Chapter I General Provisions

　　Article 1 (Basis & Purpose) In order to improve the quality and efficiency of drug registration and ensure the safety, effectiveness and quality controllability of drugs, the Provisions have been formulated in accordance with the “Drug Administration Law of The People’s Republic of China” and the “Drug Registration Regulation”.

　　Article 2 (General Requirements) The chemical drug substance (DS), pharmaceutical excipients, packaging materials and containers in direct contact with drugs (hereinafter referred to as the pharmaceutical packaging materials) shall meet the pharmaceutical use requirements, and their quality, safety and functions shall meet the needs of drug product (DP).

　　Article 3 (Bundling Review and Approval System) The National Medical Products Administration (hereinafter referred to as NMPA) shall review and approve DP with the chemical drug substances, and review the bundling pharmaceutical excipients and pharmaceutical packaging materials together.

　　The standalone review and approval can be applied for the chemical drug substance used for imitating the marketed drugs in China (hereinafter referred to as “generic chemical DS”).

　　Article 4 (Registry of DS, Pharmaceutical Excipients and Pharmaceutical Packaging Materials) The chemical DS, excipients and pharmaceutical packaging materials shall be managed through registry. In principle, the registrant of DS, pharmaceutical excipients and pharmaceutical packaging materials shall be the manufacturer of DS, pharmaceutical excipients and pharmaceutical packaging materials, and the overseas companies of DS, pharmaceutical excipients and pharmaceutical packaging materials shall designate an enterprise legal person within China to complete the relevant registry. The relevant product information shall be registered on the registry platform of chemical drug substances, excipients, packaging materials and containers in direct contact with drugs (the registry platform), and the registry dossiers shall be submitted. All foreign language dossiers shall be provided with Chinese translations as required.

　　Article 5 (Disclosure of Bundling Review Result) The Center for Drug Evaluation of NMPA (hereinafter referred to as CDE) shall establish a registry platform and set up an information disclosure column to disclose basic information such as  registry number of DS, pharmaceutical excipients and pharmaceutical packaging materials, product name, enterprise name, and the route of administration, etc. to the public for selection by relevant applicants or holders.

　　The CDE shall update the identifier of registry status on the registry platform, provided that the bundling or standalone review and approval of the chemical DS or the bundling review of pharmaceutical excipients and the pharmaceutical packaging material succeed.

　　Article 6 (Management Principle of Registry Number) The same registry number shall be followed in case where the same products of DS, pharmaceutical excipients and pharmaceutical packaging materials are produced by the same enterprise with the same manufacturing process and quality standard at the same manufacturing site.

　　The same type of DS produced by different principles of manufacturing processes (such as fermentation, synthesis, semi-synthesis, etc.) can be registered under different registry numbers, and the same type of DS produced by the same principle of manufacturing process shall be registered by selecting the optimal process.

　　Chapter II Responsibilities and Obligations

　　Article 7 (Responsibilities of Marketing Authorization Holder [MAH]) MAH shall bear the main responsibility for the quality of DP and establish a quality management system with the DP as the core and the DS, pharmaceutical excipients and pharmaceutical packaging materials as the basis. The MAH shall select the appropriate DS, pharmaceutical excipients and pharmaceutical packaging materials pursuant to the quality requirements of DP, submit the Authorization Letter for Use (see Annex 1-1) associated with the registered DS, pharmaceutical excipients and pharmaceutical packaging materials when proposing a registration application, and be responsible for the quality of the selected DS, pharmaceutical excipients and pharmaceutical packaging materials. The quality of the used DS, pharmaceutical excipients and pharmaceutical packaging materials shall be traceable, with definite source, batch, production, quality control and changes.

　　Article 8 (Responsibilities of Registrant of DS, Pharmaceutical Excipients and Pharmaceutical Packaging Materials) The registrant of DS, pharmaceutical excipients and pharmaceutical packaging materials shall be responsible for the maintenance of registry information on the registry platform, and be held accountable for the authenticity and integrity of the registry information.

　　The overseas companies of DS, pharmaceutical excipients and pharmaceutical packaging materials and the designated enterprise legal person within China shall share the responsibilities of authenticity and integrity of the registry information.

　　Article 9 (Responsibilities of Manufacturer of Drug Substance, Pharmaceutical Excipients and Pharmaceutical Packaging Materials) The manufacturer of DS, pharmaceutical excipients and pharmaceutical packaging materials shall establish a supply chain management and quality assurance system of the DS, pharmaceutical excipients and pharmaceutical packaging materials, continuously and stably supply products meeting the quality requirements of DP according to the agreement, provide necessary information for MAH to evaluate and control the quality risks of DP introduced by DS, pharmaceutical excipients and pharmaceutical packaging materials, and accept enterprise audits conducted by MAH and supervision and inspection by regulatory authorities at all levels. The manufacturer of DS, pharmaceutical excipients and pharmaceutical packaging materials shall be responsible for the quality of their products and ensure that quality, safety and functionality of DS, pharmaceutical excipients and pharmaceutical packaging materials meet the needs of DP. The manufacturing process of the chemical DS shall conform to the requirements of the Good Manufacturing Practice.

