China Reform of the Regulatory Environment

© 2020 All rights reserved | Confidential | For Syneos HealthTM use only

China

Reform of the

Regulatory

Environment

Author Name Lei Zhu Author Title Global Regulatory Consulting

Date Sep 2020

1

© 2020 All rights reserved | Confidential | For Syneos Health® use only

Contents

Abbreviations .............................................................................................................................................. 12

Background ................................................................................................................................................. 13

Reform Impacts: 2016 ................................................................................................................................. 15

Self-inspection of clinical data ................................................................................................................. 15

Priority review .......................................................................................................................................... 16

Additional capacity at CDE ...................................................................................................................... 17

Marketing Authorisation Holder rationalisation / new classification /definition of new drugs .................. 18

Generic drug quality and efficacy consistency Evaluation (GQCE) ........................................................ 18

Reform Impacts: 2017 ................................................................................................................................. 19

Opening up of first-in-human (FIH) Phase I trials to global development ............................................... 20

Simplified process for gaining a marketing approval ............................................................................... 20

Clinical trial management 11..................................................................................................................... 20

Acceleration of drug and medical device registration review process11 .................................................. 22

Drug and medical device lifecycle management11 .................................................................................. 23

Protecting innovator’s rights11 ................................................................................................................. 23

Reform Impacts: 2018 ................................................................................................................................. 25

NHC release the Rare Disease List ........................................................................................................ 25

NMPA was elected as a member of the ICH Management Committee .................................................. 25

Announcement of NMPA on Technical Guideline for Acceptance of Overseas Drug Clinical Trial Data

(2018, No.52) ........................................................................................................................................... 25

NMPA released the Circular on Adjusting the Approval Process for Drug Clinical Trial Evaluation (2018,

Circular 50) .............................................................................................................................................. 26

NPC decided that the three-year period for the MAH pilot project is extended by one year .................. 26

Accelerate approval of urgently needed overseas new drugs ................................................................ 27

Legislate independent Vaccine Administration Law17 ............................................................................. 27

CDE website add functions of IND permission ....................................................................................... 28

Reform Impacts: 2019 ................................................................................................................................. 29

Status of qualification notification of clinical site for medical device now available19 .............................. 29

MAH ADR direct reporting system online ................................................................................................ 29

High level decision on State Council executive meeting for oncology and rare disease drugs20 ........... 29

China to establish collaboration network for rare disease diagnosis, treatment21 .................................. 30

2


2018 CDE Performance Review Meeting22 ............................................................................................. 30

Drug volume purchasing pilot scheme in 4 (municipality cities)+7 (big cities)23 ..................................... 31

2019 Report on the work of the government24 ........................................................................................ 31

eCTD implementation progress and plan in China ................................................................................. 33

Medical Device Animal Study Technical Review Guideline Part I: Decision Principles25 ....................... 33

Medical device online registration system starts in Jun 201926 ............................................................... 34

Approval procedure of medical device clinical trial permit application changed to implied approval27 ... 34

Second batch of clinical urgently needs oversea new drugs 28 ............................................................... 35

NMPA advancing regulatory science initiatives in drug and medical device in China29 ......................... 35

State Council releases legislative work plan for 201930 .......................................................................... 35

CDE solicit public comments on Key Considerations in Using Real World Evidence to Support Drug

Development31 ......................................................................................................................................... 36

NHC solicited public comments on third batch of encouraging drug list for pediatric32 .......................... 36

State Council issued the human genetic resources management regulations33 ..................................... 36

NMPA published the Medical Device registration 2018 annual review34 ................................................ 37

Jiao Hong attended the first BBS conference on global health in boao Asia35 ....................................... 37

CDE published the Drug registration 2018 annual review36 .................................................................... 37

Vaccine Administration Law approved by the Standing Committee of the Chinese People's Congress37

................................................................................................................................................................. 38

NMPA Improvement Policy Concerning Bundling Review and Approval for Drugs and the

Corresponding Supervision Plan38 .......................................................................................................... 38

State Council high level opinion on building a professional and specialized team of pharmaceutical

products inspection39 ............................................................................................................................... 38

Q&A on R&D of Biosimilars40 .................................................................................................................. 39

Revision of the Drug Administration Law of the People's Republic of China 41 ...................................... 40

NHSA Publishes Drug Catalogue of the National Basic Medical Insurance, Industry Injury Insurance

and Maternity Insurance42 ....................................................................................................................... 41

Implementation Plan to Support the Development of Boao International Medical Tourism Pilot Zone 4341

NMPA Releases Technical Guideline for Clinical Trial Endpoints for the Advanced NSCLC 44 ............. 42

NMPA officially joined national competent authority report (NCAR) exchange program of IMDRF45 ..... 42

Regulations of People's Republic of China on Management of Human Genetic Resources on June 10,

201946 ...................................................................................................................................................... 43

CDE Announces Public Consultation on “Working Procedure for Breakthrough Therapy Designated

Drugs”, “Working Procedure for Priority Review and Approval”, Technical Guidelines for Conditional

3


Marketing Approval Granted to Urgently Needed Drugs in Clinical Practice (Draft for Comments), as

well as Explanatory Notes on Nov. 8, 201947 .......................................................................................... 43

CDE Announces Public Consultation on Technical Guidelines for Clinical Changes to Already Marketed

Drugs on Nov. 8, 201948 .......................................................................................................................... 43

CDE Announces Public Consultation on Technical Guidelines for Researches Regarding

Pharmaceutical Changes to Already Marketed Chinese Medicine, ........................................................ 43

Technical Guidelines for Researches Regarding Pharmaceutical Changes to Already Marketed

Chemical Drugs and Technical Guidelines for Researches Regarding Pharmaceutical Changes to

Already Marketed Biologics (Draft for Comments) on Nov. 8, 201949 ..................................................... 44

NMPA Circular on Adopting 15 ICH Guidelines Including E1: Extent of Population Exposure to Assess

Clinical Safety for Drugs Intended for Long-Term Treatment of Non-Life-Threatening on Nov. 12 201950

................................................................................................................................................................. 44

NMPA Circular on Adopting 13 ICH Guidelines Including SIA: Guideline on the Need for

Carcinogenicity Studies of Pharmaceuticals on Nov.12, 201951 ............................................................. 44

NMPA and NHC Releases “Administrative Measures for Drug Clinical Trial Organizations”on Nov. 29,

201952 ...................................................................................................................................................... 44

NMPA Circular on Guarantee the Record Filing Procedure for Drug Clinical Trial Organizations Nov. 29,

201953 ...................................................................................................................................................... 45

State Administration for Market Regulation (SAMR) SAMR Announces New Public Consultation on

“Regulations on Drug Registration (Draft for Comments)” and Explanatory Note on the Issuance of

Regulations on Drug Registration (Draft for Comments) on Dec. 10, 201954 ......................................... 45

NMPA Releases Guidance for Using Real-World Evidence to Support Drug R&D and Regulatory

Review (Interim) and Explanatory Note to Guidance for Using Real-World Evidence to Support Drug

R&D and Regulatory Review (Interim)55 .................................................................................................. 45

CDR-ADR Circular on the Launch of E2B (R3) Electronic Transmission System56 ................................ 46

NMPA Circular on Implementation of 11 ICH Guidelines Including Q2(R1) - Validation of Analytical

Procedures: Text and Methodology57 ...................................................................................................... 46

NMPA Circular on Recommended Implementation of 4 ICH Guidelines Including “Q8 (R2) –

Pharmaceutical Development”58 .............................................................................................................. 46

CDE Circular on Adjusting Administrative Procedures Regarding Drug Registration Application

Acceptance, Dossier Submission, and Information Support Service During Novel Coronavirus Outbreak

on Feb.2, 202059 ...................................................................................................................................... 46

SAMR Circular on Releasing “Forms and Templates Required During Examination and Approval of

Advertisements for Drugs, Medical Devices, Health Food and Formula Food for Special Medical Use”

on Feb 28, 201960 .................................................................................................................................... 47

NMPA Announces Public Consultation on “Guidance for Quality Agreement of Contract Drug

Manufacturing (Draft for Comments)” and “Reference Template for Quality Agreement of Contract Drug

Manufacturing (Draft for Comments)” on March 2, 202061 ...................................................................... 47

4


NMPA Announces Public Consultation on “Working Procedures for Inspection of Drug Marketing

Authorization Holders (Draft for Comments)” and “Key Points for Inspection of Drug Marketing

Authorization Holders (Draft for Comments)” on March 2, 202062 .......................................................... 47

SAMR Circular on 2020 Annual Legislation Program on March 17, 202064 ........................................... 48

NMPA Announcement on Administrative Regulations on Extended Clinical Trials for Medical Devices

(Interim) and Explanatory Note to “Administrative Regulations on Extended Clinical Trials for Medical

Devices (Interim)”65 .................................................................................................................................. 48

State Administration for Market Regulation (SAMR) SAMR Announces Regulations on Drug

Registration and NMPA Announcement on Implementing “Regulations on Drug Registration” 66 ......... 49

SAMR Announces Regulations on Supervision of Drug Manufacture on March 30, 202067 .................. 50

NMPA Announcement on Matters Concerning the Implementation of the Newly Revised “Regulations

on Supervision of Drug Manufacture” on March 31, 202068 .................................................................... 50

Explanatory Note to Policies in “Regulations on Supervision of Drug Registration”69 ............................ 50

CDE Announces Public Consultation on “Technical Guidance on Clinical Trials for R&D of Drugs

Targeting Community Acquired Bacterial Pneumonia” and “Technical Guidance on Clinical Trials for

R&D of Antimicrobial Agents Targeting Acute Bacterial Skin and Skin Structure Infection” on March 19,

2020 70 ..................................................................................................................................................... 51

CDE Announces Public Consultation on “Guidance for Clinical Trials on Adalimumab Injection

Biosimilars (Draft for Comments)” on Apr. 1, 202071 ............................................................................... 51

CDE Announces Public Consultation on “Guidance for Clinical Trials on Trastuzumab Injection

Biosimilars (Draft for Comments)” on Apr. 7, 202072 ............................................................................... 51

CDE Announces Guidance for Clinical Trials on Pertuzumab Injection Biosimilars (Draft for Comments)

on Apr.17, 202074 .................................................................................................................................... 52

CDE Announces Public Consultation on “Technical Guidance on Clinical Trial Imaging Endpoint

Process Standards for Anticancer Drugs (Draft for Comments)” on Apr.22, 202075............................... 52

NHC Circular on Releasing “Administrative Regulation on National List of Drugs in Shortage (Interim)”

on Apr. 20, 202076 ................................................................................................................................... 53

NMPA and NHC Joint Announcement on Releasing “Good Clinical Practice for Drugs” on Apr.23,

202077 ...................................................................................................................................................... 53

CDE Announces Public Consultation on ICH Guideline “Impurities: Guideline for Residual Solvents

Q3C(R8) ”on Apr.29, 202078 .................................................................................................................... 53

NMPA Announces Public Consultation on Regulatory Documents Including “Basic Requirements and

Review Key Points Regarding Application Procedure and Dossier for Re-registration of Domestically

Manufactured Drugs (Draft for Comments)” on Apr.29, 202079 .............................................................. 54

NMPA Announces Public Consultation on “M4 Module 1 Administrative Documents and Drug

Information” (Draft for Comments) on Apr.29, 202080 ............................................................................. 54

5


NMPA Announces Public Consultation on “Basic Requirements for Drug Registration Application

Dossier (Draft for Comments)”on Apr.29, 202081 .................................................................................... 54

NMPA Announces Public Consultation on “Technical Guidelines for Clinical Changes to Already

Marketed Drugs (Draft for Comments)” on Apr.29, 202082 ..................................................................... 54

NMPA Releases “List of Reference Preparations for Generic Drugs (27th List) on Apr.29, 202083 ....... 54

NMPA Announces Public Consultation on 6 Regulatory Documents Including “Special Regulations on

the Administration of Chinese Medicine Registration” on Apr. 29 202084 ............................................... 54

NMPA Announces Public Consultation on Regulatory Documents Including “Classification System for

Registration of Chemical Drugs and Requirements for Application Dossier” on Apr. 29 202085 ............ 55

NMPA Announces Public Consultation on 7 Regulatory Documents Including “Classification System for

Registration of Biologic Products and Requirements for Application Dossier (Draft for Comments)” .... 55

On Apr. 29 202086 .................................................................................................................................... 56

CDE Announces Public Consultation on “Review Guidelines for the Acceptance of Active

Pharmaceutical Ingredient (API) Registration” on Apr. 30 202087 .......................................................... 56

CDE Announces Public Consultation on “Administrative Measures for the Communication on Drug R&D

and Technical Review (Draft for Comments)” on Apr. 30 202088 ............................................................ 56

CDE Announces Public Consultation on “Procedures for Review and Approval of Drug Conditional

Marketing Authorization (Draft for Comments)” on Apr. 30 202089 ......................................................... 56

CDE Announces Public Consultation on “Regulations on Associated Review and Approval of

Pharmaceutical Active Ingredients, Pharmaceutical Excipients, Pharmaceutical Packaging Materials

and Drug Preparations (Draft for Comments)” on Apr. 30 202090 ........................................................... 56

CDE Announces Public Consultation on “Clinical Requirements for Drugs Listed Overseas but Not Yet

Marketed Domestically” Apr. 30 202091 ................................................................................................... 57

Apr. 22 202092 ......................................................................................................................................... 57

CDE Announces Public Consultation on “Guideline on the Submission of Clinical Trial Data (Draft for

Public Review)” on May 6, 202093 ........................................................................................................... 57

CDE Releases “Technical Guideline for Studies of Nitrosamine Impurities in Chemical Drugs (Interim)”

on May 8, 202094 ..................................................................................................................................... 57

CDE Announces Public Consultation on “Technical Guidelines on Preparing Safety Data Submission

for Innovative Anti-Tumor Drug Marketing Application (Draft for Comments)” on May 9, 202095 ........... 57

NMPA Circular on Requiring Quality and Efficacy Consistency Evaluation of Generic Injectable Drugs

on May 12, 202096 ................................................................................................................................... 58

CDE Announces Public Consultation on “Guideline on Adaptive Designs for Clinical Trials (Draft for

Public Review)” on May 13, 202097 ......................................................................................................... 58

6


CDE Announces Public Consultation on “Management System for Drug Clinical Trial Registration and

Information Communication” and “Provisions on Requirements and Management of Development

Safety Update Report” on Nov 8, 201998 ................................................................................................. 58

NIFDC Announces Public Consultation on “Testing Procedures and Technical Requirements for Drug

Registration (Draft for Comment)” on May 15, 202099 ............................................................................ 58

NMPA Releases “Technical Review Guideline for the Registration of Dengue Virus Nucleic Acid

Detection Reagents” on May 14, 2020100 ................................................................................................ 59

Technical Guidance for Using Real-World Evidence to Support R&D and Regulatory Review of

Pediatric Drugs (Draft for Comments) on May 18, 2020101 ..................................................................... 59

NMPA Releases “Evaluation Guideline for Raw Material Changes to Passive Medical Devices” May 19,

2020102 ..................................................................................................................................................... 59

CDE Announces Public Consultation on “Guidance for Clinical Trials on Tocilizumab Injection

Biosimilars (Draft for Comments)” May 21, 2020103 ................................................................................ 59

CDE Announces Public Consultation on “Technical Guidance for Communications on Clinical Aspects

Before the Initiation of Key Experiments During the Registration of Innovative Anticancer Drugs

Supported by Single Arm Trials (Draft for Comments)” May 22, 2020104 ................................................ 60

CFDI Announces Public Consultation on Two Regulatory Documents Including “Regulations on

Implementation Principles and Procedures of Drug Registration Inspections (Draft for Comments)” May

22, 2020105 ............................................................................................................................................... 60

CDE Notice on Gradually Restoring Office Administrative Services May 22, 2020106 ............................ 60

CDE Releases “Guidance on Clinical Trial Design for Biosimilars of Liraglutide Injections”on May 28,

2020107 ..................................................................................................................................................... 61

NMPA Releases “List of Reference Preparations for Generic Drugs (28th List)” on May 28, 2020108 ... 61

CDE Announces Public Consultation on “Technical Requirements Concerning Common

Pharmaceutical Issues in Application for Phase I Clinical Trials of Innovative Chemical Drugs (Draft for

Comments)” and “Summary Table for Information of Pharmaceutical Researches Related to Application

for Phase I Clinical Trials of Innovative Chemical Drugs (Revised Version)” on June 1, 2020109 .......... 61

CMDE Circular on Further Regulating the Procedure of Acceptance and Filing Review for Medical

Device Registration on June 5, 2020110 .................................................................................................. 61

CMDE Circular Concerning Imported Medical Device Applying for Registration as Class II Device but

Categorized Under Class III After Technical Review: Registration Application Withdrawal and Follow-up

Procedures on June 5, 2020111 ............................................................................................................... 62

NMPA Announces Public Consultation on “The Measures for record filing regulation of Medical

Representatives (Trial) (Draft for Comments)” on June 5, 2020112 ......................................................... 62

CFDI Announces Public Consultation on “Drug Safety Credit Record Management System for

Nonclinical Safety Evaluation Research Institutes and Clinical Trial Organizations (Draft for

Comments)” on June 5, 2020113 .............................................................................................................. 62

7


CDE Announces Public Consultation on the “Guidance on Clinical Trial Design for Biosimilars of

Denosumab Injections (Osteoporosis as Indications) (Draft for Comments)” June 5, 2020114 ............... 62

CDE Announces Public Consultation on “Technical Guidance for Communications Before Marketing

Approval Application on Clinical Aspects Concerning Innovative Anticancer Drugs Supported by Single

Arm Trials (Draft for Comments)” on June 5, 2020115 ............................................................................. 63

NMPA CDE Announces “The Administrative Measures for External Experts of CDE” and “The List of

The First Batch of CDE (No. 4 of 2020)” on June 5, 2020116 .................................................................. 63

NMPA Releases “Guideline on Management and Archiving of Required Documentation for Drug

Clinical Trials” June 5, 2020117 ................................................................................................................ 64

CDE Announces Public Consultation on “Guideline on Pharmaceutical Development of Medicines

(Chemical Drugs) for Paediatric Use (Draft for Comments)” on June 12, 2020118 .................................. 64

NMPA Releases “List of Reference Preparations for Generic Drugs (29th List)” ................................... 64

June 16, 2020119 ...................................................................................................................................... 64

Circular on the Release of “General Requirements for Biosafety of Vaccine Manufacturing Sites” on

June 18, 2020120 ...................................................................................................................................... 64

CDE Announces Public Consultation on “Technical Guidance on Clinical Trials for Modified New

Chemical Drugs (Draft for Comments)” on June 24, 2020121 .................................................................. 64

CDE Announces Public Consultation on “Technical Guidance on Endpoints of Clinical Trials for

Advanced Hepatocellular Carcinoma (Draft for Comments)” on June 24, 2020122 ................................. 65

NMPA Announces Launch of “Drug Registration application software (2020 version)” on June 24,

2020123 ..................................................................................................................................................... 65

CMDE Notice on Information Support Service During July and August 2020: Technical Consultation

Before Medical Device Registration Application on June 22, 2020124 ..................................................... 65

CDE Announces Public Consultation on “Guidance on Designing Clinical Trials for GnRH Agonists in

the Treatment of Advanced Prostate Cancer” on June 28, 2020125 ........................................................ 65

CHP Circular on Implementing "Chinese Pharmacopoeia Pharmaceutical Excipient Monograph

Guardianship Mechanism” on June 17, 2020126 ...................................................................................... 65

NMPA Releases “Classification System for Registration of Biologic Products and Requirements for

Application Dossier” on June 29, 2020127 ................................................................................................ 66

NMPA Releases “Classification System for Registration of Chemical Drugs and Requirements or

Application Dossier” on June 29, 2020128 ................................................................................................ 66

NMPA Circular on Updating Drug Registration Fee Charging Standards on June30, 2020129 ............... 66

NIFDC Circular on Releasing “Testing Procedures and Technical Requirements for Drug Registration

(Interim) (Version 2020)” and Related Matters on July 1, 2020130 .......................................................... 66

NMPA Releases “Revised Appendix to Good Manufacturing Practice for Drugs (2010 Revision) – Blood

Products” June30, 2020131 ...................................................................................................................... 67

8


The Chinese Pharmacopoeia Commission Releases “Working Procedures for Drug Generic Name

Review and Approval” on July 1, 2020132 ................................................................................................ 67

NMPA and NHC Circular on Publishing “Pharmacopoeia of the People’s Republic of China (Edition

