Provisions for Drug Registration
Chapter
I
General
Provisions
Article
1 The Provisions are formulated for the purposes of ensuring the safety,
efficacy and quality of drugs and regulating drug registration in accordance
with the Drug Administration Law of the People's Republic of China (hereinafter
referred to as the Drug Administration Law), Administrative Permission Law of
the People's Republic of China (hereinafter referred to as Administrative
Permission Law) and the Regulations for Implementation of the Drug
Administration Law of the People's Republic of China (hereinafter referred to
as the Regulations for Implementation of the Drug Administration Law).
Article
2 The Provisions apply to the applications for drug clinical trial, drug
production or import, and conducting drug approval, relevant testing for drug
registration, or regulation thereof, within the territory of the People's Republic
of China.
Article
3 Drug registration refers to the process of review and approval on which the
State Food and Drug Administration, in accordance with the official procedures,
evaluates the safety, efficacy and quality of the drugs applied for marketing,
and decides whether or not to approve such an application.
Article
4 The State encourages the research and development of new drugs and adopts the
special review and approval with respect to innovative drugs, new drugs for
serious and life-threatening diseases and to address unmet medical needs and
drugs.
Article
5 The State Food and Drug Administration is in charge of drug registration
nationwide, and responsible for reviewing and approving the clinical trial,
production and importation of drugs.
Article
6 The drug registration shall follow the principles of openness, fairness and
justice.
The
State Food and Drug Administration adopts the system of collective
responsibility of the chief reviewers, the system of publicizing and
challenging relevant persons, and the system of responsibility tracing, with
social supervision in such procedures as acceptance, inspection, review and
approval and sending.
Article
7 In the process of drug registration, the drug regulatory department shall
make known to the general public, and hold hearings on, the matters which it
deems of vital importance and involving public interests for the granting of
permission.
Prior
to making the decision of administrative licensing that has a direct bearing on
the vital interest between the applicant and the other party, the drug
regulatory department shall inform the applicant and the interested party of
their rights of requesting for hearings, making statements and argues.
Article
8 The drug regulatory department shall provide the applicant with access to
information on the status of the acceptance, examination, inspection, review
and approval of drug registration application and the final resolution.
The
drug regulatory department shall publicize the following information on its
official websites or at the official premises for accepting applications:
(1)
the items, procedures, fees and their basis, and timelines of the drug
registration, index of all the data needed to be submitted and model text of
the application form;
(2)
the name list and other relevant information on the persons involved in the
acceptance, examination, inspection, review and approval of drug registration;
and
(3)
general information about categories of approved drugs, etc.
Article
9 The drug regulatory department, relevant institutions and persons involved in
the drug registration have an obligation to keep the technical secrets and
trial data submitted by the applicant confidential.
Chapter
II
Application
for Drug Registration
Article
10 An applicant for drug registration (hereinafter referred to as applicant)
refers to the institution that submits a drug registration application and
assumes corresponding legal liability.
A
domestic applicant shall be an institution legally registered within the
territory of People's Republic of China that independently assumes civil
liability and an overseas applicant shall be a legal overseas drug
manufacturer. Where an overseas applicant applies for import drug registration,
it shall be done by its branch or entrusted agency within the territory of
People's Republic of China.
The
persons who handle the application for drug registration shall have
professional knowledge and be familiar with the laws and regulations on, and
the technical requirements for, drug registration.
Article
11 Drug registration applications include applications for new drugs, generic
drugs, import drugs and their supplementary applications as well as
re-registration applications.
Applications
of domestic applicants shall be handled according to the procedures and
requirements for new drugs or generic drugs, whereas applications of overseas
applicants shall be handled according to those for import drugs.
Article
12 Application for new drugs refers to application for registration of drugs
that have not been marketed within the territory of People's Republic of China.
Application
for changing dosage form or route of administration, or claiming a new
indication for marketed drugs, shall be submitted as the process of new drug
application.
Application
for generic drugs refers to registration application for producing the drugs
having existing national drug standard which is approved to be marketed by the
State Food and Drug Administration, whereas the application for biological
products shall be submitted as the process of new drug application.
Application
for import drugs refers to registration application for drugs manufactured
abroad to be marketed within the territory of the People's Republic of China.
Supplementary
application refers to application for variation, addition, or cancellation of
the items or contents approved in the original application for new drug,
generic drug or import drug.
Re-registration
application refers to application for continued production or importation of a
drug after the expiration of the valid term of the drug approval document.
Article
13 The applicant shall provide sufficient and reliable research data to prove
the safety, efficacy and quality of the drug, and be liable for the
authenticity of all the dossiers submitted.
Article
14 The cited literature of the dossier of drug registration shall indicate the
title of works or the name, volume number, issue and page of the journal. Where
the cited references are not published, an author's permission shall be
provided. For foreign literatures, Chinese translation shall be provided as
required.
Article
15 The State Food and Drug Administration shall obey the development plan and
policies on the pharmaceutical industry constituted by the State, and may
conduct assessment to the market value of drugs.
Article
16 In the process of drug registration, the drug regulatory department shall
conduct on-site inspection and causal inspection to the non-clinical studies
and clinical trials, as well as production site inspection for the
pre-marketing approval to confirm the authenticity, precision and integrity of
the dossier submitted.
Article
17 Where two or more institutions jointly apply for drugs, the application
shall be submitted to the drug regulatory department of the province,
autonomous region, or municipality directly under the Central Government, in
which the drug manufacturer is located; where the applicants are all drug
manufacturers, the application shall be submitted to the drug regulatory
department of the province, autonomous region, or municipality directly under
the Central Government, in which the manufacturer of pharmaceutical
preparations is located; where none of the applicants is a drug manufacturer,
the application shall be submitted to the drug regulatory department of the province,
autonomous region, or municipality directly under the Central Government, in
which the site for pilot production of drug samples is located.
Article
18 An applicant shall provide the information on patent and its ownership of
the applicant or other parties in China, in respect of the drug applied for
registration, its formula, manufacturing processes and/or uses, etc. Where
another party owns the patent in China, the applicant shall provide a statement
of non-infringement. The drug regulatory department shall publish the
information or the statement submitted by the applicant on its official
website.
Where
a patent dispute occurs in the process of drug registration, it shall be
settled in accordance with relevant laws and regulations on patent.
Article
19 For a drug patented in China, applicants other than the patentee may submit
the application for registration two years prior to the expiry date of the
patent. The State Food and Drug Administration shall review the drug
application in accordance with the Provisions, and after the expiry date of the
patent, check and issue the drug approval number, Import Drug License or a
Pharmaceutical Product License if the application conforms with the provisions.
Article
20 In accordance with the provisions in Article 35 of the Regulations for
Implementation of the Drug Administration Law, where a manufacturer or
distributor submits undisclosed drug experimental and other data which are
independently acquired in order to obtain approval for production or marketing of
the drug in question which contains any new chemical entity, the State Food and
Drug Administration shall, within six years from the approval date of the drug,
reject any application made by any other applicants by using the undisclosed
data of the drug in question without permission of the original applicant who
has obtained the drug approval, unless the data submitted are independently
acquired by the applicants other than the original one.
Article
21 Pre-clinical drug study for drug registration application includes drug
synthetic processes, extraction methods, physical and chemical properties,
purity, selection of dosage form, screening of formula, preparing processes,
testing methods, quality specifications, stability, pharmacology, toxicology
and animal pharmacokinetics, etc. For traditional Chinese medicine
preparations, in addition to the above-mentioned items, pre-clinical drug study
also includes the study in the source of the crude drugs, and of their
pre-treatment and processing, etc. For biological products, it also includes
study on the source, quality specifications, storage conditions, biological
characteristics and genetic stability of the starting materials such as
bacterial and viral seeds/strains, cell lines, bio-tissues, and immunological
study, etc.
Article
22 A pre-clinical drug study shall be in conformity with relevant requirements,
among which the Good Laboratory Practice for Non-Clinical Laboratory Studies
shall be implemented in the study of safety evaluation.
Article
23 The drug research institution shall have relevant staff, premises,
equipment, instruments and management system, which are appropriate to the
research project, and ensure the authenticity of all experimental data.
Experimental animals, reagents and raw materials used in the study shall
conform with the provisions of the State.