　　Article 10 (Changes in Source of Drug substance, Pharmaceutical Excipients and Pharmaceutical Packaging Materials) Where the sources of the DS, pharmaceutical excipients and pharmaceutical packaging materials are subject to changes for a marketed drug product, MAH shall conduct studies in accordance with relevant guidelines and other requirements, and submit the application pursuant to relevant registration regulations. Where the bundling review and approval has not been obtained regarding the DS, pharmaceutical excipients and pharmaceutical packaging materials to be used for DP, the relevant application shall be submitted to the NMPA and the identifier of the DS, pharmaceutical excipients and pharmaceutical packaging materials shall be updated according to evaluation results after the bundling review with DP.

　　Article 11 (Changes in Drug Substance, Pharmaceutical Excipients and Pharmaceutical Packaging Materials after Drug Product Entering the Market) Any changes in the chemical DS shall be implemented in accordance with the current registration regulations and MAH of the bundling DP shall be informed thereof in a timely manner. MAH shall fully evaluate the impact on the quality of DP and submit an application for registration as per relevant provisions.

　　In case of minor change, moderate change or major change in the marketed drug product caused by changes in pharmaceutical excipients and pharmaceutical packaging materials, MAH shall conduct an self-assessment and submit an application in accordance with the requirements of the current regulations.

　　Article 12 (Requirements for Annual Report) The manufacturer of DS, pharmaceutical excipients and pharmaceutical packaging materials shall submit an annual report to the CDE within three months upon the completion of each full year after DS, pharmaceutical excipients and pharmaceutical packaging materials passing technical review. The annual report shall include product changes and relevant study data, and the relevant statement shall be provided if there is no change. With respect to the DS, it is necessary to state whether the application for change has been submitted and the relevant information after such a change. The relevant study data shall be provided in relation to the changes in pharmaceutical excipients and pharmaceutical packaging materials, and the authorized use to MAH during the year newly occurring shall be stated (see Annex 1-2 for details of requirements). If the manufacturer of DS, pharmaceutical excipients and pharmaceutical packaging materials fails to submit the annual report on time, the registry platform will not publicize this registry number anymore.

　　Chapter III Registry, Review and Approval of Chemical Drug Substance

　　Article 13 (Basic Requirements) For the chemical DS that needs to be registered in compliance with the Provisions and applies for bundling review and approval, the DS registry shall be completed in accordance with the Provisions before the submission of DP marketing authorization application or a DP supplement involving changes of DS. For generic chemical DS, a standalone review and approval could be applied at the time of registry.

　　Article 14 (Scope of Registry) All the chemical DS sold and used within China shall be registered. Where the registered pharmaceutical excipients are used as the chemical DS, the re-registry shall be made in accordance with relevant requirements of the chemical DS.

　　The chemical DS used in the overseas production of DP do not have to do registry if the chemical DS is not sold in China, and the submission dossiers of the chemical DS that conform to requirements shall be submitted together with the application of DP.

　　The registry is not required for chemical DS used in the clinical stage of new drug application (the registration of chemical drugs classified as Class 1 and Class 2.1) and submission dossiers that meet requirements shall be submitted together with the application of DP.

　　Article 15 (Submission and Acceptance of Dossiers) The chemical DS registrant shall log in the registry platform of CDE, fill in and submit the Chemical Drug Substance Registry Form (see Annex 1-3) which shall be mailed together with the electronic version (CD) of the registry information to the CDE. The CDE shall conduct the formal examination for the registry information within 5 working days after the receipt of such information. Where the information is incomplete, the required supplementary information shall be informed at one time; if the information conforms to the requirements, it shall be accepted and publicized in the information disclosure platform of DS, pharmaceutical excipients and pharmaceutical packaging materials. The registrant can print the relevant documents for acceptance on the registry platform.

　　Article 16 (Payment Made by Registrant) Where the DS is accepted through formal examination, the acceptance department of CDE shall issue a payment notice to the DS registrant in accordance with relevant requirements, except small and micro enterprises as the registrant conforming to the regulations of the State Council.

　　Article 17 (Bundling Review and Timeline) The timeline for review and approval of the chemical DS shall be consistent with that for the review of DP bundled. For the supplement for change in the source of the DS of DP, if the chemical DS is approved, the review timeline shall be 60 working days; if it has not been approved, the review timeline shall be 200 working days.

　　Article 18 (Timeline for Standalone Review of Chemical Drug Substance) The review timeline of the chemical DS applying for standalone review and approval shall be 200 working days. The review timeline of the re-registration and supplement of the DS shall refer to similar application items for registration of drug product.

　　Article 19 (Inspection and Testing of Chemical Drug Substance) The inspection and testing procedures for the chemical DS subject to bundling review and approval shall be implemented in accordance with the “Drug Registration Regulation” and relevant regulations. The inspection and testing procedures for generic chemical DS subject to standalone review and approval shall be implemented in accordance with those for the similar drug product.

