Drug Registration in China

The revised Drug Registration Procedure was introduced on 10 July 2007, coming into effect on 1 October 2007, at which point some changes were made to the current practice, as there were loopholes in the previous regulations. The new regulation comprises 15 chapters with 177 articles, having previously been 16 chapters and 211 articles.

The main revisions to the regulations include provisions to:
- Strengthen the safety requirements for the drug.
- Specify the responsibility and strengthen the supervisory system.
- Increase registration standards and to encourage novel drug research.

In recognition of this major regulatory change in the ever-growing Chinese pharmaceutical market, URCH Publishing presents Drug Registration in China: A comprehensive overview of procedures, a 51,000 word report that clearly and comprehensibly provides a detailed overview of the procedures necessary to register a medicines in the Chinese market.

Starting with an explanation for the key changes to drug registration procedure in 2007 the 148 page report includes details on the new regulatory articles including:

• State Food and Drug Administration (SFDA)
• The openness policy and greater responsibilities of the SFDA
• Definition of re-registration and its procedures
• National economic policy
• Manufacturing process management
• Clinical trial supervision
• Dosage Form Change application requirements
• One-time submission of dossier
• More requirements of Drug Control Institute and CDE
• Clear responsibility for NICPBP during drug importation
• Drug name, packet insert and labels
• Non-approval of new drug application during re-consideration
• New penalty (fines and credit system)
• Situation to revoke the drug approval numbers.

This expert report contains:

• Full explanation of the drug registration procedure and regulations governing the process
• An outline of the major responsibilities the State Food and Drug Administration (SDFA)
• In-depth analysis of the regulations surrounding the drug registration for imported drugs.
• Comprehensive detail on applications for biologics, Chinese medicines, generics, imported medicines, OTCs, and supplementary products.
• Summary of requirements for the application material for Traditional Chinese Medicines and natural drugs

Who will benefit from this report?

• Foreign drug companies considering a market entry in China
• Individuals with an interest in understanding the latest Chinese regulations on application and approval for imported drug registration.
• Regulatory affairs professions with responsibility for China
• The report will also be an essential reference document for any company library.

1. GENERAL COMPARISION OF CHINA DRUG REGISTRATION PROCEDURES

• 1.1 Great expansion of the Chinese pharmaceutical industry
• 1.2 Increasing trend of multinational trials in China
• 1.3 SFDA and corruption
• 1.4 Series of large-scale serious adverse drug reactions (SADRs) occurring in recent years
• 1.5 The revision of Chinese drug registrations
  • 1.5.1 Temporary Drug Registration (2002)
  • 1.5.2 Drug Registration Procedure (2005)
  • 1.5.3 Drug Registration Procedure (2007)
• 1.6 Background on the revision of regulation in 2007
• 1.7 Amendment process
• 1.8 Significant changes
  • 1.8.1 Encouragement of novel drugs
    • 1.8.1.1 Change of fast-track review to special review.
    • 1.8.1.2 Decrease of the new drug scope.
    • 1.8.1.3 Separation of the New Drug Certificate from the New Drug Production Approval
    • 1.8.1.4 Change of drug application with national standard to generic drug application
  • 1.8.2 Continuous monitoring of drug safety
    • 1.8.2.1 Strengthening the responsibility of applicant on the drug quality.
    • 1.8.2.2 Strengthening the authenticity check of the submission documents & on-site GMP inspection
    • 1.8.2.3 Drug sampling changed from 'static' to 'dynamic'
  • 1.8.3 Punishment for the applicant for fake submission
    • 1.8.3.1 Fines
    • 1.8.3.2 The effect on the qualification of the applicant
    • 1.8.3.3 Credit system
  • 1.8.4 New system restriction for SFDA drug review process