2020)” on June 24, 2020133 ..................................................................................................................... 67

M4 Module 1 Administrative Documents and Drug Information on July 1, 2020134 ................................ 67

CDE Releases “Rules on Assessment and Management of Safety Information During Drug Clinical

Trials (Interim)” on July 1, 2020135 ........................................................................................................... 67

CDE Releases “Administration Rules on Development Safety Update Reports (Interim)” on July 1,

2020136 ..................................................................................................................................................... 67

CDE Releases “Administration Rules for Drug Clinical Trial Registration and Information

Communication (Interim)” on July 1, 2020137 .......................................................................................... 68

CDE Releases “Review Guidelines for the Acceptance of Chemical Drug Registration (Interim)” on July

2, 2020138 ................................................................................................................................................. 68

CDE Releases “Guidelines for the Acceptance of Biological Product Registration” on July 2, 2020139 . 68

CDE Announces Public Consultation on “General Format and Guidance for Preparing Drug Technical

Documents: ‘Manufacturing Process’, ‘Quality Standards’ and ‘Package Insert’ (Drafts for Comments)”

on July 6, 2020140 .................................................................................................................................... 68

CDE Announces Public Consultation on “Technical Guideline on Clinical Trials for Immune Cell

Therapy Products (Draft for Comments)” on July 6, 2020141 .................................................................. 68

The NMPA Releases Three Regulatory Documents Including “Working Procedure for Review and

Approval of Breakthrough Therapy Designated Drugs (Interim)” on July 7, 2020142 .............................. 69

CDE Notice on New Version of Drug Clinical Trial Registration and Information Release Platform

System on July 10, 2020143 ..................................................................................................................... 69

CDE Releases “Drug Registration Application Dossier Format, Stylistic Rules and Layout Standards” on

July 8, 2020144 ......................................................................................................................................... 69

CDE Releases “Guideline for Management of Drug Clinical Trials During the Covid-19 Outbreak

(Interim)” on July 14, 2020145 ................................................................................................................... 69

CDE announces Public Consultation on “Technical Guideline for Pharmaceutical Changes to Innovative

Drugs (Chemical Drugs) During Clinical Trials (Draft for Comments)” on July 14, 2020146 .................... 69

CDE Announces Public Consultation on “Technical Guidance on Clinical Trials for Antineoplastic Drugs

Used in Combination Therapy” on July 17, 2020147 ................................................................................ 69

CDE Announces Public Consultation on “Guidance on Statistical Design in Clinical Trials for

Antineoplastic Drugs” on July 17, 2020148 ............................................................................................... 70

CDE Releases “Guideline on the Submission of Clinical Trial Data (Interim)” on July 20, 2020149 ........ 70

The CDE Releases “Guidance for Clinical Trials on Rituximab Biosimilars” on July 20, 2020150 .......... 70

9


CDE Releases “Guidance for Clinical Trials on Trastuzumab Injection Biosimilars” on July 20, 2020151

................................................................................................................................................................. 70

NMPA Announcement on Adoption of “ICH E2C (R2) Guideline: Periodic Benefic-Risk Evaluation

Report (PBRER)” on July 17, 2020152 ..................................................................................................... 70

The Center for ADR Announces Public Consultation on “Application Dossier and Requirements for

Switching Drugs from Prescription to OTC Status (Revision Draft for Comments)” on July 24, 2020153 70

The CDE Releases “Guideline on Non-Inferiority Clinical Trials for Drugs” on July 24, 2020154 ............ 71

NMPA Opinions on Further Improving the Quality and Capacity of Adverse Event Monitoring System for

Medical Products on July 28, 2020155 ..................................................................................................... 71

The CDE Announces Public Consultation on “Technical Guideline for Pharmaceutical Researches on

Transdermal Patch Generics (Draft for Comments)” on July 24, 2020156 ............................................... 71

CDE Announces Public Consultation on 4 Technical Guidance Including “Technical Guidance on

Clinical Trials of Antibacterial Drugs for the Treatment of Complicated Urinary Tract Infection” on July

31, 2020157 ............................................................................................................................................... 71

CDE Announces Public Consultation on “Guidance on Real World Data Used to Generate Real World

Evidence (Draft for Comments)” on Aug. 3, 2020160 ............................................................................... 72

on Aug. 3, 2020161 ................................................................................................................................... 72

CDE Announces Public Consultation on “Guidance on Research and Validation of Aseptic Processing

and Sterilization of Injection Drugs” on Aug. 3, 2020166 .......................................................................... 73

The CDE Under NMPA Releases “Record Filing Procedures and Requirements for Separated

Packaging of Drugs Manufactured Overseas” on Aug. 3, 2020167 .......................................................... 73

NHSA Announces Public Consultation on “2020 Working Plan of Adjusting Drug Catalogue Covered by

National Healthcare (Draft for Comments)” on Aug. 3, 2020168 .............................................................. 73

CDE Announces Public Consultation on “Guidance on Clinical Trial Design for Oncolytic Virus- Based

Drugs” (Draft for Comments)” on Aug. 7, 2020169 ................................................................................... 73

CDE Announces Public Consultation on “Technical Guidance on Clinical Trials of Drugs for the

Treatment of Lipid Metabolism Disorders (Draft for Comments)” on Aug. 10, 2020169 ........................... 74

CDE Notice: Public Consultation on “ICH M7 Guideline: Assessment and Control of DNA Reactive

(Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk. Questions and

Answers” and “M7 Q&A Support Document” on Aug. 10, 2020170 .......................................................... 74

CDE Announces Public Consultation on “Technical Guidance on Similarity Assessment and Indication

Extrapolation of Biosimilars (Draft for Comments)” on Aug. 14, 2020171 ................................................ 74

CDE Releases 5 Technical Guidelines Including “Technical Guideline for Research and Development

of Preventive Vaccines Against Covid-19 (Interim)” on Aug. 14, 2020172 ............................................... 74

CDE Announces Public Consultation on 11 Technical Guidance Including “Technical Guidance on

Bioequivalence Study of Olanzapine Orally Disintegrating Tablets” on Aug. 19, 2020173 ...................... 75

10


CDE Announces Public Consultation on “Technical Guideline for Researches on Generic Fulvestrant

Injections (Draft for Comments)” on Aug. 19, 2020174 ............................................................................. 75

CDE Announces Public Consultation on “Guidance on Adjusting for Covariates Clinical Trials for Drugs”

on Aug. 19, 2020175 ................................................................................................................................. 75

CDE Notice on Issuing Electronic Administrative Documents for APIs on Aug. 20, 2020176 .................. 75

CDE Announces Public Consultation on “Technical Guidance on Clinical Trials for Influenza Antivirus

Drugs (Draft for Comments)” on Aug. 21, 2020177 .................................................................................. 75

CDE Announces Public Consultation on “Technical Guidance on Clinical Investigations Concerning

Medicines for the Control of Myopia Progression” on Aug. 24, 2020178 .................................................. 75

CDE Announces Public Consultation on “Technical Guidance on Clinical Trials for Human Stem Cell

Based Therapeutic Products and Their Derivatives (Draft for Comments)” on Aug. 24, 2020179 ........... 76

CDE Announces Public Consultation on “Technical Guidance on Drug Immunogenicity Studies (Draft

for Comments)” on Aug. 24, 2020180 ....................................................................................................... 76

CDE Releases “List of Chemical Drugs of Specific Clinical for Which Reference Preparations Cannot

Be Recommended (1st List)” for Public Review on Aug. 24, 2020181 ..................................................... 76

CDE Announces Public Consultation on “Technical Guideline for Nonclinical Studies of Diagnostic

Radiopharmaceuticals (Draft for Comments)” on Aug. 27, 2020182 ........................................................ 76

CDE Announces Public Consultation on “Guidance for Clinical Trials on Omalizumab Injection

Biosimilars (Draft for Comments)” on Aug. 27, 2020183 ........................................................................... 76

CDE Releases “Technical Guidance for Using Real-World Evidence to Support R&D and Regulatory

Review of Pediatric Drugs (Interim)” on Aug. 27, 2020184 ....................................................................... 77

CDE Announces Public Consultation on “Guidance on Enrichment Strategies and Design for Drug

Clinical Trials (Draft for Comments)” on Aug. 27, 2020185 ...................................................................... 77

CDE Releases “Technical Guideline for Testing Minimal Residual Disease During Clinical Trials of

Drugs for Acute Lymphoblastic Leukemia” on Aug. 28, 2020186 ............................................................. 77

CDE Announces Public Consultation on “Guideline for Subgroup Analyses in Clinical Trials for Drugs

(Draft for Comments)” on Aug. 28, 2020187 ............................................................................................. 77

CDE Announces Public Consultation on “Guidance on Clinical Pharmacology Studies for Pediatric Drug

Development” (Draft for Comments)” on Sep. 1, 2020188 ....................................................................... 77

CDE Announces Public Consultation on “Guidance on Clinical Trial Design for Oncolytic Virus- Based

Drugs” (Draft for Comments)” on Aug. 7, 2020189 ................................................................................... 77

CDE Announce Public Consultation on “Technical Guidance on Clinical Trials for Medicines Treating

Age-Related Macular Degeneration” on Sep. 9, 2020190 ........................................................................ 78

CDE Announces Public Consultation on “Technical Guidance on Pharmaceutical Research and

Changes for Biologics During Clinical Trial (Draft Published Online for Comments)” on Sep. 10, 2020191

................................................................................................................................................................. 78

11


NMPA and National Intellectual Property Administration Announce Public Consultation on

“Implementation Measures Concerning Early Resolution Mechanism for Drug Patent Disputes (Interim)

(Draft for Comments)” on Sep. 11, 2020192 ............................................................................................. 78

CDE Announces Public Consultation on “Technical Guidance on Drug-Drug Interaction Studies (Draft

for Comments)” on Sep. 11, 2020193 ....................................................................................................... 78

Conclusions ................................................................................................................................................. 79

References .................................................................................................................................................. 81

12


Abbreviations

BE Bioequivalence

CDE Center for Drug Evaluation

CFDA Chinese Food and Drug Administration (old name of NMPA)

CMDE Center for Medical Device Evaluation, NMPA

CPP Certificate of Pharmaceutical Product

CROs Contract Research Organisations

EC Ethics Committee

EU European Union

FDA Food and Drug Administration

FIH First in Human

GMP Good Manufacturing Practice

GCP Good Clinical Practice

GQCE Generic drug quality and efficacy consistency Evaluation

HGRAC Human Genetic Resource Administration of China

ICH International Council for Harmonisation

IND Investigational New Drug

MA Marketing Authorisation

MAA Marketing Authorization Application

MAH Marketing Authorization Holder

NDA(s) New Drug Application(s)

NHC National Health Committee

NMPA National Medical Products Administration (formerly CFDA)

NPC National People’s Congress

US United States

VAT Value added tax

13


Background

China is currently the second largest pharmaceutical market in the world and was estimated in 2017 to be

worth $122.6 billion. It was also the biggest emerging market for pharmaceuticals with growth tipped to

reach between $145 billion and $175 billion by 20221.

Due to its high potential for growth, China has also become one of the most important regions for global

drug development, but historically the regulatory environment in China was considered highly challenging

for the following reasons:

The Chinese drug registration process differs from that seen in many other countries, in that new

drug applications (NDAs) for all imported drugs, whether marketed overseas or not, are required

to include data from local clinical trials);

Major differences exist between international standards and some local products and

manufacturers as far as quality is concerned;

The timeframe for review and approval of new drugs is longer than for most major countries;

A lack of capacity in the regulatory body has resulted in a backlog of applications.

In August 2015, the China State Council released “Opinions on Reforming the Review and Approval

System for Drugs and Medical Devices.” The intention of this reform was to promote a structural change

and upgrade of the pharmaceutical industry and bring products already marketed in China up to

international standards in terms of efficacy, safety and quality. These reforms aim to:

Eliminate the existing backlog of registration applications;

Establish an environment for maximizing the quality of generic drugs;

Create a framework in China that encourages research and development of new drugs in line

with global development;

Improve the quality and increase the transparency of the review and approval process.

China has a large pharmaceutical industry; it is estimated that there are between 4,500 and 6,000

manufacturers 2, with businesses based on generics, active pharmaceutical ingredients or traditional

Chinese medicine. Most of the manufacturers are small or medium-sized enterprises. There are however

many manufacturing sites in China that meet global Good Manufacturing Practice (GMP) standards.

Previous regulations meant that the Marketing Authorisation Holder (MAH) also had to be the owner of

the manufacturing site. The reform has seen the separation of the activities of MAH and manufacturer

and so the environment is now more flexible allowing research companies to hold the MA whilst

contracting out the product manufacture to a third party.

Generic drugs available in China tend to have several approved manufacturers and there is a sparsity of

official guidance for the generics industry. The China Food and Drug Administration* (CFDA) has

published “restricted” and “promoted” categories of generic drugs suggesting that a more sound control

and guidance of the generics industry is expected.

14


There has traditionally been stiff competition in the generics arena, which has meant that local Chinese

companies have not been interested in developing innovative new drugs, thus their current capacity for

such development is low. In the recent past, these companies have relied on bioequivalence (BE) trials

for generic drug registration but with CFDA’s* new requirements they will need to start focusing on

generic quality and efficacy; as such, any data considered inaccurate or incomplete will not be accepted

and therefore there is potential for existing licenses to be withdrawn.

*Note: CFDA became NMPA (National Medical Products Administration) in 2018. CFDA has been used

in this document to relate to any Guidance or procedure that pre-dates the 2018 reforms.

15


Reform Impacts: 2016 Table A: Reforms 2016

Reform Detail / Opportunity

Self-inspection of clinical data CFDA announced a self-inspection programme for clinical data, this required MA applicants, contract research

organisations (CROs) and clinical sites to self-inspect. More than 1600 applications pending approval1

This initiative began in July 2015 and uncovered fake and incomplete data which resulted in non-approvals and in

some cases investigations by CFDA.

CFDA used its experts to inspect selected studies that were suspicious in terms of data authenticity.

For future new drug applications, CFDA requires applicants to include a clinical trial self-inspection report,

which CFDA will review.

After 12 months, CFDA reported that around 90% of the backlogged applications had been withdrawn by

applicants or rejected by CFDA4.

16



Priority review In February 2016, CFDA announced a new ‘priority review’ process to encourage new drug innovation to meet

unmet medical needs and to encourage overseas sponsors to plan and perform clinical development in China in

parallel with the US, EU, Japan and other countriesError! Reference source not found.. An updated version was published in 2

017.

‘Priority review’ status can be requested based on the following criteria:

Innovative drug which is not approved anywhere worldwide

Innovative drug where the manufacturing is to be transferred to a site in China

Global clinical trial application to China in parallel with the US or EU

The innovative drug is for HIV/AIDS, viral hepatitis, a rare disease(s), for malignant tumours and for

paediatric indications

The product is a newly launched generic drug.

Positive priority review status provides applicants with ‘priority reviewer resources’ allocated by the Center for

Drug Evaluation (CDE) and priority communication pathways to obtain advice and expedited feedback from the

CDE/CFDA.

CFDA considers that the target approval time for a priority review, from submission, is six months or less however

this is not yet being seen consistently. The scheme seems to have worked well for applications submitted after

February 2016.

On Dec 28, 2017, NMPA updated opinions on priority review with two modifications in the scope, which

are in line with State Council Opinions of Deepening the Reform of the Review and Approval System and

Encouraging the Innovation of Drugs and Medical Devices (6).New drug application with clinical trial

performed by National Clinical Medical Research Center and confirmed by CDE management department

shall be given priority review and approval.

17



Under the circumstances in which there is a major threat to the public health, registration applications for

drugs that have been granted compulsory licensing shall be given priority review and approval. The

specific circumstances under which there is a major threat to the public health and the specific procedures

for initiating compulsory licensing shall be promulgated separately by National Health and Family

Planning Commission together with relevant authorities.

Additional capacity at CDE In 2015 there were only around 70 reviewers to handle an annual load of more than 7,000 drug applications in the

CDE. Following a new hiring exercise, 600 new drug reviewers were in place by the end of 20164.

Additional hiring of reviewers has continued in 2017–2018.

18



Marketing Authorisation Holder

rationalisation / new

classification /definition of new

drugs

MAH system reform ensures that drug research and development institutions can obtain and hold MAs without

needing to own the manufacturing site7.

Encourages drug research and development institutions to transfer manufacturing to an established drug

manufacturer with an associated site inspection in order to validate the manufacturing process.

Major incentive for local new drug innovators in China, who can now hold marketing authorisations

independently.

Reform implemented in a phased manner starting with a trial in ten selected provinces, mostly on China’s

east coast, over three years

Encourages drug researchers/institutions to focus on Research and Development and alleviates the need

to invest in their own manufacturing plants.

Creation of a new classification of drug, “new to the world”, to replace the previous “new to China” category8.

Based on the global marketing authorisation approval status and the location of the manufacturing site(s)

(inside or outside China).

Removes the previous definitions that were based on the specific status in China, and aligns classification

more closely to other regulatory agencies.

Generic drug quality and

efficacy consistency Evaluation

(GQCE)

Generic drug manufacturers are required to start drug consistency research on quality and efficacy; target

completion date by the end of 20189.

Product list has been developed by CFDA that lists which generic drugs need this consistency evaluation.

For evaluation purposes, the comparator product is the “innovator drug,” or a globally recognised similar drug.

Innovator drug means the first marketed drug globally with the full data package to support its safety and efficacy.

19


Reform Impacts: 2017

On March 17 2017, CFDA announced its decision to change the requirement on imported drug

registration. The changes are to encourage foreign-developed new drugs to undergo clinical

investigation within China and outside China in parallel, intended to shorten the time period between

approval outside China and approval inside China to meet the need for new drugs for Chinese

patients.

These changes bring China more into line with global standards, processes and timelines. It is

expected that the new policy will have a positive impact on Ex-China sponsors who can develop a full

clinical development program inside China, with significantly shortened regulatory review processes.

The CFDA marketing authorization approval can be in parallel with the US, EU or any other country’s

approval.

It is envisaged that more foreign (ex-China) sponsors will want to conduct research in China and more

foreign new drugs are likely to be approved. There is hope that the changes will encourage foreign

sponsors to invest in China and set up new drug research centers, with an associated increase in

activity for Chinese clinical trial sites and investigators and potentially CROs in China.

Key changes in 2017 are shown in Table B: Reforms 2017.

20


Table B: Reforms 2017


Opening up of first-in-human (FIH)

Phase I trials to global development

This means that for new chemical drugs and new therapeutic biological products foreign

applicants can have a full clinical development plan executed inside China in parallel with the

global development programmeError! Reference source not found..

This change effectively opens an FIH Phase I market in China

.

Note: preventative vaccines still may not undergo a global trial inside China.

Simplified process for gaining a

marketing approval

Previously, foreign-developed new drugs needed three submissions:

Multinational clinical trial submission to request global Phase II or III trial in China;

After the drug had been approved in US or EU and a certificate of pharmaceutical

product (CPP) was available, submission to CFDA to request clinical trial waiver

(requesting exemption from need to do any additional local trials);

NDA submission to CFDA for market approval.

Under the new policy, there is no need for the second submission (clinical trial waiver) and the

sponsor can move directly to the NDA submissionError! Reference source not found..

This simplified process could shorten the whole approval process by about one year.

Clinical trial management 11 CFDA will no longer accredit clinical sites with Good Clinical Practice (GCP).

Opens up potential for clinical sites in all qualified hospitals,

Likely increase in the number of sites able to manage clinical trials

CFDA retains responsibility for site inspections

21



Opens clinical trial market to all qualified hospitals and to social funds, creating increased

capacity for clinical trials in China

Sponsor can sub-contract inspection or audit for sites to check if they are qualified.

Opportunities for CRO QA departments to expand to take on extra work

Improvement in Ethics Committee (EC) process and review

Each region or province may set up a regional EC to guide EC activities and monitor

trials and investigators in the region.

Includes proposal for EC submission and approval prior to investigational new drug

(IND) submission to CFDA/CDE.

For a multi-centre trial, after EC approval by the lead site, other sites can accept lead

site’s approval without repeating review.

With EC review before IND submission, CFDA/CDE reviewers will be able to review

comments from sites, including trial design comments, encouraging a more active

review of protocol by ECs.

Improvement in the clinical trial/IND review process means a pre-submission consultation

meeting between CFDA and the sponsor will be required for all Phase I or Phase III trial

applications. If after 60 working days following submission, there are no comments from

CFDA/CDE, the submission can be considered approved. Any substantial amendment for an

ongoing trial must be submitted to CFDA in timely manner.