　　Article 20 (Supplementary Information during Review of Chemical Drug Substance) In the event that the supplementary information is required during the process of review for the chemical DS, DP applicant or the chemical DS registrant shall provide such supplementary information based on the requirements of the procedure for supplementary information. The time consumed for supplement submission shall not be included in the review timeline. The CDE shall start the review after the receipt of all the supplement submission from the applicant, and the review timeline shall be extended by one third. The relevant provisions on the management of supplement submission for the chemical DS subject to the bundling review and approval are consistent with those for bundled DP.

　　Article 21 (Explanation of Review for Chemical Drug Substance) The CDE shall notify DP applicant or the chemical DS registrant to submit relevant explanation as required within five days, provided that it is unnecessary for DP applicant or the chemical DS registrant to supplement new technical dossier, but to make explanations on the registry information.

　　Article 22 (Approval and Result of Chemical Drug Substance) The “Notice of Approval for Chemical Drug Substance” with the registry number stated therein as well as the verified manufacturing process, specification and label shall be issued, provided that the bundling review and approval for the chemical DS and DP have been passed, or the standalone review and approval for generic chemical DS has been passed. The relevant identifier on the registry platform shall be updated, and the “Notice of Disapproval for Chemical Drug Substance” shall be issued in cased of failure in the review and approval. The registrant can print the relevant documents on the registry platform by itself.

　　The DS can be approved for marketing separately, in the event that the conclusion made about the review of the DP marketing authorization application shows approval of clinical trials and the bundling DS conforms to requirements for standalone review and approval.

　　Article 23 (Changes in Chemical Drug Substance) In case of any changes in the DS during clinical trials, the clinical trial sponsor shall conduct studies as required and submit an application under the application for DP bundled according to relevant regulatory requirements for registration.

　　In case of any change in approved chemical DS, the supplement, filing or report shall be submitted in accordance with the relevant provisions of the current drug registration regulation. The supplement subject to review and approval by NMPA shall be submitted on the registry platform; filling and reporting changes that are managed by provincial drug regulatory departments shall be submitted to the drug regulatory departments of the provinces, autonomous regions and municipalities directly under the Central Government where they are located. The changes shall be updated on the registry platform within 5 days after the completion of filing or reporting.

　　Article 24 (Main Responsibilities Related to Changes in Chemical Drug Substance) When the changes in chemical DS occur, its manufacturer shall take the initiative to conduct studies, submit an application as required, state relevant information in the annual report and send a notice to the related MAH without delay. Upon the receipt of such notice, the MAH shall promptly evaluate or study the impact of corresponding changes on the quality of DP and submit an application as required.

　　Article 25 (Change of Registry Agency) The overseas company for the chemical DS shall change its designated enterprise legal person for registry in China after submitting relevant documents and materials. Such documents and materials include: Power of Attorney from the overseas company for chemical DS, Notarization Document with Chinese version, photocopies of Business License from newly designated enterprise legal person within China, Document and Notarization Document (with Chinese version) of the overseas company for chemical DS that rescinds the commission relationship with originally designated enterprise legal person in China. The registry dossiers shall be submitted by the newly designated enterprise legal person in China.

　　Article 26 (Re-registration of Chemical Drug Substance) The registrant shall apply for re-registration 6 months before the expiration of the “Notice of Approval for Chemical Drug Substance”. The re-registration of the chemical DS manufactured within China shall be proposed by the registrant to the provincial drug regulatory department, while the re-registration of the chemical DS manufactured overseas shall be proposed by the registrant to CDE. After the approval of re-registration of the chemical DS, the information shall be updated on the registry platform within 5 days.

　　Article 27 (Termination of Registry of Chemical Drug Substance) If the chemical DS enterprise fails to re-register or its re-registration has not been approved, the registry of the chemical DS shall be terminated and the chemical DS shall not be used in marketed drug products; if the chemical DS is no longer manufactured, the manufacturer shall inform the relevant MAH in advance and apply for termination of registry on its own initiative; if the chemical DS manufacturer is disqualified for manufacturing in violation of laws and regulations, the NMPA shall terminate the registry of the related product which shall not be used in marketed DP.

　　Article 28 (Deregistration of Chemical Drug Substance Enterprise) When proposing to deregister the DS, the registrant can deregister voluntarily the chemical DS that has not been publicized; for the chemical DS that has been publicized but not been approved, the registrant shall apply for deregistration on the premise of confirming that there is no registration application for DP bundled in the process of review under the registry number; the registrant shall apply to NMPA for deregistration of chemical DS that have been publicized and approved.

　　Chapter IV  Registry and Bundling Review of Pharmaceutical Excipients and Pharmaceutical Packaging Materials

　　Article 29 (Scope of Registry) The pharmaceutical excipients and pharmaceutical packaging materials (including packaging systems and functional accessories that are not in direct contact with medicinal liquid) used in the marketing authorization application of various drugs, and the pharmaceutical excipients and pharmaceutical packaging materials involved in changes in the supplement shall be registered on the registry platform, or submission dossiers that meet the requirements can be submitted together with the DP registration application. The packaging materials and containers that are used for and in direct contact with the chemical DS shall be registered, or the submission dossiers meeting the requirements shall be submitted in the registry dossiers of the chemical DS. The registry requirements for new pharmaceutical excipients and packaging materials are the same as those for the DS.

