For Chinese Version, please see 药品注册管理办法. It is important to read the appendices.
DRUG REGISTRATION REGULATION
Chapter 1: General Principles 1
Chapter 2: Application for Drug
Registration 2
Chapter 3: Pre-clinical Laboratory Study of
Drugs 3
Chapter 4: Clinical Study of Drugs 4
Chapter 5: Application and Approval of New
Drugs 8
Chapter 6: Application and Approval of Drugs Already
with National Standards 14
Chapter 7: Application and Approval for Import
Drugs 15
Chapter 8: Application and Approval for OTC
Drugs 18
Chapter 9: Supplemental Application for Drug
Registration 19
Chapter 10: Re-registration of Drugs 20
Chapter 11: Administration of Drug Inspection for
Registration 21
Chapter 12: Administration of Drug Registration
Standards 23
Standard Substance 24
Chapter 13: Drug Registration Prescribed
Timeline 25
Chapter 14: Reconsideration 28
Chapter 15: Legal Liability 28
Chapter 16: Miscellaneous 30
Annex 1: Registration Categories and Application
Information Requirements of TCM and Natural Drugs 32
Annex 2: Registration Categories and Application
Information Requirements of Chemical Drugs 33
Annex 3: Registration Categories and Application
Information Items Requirements of Biological Products 49
Annex 4: Registration Items and Application Information
Requirements of Supplemental Application of Drug Registration 69
Annex 5: Application Information Items of Drug
Re-Registration 81
Chapter 1: General Principles
Article 1: This Regulation is promulgated according to
the Drug Administration Law of The People’s Republic of China (Drug
Administration Law) and the Implementing Regulation of the Drug Administration
Law of The People’s Republic of China (Implementing Regulation) to ensure the
safety, efficacy and quality control of drugs and standardize drug
registration.
Article 2: This Regulation shall apply to all drug research
and clinical studies, application for clinical study, drug production or
importation, as well as the related drug registration inspection and drug
administration in The People’s Republic of China (PRC).
Article 3: Drug registration means the legal process by
which a decision is made by SFDA, upon application of registration applicant,
to either approve or not approve the conducting of a drug clinical trial,
production or importation of a drug to be marketed, based on a systematic
evaluation of the safety, efficacy and quality control of the drug.
Article 4: The State shall encourage research and
development of new drugs and exercise fast track approval for innovative new
drugs, those for difficult to treat and life threatening diseases, and drugs needed
for emergency use.
Article 5: The State Food and Drug Administration (SFDA)
is the competent national authority for drug registration, responsible for the
review and approval of clinical studies, production and importation of drugs.
Provincial Drug Authorities (PDA) shall be authorized by
SFDA to examine the completeness, standardization and authenticity of an
application dossier, and organize inspection of the pilot manufactured drugs.
Article 6: A drug registration applicant (applicant)
means an institution which makes application for and assumes corresponding
liability for drug registration, and holds the drug approval certificate after
approval has been obtained.
A local applicant shall be a legally registered
institution in China
and be competent to independently assume legal liability. A foreign applicant
shall be a legally established pharmaceutical company outside of China. In
making application for an import drug registration, the foreign applicant shall
use its office in China, or
authorize an agent in China
to handle the application.
The person;)
handling the
drug registration application shall have technical expertise, and be familiar
with drug administration laws, regulations and technical requirements.
Chapter 2: Application for Drug Registration
Article 7: Drug registration application includes
application for new drug, application for a drug already with national
standards, and application for import drug as well supplemental application. A
local applicant shall make application according to new drug or a drug already
with national standards; a foreign applicant shall make application according
to import drug.
Article 8: A new drug application means a registration
application for a drug that has not been marketed in China. A drug that has been
marketed in China for which an application is made for a change in dosage form,
or route of administration, add new indication shall be treated as a new drug
application
Application for a drug already with national standards
means application for production of a drug for which SFDA has already issued
formal standards.
Application for import drug means application for a drug
produced outside China to be
marketed in China.
Supplemental application means an application for the
change, addition, or cancellation of any item or contents in the existing
registration approval of a new drug, drug already with national standards, or
import drug.
Article 9: Application for registration shall be made to
PDA with submission of relevant documents and drug samples. However,
application for import drug shall be made to SFDA.
Applicant should assume the liability for the
truthfulness of all the application dossier..
Article 10: If two or more institutions jointly apply
for new drug registration, the application shall be made to the PDA where the
drug manufacturer is located. If all the applicants are manufacturers, the
application shall be made to the PDA where the drug manufacturer of the
preparation is located. If none of the applicants is a drug manufacturer, the
application shall be made to the PDA where the drug sample is pilot
manufactured.
Article 11: Regarding the drug or its formulation,
manufacture processing, indication etc. the applicant shall submit documents
explaining the China
patent status and ownership rights. If other party holds patent in China, the
applicant shall submit a letter of guarantee stating that the drug will not
infringe on the patent rights of others and that the applicant assumes
liability for any possible infringement.
Article 12: If an infringement dispute occurs after
completion of registration, the parties shall try to negotiate a resolution, or
resolve the matter according to relevant laws, regulations, or rules through
judicial organs or patent administration institutions.
Once there is a final rule from the Patent
Administration or an enforcement judgment from People’ Court to determine the
fact of infringement, Patent holder may apply at SFDA for cancellation of drug
approval number of infringing party. SFDA shall based on the facts, cancel the
certified drug approval of infringing party.
Article 13: For a drug that has obtained patent
protection in China,
another applicant may apply for registration within two years prior to the
patent expiration. SFDA shall review the application according to this
Regulation and, after expiration of the patent, approve production or import
for an application that meets requirements.
Article 14: For a period of 6 years from the date of the
original applicant's approval, SFDA shall not approve a subsequent application
that used, without the express consent of the original applicant, the
undisclosed R&D data and other data generated by the original applicant for
submission of application of manufacturing or marketing of a drug containing
new chemical ingredients unless the submitted data is generated by the
subsequent applicant itself.
Chapter 3: Pre-clinical Laboratory Study of Drugs
Article 15: The scope of pre-clinical laboratory study
(pre-clinical study) of a drug for registration includes synthetic process,
extraction methods, physical-chemical properties and purity, dosage form
selection, screening of formulas, preparation process, inspection methods,
specification, stability, pharmacology, toxicology and pharmacokinetic study.
For TCM preparations, information such as the source and the processing of raw
materials should also be included. For biological products, information such as
specification, storage condition, genetic stability and immunology study of
strain, cell strain as well as biological tissue should also be included.
Article 16: Pre-clinical study of a drug shall be
conducted in accordance with relevant regulations; the drug safety evaluation
shall be conducted in accordance with Good Laboratory Practice for Pre-Clinical
Laboratory Studies (GLP).
Article 17: Institutions engaged in drug research and
development shall have the necessary personnel, facility, equipment, instruments,
conditions and management system needed corresponding to the research project.
The animals, reagents and raw materials used for experiments shall comply with
relevant national regulations and requirements. The authenticity of all data
and materials shall be ensured.
Article 18: When an application is only made for
registration of preparation, the raw materials of the investigative drug
substance used for this preparation shall have a Drug Approval Number, Import
Drug Certificate or Pharmaceutical Product Certificate, and the raw materials
shall have been obtained from legal channels. Relevant certified documents
should be provided if the drug substances registered by other party or still
pending the approval process have been used. Any investigative drug substance
which does not have a Drug Approval Number, Import Drug Certificate or
Pharmaceutical Product Certificate shall go through SFDA approval process.
Article 19: If an applicant authorizes another
institution to conduct the study of drugs, or any single experiment, inspection
or pilot production and manufacture, the applicant shall sign a contract with
the authorized party and maintain responsibility for the authenticity of study
data.
Article 20: If an applicant uses the pre-clinical study
documents from a foreign drug research institution as supporting materials for
a drug registration application, an explanation for the items referencing the
page numbers shall be provided by the institution and notarized certificate of
the institution's legal overseas registration shall be attached. Only after the
documents are authenticated by SFDA may they be included in the registration
documents. SFDA may send people to conduct on-site inspections, if necessary.