Article
24 An applicant who entrusts other institutions with a drug research,
individual experiment, testing, or pilot production, etc. shall conclude a
contract with the trustee, and state it clearly in the registration
application. The applicant shall be responsible for the authenticity of the
research data in the application dossier.
Article
25 Where the application is only for registration of pharmaceutical
preparations, any drug substance used for the study shall have a drug approval
number, an Import Drug License or a Pharmaceutical Product License, and be
acquired through legitimated means. Where a drug substance used for the study
has no drug approval number, Import Drug License or Pharmaceutical Product
License, the use of drug substance in study shall be approved by the State Food
and Drug Administration.
Article
26 The research data in application dossier for drug registration provided by
an overseas drug research institution shall be attached with the items and
pages of the information, and with notarized documents proving that the said
drug research institution is legally registered overseas. The State Food and
Drug Administration may send staff to conduct on-site inspection in needs of
drug review.
Article
27 The drug regulatory department may request the applicant or the drug
research institution responsible for testing to repeat the test based on the
items, methods and data specified in the application documents, and may also authorize
a drug testing institute or another drug research institution to repeat the
test or conduct methodological verification.
Article
28 The drug study shall be conducted according to the relevant technical
guidelines issued by the State Food and Drug Administration. Where an applicant
conducts the study by adopting other evaluation methods and techniques,
supporting data proving the scientific feasibility of such methods and
techniques shall be provided.
Article
29 An applicant who obtains the drug approval number shall manufacture
according to the manufacturing processes approved by the State Food and Drug
Administration.
The
drug regulatory department shall supervise and inspect the applicant's
manufacture in accordance with the approved manufacturing processes and quality
specifications.
Chapter
III
Drug
Clinical Trials
Article
30 Any drug clinical trial, including bioequivalence study, shall be approved
by the State Food and Drug Administration, and shall be in compliance with the
Good Clinical Practice.
Drug
regulatory department shall supervise and inspect the approved clinical trials.
Article
31 Clinical trials shall be conducted for new drug registration applications.
As for generic drug registration applications and supplementary applications, clinical
trials shall be conducted in accordance with the requirements in the Annex of
the Provisions.
A
clinical trial consists of phases I, II, III and IV.
Phase
I Clinical Trial: initial clinical pharmacology and safety evaluation studies
in humans. These studies are designed to observe tolerability of humans to and
pharmacokinetics of a new drug, in order to provide basis for establishing the
administration regimen.
Phase
II Clinical Trial: preliminary evaluation of therapeutic effectiveness of a
drug. The purposes are to preliminarily evaluate the therapeutic effectiveness
and safety of the drug for particular indication(s) in patients, and provide
evidence for design of Phase III clinical trial and settlement of
administrative dose regimen. According to specific trial objectives, this phase
of trial may be designed in various forms, including the randomized blind
controlled clinical trial.
Phase
III Clinical Trial: confirmation of therapeutic effectiveness of a drug. The
purposes are to further verify drug therapeutic effectiveness and safety on
eligible patients with target indication(s), to evaluate overall benefit-risk
relationships of the drug, and to ultimately provide sufficient evidence for
the review of drug registration application. The study, in general, shall be a
randomized blind controlled trial with an adequate sample size.
Phase
IV Clinical Trial: a new drug post-marketing study. The purposes are to assess
therapeutic effectiveness and adverse reactions when a drug is widely used, to
evaluate overall benefit-risk relationships of the drug when used among general
population or specific groups, and to adjust the administration dose, etc.
Bioequivalence
study refers to a human study, which applies bioavailability study methods with
pharmacokinetic parameters as indicators to compare active ingredient
absorption rate and extent of the preparations in the same or different dosage
forms of a drug in terms of statistical differences under the same experimental
condition.
Article
32 The sample size of a drug clinical trial shall conform to the objectives of
the clinical trial and fulfill statistical requirements, and shall be no
smaller than the minimum number of subjects required by the Annex of the
Provisions. Where there are circumstances, regarding rare or special diseases,
etc., which request clinical sample size reduction or clinical trial exemption,
a request shall be made with the clinical trial application, and reviewed and
approved by the State Food and Drug Administration.
Article
33 As for vaccines prepared during bacterial or viral strain screening or other
special drugs, if confirmed without any suitable animal model and laboratory
measurement in terms of curative effectiveness, clinical trials may be applied
for to the State Food and Drug Administration, subject to ensuring the safety
of trial subjects.
Article
34 When a drug clinical trial is approved, the applicant shall select
institutions for the clinical trial from those certified for conducting drug
clinical trials.
Article
35 Drugs used for clinical trials shall be manufactured in facilities in
compliance with the Good Manufacturing Practice for Pharmaceutical Products
(GMP). The manufacturing process shall strictly meet the requirements of the
GMP.
The
applicant shall be responsible for the quality of the drugs used for clinical
trials.
Article
36 The applicant may conduct the testing for clinical trial drugs by itself, or
entrust a drug testing institute specified in the Provisions to conduct such
testing, according to its proposed specifications. Vaccines, blood products and
other biological products specified by the State Food and Drug Administration
shall be tested by drug testing institutes designated by the State Food and
Drug Administration.
A
drug can be used for a clinical trial only after tested as qualified.
Drug
regulatory departments may conduct sampling and testing on drugs used for
clinical trials.
Article
37 Prior to conducting a clinical trial, the applicant shall report to the
State Food and Drug Administration for record while copying to the drug
regulatory department of the seat of the clinical trial institution and that of
the province, autonomous region or municipality directly under the Central
Government to receive the application a confirmed clinical trial protocol, the
name of the principal investigator at the institution in charge of the clinical
trial, a list of participating institutions and names of investigators
wherefrom, an ethic committee approval letter, and a template of the informed
consent form, etc.
Article
38 Where the applicant finds a clinical trial institution violating relevant
regulations or failing to implement the clinical trial protocol, it shall urge
the institution to make corrections; if the circumstances are serious, the
applicant may demand suspension or termination of the clinical trial, and shall
report the matter to the State Food and Drug Administration and the drug
regulatory departments of the relevant provinces, autonomous regions or
municipalities directly under the Central Government.
Article
39 After completion of a clinical trial, the applicant shall submit a clinical
trial final report, a statistical analysis report and its database to the State
Food and Drug Administration.
Article
40 A clinical trial shall be conducted within three years after approval. If
overdue, the original approval documents shall be invalid. If the clinical
trial is still needed, the application shall be reapplied for.
Article
41 If any serious adverse event occurs during the clinical trial, the investigators
shall report to the drug regulatory departments of the relevant provinces,
autonomous regions or municipalities directly under the Central Government and
the State Food and Drug Administration and notify the applicant within 24
hours, and report to the ethic committee in time.
Article
42 In any of the following circumstances during a clinical trial, the State
Food and Drug Administration may order the applicant to modify the protocol,
suspend or terminate the clinical trial,:
(1)
the ethic committee fails to perform its duty;
(2)
safety of the subjects cannot be adequately ensured;
(3)
a serious adverse event is not reported within the specified timeline;
(4)
there is evidence to prove that the drug used for the clinical trial is not
effective;
(5)
a quality problem of the drug used for the clinical trial occurs;
(6)
there is a fraud in the clinical trial; or
(7)
there is any other case violating the Good Clinical Practice.
Article
43 Where there is any large-scale of and unexpected adverse reaction or serious
adverse event, or there is evidence to prove any serious quality problem of the
drug used for a clinical trial, the State Food and Drug Administration or the
drug regulatory department of the province, autonomous region or municipality directly
under the Central Government may take emergency control measures and order to
suspend or terminate the clinical trial. The applicant and clinical trial
institution must stop the clinical trial immediately.
Article
44 An overseas applicant intending to conduct an international multi-center
clinical trial in China shall submit an application to the State Food and Drug
Administration in accordance with the Provisions, and fulfill the following
requirements:
(1)
the drugs used for clinical trials shall be already approved or in phase II or
III clinical trial overseas. The State Food and Drug Administration does not
accept any overseas applicant’s international multi-center clinical trial
application for any preventive vaccine not being registered overseas yet;
(2)
while approving to conduct an international multi-center clinical trial, the
State Food and Drug Administration may require the applicant to conduct phase I
clinical trial first in China;
(3)
when conducting an international multi-center clinical trial in China, if there
are any observed serious adverse reaction and unexpected adverse reaction
associated with the drug in any country, the applicant shall, in accordance
with relevant regulations, report to the State Food and Drug Administration in
time;
(4)
the applicant shall submit a complete clinical trial report to the State Food
and Drug Administration after the completion of a clinical trial; and
(5)
the data obtained from an international multi-center clinical trial for drug
registration application in China shall be in conformity with the requirements
on clinical trial in the Provisions. All the study materials of the
international multi-center clinical trial shall be submitted.