　　The registered chemical DS can be used as the pharmaceutical excipients.

　　Article 30 (Pharmaceutical Excipients and Pharmaceutical Packaging Materials with Abbreviated Registry Dossiers) The requirements for submission dossiers can be abbreviated for pharmaceutical excipients and pharmaceutical packaging materials that have been used for a long time in food and drugs with established safety under the condition that the usage, dosage and function are within the scope of routine use. The applicant for DP registration shall state the product information and submit relevant documents meeting the requirements in DP dossiers (see Annex 1-4 for details). The CDE can require the applicant of DP registration to supplement and provide corresponding technical dossiers if it deems necessary during the review of the marketing authorization application for drug product. The list of such products shall be updated and published by CDE in due course.

　　The raw materials and intermediate products used by the companies of pharmaceutical packaging materials in the manufacturing process are not included in the scope of registry and bundling review (see Annex 1-5 for details).

　　Article 31 (Registry and Integrity Review) The registrant of pharmaceutical excipients and packaging materials can log on the registry platform of CDE, and fill in and submit the registry form of pharmaceutical excipients and pharmaceutical packaging materials to obtain the registry number and version number, and mail the electronic version (CD) of the registry dossiers to CDE. The Acceptance Department of CDE shall conduct an integrity review for the registry dossiers within 5 working days after the receipt of such registry dossiers from the registrant. Where the dossiers are incomplete, the required supplementary information shall be informed at one time; if the dossiers conform to the requirements, it shall be publicized in the information disclosure column of the DS, pharmaceutical excipients and pharmaceutical packaging materials.

　　Article 32 (Bundling Review) When reviewing an application for DP, the CDE shall conduct a bundling review of the pharmaceutical excipients and pharmaceutical packaging materials used in that DP. If the additional information is needed, it shall require DP applicant or the registrant of the pharmaceutical excipients and pharmaceutical packaging materials to provide additional information according to the supplementary information procedures. The time consumed for supplement submission shall not be included in the review timeline. If necessary, extended inspections and testing of pharmaceutical excipients and pharmaceutical packaging materials can be proposed based on risks.

　　Article 33 (Timeline for Bundling Review) The timelines for bundling review and approval of pharmaceutical excipients and pharmaceutical packaging materials shall be consistent with that for the review of DP bundled.

　　As for the supplement for change in the source of pharmaceutical excipients and pharmaceutical packaging materials for DP, if pharmaceutical excipients and pharmaceutical packaging materials do not pass technical reviews, the review timeline shall be 130 working days.

　　Article 34 (Results of Bundling Review) The status identifier on the registry platform shall be updated when the bundling review of pharmaceutical excipients and pharmaceutical packaging materials succeeds; the identifier shall not be updated if the bundling review fails or it has not been conducted. Where the bundling review of pharmaceutical excipients and pharmaceutical packaging materials fails, the application for the related DP shall not be approved.

　　Article 35 (Change in Pharmaceutical Excipients and Pharmaceutical Packaging Materials) When there are changes in pharmaceutical excipients and pharmaceutical packaging materials, the registrant shall actively carry out studies, update relevant information on the registry platform, and summarize in the annual report. Simultaneously, the registrant of pharmaceutical excipients and pharmaceutical packaging materials shall send a notice to the relevant MAH of such changes and study information in a timely manner. Upon the receipt of such notice, the MAH shall promptly evaluate or study the impact of corresponding changes on the quality of DP and submit a supplement, filing or reporting to the corresponding departments according to current regulations on drug registration.

　　Article 36 (Change in Designated Domestic Enterprise Legal Person) Where the overseas company of pharmaceutical excipients and pharmaceutical packaging materials changes its designated enterprise legal person for the registry, the change shall be made after the changed domestic enterprise legal person that has been designated for registry submits the relevant documents and information. Such documents and information include: Statement on Reason for Change, Power of Attorney from the overseas company for pharmaceutical excipients and pharmaceutical packaging materials, Notarization Document with Chinese version, photocopies of Business License from newly designated enterprise legal person within China, Document and Notarization Document (with Chinese version) of the overseas company of chemical DS that rescinds its commission relationship with originally designated enterprise legal person in China.

　　Chapter V  Supervision and Management

　　Article 37 The NMPA shall collect the registry information of the products of DS, pharmaceutical excipients and pharmaceutical packaging materials, information on verified manufacturing process and specifications after the review and approval of the chemical DS, annual report of the products of DS, pharmaceutical excipients and pharmaceutical packaging materials and information on daily supervision by regulatory authorities at all levels on the enterprise of DS, pharmaceutical excipients and pharmaceutical packaging materials, as the basis for daily supervision and for use by regulatory authorities at all levels.