Article 21: When there is a need to audit and inspect
drug studies, SFDA and PDA may request the applicant or the drug research
institute which conducted the experiments to repeat an experiment for any items
by using the methods and data listed in the application dossier, and SFDA and
PDA may send people to conduct on-site inspections of the experiment process.
SFDA may also designate other drug control institutes or drug research
institutions to repeat the experiments.
Article 22: The pre-clinical study of drugs shall be
conducted in accordance with relevant technical guidelines issued by SFDA. If
the applicant conducts the experiments according to other methods and
techniques, the applicant shall provide information to evidence that the
methods and techniques are scientific.
Chapter 4: Clinical Study of Drugs
Section 1: Basic Requirements
Article 23: Clinical study of drugs includes clinical
trials and bioequivalence trials.
Only after approval from SFDA may a clinical trial study
be conducted, and it shall be conducted in accordance with Good Clinical
Practice (GCP).
Article 24: Clinical trials shall be conducted for the
registration of a new drug.
Clinical trials are divided into Phase I, Phase II,
Phase III and Phase IV. Clinical trials of Phase I, Phase II and Phase III are
needed for a new drug application. In some cases only Phase II and Phase III
clinical trials or, only Phase III clinical trials, are needed for a new drug
application.
Phase I: Basic clinical pharmacology and human safety
evaluation studies. To observe tolerance in human bodies and pharmacokinetics,
providing a basis for a drug administration program.
Phase II: A preliminary exploration on the therapeutic
efficacy. The purpose is to evaluate the safety and efficacy of a new drug on
patients within the target indication of the drugs, and providing the basis to
devise Phase III Clinical Trial and to determine a drug administration program.
Phase II Clinical Trial may be conducted in many ways including randomized
blind controlled clinical trial in accordance with the purpose of the study.
Phase III: The phase to confirm the therapeutic
efficacy. The purpose is to further verify the safety and efficacy of a new
drug for patients with targeted indication, to evaluate the benefit and risks
relationship, and finally to provide sufficient data to support the
registration approval of the drug. The trials usually are randomized, blind and
controlled clinical trial with a large number of sample subjects.
Phase IV: A new drug post-marketing study, conducted by
the applicant. The objective is to investigate the efficacy and adverse
reactions under the conditions of wide use, and to evaluate the benefit and
risk relationship when used by ordinary and special groups of patients and to
improve dosage of the drug.
Article 25: Generally there is no need for clinical
studies for the registration of a drug already with national standards. If
clinical studies are needed, for a chemical drug only bioequivalence trials may
be required. If the drug quality has to be controlled through the production
processes and standards, clinical trials shall be conducted. For a supplemental
application for a drug already marketed, clinical studies shall be conducted
for an additional indication, or a significant change in the production
process, or for any additional indication of TCM.
Bioequivalence Trials refers to the human trials of
Bioequivalence study, where statistical difference of absorption degree and
speed of active components, in term of parameter of pharmacokinetics, will be
determined by comparison the same or different dosage form of the preparation
at the same test conditions,
Article 26: The number of cases in the clinical study of
a drug should be decided in accordance with the objective of the clinical
trials and shall meet both the statistical requirements and the minimal cases
required by this Regulation for a clinical study. For a drug used for the
treatment of rare and special diseases or other special circumstances, any
reduction in the number of cases in the clinical study or exemption must be
approved by SFDA.
Article 27: For a vaccine and other special drugs
prepared during the strains selection stage, if there is neither suitable
animal experimental model nor a way to evaluate the efficacy of the drugs in
laboratory study, application of clinical trials may made to SFDA, provided
that safety of the subjects can be ensured.
Section 2: Requirements Before Implementation
Article 28: After approval of a clinical study, the
applicant shall select qualified institutions to conduct the clinical study,
negotiate and determine leading institution, principal investigator and
participating institutions.
Article 29: The applicant shall sign a Clinical Trial
Agreement with the leading and the participating institutes selected for the
clinical study, and then provide the draft Informed Consent Form and
Investigator’s Brochure, jointly improve the clinical trial protocol with
reference to technical guidelines.
The applicant shall request the Ethics Committee of the
institutions to review the clinical trial protocol.
Article 30: The applicant shall provide the institutions
with the investigational drugs and comparator drugs (expect for Phase IV
clinical trials) together with COA of drug samples, at no charge. The applicant
shall bear the costs related to conducting the clinical study.
Article 31: The investigational drugs shall be produced
in a workshop which meets GMP requirements and the production process shall be
strictly in accordance with the requirements of GMP.
SFDA or the authorized PDA may conduct on-site audit, as
necessary.
Article 32: The applicant may inspect the
investigational drug itself in accordance with the drug's standards approved by
SFDA, or authorize a drug control institute designated by Article 147 and Article
148 of this Regulation to conduct the quality test. The drug may not be used
for Clinical Trails before it has passed the inspection. SFDA may designate a
drug control institute to conduct a random inspection for the investigational
drug.
Vaccine, blood products and other bio-products
designated by SFDA as well as investigational drugs produced overseas must be
inspected by a drug control institute designated by SFDA. The drug may not be
used before it has passed the inspection. The applicant assumes all
responsibility for the quality of the investigational drug.
Article 33: Before conducting the clinical study, the
applicant shall file with SFDA information such as the clinical study protocol,
name of the principle investigator of the leading institution, participating
institutions and investigators, approval letter from ethics committee, and the
sample of the Informed Consent Form, also providing a copy to the PDA where the
institutions are located.
Section 3: Administration of a Clinical Study
Article 34: During the clinical study, the applicant
shall designate inspectors to monitor the implementation of GCP.
Article 35: If an applicant discovers that an
institution conducting clinical study is in violation of relevant regulations,
or is not following the clinical study protocol, the applicant shall try to
correct the situation. For serious violation, the applicant may request to
suspend or stop the clinical study and shall submit a written report to SFDA
and the relevant PDA.
Article 36: Upon the completion of each phase of the
clinical study, the applicant shall submit a clinical study and statistical
analysis report to SFDA and relevant PDA.
If the duration of clinical study exceeds 1 year, the
applicant shall submit an annual clinical study progress report to SFDA and
relevant PDA from the date of the approval of the study.
Article 37: A clinical study shall start within 2 years
of approval. Otherwise the approval certificate shall automatically become null
and void. A re-application shall be submitted to resume the study.
Article 38: The institutions and personnel participating
in the clinical study shall be familiar with the characteristics, therapeutic
activities, efficacy and safety of the investigational drugs and clearly
understand their responsibility and liabilities, obtain Informed Consent Forms
signed voluntarily by the subjects, keep accurate and true clinical study
records.
Article 39: If an applicant violates GCP or requests to
change the data and conclusions of clinical study, the participating
institutions and personnel shall report the circumstances to PDA and SFDA.
Article 40: The institutions and investigators
participating in the clinical study shall be responsible for taking all
necessary measures to ensure the safety of the subjects.
During the clinical study the investigator shall
carefully watch for the occurrence of adverse events, adopt appropriate
measures, and keep a record.
The institutions shall report a serious adverse event to
PDA and SFDA within 24 hours of occurrence, and immediately report to the
Ethics Committee.
Article 41: SFDA and PDA shall conduct inspection or
data audits for the approved clinical study.
Article 42: SFDA may request the applicant to amend the
clinical study protocol, suspend or stop the clinical study in any of the
following circumstances:
1) the Ethics Committee has failed to perform
its duty; or;
2) the safety of the subjects cannot be
effectively ensured;
3) serious adverse event was not timely
reported;
4) the clinical study progress report was not
timely submitted,
5) the completion of the clinical study is
more than 2 years behind the original completion date and there are still no
results which can be evaluated;
6) evidence that the investigative drug is
not effective;
7) quality problems in the drug used for
clinical trials;
8) fraud in the clinical study;
9) other circumstances violating GCP.
Article 43: The applicant or institutions shall
implement the decision regarding amendment of the clinical study protocol, or
suspension or cessation of the clinical study made by SFDA
Article 44: During the clinical study, in case a large
range or unexpected adverse reaction or serious adverse event occurs, or there
is evidence to prove that the investigational drug has significant quality
problems, SFDA or PDA may adopt emergency mandatory administrative measures to
suspend or stop the clinical study, and the applicant and institutions must
immediately stop the study.