Potential for CRO regulatory affairs functions to expand to co-ordinate/lead meetings.

Clinical trial data from studies outside China can be used in China for registration, including

any BE studies for generic drugs approved in the US, or EU or Japan. These studies will be

subject to an on-site inspection by CFDA.

22



Acceleration of drug and medical device

registration review process11

For drugs and medical devices which are indicated for serious life-threatening conditions or for

significant unmet medical needs, where early- or mid-stage clinical data predicts outstanding

clinical benefit, CFDA can grant a conditional approval to allow early marketing in China. The

conditional approval requires an approved risk management plan and a commitment to

complete required clinical trial(s) based on CFDA’s review and conclusion, much the same as

is currently the norm in the EU.

China’s Ministry of Health issued a rare disease list for China (See 2018 section) and set up a

rare disease patient registration process.

The orphan drug and medical device manufacturer/applicant can apply for a clinical

trial waiver or an agreed decrease in trial subject numbers.

For orphan drugs or medical devices that are already approved outside China, CFDA

can issue a conditional approval to allow marketing in China, while the sponsor

completes commitment for clinical trial based on CFDA’s review and conclusion.

Stricter controls on injectable formulations mean that they will not be approved if an oral

formulation of same product already meets clinical needs.

Active pharmaceutical ingredient, excipient and package material management moves from a

specific approval process to a drug master file process.

Brings this in line with the majority of the rest of the world

Support for new drugs to enter the market by encouraging hospitals to give priority to the

purchase of new drugs that have established safety and efficacy data at a reasonable price.

23



The Chinese Government are looking for a process for maintaining an insurance drug

list following price negotiation with the sponsor but in the meantime they have

committed to have new drugs included on the insurance drug list.

Drug and medical device lifecycle

management11

The new MAH policy has been on trial in ten provinces since November 2015.

The MAH holds all responsibilities for the drug development, regulatory and supply

process, including nonclinical, clinical, manufacture, drug quality, marketing and

delivery, clinical use and safety reporting.

The MAH is responsible for safety reporting and should propose the actions to improve

quality control, timely labelling change or other change initiated from safety analysis.

Re-evaluation of marketed injectable drugs for safety, efficacy and quality control is

consistent with the re-evaluation of generic drug quality and efficacy re-evaluation

started in 2016. The purpose is to upgrade drug quality and remove low-quality

products from the market. The same exercise is ongoing for medical devices.

Inspection system for whole regulatory, development and supply process will be put in

place. Nonclinical and clinical process will be inspected by CFDA; manufacturing

process and quality control will be inspected by provincial-level FDA; sales and

marketing processes will be inspected by city-level FDA.

Protecting innovator’s rights11 Establishment of an effective drug-patent system

Every application for drug approval will include a statement on drug patent non-

infringement.

If an applicant is challenging another party’s patent, the applicant should inform the

patent-holder within 20 days after formal submission; the patent-holder should initiate

any necessary legal action against the applicant within 20 days after being informed by

the applicant and, in parallel, inform CFDA.

CFDA can implement a waiting period of up to 24 months while any decision from a

legal process is pending.

24



If no legal decision has been given within 24 months, CFDA has the right to issue the

new MA.

Clinical trial data protection

An applicant can apply for a clinical trial data protection request, along with their NDA

application.

Six-year protection for new drug, ten-year protection for new orphan drug or new

pediatric drug, three-year protection for modified orphan drug or pediatric drug and ten-

year protection for new biological products.

The protection starts from the date of drug approval. Within this protection period,

CFDA will not approve the same drug from different applicants.

25



Note: CFDA became National Medical Products Administration (NMPA) in 2018

Table C: Reforms 2018


NHC release the Rare Disease List The National Health Committee issued the 1st batch list of Rare Diseases on May 11, 2018.

The list is attached as a PDF below: note this is in Chinese, with bilingual disease list.

41) 关于公布第一批罕见病目录的通知.pdf

NMPA was elected as a member of the

ICH Management Committee

On June 7, NMPA issued a notice saying that at the first meeting of the International

Conference on Technical Registration of Human Drugs in Kobe, Japan, NMPA was elected as

a member of the International Council for Harmonisation (ICH) Management Committee12.

Announcement of NMPA on Technical

Guideline for Acceptance of Overseas

Drug Clinical Trial Data (2018, No.52)

On July 10, 2018, NMPA released the final version of “Technical Guideline for Acceptance of

Overseas Drug Clinical Trial Data”13.

As per the Basic Principles for Acceptance of Overseas Clinical Trial Data, applicants

should ensure the authenticity, integrity, accuracy and traceability of overseas clinical

trial data.

The generation process of overseas clinical trial data should comply with relevant

requirement of ICH Good Clinical Practice (GCP).

Applicants should ensure the design of clinical trials are scientific, the quality

management systems of clinical trials comply with the requirements, as well as clinical

data statistical analysis is accurate and integrated.

26



For drugs which undertake research and development synchronously in China and

abroad (ex-China), for which the clinical trials are to be conducted in China, in order to

ensure the scientific nature and validity of clinical trial designs and data statistical

analysis, applicants/sponsors may communicate with CDE before conducting the

pivotal clinical trials so as to ensure that the designs of pivotal clinical trials are

consistent with the basic technical requirements for drug registration in China.

NMPA released the Circular on

Adjusting the Approval Process for Drug

Clinical Trial Evaluation (2018, Circular

50)

Circular 50 was released by NMPA on July 27, 201814.

In order to encourage innovation, speed up the creation of new drugs, meet the needs of public

drug use, and implement the responsibility of the applicant's research and development,

according to the General Office of the CPC Central Committee and the General Office of the

State Council "Opinions on Deepening the Reform of the Examination and Approval System

and Encouraging the Innovation of Pharmaceutical Medical Devices", related to the review and

approval of drug clinical trials:

For drug clinical trial applications in China, if within 60 days from the date of

application acceptance and payment, the applicant has not received a refusal or

questions from CDE, the drug clinical trial may be carried out in accordance with the

submitted clinical trial protocol.

NPC decided that the three-year period

for the MAH pilot project is extended by

one year

On Oct. 26, 2018, in order to better summarize the pilot experience of the MAH pilot project,

and to lay down a good foundation for reform and improvement of the drug management

system, and pave the way for the revision of the Drug Administration Law of the People's

Republic of China, The Sixth Session of the Standing Committee of the 13th National People's

Congress (NPC) decided that the three-year period for the MAH pilot project should be

extended by one yearError! Reference source not found..

27



This pilot project authorized the State Council to launch MAH system in some places at

the 17th meeting of the Standing Committee of the 12th National People's Congress on

November 4, 2015.

This decision came into force on November 5, 2018.

Accelerate approval of urgently needed

overseas new drugs

On October 30, 2018, the NMPA official website issued the "Notice on the Release of the First

Batch of Clinically Urgently Needed New Drugs List"16.

In order to implement the spirit of the meeting of the State Council and speed up the urgent

need for new overseas drugs to enter China, the NMPA and the NHC have formulated the

“Clinical Urgent Need for Overseas Drug Evaluation and Approval Work Procedures”:

There are 8 new overseas drugs which have been approved recently, and the list of

the other 40 new overseas drugs has now been announced in accordance with the

procedures.

临床急需境外新药审评审批工作程序（2018年第79号）_CN_EN.doc

Drugs in the urgently needed new overseas drug list may be submitted in accordance with the

"Clinical Urgent Need for Overseas New Drug Evaluation and Approval Work Procedures", and

the NDA application shall be directly submitted.

The CDE shall establish a special channel to expedite review.

If NDA application has not yet been submitted, the applicant can contact the CDE at

any time for consultation meeting and submit NDA application as soon as possible.

Legislate independent Vaccine

Administration Law17

http://www.nmpa.gov.cn/WS04/CL2101/331940.html

Nov 11 2018 NMPA published draft version of Vaccine Administration Law for public

comments18.


28



Shaken by Changsheng Bio-technology Co in Changchun vaccine scandal (Changsheng Bio-

technology Co, the vaccine manufacturer, which is based in Jilin province, was found to have

committed serious law violations by China's drug authorities in July and August in connection

with the production of a rabies vaccine. The violations included fabricating production records

and using expired ingredients) the Chinese authority will legislate via an independent Vaccine

Administration Law in parallel with pharmaceutical products. The new Vaccine Administration

Law aims to impose "the strictest" regulations on vaccines to ensure the safety and quality of

these products. The new law intends to improve China's vaccine management system and

eliminate regulatory loopholes exposed by the scandal.

Under the released draft, health and drug authorities will supervise the entire production chain

of vaccines. Drug authorities should also be more thorough in inspecting vaccine production

sites. Manufacturers must digitally record data related to production and inspection of vaccines,

and must also certify the authenticity, integrity and traceability of the data, according to the

draft document. Approval procedures and inspections must cover every batch of vaccines

before they enter the market. Authorized institutes must inspect and approve vaccines, and

report to China's top drug authority and provincial-level drug authorities if there are any major

safety or quality risks found, so that they can be dealt with immediately.

Serious violations of the law, such as producing fake or substandard vaccines, will receive

harsh penalties.

CDE website add functions of IND

permission

In Dec 2018, CDE website added new functions on IND to allow the public access to the IND

application (including progress, supplement notice, and download of IND permission) This was

previously accessible by applicant only. So far, 8 IND permissions were public in CDE website

signifying the formal establishment of the system in China.

29



Table D: Reforms 2019


Status of qualification notification of

clinical site for medical device now

available19

From January 1, 2019, all sites participating in a Medical Device Clinical Trial shall complete

their medical device site qualification notification, which was according to “Medical Device

Clinical Study Institution Notification Regulation, [CFDA Notice 2017 No.145], effective from

January 1, 2018, transition period until December 31, 2018.

The status of medical device sites qualification notification is now available in the old

website of NMPA with link as below (data migration ongoing).

http://218.240.145.213:9000/CTMDS/apps/pub/public.jsp#

MAH ADR direct reporting system online This system is associated with the NMPA reform of ADR reporting which emphasises that

MAH is the main responsible body of pharmaceuticals is now online.

High level decision on State Council

executive meeting for oncology and rare

disease drugs20

China will further shorten the time required for the registration and approval of new oncology

drugs and cut prices, a State Council executive meeting chaired by Premier Li Keqiang

decided on February 11, 2019.

Experts will select overseas new drugs to meet urgent clinical needs, while import policies

will be improved for faster launch of the drugs in China.

China will step up efforts to ensure more early diagnosis and treatment of cancer, and offer

preferential value added tax (VAT) policies for drugs for treatment of rare diseases. Starting

http://218.240.145.213:9000/CTMDS/apps/pub/public.jsp

30



on March 1, 2019 for the first group of drugs, which includes 21 drugs for treatment of rare

disease, VAT will be 3% to align with oncology drugs.

China to establish collaboration network

for rare disease diagnosis, treatment21

China will establish a national collaborative network of hospitals for rare disease diagnosis

and treatment to promote the early detection and effective treatment of such diseases,

according to a decision by the National Health Commission (NHC).

Comprised of 324 hospitals selected for their capacity and experience in treating patients

with rare diseases, the network will facilitate the timely transfer of difficult and complicated

cases between hospitals and the allocation of quality medical resources for them.

Meanwhile, hospitals in the network are urged to further train medical workers on rare

disease knowledge and clinical skills, focusing on improving their abilities to identify,

diagnose and treat such cases.

China will establish a system for rare disease patients to be registered.

2018 CDE Performance Review Meeting22 In their performance review meeting CDE looked at key achievements in 2018:

enforcement of process reform,

implementation and acceleration of the approval of urgently needed overseas new

drugs16;

reducing approval process time for drug clinical trial evaluation14,

excipient/active ingredient/package material bundling review

China marketed drug catalogue (Orange Book)

GQCE9 and ICH.

31



In 2018, total 7336 applications submitted to CDE, 9796 applications completed

evaluation, backlog application reduced to 3440 applications, which was a reduction

of 14% compared to 2017.

In 2018, a batch of new and effective drugs for public health prevention and control,

oncology, rare diseases and other urgently needed drugs completed the technical review

and approval, which provided motivation for innovation in research in China.

Drug volume purchasing pilot scheme in 4

(municipality cities)+7 (big cities)23

The purpose of the 4+7 volume purchasing is to cut the drug price, increase market access,

support to reform of healthcare system.

Although the National Health Insurance Bureau has successively published explanations for

the policy, this policy still shook the pharmaceutical industry. For mature products entering

into the policy scope, the price pressure is very high and industry is concerned about

whether the purchase price reduction and quantity are complementary.

Innovation is undoubtedly the direction that is very key in the future.

2019 Report on the work of the

government24

2018 Key achievements in healthcare:

Coordinated medical service, medical insurance, and pharmaceutical reforms

continued.

Made steady progress in developing the tiered diagnosis and treatment model.

Raised the level of government subsidies for rural and non-working urban residents'

basic medical insurance and the reimbursement rate of their serious illness

insurance.

32



The reform for evaluation and approval of new medicines was stepped up; the

prices of 17 oncology drugs were slashed and these drugs were included in the

national medical insurance catalogue.

Strengthened oversight over food and drug safety and investigated and took stern

action in defective vaccines cases.

Tasks in 2019:

Strengthen R&D and the application of big data and artificial intelligence

technologies, foster clusters of emerging industries like bio-medicine.

Ensure access to basic medical and health services. Continue to increase basic

medical insurance and serious disease insurance protection for rural and non-

working urban residents. Lower and unify the deductible line for serious disease

insurance, raise the reimbursement rate, and further reduce the burden of medical

care for people with serious diseases and people living in poverty.

Strengthen the prevention and treatment of serious diseases. Take action in cancer

prevention and treatment, and promote preventive screening, early diagnosis and

treatment, and promote breakthroughs in cancer research.

Improve prevention and treatment of common chronic illnesses. Outpatient

medicines for treating high blood pressure, diabetes, etc., will be made

reimbursable under the medical insurance scheme.

Implement and improve the policy on interprovincial on-the-spot settlement of

medical bills through basic medical insurance accounts; enable patients to use their

medical insurance cards for medical treatment in any designated hospital and settle

their bills straight away regardless of the locality.

Continue the reform of public hospitals and encourage the development of privately

run hospitals.

33



Establish a system for remote medical care services, enhance the training of

community medical workers, and improve services provided both under the tiered

diagnosis and treatment model and by contracted family doctors.

Prevention will continue to be a priority.

Maternal and child healthcare services will be improved.

Support the preservation, innovation, and development of traditional Chinese

medicine.

Drugs and vaccines - strengthen the entire process of their regulation from

production to use.

eCTD implementation progress and plan in

China

On Mar 8, CDE presented the eCTD progress and plan in 2019 annual meeting of China

Association of Pharma Equipment.

The China specification and technical requirement are published for public

comments in March 2019.

China eCTD pilot implementation date will be May 2019, no formal implementation

timeline available yet.

In the early phase, submission of dossier will use CD plus hardcopy, then transfer to

gateway submission gradually.

CDE suggested that industry should be well prepared for eCTD.

For cost efficiency, small and medium companies may consider outsourcing (to

CRO).

Medical Device Animal Study Technical

Review Guideline Part I: Decision

Principles25

NMPA issued “Medical Device Animal Study Technical Review Guideline Part I: Decision

Principles” on April 19. The guideline provided the principles considerations on using live

animal for medical devices development, decision tree and listed 12 devices as examples to

discuss if study in live animals is needed:

1. Porous coated bioprosthetic hip prosthesis

2. Electrocardiography machine

34



3. Cross-linked sodium hyaluronate gel for injection

4. Absorbable hernia patch

5. External defibrillation products

6. Ultrasound soft tissue cutting hemostasis system

7. Implantable pacemaker

8. Drug eluting stent

9. Degradable metal screws for internal fixation

10. Stapler

11. Anastomat

12. Absorbable surgical anti-adhesion products

Medical device online registration system

starts in Jun 201926

CMDE (Center for Medical Device Evaluation, NMPA) announced that medical device online

registration system (eRPS) is implemented in Jun 2019. This system allows local Category

3, import Category 2 & 3 medical device registration and Category 3 high risk medical

device clinical trial applications. E-submission is optional and paper dossier under current

requirement are still allowed before Oct 31. From Nov 1, submission dossier including

paper and e-dossier should follow the Table of Contents by International Medical Device

Regulators Forum (IMDRF).

This is the gateway for the online submission. http://erps.cmde.org.cn/

Approval procedure of medical device

clinical trial permit application changed to

implied approval27

On April 1 2019, NMPA issued the Adjustment of Medical Device Clinical Trial Approval

Procedure. Since the date, for clinical trial permit application, if no feedback from NMPA

within 60 working days, sponsor can directly start the clinical trial. NMPA will no longer issue

the trial approval letter. Similar to drug, applicant can download and print the trial approval

letter from NMPA website. If necessary, pre-IND meeting can be required by sponsor.

Other requirements of medical device clinical trial, continuous follow the Registration

Regulation of Medical Device.

http://erps.cmde.org.cn/

35



Second batch of clinical urgently needs

oversea new drugs 28

Following the 1st batch released in October 2018, CDE released the 2nd batch of drug

products of urgently medical needs in China on May 29, in which 26 products are included.

If there is no ethnic difference, local clinical trial data can be waived for NDA/BLA.

The new drugs added include orphan drugs, paediatric drugs, also include treatments for

life-threatening diseases for which there is either currently no approved product, or for which

the new drug offers a substantial clinical advantage over existing approved therapies.

The draft list was published for public comments in Mar.

NMPA advancing regulatory science

initiatives in drug and medical device in

China29

In Apr 2019, NMPA initiated the strategic plan of China Regulatory Science project and

identified nine priority areas in first batch. The areas include cell and gene therapy products,

nanomedicine, drug-device combination products, post-market drug safety vigilance and

evaluation, AI devices, new material in medical devices, real world data for medical device,

and safety assessment of Chinese traditional medicine and cosmetics.

Three key objectives for the project are specified: establish 3-5 bases for regulatory science;

initiate key regulatory science projects; introduce series drug evaluation and supervision

policies/tools/standards/methods.

State Council releases legislative work

plan for 201930

State Council announced the China 2019 legislative work plan in May 2019. Four healthcare

related legislation are involved:

1. Regulation of safety in Biotech development (lead by Ministry of Science and

Technology)

2. Regulation of clinical practice management on new technology of biomedical (lead

By NHC)

3. Human Genetic Resource Administration of China (lead by Ministry of Science and

Technology)

4. Revision of Regulation of medical device management (by NMPA)

36



CDE solicit public comments on Key

Considerations in Using Real World

Evidence to Support Drug Development31

Real-world data (RWD) and real-world evidence (RWE) are playing an increasing role in

health care decisions. In China, CDE has already begun to utilize RWE in the review

practices. This guideline will facilitate industry and CDE to clarify the scope of RWE, explore

the principle of the RWE evaluation, and provide a feasible guidance to use of the RWE.

Key Considerations in Using Real-World Evidence to Support Drug Development(Draft for Public Review).docx

NHC solicited public comments on third

batch of encouraging drug list for

pediatric32

The third batch of encouraging drug list for pediatric selection is led by NHC and national

pediatric expert committees. The screening principles are: not registered in China, urgently

unmet medical needs, evidence-based, expert opinion.

State Council issued the human genetic

resources management regulations33

National regulations on the management of human genetic resources recently released by

the State Council, which will go into effect on July 1. The regulations apply to the collection,

preservation and using of a range of genetic materials containing human genomes and

genes (organs, tissues and cells) and impose requirements on human genetic resource

information (data derived from the genetic resource materials). It is issued to regulate and

encourage reasonable employing of human genetic resources in scientific researches,

developing biological medicine (drugs or medical devices) and improving diagnosis and

treatments. According to the regulations, foreign organizations and individuals, as well as

organizations directly controlled by them, are not allowed to collect or preserve China’s

human genetic resources, nor is providing such resources abroad.

Collecting, preserving, utilizing, and providing human genetic resources abroad should be in

accordance with ethics principles, submit to corresponding ethics investigations, and meet

the technical standards formulated by scientific administrative departments of the State

Council, with no violations on the country’s public health, national security, and public

interests.

Sales of human genetic resources are prohibited, said the regulations.

37



It is mentioned in the regulation that “In order to obtain the market approval of relevant drugs

and medical devices in China, international cooperative clinical trials conducted in clinical

institutions using human genetic resources of China, which do not involve the exit of human

genetic resources materials, do not need approval”.