　　Article 38 The drug regulatory departments at all levels shall be responsible for the daily supervision and inspection of the enterprises of DS, pharmaceutical excipients and pharmaceutical packaging materials within their jurisdiction, and extended inspections on such enterprises as needed for the supervision of marketed drug products, and shall report the supervision and inspection to NMPA on a regular basis.

　　Article 39 The NMPA shall make public announcements and cancel the registry of related products under the name of the enterprises of DS, pharmaceutical excipients and pharmaceutical packaging materials that refuse to accept the inspection by the drug regulatory departments at any level and to correct defects identified in the inspection. The related products shall not be used in marketed drug products.

　　Article 40 Where problems with the products of DS, pharmaceutical excipients and pharmaceutical packaging materials that may affect the quality of DP are identified by MAH and the enterprises of DS, pharmaceutical excipients and pharmaceutical packaging materials during the process of manufacturing and distribution, they shall promptly inform each other, conduct evaluation on and deal with such problems, recall the corresponding products when necessary, and report to the provincial drug regulatory department.

　　MAHs and the enterprises of DS, pharmaceutical excipients and pharmaceutical packaging materials shall be responsible and obligated to report to the NMPA or drug regulatory departments at all levels if they discover fraud committed by either of them.

　　Article 41 The drug regulatory department shall clarify the responsible subject in case of any major quality problem of DP. If it falls in the responsibility of MAH, the MAH shall be held accountable in accordance with the law; any illegal acts in the enterprises of DS, pharmaceutical excipients and pharmaceutical packaging materials shall be investigated according to law if any.

　　Article 42 MAHs shall be solely responsible for the quality problems of DP caused by the illegal use of the DS, pharmaceutical excipients and pharmaceutical packaging materials.

　　Article 43 If there is any problem with the authenticity of the registry information about the DS, pharmaceutical excipients and pharmaceutical packaging materials, the NMPA shall cancel the registry number of the products of the DS, pharmaceutical excipients and pharmaceutical packaging materials, prohibit such products from using in the marketed drug product, and investigate for the responsibility of the enterprises of DS, pharmaceutical excipients and pharmaceutical packaging materials according to law.

　　Chapter VII  Supplementary Provisions

　　Article 44 The scope to which these Provisions apply includes chemical DS, pharmaceutical excipients used in various drug products, and pharmaceutical packaging materials (including packaging systems), as well as other pharmaceutical packaging materials and containers (including packaging systems) prescribed by NMPA.

　　Article 45 The registry number of DS, pharmaceutical excipients and pharmaceutical packaging materials shall be Y/F/B+ 4-digit calendar year + 7-digit serial number, in which Y represents chemical DS, F represents pharmaceutical excipients, and B represents pharmaceutical packaging materials. In principle, the registry number will not be changed the change in product or enterprise.

　　Article 46 The Provisions shall be implemented as of the date of formal promulgation.

　　Annex:

　　1-1. Letter for of Authorization for Use from Enterprise of Chemical Drug Substance, Pharmaceutical Excipients and Pharmaceutical Packaging Materials.

　　1-2. General Requirements for Annual Report of Drug Substance, Pharmaceutical Excipients and Pharmaceutical Packaging Materials

　　1-3. Drug Substance Registry Form and Instructions

　　1-4. Catalogue of pharmaceutical excipients and pharmaceutical packaging materials of which the dossier requirements may be abbreviated

　　1-5. Catalogue of pharmaceutical packaging materials excluded in the scope of registry and bundling review

　　Annex1-1

　　Letter of Authorization for Use from Enterprise of Chemical Drug Substance, Pharmaceutical Excipients and Pharmaceutical Packaging Materials.

　　Center for Drug Evaluation, NMPA (National Medical Products Administration):

　　We, the enterprise of drug substance, pharmaceutical excipients and pharmaceutical packaging materials (or the authorized person) _____________, agrees to provide our product(s) to the marketing authorization holder (the applicant) ____________ for research, development and manufacturing for marketing of drug product _______.

　　The registered name of the product(s) is _____, the product registry number is ______, the route of administration is _____, and the specification\model is _____.

　　The enterprise of drug substance, pharmaceutical excipients and pharmaceutical packaging materials (or the authorized person)

　　Signature and Seal _________

　　Date:

　　Note: 1. This sample letter is for reference only and it can be provided in a tabular form if there are many products.

　　2. If it is an enterprise, the authorization from enterprise of drug substance, pharmaceutical excipients and pharmaceutical packaging materials is required, and the authorization letter shall be attached.

　　Annex1-2

　　General Requirements for Annual Report of Drug Substance, Pharmaceutical Excipients and Pharmaceutical Packaging Materials

　　I. The manufacturer of drug substance, pharmaceutical excipients and pharmaceutical packaging materials shall submit an annual report to CDE within three months upon the completion of each full year after passing technical review .

　　II. The annual report shall include the product changes and related research information of the previous year, and there shall be a relevant statement in case of no any changes. With regards to the drug substance, it is necessary to explain whether a supplement has been submitted as well as approval status after changes. As for excipients and packaging materials, the relevant research information about changes shall be provided.