2. MAIN CHANGES IN DRUG REGISTRATION PROCEDURES (2007)

• 2.1 Major changes
• 2.2 Details of the change
  • 2.2.1 The withdrawn articles
    • 2.2.1.1 Fasttrack for emergency use
    • 2.2.1.2 PDA responsibilities
    • 2.2.1.3 Situation for study termination by the SFDA
    • 2.2.1.4 Rejection of repeated new drug application
    • 2.2.1.5 Revocation of application due to unacceptable drug standard
    • 2.2.1.6 New Drug Technology Transfer
    • 2.2.1.7 Transfer of Temporary Drug Standards to Formal Standards
  • 2.2.2 New articles
    • 2.2.2.1 Openness policy, hearing meeting system and greater responsibilities of the SFDA
    • 2.2.2.2 Definition of re-registration and its procedures
    • 2.2.2.3 National economic policy
    • 2.2.2.4 Manufacturing process management
    • 2.2.2.5 Clinical trial supervision
    • 2.2.2.6 Dosage Form Change application requirements
    • 2.2.2.7 One-time submission of dossier
    • 2.2.2.8 More requirements of Drug Control Institute and CDE
    • 2.2.2.9 Clear responsibility for NICPBP during drug importation
    • 2.2.2.10 Drug name, packet insert and labels
    • 2.2.2.11 Non-approval of new drug application during re-consideration
    • 2.2.2.12 New penalty (fines and credit system)
    • 2.2.2.13 Situation to revoke the drug approval numbers
  • 2.2.3 Amended articles
    • 2.2.3.1 Change of fasttrack review to special review
    • 2.2.3.2 Expanded qualification of the applicant
    • 2.2.3.3 The enlarge scope of drug application
    • 2.2.3.4 Change of drug application with National Standards to generic drug application
    • 2.2.3.5 Simplification of management in patent issue
    • 2.2.3.6 Clinical trial requirements
    • 2.2.3.7 No products will be sampled by PDA, except for biological product
    • 2.2.3.8 Certificate of Analysis (COA) test report will not copy to PDA
    • 2.2.3.9 Definition of supplementary application
    • 2.2.3.10 Imported drug supplementary application
    • 2.2.3.11 National drug standard
    • 2.2.3.12 Shorter timeline in clinical trial approval, and extended timeline to new drug production and generic drug application approvals

3. GENERAL REQUIREMENTS & APPLICATION PROCEDURES

• 3.1 National encouragement policy
• 3.2 Responsibilities of the SFDA and provincial drug administrations
• 3.3 Openness policy and hearing meeting system
• 3.4 Registration classification
• 3.5 The applicant qualification
• 3.6 To whom is the application submitted?
• 3.7 Submission documents requirements
• 3.8 Patent issue
• 3.9 Undisclosed data issue
• 3.10 Application procedures
  • 3.10.1 Drugs made in China
    • 3.10.1.1 Clinical trial application
    • 3.10.1.2 Drug production application
  • 3.10.2 Generic drug application approval
    • 3.10.2.1 Clinical trial application
    • 3.10.2.2 Prodution application
  • 3.10.3 Imported drug
    • 3.10.3.1 Clinical Trial application
    • 3.10.3.2 Importation application
  • 3.10.4 Supplementary application of drugs made in China
    • 3.10.4.1 Clinical trial application
    • 3.10.4.2 Production application
  • 3.10.5 Supplementary application of imported drugs
    • 3.10.5.1 Clinical trial application
    • 3.10.5.2 Product registation application

4. DRUG RESEARCH AND REGISTRATION

• 4.1 Pre-clinical research
  • 4.1.1 Research contents
  • 4.1.2 Requirements of research institution
  • 4.1.3 Contracting research
  • 4.1.4 Research material of pre-clinical documents by a foreign drug research institution
  • 4.1.5 Repeat experiments
  • 4.1.6 Technology requirements
• 4.2 Clinical research
  • 4.2.1 Clinical trial requirements
  • 4.2.2 Clinical trial
    • 4.2.2.1 Phases of clinical trial
    • 4.2.2.2 Patient number requirement
    • 4.2.2.3 Exception
  • 4.2.3 Responsibilities of the applicant
  • 4.2.4 Responsibilities of principal investigator and participating institutions
  • 4.2.5 Suspension or cessation of the clinical trial
• 4.3 Special approval
• 4.4 New drug application
  • 4.4.1 Co-research for an application
  • 4.4.2 New drug application for drug dosage form change
  • 4.4.3 Dossier requirements if the ingredient is marketed in China or other countries
  • 4.4.4 No supplementary document is allowed during the SFDA review procedure
• 4.5 Approval of new drug clinical trial
  • 4.5.1 Withdrawal of application
• 4.6 Approval of new drug production
• 4.7 Drug specification
• 4.8 Management of drugs in monitoring period
  • 4.8.1 The establishment of the monitoring period
  • 4.8.2 Responsibility of the manufacturer of the monitored drugs
  • 4.8.3 Another trial has been approved when a drug is in monitoring period
  • 4.8.4 Another trial of application is submitted, but not approved yet
  • 4.8.5 Imported drug monitoring period
• 4.9 Investigational product
  • 4.9.1 The inspection of pilot drug
  • 4.9.2 Management of the pilot drug