During the period before effective date, applications accepted before 5 pm June 28 2019 will

follow the “old” procedure. Applications accepted after this time point will follow the

procedure in the new regulation.

NMPA published the Medical Device

registration 2018 annual review34

This report summarized the 2018 data of key regulations update, registration project

submission & approval, and key innovative medical devices approval information.

Jiao Hong attended the first BBS

conference on global health in boao

Asia35

In June, 2019, Jiao Hong, Director of the NMPA, attended the first BBS conference on

global health in Boao Asia BBS. Jiao Hong said that China, as an important part of the

global pharmaceutical supply chain, is providing a large number of high-quality

pharmaceutical products to the world. NMPA always gives top priority to public health

protection, adheres to the bottom line of drug safety, promotes innovative development,

improves regulatory capacity, and deepens international cooperation, so as to make every

effort for drug safety and effectiveness and contribute to global health.

During the meeting, Jiao Hong met with who Deputy Director-general Dr. Suzanne Jacobs

and GAVI CEO Dr. Seth Berkley respectively, and had in-depth discussions on topics such

as vaccine regulatory system, drug and vaccine pre-certification, and innovative vaccine

development.

CDE published the Drug registration 2018

annual review36

This report summarized the 2018 data of key technical guidelines, registration project

submission & approval, and key innovative drug approval information.

In 2019, CDE objectives include:

(I) Actively promoting the implementation of various reform tasks

38



(II) Performing law-based duties for better drug review & approval

(III) Continue to promote the evaluation system to keep abreast of the international

standards

(IV) Continue to promote the modernization of review system and construction of the CDE

talent team

Vaccine Administration Law approved by

the Standing Committee of the Chinese

People's Congress37

The Vaccine Administrative Law approved in end of June, and effective from December 1,

2019. This is the first law focus on vaccine management that features penalties on the

production and sale of substandard or fake vaccines.

The new law, which is the strictest and most comprehensive on vaccines in China, will cover

the research and development, production, distribution, use, supervision and management

of vaccines in the country.

Background story: Legislate independent Vaccine Administration Law17

NMPA Improvement Policy Concerning

Bundling Review and Approval for Drugs

and the Corresponding Supervision Plan38

NMPA announce a new policy to optimize and replace all former regulations about active

ingredient, excipient and packaging material. The regulation effective on Aug 15, 2019. Any

inconsistency between this policy and the former relevant documents of the

Bundling Review, this policy shall prevail.

Dossier requirement of excipient (trial), packaging material (trial), Product list which

exempted from registration, and basic requirement of annual report are attached.

State Council high level opinion on

building a professional and specialized

team of pharmaceutical products

inspection39

The State Council recently issued a high level opinion on building a team of professional

and specialized team of pharmaceutical drug inspectors.

The document advances improving the pharmaceutical drug inspection system by

establishing national and provincial teams of specialized inspectors.

According to the document, the inspectors will be an important force for strengthening drug

supervision and ensuring drug safety.

39



A professional, specialized drug inspection system with full-time inspectors as the main

body and part-time inspectors as the supplement will be established within the next three

years.

Q&A on R&D of Biosimilars40 CDE summarized their considerations on the most frequently asked questions during

biosimilar drug review, and released the Q&A on Jul 31, 2019.

Registration strategy:

Recommend of stepwise development of CMC, pre-clinical and clinical. After completion of

CMC and pre-clinical similarity comparison, suggest to have pre-IND meeting with CDE to

clarify the follow-up studies and study design. Suggest to perform a comparative PK study

first in the stage of clinical research, which is followed up by a process o communication

with CDE before following head to head safety and efficacy studies.

Reference Drug selection:

Highly recommend to select China approved originator as the reference drug. If the

reference drug manufactured by different site (same license holder with originator), the

evidence of comparability with the originator should be approved by CDE before starting

the trial.

Immunogenicity comparative study:

Suggest to collect immunogenicity data in all clinical studies, including PK and PD

studies.

Equivalence margin of clinical similarity comparative study:

The equivalence margin is generally estimated based on the Confidence Interval of the

efficacy of the originator, and is determined with consideration of clinical significance.

Indication extrapolation:

Applicants must provide sufficient scientific evidence to support the application for

indication extrapolation. For the reference drug has been approved for multiple indication, if the candidate drug is

clinically similar to the reference drug through the comparison study, an extrapolation to

40



other indications of the reference drug can be considered if the comparative study shows

that the candidate drug is clinical similar to the reference drug. Extrapolation of indications

must be considered case by case according to variety features and sufficiency of data on

similarity.

Indications for extrapolation should be those with clinically related pathological

mechanism and/or identical relevant receptor, together with the same working

mechanism and target. In a clinical comparative test, appropriate indication is selected

and the safety and immunogenicity of indication for extrapolation are fully evaluated.

Prescription Information:

Prescription Information of biosimilar drugs should be drafted generally based on the

consideration not to affect their clinical use and to be conducive to post-marketing safety

monitoring.

Data on the clinical trial in the instructions of biosimilar drugs should reflect effectiveness

and safety rather than similarity. Attention should be paid to the difference of the trade

names of the reference drugs and the biosimilar drugs from the generic names. It is

advised that the generic name instead of its trade name of the reference drugs be used

in the reference to data on clinical studies of reference drugs.

Revision of the Drug Administration Law of

the People's Republic of China 41

The Standing Committee of the National People's Congress on Aug 26 2019 approved the

2nd revision to the Drug Administration Law, the core piece of legislation governing the

pharmaceutical industry in China. The revision, effective as of Dec 1 2019, introduce several

welcome changes to the original Drug Administration Law:

Most of the current regulatory reforms are legally banded in the Law: encourage

clinical value-oriented drug innovation, drug for urgent needs (e.g. rare disease and

severe disease), traditional medicine development, pediatric drug; IND approval

within 60 working days; clinical trial in process control; bundling review; conditional

41



approval; priority review; MAH; online drug sell; post market management; risk

management; drug reserve & supply system; build professional and specialized

inspector team, etc.

Update the scope of fake drugs. In general, importing drugs without approval will

still result in serious legal consequences, including the revocation of business

permits. However, importing "a small amount" of drugs that do not cause health

damage or interfere with existing treatment can be exempt from legal

consequences,

Increase penalties for legal violations. Producing and selling fake drugs, for

example, results in suspension of the business and revocation of certificates. A fine

of up to 30 times the value of the products produced or sold will be levied,

compared to the penalty of five times the value that is stipulated in the existing law.

Intelligence property reform is not included in this revision.

As all these updates need details instruction to landing, more regulatory updates is expected

in the future.

NHSA Publishes Drug Catalogue of the

National Basic Medical Insurance, Industry

Injury Insurance and Maternity Insurance42

New version of the National Medical Insurance drug catalogue is released with

comprehensive adjustment made aiming at optimizing the structure, reducing the drug cost

burden of the public and improving the efficiency in the use of medical insurance funds. The

catalogue establishes standard for drug payment by the insurance funds. The circular also

announces a series of decisions regarding the implementation policies, covering the

following aspects: reimbursing standard; implementation on local levels; centralized

procurement and national drug database; price negotiation of drugs entering the catalogue.

The new version will be effective on Jan 1 2020.

Implementation Plan to Support the

Development of Boao International Medical

Tourism Pilot Zone 43

This is the level plan announced on Sep 17, 2019, which is an optimize version of previous

plan in 2013.

42



The plan outlined major tasks of the pilot zone, located in Hainan, including developing top

level medical service providers and research institutes and developing quality medical

tourism services.

By 2025, the zone will boast world class medical technologies, equipment and drugs,

according to the plan.

With the new policy, import approval of drug and medical device to the pilot zone will be

faster. Data gathered on clinical use in the zone can be used for future registration in China.

The measure may help to reduce the time for innovative overseas drugs to enter the

domestic market.

The administration is working with the Hainan provincial government to formulate detailed

regulations to promote domestic access of overseas drugs, she said.

NMPA Releases Technical Guideline for

Clinical Trial Endpoints for the Advanced

NSCLC 44

Lung cancer is the number one cause of death among people with malignant tumors in

China. In lung cancer, 85% is non-small cell lung cancer (NSCLC). This guideline provides

the general consideration on different clinical trial endpoints, and expect to give reference to

NSCLC clinical trial design.

NMPA officially joined

national competent authority report (NCAR)

exchange program of IMDRF45

On September 19 2019, IMDRF-16 meeting in Yekaterinburg, Russian, NMPA officially

joined national competent authority report (NCAR) exchange program of IMDRF.

The NCAR Exchange Program facilitates the exchange of relevant post market safety

information on medical devices with global distribution. The aim is to trigger rapid adoption

of field safety corrective actions in all concerned geographies to avoid death or serious

deterioration of health. Up to date, there are more than 20 countries/regions joined this

program.

NMPA next step is share and exchange the information with member countries, timely

obtain serious adverse events of medical device globally, which to secure the safety use of

medical device in China.

43



Regulations of People's Republic of China

on Management of Human Genetic

Resources on June 10, 201946

The newly issued national regulations aim at effectively protecting and reasonably utilizing

human genetic resources. The regulations apply to the collection, preservation and using of

a range of genetic materials containing human genomes and genes (organs, tissues and

cells) and impose requirements on human genetic resource information (data derived from

the genetic resource materials). It is issued to regulate and encourage reasonable

employing of human genetic resources in scientific researches, developing biological

medicine (drugs or medical devices) and improving diagnosis and treatments. According to

the regulations, foreign organizations and individuals, as well as organizations directly

controlled by them, are not allowed to collect or preserve China’s human genetic resources,

nor is providing such resources abroad.

CDE Announces Public Consultation on

“Working Procedure for Breakthrough

Therapy Designated Drugs”, “Working

Procedure for Priority Review and

Approval”, Technical Guidelines for

Conditional Marketing Approval Granted to

Urgently Needed Drugs in Clinical Practice

(Draft for Comments), as well as

Explanatory Notes on Nov. 8, 201947

These three guidance documents are issued according to new requirements established in

the updated Regulations on Drug Registration. The drafts are released for public

consultation until November 13 2019. Any suggestions and feedback can be submitted

through the feedback form attached as second reference file and sent to CDE s contact

email boxes.

These notes gives supplementary information on the issuing of this draft guidance,

explaining the background, drafting process, key considerations and major content, and

special issues that need to be highlighted.


Technical Guidelines for Clinical Changes

to Already Marketed Drugs on Nov. 8,

201948

This document is intended to give instructions as well as to further regulate studies and

administration on post-approval clinical changes to drugs that are already in the market,

following the newly revised Drug Administration Law. The draft is now released to invite

public review. Any suggestions and feedback should be submitted to CDE s contact email

box before November 13 2019.


Technical Guidelines for Researches

44



Regarding Pharmaceutical Changes to

Already Marketed Chinese Medicine,



Already Marketed Chemical Drugs and



Already Marketed Biologics (Draft for

Comments) on Nov. 8, 201949

These documents are intended to give instructions as well as to further regulate studies on

post-approval pharmaceutical changes to chemical drugs and biologics that are already in

the market, following the newly revised Drug Administration Law. The drafts are now

released to invite public review. Any suggestions and feedback should be submitted through

the feedback form attached as second reference file to CDE s contact email box before

November 13 2019.

NMPA Circular on Adopting 15 ICH

Guidelines Including E1: Extent of

Population Exposure to Assess Clinical

Safety for Drugs Intended for Long-Term

Treatment of Non-Life-Threatening on Nov.

12 201950

NMPA announces the decision to adopt 15 ICH guidelines of “E Series” in China. The

circular explains specific requirements and effective date of each of these guidelines.

Relevant guidance documents are available on the website of Center for Drug Evaluation

(CDE). These 15 ICH guidelines are listed in the annex.

NMPA Circular on Adopting 13 ICH

Guidelines Including SIA: Guideline on the

Need for Carcinogenicity Studies of

Pharmaceuticals on Nov.12, 201951

NMPA announces the decision to adopt 13 ICH guidelines in China. Applicants are required

to conduct researches following ICH guidelines as soon as possible, but always based on

the current technical requirements. Non clinical studies that start from May 1 2020 should

adopt these 13 ICH non clinical guidelines. Relevant guidance documents are available on

the website of Center for Drug Evaluation (CDE). These 13 ICH guidelines are listed in the

annex.

NMPA and NHC Releases “Administrative

Measures for Drug Clinical Trial

Organizations”on Nov. 29, 201952

NMPA and National Health Commission jointly releases these administrative measures

following the newly established Drug Administration Law. These measures are effective

from December 1 2019.

45



NMPA Circular on Guarantee the Record

Filing Procedure for Drug Clinical Trial

Organizations Nov. 29, 201953

This circular is issued following the newly released “Administrative Measures for Drug

Clinical Trial Organizations”, which gives further instructions on the implementation of

these measures. The administration of clinical trial organizations has changed from

qualification accreditation to record filing.

State Administration for Market Regulation

(SAMR) SAMR Announces New Public

Consultation on “Regulations on Drug

Registration (Draft for Comments)” and

Explanatory Note on the Issuance of

Regulations on Drug Registration (Draft for

Comments) on Dec. 10, 201954

This draft regulation is issued to meet the requirements established by the newly released

Drug Administration Law and Law on Vaccine Administration. Any suggestions and

feedback should be submitted through SAMR’s web portal, the authority’s contact email or

by email before December 17 2019. The draft regulation as well as an explanatory note on

its issuance are attached as annexes.

These regulations apply to activities of drug R&D, registration and supervision for the

purpose of marketing authorization. The content contains the following chapters: General

Provisions; Basic Systems and Requirements; Registration for Drug Marketing

Authorization; Accelerating Drug Marketing Authorization; Changes and Re-registration after

Market Approval; Application Acceptance, Supplementary Dossier and Procedure

Withdrawal; Dispute Resolution; Procedure Timing; Administration and Supervision; Legal

Liabilities; Supplementary Provisions.

This note gives further explanations on the issuance of this draft regulation, providing

supplementary information on the following aspects: background and necessity of its

issuance; drafting process; key considerations and major content of the new draft.

NMPA Releases Guidance for Using Real-

World Evidence to Support Drug R&D and

Regulatory Review (Interim) and

Explanatory Note to Guidance for Using

Real-World Evidence to Support Drug R&D

and Regulatory Review (Interim)55

NMPA announces the issuance and release of this guidance document, which is intended to

give further instructions and set requirements regarding the application of real-world

evidence in drug R&D as well as regulatory review/approval. The guidance and an

explanatory note to its issuance are provided as annexes.

This document gives supplementary information on the issuance of this guidance regarding

the background and process of its drafting, as well as further explanation on its major

content.

46



CDR-ADR Circular on the Launch of E2B

(R3) Electronic Transmission System56

The Center for Drug Reevaluation and National Center for ADR Monitoring announces the

launch of E2B (R3) electronic transmission system intended for the submission of individual

case safety reports, starting from January 1 2020. Detailed instructions on the submission

process are provided in the “Working Procedure of Individual Case Safety Report

Submission Through E2B (R3) Electronic Transmission System”, which is attached as

annex. There will be trial period for the system operation, during which the previous channel

and requirements for submission remain valid.

NMPA Circular on Implementation of 11

ICH Guidelines Including Q2(R1) -

Validation of Analytical Procedures: Text

and Methodology57

NMPA issues this circular to inform the implementation of 11 ICH guidelines.

Pharmaceutical researches starting 6 months after the publication date of this circular are

required to follow these ICH guidelines, otherwise applicants should follow them as soon as

possible. List of these 11 ICH guidelines and the corresponding Chinese titles is provided as

Annex.

NMPA Circular on Recommended

Implementation of 4 ICH Guidelines

Including “Q8 (R2) – Pharmaceutical

Development”58

NMPA issues this circular to inform the recommended implementation of 4 ICH guidelines:

Q8(R2) - Pharmaceutical Development; Q9 - Quality Risk Management; Q10 -

Pharmaceutical Quality System; Q11- Development and Manufacture of Drug Substances

(Chemical Entities and Biotechnological/Biological Entities). Since the date of publication,

drug applicants are suggested to follow the requirements established in these guidelines in

the product R&D. List of these four ICH guidelines and the corresponding Chinese titles

is provided as Annex.

CDE Circular on Adjusting Administrative

Procedures Regarding Drug Registration

Application Acceptance, Dossier

Submission, and Information Support

CDE has decided to temporarily adjust its administrative services related to drug registration

application, dossier submission and consultation. From February 3 2020: 1). Online

submission platform “Applicant’s Window” will be the channel for submission of electronic

dossier; 2). On-site channels for accepting documents of registration application, corrective

and supplementary submission will be shut down and be replaced by postal service

47



Service During Novel Coronavirus

Outbreak on Feb.2, 202059

channel; 3). On-site consultation and information support will be closed and replaced by

telephone communication.

SAMR Circular on Releasing “Forms and

Templates Required During Examination

and Approval of Advertisements for Drugs,

Medical Devices, Health Food and Formula

Food for Special Medical Use” on Feb 28,

201960

SAMR announces to release a compilation of reference forms and templates that are to be

used during the examination and approval of advertisements of drugs, medical devices,

health food and formula food for special medical use. These document models are issued

under the framework of “Interim Administrative Measures for the Examination and Approval

of Advertisements for Drugs, Medical Devices, Health Food and Formula Food for Special

Medical Use”, which are intended to establish unified document format and standards for

administrative procedures. The compilation of documents is provided as Annex.

NMPA Announces Public Consultation on

“Guidance for Quality Agreement of

Contract Drug Manufacturing (Draft for

Comments)” and “Reference Template for

Quality Agreement of Contract Drug

Manufacturing (Draft for Comments)” on

March 2, 202061

NMPA issues these two draft documents following requirements of the newly released

national Drug Administration law. They are intended to give guidance to drug Marketing

Authorization Holders (MAHs) and contracted drug manufacturers in assuming

responsibilities and guarantee product quality. These two draft documents are now released

for public consultation and they are provided as Annexes. Any suggestions and comment

should be submitted to NMPA’s contact email before March 18 2020.


“Working Procedures for Inspection of

Drug Marketing Authorization Holders

(Draft for Comments)” and “Key Points for

Inspection of Drug Marketing Authorization

Holders (Draft for Comments)” on March 2,

202062

NMPA issues these two draft documents to give specific guidance on the implementation of

the newly released national Drug Administration Law and Vaccine Administration Law. They

are intended to further regulate the inspection procedure on drug Marketing Authorization

Holders (MAHs), requiring MAHs to assume responsibilities for drug safety, efficacy and

quality control during manufacturing, distribution and drug use. These two draft documents

are now released for public consultation and are provided as Annexes. Any suggestions and

comment should be submitted to NMPA’s contact email before March 18 2020.

48



CDE issued Guidance for Clinical Trials on Rituximab Biosimilars (Draft for Comments) on March 17, 202063

The patent on rituximab in China expired on 2013, following which many manufacturers of

China and overseas have initiated R&D on its biosimilars. This draft guidance is issued

based on “Technical Guideline for Development and Evaluation of Biosimilars (Interim)” as

well as characteristics of rituximab, which is intended to provide technical reference for its

clinical research and development. It covers content of the following aspects: general

introduction; major considerations in clinical research design for rituximab (pharmacokinetics

comparison study; effectiveness comparison study; safety and immunogenicity studies); and

summary.

SAMR Circular on 2020 Annual Legislation

Program on March 17, 202064

The SAMR announces the approval of 2020 annual legislation program and work plan,

which covers 7 final drafts of administrative laws and regulation, revision of 48 ministerial

regulations, and a series of legislative proposals regarding market supervision and

administration. Regulations on drug registration, manufacturing, distribution; release of

biologics; online drug selling; medical device registration, manufacturing, distribution,

adverse event monitoring; IVD registration, etc. are within this annual plan. The circular

establishes procedure and principles for legislation drafting and revision, as well as gives

detailed information on the implementation of the plan. A list of regulations included in the

plan is provided within the circular.