Article 45: The investigators shall be responsible for
use of the investigational drug and ensure the investigational drug is only
used by the subjects of the study and the dosage and usage of the drug are in
accordance to the clinical study protocol. The investigators shall not give the
drug to any person not participating in the clinical study. The investigational
drug shall not be sold.
Article 46: A foreign applicant who wants to conduct an
international multi–center clinical study shall apply at SFDA in accordance
with the following provisions:
1) The drug used for an international
multi–center clinical study shall be one already registered in a foreign
country or in phase II or phase III clinical trials. An application for an
international multi–center clinical study of new preventive vaccine from a foreign
applicant still not registered outside China shall not be accepted.
2) In approving an international multi–center
clinical study in China,
SFDA may first request the applicant to firstly conduct the Phase I clinical
trials in China,
if needed.
3) During a study conducted in China, the
Applicant shall, in accordance with the relevant regulations, report to SFDA
any serious adverse events or unexpected adverse events which occur in any
countries.
4) Upon the completion of the study, the
Applicant shall submit the complete clinical study report to SFDA.
5) Data generated from an international
multi–center clinical trial used for drug registration in China, shall be
in accordance with the relevant provision of this Regulation, and the applicant
shall submit the complete research information of the study.
Chapter 5: Application and Approval of New Drugs
Section 1: Basic Requirements
Article 47: The application dossier submitted for new
drug registration shall be complete and standardized with authentic and
reliable data. In citing literature and materials, the name of the work and journal as well as
volume, issue and page number shall be provided. For unpublished literature and
materials, an authorization letter from the owner must be provided. For any
foreign language materials a Chinese translation should be provided in
accordance with relevant requirements.
Article 48: SFDA may use fast track approval process for
the following new drug:
1) New active ingredients and its preparation
extracted from TCM, natural drugs, or preparation made of material from plant,
animal and minerals, which have not been marketed in China and;
2) drug raw material and its preparations,
and biological product that have not been marketed domestically or outside
China;
3) new antiviral drug for AIDS and drug used
for diagnosis and prevention of AIDS, cancer and orphan drug;
4) new drugs which treat diseases for which
there is no effective therapy.
5) Drugs needed for emergency.
Article 49: After receipt of an application for a drug
described in Article 48 of this Regulation, PDA shall examine and made
recommendations as to whether the application meets the requirements for fast
track approval. Upon receipt of PDA recommendations, SFDA shall then decide
whether to use fast track approval for the drug application.
Article 50: When a new drug is jointly developed, the
application shall be made by one of the parties, and other parties shall not
apply. When a joint application needs to be made, the application shall be
signed by all the parties. Except for a drug described in Article 48.1 and 48.2,
after approval, the new drug shall only be manufactured by one party. Different
strengths of one drug shall not be manufactured by different parties.
No one should attempt to make different applicant to
apply for registration for the same technology of new drug, or make repeat
application in any way. SFDA and PDA will organize the related inspection, if
any needs. Once the foresaid fact is confirmed, the application will not be
accepted, and the application will be returned if already accepted.
Article 51: During review process of new drug, even if
the marketing approval of other domestic drug of the same active substance is
approved overseas, the registration category and technical requirements of the
drug shall remain unchanged in the review process in China.
During the review process of new drug, even when the
marketing approval of other domestic drug of the same active substance is
approved in China, the
registration category and technical requirements of the same kind of drug shall
remain unchanged in the review process in China.
Section 2: Approval of Clinical Study for New Drugs
Article 52: Upon the completion of the pre-clinical
study, the applicant shall complete the Application Form for Registration of
New Drugs, and submit the authentic materials and sample drugs to PDA.
Article 53: PDA shall examine for form the application
dossier, and if the requirement are met, the application will be accepted with
issuing of acceptance notification of drug registration application. If the
requirements are not met, the application will not be accepted with issuing of
non-acceptance notification of drug registration application, with explanation
of reasons.
PDA shall, within 5 days upon acceptance of the
application, organize and conduct on-site inspection for production and
research of the drug, take sample drugs of 1-3 batches, and notify the drug
control institute for inspection. PDA shall, within the prescribed time limit,
submit recommendations, inspection report and application dossier to SFDA, and
notify the applicant.
Article 54: The drug control institute shall conduct
drug inspections and drug standard inspection upon receiving notification, and
submit the inspection reports to SFDA within the described time, notify the PDA
which requested the inspection, and notify the applicant.
Article 55: Upon receipt of the application dossier,
SFDA shall organizes the pharmaceutical, medicals and other technical people to
conduct technical review of the new drug, and SFDA may request the applicant to
provide supplemental information and drug sample. When SFDA consider the
requirements are met, Approval for Drug Clinical Study will be issued. When
SFDA does not consider the requirements are met, Notification of Approval
Opinion will be issued with explanation.
Article 56: Upon receipt of verification recommendation,
if the drug control institute concludes that the quality cannot be controlled
by the drug standards, the applicant may withdraw the new drug application. If
the applicant did not withdraw the new drug application, when SFDA proves the
quality indeed cannot be controlled by the drug standards through a technical
review, the application shall be returned.
Article 57: After inspection, if the drug sample does
not meet the submitted drug standards, after verification, SFDA shall return
the application of new drug.
Article 58: During SFDA's drug application review
process, except for new information related to the innovative drug ingredients
or drug safety, or the supplemental information required by SFDA, the applicant
shall not submit supplemental technical material to SFDA. If new technical
materials must be added, the applicant shall withdraw the application, and
re-apply according to the original application procedures.
Article 59: For those withdrawn or returned application,
after further studies, if the requirements of the Regulation are met and there
is no new drug of the same kind enter into monitoring period, the original
applicant may resubmit the application according to original application
procedures.
Section 3: Approval of New Drug Production
Article 60: After completion of a clinical study, the
applicant shall fill out the Drug Registration Form, and submit clinical study
information, changes and supplemental information, with detailed explanation
and justifications, to the PDA where the applicant is located. At the same
time, the applicant shall submit raw material for the preparation of the
standard substance to NICPBP.
Article 61: PDA shall examine for form the application
dossier, and if the requirement are met, the application will be accepted with
issuing of acceptance notification of drug registration application. If the
requirements are not met, the application will not be accepted with issuing of
non-acceptance notification of drug registration application, with explanation
of reasons.
Article 62: PDA shall, within 5 days upon acceptance of
the application, organize and conduct on-site inspection for production and
research of the drug, take sample drugs of 3 consecutive batches, and notify
the drug control institute for inspection. Upon completion, PDA shall, within
the prescribed time limit, submit recommendations and , inspection report and
application dossier to SFDA, and notify the applicant..
Article 63: The 3 consecutive batches of sample product
used for new drug application shall be manufactured in a workshop with the GMP
Certificate. For a newly established drug manufacturing enterprise or workshop
or for the manufacture additional drug dosage forms, the production process of
the sample product shall be in accordance with the requirements of GMP.
Article 64: The notified drug control institute shall
inspect the sample product taken for registration inspection, and submit the
drug inspection report within the prescribed time, send copies to the PDA which
requested the inspection, and notify the applicant.
Article 65: Upon receipt of the application dossier,
SFDA shall conduct a comprehensive review of the application dossier, and SFDA
may request the applicant to provide supplemental information. SFDA will issue
its decision through Drug Registration Approval Form. An application which
meets requirements shall be issued a New Drug Certificate. If the applicant
already has a Drug Manufacturing License and meets the necessary conditions for
manufacture, the Drug Approval Number will also be issued at the same time.
When SFDA does not consider the requirements are met, Notification of Approval
Opinion will be issued with explanation.
Article 66: The insert sheet shall be approved by SFDA
according to materials submitted by the applicant. SFDA shall simultaneously
issue a registration standard and insert sheet in approving a new drug. The
manufacturer shall be responsible for correctness and accuracy of the insert
sheet, and monitor the efficacy and safety of the drug after launch, and apply
to modify the insert sheet, if necessary.
Drug manufacture enterprise should be responsible for
monitoring the post-marketing safety and efficacy of the drug, and if
necessary, timely apply for revision of the insert sheet.
The insert sheet shall be printed according to relevant
SFDA regulations.