5. IMPORTED DRUG REGISTRATION

• 5.1 The registration of imported drug
  • 5.1.1 Definition
  • 5.1.2 Applicant of the imported drug
  • 5.1.3 Application agent requirements
  • 5.1.4 Classification of imported drug
  • 5.1.6 To whom to apply?
  • 5.1.7 The approving procedure of imported drug
  • 5.1.8 Requirements for imported of chemical drugs
  • 5.1.9 Certificates
    • 5.1.9.1 GMP certificate
    • 5.1.9.2 Company certificate
    • 5.1.9.3 Patent certificate
  • 5.1.10 Certificate of the application agent
  • 5.1.11 Special requirements of packet insert of the imported drugs
  • 5.1.12 Clinical research approval procedure for imported drugs
  • 5.1.13 General clinical research rules for imported drug
    • 5.1.13.1 Clinical research rules and patient number requirements for imported chemical drugs
    • 5.1.13.2 Clinical trial rule for imported preventive bio-products
    • 5.1.13.3 Clinical trial rule for imported therapeutic bio-products
  • 5.1.14 Re-registration procedure for imported drugs
  • 5.1.15 Supplementary applications of imported drugs
    • 5.1.15.1 The approval procedure for supplementary applications
    • 5.1.15.2 The supplementary application classification for an imported drug
  • 5.1.16 Situations that will result in the non-approval of an imported drug
• 5.2 Repackaging of imported drugs
  • 5.2.1 Definition
  • 5.2.2 Regulatory requirements to approve the repackaging
  • 5.2.3 Procedure to apply for repackaging
  • 5.2.4 Drug standard and package insert sheet
  • 5.2.5 The responsibility of foreign companies
  • 5.2.6 Responsibilities undertaken by a foreign manufacturer
  • 5.2.7 Other relevant provisions
• 5.3 International multinational clinical trial

6. GENERIC DRUG APPLICATION AND SUPPLEMENTARY APPLICATION

• 6.1 Generic drug application
  • 6.1.1 Definition
  • 6.1.2 Barrier to submission of generic drug application is changed
    • 6.1.2.1 Approval timeline prolonged
    • 6.1.2.2 Technology requirement for simplified dosage formulation change is improved
    • 6.1.2.3 Technology requirement for generic drug application is improved
  • 6.1.3 How to submit the generic drug application
  • 6.1.4 Responsibility of the PDA
  • 6.1.5 Responsibility of the SFDA
  • 6.1.6 Generic drug that will be not approved
• 6.2 Supplementary application
  • 6.2.1 Definition
  • 6.2.2 How to submit supplementary application
  • 6.2.3 Classification of supplementary application
  • 6.2.4 Application procedures
  • 6.2.5 Approval of supplementary application
    • 6.2.5.1 Supplemental applications to be approved by SFDA
    • 6.2.5.2 Supplemental applications to be approved by PDA and be filed for record at SFDA, or directly be filed for record at SFDA
    • 6.2.5.3 Supplemental applications to be filed for record at PDA
  • 6.2.6 Approval conclusion: approval of supplementary application
  • 6.2.7 Imported drug supplementary application
  • 6.2.8 Other situations

7. OTC DRUG APPLICATION

• 7.1 Definition
• 7.2 Drugs that could be applied for as OTC during submission
• 7.3 Packet insert sheet and labelling
• 7.4 Imported drug to apply for an OTC

8. THE RE-REGISTRATION OF A DRUG

• 8.1 Law sources
• 8.2 Definition
• 8.3 Drugs needing re-registration
• 8.4 Time limit
• 8.5 Application process
• 8.6 The re-registration will not be accepted
• 8.7 The application material
  • 8.7.1 Drugs made in China
  • 8.7.2 Imported drugs

9. DRUG REGISTRATION INSPECTION

• 9.1 Drug registration inspection
• 9.2 Testing scope
• 9.3 Testing institution
• 9.4 Responsibilities of the applicant
• 9.5 The responsibilities of the drug inspection institution
• 9.6 Timeline

10. DRUG REGISTRATION STANDARDS, NAMING AND LABELLING

• 10.1 Drug registration standards
• 10.2 Drug standard substance
• 10.3 Drug name, packet insert sheets and labels