NMPA Announcement on Administrative

Regulations on Extended Clinical Trials for

Medical Devices (Interim) and Explanatory

Note to “Administrative Regulations on

Extended Clinical Trials for Medical

Devices (Interim)”65

These regulations apply to all extended clinical trials for medical devices that are conducted

within China. “Extended clinical Trials” refer to the following practice: For a medical device

that has not been approved for marketing, it is allowed to be used by institutions that are

conducting its clinical trials on patients diagnosed with life-threatening diseases for which

effective treatment is not available yet. The use of medical devices for extended clinical

trials should be based on the observation that existing clinical trials may benefit the subject,

and the patient cannot be admitted to the clinical trials that are already in process because

the selection of participants has been completed. The regulations include the following

https://syneoshealth.tarius.com/RegionTopic/ShowDocument?id=%7b03795B93-59E2-468B-9CF2-71B9858FA209%7d



https://syneoshealth.tarius.com/RegionTopic/ShowDocument?id=%7b317CE1EB-BC75-4543-9B2A-FE12F3968913%7d

https://syneoshealth.tarius.com/RegionTopic/ShowDocument?id=%7b317CE1EB-BC75-4543-9B2A-FE12F3968913%7d

49



This document was not published and

available on the website of NMPA until March

20, 2020.

chapters: General Principles; Rights and Responsibilities; Conditions for Starting; Procedure

Management; Data Collection; Supplementary Provisions.

This note provides further explanations and guidance concerning some major aspects

established by the newly released regulations: 1). Application scope of extended clinical

trials; 2). Proposal for starting extended clinical trials; 3). Agreement with trial participants;

4). Recording filing; 5). Data submission.

State Administration for Market Regulation

(SAMR) SAMR Announces Regulations on

Drug Registration and NMPA

Announcement on Implementing

“Regulations on Drug Registration” 66



30, 2020.

These regulations are released under the State Administration for Market Regulation Decree

No. 27 after the approval. They apply to activities of drug R&D, registration and supervision

for the purpose of marketing authorization within China, covering drugs, biologics and

traditional Chinese medicines. The content contains the following chapters: General

Provisions; Basic Systems and Requirements; Registration for Drug Marketing

Authorization; Expedite Approval for Drug Marketing Authorization; Changes and Re-

registration after Market Approval; Application Acceptance, Withdrawal and Dispute

Resolution; Procedure Timing; Administration and Supervision; Legal Liabilities;

Supplementary Provisions.

Effective Date

Jul 1, 2020

The NMPA announcement is issued following the newly released “Regulations on Drug

Registration” as supplementary decision on its implementation, aiming to facilitate a smooth

transition from the old regulation to the new one. The document clarifies regulatory

requirements and gives specific explanations on administrative procedures regarding drug

registration before and after the new regulation take effect.

50



SAMR Announces Regulations on

Supervision of Drug Manufacture on March

30, 202067



30, 2020.

These regulations are released under the State Administration for Market Regulation Decree

No. 28 after the approval. They apply to administrative activities of supervision and

inspection on manufacturing of drugs marketed in China. The content is organized in the

following chapters: General Provisions; Drug Production Permission; Administration of Drug

Manufacture; Supervision and Inspection; Legal Liabilities; and Supplementary

Supervisions.

Effective Date

Jul. 12020

NMPA Announcement on Matters

Concerning the Implementation of the

Newly Revised “Regulations on

Supervision of Drug Manufacture” on

March 31, 202068

This announcement is issued following the newly released “Regulations on Supervision of

Drug Manufacture” as supplementary decision on its implementation. The document clarifies

regulatory requirements and gives specific explanations on administrative procedures

regarding drug manufacturing, license application, approval and renewal etc. before and

after the new regulation takes effect. The announcement includes the following checklists

and forms that are required in the procedures mentioned: 1). Checklist for Drug Manufacture

License Application Dossier; 2). Checklist for GMP Compliance Inspection Application

Dossier; 3). Drug Manufacture License Application Form; 4). GMP Compliance Inspection

Application Form. These checklists and forms are provided as Annexes.

Explanatory Note to Policies in

“Regulations on Supervision of Drug

Registration”69

This note gives further explanations to the issuance of the newly released “Regulations of

Drug Registration” as well as new policies and measures established through a series of

Q&As. It covers key topics including regulation issuing background; issuing purpose and

principles; strengthened supervision on drug life circle; reform on administrative procedures

regarding drug review and approval; new concepts and mechanism introduced; measures to

encourage drug innovation and research, etc.

51




“Technical Guidance on Clinical Trials for

R&D of Drugs Targeting Community

Acquired Bacterial Pneumonia” and


R&D of Antimicrobial Agents Targeting

Acute Bacterial Skin and Skin Structure

Infection” on March 19, 2020 70

CDE has issued these two draft guidance documents to give technical reference to the R&D

and clinical trials of medicines targeting bacterial infection. Now the administrative authority

is inviting public opinions on these two drafts, which are provided as Annexes. Any

suggestions and feedback should be submitted to CDE’s contact email boxes.


“Guidance for Clinical Trials on

Adalimumab Injection Biosimilars (Draft for

Comments)” on Apr. 1, 202071

Currently many companies of China and overseas are in the process of developing

biosimilars of Adalimumab, which was originally developed and marketed by Abbot

Laboratories. This draft guidance is intended to provide technical reference for conducting

clinical researches on Adalimumab biosimilars. The draft guidance is now released online to

invite public opinion. Any feedback and suggestions should be submitted to CDE’s contact

email boxes. The draft guidance is provided as Annex.



Trastuzumab Injection Biosimilars (Draft

for Comments)” on Apr. 7, 202072

Trastuzumab, sold under the brand name Herceptin; and originally developed by Roche, is a

monoclonal antibody specially used for cancer that is HER2 receptor positive. Currently

many companies of China and overseas are in the process of developing trastuzumab

Injection biosimilars. This draft guidance is intended to provide technical reference for

conducting clinical researches for developing trastuzumab biosimilars and is now released

online to invite public opinion. Any feedback and suggestions should be submitted to CDE’s

contact email boxes. The draft guidance is provided as Annex.

CDE Announces Guidance for Clinical

Trials on Denosumab Injection Biosimilars

Denosumab entered Chinese market under the brand name Xgeva® in 2019 and its patent

in China will be expired on 2022. Currently many manufacturers in China have initiated R&D

on denosumab injection biosimilars. This draft guidance is issued based on “Technical

https://syneoshealth.tarius.com/Documents/ShowDocument?id=15f4867a-172c-470a-a7dd-371e0776191f


52



(Malignant Tumors as the Indications)

(Draft for Comments) on Apr. 10, 202073

Guideline for Development and Evaluation of Biosimilars (Interim)” as well as characteristics

of denosumab, which is intended to provide technical reference for its clinical research and

development. This guidance only discusses denosumab biosimilars targeting cancer

patients. It covers content of the following aspects: general introduction; clinical research

strategies for denosumab biosimilars; major considerations in clinical study design

(pharmacokinetics comparison study; effectiveness comparison study; other aspects such

as safety and immunogenicity studies and extrapolation of indications); and summary.

This note gives further information regarding the issuance of this draft guidance on the

following aspects: 1). Background and purpose; 2). Process of issuance; 3). Major content

and key consideration in the guidance.

CDE Announces Guidance for Clinical

Trials on Pertuzumab Injection Biosimilars

(Draft for Comments) on Apr.17, 202074

Pertuzumab entered Chinese market under the brand name Perjeta® in 2018. It is a

monoclonal antibody used in treatment of metastatic HER2-positive breast cancer. The

patent of Pertuzumab will be soon be expired in EU (2023) and US (2024), and currently

many manufacturers in China have initiated R&D on Pertuzumab biosimilars.This draft

guidance is issued based on “Technical Guideline for Development and Evaluation of

Biosimilars (Interim)” as well as characteristics of Pertuzumab, which is intended to provide

technical reference for its clinical research and development. It covers content of the

following aspects: general introduction; clinical research strategies for Pertuzumab

biosimilars; major considerations in clinical study design (pharmacokinetics comparison

study; effectiveness comparison study; other aspects such as safety and immunogenicity

studies); and summary.


“Technical Guidance on Clinical Trial

Imaging Endpoint Process Standards for

Anticancer Drugs (Draft for Comments)” on

Apr.22, 202075

This draft guidance is issued to set up a standard process regarding the clinical trial imaging

endpoint for the R&D of anticancer drugs, aiming at further regulating industrial standard

and establishing technical requirements. Any suggestions and feedback should be



53



submitted through the Feedback Form and sent to CDE s contact email boxes. The form,

the draft guidance and an explanatory note are provided as Annexes.

NHC Circular on Releasing “Administrative

Regulation on National List of Drugs in

Shortage (Interim)” on Apr. 20, 202076

Following “State Council Circular on Guarantee Supplies and Maintaining Prices of Drugs in

Shortage”, NHC has established these administrative measures to further strengthen the

supply and supervision of drugs in shortage. The interim regulation is provided as Annex 1.

Drug shortage that cannot be solved on local level should be reported through the form

provided as Annex 2 to the administration of central government.

NMPA and NHC Joint Announcement on

Releasing “Good Clinical Practice for

Drugs” on Apr.23, 202077

NMPA and NHC have jointly established the new Good Clinical Practice (GCP) for drugs

and now announce its release. This guidance is intended to further regulate research and

clinical trials on drugs as well guarantee the quality of these practices. The guidance

document is provided as Annex.

This guidance applies to clinical trials conducted for the application of drug registration and

regulates activities that are relevant to drug clinical trials. The Good Clinical Practice (GCP)

established here are quality standards for the whole process of clinical trials, covering trial

design, organization and implementation, supervision, inspection, record registration,

analysis, making conclusion and report submission. Content of the document are organized

in the following chapters: General Principles; Terminologies and Definitions; Ethics

Committee; Investigators; Clinical Trial Organizers and Sponsors; Trial Program Design;

Investigator’s Brochure; Management of Required Dossier; Supplementary Provisions.

Effective Date

Jul 1 2020


ICH Guideline “Impurities: Guideline for

Residual Solvents Q3C(R8) ”on Apr.29,

202078

This ICH guideline is now in the third stage of regional regulatory consultation and

discussion. The CDE announces to collect opinion on the step 2b draft guideline on regional

level. Any suggestions and feedback should be submitted to CDE s contact email boxes

before the deadline for comments.

54




Regulatory Documents Including “Basic

Requirements and Review Key Points

Regarding Application Procedure and

Dossier for Re-registration of Domestically

Manufactured Drugs (Draft for Comments)”

on Apr.29, 202079

Following the NMPA announcement on the implementation of the newly released

“Regulations on Drug Registration”, the administrative authority has drafted these two

regulatory documents concerning re-registration application for domestically manufactured

drugs and drugs manufactured overseas. These two drafts are provided as Annex 1 and

Annex 2. Any suggestions and feedback should be submitted through the feedback form

provided as Annex 3 and sent to NMPA’s contact emails.


“M4 Module 1 Administrative Documents

and Drug Information” (Draft for

Comments) on Apr.29, 202080

The NMPA has decided to revise Module 1 of M4 CTD guidance document following

requirements established in the newly released “Regulations on Drug Registration”. The

draft of the revision is now released to invite public opinion. Any suggestions and feedback

should be submitted to the authority’s contact email box. The draft is provided as Annex.


“Basic Requirements for Drug Registration

Application Dossier (Draft for

Comments)”on Apr.29, 202081

This draft guidance document is issued as a follow up of NMPA announcement on the

implementation of the newly released “Regulations on Drug Registration” to further improve

the administrative procedure. Any suggestions and feedback on the draft should be

submitted through the feedback form provided as Annex 2 and sent to the authority s

contact email box. The draft guidance is provided as Annex 1.


“Technical Guidelines for Clinical Changes

to Already Marketed Drugs (Draft for

Comments)” on Apr.29, 202082

NMPA revised this draft guidance according to requirements established in the newly issued

“Regulations on Drug Registration”. The draft is now released to invite public review. All

suggestions and feedback should be submitted to the authority’s contact email before the

deadline. The draft guidance is provided as Annex.

NMPA Releases “List of Reference

Preparations for Generic Drugs (27th List)

on Apr.29, 202083

The 27th list of reference preparations for generic drugs has been given approval by the

Generic Drug Advisory Committee and now is announced to be released by NMPA. The list


NMPA Announces Public Consultation on 6

Regulatory Documents Including “Special

Regulations on the Administration of

The NMPA has issued the following six draft regulatory documents regarding the

administration and supervision of Chinese medicine registration and marketing: “Special

Regulations on the Administration of Chinese Medicine Registration”, “Classification System

55



Chinese Medicine Registration” on Apr. 29

202084

for Chinese Medicine Registration and Requirements for Application Dossier”, “Post-

approval Changes to Marketed Chinese Medicines and Requirements for Application

Dossier”, “Technical Guidelines for Researches Regarding Pharmaceutical Changes to

Already Marketed Chinese Medicines”, “Review Guidelines for the Acceptance of Chinese

Medicine Registration”, and “Review Guidelines for the Acceptance of Chinese Medicine

Post-approval Changes”. All these drafts are now released for public review. Any

suggestions and feedback can be submitted through the online portal, or through feedback

forms provided as Annex 12 then sent to corresponding contact person according to the

information sheet provided as Annex 13. An explanatory note is released for each draft for

further reference. All drafts and notes are provided as Annexes.


Regulatory Documents Including

“Classification System for Registration of

Chemical Drugs and Requirements for

Application Dossier” on Apr. 29 202085

Following the newly issued Regulations on Drug Registration, the NMPA has issued the

following five draft regulatory documents regarding the administration and supervision of

chemical drug registration and marketing approval: Classification System for Registration of

Chemical Drugs and Requirements for Application Dossier; Post-approval Changes to

Marketed Chemical Drugs and Requirements for Application Dossier; Technical Guidelines

for Researches Regarding Pharmaceutical Changes to Already Marketed Chemical Drugs;

Review Guidelines for the Acceptance of Chemical Drug Registration; Review Guidelines for

the Acceptance of Chemical Drugs Post-approval Changes. These drafts together with an

explanatory note for each are provided as Annexes. Any suggestions and feedback can be

submitted through feedback form provided as Annex 6 then sent to NMPA’s contact email

boxes.

NMPA Announces Public Consultation on 7

Regulatory Documents Including

“Classification System for Registration of

Biologic Products and Requirements for

Application Dossier (Draft for Comments)”

Following the newly issued “Regulations on Drug Registration”, the NMPA has issued the

seven draft regulatory documents regarding the administration and supervision of biological

product registration and marketing approval. They cover aspects of registration classification

system, post-approval changes, post-marketing researches on pharmaceutical changes,

56



On Apr. 29 202086 review guidelines for acceptance of application. These drafts together with an explanatory

note for issuance are provided as Annexes. Any suggestions and feedback can be

submitted through feedback form provided as Annex 9 then sent to NMPA’s contact email

boxes.


“Review Guidelines for the Acceptance of

Active Pharmaceutical Ingredient (API)

Registration” on Apr. 30 202087

These guidelines are drafted following requirements established in the newly issued

“Regulations on Drug Registration”. The draft is now released online to invite public opinion.

Any suggestions and feedback should be submitted through the feedback provided as

Annex 3 and sent to CDE’s contact email boxes. The draft together with an explanatory note

on its issuance are provided as Annex 1 and Annex 2.


“Administrative Measures for the

Communication on Drug R&D and

Technical Review (Draft for Comments)” on

Apr. 30 202088

CDE has drafted an updated version of these guidelines to meet new needs from the

industry for a more efficient and faster channel of communication with the administrative

authority during drug registration and review. This draft (provided as Annex) is now released

to invite public consultation. Any suggestions and feedback should be submitted through the

feedback form provided as Annex and sent to CDE s contact email box.


“Procedures for Review and Approval of

Drug Conditional Marketing Authorization

(Draft for Comments)” on Apr. 30 202089

These procedures are established to follow up the newly issued “Regulation of Drug

Registration” and as a revision of previous draft version. This draft is now released online to

invite public review. Any suggestion and feedbacks can be submitted through the feedback

from provided as Annex and sent to CDE s email box. The draft together with an

explanatory note to its issuance are also provided as Annexes.


“Regulations on Associated Review and

Approval of Pharmaceutical Active

Ingredients, Pharmaceutical Excipients,

Pharmaceutical Packaging Materials and

Drug Preparations (Draft for Comments)”

on Apr. 30 202090

These draft regulations are made according to requirements established in the newly issued

“Regulations on Drug Registration” and now are released online to invite public review. Any

suggestions and feedback should be submitted through the feedback form provided as

Annex and sent to CDE’s email box. The draft together with an explanatory note are also

provided as Annexes.

57




“Clinical Requirements for Drugs Listed

Overseas but Not Yet Marketed

Domestically” Apr. 30 202091

The administrative authority in China is in the process of accelerating the marketing of brand

name drugs and generic drugs that are already listed overseas in China. This guidance is

drafted to provide technical standard for the industry and regulators. It is now released

online to invite public opinion. Any suggestions and feedback should be submitted through

the annexed feedback form and sent to CDE’s contact email box. The draft guidance is also

provided as Annex.


“Technical Guidance on Clinical Trial

Imaging Endpoint Process Standards for

Anticancer Drugs (Draft for Comments)”

Apr. 22 202092

This draft guidance is issued to set up a standard process regarding the clinical trial imaging

endpoint for the R&D of anticancer drugs, aiming at further regulating industrial standard

and establishing technical requirements. Any suggestions and feedback should be

submitted through the Feedback Form and sent to CDE s contact email boxes. The form,

the draft guidance and an explanatory note are provided as Annexes.


“Guideline on the Submission of Clinical

Trial Data (Draft for Public Review)” on May

6, 202093

This guideline is drafted to further standardize the procedure of drug clinical trial data

submission. Now the draft is released online to invite public opinions. Any suggestions and

feedback should be submitted to CDE’s contact email boxes. The draft guideline together

with an explanatory note to its issuance are provided as Annexes.

CDE Releases “Technical Guideline for

Studies of Nitrosamine Impurities in

Chemical Drugs (Interim)” on May 8, 202094

CDE Releases “Technical Guideline for Studies of Nitrosamine Impurities in Chemical Drugs

(Interim)”


“Technical Guidelines on Preparing Safety

Data Submission for Innovative Anti-Tumor

Drug Marketing Application (Draft for

Comments)” on May 9, 202095

These guidelines are intended to provide instructions on the organization, analysis and

summarizing of safety data for innovative anti-tumor drugs that are under applications to be

marketed for the first time. The document gives specific guidance and explanations on data

source; standardization of data presentation and suggestions for adverse reaction

determination; and suggestions for preparing the safety data dossier.

https://syneoshealth.tarius.com/RegionTopic/ShowDocument?id=%7b470F4FBA-8A3D-4266-BF8E-71C171D0B6FC%7d




https://syneoshealth.tarius.com/Documents/ShowDocument?id=%7bD0919358-B423-4DD1-BCFE-C0EDE9F7A53F%7d&freetext=innovative%20anti-tumor%20drugs%22





58



NMPA Circular on Requiring Quality and

Efficacy Consistency Evaluation of Generic

Injectable Drugs on May 12, 202096

This circular is issued to inform drug marketing authorization holders (MAHs) of NMPA’s

requirements for quality and efficacy consistency evaluations of generic injectable drugs.

For products that are already marketed but have not been reviewed according to principles

of consistency evaluation, the MAH is required to carry out this activity and submit the

application for authority’s review following administrative procedure of “supplementary

application”.


“Guideline on Adaptive Designs for Clinical

Trials (Draft for Public Review)” on May 13,

202097

This guideline focuses on the important concepts and principles for adaptive designs in

clinical trials, primarily on the use of adaptive designs in confirmatory clinical trials of

chemical drugs, biological products and traditional Chinese medicines, although the

concepts are also relevant for exploratory studies. It provides guidance to sponsors and

applicants submitting investigational new drug applications, new drug applications, biologics

licensing applications, or supplemental applications on whether and/or how to appropriately

use adaptive designs for clinical trials. Some commonly used adaptive designs will be

discussed from a regulatory perspective, including recommendations for the sponsor to

consider and some specific requirements.


“Management System for Drug Clinical

Trial Registration and Information

Communication” and “Provisions on

Requirements and Management of

Development Safety Update Report” on

Nov 8, 201998

These two regulatory documents are issued to meet new requirements established in

relevant regulations: After the application of conducting clinical trials is approved for a drug,

applicants are required to register and update information of the trials as well as submit the

development safety update reports. These two drafts are released for public consultation

until November 15 2019. Any suggestions and feedback should be sent to CDE’s contact

emails through the feedback from attached as second reference document before the

deadline for comments.

NIFDC Announces Public Consultation on

“Testing Procedures and Technical

Requirements for Drug Registration (Draft

for Comment)” on May 15, 202099

This regulatory decision is drafted as supportive document to the newly issued “Regulation

on Drug Registration” to reflect updated requirements concerning testing and inspection

required in drug registrations. The draft decision together with its annexes are now released

59



to invite public review and are provided as Annex 1. Any suggestions and feedback should

be submitted through the feedback form provided as Annex 3 and sent to NIFDC s contact

email box. An explanatory note to the issuance is provided as Annex 2.