Chapter
IV
Application
and Approval of New Drugs
Article
45 The State Food and Drug Administration may implement special review and
approval in cases of the following applications:
(1)
active ingredients extracted from plants, animals and minerals, etc. and their
preparations not yet marketed in China, and newly discovered Chinese crude
drugs and their preparations;
(2)
chemical drug substances and their preparations and biological products not yet
approved for marketing in China or abroad;
(3)
new drugs for the treatment of diseases such as AIDS, malignant tumors and rare
diseases, etc. with significant clinical advantage; and
(4)
new drugs for the treatment of diseases, for which effective therapeutic
methods are not available.
For
drugs specified in the previous clause, applicants may apply for special review
and approval in the process of drug registration. The Center for Drug
Evaluation of the State Food and Drug Administration shall organize expert
meetings to discuss and determine whether or not to conduct special review and
approval for the drugs.
Specified
measures for special review and approval shall be formulated separately.
Article
46 Where a new drug is co-developed by several institutions, the registration
can be applied for by one of the institutions, and its duplicate application
shall not be made by the others. If a joint application for registration is
needed, the institutions shall co-sign as the applicant of the new drug. Each
approved new drug, including its different strengths shall be produced by only
one institution.
Article
47 For the registration application to change the dosage form without changing
administration route of a marketed drug, new techniques shall be employed to
improve the drug quality and safety, and the changed dosage form shall have
significant clinical advantage compared with the previous dosage form.
Registration
applications to change the dosage form without changing the route of
administration or to claim any new indication shall be submitted by certified
manufacturers, with exceptions for special dosage forms such as targeting
delivery, sustained release and controlled release preparations, etc.
Article
48 In the process of the review and approval of a new drug, the registration
classification and technical requirements thereof shall not be changed, even
though the preparations of the same active ingredients are approved for
marketing abroad.
In
the process of the review and approval of a new drug, the registration
classification and technical requirements thereof shall not be changed, even
though the preparations of the same active ingredients applied for by domestic
manufacturers are approved for marketing in China.
Article
49 The dossier for drug registration application shall be submitted at one
time. No other technical materials should be added by the applicant after a
drug registration application is accepted, with the exceptions for applications
of special review and approval, new finding regarding drug safety, or
supplementary materials as required. Where an applicant deems it integrant for
any new technical material to be supplemented, the submitted application shall
be withdrawn. Only if no same product is in the new drug observation period,
the applicant may re-apply in compliance with the relevant requirements in the
Provisions.
Section
1
Clinical
Trials for New Drugs
Article
50 After completing the pre-clinical study, the applicant shall fill the
Application Form for Drug Registration, and report authentically relevant
materials to the drug regulatory department of the province, autonomous region
or municipality directly under the Central Government where the applicant is
located.
Article
51 Drug regulatory departments of provinces, autonomous regions, or
municipalities directly under the Central Government shall conduct the
preliminary review of the application dossiers, and issue a acceptance notice
of drug registration application if requirements are met, or issue a
non-acceptance notice, in which reasons shall be given, of drug registration
application if requirements are not met.
Article
52 Drug regulatory departments of provinces, autonomous regions, or
municipalities directly under the Central Government shall organize to conduct
on-site inspections of the drug research and development conditions and raw
data, make preliminary review of the submitted dossiers, and provide review
opinions within five days from the date it accepts an application. Where the
drug for which the registration is applied is a biological product, samples
from three production batches thereof shall also be collected for testing, and
a notice for the testing for registration shall be issued to the drug testing
institute.
Article
53 Drug regulatory departments of provinces, autonomous regions, or
municipalities directly under the Central Government shall deliver the review
opinions, inspection reports and the application dossiers to the Center for
Drug Evaluation of the State Food and Drug Administration within the specified
timeline, and notice the applicants.
Article
54 The drug testing institute that receives a notice for the testing for
registration shall test the samples according to the drug specifications
submitted by the applicant, verify the submitted drug specifications, and
submit a certificate of analysis for drug registration to the Center for Drug
Evaluation of the State Food and Drug Administration within the specified
timeline, and copy to the applicant.
Article
55 After receiving submitted dossiers, the Center for Drug Evaluation of the
State Food and Drug Administration shall organize pharmaceutical, medical and
other technical personnel to conduct technical review of the submitted dossiers
within the specified timeline, and may request, with reasons, applicants to
provide supplementary materials when necessary. After completing technical
reviews, the Center for Drug Evaluation shall give technical review opinions
and report together with relevant documents to the State Food and Drug
Administration.
The
State Food and Drug Administration shall make review and approval decisions
based on the technical review opinions. Where the regulations are conformed to,
a Drug Clinical Trial Approval shall be issued; where the regulations are not
conformed to, a Disapproval Notice shall be issued with reasons provided.
Section
2
Production
of New Drugs
Article
56 After completing drug clinical trials, applicants shall fill the Application
Form for Drug Registration, submit production application dossiers to the drug
regulatory departments of the provinces, autonomous regions, or municipalities
directly under the Central Government where the applicant is located, and at
the same time provide the raw materials and research information for preparing
reference standards to the National Institute for the Control of Pharmaceutical
and Biological Products.
Article
57 Drug regulatory departments of provinces, autonomous regions, or
municipalities directly under the Central Government shall conduct the
preliminary review of the application dossiers, and issue an acceptance notice
of drug registration application if requirements are met, or issue a non-acceptance
notice, in which reasons shall be given, of drug registration application if
requirements are not met.
Article
58 Drug regulatory departments of provinces, autonomous regions, or
municipalities directly under the Central Government shall organize to conduct
on-site inspections of the drug research and development conditions and raw
data, make preliminary review of the submitted dossiers, and provide review
opinions within five days from the date it accepts an application. For the
other drugs except biological products, samples of three production batches
shall also be collected for testing, and a notice of specifications
verification shall be issued to the drug testing institute.
Drug
regulatory departments of provinces, autonomous regions, or municipalities
directly under the Central Government shall deliver the review opinions,
inspection reports and the application dossiers to the Center for Drug
Evaluation of the State Food and Drug Administration within the specified
timeline, and notice the applicants.
Article
59 Drug testing institutes shall verify the submitted drug specifications and
give the verification opinions to the Center for Drug Evaluation of the State
Food and Drug Administration within the specified timeline, and at the same
time copy to the drug regulatory departments of the provinces, autonomous
regions, or municipalities directly under the Central Government that notify
them to conduct the verification, and the applicants.
Article
60 After receiving submitted dossiers, the Center for Drug Evaluation of the
State Food and Drug Administration shall organize pharmaceutical, medical and
other technical personnel to conduct technical review of the submitted dossiers
within the specified timeline, and may request, with reasons, applicants to
provide supplementary materials when necessary.
Where
the regulations are conformed to as reviewed, the Center for Drug Evaluation of
the State Food and Drug Administration shall notice the applicant to apply for
production site inspection and inform the Center for Drug Certification of the
State Food and Drug Administration. Where the regulations are not conformed to
as reviewed, the Center for Drug Evaluation of the State Food and Drug
Administration shall report the review opinions and relevant documents to the
State Food and Drug Administration; the State Food and Drug Administration
shall make a disapproval decision to the application based on the technical
review opinions, and issue a Disapproval Notice with reasons.
Article
61 The applicant shall apply for on-site inspection to the Center for Drug
Certification of the State Food and Drug Administration within six months from
the date it receives the notice of production site inspection.
Article
62 The Center for Drug Certification of the State Food and Drug Administration
shall, within 30 days from the date it receives the application for production
site inspection, organize on-site inspection of large-scale samples production,
verify the applicability of the manufacturing processes and at the same time
take samples of one batch of products (samples of three batches of products for
biological products), and provide production site inspection report to the
Center for Drug Evaluation of the State Food and Drug Administration within ten
days after the site inspection.