　　III. The annual report should include information related to the drug product, such as the name of company, the name of drug product, etc. It should state the date when the manufacturer of relevant drug product has been notified after changes occurs, and whether the drug product manufacturer submit a supplement after evaluating the impact of the changes on the drug product.

　　Annex1-3

　　Annex 1-3-1 Drug Substance Initial Registry Form and Instructions

　　Registry No.:

Check code and bar code (shown on the top of each page)

　　Drug Substance Registry Form

　　Printing Date: MMM DD, YYYY

　　Drug Substance Initial Registry －Instructions

　　We hereby warrant that: this content is the solemn assurance of all application organizations that this registry conforms to the laws, regulations and rules, and all application organizations shall agree to it unanimously.

　　Other special statements: items that need to be declared separately, such as preferential treatment for small and micro enterprises, etc.

　　1. The registered drug substance is manufactured: means that the “Within China” shall be selected if the drug substance is produced in China mainland, the “Overseas” shall be selected if it is produced overseas, and “In Hong Kong, Macao and Taiwan” shall be selected if it is produced in China Hong Kong, Macao and Taiwan. This item is mandatory.

　　2. In the case of marketing registration, select the standalone review procedure if the drug substance is the generics which has already been used in the marketed drug product in China, and fill in the information on the drug product that has been marketed in China (fill in at least one drug product). This item is mandatory.

　　3. Chinese name: It should be the approved drug name included in the National Drug Standard that has been officially launched, or in the “China Approved Drug Names” and its supplements published by the “Chinese Pharmacopoeia Commission”. The duplicate checking shall be carried out in advance for newly-named drug generic name. In case of any inconsistencies with the name of the product that has been approved for marketing, the change principle should be explained in “Other Special Application Items” and relevant supporting materials should be provided. This item is mandatory..

　　4. English name: Fill in the INN of the drug. This item is mandatory..

　　5. Packaging: If there are multiple packaging materials, fill in them separately by a full stop between them, such as “Glass bottle. Plastic bottle.” Packaging size: It is the minimum package of the drug produced by the drug manufacturer for marketing, in principle, which shall be shown by the specific and definite numerical units. Multiple packaging sizes can be filled in one registry form. This item is mandatory.

　　6. Route of administration of the proposed drug product: It should be accurately filled in according to the actual situation of the drug. This item is mandatory(multiple choices are allowed).

　　7. Shelf life of drug: It shall be filled in with the unit as month. If there are multiple packaging materials, they shall be filled in separately in case of their different shelf lives. If the packaging materials are “Glass bottle. Plastic bottle”, their shelf lives are 18 months and 12 months respectively, which shall be written as “18 months. 12 months”. For the product with a particularly short shelf life (such as radioactive drug), its shelf life can be filled in for xx hours. This item is mandatory..

　　8. Source of packaging materials: The relevant information on packaging materials that come in direct contact with drugs must be filled in. If the bundling review for the packaging materials is required, its registry number should be filled in. This item is mandatory..

　　9. Justification of specification: The source or implementation rationale of the drug specification submitted in this drug application. If such specification is derived from the Chinese pharmacopoeia, the pharmacopoeia version must be clearly stated; Where it is issued by the NMPA or MoH, its type and volume should be indicated and the drug specification number should be indicated for specification with scattered pages; if it comes from the registration specification for overseas manufactured drug, the registration specification number or registration certificate number of the overseas manufactured drug should be clearly stated; if it is included in the foreign pharmacopoeia, the name and version of such pharmacopoeia should be indicated; others means sources not mentioned above, the specific sources should be indicated, such as self-research, registration specification for domestically manufactured drugs, etc. This item is mandatory.

　　10. Patent Information: The patent information on the applied drug should be determined after searching, and this item should be filled at the time of discovering the information on the protected Chinese patents or foreign patents of the drug. If there are known Chinese patents, please fill in the type of patent, including compound patent, process patent, formulation patent, etc. And the statement on patent non-infringement should be provided.

　　11. Whether any drugs or ingredients under special regulation are involved: It shall be optional separately for special drugs that are regulated under the regulations on narcotic drugs, psychotropic drugs, toxic drugs for medical use and radioactive drugs.

　　12. Applicant: The applicant, manufacturer and local registration agency for the drug substance that is manufactured overseas should be filled in as required. The manufacturer should be filled in as required for the drug substance that is manufactured within China at registry. This item is mandatory.

　　The column of each application organization: The name registered by the statutory registry authority should be filled in the “Name”. The option of “It will be responsible for registration fee payment” is for the applicant to designate one of the application organizations to be responsible for payment, and the registered address of such organization shall be the mailing address of the payment receipt. “Province” refers to the province where the applicant is located. “Social credit code/organization code” refers to the organization code or social credit code issued by the domestic organization code management agency, which is exempted for the overseas application organization. “Product Quality Responsible Person” refers to the person in charge of quality management of the enterprise. “Contact Person” means the person in charge of the registry of the drug substance. Telephone, mobile phone, fax and e-mail are the contact information with the person in charge of the registry, in which the multiple valid telephone numbers should be provided to ensure timely contact. The area code should be included when filling in (the country or region code should be included for overseas applicants), and the extension number should be provided for the transfer through the switchboard. For the “Contact Person”, the name of the person who handles the registry should be filled in for contact.