NMPA Releases “Technical Review

Guideline for the Registration of Dengue

Virus Nucleic Acid Detection Reagents” on

May 14, 2020100

The administrative authority announces to release this technical review guideline expecting

to further improve the efficiency and quality of device registration. The guideline is provided

as Annex.

Technical Guidance for Using Real-World

Evidence to Support R&D and Regulatory

Review of Pediatric Drugs (Draft for

Comments) on May 18, 2020101

This guidance is drafted based on the practical needs of pediatric drug R&D and regulatory

review of China as well as the implementation of ICH E11 (R1). It focuses on major

considerations in using real-word evidence (RWE) to support pediatric drug R&D procedure,

which are applicable to pediatric drugs including chemical drugs, Chinese medicines and

biological products. The document includes content in the following sessions: Introduction;

basic considerations (applicable scope of RWE, application time of RWE; relations between

RWE and common clinical trials; cases of RWEs in supporting the R&D pediatric drugs; and

key aspects worth special attention.

NMPA Releases “Evaluation Guideline for

Raw Material Changes to Passive Medical

Devices” May 19, 2020102

The NMPA announces the issuance and publication of this guideline to further improve the

quality in device registration review and supervision. The guideline is provided as Annex.



Tocilizumab Injection Biosimilars (Draft for

Comments)” May 21, 2020103

Tocilizumab, sold under the brand name Actemra® and originally developed by Roche, is a

humanized igG1 monoclonal antibody against the human interleukin-6 (IL-6) receptor

produced in Chinese hamster ovary (CHO) cells by recombinant DNA technology. Currently

many companies of China and overseas have initiated the development of tocilizumab

Injection biosimilars, and this draft guidance is issued expecting to provide technical

reference for clinical researches of this aspect. Now the draft is released online to invite

public opinion. Any feedback and suggestions should be submitted through the attached

60



feedback form and sent to CDE’s contact email boxes. The draft guidance, feedback form

and an explanatory note are provided as Annexes.


“Technical Guidance for Communications

on Clinical Aspects Before the Initiation of

Key Experiments During the Registration

of Innovative Anticancer Drugs Supported

by Single Arm Trials (Draft for Comments)”

May 22, 2020104

This draft guidance is issued to encourage drug innovation facilitate the communication of

technical issues between applicants and regulatory authority during the R&D of innovative

anticancer drugs supported by single arm trials. This guidance does not apply to cell therapy

and gene therapy products. Now it is released online to invite public review. Any

suggestions and feedback should be submitted through the attached feedback form and

sent to CDE s contact email boxes. The draft together with an explanatory note to its

issuance are provided as Annexes.

CFDI Announces Public Consultation on

Two Regulatory Documents Including

“Regulations on Implementation Principles

and Procedures of Drug Registration

Inspections (Draft for Comments)” May 22,

2020105

CFDI has drafted these two regulatory documents as supportive documents to the newly

issued Regulation on Drug Registration, specifying general principles, administrative

procedures, timing and requirements for drug inspections during registration; Regulations on

Implementation Principles and Procedures of Drug Registration Inspections; Key Points and

Determination Principles for Drug Registration Inspections. These drafts are now released to

invite public review. Any suggestions and feedback should be submitted through the

attached feedback form and sent to CFDI contact email box. Draft documents, together with

an explanatory note to the issuance and the feedback form are provided as Annexes.

CDE Notice on Gradually Restoring Office

Administrative Services May 22, 2020106

This notice is issued to inform the public that CDE’s administrative services provided in

office that were suspended during the Covid-19 pandemic are partially restored from May 25

2020. The office for dossier submission and pick-up is opened, while on-site consultation

and information service are still suspended. Meanwhile, document submission and

administrative procedures are still encouraged to be carried out through postal service

channel. Visitors to CDE office are required to make appointment in advance by registering

their health information in the form provided as Annex and sending it to CDE’s email box.

61



CDE Releases “Guidance on Clinical Trial

Design for Biosimilars of Liraglutide

Injections”on May 28, 2020107

CDE Releases “Guidance on Clinical Trial Design for Biosimilars of Liraglutide Injections”

CDE releases this guidance after the official approval, expecting to give technical guidance

for the R&D of liraglutide injection biosimilars. The guidance together with an explanatory

note to its issuance are provided as Annexes.


Preparations for Generic Drugs (28th List)”

on May 28, 2020108





“Technical Requirements Concerning

Common Pharmaceutical Issues in

Application for Phase I Clinical Trials of

Innovative Chemical Drugs (Draft for

Comments)” and “Summary Table for

Information of Pharmaceutical Researches

Related to Application for Phase I Clinical

Trials of Innovative Chemical Drugs

(Revised Version)” on June 1, 2020109

Aiming at encouraging the R&D of new drugs and providing technical reference for common

pharmaceutical issues concerning drug safety that constantly occur during the application

for phase I clinical trials of innovative drugs, the CDE has drafted the Technical

Requirement document and proposed a revision on the “Summary Table for Information of

Pharmaceutical Researches Related to Application for Phase I Clinical Trials of Innovative

Chemical Drugs”, which is the annex part of “Technical Guidance on Phase I New Drugs

Registration” released by the former CFDA in 2018. These two drafts together with an

explanatory note to the issuance and the feedback form are provided as Annexes. Any

suggestions and feedback should be submitted through the feedback form to CDE s email

addresses.

CMDE Circular on Further Regulating the

Procedure of Acceptance and Filing

Review for Medical Device Registration on

June 5, 2020110

The CMDE has this issued this circular to inform device registration applicants of

supplementary requirements related to filing review procedures: In case of lack of

documents in the application dossier, the CMDE will issue a letter with comprehensive

information and applicants should make one single supplementary/corrective submission;

supplementary/correction submission should be made as associated submission to the

initial submission; the regulatory authority will include advices on technical review in the

feedback given for filing review.

https://syneoshealth.tarius.com/RegionTopic/ShowDocument?id=%7bA301608D-EAC4-4278-ACCB-5272C24BB6E8%7d



62



CMDE Circular Concerning Imported

Medical Device Applying for Registration

as Class II Device but Categorized Under

Class III After Technical Review:

Registration Application Withdrawal and

Follow-up Procedures on June 5, 2020111

The CMDE has noted numerous cases in regulatory review of imported device registration

applications that many devices categorized as class II by applicants in submission are

designated as class III device after the technical review by the authority. These applications

with error in classification are required to be withdrawn and re-submitted after correction.

This circular gives specific explanations on how to withdraw submitted application in this

case and how to make new submission after having received feedback from the

administrative authority.


“The Measures for record filing regulation

of Medical Representatives (Trial) (Draft for

Comments)” on June 5, 2020112

To implement the General office of the central committee of the communist party of China

and the General Office of the State Council about "The opinion on deepening the reform of

the review and approval system and encouraging the innovation of drugs and medical

devices ([2017] no. 42)”, to standardize the working behaviour of medical representatives,

NMPA organized to draft “The Measures for record filing regulation of Medical

Representatives (trial) (draft)". Now it is released online to invite public review. Please send

comments via email to [email protected] before June 19, 2020, with the subject line

"Feedback on Measures for record filing regulation of Medical Representatives".

CFDI Announces Public Consultation on

“Drug Safety Credit Record Management

System for Nonclinical Safety Evaluation

Research Institutes and Clinical Trial

Organizations (Draft for Comments)” on

June 5, 2020113

This regulatory document is drafted according to the Regulations for Drug Registration to

establish specific administrative measures for managing drug safety credit record in

nonclinical safety evaluation research institutes and clinical trial organizations. Any


sent to CFDI’s contact email box. The draft, together with an explanatory note and the

feedback form are provided as Annexes.


the “Guidance on Clinical Trial Design for

Biosimilars of Denosumab Injections

(Osteoporosis as Indications) (Draft for

Comments)” June 5, 2020114

Denosumab, sold under brand name Prolia® for the treatment of osteoporosis and originally

developed by Amgen, is a is a fully human monoclonal antibody directed against receptor

activator of nuclear factor-κB ligand (RANKL), which interferes with the formation, activation,

and survival of osteoclasts. Currently many companies of China and overseas have initiated

63



the development of denosumab Injection biosimilars, and this draft guidance is issued

expecting to provide technical reference for clinical researches of this aspect. Any


sent to CDE s contact email boxes. The draft guidance, together with an explanatory note

and the feedback form are provided as Annexes.


“Technical Guidance for Communications

Before Marketing Approval Application on

Clinical Aspects Concerning Innovative

Anticancer Drugs Supported by Single Arm

Trials (Draft for Comments)” on June 5,

2020115

This draft guidance is issued based on the “Technical Guidance for Communications on

Clinical Aspects Before the Initiation of Key Experiments During the Registration of

Innovative Anticancer Drugs Supported by Single Arm Trials (Draft for Comments)”, which is

intended to facilitate the communication of technical issues between applicants and

regulatory authority before the submission of marketing approval application. Any


sent to CDE s contact email boxes. The draft together with an explanatory note to its

issuance are provided as Annexes.

NMPA CDE Announces “The

Administrative Measures for External

Experts of CDE” and “The List of The First

Batch of CDE (No. 4 of 2020)” on June 5,

2020116

To protect drug approval science fair, give full play to the important role of experts in drug

registration evaluation decision, according to the State Council about “The opinion on the

reform of review and approval system of drugs and medical devices"(guo fa [2015] 44), the

General office of the central committee of the communist party of China and General Office

of the State Council about "The opinion on deepening the reform of the review and approval

system and encouraging the innovation of drugs and medical devices([2017] no. 42)”, and

drug administration relevant regulations of China, CDE has formulate “The Administrative

Measures for External Experts of CDE” (see appendix 1), and approved by NMPA, It is

hereby issued.

In accordance with the prescribed procedures, CDE has organized the selection of external

experts, and with the approval of the NMPA, hereby publish the list of the first batch of

external experts of CDE (see Annex 2). If there is any change in the expert information,

64



please inform CDE to update. CDE will continue to carry out external expert selection work,

specific issues will be announced later.

NMPA Releases “Guideline on

Management and Archiving of Required

Documentation for Drug Clinical Trials”

June 5, 2020117

Following requirements established in updated major regulations on drug administration, the

NMPA announces the issuance and release of this guideline expecting to provide technical

instructions on the management of drug clinical trial files. The guideline is provided as

Annex.


“Guideline on Pharmaceutical

Development of Medicines (Chemical

Drugs) for Paediatric Use (Draft for


The CDE has drafted this guideline expecting to promote and give instructions to the

development of paediatric medicines. Any suggestions and feedback should be submitted

through the feedback form attached and sent to CDE’s contact email box. The draft

guideline together with a note to its issuance and the feedback form are provided as Annex.


Preparations for Generic Drugs (29th List)”

June 16, 2020119




Circular on the Release of “General

Requirements for Biosafety of Vaccine

Manufacturing Sites” on June 18, 2020120

The circular jointly issued by 5 administrative authorities announces the establishment and

publication of the requirements for vaccine manufacturing biosafety, which are temporary

emergency requirements during the Covid-19 prevention and control. The requirement

document is provided as Annex



Modified New Chemical Drugs (Draft for


The CDE has drafted this guidance that particularly applies to the category of “modified new

drugs” specified in article 4 on the classification for drug registration in the newly issued

“Regulations for Drug Registration”. It is intended to explain the expected clinical

advantages of drugs under this category and how these advantages can be proved by

clinical trials. The draft guidance together with an explanatory note and a feedback form are

provided as Annexes. Any suggestions and feedback on the draft should be submitted

through the form and sent to CDE’s contact email addresses.

65




“Technical Guidance on Endpoints of

Clinical Trials for Advanced Hepatocellular

Carcinoma (Draft for Comments)” on June

24, 2020122

The CDE has drafted this guidance expecting to provide technical instructions and

suggestions in clinical research pathways and design for the R&D of drugs targeting

advanced hepatocellular carcinoma. The draft guidance, together with an explanatory note

and a feedback form are provided as Annexes. Any suggestions and feedback should be

submitted through the form and sent to the CDE’s contact email addresses.

NMPA Announces Launch of “Drug

Registration application software (2020

version)” on June 24, 2020123

According to the relevant requirements of the newly released Drug Registration Regulation,

drug registration applicants are required to download the drug registration application

software (Version 2020) in a timely manner from July 1, 2020.

Effective Date

Jul 1, 2020

CMDE Notice on Information Support

Service During July and August 2020:

Technical Consultation Before Medical

Device Registration Application on June

22, 2020124

CMDE releases this notice to inform the public regarding its consultation service available

during July and August of 2020 on medical device registration procedure before submitting

the application. Detailed information on related department and service available timetable

are provided in the notice. The arrangement of consultation service during Covid-19

outbreak will temporarily follow the circular No. CMDE2020/3, which is provided as “Related

Document”.


“Guidance on Designing Clinical Trials for

GnRH Agonists in the Treatment of

Advanced Prostate Cancer” on June 28,

2020125

The CDE has drafted this guidance to establish the technical standards, expecting to

provide instructions on the drug R&D process. The draft guidance together with an

explanatory note and a feedback form are provided as Annexes. Any suggestions and

feedback should be submitted through the form and sent to CDE’s contact email boxes.

CHP Circular on Implementing "Chinese

Pharmacopoeia Pharmaceutical Excipient

Monograph Guardianship Mechanism” on

June 17, 2020126

As follow-up measures to the newly issued Chinese Pharmacopeia Version 2020, this

“guardianship mechanism” is to be implemented on the administration of pharmaceutical

excipient standard monograph. The monograph of each pharmaceutical excipient included

in the Chinese Pharmacopeia will be assigned to a responsible “guardian” institute for drug

testing and control to guarantee its implementation. The “guardian” institute has the

66



following responsibilities: Providing technical consultation service regarding the application

of pharmacopeia standards; collecting feedback and opinions from the public on the current

pharmacopeia and staying updated with industrial development to coordinate in the

assessment and revision of pharmacopeia standards. The contact information of all

“guardian institutes” and their assigned responsible pharmaceutical excipients are provided

in the Annex.

NMPA Releases “Classification System for

Registration of Biologic Products and

Requirements for Application Dossier” on

June 29, 2020127

The guidance on classification of biologics and submission dossier for product registration is

issued following the new requirements established in the Regulations on Drug Registration.

Apart from announcing the release of this guidance, the circular also specifies the effective

date and requirements for transitional period. The guidance is provided as Annex.

NMPA Releases “Classification System for

Registration of Chemical Drugs and

Requirements or Application Dossier” on

June 29, 2020128

The guidance on classification of chemical drugs and submission dossier for product

registration is issued following the new requirements established in the Regulations on Drug

Registration. Apart from announcing the release of this guidance document, the circular also

specifies the effective date and requirements for transitional period. The guidance is

provided as Annex.

NMPA Circular on Updating Drug

Registration Fee Charging Standards on

June30, 2020129

The NMPA has issued two regulatory documents to reflect the decision of adjusting

administrative fees for drug registration: “Charging Standards for Drug Registration Fees”

and “Implementing Rules for Drug Registration Fees”. For drug registration application

accepted before July 1, 2020, applicants are required to make the payment within 15

working days from July 1 2020. Drug registration fee will be exempt for medicines targeting

the treatment and prevention of Covid19 during the pandemic.

NIFDC Circular on Releasing “Testing

Procedures and Technical Requirements

for Drug Registration (Interim) (Version

2020)” and Related Matters on July 1,

2020130

These requirements are established in line with the newly issued Regulations on Drug

Registration. The NIFDC circular stipulates measures on the implementation of these

requirements, covering aspects of applications submitted before the document issuance;

administrative timeline; registration standard reevaluation; testing reports for drugs and

biologics manufactured overseas; and communication channel with the authorities. The

67



“Testing Procedures and Technical Requirements for Drug Registration (Interim) (Version

2020)” is provided as Annex.

NMPA Releases “Revised Appendix to

Good Manufacturing Practice for Drugs

(2010 Revision) – Blood Products” June30,

2020131

The NMPA has revised the Good Manufacturing Practice of Blood Products according to

article 310 of GMP (2010 Revision). Now the new version of GMP- Blood Products is

released as supportive document to the GMP (2010 Revision). The new guidance is

provided as Annex.

The Chinese Pharmacopoeia Commission

Releases “Working Procedures for Drug

Generic Name Review and Approval” on

July 1, 2020132

Following the newly issued “Regulations for Drug Registration”, the Chinese Pharmacopoeia

Commission has issued a set of regulatory decision and guidance on the determination,

review and approval of generic names for innovative Chinese proprietary medicines,

chemical drugs and biological products. These documents apply to the review and approval

of drug generic names as part of certain marketing authorization applications. The decision

and guidance are provided as Annexes 1- 4.

NMPA and NHC Circular on Publishing

“Pharmacopoeia of the People’s Republic

of China (Edition 2020)” on June 24, 2020133

The Pharmacopoeia of China 2020 Edition has been reviewed and approved during the

plenary meeting of the 11th executive committee. The new pharmacopoeia will be effective

from December 30, 2020. Catalogue of 4 volumes that compose the pharmacopeia are

provided as Annexes.

M4 Module 1 Administrative Documents

and Drug Information on July 1, 2020134

CDE has revised the M4 Module 1 document following requirements established by newly

issued regulation on drug administration, drug registration and vaccine administration.

CDE Releases “Rules on Assessment and

Management of Safety Information During

Drug Clinical Trials (Interim)” on July 1,

2020135

The CDE has issued this regulatory document on administrative rules applying to safety

information management during drug clinical trials. These are supportive rules to the newly

released Regulations on Drug Registration. The document is provided as Annex.

CDE Releases “Administration Rules on

Development Safety Update Reports

(Interim)” on July 1, 2020136

The CDE has issued these administrative rules to regulate the creation and management of

“development safety update reports (DSUR)” following the requirements established in the

new Regulations on Drug Registration. The regulation is provided as Annex.

68



CDE Releases “Administration Rules for

Drug Clinical Trial Registration and

Information Communication (Interim)” on

July 1, 2020137

The CDE has issued these administrative rules to regulate registration and information

communication concerning drug clinical trials following the requirements established in the

new Regulations on Drug Registration. The regulation is provided as Annex.

CDE Releases “Review Guidelines for the

Acceptance of Chemical Drug Registration

(Interim)” on July 2, 2020138

The CDE has issued these guidelines on authority’s acceptance of chemical drug

registration applications. The guidelines include two parts: Part I applies to drugs under

category 1,2 and 5,1 according to registration classification system; Part I applies to drugs

under category 3, 4 and 5,2. Each part is a separate guideline, and they are provided as

Annex 1 and Annex 2.

CDE Releases “Guidelines for the

Acceptance of Biological Product

Registration” on July 2, 2020139

The CDE has issued these interim guidelines on authority’s review and acceptance of

biological product registration applications. The guidelines include three parts: Part I applies

preventive biological products; Part II applies to therapeutic biological products; and Part III

applies to IVDs that are regulated as biologics. Each part is a separate guideline and is

provided as Annex 1, Annex 2 and Annex3.


“General Format and Guidance for

Preparing Drug Technical Documents:

‘Manufacturing Process’, ‘Quality

Standards’ and ‘Package Insert’ (Drafts for

Comments)” on July 6, 2020140

Following the new Regulations of Drug Registrations, the CDE has drafted a set of guidance

documents on the preparation of drug registration application dossier concerning

“manufacturing process”, “Quality Standards” and “Package Inserts” of Chinese medicines,

chemical drugs and biological products. All these draft guidance documents, together with

corresponding explanatory notes and a feedback form are provided as Annexes. Any

suggestions and feedback should be submitted through the form and sent to CDE’s contact

email boxes.


“Technical Guideline on Clinical Trials for

Immune Cell Therapy Products (Draft for


The CDE has drafted this guideline as part of technical review system for cellular and gene

therapy products, expecting to provide instructions and reference for drug registration

applicants in product R&D. The draft guideline, together with an explanatory and a feedback

form are provided as Annexes. Any suggestions and feedback should be submitted through

the form and sent to CDE s contact email boxes.

69



The NMPA Releases Three Regulatory

Documents Including “Working Procedure

for Review and Approval of Breakthrough

Therapy Designated Drugs (Interim)” on

July 7, 2020142

The NMPA has issued and released the following three interim regulatory decisions

regarding drug prioritized and conditional review and approval as supportive measures to

the implementation of the new Regulations of Drug Registration: “Working Procedure for the

Review and Approval of Breakthrough Therapy Designated Drugs”, “Working Procedure for

Drug Conditional Marketing Authorization Application, Review and Approval” and “Working

Procedure for Drug Prioritized Marketing Authorization Review and Approval”. All three

decisions are provided as Annexes.