Article 67: The 3 batches of new drug used for the new
drug application, after passing the inspection by NICPBP and obtaining a Drug
Approval Number, those manufactured in the workshop with Drug Manufacturing
License and GMP Certificate may be sold within the expiration date.
Section 4: Administration of Monitoring Period of New
Drugs
Article 68: In order to ensure public health, SFDA may
implement a monitoring period for the approved new drugs to be produced so as
to continue the safety monitoring of the new drug.
During the monitoring period, SFDA shall not approve
production and/or importation of the drug by other enterprises.
Article 69: Different monitoring period will be set for
different new drugs based on the existing safety information and research from
inside and outside China.
The drug-monitoring period shall start from the date of approval for
production, and shall not exceed 5 years.
Article 70: During the monitoring period of a new drug,
drug manufacture enterprise shall regularly inspect the production process,
quality, stability, efficacy and adverse reaction, and annually report to PDA.
When a serious quality problem, or serious or unexpected
adverse reactions is discovered by relevant institutions of drug manufacture,
distribution, use or inspection, or administration, it shall be reported to PDA
immediately.
Article 71: PDA shall organize an investigation of a
drug with serious quality problems, serious and / or unexpected adverse
reactions, and report to SFDA.
Article 72: PDA shall order an enterprise that fails to
fulfill its responsibilities within the drug-monitoring period to take
corrective action.
Article 73: If a new drug with a monitoring period has
not begun production within 2 years from the approval date, SFDA may approve
the production application for the new drug of another applicant and continue
to monitor.
Article 74: As a new drug enters monitoring period, for
an application whose clinical study has already been approved by SFDA, the
application shall continue in the regular review process. SFDA may approve the
production or importation of an application meeting requirements; monitor the
new drug within the monitoring period of the previously approved new drug.
Article 75: As a new drug enters the monitoring period,
for an application which has been accepted but whose clinical study has not
been approved by SFDA, the application shall be returned. Upon the completion
of monitoring period, another applicant may apply as for a drug already with
national standards.
Article 76: For an import drug that has already received
marketing approval, for an application whose clinical study has already been
approved, the application may continue in the regular review process. SFDA may
approve the production of a drug whose application meets the requirements. The
applicant may withdraw the application and apply as for a drug already with
national standards.For an application which has been accepted but whose
clinical study has not been approved, the application shall be returned and
application shall be made as for a drug already with national standard
Section 5: New Drug Technology Transfer
Article 77: New drug technology transfer means the
process by which the owner of a New Drug Certificate transfers its new drug
processing technology to a drug manufacturing enterprise that will apply for
the drug production.
Article 78: The transferor usually is a party holding a
New Drug Certificate. In the event that a Drug Approval Number has been
obtained, the application for cancellation of the Drug Approval Number should
also be made at the time of the application for new drug technology transfer.
Article 79: The new drug technology shall be transferred
in whole at one time to a pharmaceutical production enterprise. If the
transferee for special reasons is unable to produce the drugs, the holder of
New Drug Certificate may re-transfer the technology by evidencing a written
waiver to produce the drugs from the original transferee. SFDA shall cancel the
Drug Approval Number from the original transferee in accordance with
requirements.
A transferee may not re-transfer the technology to any
other party.
Article 80: The transferee shall have obtained a Drug
Manufacturing License, GMP Certificate and the new drug shall be consistent
with the production scope described in Drug Manufacturing License and GMP
Certificate of the transferee.
In the newly established drug manufacture enterprise,
newly established drug manufacture workshop of any enterprise and / or for a
newly added dosage form, if the GMP Certificate has not been obtained for the
corresponding scope, GMP Certificate should be obtained within the time limit
setout in Article 6 of Implementing Regulation. The drug with an approval
number cannot be marketed before the certificate is obtained.
Article 81: In transferring the new drug technology, the
transferor shall sign a Technology Transfer Contract with the transferee and
transfer all technology and materials to the transferee without reservation,
and guide the transferee in trial manufacture of 3 continuous batches of
qualified products.
Article 82: For a new drug technology jointly developed
by more than one party, any transfer should be made by all the signatories of
the New Drug Certificate, who will sign a Technology Transfer Contract.
Article 83: An application for a new drug technical
transfer shall be jointly submitted by the owner of the New Drug Certificate
and the transferee at PDA where the transferee is located. The applicant shall
complete the Drug Supplemental Application Form, submit relevant materials and
the Technology Transfer Contract shall be attached.
Article 84: Upon acceptance of the application for a new
drug technology transfer, PDA shall inspect the trial production site,
equipment, production of sample products and inspection records of the
transferee, take sample product and notify the drug control institute for drug
inspection.
Article 85: The drug control institute responsible for
drug inspection shall complete inspection within the prescribed time, issue an
inspection report and submit it to PDA.
Article 86: PDA shall examine the inspection report it
has received and the relevant information provided by the drug control
institute, make recommendations and report to SFDA, and notify the applicant
about the recommendations.
Article 87: SFDA shall conduct a comprehensive review of
the supplemental application of new drug technology transfer, and issue an
Approval for Clinical Study of Drugs, if a clinical study is needed.
Upon the completion of the clinical study, the applicant
shall submit clinical study information to SFDA.
Article 88: SFDA shall issue its decision on whether to approve
the production through Drug Supplemental Application Approval Form. If the
requirements are met, Drug Approval Number will be issued. If the Drug Approval
Number has already been issued to the transferor, it shall be canceled. When
SFDA does not consider the requirements are met, Notification of Approval
Opinion will be issued with explanation.
Article 89: No new drug technology transfer is allowed
for the drug within its monitoring period. After the monitoring period,
applicant may make application of drug already with National Standards.
Chapter 6: Application and Approval of Drugs Already
withNational Standards
Article 90: To apply as for a drug already with national
standards, the applicant shall hold Drug Manufacturing License, and GMP Certificate.
The drug for which application is made shall be consistent with the production
scope described in Drugs Manufacturing License and GMP Certificate of the
enterprises.
Article 91: A newly established drug manufacturing
enterprise or workshop or the production of additional drug dosage forms
without GMP Certificate shall obtain GMP Certificate within the time prescribed
in Article 6 of Implementing Regulation. The drug with an approval number
cannot be marketed before the certificate is obtained.
Article 92: After completion of pilot production
according to relevant technical requirements, the applicant shall complete the
Application Form for Drug Registration and submit relevant technical materials
and sample products to PDA.
Article 93: PDA shall examine for form the application
dossier, and if the requirement are met, the application will be accepted with
issuing of acceptance notification of drug registration application. If the
requirements are not met, the application will not be accepted with issuing of
non-acceptance notification of drug registration application, with explanation
of reasons.
PDA shall, within 5 days upon acceptance of the
application, organize and conduct on-site inspection for production and
research of the drug, take sample drugs of 3 consecutive batches, and notify
the drug control institute for inspection. Upon completion, PDA shall, within
the prescribed time limit, submit recommendations and , inspection report and
application dossier to SFDA, and notify the applicant.
Article 94: The notified drug control institute shall
inspect the 3 batches of the sample products taken for registration inspection,
and submit the drug inspection report within the prescribed time, send copies
to PDA requesting the inspection and notify the applicant.
Article 95: SFDA shall conduct review of the application
dossier submitted by PDA, and SFDA may request the applicant to provide
supplemental information. If a clinical study is needed, SFDA shall issue an
Approval for Clinical Study of Drugs.
After completion of the clinical studies, the applicant
shall submit the clinical study information to SFDA.
Article 96: SFDA shall issue its decision of whether to
approve the production of the drug through the Drug Registration Approval
decision form. If the requirements are met, a Drug Approval Number will be
issued. When SFDA does not consider the requirements are met, Notification of
Approval Opinion will be issued with explanation.
Article 97: No application will be accepted by SFDA or
PDA for registration of drug with temporary national standards.
Article 98: SFDA may suspend the acceptance and approval
of the application of a drug already with National Standards when there is a
need to further evaluate the efficacy and safety of the drug.
Article 99: The 3 batches of new drug used for the
application of a Drug Approval Number manufactured in the workshop with Drug
Manufacturing License and GMP Certificate, after passing the inspection by the
drug control institute designated by SFDA and obtaining a Drug Approval Number,
may be sold within the expiration date of the drugs.
