Drug Evaluation Report 2020 – Accestra Consulting

2020 China Drug Evaluation Report – Part 4

Accestra — Fri, 28 Jan 2022 03:49:26 +0000

Drug review and approval challenges in 2020 included overcoming difficulties in completing facility inspection, conducting remote advisory meetings, and facilitating communications through a variety of tools to help advance drug development and accelerate approval.

As a follow-up on part 3 of the Drug Evaluation Report 2020, part 4 gives an overview of on-site/distant GMP/GCP/GLP inspection, advisory meetings, and technical issue communication pathways, including phone calls, e-mails, and e-platform services by CDE..

1. Drug GMP Inspection

To assess the compliance of a site with the GMP/GCP/GLP of China, the Center of Drug Evaluation (CDE) requests the Center for Food and Drug Inspection (CFDI) for facility inspection when information, such as high-risk products, quality complaints, adverse events or data from an application dossier or other sources, indicate that potential problems or risks exist with a drug product (“For-cause” Inspection). For any application (NDA or ANDA) submitted after July 1st, 2020, a notice of on-site inspection is issued by CDE within 40 workdays after application acceptance if a “cause” warrants a timely investigation of that product. The notice and any other Information to guide the preparation for on-site inspection can be found on the e-platform of CDE through the “Gateway for Applicant”.

1.1 On-site Inspection

In 2020, CDE requested 1,235 on-site inspections, including 792 GMP inspections, 439 GCP inspections, and 4 GLP inspections. Including the backlog of previous year, 818 on-site inspections were completed by CFDI, correspondingly, 449 GMP reports, 363 GCP reports and 6 GLP reports were submitted to CDE.

1.2 Distant Inspection

Under the international impact of COVID-19 pandemic, overseas on-site inspections were not conducted for a number of reasons such as travel restrictions or risk to health. In these circumstances, distant inspections can represent a suitable means of determining GMP/GCP/GLP compliance based on documents and interviews while supported by IT technologies. In November 2020, CFDI conducted distant inspections for two drug products produced outside of China, the outcome of which was basically in line with the principles of on-site inspection. Nevertheless, on-site inspections should still be conducted once circumstances permit.

2. CDE Advisory Meetings and Communications

Advisory meetings and communications are activities of discussing crucial scientific, technical, and policy issues which are not specified in the guidelines for drug development and review of drug registration. They can be proposed by the applicant of drug registration or requested by CDE if clarifications are required during application review. To provide better guidance on these activities, CDE revised and NMPA issued the Provisions for Communications about Drug Development and Technical Review (NMPA [2020] Decree No.48) in 2020. To expedite drug review and approval, CDE took the initiative and newly established e-platform communication services for technical Q&As both before and after a deficiency notification letter is issued for a drug.

2.1 Overview

In the new model of communication, 3,229 applications were received in 2020 for advisory meetings with an increase of 22.6% comparing to 2019 and among which 2,451 applications were approved. On the e-platform of CDE, 20,285 questions were received about general technical issues in 2020 with an increase of 22.4%. In addition, more than ten thousand of phone calls and e-mails were received and answered. To compare the number of advisory meetings and communications between the last years, please see the diagrams below (Fig. 1 and 2).

Fig. 1 Number of Applications for Advisory Meetings from 2016 to 2020

Fig. 2 Number of General Technical Issue Q&As from 2017 to 2020: the e-platform of general technical issue Q&As has been in operation since 2017.

2.2 CDE Advisory Meetings

To improve the efficiency with which expert advice on crucial issues is obtained, CDE determines whether a formal conference is required for a drug or quick answers can be given in writing after receiving the application. If a formal conference is confirmed, it can be held as a teleconference, videoconference, or face-to-face (F2F) meeting. Among 2,451 applications approved for advisory meetings in 2020, 268 conferences were held, and the rest were replied in writing. Classify these meetings according to their topics, Class II meetings shared 76.42% of total approvals, among which pre-IND meetings were the most requested (37.49%). To learn the classification of advisory meetings, please see the overview of advisory meetings below for 2020 (Table 1).