CDE Notice on New Version of Drug

Clinical Trial Registration and Information

Release Platform System on July 10,

2020143

The CDE informs that its “Drug Clinical Trial Registration and Information Release Platform

System” has completed the process of update and improvement. A new version is launched

and has started to operate. The new system can be accessed with the same user account

as the one used for “applicant’s window”, but a procedure of account connection is needed.

The notice also provides contact information of CDE for technical support regarding the new

system.

CDE Releases “Drug Registration

Application Dossier Format, Stylistic Rules

and Layout Standards” on July 8, 2020144

The CDE has issued and released these set of rules and standards as supportive document

to the new Regulations of Drug Registration. The regulatory document is provided as Annex.

CDE Releases “Guideline for Management

of Drug Clinical Trials During the Covid-19

Outbreak (Interim)” on July 14, 2020145

This interim guidance is issued to standardize drug clinical trials during the Covid-19

pandemic, aiming to provide safety management measures. The guidance is provided as

Annex.

CDE announces Public Consultation on

“Technical Guideline for Pharmaceutical

Changes to Innovative Drugs (Chemical

Drugs) During Clinical Trials (Draft for


The CDE has drafted this guideline as supportive document to the new Regulations on Drug

Registration. The draft guideline together with an explanatory note and the feedback form

are provided as Annexes. Any suggestions and feedback should be submitted through the

form and sent to CDE’s contact email box.



The CDE has drafted this guidance expecting to provide technical instructions for efficient

R&D of antineoplastic drugs applied in combination therapy. The draft guidance, together

70



Antineoplastic Drugs Used in Combination

Therapy” on July 17, 2020147

with an explanatory note and feedback form, are provided as Annexes. Any suggestions and



“Guidance on Statistical Design in Clinical

Trials for Antineoplastic Drugs” on July 17,

2020148

This draft guidance is issued to facilitate the understanding and application of statistical

design in clinical trials concerning the R&D of antineoplastic drugs. The draft guidance and

an explanatory note to its issuance are provided as Annexes. Any suggestions and

feedback should be submitted to CDE’s contact email addresses.

CDE Releases “Guideline on the

Submission of Clinical Trial Data (Interim)”

on July 20, 2020149

This guideline is issued to further standardize the procedure of drug clinical trial data

submission following the new requirements on drug registration application dossier. The

guideline is effective on October 1, 2020 for chemical drugs and biological products. Its

effective date for Chinese medicines will be explained in “Classification System for Chinese

Medicine Registration and Requirements for Application Dossier”.

The CDE Releases “Guidance for Clinical

Trials on Rituximab Biosimilars” on July

20, 2020150

The CDE has issued and released this guidance after public consultation, expecting to

provide a technical reference for conducting clinical researches on Rituximab biosimilars as

well as establish criteria regarding product technical review. The guidance is provided as

Annex.

CDE Releases “Guidance for Clinical Trials

on Trastuzumab Injection Biosimilars” on

July 20, 2020151

The CDE has issued and released this guidance after public consultation, expecting to

provide a technical reference for conducting clinical researches on developing trastuzumab

biosimilar. The guidance is provided as Annex

NMPA Announcement on Adoption of “ICH

E2C (R2) Guideline: Periodic Benefic-Risk

Evaluation Report (PBRER)” on July 17,

2020152

The NMPA announces that marketing authorization holders (MAHs) can submit periodic

safety update report following the ICH E2C (R2) guideline: Periodic Benefic-Risk Evaluation

Report (PBRER) since publication date of this announcement. Meanwhile, reports prepared

according to national regulations and guidelines are also accepted.

The Center for ADR Announces Public

Consultation on “Application Dossier and

Requirements for Switching Drugs from

Prescription to OTC Status (Revision Draft

for Comments)” on July 24, 2020153

The ADR has drafted this administrative regulation as a revised version on current

regulatory documents following new requirements established in the updated Drug

Administration Law and Regulations for Drug Registration. The draft together with an

explanatory note to its issuance and a feedback form are provided as Annexes. Any

https://syneoshealth.tarius.com/RegionTopic/ShowDocument?id=%7b3546710F-C616-4BAC-9890-8C6AEE9819D4%7d





71



suggestions and feedback should be submitted through the form and sent to the center’s

contact email box.

The CDE Releases “Guideline on Non-

Inferiority Clinical Trials for Drugs” on July

24, 2020154

The CDE releases this guideline after public consultation to give instructions to sponsor in

understanding, implementing and evaluation non-inferiority clinical for drugs. The guideline


NMPA Opinions on Further Improving the

Quality and Capacity of Adverse Event

Monitoring System for Medical Products on

July 28, 2020155

This policy paper describes NMPA’s five-year plan on strengthening adverse event

monitoring system for drug and medical device through a series of measures concerning a

comprehensive and efficient administrative and regulatory framework; more professional

personnel; an updated monitoring system featuring multichannel for reporting, advanced

function of data analysis and efficient tracking mechanism; and extended international

collaboration. The paper further specifies authority’s action plan on each aspect.

The CDE Announces Public Consultation

on “Technical Guideline for

Pharmaceutical Researches on

Transdermal Patch Generics (Draft for


The CDE has drafted this guideline to specify research considerations and technical

requirements for generics of transdermal patches, which is intended to provide instructions

for registration applicants in product R&D. The draft guideline, together with an explanatory

note to its issuance and a feedback form are attached as Annexes. Any suggestions and

feedback should be submitted through the form to CDE s contact email boxes.

CDE Announces Public Consultation on 4

Technical Guidance Including “Technical

Guidance on Clinical Trials of Antibacterial

Drugs for the Treatment of Complicated

Urinary Tract Infection” on July 31, 2020157

The CDE has drafted 4 technical guidance on clinical trials for antibacterial drugs for the

treatment of uncomplicate urinary tract infection, complicated intra-abdominal infection,

complicated urinary tract infection, and hospital-acquired bacterial pneumonia/ventilator-

associated bacterial pneumonia. All 4 draft guidance together with their corresponding

feedback forms are provided as Annexes. Any suggestions and feedback should be

submitted through the forms and sent to CDE’s contact email boxes.


“Administrative Measures for Post-

Marketing Changes to Drug (Interim) (Draft

for Comments)” on July 31, 2020158

The NMPA has drafted these regulations to further strengthen the administration of post-

marketing changes made to drugs and highlight the responsibility of marketing authorization

holders (MAHs). The draft together with a feedback form are provided as Annexes. Any

suggestions and feedback should be submitted through the form and sent to NMPA’s

contact email box.

https://syneoshealth.tarius.com/RegionTopic/ShowDocument?id=%7b8495C4D1-0F63-4060-8337-0D112F6CE2FB%7d

https://syneoshealth.tarius.com/RegionTopic/ShowDocument?id=%7b8495C4D1-0F63-4060-8337-0D112F6CE2FB%7d

https://syneoshealth.tarius.com/RegionTopic/ShowDocument?id=%7bB09CB3D3-F6A2-40A7-AF19-9496D7C92CCD%7d





https://syneoshealth.tarius.com/RegionTopic/ShowDocument?id=%7bB3D1FCF1-7607-4878-A32B-6457C4A99EC0%7d




72




“Interim Regulations for Local Agents of

Overseas Drug Marketing Authorization

Holders (Draft for Comments)” on Aug. 3,

2020159

The NMPA has drafted these interim regulations to strengthen the administration on

activities related to local agents appointed by overseas marketing authorization holders

(MAHs). The draft regulations are provided as Annex. Any suggestions and feedback should

be submitted to the authority s contact email box.


“Guidance on Real World Data Used to

Generate Real World Evidence (Draft for

Comments)” on Aug. 3, 2020160

The CDE has drafted this guidance to provide technical suggestions for clinical researches

of therapeutic protein drugs. The draft guidance together with an explanatory note and

feedback form are provided as Annexes. Any suggestions and feedback should be

submitted through the form and sent to CDE s contact email boxes.


on Bevacizumab Injection Biosimilars”

on Aug. 3, 2020161

The CDE has issued and published this guidance after public consultation to provide

technical reference for conducting clinical researches on developing bevacizumab

biosimilars. The guidance is provided as Annex


on Adalimumab Injection Biosimilars”

on Aug. 3, 2020162

The CDE has issued and published this guidance after public consultation to provide

technical reference for conducting clinical researches on Adalimumab biosimilars. The

guidance is provided as Annex.

Technical Guidance on Pharmacokinetic

Research of Therapeutic Protein Drugs

(Draft for Comments) on Aug. 3, 2020163

This guidance applies to the clinical R&D of therapeutic protein drugs, particularly focusing

on the differences in pharmacokinetics (PK) between therapeutic protein drugs and common

small molecule drugs. It is intended to specify key considerations in PK studies and propose

suggestions in research plan design. Content of the guidance is structured in general

introductions, aspects of PK research and bioanalysis.


“Technical Guidance on Bioequivalence

Studies of Drugs with Narrow Therapeutic

Index (Draft for Comments)” on Aug. 3,

2020164

The CDE has drafted this guidance expecting to provide technical suggestions on

bioequivalence studies of narrow therapeutic index drugs with pharmacokinetic parameters

as the primary. The draft guidance together with an explanatory note and feedback form are

attached as Annexes. Any suggestions and feedback should be submitted through the form

and sent to CDE s contact email boxes.

https://syneoshealth.tarius.com/RegionTopic/ShowDocument?id=%7bCB078498-32C3-4891-AA17-07D49E043E40%7d




https://syneoshealth.tarius.com/RegionTopic/ShowDocument?id=%7bC60F76BE-9A55-4307-AB5E-D46EB309BEF4%7d




https://syneoshealth.tarius.com/RegionTopic/ShowDocument?id=%7b5968D87A-8294-4A99-A34F-9FB20654046D%7d

https://syneoshealth.tarius.com/RegionTopic/ShowDocument?id=%7b5968D87A-8294-4A99-A34F-9FB20654046D%7d

https://syneoshealth.tarius.com/RegionTopic/ShowDocument?id=%7b48A434B7-63E0-40BF-8319-2E95C815A8CF%7d

https://syneoshealth.tarius.com/RegionTopic/ShowDocument?id=%7b48A434B7-63E0-40BF-8319-2E95C815A8CF%7d

https://syneoshealth.tarius.com/RegionTopic/ShowDocument?id=%7bCB7BF332-CB2A-4610-BC76-A0170E5DB1FF%7d



https://syneoshealth.tarius.com/RegionTopic/ShowDocument?id=%7b6613B6D8-869C-4717-820C-2A2B013FFC53%7d




73




“Technical Guidance on Model-Informed

Drug Development (Draft for Comments)”

on Aug. 3, 2020165

The CDE has drafted this guidance expecting to provide technical suggestions on rational

application of model-informed drug development approach in R&D. The draft guidance

together with an explanatory note and feedback form are attached as Annexes. Any

suggestions and feedback should be submitted through the form and sent to CDE s contact

email boxes.


“Guidance on Research and Validation of

Aseptic Processing and Sterilization of

Injection Drugs” on Aug. 3, 2020166

The CDE has drafted this guidance expecting to provide technical suggestions on R&D and

regulatory review on injection drugs. The draft guidance together with an explanatory note

are provided as Annexes. Any feedback should be submitted to CDE s contact email boxes.

The CDE Under NMPA Releases “Record

Filing Procedures and Requirements for

Separated Packaging of Drugs

Manufactured Overseas” on Aug. 3, 2020167

The CDE has issued this regulatory document following new requirements established in

Regulations on Drug Registration. The circular specifies the implementation of new

requirements of record filing for separated packaging of overseas produced drugs before

and after the Regulations on Drug Registration takes effective. The document is provided as

Annex.

NHSA Announces Public Consultation on

“2020 Working Plan of Adjusting Drug

Catalogue Covered by National Healthcare

(Draft for Comments)” on Aug. 3, 2020168

The National Healthcare Security Administration has drafted the 2020 working plan

regarding adjustments to drug reimbursement catalogue covered by the national healthcare

system and invites public review. According to the plan, western medicines, Chinese patent

drugs and herbal decoction pieces will be in the scope of adjustments. Drugs of urgent

clinical needs, generics, pediatric drugs and medicines for the treatment of Covid19 will be

included in the list. A detailed working procedure is also unveiled covering the whole

process of preparation of the catalogue, review and approval, issuing the list of drugs for

price negotiation, price negotiation and confirmation of the list. Any suggestions and

feedback to the draft should be submitted to NHSA s email box.


“Guidance on Clinical Trial Design for

Oncolytic viruses are a form of immunotherapy that uses viruses to infect and destroy

cancer cells, which has shown potentials to provide treatment for many types of malignant

https://syneoshealth.tarius.com/RegionTopic/ShowDocument?id=%7b42B5B5E8-BE63-4C94-AF77-854BDC3005FF%7d



https://syneoshealth.tarius.com/RegionTopic/ShowDocument?id=%7bC7DFBCA4-A237-46FF-9BD3-96D6F3AA3A95%7d




https://syneoshealth.tarius.com/RegionTopic/ShowDocument?id=%7b93B12AFA-0975-4AFE-B2F7-ED4231600921%7d




74



Oncolytic Virus- Based Drugs” (Draft for


tumors. The CDE has drafted this guidance expecting to give technical suggestions on

clinical design regarding oncolytic virus-based therapy and drugs. The guidance, an




“Technical Guidance on Clinical Trials of

Drugs for the Treatment of Lipid

Metabolism Disorders (Draft for


The CDE has drafted this guidance to provide technical suggestions to support the R&D of

drugs targeting lipid metabolism disorders. The draft guidance together with an explanatory

note and a feedback form are provided as Annexes. Any suggestions and feedback should

be submitted through the form and sent to CDE s contact email boxes.

CDE Notice: Public Consultation on “ICH

M7 Guideline: Assessment and Control of

DNA Reactive (Mutagenic) Impurities in

Pharmaceuticals to Limit Potential

Carcinogenic Risk. Questions and

Answers” and “M7 Q&A Support

Document” on Aug. 10, 2020170

This ICH guideline is now in step 3 for regulatory consultation and discussion. According to

the organization’s procedure requirement, CDE announces the launch of regional regulatory

consultation on these draft documents (step 2b) in China. Any suggestions or feedback can

be communicated in Chinese or English and submitted to CDE s contact email boxes.


“Technical Guidance on Similarity

Assessment and Indication Extrapolation

of Biosimilars (Draft for Comments)” on

Aug. 14, 2020171

The CDE has drafted this guidance to provide technical suggestions on the R&D and

regulatory review of biosimilars. The draft together with the feedback form are provided as

Annexes. Any suggestions and feedback should be submitted through the form and sent to

CDE s contact email boxes.

CDE Releases 5 Technical Guidelines

Including “Technical Guideline for

Research and Development of Preventive

Vaccines Against Covid-19 (Interim)” on

Aug. 14, 2020172

The CDE announces to release the following 5 technical guidelines to provide technical

standards concerning R&D of vaccines for the prevention and control of Covid-19 pandemic.

These guidelines cover aspects of vaccine R&D, pharmaceutical research on mRNA

vaccines, non-clinical effectiveness studies and evaluation and clinical evaluation. All 5

guidelines are provided as Annexes.

75



CDE Announces Public Consultation on 11

Technical Guidance Including “Technical

Guidance on Bioequivalence Study of

Olanzapine Orally Disintegrating Tablets”

on Aug. 19, 2020173

The CDE has drafted 11 technical guidance on bioequivalence study of the following

generics: Olanzapine Orally Disintegrating tablets, Abiraterone Acetate Tablets, Calcium

Acetate Tablets, Entecavir Tablets, Imatinib Mesylate Tablets, Carbamazepine Tablets,

Leflunomide Tablets, Rivaroxaban Tablets, Sacubitril Valsartan Sodium Tablets, Lanthanum

Carbonate Chewable Tablets, and Vildagliptin Tablets. All 11 draft guidance together with

their corresponding explanatory note to issuance and a feedback form are provided as

Annexes. Any suggestions and feedback should be submitted through the form and sent to

CDE s contact email box.


“Technical Guideline for Researches on

Generic Fulvestrant Injections (Draft for


The CDE has drafted this guideline to specify research plan and technical requirements for

generic fulvestrant injections. The draft guideline together with an explanator note and a

feedback for are provided as Annexes.


“Guidance on Adjusting for Covariates

Clinical Trials for Drugs” on Aug. 19,

2020175

The CDE has drafted this guidance expecting to facilitate the understanding and technical

requirements regarding the covariate adjustment during clinical trials for drugs. The draft

guidance together with a note to its issuance are provided as Annexes. Any suggestions

and feedback should be submitted to CDE’s contact email boxes.

CDE Notice on Issuing Electronic

Administrative Documents for APIs on

Aug. 20, 2020176

The CDE informs applicants that the electronic API registration system has finished

improvement and upgrading process. Administrative permits and other related documents

for APIs are issued in electronic version from now on and are available through “Applicant’s

Window”.



Influenza Antivirus Drugs (Draft for


The CDE has drafted this guidance based on “Clinical Trials Guidance on Influenza

Treatments” issued in 2012 to provide further technical instructions on drug R&D and

improve clinical accessibility for patients. The draft together with a feedback form are

provided as Annexes. Any suggestions and feedback should be submitted through the form

and sent to CDE’s contact email boxes.


“Technical Guidance on Clinical

The CDE has drafted this guidance expecting to give technical suggestions on R&D and

evaluation of medicines for the treatment and control of myopia progression. The draft

76



Investigations Concerning Medicines for

the Control of Myopia Progression” on

Aug. 24, 2020178

guidance and a feedback form are provided as Annexes. Any suggestions and feedback

should be submitted through the form and sent to CDE s contact email boxes.



Human Stem Cell Based Therapeutic

Products and Their Derivatives (Draft for


The CDE has drafted this guidance as part of its plan for establishing the regulatory review

framework for cell and gene therapy products. The draft guideline, an explanatory note to its

issuance and a feedback form are provided as Annexes. Any suggestions and feedback

should be submitted through the form and sent to CDE’s contact email boxes.


“Technical Guidance on Drug

Immunogenicity Studies (Draft for


Facing the increasing development of therapeutic protein drugs, the CDE has drafted this

guidance to provide technical suggestions to immunogenicity studies during drug R&D.

The draft guidance and an explanatory note to its issuance are provided as Annexes. Any

suggestions and feedback should be submitted to CDE’s contact email boxes.

CDE Releases “List of Chemical Drugs of

Specific Clinical for Which Reference

Preparations Cannot Be Recommended

(1st List)” for Public Review on Aug. 24,

2020181

The CDE has drafted this list following NMPA’s Circular on Requiring Quality and Efficacy

Consistency Evaluation of Generic Injectable Drugs and now publishes it online to invite

public review. The list and a feedback form are provided as Annexes. Any suggestions and



“Technical Guideline for Nonclinical

Studies of Diagnostic

Radiopharmaceuticals (Draft for


The CDE has drafted this guidance to support and regulate the R&D of diagnostic

radiopharmaceuticals in China. The draft guidance together with an explanatory note to its





Omalizumab Injection Biosimilars (Draft for


Omalizumab is a recombinant, humanized, monoclonal antibody against human

immunoglobulin E (IgE). Currently the R&D of omalizumab biosimilars has been initiated by

several manufacturers. This draft guidance is intended to provide technical reference for

conducting clinical researches on developing omalizumab biosimilars and is now released

online to invite public opinion. The draft guidance together with an explanatory note to its

77





CDE Releases “Technical Guidance for

Using Real-World Evidence to Support

R&D and Regulatory Review of Pediatric

Drugs (Interim)” on Aug. 27, 2020184

The CDE has issued this guidance to assist researchers in understanding the application of

real-world evidence in the R&D and clinical trials concerning pediatric drugs after the public

consultation on the draft. The guidance is provided as Annex.


“Guidance on Enrichment Strategies and

Design for Drug Clinical Trials (Draft for


The CDE has drafted this guidance expecting to facilitate more accurate definition of target

population for drug clinical trials as well as to improve the efficiency. The draft guidance and

an explanatory note to its issuance are provided as Annexes. Any suggestions and

feedback should be submitted to CDE’s contact email boxes.

CDE Releases “Technical Guideline for

Testing Minimal Residual Disease During

Clinical Trials of Drugs for Acute

Lymphoblastic Leukemia” on Aug. 28,

2020186

The CDE has issued this guideline after public consultation on the draft expecting to provide

technical standard for industry regarding the application of minimal residual disease (MRD)

as an important biomarker to measure effectiveness of treatment during the R&D of drugs

for Acute lymphoblastic leukemia (ALL). The guideline is provided as Annex.