Chapter 7: Application and Approval for Import Drugs
Section 1: Registration of Import Drugs
Article 100: An import drug, for which application is
made, shall have obtained marketing approval in its country/region of
manufacture. An import drug without such a marketing approval may still be
approved after SFDA confirms the safety and efficacy of the kind of drug, and
there is a clinical need for the drug.
The drug for which import application is made shall meet
the GMP standard in the foreign country / region as well as the requirements of
GMP in China
Article 101: For an import drug application, the
applicant shall complete Application Form for Drug Registration and submit the
relevant application dossier and sample product and relevant certified
documents. The application shall be made with SFDA.
Article 102: SFDA shall examine for form the application
dossier, if the requirements are met, the application shall be accepted, and an
acceptance notification shall be issued. SFDA shall notify NICPBP for drug
registration inspection. When SFDA does not consider the requirements are met,
Notification of Non- Acceptance will be issued with explanation. SFDA may
organize the on-site inspection about the research status and manufacturing
condition, if necessary.
Article 103: Upon completion of the drug inspection,
NICPBP shall submit the verified drug standards, the drug inspection report and
inspection recommendations to SFDA.
Article 104: SFDA shall conduct a comprehensive review
of the application dossier submitted and if necessary SFDA may request the
applicant to provide supplemental information. SFDA shall issue its decision of
whether clinical study is approved through Approval of Clinical Study of Drugs
Form. When SFDA does not consider the requirements are met, Notification of
Approval Opinion will be issued with explanation
Article 105: Upon approval of the clinical study, the
applicant shall conduct the clinical study in accordance with the provision
under Chapter 4 of this Regulation.
Upon the completion of clinical study, the applicant
shall, in accordance with relevant requirements, submit to SFDA the clinical
study report, sample products, relevant changes and supplemental information,
with detailed explanation and justifications, and the relevant certified
documents.
Article 106: SFDA shall organize and conduct a
comprehensive review of the submitted clinical study information and if
necessary SFDA may request the applicant to provide supplemental information.
If the requirements are met, issue an Import Drug Certificate. Regulation for
import drug will apply for applicants from Hong Kong, Macao
and Taiwan of China. If the requirements are met, a Pharmaceutical Product
Certificate shall be issued to the When SFDA does not consider the requirements
are met, Notification of Approval Opinion will be issued with explanation.
Article 107: For an import drug preparations
application, documents to evidence the legal channels of immediate packaging
materials or containers of the drug, documents to evidence the legal channels
of drug raw material and supplemental material must be provided. For raw
material and supplemental material of drug that has not been approved by SFDA,
the information of relevant production processes, quality specification, and
inspection methods should be submitted.
Article 108: SFDA shall simultaneously issue a
registration standard and insert sheet in approving an import drug.
Section 2: Approval of Repackaging of Import Drugs
Article 109: Repackaging of import drugs means taking
from offshore finished drug preparation in large packaging and putting them
into smaller packaging, or taking drugs in smaller packaging and placing them
into final (outside) packaging with an insert sheet, labeling, etc. in China.
Article 110: The application for repackaging of import
drug shall comply with following requirements:
1) an Import Drug Certificate or
Pharmaceutical Product Certificate has already been obtained for the import
drugs;
2) the drug should not yet be manufactured in
China or, if manufactured, not able to meet the clinical demand;
3) the drug of one pharmaceutical company
shall only be repackaged by one pharmaceutical production enterprise, generally
for a period not exceeding the valid period of Import Drug Certificate or
Pharmaceutical Product Certificate.
4) The onshore pharmaceutical production
enterprise shall have a Drug Manufacturing License. If the tablet with no
packing or capsule is to be repacked in China, the drug to be repackaged
shall be within the production scope described in its Drug Manufacturing
License and GMP Certificate.
5) Any application for repacking of import
drug should be made one year prior to expiration of Import Drug Certificate or
Pharmaceutical Product Certificate.
Article 111: The offshore pharmaceutical company shall
sign a Repackaging Contract for Import Drugs with an onshore pharmaceutical
production enterprise, complete the Drug Supplemental Application Form.
Article 112: An application for repackaging a drug shall
be submitted by the onshore pharmaceutical production enterprise to the PDA
where the party is located, and the Drug Supplemental Application Form signed
by the offshore pharmaceutical company should be submitted with the relevant
information and sample products. PDA shall examine for form the application
dossier, and if the requirements are met, the application will be accepted with
issuing of acceptance notification of drug registration application. If the
requirements are not met, the application will not be accepted with issuing of
non-acceptance notification of drug registration application, with explanation
of reasons.
PDA should make recommendation after completion of the
review process and submit the application dossier and recommendation to SFDA
for approval, and notify the applicant.
Article 113: Upon receipt of the application dossier,
SFDA shall review the submission. When SFDA consider the requirements are met,
Approval for Drug Supplemental Application and Drug Approval Number will be
issued. When SFDA does not consider the requirements are met, Notification of
Approval Opinion will be issued with explanation.
Article 114: The registration standards for the import
drug shall be applied to the repackaged drug.
Article 115: The package, label and insert sheet of a
repackaged drug shall be consistent with that of the import drug to be
repacked, and shall include the approval number for drug to be repacked and
name of the drug repackaging manufacturer.
Article 116: The import inspection of finished drug
preparations in large packaging should be conducted in accordance with SFDA
regulations. The same standards shall be applied to both the inspection of the
repackaged drug and import drug.
Article 117: The offshore pharmaceutical company shall
be responsible for the quality of the repackaged drugs. If a quality problem
arisen, SFDA may cancel the approval number of the drug repackaging, and if
necessary, cancel the Import Drug Certificate or Pharmaceutical Product
Certificate of the drug in accordance with Article 42 of Drug Administration
Law.
Chapter 8: Application and Approval for OTC Drugs
Article118: An OTC drug means a drug designated by SFDA,
for which consumers may purchase and use by own judgment without a prescription
from a practicing physician or a practicing assistant physician.
Article 119: In the following circumstances, an
applicant may apply for OTC drug registration, in making drug application:
1) the production and / or importation of OTC
drugs already with national standards;
2) change in dosage form, but without change
in indications, dosage, route of administration of an OTC drug as designated by
SFDA;
3) new combination preparations developed
from active OTC ingredients designated by SFDA.
Article 120: For a drug meeting the requirement of
Article 119.1), applicant should check the OTC items in the “supplemental
application item” of the Drug Registration Form. SFDA shall designate the drug
as OTC in approving its registration. In the event of failure to check the OTC
items in the Drug Registration Form, after SFDA approved the drug registration,
applicant should proceed the registration according to the Regulation of
Categorized Administration of Prescription Drug and OTC Drugs (temporary) and
the provision of OTC registration.
Article 121: For a drug meeting the requirement of
Article 119.2) or 3), applicant should check the OTC items in the “supplemental
application item” of the Drug Registration Form. When SFDA consider the drug
meet the OTC drug requirement, SFDA shall designate the drug as OTC in
approving its registration. When SFDA does not consider the drug meet the OTC
drug requirement, SFDA shall approve the drug as prescription drug. .
Article 123: Generally, for a drug meeting the
requirement of Article 119.1) or 2), a clinical study is not needed. However,
bioequivalence trials may be needed for solid oral dosage forms of drug. A
clinical trial setout in this Regulation is needed for TCM preparation.
Article 124: For a drug meeting the requirement of
Article 119.3), basis of formula should be explained, and if necessary, a
clinical study is needed.
Article 125: OTC regulation should apply for OTC
registration, drug insert sheet and packing as well as label. Prescription
regulation should apply for other application information.
Article 126: Import drug application and approval
process should apply for application of import OTC drug, where technical
requirement of import OTC drug should e the same of the domestic one.
Article 127: SFDA shall approve the re-registration
application of import OTC drug based on the procedure of import drug
re-registration application and approval process and OTC administration
regulation. Applicant need not to complete OTC registration at PDA when
applying the re-registration application of import OTC drug
Article 128: If an OTC drug has been approved by SFDA
for marketing, but if during its use if discovered if is not suitable for use
as OTC drug, SFDA can change the drug to prescription status.
Chapter 9: Supplemental Application for Drug
Registration
Article 129: An applicant should submit a supplemental
application for changes in the items in the drug approval certificate and its
attached drug standards, insert sheet, content on the label, as well as a
change in production process that might affect drug quality.