Table 1. Overview of CDE Advisory Meeting Applications and Approvals in 2020

Classification of CDE Advisory Meetings		Number of Applications	%	Number of Approvals	%
Class I (Meetings for crucial safety issues in clinical trials or major technical issues in drug development of breakthrough therapies)		202	6.26%	138	5.63%
Class II	Pre-IND Meeting	1,250	38.71%	919	37.49%
	IND Meeting	228	7.06%	171	6.98%
	End of Phase I Trial Meeting	231	7.15%	213	8.69%
	End of Phase II Trial Meeting	241	7.46%	188	7.67%
	Pre-NDA Meeting	417	12.91%	324	13.22%
	NDA Meeting	71	2.20%	45	1.84%
	Generic Consistency Evaluation Meeting	1	0.03%	3	0.12%
	Complex Generic ANDA Meeting	17	0.53%	10	0.41%
Class III (Other meetings)		571	17.68%	440	17.95%
In Total		3,229	100%	2,451	100%

Note: Some of the advisory meetings approved in 2020 were backlog of the previous year.

2.3 Fast-track Review Meetings

Under the COVID-19 public health emergency, CDE approved many new drug therapies in 2020 for patients suffering from the pandemic through fast-track review pathways. To shorten the timeline for approval, CDE encouraged drug innovators to file applications while development and study of drugs were ongoing. Within 24 hours after an application is received, CDE communicated with the applicant proactively about any crucial scientific matters and the feasibility of approval. For any new technological challenges, CDE invited independent experts for advisory meetings and consultations to obtain advice and discuss solutions. The decisions made on these approvals were further included in the technical guidelines to support drug development and speed new therapies to market.

2.4 Technical Issue Communications

Except for the advisory meetings, applicants of drug registration can also ask questions about general technical issues on the e-platform of CDE. Classify the questions received according to their topics, issues about application acceptance and Active Pharmaceutical Ingredient (API)/Excipient/Packaging were the most asked. Classify the questions received according to drug categories, issues about chemical drugs were the most asked. For more details, please see the overview of general technical issue Q&As below for 2020 (Table 2).

Table 2. Number of Q&As for General Technical Issues in 2020

CLASSIFICATION OF Q&As	API/ EXCIPIENT / PACKING	CHEMICAL DRUG	BIOLOGICAL PRODUCT	TRADITIONAL CHINESE MEDICINE & NATURAL MEDICINE	OTHERS	IN TOTAL
Application Acceptance	315	2,396	790	141	397	4,39
API/ Excipient / Packing	2,764	1,055	85	30	18	3,952
Techical Review – CMC	47	1,077	482	46	18	1,670
Genric Consistency Evaluation	10	1,258	7	2	35	1,312
Technical Review – Clinical Trials	0	824	335	59	37	1,255
Technical Review – Regulatory Compliance	47	668	216	64	47	1,042
Material Supplements for Deficiency Letter	163	718	87	28	14	1,010
Guidelines	33	519	164	58	118	892
CDE e-Platform	225	151	29	4	52	461
Technical Review – Pharmacology, Toxicology	0	158	113	16	3	290
Technical Review – Statistics / Clinical Pharmacology	0	111	34	4	3	152
Others	197	2,331	607	175	381	3,691
In Total	3,804	11,338	3,381	636	1,125	20,285

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.

Read part 2 of the 2020 Drug Evaluation Report.

Contact Accestra Consulting Group

2020 China Drug Evaluation Report – Part 3

Samantha Beneke — Sat, 14 Aug 2021 01:11:28 +0000

Part 3. Administrative Approval and Fast Track Review Pathways

Administrative approval.
Fast track review pathways.
2.1. Specialized pathway.
2.2. Breakthrough therapy.
2.3. Conditional approval.
2.4. Priority Review.

In 2020 CDE approved:

1,435 Investigational New Drug (IND) applications,
208 New Drug Applications (NDAs),
918 Abbreviated New Drug Applications (ANDAs).

This includes 59 drugs for the treatment of COVID-19.

As a follow-up on part 2 of the Drug Evaluation Report 2020, part 3 gives an overview of administrative drug approvals and fast track review pathways by CDE.