“Guideline for Subgroup Analyses in

Clinical Trials for Drugs (Draft for


The CDE has drafted this guideline expecting to provide technical advices on exploring

efficacy and safety differences in patients of different characteristics during clinical trials and

evaluating the risk-benefit of subgroups. The draft guideline and an explanatory note are

provided as Annexes. Any suggestions and feedback should be submitted to the CDE’s

contact email boxes.


“Guidance on Clinical Pharmacology

Studies for Pediatric Drug Development”

(Draft for Comments)” on Sep. 1, 2020188

The CDE has drafted this guideline to clarify technical requirements for clinical

pharmacology considerations during pediatric drug R&D. The draft together with an


suggestions and feedback should be submitted through the form to CDE’s contact email

box.


“Guidance on Clinical Trial Design for

Oncolytic viruses are a form of immunotherapy that uses viruses to infect and destroy

cancer cells, which has shown potentials to provide treatment for many types of malignant

78



Oncolytic Virus- Based Drugs” (Draft for


tumors. The CDE has drafted this guidance expecting to give technical suggestions on

clinical design regarding oncolytic virus-based therapy and drugs. The guidance, an



CDE Announce Public Consultation on


Medicines Treating Age-Related Macular

Degeneration” on Sep. 9, 2020190

The CDE has issued this guidance to give technical advices for the R&D of medicines for

the treatment of age-related macular degeneration (AMD). The guidance is provided as

Annex.


“Technical Guidance on Pharmaceutical

Research and Changes for Biologics

During Clinical Trial (Draft Published

Online for Comments)” on Sep. 10, 2020191

The CDE has draft this technical guidance expecting to specify requirements and provide

scientific advices for pharmaceutical researches and changes in this aspect concerning

biologic products during clinical trials. The draft guidance, an explanatory note to its



NMPA and National Intellectual Property

Administration Announce Public

Consultation on “Implementation Measures

Concerning Early Resolution Mechanism

for Drug Patent Disputes (Interim) (Draft for

Comments)” on Sep. 11, 2020192

This draft interim regulation is drafted jointly by two administrative authorities to set specific

measures towards the establishing of patent linkage mechanism. The draft regulation, an


suggestions and feedback


“Technical Guidance on Drug-Drug

Interaction Studies (Draft for Comments)”

on Sep. 11, 2020193

The CDE has drafted this guidance expecting to provide technical advices on designing

drug R&D strategies. The draft guidance, an explanatory note to its issuance and a

feedback form are provided as Annexes. Any suggestions and feedback should be

submitted through the form and sent to CDE’s contact email boxes.

79


Conclusions

The 2016 - 2019 reforms represent major changes for China’s regulatory environment and are expected

to better align the country with global regulatory norms by:

Reducing the IND (clinical trial) and NDA review timeline.

Strengthening the standards for generic drugs,

Reforming clinical trial data quality requirements and

Introducing a priority review process for innovative drugs,

Accelerate the registration speed for unmet medical needs.

NMPA (formerly CFDA) is clearly encouraging foreign sponsors and applicants to undertake global

studies in China and recommending that local clinical sites are part of global studies to help ensure

clinical trial data meet the requirements needed for China and for global registration. The clinical trial

reforms announced by NMPA will hopefully overcome some of the reluctance of foreign sponsors to

include China in global programs as the IND review timeline of 60 days mirrors that seen outside of

China.

It is anticipated that the new requirements for generic drug quality and efficacy evaluation and self-

inspection of clinical data will upgrade generic drug standards, clinical trial quality and clinical site GCP

compliance. It is acknowledged however that these new standards may also present some initial

challenges for generic pharmaceutical companies; however CROs should be able to advise, fill any

knowledge gaps and conduct required BE studies. This evolution is likely to provide a boost for China’s

CRO industry but it is likely that local CROs will face major hurdles as they attempt to enhance their own

quality processes in order to meet the NMPA’s stricter requirements. Sponsors will be motivated to use

reliable CROs with established standards to manage their trials and generate reliable data to meet

requirements and support approvals.

The reforms will undoubtedly benefit new drug innovators planning to conduct meaningful, scientific trials.

This should ensure that trial site resources are used more effectively on good quality research which will

have a long-term, positive impact for the Chinese pharmaceutical industry. The reforms will have a

profound and lasting impact on China’s pharmaceutical industry. It is likely some of the manufacturers

and their drugs will disappear over the next few years. However, there is a major incentive for innovative

local companies to progress their efforts in new drug development.

More reforms can be anticipated and indeed the Government has already laid out some of the plans for

2019 therefore it is essential that local China regulatory expertise is available to closely monitor these

changes and ensure accurate and timely communication to all relevant stakeholders. In addition, a robust

China regulatory strategy consultation or assessment will need to be prepared and agreed on much

earlier than before in order that Chinese activities can be effectively integrated into the global program

from the start.

80


On March 30, 2020, State Administration for Market Regulation (SAMR) announces “Regulations on Drug

Registration” and NMPA Announcement on Implementing “Regulations on Drug Registration”, to be

effective on July 1, 2020. The key features are set as below:

The 2020 DRR summarized the experience and stabilize the achievements of the reform of

review and approval system of drugs and medical devices, according to the State Council about

“The opinion on the reform of review and approval system of drugs and medical devices"(guo fa

[2015] 44), and the General office of the central committee of the communist party of China and

General Office of the State Council about "The opinion on deepening the reform of the review and

approval system and encouraging the innovation of drugs and medical devices([2017] no. 42)”.

The 2020 DRR optimize the management process to implement the reform requirements of

"delegating control and service".

In drug registration, through introduction of "60 working days IND review and approval, the drug

evaluation, registration inspection, testing carried out by "parallel" instead of "sequential", and set

start and finish time points and total timeline, further improve the efficiency of the review and the

applicant within the timeline for drug approval is expected.

The 2020 DRR take risk management as the principle, play precision management.

If safety problems or other risks are found during the drug clinical trial, the sponsor shall promptly

adjust the clinical trial protocol, suspend or terminate the clinical trial, and report to CDE;

Changes during clinical trials shall be evaluated for their impact on subject safety risks and shall

be reported in the safety update report during development or supplementary application shall be

submitted.

The 2020 DRR also consider how to maintain stable and highlight management attributes, at a

time new technologies, new production organization methods, new therapeutic and research

ideas are emerging. Therefore, the 2020 DRR is based on frame work and no appendix, while the

flexibility will be reflected in the accompanying guidelines and working procedures.

More than 50 accompanying guidelines and working procedures are planned, so far, there are 30

announced for public consultation. The plan is to be implemented in stages by the end of 2020.

81


References

1 https://www.pharmaceutical-technology.com/features/opening-chinese-drug-market/

2 https://www.trade.gov/topmarkets/pdf/Pharmaceuticals_China.pdf

3 http://www.nmpa.gov.cn/WS04/CL2182/299803.html

4 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=314402







11 http://www.gov.cn/xinwen/2017-10/08/content_5230105.htm




15 http://cpc.people.com.cn/n1/2018/1027/c419242-30366036.html





20 http://www.gov.cn/premier/2019-02/11/content_5364822.htm

21 http://www.nhfpc.gov.cn/yzygj/s7659/201902/3a8228589bf94e6d9356008763387cc4.sh

tml

22 http://www.cde.org.cn/newspic.do?method=view&id=314810

23 http://shs.ndrc.gov.cn/zcyj/200704/t20070420_130674.html

24 http://www.gov.cn/premier/2019-03/05/content_5370734.htm


26 https://www.cmde.org.cn/CL0004/19232.html




30 http://english.gov.cn/policies/latest_releases/2019/05/11/content_281476655091234.ht

m


32 http://www.nhc.gov.cn/yaozs/s3577/201905/80c7ad723b334fa187bb79cf371ea96f.shtm

l

33 http://www.gov.cn/zhengce/content/2019-06/10/content_5398829.htm





https://www.pharmaceutical-technology.com/features/opening-chinese-drug-market/

https://www.trade.gov/topmarkets/pdf/Pharmaceuticals_China.pdf





http://www.gov.cn/xinwen/2017-10/08/content_5230105.htm




http://cpc.people.com.cn/n1/2018/1027/c419242-30366036.html



http://www.gov.cn/premier/2019-02/11/content_5364822.htm

http://www.nhfpc.gov.cn/yzygj/s7659/201902/3a8228589bf94e6d9356008763387cc4.shtml

http://www.nhfpc.gov.cn/yzygj/s7659/201902/3a8228589bf94e6d9356008763387cc4.shtml

http://www.cde.org.cn/newspic.do?method=view&id=314810

http://shs.ndrc.gov.cn/zcyj/200704/t20070420_130674.html

http://www.gov.cn/premier/2019-03/05/content_5370734.htm


https://www.cmde.org.cn/CL0004/19232.html


http://www.cde.org.cn/news.do?method=viewInfoCommon&id=314862


http://english.gov.cn/policies/latest_releases/2019/05/11/content_281476655091234.htm

http://english.gov.cn/policies/latest_releases/2019/05/11/content_281476655091234.htm


http://www.nhc.gov.cn/yaozs/s3577/201905/80c7ad723b334fa187bb79cf371ea96f.shtml

http://www.nhc.gov.cn/yaozs/s3577/201905/80c7ad723b334fa187bb79cf371ea96f.shtml

http://www.gov.cn/zhengce/content/2019-06/10/content_5398829.htm





82






42 http://www.nhsa.gov.cn/art/2019/8/20/art_37_1666.html





47 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=314970;


48 http://www.cde.org.cn/news.do?method=largeInfo&id=314974

49 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=314972;

http://www.cde.org.cn/news.do?method=largeInfo&id=314965；

http://www.cde.org.cn/news.do?method=largeInfo&id=314973



52 http://www.nmpa.gov.cn/WS04/CL2050/371670.html?from=groupmessage&isappinstalled=

0

53 http://www.nmpa.gov.cn/WS04/CL2199/371671.html?from=singlemessage&isappinstall

ed=0

54 http://www.samr.gov.cn/hd/zjdc/201912/t20191210_309138.html


56 http://www.cdr-adr.org.cn/tzgg_home/201912/t20191231_47005.html




60 http://gkml.samr.gov.cn/nsjg/ggjgs/202002/W020200302287266175887.pdf




64 http://gkml.samr.gov.cn/nsjg/fgs/202003/t20200326_313464.html















http://www.nhsa.gov.cn/art/2019/8/20/art_37_1666.html




http://www.gov.cn/zhengce/content/2019-06/10/content_5398829.htm



http://www.cde.org.cn/news.do?method=largeInfo&id=314965

http://www.nmpa.gov.cn/WS04/CL2138/360014.htm

http://www.nmpa.gov.cn/WS04/CL2138/360015.htm

https://urldefense.com/v3/__http:/www.nmpa.gov.cn/WS04/CL2050/371670.html?from=groupmessage&isappinstalled=0__;!p2sQadyfD5s!ZRmSZvB_NSBUubv-uDbDrzYFmLBoK4cxIqLhgsmWnA3UA6-9t28Owq4daDpFed8kVDo$

https://urldefense.com/v3/__http:/www.nmpa.gov.cn/WS04/CL2050/371670.html?from=groupmessage&isappinstalled=0__;!p2sQadyfD5s!ZRmSZvB_NSBUubv-uDbDrzYFmLBoK4cxIqLhgsmWnA3UA6-9t28Owq4daDpFed8kVDo$

http://www.nmpa.gov.cn/WS04/CL2199/371671.html?from=singlemessage&isappinstalled=0

http://www.nmpa.gov.cn/WS04/CL2199/371671.html?from=singlemessage&isappinstalled=0

http://www.samr.gov.cn/hd/zjdc/201912/t20191210_309138.html



http://gkml.samr.gov.cn/nsjg/fgs/202003/t20200330_313670.html

http://gkml.samr.gov.cn/nsjg/fgs/202003/t20200330_313672.html







83


76 http://www.nhc.gov.cn/yaozs/s7655g/202004/f1cbe67ec7ef4c228ed2290946745d04.sht

ml























99 https://www.nifdc.org.cn/nifdc/zxgx/20200515102723648.html






105 http://www.cfdi.org.cn/resource/news/12320.html








113 http://www.cfdi.org.cn/resource/news/12399.html






















http://www.cfdi.org.cn/resource/news/12320.html






http://www.cfdi.org.cn/resource/news/12399.html





84





121 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=bdcf2b9693e63dbe

122 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=dbc7fe3f30d22975



125 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=1812c9b0e72d9467

126 http://www.chp.org.cn/gjydw/tz/15246.jhtml




130 https://www.nifdc.org.cn/nifdc/zxgx/20200701134238784.html


132 http://www.chp.org.cn/view/ff80808172917da7017309ac230c1725?a=tz


134 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=7e71bc17436bcafa

135 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=938b81c153eaf85e

136 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=3cad3925b893ab31

137 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=7315d8bd5b22d56b

138 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=cf49ee232197abb1

139 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=3aa9f3d2b7cd3df1

140 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=433a41fade014896

141 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=a8cbdcac9a105c3c


143 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=0ce613a6f78c7af2

144 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=4fcb14858a8d3037

145 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=52016e68a65b6161

146 http://www.cde.org.cn/news.do?method=largeInfo&id=ab0e48d661735cfe

147 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=5d938422a5c1c7e6

148 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=8c3d027173d2ac7c

149 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=7a43c3abfde95950

150 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=83c6963a54c47d8d

151 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=4a8adcac1fbf6ba3


153 http://www.cdr-adr.org.cn/tzgg_home/202007/t20200724_47652.html

154 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=31c0a47beeb92f8f

155 https://www.nmpa.gov.cn/xxgk/fgwj/gzwj/gzwjyp/20200731134330152.html

156 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=848a4df9067d6c66

157 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=d8081df6bbf2cb73

158 https://www.nmpa.gov.cn/xxgk/zhqyj/zhqyjyp/20200731191306178.html

159 https://www.nmpa.gov.cn/xxgk/zhqyj/zhqyjyp/20200803190645124.html

160 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=6daa3c4fa676021c





https://www.nifdc.org.cn/nifdc/zxgx/20200701134238784.html

http://www.cde.org.cn/news.do?method=viewInfoCommon&id=3cad3925b893ab31

http://www.cde.org.cn/news.do?method=viewInfoCommon&id=7315d8bd5b22d56b

http://www.cde.org.cn/news.do?method=viewInfoCommon&id=cf49ee232197abb1

http://www.cde.org.cn/news.do?method=viewInfoCommon&id=3aa9f3d2b7cd3df1


http://www.cde.org.cn/news.do?method=viewInfoCommon&id=4fcb14858a8d3037

http://www.cde.org.cn/news.do?method=viewInfoCommon&id=52016e68a65b6161

http://www.cde.org.cn/news.do?method=viewInfoCommon&id=52016e68a65b6161

http://www.cde.org.cn/news.do?method=largeInfo&id=ab0e48d661735c

http://www.cde.org.cn/news.do?method=viewInfoCommon&id=5d938422a5c1c7e6

http://www.cde.org.cn/news.do?method=viewInfoCommon&id=8c3d027173d2ac7c

http://www.cde.org.cn/news.do?method=viewInfoCommon&id=7a43c3abfde95950

http://www.cde.org.cn/news.do?method=viewInfoCommon&id=7a43c3abfde95950

http://www.cde.org.cn/news.do?method=viewInfoCommon&id=83c6963a54c47d8

http://www.nmpa.gov.cn/WS04/CL2138/378851.ht

http://www.cdr-adr.org.cn/tzgg_home/202007/t20200724_47652.ht

http://www.cde.org.cn/news.do?method=viewInfoCommon&id=31c0a47beeb92f8f

https://www.nmpa.gov.cn/xxgk/fgwj/gzwj/gzwjyp/20200731134330152.ht

http://www.cde.org.cn/news.do?method=viewInfoCommon&id=848a4df9067d6c66

http://www.cde.org.cn/news.do?method=viewInfoCommon&id=848a4df9067d6c66

http://www.cde.org.cn/news.do?method=viewInfoCommon&id=d8081df6bbf2cb73

https://www.nmpa.gov.cn/xxgk/zhqyj/zhqyjyp/20200803190645124.ht

http://www.cde.org.cn/news.do?method=viewInfoCommon&id=6daa3c4fa676021

85


161 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=d6ea44de804de759

162 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=c9d19a6d490b85db

163 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=2dd83af68add0c19

164 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=ac22bd0e8f49a0f9

165 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=00a31adbd9c46907

166 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=8fc5b92e50b285b1

167 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=b993f5cd86ec321e

168 http://www.nhsa.gov.cn/art/2020/8/3/art_48_3394.html

169 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=14239761d134c4ee

170 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=6422e134eb3f493a

171 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=b86dec18fe41c7db

172 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=137cd502f7584a3a

173 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=4a3f89bc989a72f4

174 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=7b212611a49f3ba7

175 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=12a99a6fd062ada9

176 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=f7583dea1bd8098f

177 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=b4561098310a44ca

178 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=a216c9465217ce2d

179 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=6cf5b4fbef3256d9

180 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=d92cbf7b3c5addea

181 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=443aff5cfcdde510

182 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=252d34af23b1cab3

183 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=1f3481c7c408e549

184 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=32199bb0bf19b635

185 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=be7daf80df7cd9a2

186 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=434faf0a06029b0b

187 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=9bc3c4eeab71cf7f

188 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=0d0e76f02b923a4c

189 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=18e2301313fa14dc

190 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=cb4aa5e5fae6af17

191 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=88a3ca8d643c1558

192 https://www.nmpa.gov.cn/xxgk/ggtg/qtggtg/20200911175627186.html

193 http://www.cde.org.cn/news.do?method=viewInfoCommon&id=a24d50a14e59b266

http://www.cde.org.cn/news.do?method=viewInfoCommon&id=d6ea44de804de759

http://www.cde.org.cn/news.do?method=viewInfoCommon&id=d6ea44de804de759

http://www.cde.org.cn/news.do?method=viewInfoCommon&id=c9d19a6d490b85

http://www.cde.org.cn/news.do?method=viewInfoCommon&id=2dd83af68add0c19

http://www.cde.org.cn/news.do?method=viewInfoCommon&id=2dd83af68add0c19

http://www.cde.org.cn/news.do?method=viewInfoCommon&id=00a31adbd9c46907

http://www.cde.org.cn/news.do?method=viewInfoCommon&id=00a31adbd9c46907

http://www.cde.org.cn/news.do?method=viewInfoCommon&id=b993f5cd86ec321

http://www.nhsa.gov.cn/art/2020/8/3/art_48_3394.html

http://www.cde.org.cn/news.do?method=viewInfoCommon&id=14239761d134c4ee

http://www.cde.org.cn/news.do?method=viewInfoCommon&id=4a3f89bc989a72f4

http://www.cde.org.cn/news.do?method=viewInfoCommon&id=7b212611a49f3ba7

http://www.cde.org.cn/news.do?method=viewInfoCommon&id=12a99a6fd062ada9

http://www.cde.org.cn/news.do?method=viewInfoCommon&id=f7583dea1bd8098f

http://www.cde.org.cn/news.do?method=viewInfoCommon&id=b4561098310a44ca

http://www.cde.org.cn/news.do?method=viewInfoCommon&id=a216c9465217ce2d

http://www.cde.org.cn/news.do?method=viewInfoCommon&id=6cf5b4fbef3256d9

http://www.cde.org.cn/news.do?method=viewInfoCommon&id=d92cbf7b3c5addea

http://www.cde.org.cn/news.do?method=viewInfoCommon&id=443aff5cfcdde510

http://www.cde.org.cn/news.do?method=viewInfoCommon&id=252d34af23b1cab3

http://www.cde.org.cn/news.do?method=viewInfoCommon&id=1f3481c7c408e549

http://www.cde.org.cn/news.do?method=viewInfoCommon&id=434faf0a06029b0b

http://www.cde.org.cn/news.do?method=viewInfoCommon&id=0d0e76f02b923a4c

http://www.cde.org.cn/news.do?method=viewInfoCommon&id=18e2301313fa14dc

http://www.cde.org.cn/news.do?method=viewInfoCommon&id=cb4aa5e5fae6af17

http://www.cde.org.cn/news.do?method=viewInfoCommon&id=88a3ca8d643c1558

https://www.nmpa.gov.cn/xxgk/ggtg/qtggtg/20200911175627186.html