　　The name, official seal, signature of the legal representative, and signature date of each application organization: Each organization that has been filled in shall have its legal representative signed and its official seal affixed here. The date format should be XXX.XX.XXXX (MMM DD YYYY). This item shall be handwritten.

　　The name, official seal, signature of the legal representative, and signature date of each local registration agency: The local registration agency should have its legal representative signed and its official seal affixed here.

　　14. Entrusted Research Organization: The research organization from which the study information and data (including pharmaceutical, pharmacology and toxicology, etc.) included in the registry dossiers that are not obtained by the application organization through their own researches, but are obtained through the entrustment.

　　15. The form should be completed in simplified Chinese characters, except as otherwise filled in English when necessary. The written statement should be concise and accurate. In optional items, “○” means the single option box, for which only one or none of them can be selected; “□” means multiple option box, for which multiple options or none of them can be selected. An autograph is required where a signature is required.

　　16. This registry form should be filled in, modified and printed through the registry platform of drug substance, pharmaceutical excipients and pharmaceutical packaging materials on the website of Center for Drug Evaluation, NMPA (hereinafter referred to as CDE), and its scanned electronic form with signature and seal should be submitted at the time of application. The applicant should ensure that the data on the electronic form is consistent with that on the form submitted on the platform. In order to help judge whether the data in the two forms are completely consistent, the system will automatically generate a new “data check code” once the electronic form is filled in or modified. The consistency of the two sets of “data check codes” means that the data in the two forms are consistent. Modifications to the content filled in the registry form must be made through the platform. After the modification, the system will automatically generate a new “data check code” in the electronic form, and the entire set of forms will be printed with the same “data check code(s)”. The application will not be accepted in the following circumstances: a) the electronic form has not been submitted, b) the "data check code(s)" of the electronic form is inconsistent with that of the form submitted through the system, or c) other items in this registry form, except for the items that should be filled in by hand, are filled in or modified by using the non-platform registry system.

　　17. The official seal of the agency responsible for registry or the registry agency should be stamped spanning across the edge of each page in this registry form, and then the registry form shall be scanned into electronic document to ensure that this registry form is filled in or modified on the registry platform of drug substance, pharmaceutical excipients and pharmaceutical packaging materials in full compliance with regulations.

　　Remarks: The information filled in the registry form should be consistent with that of supporting documents and application dossiers.

　　Annex 1-3-2 Drug Substance Change Registry Form and Instruction

　　Check code and bar code (shown on the top of each page)

　　Drug Substance Change Registry Form

　　Printing Date: MMM DD, YYYY

　　Change Registry – Instructions

　　We hereby warrant that: this content is the solemn assurance of all application organizations that this application conforms to the laws, regulations and rules, and all application organizations shall agree to it unanimously.

　　Other special statements: Items that need to be declared separately.

　　1. The registered drug substance is manufactured: means that the “Within China” shall be selected if the drug substance is produced in China mainland, the “Overseas” shall be selected if it is produced overseas, and “In Hong Kong, Macao and Taiwan” shall be selected if it is produced in Hong Kong, Macao and Taiwan. This item is mandatory.

　　2. Original registry number: The registry number assigned when the product is approved. This item is mandatory.

　　3. The standalone review procedure can be selected in case that the change is not required for bundling review with the drug product. This item is mandatory.

　　4. Route of administration of the proposed drug product: It should be accurately filled in according to the approval and changes concerning the drug. This item is mandatory (multiple choices are allowed).

　　5. Chinese name: It should be the approved drug name included in the National Drug Standard that has been officially launched, or in the “China Approved Drug Names” and its supplements published by the “Chinese Pharmacopoeia Commission”. The duplicate checking shall be carried out in advance for newly-named drug generic name. In case of any inconsistencies with the name of the product that has been approved for marketing, the change principle should be explained in “Other Special Application Items” and relevant supporting materials should be provided. This item is mandatory.

　　6. English name: Fill in the INN of the drug. This item is mandatory.

　　7. Packaging: If there are multiple packaging materials, fill in them separately by a full stop between them, such as “Glass bottle.  Plastic bottle.” Packaging size: It is the minimum package of the drug produced by the drug manufacturer for marketing, in principle, which shall be shown by the specific and definite numerical units. Multiple packaging sizes can be filled in one registry form. This item is mandatory.

　　8. Shelf life of drug: It shall be filled in with the unit as month. If there are multiple packaging materials, they shall be filled in separately in case of their different shelf lives. If the packaging materials are “Glass bottle. Plastic bottle”, their shelf lives are 18 months and 12 months respectively, which shall be written as “18 months. 12 months”. For the product with a particularly short shelf life (such as radioactive drug), its shelf life can be filled in for xx hours. This item is mandatory.

　　9. Source of packaging materials: The relevant information on packaging materials that come in direct contact with drugs must be filled in. If the bundling review for the packaging materials is required, its registry number should be filled in. This item is mandatory.