Article
63 Samples shall be produced at a plant with the GMP Certificate. As for a new
manufacturer, a new workshop established or the production of a dosage form
added at an existing manufacturer, the sample production shall meet the GMP
requirements.
Article
64 Drug testing institutes shall conduct sample testing according to the
verified specifications, and within the specified timeline, provide testing
reports to the Center for Drug Evaluation of the State Food and Drug
Administration, and copy to the relevant drug regulatory departments of the
provinces, autonomous regions, or municipalities directly under the Central
Government and the applicants.
Article
65 The Center for Drug Evaluation of the State Food and Drug Administration shall
make a general opinion based on the technical review opinions, production site
inspection reports and sample testing results, and report the general opinion
together with relevant documents to the State Food and Drug Administration. The
State Food and Drug Administration shall make a review and approval decision
based on the general opinion. Where the regulations are conformed to, a New
Drug Certificate shall be issued; if the applicant already has a Drug
Manufacturing Certificate and possesses the production conditions, a drug
approval number shall be issued at the same time; where the regulations are not
conformed to, a Disapproval Notice shall be issued with reasons.
A
New Drug Certificate shall not be issued to the approved registration applications
for changing dosage forms without changing route of administration or claiming
for new indications, with exceptions for special dosage forms such as targeting
delivery, sustained release and controlled release preparations, etc.
Section
3
New
Drug Observation Period
Article
66 In order to protect the public health, the State Food and Drug
Administration may set an observation period for any new drug approved for
production. The observation period of a new drug shall be no longer than five
years from the date the drug is approved for production.
During
the observation period of a new drug, the State Food and Drug Administration
shall not approve other manufacturers to produce, change dosage form of or
import the drug.
Article
67 A drug manufacturer shall investigate the manufacturing processes, quality,
stability, therapeutic effect and adverse reactions, etc. of a new drug in the
observation period, and report annually to the drug regulatory department of
the province, autonomous region, or municipality directly under the Central
Government, where it is located. Where a drug manufacturer fails to perform its
duties in the observation period, the drug regulatory department of the
province, autonomous region, or municipality directly under the Central
Government shall order it to make rectifications.
Article
68 Where institutions for drug manufacturing, distribution, use, testing or
supervision find any critical quality problem, serious or unexpected adverse
reaction of a new drug, they shall report to the drug regulatory department of
the province, autonomous region, or municipality directly under the Central
Government in time. Once receiving the report, the drug regulatory department
of a province, autonomous region, or municipality directly under the Central
Government shall organize prompt investigation, and report to the State Food
and Drug Administration.
Article
69 Where a drug manufacturer does not conduct production of the new drug, for
which an observation period is set, within two years from the date of the
approval, the State Food and Drug Administration may approve the application of
another drug manufacturer to produce the new drug and reset the observation
period of the drug.
Article
70 Starting from the date a new drug enters the observation period, any other
application for the clinical trial of the same drug already approved by the
State Food and Drug Administration may proceed along drug registration
application, review and approval procedures; where regulations are conformed
to, the State Food and Drug Administration shall approve the production or
importation of the same drug. The observations of the drugs produced by the
domestic manufacturers should be conducted together with the drug already in
the observation period.
Article
71 Starting from the date a new drug enters the observation period, other
registration applications for the same drug shall no longer be accepted. The
other applicants' applications for the same drug already accepted but not yet
approved for clinical trials shall be returned; upon the expiration of the
observation period of the drug, the registration of a generic or import drug
may be applied for.
Article
72 Where an application for an import drug registration is approved first, the
domestic application already approved for clinical trial of the drug may
proceed along drug registration application, review and approval procedures;
where regulations are conformed to, the State Food and Drug Administration
shall approve the production of the drug; or, the applicant may withdraw the
application, and submit a generic drug application. The other applications for
the same drugs already accepted but not yet approved for clinical trials shall
be returned; the registration of a generic drug may be applied for.
Chapter
V
Application
and Approval of Generic Drugs
Article
73 The applicant applying for registration of a generic drug shall be a drug
manufacturer. The applied drug shall be within the production scope specified
in the Drug Manufacturing Certificate.
Article
74 The generic drug shall have the identical active ingredients, route of
administration, dosage form, strength and therapeutic effects with the
registered drug. Where a drug has been produced by more than one manufacturer,
the selection of registered drugs for comparative study shall be in accordance
with relevant technical guidelines.
Article
75 To apply for the registration of a generic drug, the applicant shall fill
the Application Form for Drug Registration, submit relevant dossiers and apply
for production site inspection to the drug regulatory department of the
province, autonomous region, or municipality directly under the Central
Government where the applicant is located.
Article
76 Drug regulatory departments of provinces, autonomous regions, or municipalities
directly under the Central Government shall conduct the preliminary review of
the application dossiers, and issue an acceptance notice of drug registration
application if requirements are met, or issue a non-acceptance notice, in which
reasons shall be given, of drug registration application if requirements are
not met.
As
for a drug for which the protection of traditional Chinese medicine
preparations has been applied, from the date the application for the protection
is accepted through the date an administrative decision is made, the acceptance
of the application of its generic drug shall be suspended.
Article
77 Drug regulatory departments of provinces, autonomous regions, or
municipalities directly under the Central Government shall organize to conduct
on-site inspections of the drug research and development conditions as well as
raw data, and production site inspections according to the manufacturing
processes and quality specifications provided by the applicant, and take
samples of three consecutive batches of products, and send to the drug testing
institutes for testing within five days starting from the date they accept an
application.
The
production of samples shall be in conformity with the requirements in Article
63 in the Provisions.
Article
78 Drug regulatory departments of the provinces, autonomous regions, or
municipalities directly under the Central Government shall review the submitted
dossiers within the specified timeline and give review opinions. Where the
regulations are conformed to, they shall provide for the Center for Drug
Evaluation of the State Food and Drug Administration with the review opinions,
the check report, the production site inspection report and the application
dossiers, and inform the applicant. Where the regulations are not conformed to,
they shall issue a Disapproval Notice with reasons, and notify the drug testing
institute to terminate the testing for registration.
Article
79 Drug testing institutes shall conduct sample testing, provide testing
reports to the Center for Drug Evaluation of the State Food and Drug
Administration within the specified timeline, and copy to the drug regulatory
departments of the provinces, autonomous regions, or municipalities directly
under the Central Government that notify them to conduct the verification, and
the applicants.
Article
80 The Center for Drug Evaluation of the State Food and Drug Administration
shall organize pharmaceutical, medical and other technical personnel to conduct
technical review of the submitted dossiers within the specified timeline, and
may request, with reasons, applicants to provide supplementary materials when
necessary.
Article
81 The Center for Drug Evaluation of the State Food and Drug Administration
shall make a general opinion based on the technical review opinions, production
site inspection reports and sample testing results, and report the general
opinion together with relevant documents to the State Food and Drug
Administration. The State Food and Drug Administration shall make a review and
approval decision based on the general opinion. Where the regulations are
conformed to, it shall issue a drug approval number or a Drug Clinical Trial
Approval; where the regulations are not conformed to, it shall issue a
Disapproval Notice with reasons.
Article
82 After completing drug clinical trials, applicants shall submit clinical
trial data to the Center for Drug Evaluation of the State Food and Drug
Administration. The State Food and Drug Administration shall issue a drug
approval number or a Disapproval Notice based on the technical review opinions.
Article
83 As for a marketed drug with confirmed safety problems, the State Food and
Drug Administration may decide to suspend the acceptance or review and approval
of the application of its generic drugs.
Chapter
VI
Application
and Approval of Import Drugs
Section
1
Registration
of Import Drugs
Article
84 A drug being applied for importation shall have already obtained the drug
marketing authorization in the producing country or region where the overseas
pharmaceutical manufacturer is located; those not yet obtained marketing
authorization in the producing country or region, however confirmed with
safety, efficacy and clinical needs by the State Food and Drug Administration
may be approved for importation.
The
production of a drug applied for importation shall comply with the GMP
requirements of both the producing country or region where the drug
manufacturer is located and China.
Article
85 To apply for import drug registration, the applicant shall fill the
Application Form for Drug Registration, submit relevant dossiers and samples,
provide relevant approval documents, and submit the application to the State
Food and Drug Administration.