Article 130: The applicant shall complete the
Supplemental Application Form, submit to PDA where the applicant is located
with relevant documents and explanations. PDA shall examine for form the
application dossier, and if the requirements are met, the application will be
accepted with issuing of acceptance notification of drug registration
application. If the requirements are not met, the application will not be
accepted with issuing of non-acceptance notification of drug registration
application, with explanation of reasons..
Article 131: For a supplemental application related to
import drugs, the applicant shall apply to SFDA with relevant information and
document, and the approval document of incorporating the change from the
competent authorities of the foreign country or region where the drug is
manufactured. SFDA shall examine for form the application dossier, and if the
requirements are met, the application will be accepted with issuing of
acceptance notification of drug registration application. If the requirements
are not met, the application will not be accepted with issuing of
non-acceptance notification of drug registration application, with explanation
of reasons.
Article 132: For a supplemental application of change of
enterprise name, amendment of drug packing and label as requirement by
regulation, and amendment of insert sheet required by SFDA, the application
should be accepted and approved by PDA. When PDA consider all the requirements
are met, Approval of Drug Supplemental Application will be issued and file the
approval at SFDA for record. If the requirements are not met, Notification of
Approval Opinion will be issued with explanation.
Article 133: For a supplemental application for changes
such as change of drug standards, change of supplemental materials, or addition
of new indications or functions of TCM, , the application should be accepted by
PDA, who shall submit review recommendations to SFDA for approval, and then
notify the applicant.
Article 134 Any supplemental application related to an
import drug shall be approved by SFDA. For some of supplemental application of
import drug, such as amendment of insert sheet according to the National
Standard or requirement of SFDA, supplementing and perfecting of safety related
content of insert sheet, change of design of packing or label of import drug or
drug appearance, change of registration agent, the application needs to be
filed for record, and the applicant shall implement the supplemental
application if SFDA has not commented within 30 days of its receipt by SFDA.
Article 135 For a supplemental application for a drug
approval number by a New Drug Certificate holder, or for a change of drug
manufacturing location and / or production process, PDA shall organize on-site
inspection of the pilot production, take sample product for inspection, and
notify the designated drug control institute to conduct inspection of the
sample product.
For a supplemental application for change of drug
standards, if necessary, drug control institute shall conduct a quality
inspection of the standards.
Article 136 SFDA shall examine the supplemental
application of a drug, and SFDA may request the applicant to provide
supplemental information. When SFDA consider the requirements are met, Drug
Supplementary Application Approval Form will be issued. When SFDA does not
consider the requirements are met, Notification of Approval Opinion will be
issued with explanation.
When the drug approval certificate needs to be renewed,
the old drug approval certificate shall be canceled. When additional drug
approval certificate needs to be issued, the old certificate shall continue to
be effective.
Article 137 The expiration date of the Drug
Supplementary Application Approval Form shall be same with the original
certificate, upon expiration, re-application needs to be made for all
certificates together.
Chapter 10: Re-registration of Drugs
Article 138: The re-registration of drug means the
approval process for continuing the production and / or importation of the drug
upon expiration of the current approval certificate of the drug.
Article 139: The validity period of the Drug Approval
Number, the Import Drug Certificate and Pharmaceutical Product Certificate
issued by SFDA is 5 years. 6 months prior to the expiration, application for
re-registration shall be made.
Article 140: An applicant holding the Drug Approval
Number shall apply for re-registration of the drug with PDA, complete the
Application Form for Drug Re-registration according to relevant requirements
and submit relevant application material.
The application for re-registration of an import drug
shall be submitted to SFDA.
Article 141: PDA shall examine the application dossier,
and if the requirement are met, the application will be accepted with issuing
of acceptance notification of drug registration application. If the
requirements are not met, the application will not be accepted with issuing of
non-acceptance notification of drug registration application, with explanation
of reasons..
Article 142: PDA shall issue review recommendation for
the re-registration within 3 months, and submit to SFDA for examiniation.
Upon receipt of the recommendation, if there is no
notification from SFDA not to approve the re- registration, PAD should approve
the re-registration.
Article 143: SFDA shall complete review of the
application for re-registration of the import drug within 6 months of receipt,
and approve the re-registration of an application that meets the requirements.
Article 144: An application for re-registration shall
not be accepted in any of the following situations:
1) failure in applying for re-registration of
the drug within the prescribed time;
2) failure in meeting the relevant
requirements of SFDA upon approval for marketing;
3) failure in completing Phase IV clinical
trials according to relevant requirements;
4) failure in monitoring drug adverse
reactions according to relevant requirements;
5) the kind of drug whose registration should
be canceled based on the re-evaluation of SFDA,
6) the kind of drug that should be withdrawn
according to the requirements of Drug Administration Law;
7) a drug which does not meet production
requirements in the Drug Administration Law;
8) failure to fulfill the responsibility
during the monitoring period; or,
9) other situations in which relevant
requirements have not been met.
Article 145: In the event that relevant requirements of
re-registration are not met, SFDA shall issue the notification of rejection of
the drug for re-registration with explanations, and in addition to the
certified drug approval document need to be canceled by regulation, the Drug
Approval Number, Import Drug Certificate or Pharmaceutical Product Certificate
of the drug shall be canceled before the valid period expire.
Chapter 11: Administration of Drug Inspection for
Registration
Article 146: Drug reverse registration inspection must
be conducted for application for registration. The inspection includes
inspection of sample products and inspection of drug quality standards.
Inspection of sample products means a drug control
institute conducts drug inspection according to the quality standards submitted
by the applicant.
Inspection of drug quality standards means laboratory
inspection by a drug control institute to verify the feasibility and
scientificness of inspection methods described in the quality standards of the
drug and whether or not the assumed parameters can control the drug quality.
Article 147: Drug inspections for registration usually
shall be conducted by the provincial drug control institute, inspections for
import drug registration shall be conducted by NICPBP.
Article 148: Drug inspection shall be conducted by NICPBP
or the designated drug control institute for the following:
1) a drug belonging to categories of Article
48.1 and 48.2 of this Regulation;
2) biological product;
3) other drugs designated by SFDA.
Article 149: The drug control institute shall give
priority to a drug belonging to categories in Article 49 for inspection and
verification.
Article 150: A drug control institute engaged in drug
inspection for registration shall be staffed and equipped according to
requirements of the Good Laboratory Practice of Drug Control Institutes and
National Measurement Certification, and meet the needs of the quality assurance
system and technical requirements of the drug registration inspection.
Article 151: The applicant shall provide the drug
control institute with information needed for drug registration inspection,
submit sample product or co-operate in taking sample products used for
inspection, and provide the standard drug substance used for inspection. The
amount of sample products supplied shall be three times the amount of the drug
needed for inspection. For a biological product, the record of preparation and
inspection for the corresponding batches shall also be provided.
Article 152: During the application for production of
drugs already with national standards, the drug control institute shall conduct
drug inspection according to national standards. A comprehensive analysis
should be made to analyze the change in quality parameters caused by the
changes in production process. If necessary, the institute shall request the
applicant to establish necessary quality parameters to ensure the control of
drugs quality.
Article 153: During the inspection of drug standards, in
addition to inspection of the sample products, the drug control institute shall
also issue an inspection recommendation regarding the drug standards of the
drug, items to be inspected and inspection methods, based on the research data
of the drug, the drug standards of similar products domestic and in the foreign
countries as well as national requirements.
Before the issuance of inspection recommendations, the
drug control institute should notify the applicant if necessary. If the
applicant disagrees with the recommendations, it should file an objection with
the drug control institute within 10 days. If the drug control institute
disagrees with the applicant's objection (explanation), it shall submit the
recommendation together with the applicant's explanation to SFDA with copies to
the applicant and PDA which requested the drug registration inspection.
Article 154: In re-making a drug's standards, the
applicant shall not authorize the drug control institute which issued the
recommendations to conduct the research work. Similarly, such Institute shall
not accept such authorization.
Chapter 12: Administration of Drug Registration
Standards
Section 1: Basic Requirements
Article 155: “National drug standards” means the
technical requirements for quality parameters, inspection methods and
production processes of drugs established by the State to ensure the drug
quality, including Pharmacopoeia of People’s Republic of China, drug
registration standards and other drug standards issued by SFDA.