　　10. Justification of specification: The source or implementation rationale of the drug specification submitted in this drug application. If such a specification is derived from the Chinese pharmacopoeia, the pharmacopoeia version must be clearly stated; Where it is issued by the NMPA or MoH, its type and volume should be indicated and the drug specification number should be indicated for specification with scattered pages; if it comes from the registration specification for overseas manufactured drug, the registration specification number or registration certificate number of the overseas manufactured drug should be clearly stated; if it is included in the foreign pharmacopoeia, the name and version of such pharmacopoeia should be indicated; others means sources not mentioned above, the specific sources should be indicated, such as self-research, domestic registration specification for manufactured drugs, etc. This item is mandatory.

　　11. Contents of change registry: The specific content of this change should be briefly described and the content of such a change described should be consistent with the category of the application items. This item is mandatory.

　　12. Brief description of the reason for proposing the change: The applicant shall state the reason for the change. This item is mandatory.

　　13. Patent Information: The patent information on the applied drug should be determined after searching, and this item should be filled at the time of discovering the information on the protected Chinese patents or foreign patents of the drug. Where the patent of other patentees has been exploited in this application, it should indicate whether a license for exploitation has been obtained. If there are known Chinese patents, please fill in the type of patent, including compound patent, process patent, formulation patent, etc. And the statement on patent non-infringement should be provided.

　　14. Applicant: The applicant, manufacturer and local registration agency for the drug substance that is manufactured overseas should be filled in as required. The manufacturer should be filled in as required for the drug substance that is manufactured within China at registry. This item is mandatory.

　　The column of each application organization: The name registered by the statutory registry authority should be filled in the “Name”. The option of “It will be responsible for registration fee payment” is for the applicant to designate one of the application organizations to be responsible for payment to the state, and the registered address of the organization shall be the mailing address of the payment receipt. “Province” refers to the province where the organization is located. “Organization code” refers to the organization code issued by the domestic organization code management agency, which is exempted for the overseas application organization. “Product Quality Responsible Person” refers to the person in charge of quality management of the enterprise. “Contact Person” means the person in charge of the registry of the drug substance. Telephone, mobile phone, fax and e-mail are the contact information of the person in charge of the registry, in which the multiple valid telephone numbers should be provided to ensure timely contact. The area code should be included when filling in (the country or region code should be included for overseas applicants), and the extension number should be provided for the transfer through the switchboard. For the “Contact Person”, the name of the person who handles the registry should be filled in for contact.

　　The name, official seal, signature of the legal representative, and signature date of each application organization: Each organization that has been filled in shall have its legal representative signed and its official seal affixed here. The date format should be XXX.XX.XXXX (MMM DD YYYY). This item shall be handwritten.

　　The name, official seal, signature of the legal representative, and signature date of each local registration agency: The local registration agency should have its legal representative signed and its official seal affixed here.

　　15. Entrusted Research Organization: The research organization from which the study information and data (including pharmaceutical, pharmacology and toxicology, etc.) included in the registry dossiers that are not obtained by the application organization through their own researches, but are obtained through the entrustment.

　　16. The form should be completed in simplified Chinese characters, except as otherwise filled in English when necessary. The written statement should be concise and accurate. In optional items, “□” means the single option box, for which only one or none of them can be selected; “□” means multiple option box, for which multiple options or none of them can be selected. An autograph is required where a signature is mandatory.

　　17. This registry form should be filled in, modified and printed through the registry platform of drug substance, pharmaceutical excipients and pharmaceutical packaging materials on the website of Center for Drug Evaluation, NMPA (hereinafter referred to as CDE), and its scanned electronic form with signature and seal should be submitted at the time of application. The applicant should ensure that the data on the electronic form is consistent with that on the form submitted on the platform. In order to help judge whether the data in the two forms are completely consistent, the system will automatically generate a new “data check code” once the electronic form is filled in or modified. The consistency of the two sets of “data check codes” means that the data in the two forms are consistent. Modifications to the content filled in the registry form must be made through the software. After the modification, the system automatically generates a new “data check code” in the electronic form, and the entire set of forms will be printed with the same “data check code(s)”. The application will not be accepted in the following circumstances: a) the electronic form has not been submitted, b) the "data check code(s)" of the electronic form is inconsistent with that of the form submitted through the system, or c) other items in this registry form, except for the items that should be filled in by hand, are filled in or modified by using the non-platform registry system.

　　18. The official seal of the agency responsible for registry or the registry agency should be stamped spanning across the edge of each page in this registry form, and then the registry form will be scanned into electronic document to ensure that this registry form is filled in or modified on the registry platform of drug substance, pharmaceutical excipients and pharmaceutical packaging materials in full compliance with regulations.

　　Remarks: The contents post change should be filled in the registry form, and other information filled in should be consistent with that of supporting documents and application dossiers except for the change.

　　Annex 1-3-3 Drug Substance Re-registration Form and Instructions

　　Registry No.:

Check code and bar code (shown on the top of each page)

　　Drug Substance Re-registration Form

　　Printing Date: MMM DD, YYYY