Article
86 The State Food and Drug Administration shall conduct the preliminary review
of the application dossiers, and issue an acceptance notice of drug
registration application and notify the National Institute for the Control of
Pharmaceutical and Biological Products to conduct testing for registration of
samples from three batches if requirements are met; or issue a non-acceptance
notice of drug registration application with reasons if requirements are not
met.
The
State Food and Drug Administration may organize to conduct on-site inspection
of development and production conditions, and take samples.
Article
87 The National Institute for the Control of Pharmaceutical and Biological
Products shall organize to conduct the testing for drug registration within
five days from the date it receives the dossiers and samples.
Article
88 The drug testing institutes undertaking the import drug testing shall
complete the testing for registration and submit the certificate of analysis
for drug registration to the National Institute for the Control of
Pharmaceutical and Biological Products within 60 days from the date they
receive the documents, samples and relevant reference standards.
Sample
testing and verification of specifications for controlled drugs or vaccines
shall be completed within 90 days.
Article
89 The National Institute for the Control of Pharmaceutical and Biological
Products shall organize experts to conduct technical review within 20 days from
the date it receives the certificate of analysis for drug registration and the
verified import specifications, and if necessary, conduct further verification
according to the review opinions.
Article
90 After completing the testing for import drug registration, the National
Institute for the Control of Pharmaceutical and Biological Products shall give
the verified specifications, certificate of analysis and opinions thereof to
the Center for Drug Evaluation of the State Food and Drug Administration, and
copy the applicants.
Article
91 The Center for Drug Evaluation of the State Food and Drug Administration
shall organize pharmaceutical, medical and other technical personnel to conduct
technical review of the submitted dossiers within the specified timeline, and
may request, with reasons, applicants to provide supplementary materials when
necessary.
Article
92 The Center for Drug Evaluation of the State Food and Drug Administration
shall make a general opinion based on the technical review opinions and sample
testing results, and report the general opinion together with relevant
documents to the State Food and Drug Administration. The State Food and Drug
Administration shall make a review and approval decision based on the general
opinion. Where the regulations are conformed to, a Clinical Trial Approval
shall be issued; where the regulations are not conformed to, a Disapproval
Notice shall be issued with reasons.
Article
93 After a clinical trial application is approved, the applicant shall conduct
the trial in accordance with the requirements in Chapter III of the Provisions
and the other relevant requirements.
After
a clinical trial is completed, the applicant shall fill the Application Form
for Drug Registration, submit the clinical trial data, other altered and
supplementary data in accordance with regulations, give in detail the basis and
reasons, and provide relevant approved documents.
Article
94 The Center for Drug Evaluation of the State Food and Drug Administration
shall organize pharmaceutical, medical and other technical personnel to conduct
comprehensive review of the submitted clinical trial data within the specified
timeline, and may request, with reasons, applicants to provide supplementary
materials when necessary.
The
State Food and Drug Administration shall make a review and approval decision
based on the general opinion. An Import Drug License shall be issued if
regulations are conformed to. For a drug applied for registration by a drug
manufacturer in Hong Kong, Macao or Taiwan of China, its application shall be
handled in reference to the application procedures for import drug
registration. If requirements are met, a Pharmaceutical Product License shall
be issued; if requirements are not met, a Disapproval Notice shall be issued
with reasons.
Article
95 To apply for importation of pharmaceutical preparations, approved documents
for the lawful sources of the immediate packaging materials and containers and
those of the drug substances and the excipients used for the pharmaceutical
preparations shall be provided. Where drug substances and excipients are not
yet approved by the State Food and Drug Administration, relevant data of
manufacturing processes, specifications and testing methods, etc. shall be
submitted.
Section
2
Registration
of Import Drug Repackaging
Article
96 The import drug repackaging refers to dividing a large pack into small ones
in China or adding outer-package to a drug with inner-package, placing insert
sheets and attaching labels, etc., after the production process of the finished
pharmaceutical preparations for the drug are completed overseas .
Article
97 To apply for import drug repackaging, the following requirements shall be
met:
(1)
the Import Drug License or Pharmaceutical Product License of the drug is
already obtained;
(2)
the drug shall be one that is not produced within the territory of China, or is
produced in China but unable to meet clinical needs;
(3)
one drug produced by a drug manufacturer shall be repackaged by only one drug
manufacturer. The term allowed for repackaging shall not exceed the expiry date
of the Import Drug License or Pharmaceutical Product License;
(4)
the inner–packaging of a drug in any dosage form for repackaging, except
tablets and capsules, shall be completed overseas;
(5)
a drug manufacturer that conducts repackaging shall hold the Drug Manufacturing
Certificate. To apply for repackaging of import unpackaged tablets and
capsules, the manufacturer shall also hold the GMP certificate covering the
dosage forms for repackaging; and
(6)
An application for drug repackaging shall be made one year prior to the
expiration of the Import Drug License or the Pharmaceutical Product License.
Article
98 An overseas drug manufacturer shall sign a contract for import drug
repackaging with a domestic drug manufacturer, and fill in the Drug
Supplementary Application Form.
Article
99 To apply for the repackaging of an import drug, the drug manufacturer
entrusted with repackaging of the drug shall submit an application to the drug
regulatory department of the province, autonomous region, or municipality
directly under the Central Government where it is located. The trustee shall
submit the Supplementary Drug Application Form filled in by the truster, the
relevant data and samples as well as the contract of entrustment, etc. The drug
regulatory department shall conduct the preliminary review of the submitted
documents. Where requirements are met, it shall issue a notice of acceptance;
where requirements are not met, it shall issue a notice of non-acceptance with
reasons.
The
drug regulatory department shall make review opinions, then submit the
application documents and review opinions to the State Food and Drug
Administration and inform the applicant at the same time.
Article
100 The State Food and Drug Administration shall review the submitted
documents. Where the regulations are conformed to, it shall issue an Approval
for Supplementary Drug Application and a drug approval number; where the
regulations are not conformed to, it shall issue a Disapproval Notice with
reasons.
Article
101 The repackaged import drugs shall comply with the registration
specifications for import drugs.
Article
102 The insert sheets and labels of a repackaged import drug shall be in
conformity with those of the import drug, and shall be indicated with the
approval number of the repackaging drug and the name of drug manufacturer.
Article
103 The testing for import of overseas pharmaceutical preparation in large
package shall be conducted according to the State Food and Drug Administration
regulations. The same specifications shall be used for the testing of both
repackaged and import products.
Article
104 The overseas drug manufacturer providing the drug shall be responsible for
the quality of the repackaged drug. If there is any quality problem, the State
Food and Drug Administration may withdraw the approval number of the repackaged
drug, revoke the Import Drug License or the Pharmaceutical Product License when
necessary according to the requirements of Article 42 of the Drug
Administration Law.
Chapter
VII
Application
of Non-Prescription Drugs
Article
105 Where the applied generic drug is regulated as a non-prescription drug, the
applicant shall indicate the item of non-prescription drug in the
"additional application items" of the Application Form for Drug
Registration.
Article
106 Where the applied generic drug is regulated as both a prescription and non-prescription
drug, the applicant may submit an application for either a prescription or
non-prescription drug according to the respective requirements.
Article
107 For any of the following circumstances, the applicant may indicate the item
of non-prescription drug in the "additional application items" of the
Application Form for Drug Registration. If relevant requirements for
non-prescription drugs apply, the drug shall be reviewed and approved, and
regulated as a non-prescription drug; if relevant requirements for
non-prescription drugs do not apply, it shall be reviewed and approved, and
regulated as a prescription drug:
(1)
To alter the dosage form of a non-prescription drug determined by the State
Food and Drug Administration without changing the indications or functions,
dosage and route of administration; or
(2)
To formulate a new fixed dose combination using active ingredients of
non-prescription drugs determined by the State Food and Drug Administration.
Article
108 For the registration application of a non-prescription drug, the insert
sheet and package label shall comply with the relevant regulations on
non-prescription drugs.
Article
109 For the registration application of an import drug categorized as
non-prescription drug, the application, review and approval procedures for
import drugs shall apply, and the technological requirements shall be the same
as those for the domestically produced non-prescription drugs.
Chapter
VIII
Submission,
Review and Approval of Supplementary Application
Article
110 For the variation of the items specified in the approval document and its
attachment for approved new drug development, drug production and import drug,
supplementary applications shall be made.
