias have been further harmonized with each other and the international impact of Chinese Pharmacopoeia has been amplified.

2. Chinese Pharmacopoeia 2015 Edition VS 2020 Edition

You can find the differences between the number of products listed in the 2015 edition and 2020 edition of Chinese Pharmacopoeia below (Table 1).

CATEGORY		NUMBER OF PRODUCTS LISTED IN 2015 EDITION	NUMBER OF PRODUCTS LISTED IN 2020 EDITION
			Record	Addition	Revision
Traditional Chinese Medicines		2594	2711	117	452
Chemical Drugs		2595	2712	117	2387
Biological Products		133	153	20	126

General Chapters	Finished Dosage Forms	38	38	0	35
	Test Methods and Others	246	281	35	51
	Guidelines	30	42	12	12
	Excipients	270	335	65	212
Total Number		5906	6272	366	3275