“Drug registration standards” means the standards
approved by SFDA for the specific drug of the applicant. The pharmaceutical
production enterprise shall comply with the drug registration standards for the
drug.
Article 156: The determination of items and inspection
methods for drug registration standards shall meet the requirements of the
technical guidance principles, relevant principles and rules for compiling
national drug standards issued by SFDA.
Article 157: An applicant shall, conditioned on the
stability of the quality of raw materials and production process, select
representative sample products for the study of standards.
Section 2: Transfer of Temporary Drug Standards to
Formal Standards
Article 158: After approval of a new drug for production,
the quality standards of the new drug will be temporary standards for a trial
period of 2 years. If after the approval of other drugs, the stability of
production processes and quality standards needs further review, the quality
standards may be approved as temporary standards.
Article 159: For the drug produced with temporary drug
standards, three months prior to the expiration of temporary standards, the
enterprise shall apply to transfer the temporary standards to formal standards
at the PDA where the enterprise is located, by filling out the Drug
Supplemental Application Form and with the submission of quality inspection
information during the trial period of the drug standards and recommendations
for modification of the temporary standards.
After approval of supplemental application of change of
drug standards, if the drug standard is still temporary, the enterprise should
apply to transfer the temporary standards to formal standards three months
prior to the expiration of original temporary standards,
Article 160: PDA shall complete the review of the
application for the transfer of temporary standards to formal standards within
10 days of receipt of the application, and submit the recommendations and
relevant documents to SFDA.
Article 161: SFDA shall organize the State Pharmacopoeia
Commission to examine the temporary standards of a drug.
The State Pharmacopoeia Commission shall, based on the
use of the drugs during the period of the temporary standards, quality
standards of the relevant products domestic and overseas and relevant national
requirements, issue recommendations as to whether inspection of the temporary
quality standards is needed. If an inspection is needed, the relevant drug
control institute should be organized for inspection and inspection of the
temporary standards, and other inspection work.
Article 162: If more than one pharmaceutical production
enterprise manufactures the same drug, drug inspection and inspection of
quality standards for transfer of temporary quality standards to formal
standards should be conducted by NICPBP or drug control institute designated by
SFDA.
Article 163: If more than one applicant has applied to
transfer temporary standards of the same drug into formal standards, the
proposed standards may not be lower than already approved drug standards. The
subsequent applicant may include additional inspection items depending on the
characteristics of its drug production process.
Article 164: When there is a need for supplemental test
or supplemental inforation, upon receipt of the notification of stardard
inspection or verification, applicant shall, within 50 days of notification for
quality standard inspection, complete and update relevant supplemental
experiment or information and submit to the PDA.
Article 165: SFDA shall comprehensively examine the
information submitted by State Pharmacopoeia Commission, and when SFDA consider
the requirements are met, Publication for National Drug Standard will be
issued. When SFDA does not consider the requirements are met, Notification of
Approval Opinion will be issued with explanation. At the same time, SFDA will cancel
the temporary standards and the drug approval number approved according to the
temporary standards. .
Article 166: For the same kind of drug with different
trial period expiration dates, the drug with temporary standards which will
first expire shall begin the process of transferring to formal standards. For
the drug with temporary standards which will subsequently expire, the State
Pharmacopoeia Commission shall notify the applicant to make early application
to PDA to transfer to formal standards.
Article 167: If an applicant fails to apply to transfer
to formal standards before the expiration of the temporary standards according
to relevant regulations, SFDA shall cancel the temporary standards and the
corresponding drug approval number for drug production.
During the application process to transfer of the
temporary standards into formal standards, the pharmaceutical production
enterprise shall continue to manufacture the drug in accordance with the
requirements of the temporary standards.
Section 3: Establishment and Administration of Drug
Standard Substance
Article 168: Drug standard substance means a substance
with specific values, used in physical, chemical inspection and biological
methods inspection needed for the drug quality standards, and used to calibrate
equipments, to evaluate the measuring methods or to assay the inspection drugs
including standards, control products, raw material control products, and
reference products.
Article 169: NICPBP shall be responsible for
standardization and administration of national drug standard substances.
NICPBP may organize the relevant provincial drug control
institute, research institutions or pharmaceutical production enterprise for
cooperation in standardization and administration.
Article 170: During the application process for
production of a new drug, the applicant shall provide NICPBP with raw materials
needed for preparation and standardization of the standard substances, with the
relevant research information of the standard substances.
Article 171: NICPBP shall be responsible for the
comprehensive technical review of the standard substance regarding the
selection of raw materials, production methods, standardization methods,
standardization results, accuracy of assay values, tracing of origin of various
values, stability and conditions for repackaging and packaging, to reach a
conclusion as to whether they can be used as national standard substances.
Chapter 13: Drug Registration Prescribed Timeline
Article 172: SFDA and PDA shall publicly publish in the
official website and registering office the condition, procedure, duration and
list of all the document of application dossier needed for drug registration,
as well as template of application forms.
Article 173: SFDA and PDA shall issue notification in
writing of acceptance and non-acceptance of the drug registration application,
which will be chopped, dated and server as future evidence.
Article 174: The prescribed timeline for drug
registration means the maximum allowed time for the relevant review,
inspection, and providing of supplemental information related to drug
registration. If any work is finished within the timeline of drug registration,
the dossier should be forwarded into the next step timely.
Article 175: Upon receipt of an application, PDA shall,
within 5 days , notify the applicant in one notification all of supplemental
information and incomplete information required by the examination, and in the
event of failure to notify, the application will be deemed to consider as
accepted.
Application should be accepted within 5 days for an
application with complete information meeting the examination for form, or
after applicant complete all the required supplemental information.
Article 176: Upon acceptance of the application, PDA
shall begin within 5 days, and complete within 30 days the on-site inspection,
taking of sample products, notification of the drug control institute for
inspection of sample product and submission of the recommendation and
inspection report together with information submitted by the applicant to SFDA,
and at the same time, notify the applicant of the inspection recommendations.
Article 177: A drug control institute shall, within 30
days of receipt of the notification and sample products, complete the
inspection and issue the inspection report.
The inspection for special drugs and vaccine products
shall be completed within 60 days.
Article 178: If inspection of sample products and
verification of drug standards are needed, drug control institutes shall
complete such work within 60 days.
An inspection for special drugs and vaccine products
shall be completed within 90 days.
Article 179: For registration of import drug, DA shall
examine for form the application dossier, and if the requirements are met, the
application will be accepted. SFDA shall begin the relevant work within 5 days,
and complete examination of application information within 30 days, and notify
NICPBP to conduct the inspection. SFDA shall, if necessary, organize on-site
inspection of the research and production condition, and take sample products.
.
When SFDA does not consider the requirements are met,
SFDA shall within 5 days notify the applicant with explanation. Failure to
notify the application should be deem as acceptance of application.
Article 180: NICPBP shall, within 5 days upon receipt of
the information and the sample product, arrange for a drug control institute to
conduct the inspection.
Article 181: The drug control institute responsible for
inspection of import drug shall complete the inspection and submit to NICPBP
within 60 days of receipt of the information, the sample products and the
related standard substances.
Article 182: NICPBP shall organize the experts to
conduct a technical review within 20 days of receipt of the inspected import
drug standards, and conduct a re-inspection of specific items based on the
review recommendation, if necessary.
Article 183: SFDA shall administer the technical review
during the drug registration in accordance with the following prescribed
timeline.
1) complete in 120 days for a new clinical
study, complete in 100 days if a drug meets the requirements under Article 48
of this Regulation;
2) complete in 120 days for production of new
drug, complete in 100 days if a drug meets the requirements under Article 48 of
this Regulation; and,
3) complete in 80 days for application
registration of a drug already with national standards.
4) Complete in 40 days for supplemental
application if a technical review is needed.
This Article shall also apply to the technical review of
import drugs.
Article 184: During the technical review, SFDA shall
issue one notification regarding submission of all needed supplementary
materials.
Except for application meeting the requirement of
Article 48 of this Regulation, the applicant shall at one time submit all the
required supplemental materials within 4 months. If the applicant fails to
submit within the prescribed time SFDA shall return the application.