The
applicant shall assess the implications of the variation to the safety,
efficacy and quality of the drug, and conduct corresponding technical studies
in reference to relevant technical guidelines.
Article
111 The applicant shall fill in Supplementary Drug Application Form and submit
relevant dossier and explanation to the drug regulatory department of the
province, autonomous region, or municipality directly under the Central
Government where the applicant is located. Drug regulatory departments of
provinces, autonomous regions, or municipalities directly under the Central
Government shall conduct the preliminary review of the application dossiers,
and issue an acceptance notice of drug registration application if requirements
are met, or issue a non-acceptance notice, with reasons, of drug registration
application if requirements are not met.
Article
112 For the supplementary application of an import drug, the applicant shall
submit relevant dossier and explanations to the State Food and Drug
Administration, and provide documents approving the variation issued by the
drug regulatory department of the producing country or region. The State Food
and Drug Administration shall conduct the preliminary review of the application
dossiers, and issue an acceptance notice of drug registration application if
requirements are met, or issue a non-acceptance notice, in which reasons shall
be given, of drug registration application if requirements are not met.
Article
113 For any supplementary application to amend the drug registration
specifications, change excipients for pharmaceutical use in the drug
formulation, or modify the manufacturing process that affects the drug quality,
etc., the drug regulatory department of the province, autonomous region, or
municipality directly under the Central Government shall provide a review
opinion, report it to the State Food and Drug Administration for review and
approval, and inform the applicant at the same time.
For
supplementary application to amend the drug registration specifications, the
drug testing institute shall verify the specifications when necessary.
Article
114 For any supplementary application to change the name of a domestic drug
manufacturer, the shelf-life of a domestically produced drug, or the production
site by a domestic drug manufacturer internally, etc., the drug regulatory
departments of the provinces, autonomous regions, or municipalities directly
under the Central Government shall conduct the acceptance, review and approval.
Where the regulations are conformed to, it shall issue an Approval for
Supplementary Drug Application, and report to the State Food and Drug
Administration for record; where the regulations are not conformed to, it shall
issue a Disapproval Notice with reasons.
Article
115 Any supplementary application to alter drug packaging label in accordance
with regulations, or amend the insert sheet as required by the State Food and
Drug Administration, etc. shall be filed to the drug regulatory department of
the province, autonomous region, or municipality directly under the Central
Government for record.
Article
116 Supplementary applications of import drugs shall be reviewed and approved
by the State Food and Drug Administration. Those supplementary applications to
change the place of production of the drug substance used for any import drug
preparation, change the appearance of an import drug not resulting in
specification changes, amend the insert sheet of an import drug according to
the national specifications or the requirements of the State Food and Drug
Administration, update the safety information in the insert sheet of an import
drug, alter drug packaging label in accordance with regulations, or change the
registration agent shall be filed to the State Food and Drug Administration for
record.
Article
117 For supplementary applications of drug manufacturing technology transfer,
altering formula or manufacturing process that may affect product quality,
etc., the drug regulatory department of the province, autonomous region, or
municipality directly under the Central Government shall organize production
site inspection, according to the attachment of the Letter of Approval for Drug
Registration or the verified manufacturing process. Drug testing institutes
shall conduct testing on samples of three batches of product.
Article
118 While reviewing drug supplementary applications, the State Food and Drug
Administration may require, with reasons, the applicants to submit additional
documents when necessary. Where the regulations are conformed to, it shall
issue an Approval for Supplementary Drug Application and a drug approval
number; where the regulations are not conformed to, it shall issue a
Disapproval Notice with reasons.
Article
119 After the supplementary application is approved, if a drug approval
document is to be renewed, the original one shall be cancelled by the State
Food and Drug Administration; if an additional drug approval certificate is to
be issued, the original one shall remain valid.
Chapter
IX
Drug
Re-Registration
Article
120 The valid term of a drug approval number, Import Drug License or
Pharmaceutical Product License issued by the State Food and Drug Administration
is five years. To continue its drug production or importation, the applicant
shall submit a re-registration application six months prior to the expiry date.
Article
121 Within the valid term of a drug approval number, Import Drug License or
Pharmaceutical Product License, the applicant shall conduct systematic
assessment on the safety, efficacy and quality control of the drug such as
relevant research results in the observation period, adverse reaction
monitoring, production control and product quality consistency, etc.
Article
122 Where applying for drug re-registration, the holder of a drug approval
number shall submit the application to the drug regulatory department of the
province, autonomous region, or municipality directly under the Central
Government, fill in the Application Form for Drug Re-registration, and provide
relevant data.
Where
applying for an import drug re-registration, the applicant shall submit the
application to the State Food and Drug Administration.
Article
123 Drug regulatory departments of provinces, autonomous regions, or
municipalities directly under the Central Government shall review the
application dossiers, and issue a acceptance notice of drug re-registration
application if requirements are met, or issue a non-acceptance notice, in which
reasons shall be given, of drug re-registration application if requirements are
not met.
Article
124 Drug regulatory departments of provinces, autonomous regions, or
municipalities directly under the Central Government shall review the
application dossiers within six months starting from the date of acceptance,
and approve the re-registration application if regulations are conformed to, or
report to the State Food and Drug Administration if regulations are not
conformed to.
Article
125 The State Food and Drug Administration shall deal with import drug
re-registration applications, complete the review within six months, and
approve the re-registration application if regulations are conformed to, or
issue a non-acceptance notice, in which reasons shall be given, if regulations
are not conformed to.
Article
126 In any of the following circumstances, a drug shall not be re-registered:
(1)
the application for re-registration is not made prior to the expiry date;
(2)
the relevant requirements set by the State Food and Drug Administration when
approved for marketing are not met;
(3)
the phase IV clinical trial is not completed as required;
(4)
the adverse drug reaction monitoring is not conducted in accordance with
regulations;
(5)
there are uncertain therapeutic efficacy, serious adverse reaction or other
factors harmful to human health upon re-evaluation by the State Food and Drug
Administration;
(6)
the drug approval documents shall be withdrawn in accordance with the
provisions of the Drug Administration Law;
(7)
the production conditions prescribed in the Drug Administration Law are not
met;
(8)
the obligation of observation period is not fulfilled in accordance with
regulations; or
(9)
there are other circumstances not in conformity with relevant regulations.
Article
127 After receiving the opinions from the drug regulatory departments of the
provinces, autonomous regions, or municipalities directly under the Central
Government, the State Food and Drug Administration shall review the
application. Where the regulations on drug re-registration are not conformed
to, a notice of rejection for re-registration shall be issued with reasons.
Where
a re-registration application has been rejected, except where the drug approval
document is withdrawn due to lawfully defined reasons, the drug approval
number, Dug Import License or Pharmaceutical Production Certificate shall be
withdrawn on the expiry date.
Chapter
X
Testing
for Drug Registration
Article
128 Testing for drug registration consists of sample testing and verification
of specifications.
Sample
testing refers to the testing of samples conducted by a drug testing institute
according to the specifications submitted by an applicant or checked by the
State Food and Drug Administration.
Verification
of specifications refers to the laboratory testing and review conducted by a
drug testing institute on the feasibility and scientific basis of the testing
methods and the controllability of the set items and indicators of drug quality
in the submitted specifications.
Article
129 The National Institute for the Control of Pharmaceutical and Biological
Products or the drug testing institutes of the provinces, autonomous regions,
and municipalities directly under the Central Government shall take charge of
the testing for drug registration. The National Institute for the Control of
Pharmaceutical and Biological Products shall arrange testing for import drug registration.
Article
130 The testing for registration of the following drugs shall be conducted by
the National Institute for the Control of Pharmaceutical and Biological
Products or the drug testing institutes designated by the State Food and Drug
Administration:
(1)
drugs prescribed in subparagraph (1) and (2) of Article 45 of the Provisions;
(2)
biological products and radioactive pharmaceuticals; and
(3)
other drugs specified by the State Food and Drug Administration.
Article
131 Where a drug is permitted entering a special review and approval procedure,
the drug testing institute shall give priority to sample testing and
specification verification.
Article
132 A drug testing institute engaged in testing for drug registration shall, in
compliance with the requirements set forth by the Good Laboratory Practice of
drug testing institute and national metrology accreditation, have qualified
personnel and adequate equipment, and comply with the quality assurance system
and technical requirements of the testing for drug registration.