This includes specialized pathways, breakthrough therapy, conditional approval, and priority review.

1. Administrative Approval

CDE administratively approves a drug application regardless of whether it needs a technical review.

In 2020, there was a total of 8,646 approved applications, an increase of 44.51% year on year.

Most of these applications (5,647) were reviewed technically before approval, such as:

Clinical Trial Applications (CTAs),
New Drug Applications (NDAs),
Abbreviated New Drug Applications (ANDAs),
License renewal of imported drugs.

Other applications (2,972) were approved without technical reviews, such as temporary drug import applications.

Table 1 below gives an overview of applications administratively approved in 2020.

APPLICATION TYPE		NUMBER OF APPROVALS
		CHEMICAL DRUGS	BIOLOGICAL PRODUCTS	TRADITIONAL CHINESE MEDICINE	IN TOTAL
Approval after technical review	CTAs (incl. confirmatory clinical trials)	1,085	564	37	1,686
	Consistency Evaluations	623	0	0	623
	Supplementary Applications	1,955	615	290	2,860
	License Renewal of Imported Drugs	406	49	23	478
	Re-Review	17	3	7	27
Approval without technical review	Directly Approved Supplementary Applications	2,048	348	141	2,537
	Temporary Import Application	363	60	12	435
IN TOTAL		6,497	1,639	510	8,646

Comparing to 2019, 39.24% more applications were approved after technical review and 55.77% more applications were approved directly (without technical review).

View the diagram below for a comparison between the last three years (Fig. 1).

Fig. 1 Number of Administrative Approvals from 2018 to 2020.

2. Fast Track Review Pathways

CDE used several regulatory pathways to enhance efficiency as well as expedite drug development and approval in 2020.

According to the Provisions for Drug Registration (State Administration for Market Regulation [2020] Decree No. 27), the fast track review pathways are:

Specialized pathway,
Breakthrough therapy,
Conditional approval,
Priority review.

These pathways use a range of approaches, including:

More interactions between CDE reviewers and drug developers,
Greater application process flexibility,
Shortened timelines for review and approval.

During the COVID-19 pandemic, fast track review pathways advanced patient treatments in approving drugs for unmet clinical needs and significant improvements on medical care. This better protected the health of the Chinese public.

Specialized Pathway

A drug reviewed by the Specialized Pathway is used for the treatment or prevention of pandemic disease as part of a declared public health emergency.

The drug review is expedited with:

Increased flexibility:
Accelerated application acceptance,
Parallel proceeding of review,
On-site inspection/audit,
Product testing.

The drug can only be used in a specified period and is based on its medical need for controlling that pandemic disease.

During the COVID-19 pandemic, CDE reviewed 59 chemical drugs, biological products, and traditional Chinese medicines by the specialized pathway in 2020.

Among these:

1 novel drug (i.e., COVID-19 Vaccine (Vero Cell) Inactivated) was approved under controlled conditions,
53 novel drugs were approved for clinical trials,
5 listed drugs were approved to include a new indication of treating coronavirus.

2.2.Breakthrough Therapy

Breakthrough Therapy is a drug for a serious or life-threatening disease for which there is an unmet clinical need or for which there is preliminary clinical evidence demonstrating that the drug may have a substantial clinical improvement over other available therapies.

An application can be submitted to CDE in Phase I or II clinical trial for a drug to be designated as a Breakthrough Therapy.

Once accepted, a breakthrough therapy designation will have the following features:

Priority of advisory communication and meetings with CDE as well as more intensive CDE guidance on drug development.
Priority review with shortened approval timeline.
Priority of on-site inspection/audit and product testing.

In 2020, CDE designated 24 of the 147 applied drugs (16%) as breakthrough therapies.

2.3. Conditional Approval

A drug receives Conditional Approval if there is an urgent medical need for the drug to treat a serious, life-threatening, or public health emergency disease.

The drug can result in having surrogate endpoints, intermediate endpoints, or early clinical data as to efficacy measures.

If the clinical study demonstrates that the benefit of the drug overweighs its risk, it will be approved under controlled conditions.