Article 185: If an applicant objects to providing the
materials described in the notification for supplementary materials by SFDA,
the applicant shall object within the prescribed time. If there is still
disagreement, the applicant may submit a written report to SFDA, explaining its
reasons and providing technical materials and the scientific basis to support
its reasons. SFDA shall issue its decision after review.
Article 186: When an application is returned or
withdrawn by the applicant, if the applicant need to re-apply, after the
applicant supplements and completes relevant experiments and gathering of
information, the application may be re-submitted following the original
procedure.
If an application meets the provision of this regulation
and there is no other drug of the same kind enter into monitoring period, SFDA
or PDA should accept the application.
Article 187: Upon receipt of the supplemental
information, SFDA shall complete the technical review within one third of
original prescribed time, for a drug meets the requirements under Article 48,
SFDA shall complete the technical review within one fourth of original
prescribed time.
Article 188: SFDA shall complete the approval process
within 20 days upon the completion of technical reviewFor a supplemental drug
application that needs SFDA approval, SFDA shall complete the approval process
within 20 days.
When approval cannot be completed with 20 days, an
extension of 10 can be granted by approval from the management, and further
extension exceeding 10 days will need approvals from State Council.
Article 189: The State Pharmacopoeia Commission shall
complete the review of the transfer of temporary drug standards to formal
standards within 60 days.
The responsible drug control institute shall complete
the inspection for drug and quality standards within 60 days, and deliver the
inspection recommendations and inspection report to the State Pharmacopoeia
Commission. For special drugs and vaccine products, the inspection for drug and
quality standards shall be completed within no more than 90 days and for same
kind of drug manufactured by more than one manufacturer, shall be completed
with 80 days.
Article 190: During the examination of drug registration
application, SFDA or PDA should public pubis the approval procedure and
approval result. For those matter of significant interest, the applicant and
related party may submit written opinion as statement or for defending.
Article 191: When making decision of the drug
registration application from lawful authority, SFDA and PDA shall issue notification
in writing of registration acceptance or approval and registration
non-acceptance or non- approval, with explanation of reminder that applicant is
lawfully entitled to applying for re-consideration, administrative
re-consideration or filing administrative lawsuit.
Article 192: SFDA and PDA shall notify applicant of the
entitlement to applying for hearing. During drug registration, food and drug
administration consider approval as an issue of significant public interest,
the issues should be publicly announced and hearing should be held.
Article 193: Once a decision of drug registration
approval is made, SFDA should, within 10 das, announce and deliver the
decision.
Article 194: SFDA should periodically publicly publish
over its official website a list of drug formulary of the drug already approved
by SFDA to provides access for public retrieval.
Article 195: In special situations, if there is a need
to extend the time limit for drug registration inspection or technical review,
the extension should be submitted to SFDA for approval.
Article 196: If one of the provisions of Article 70 of
Administrative Permitting Laws of People’s Republic of China (Administrative
Permitting Laws) occurs, SFDA should proceed with the cancellation of relevant
drug approval document.
Chapter 14: Reconsideration
Article 197: When an applicant object to the decision of
non approval, before applying for administrative re-consideration, and filing
an administrative lawsuit, the applicant may apply for reconsideration with
SFDA within 10 days upon receipt of rejection decision for drug registration by
filling out Drug Supplemental Application Form together with an explanation and
its reasons.
The scope of reconsideration shall only be for original
application items.
Article 198: SFDA shall complete the review and issue
its decision and notify the applicant within 50 days upon receipt of the
application for reconsideration. If SFDA maintains its original rejection
decision, no further review will be given to the application.
Article 199: When there is a need for technical review
during the reconsideration, SFDA shall organize the technical experts to
complete the review within the original prescribed time.
Chapter 15: Legal Liability
Article 200: If one of the provisions of Article 69 of
Administrative Permitting Laws occurs, SFDA should proceed with the
cancellation of relevant drug approval document, based on the request of the
related party or from its lawful authority.
Article 201: If an applicant is found to have provided
fraudulent drug registration information and / or sample product of the drugs
during the application of clinical study, SFDA shall not approve the
application, and warn the applicant. No more new application for clinical trail
from the same applicant will be accepted for one year. If the application has
already been approved, the approval certificate shall be canceled, and a fine
of RMB 10,000 - 30,000 shall be imposed. An application for the drug which is
signed by this individual or institution shall not be accepted for 3 years.
A database of fraudulent conduct by applicants shall be
maintained, and may be published.
Article 202: If an applicant is found to have provided
fraudulent drug registration information and / or sample product of the drugs
during the application of drug production or importation, SFDA shall not
approve the application, and warn the applicant. No more new application for
clinical trail from the same applicant will be accepted for one year. If the
application of production and / or importation of the drugs has already been
approved, the approval certificate shall be canceled, and a fine of RMB 10,000
- 30,000 shall be imposed, an application for the drug which is signed by this
individual or institution not be accepted for 5 years.
A database of fraudulent conduct by applicants shall be
maintained, and may be published.
Article 203: During the drug registration, if SFDA and
/or PDA and its staff are found to violate the provisions of this regulation
with one of the following occurrences, provisions of Article 72, Article 73,
Article 74, and Article 72 of Administrative Permitting Laws shall apply:
1) Did not want to accept a drug regulation
that met the lawful requirement.
2) Did not want to publicly publish the information
items of drug registration.
3) Failure to fulfill obligation to notify
applicant during the process of acceptance and approval.
4) Failure to notify the applicant in one
notification of all the supplemental information that must be supplemented, when
information submitted by applicant is incomplete or not meeting the statutory
form.
5) Failure to explain the reasons not to
accept or not to approval.
6) Approval of an application not meeting the
requirement of this regulation, or approval made beyond its authority.
7) Decision to not approve an application
meeting the requirement of this regulation, or failure to approve within the
time limit set out in this regulation.
8) Collect fee with no consultation, or
collect fee without reference to the statutory regulation.
9) Ask for or accept valuables or other
interest from any party.
Article 204: Upon the cancellation of Drug Manufacturing
License of a drug manufacturer, the Drug Approval Number held by the
manufacturer shall subsequently become null and void, and shall be cancelled by
SFDA, and the cancellation should be public announced.
Article 205: In the event that GLP or GCP requirements
were not complied with during the drug registration, sanctions shall be imposed
according to Article 79 of the Drug Administration Law.
Article 206: If a drug control institute issues a
fraudulent inspection report during performance of its legal duty for drug
inspection during the drug registration process, sanctions shall be imposed
according to Article 87 of the Drug Administration Law.
Article 207: If provision of Article 21 calls for an
experiment to be repeated, but an applicant refuses to repeat the experiment
according to relevant requirements, the applicant shall be warned, and ordered
to correct the situation. If the applicant refuses to make corrections, the
application entitlement shall be canceled.
Chapter 16: Miscellaneous
Article 208: Format of Drug Approval Number should read
Guoyaozhun H(Z, S, J)+ 4 digit of year + 4 digit of serial number, where H
denote chemical drug, Z denote TCM, S denote biological products and J denote
import drug.
Format of Import Drug License should read H(Z, S)+ 4
digit of year + 4 digit of serial number, and Format of Drug Product License
should read H(Z, S)C+ 4 digit of year + 4 digit of serial number, where H
denote chemical drug, Z denote TCM, and S denote biological products. For the
registration certificate number of repacking of large package from ex-China, B
will added as the prefix of the original certificate number.
Format of New Drug Certificate should read Guoyaozheng
H(Z, S)+ 4 digit of year + 4 digit of serial number, where H denote chemical
drug, Z denote TCM, and S denote biological products.
Article 209: In addition to this Regulation, the application
for narcotics, psychotropic, medical-use toxic drugs and radioactive drugs
shall also be administered according to other relevant national regulations.
Article 210: SFDA shall promulgate separate regulation
for the registration of TCM material, TCM herb and import TCM material that
regulated with approval number.
SFDA shall promulgate separate regulation for the
registration of in vitro diagnosis reagent that regulated with drug regulation.
Article 211: This Regulation is effective date of
publication. Drug Registration Regulation (temporary) promulgated by SDA (SDA
order 35) on October 30, 2002 shall be abolished accordingly.