Article
133 An applicant shall provide the relevant data, samples and reference
standards, or assist in sampling, which are required for the testing for drug
registration. The amount of samples shall be three times the amount used for testing
and, for biological products, manufacturing record for the relevant batches of
products shall also be provided.
Article
134 While verifying the specifications of a new drug, the drug testing
institute shall, in addition to sample testing, give verification opinions in
respect of the specifications and test items, etc., of the drug referring to
the study data, the specifications of the same kind of products at home and
abroad and relevant requirements.
Article
135 Where the specifications are required to be reestablished, the applicant
shall not entrust the drug testing institute that gave verification opinions to
conduct the specification study of the drug; and the drug testing institute
shall not accept such entrustment.
Chapter
XI
Drug
Registration Specifications and Insert Sheet
Section
1
Drug
Registration Specifications
Article
136 National drug standards refer to the Pharmacopoeia of the People's Republic
of China, drug registration specifications, etc. published by the State Food
and Drug Administration, including the technical requirements such as
specifications, testing methods and manufacturing processes, etc.
Drug
registration specifications refer to the specified specifications of the
applied drug approved by the State Food and Drug Administration to the
applicant. The specifications shall be implemented by the drug manufacturer
producing the drug.
Drug
registration specifications shall not be lower than those required by the
Chinese Pharmacopoeia.
Article
137 The establishment of items and the testing methods for drug registration
specifications shall be in conformity with the basic requirements of the
Chinese Pharmacopoeia, the technical guidelines and rules for compiling the
national drug standards published by the State Food and Drug Administration.
Article138
An applicant shall select representative samples for drug registration
specifications study.
Section
2
Drug
Reference Standards
Article
139 Drug reference standards refer to the materials used in physical, chemical
or biological testing specified in specifications and have assigned values of a
quantity, and are used for equipment calibration, method validation or value
assignment of drugs to be tested, and include reference standards, reference
substances, reference crude drugs and reference reagents.
Article
140 The National Institute for the Control of Pharmaceutical and Biological
Products shall be responsible for the characterization of national reference
standards.
The
National Institute for the Control of Pharmaceutical and Biological Products
may organize relevant drug testing institute of provinces, autonomous regions,
and municipalities directly under the Central Government, drug research
institutions or drug manufacturers to undertake collaborative assays of such
standards.
Article
141 The National Institute for the Control of Pharmaceutical and Biological
Products shall be responsible for the overall technical evaluation of the
characterized reference standards in respect of the data of source material
selection, preparation methods, testing methods and results, accuracy of value
assignment, traceability, stability, filling and packaging conditions, etc. and
shall conclude whether or not the candidate materials can be used as national
reference standards.
Section
3
Drug
Name, Insert Sheet and Label
Article
142 The name, insert sheet and label of any drug for which the registration is
applied, shall comply with the provisions of the State Food and Drug
Administration.
Article
143 The drug insert sheet and label shall be provided by the applicant. The
Center for Drug Evaluation of the State Food and Drug Administration shall
review the contents thereof except the manufacturer information, and the State
Food and Drug Administration shall review and approve the data when approving
the drug production.
The
applicant shall be responsible for making the drug insert sheet and label
scientific, standard and accurate.
Article
144 The applicant shall monitor the safety and efficacy of a marketed drug, and
submit supplementary application to modify the drug insert sheet in time.
Article
145 The applicant shall print the insert sheets and labels according to the
format and requirements established by the State Food and Drug Administration,
and in conformity with the contents approved.
Chapter
XII
Timeline
Article
146 The drug regulatory department shall follow the provisions on the timeline
for drug registration set forth in the Drug Administration Law, the
Administrative Permission Law and the Regulations for Implementation of the
Drug Administration Law. The timeline for drug registration in the Provisions
refers to the maximum time for acceptance, review and approval of drug
registration. The time for the suspension of the review and approval prescribed
in laws and regulations or for the applicant to supplement data is not
included.
The
time for the testing for drug registration and for the review shall be kept in
accordance with the Provisions. Where there is a need for time extension in
particular situation, it, with reasons provided, shall be reported to the State
Food and Drug Administration for approval, and the applicant shall be informed
thereof.
Article
147 Drug regulatory departments shall conduct preliminary review on
applications, and proceed according to the following circumstances
respectively:
(1)
Where no administrative approval is needed for any application item by law, the
non-acceptance of the application thereof shall be informed to the applicant in
time;
(2)
Where an application item is not subject to the jurisdiction of the concerned
departments by law, it shall be decided not to accept the application in time
and informed to the applicant to apply to the relevant administrative
departments;
(3)
Where there is an error that can be corrected on-site in the dossier, the
on-site correction shall be allowed;
(4)
Where the dossier is incomplete or not conformed with the defined format, the
applicant shall be informed on-site or within five days at once of what to be
supplemented or corrected; if it is not informed to the applicant within the
timeline, the application is regarded as accepted on the date the dossier is
received; and
(5)
Where the application item is subject to the jurisdiction of the concerned
departments, and the dossier is complete and conformed with the defined format
or the applicant has submitted all the required supplementary or corrected
data, the application of drug registration shall be accepted.
Where
a drug regulatory department accepts or rejects a drug registration
application, it shall issue a written receipt on which there shall be a stamp
of registration and date.
Article
148 The drug regulatory department of a province, autonomous region, or
municipality directly under the Central Government shall complete the check of
drug development conditions and raw data, the review of application dossiers,
sampling, the notice to drug testing institutes for conducting testing for drug
registration, the submission of review opinions, inspection report and
application dossiers to the State Food and Drug Administration, and the notice
to the applicant of the review opinions within 30 days starting from the date
an application is accepted.
Article
149 The time for the testing for drug registration shall be kept in accordance
with the following provisions:
(1)
sample testing: 30 days; sample testing and specifications verification : 60
days; and
(2)
sample testing of a controlled drug or vaccine: 60 days; sample testing and
specifications verification: 90 days.
The
sample testing for a drug used for clinical trial conducted by a drug testing
institute, as prescribed in Article 36 of the Provisions, shall be completed
within the time for sample testing in the previous clause.
Article
150 The time for technical review shall be kept in accordance with the following
provisions:
(1)
new drug application for clinical trial: 90 days; any drug permitted to enter
the special review and approval procedures: 80 days;
(2)
new drug application for production: 150 days; any drug permitted to enter the
special review and approval procedures: 120 days;
(3)
the application for changing the dosage form of a marketed drug or for a
generic drug: 160 days; and
(4)
the supplementary application subject to technical review: 40 days.
The
time for the technical review of an import drug registration application shall
be kept in accordance with the previous clause.
Article
151 Where the applicant is required to supplement data in the process of
technical review, a Deficiency Notice should be issued at one time. Where the
applicant disagrees on the contents of the Deficiency Notice, the opinions of
the applicant may be heard vis-à-vis. The applicant shall provide supplementary
data at one time according to the requirements in the notice within four
months; where an application enters the special review and approval procedures,
it shall be handled in conformity with the requirements of the relevant
procedures.
After
receiving the supplementing data, the technical review shall be completed in no
more than one third of the original time; for applications entering the special
review and approval procedures, the review shall be completed in no more than
one fourth of the original time.
Where
an application is recalled by the applicant in the process of drug
registration, the review and approval procedure is terminated henceforth.
Article
152 The State Food and Drug Administration shall make the review and approval
decision within 20 days; where a decision cannot be made within 20 days,
another ten days may be extended with the approval of the State Food and Drug
Administration head in charge, and the applicant shall be informed of the
reason of the time extended.
Article
153 The State Food and Drug Administration shall issue and deliver relevant
administrative licensing certificates within ten days from the date the review
and approval decision is made.
Chapter
XIII
Second
Review
Article
154 Where there is any of the following circumstances, the State Food and Drug
Administration shall not approve the application:
(1)
different applicants submit the same or almost the same research data without
justified reasons;
(2)
when the application dossier is found false in the process of registration, and
the applicant cannot prove the authenticity thereof;
(3)
the design and performance of the research project are not able to support to
evaluate the safety, efficacy and quality of the drug applied for registration
;
(4)
there are critical defects regarding the safety, efficacy and quality in the
submitted dossier of the drug applied for registration;
(5)
an applicant fails to provide supplementary data within the prescribed
timeline;
(6)
the source of drug substances does not meet the requirements;
(7)
the result of production site inspection or sample testing does not meet the
requirements;
(8)
other circumstances in which applications shall not be approved according to
laws and regulations.