In 2020, 15 novel drugs received conditional approvals from CDE and provided new therapies for:

COVID-19 pandemic,
Non-small cell lung cancer,
Ovarian cancer and more.

2.4. Priority Review

A drug receives a Priority Review if CDE determines that the drug could potentially provide significant advances in medical care or serve previously unmet medical needs.

The drug is reviewed in an expedited timeline, within 130 workdays instead of the standard 200 workdays, and within 70 workdays for a drug already approved overseas to treat a rare or “orphan” disease.

219 drugs were designated Priority Review by CDE in 2020, among which 42 drugs were pediatric and rare disease drugs.

Including the backlog of priority reviews of the previous year, 217 drugs (of 121 categories) were approved in 2020, an increase of 51.7% compared to 2019.

The highlight examples were:

Almonertinib mesylate tablets,
Agalsidase,
Concentrated injection,
Mulberry twig alkaloids tablets.

Table 2 gives an overview of priority review and approval in 2020 and compares the number of approvals from 2016 to 2020.

REGISTRATION APPLICATION	2016		2017		2018		2019		2020
	NUMBER OF CATEGORIES	RATIO	NUMBER OF CATEGORIES	RATIO	NUMBER OF CATEGORIES	RATIO	NUMBER OF CATEGORIES	RATIO	NUMBER OF CATEGORIES	RATIO
Novel Drug with substantial clinical advance	0	14.30%	33	66%	39	47%	40	48.80%	36	29.80%
Parallel application	0	0%	4	8%	14	16.90%	7	8.50%	30	24.80%
AIDS Drug	0	0%	0	0%	0	0%	0	0%	3	2.50%
Orphan designation for rare disease	0	0%	0	0%	3	3.60%	6	7.30%	11	9.10%
Pediatric drug	4	57.10%	1	2%	9	10.80%	7	8.50%	8	6.60%
Re-application after generic consistency evaluation	0	0%	0	0%	5	6%	8	9.80%	20	16.50%
Major national R&D program drug	0	0%	0	0%	0	0%	5	6.10%	9	7.40%
Generic of coming off-patient drug	1	14%	2	4%	4	4.80%	7	8.50%	4	3.30%
Drug of urgent clinical need or of market shortage	0	0%	2	4%	3	3.60%	0	0%	0	0.00%
First generic drug approval	1	14.30%	8	16%	6	7.20%	2	2.40%	0	0.00%
IN TOTAL	7	100%	50	100%	83	100%	82	100%	121	100%

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.

Read part 2 of the 2020 Drug Evaluation Report.

Contact Accestra Consulting Group

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

Drug Evaluation Report 2020 – Accestra Consulting

2020 China Drug Evaluation Report – Part 4

Part 4. On-site/Distant Inspection and Advisory Meetings

Table of contents

1. Drug GMP Inspection

1.1 On-site Inspection

1.2 Distant Inspection

2. CDE Advisory Meetings and Communications

2.1 Overview

2.2 CDE Advisory Meetings

2.3 Fast-track Review Meetings

2.4 Technical Issue Communications

2020 China Drug Evaluation Report – Part 3

Part 3. Administrative Approval and Fast Track Review Pathways

Table of contents

1. Administrative Approval

2. Fast Track Review Pathways

Specialized Pathway

2.2.Breakthrough Therapy

2.3. Conditional Approval

2.4. Priority Review

2020 China Drug Evaluation Report – Part 2

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

Table of contents

1. Chemical Drugs

1.1 Application Overview

1.2. Approval

1.2.1. IND Approval

1.2.2. NDA Approval

2. Biological Products

2.1 Application Overview

2.2 Approval

2.2.1. IND Approval

2.2.2. NDA Approval

3. Traditional Chinese Medicines

3.1 Application Overview

3.2 Approval

3.2.1. IND Approval

2020 China Drug Evaluation Report – Part 1

Table of contents

1. China Drug Evaluation Report Summary

2. Technical Review & Approval

3. Reasons for Application Rejections

3.1 New Drug Application Rejections

3.1.1. IND Application Rejections.

3.1.2. NDA Rejections

3.2. ANDA Rejections

3.3. Supplementary Application Rejections

3.4. Other Application Rejection