11. RECONSIDERATION OF DRUG REGISTRATION APPLICATION

• 11.1 Situations for non-approval by SFDA
• 11.2 Re-consideration procedure

12. LIABILITIES

• 12.1 Regulatory authority liabilites
  • 12.1.1 Liability 1
• 12.1. 2 Liability 2
  • 12.1.3 Liability 3
• 12.2 Applicant liabilities
  • 12.2.1 Fines
  • 12.2.2 The effect on the qualification of applicant
  • 12.2.3 Credit system
  • 12.2.4 Situations to revoke the drug approval number

13. THE APPLICATION MATERIAL REQUIREMENTS OF TCM AND NATURAL DRUGS

• 13.1 Registration categories and notes
  • 13.1.1 Registration categories
  • 13.1.2 Notes
• 13.2 Application information items and notes
  • 13.2.1 Application Information Items
  • 13.2.2 Notes
• 13.3 The application material table and its explanation for TCM and natural drugs
  • 13.3.1 Table of application information item for TCM and natural drugs

14. APPLICATION MATERIAL REQUIREMENTS FOR A CHEMICAL DRUG

• 14.1 Registration category
• 14.2 Application dossier items
  • 14.2.1 Summary
  • 14.2.2 Pharmaceutical data
  • 14.2.3 Pharmacology and toxicology study information
  • 14.2.4 Clinical study information
• 14.3 Notes to Application Information Items
• 14.4 Table of application information item and notes
  • 14.4.1 Table of application information item
  • 14.4.2 Notes
• 14.5 Requirement for clinical study
• 14.6 Requirement for am imported chemical drug
  • 14.6.1 Requirement of application information items
  • 14.6.2 Requirement and notes to Information Item 2, certified documents
  • 14.6.3 Requirement for the clinical study conducted in China
• 14.7 Application information and requirement for radioactive drugs
  • 14.7.1 Requirement of information items
  • 14.7.2 Notes to the information items
  • 14.7.3 Requirement of clinical study
  • 14.7.4 Definition

15. APPLICATION MATERIAL REQUIREMENTS FOR BIOLOGICAL PRODUCTS

• 15.1 Section 1 - therapeutic biological product
  • 15.1.1 Classification
  • 15.1.2 Application information items
  • 15.1.3 Requirement of the application information
    • 15.1.3.1 Table of Application Information Items for therapeutic biological products, (Information Items 1-15, 29-38)
    • 15.1.3.2 Table of Application Information Items for pharmacology and toxicology information for therapeutic biological product (Information Items 14-29)
  • 15.1.4 Notes to the application information
  • 15.1.5 Notes to the clinical study
  • 15.1.6 Application information and requirement for imported therapeutic biological products
    • 15.1.6.1 Requirement for application information items
    • 15.1.6.2 Requirement and notes to the Information Item 2, certified documents
    • 15.1.6.3 Requirement for other information items
    • 15.1.6.4 Requirements for clinical study conducted in China
• 15.2 Preventive biological products
  • 15.2.1 Registration categories
  • 15.2.2 Application Information Items
  • 15.2.3 Application information items table
  • 15.2.4 Notes to the Application Information Items
  • 15.2.5 Notes to the clinical study
  • 15.2.6 Application information and requirement for imported preventive biological products
    • 15.2.6.1 Requirement with information items
    • 15.2.6.2 Requirement and notes to the Information Item 1 (ii), certified documents
    • 15.2.6.3 Requirement for other information items
    • 15.2.6.4 Requirements for clinical studies conducted in China

16. APPLICATION MATERIAL AND REQUIREMENTS OF SUPPLEMENTARY APPLICATION

• 16.1 Registration classification
  • 16.1.1 Supplemental applications to be approved by SFDA
  • 16.1.2 Supplementary applications to be approved by PDA and be filed for record at SFDA, or directly be filed for record at SFDA
  • 16.1.3 Supplemental applications to be filed for record at PDA
• 16.2 Application information items
• 16.3 Table of application information items
• 16.4 Notes and relevant requirement of the registration items and application information items

17. APPLICATION MATERIAL FOR RE-REGISTRATION

• 17.1 Drugs made in China
• 17.2 Imported drugs

18. TIMEFRAME FOR MONITORING PERIOD OF NEW DRUGS

(NOTE: NO MONITORING PERIOD WILL BE ESTABLISHED FOR DRUGS OTHER THAN THOSE LISTED) (TABLES 1-3)

• 18.1 A 5-year monitoring period will be established for new drugs listed in Table 1
• 18.2 A 4-year monitoring period will be established for new drugs listed in Table 2
• 18.3 A 3-year monitoring period will be established for the new drugs listed in Table 3