Article
155 The written non-acceptance or unapproval decision made by drug regulatory
departments by law shall provide the reasons thereof, and inform the applicant
of the right to apply for administrative reconsideration or to bring an
administrative suit by law.
Article
156 If holding any dispute on the unapproval decision made by the State Food
and Drug Administration, an applicant may, within 60 days after receiving the
decision, fill in the Application Form for Drug Registration Second Review, and
submit the application to the State Food and Drug Administration and provide
reasons.
The
content of second review shall not exceed the originally applied items and the
original application dossier.
Article
157 The State Food and Drug Administration shall make a second review decision,
and notify the applicant the decision within 50 days after receiving an
application for second review. Where the original decision is affirmed, the
State Food and Drug Administration shall not accept any further application for
second review thereof.
Article
158 Where there is any need for technical review in second review, the State
Food and Drug Administration shall organize relevant technical personnel to
conduct review within the timeline as that for the original application.
Chapter
XIV
Legal
Liabilities
Article
159 In any of the circumstances prescribed in Article 69 of the Administrative
Permission Law, the State Food and Drug Administration may withdraw the
relevant drug approval documents upon the request of any interest party or
according to its responsibilities and authorities.
Article
160 Any drug regulatory department or its staff members that violate the
provisions of this Provisions and constitute any of the circumstances below
shall be instructed by its superior administrative department or supervisory
departments to make rectification. If the circumstances are serious,
administrative sanctions shall be given to the persons directly in charge and
the other persons directly responsible in accordance with law:
(1)
not accepting a drug registration application that is in conformity with
regulatory requirements;
(2)
not publicizing at the acceptance place the information that shall be
publicized by la]w;
(3)
in the process of acceptance, review and approval, not fulfilling the
regulatory informing obligation to the applicant or interest party;
(4)
not informing the applicant at once of all the contents needed to be
supplemented or corrected, where the drug application dossier submitted is
incomplete or not conformed with the required format;
(5)
not stating the reasons of non-acceptance or unapproval of a drug registration
application by law; and
(6)
not holding hearings that shall be held by law.
Article
161 If any drug regulatory department and its staff members request for or
accept money or valuable articles from others, or pursue other interests in the
process of drug registrations, where a crime is committed, criminal liabilities
shall be investigated by law; where a crime is not committed, administrative
sanctions shall be given by law.
Article
162 Any drug regulatory department that constitutes any of the following
circumstances in the process of drug registration shall be instructed by its
superior administrative department or supervisory departments to make
rectification, and administrative sanctions shall be given to the persons
directly in charge and the other persons directly responsible by law; if a
crime is committed, criminal liabilities shall be investigated by law:
(1)
making a decision to approve any registration application that does not meet
the regulatory requirements prescribed in the Provisions or acting beyond
regulatory responsibilities and authorities to make such a decision;
(2)
making a decision to disapprove a registration application conformed with the
regulatory requirements, or failing to make a decision to approve a
registration application within the regulatory timeline; and
(3)
failing to perform the confidentiality obligation in violating the requirements
prescribed in Article Nine of the Provisions.
Article
163 When undertaking testing for drug review and approval, a drug testing
institute that issues a false certificate of analysis shall be punished in
accordance with the provisions in Article 87 of the Drug Administration Law.
Article
164 Any drug regulatory department that charges fees without permission or does
not charge fees according to set items and rates shall be instructed by its
superior administrative department or supervisory departments to return the
illegal charges; and administrative sanctions shall be given to the persons
directly in charge and the other persons directly responsible by law.
Article
165 Where the Good Laboratory Practice for Non-Clinical Laboratory Studies or
the Good Clinical Practice is not executed in the process of drug registration
according to regulations, punishments shall be given in accordance with the
provisions in Article 79 of the Drug Administration Law.
Article
166 Where an applicant submits false drug registration dossier and samples when
applying for clinical trial, the drug regulatory department shall not accept
the application or disapprove the applied clinical trial, give a disciplinary
warning to the applicant, and not accept any further application for clinical
trial of the drug made by the applicant within one year; where clinical trial
of the drug is already approved, the Drug Clinical Trial Approval shall be
withdrawn, a fine of no less than 10,000 yuan but no more than 30,000 yuan
shall also be imposed, and no further application for clinical trial of the
drug made by the applicant shall be accepted within three years.
The
State Food and Drug Administration shall keep records of the fraud acts of
applicants that submit false dossier and samples, and publicize such records.
Article
167 Where an applicant submits false drug registration dossier and samples when
applying for drug production or importation, the State Food and Drug
Administration shall not accept or disapprove the application, give a
disciplinary warning to the applicant, and not accept any further application
made by the applicant within one year; where the production or importation of
the drug is already approved, the drug approval documents shall be withdrawn,
no further application made by the applicant shall be accepted within five
years, and a fine of no less than 10,000 yuan but no more than 30,000 yuan
shall also be imposed.
Article
168 According to the provisions in Article 27 of the Provisions, where a drug
testing needs to be repeated but the applicant refuses to do so, the State Food
and Drug Administration shall give a warning and instruct to make
rectification; if the applicant refuses to make rectification, the application
thereof shall not be approved.
Article
169 Where there is any of the following circumstances, the State Food and Drug
Administration shall withdraw the drug approval number, and announce to the
public:
(1)
the applicant requests to annul its own drug approval number before the drug
approval document expires;
(2)
the re-registration is not allowed according to provisions in Article 126 of
the Provisions;
(3)
the Drug Manufacturing Certificate is revoked or withdrawn by law;
(4)
according to provisions in Article 42 of the Drug Administration Law or Article
41 of the Regulations for Implementation of the Drug Administration Law, the
drug approval document is withdrawn for any drug with serious adverse reactions
or other factors harmful to human health;
(5)
a decision is made to give an administrative sanction of revoking the drug
approval document by law; and
(6)
other circumstances in which the drug approval documents shall be withdrawn or
recalled by law.
Chapter
XV
Supplementary
Provisions
Article
170 The application dossier and requirements of traditional Chinese medicines
and natural medicines, pharmaceutical products, biological products,
supplementary applications and re-registration application shall be referred to
Annex 1, 2, 3, 4, 5 of the Provisions, seriatim. Provisions on observation
period are prescribed in Annex 6.
Article
171 The format of drug approval number: Guo Yao Zhun Zi H (or Z/S/J)+
four-digit year number+ four-digit sequence number; H standing for
pharmaceutical products, Z for traditional Chinese medicines, S for biological
products and J for repackaged import drugs.
The
format of Import Drug License number: H (or Z/S)+ four-digit year number+
four-digit sequence number; that of Pharmaceutical Product License number: H
(or Z/S) C+ four-digit year number+ four-digit sequence number; H standing for
pharmaceutical products, Z for traditional Chinese medicines, S for biological
products. For a drug repackaged in China using the license for the large
package, the letter B shall be added before the registration number of the
original license thereof.
The
format of new drug certificate number: Guo Yao Zheng Zi H (or Z/S)＋four-digit year number+
four-digit sequence number; H standing for pharmaceutical products, Z for
traditional Chinese medicines, S for biological products.
Article
172 The acceptance of applications, review and approval of supplementary applications
and of re-registration applications undertaken by the drug regulatory
departments of provinces, autonomous regions, or municipalities directly under
the Central Government prescribed by the Provisions are items delegated by the
State Food and Drug Administration. The State Food and Drug Administration may
also delegate the drug regulatory departments of provinces, autonomous regions,
or municipalities directly under the Central Government to conduct other
technical review and review and approval of drug registration.
Article
173 The State Food and Drug Administration adopts the coding management for
drugs approved for marketing. The provisions for coding management are
separately formulated.
Article
174 The registration applications for narcotic drugs, psychotropic substances,
toxic medicines and radioactive pharmaceuticals, besides complying with the
Provisions, shall also conform with other relevant State regulations.
Article
175 The provisions for registration of Chinese crude drugs, prepared slices of
Chinese crude drugs and import Chinese crude drugs regulated via approval
numbers shall be separately formulated by the State Food and Drug
Administration.
Article
176 The provisions for drug technology transfer and entrusted manufacturing
shall be separately formulated.
No comments:
Post a Comment