To implement the relevant provisions of the Drug Administration Law and further strengthen the supervision and management of drug production, the National Medical Products Administration has developed the “Guidelines for Quality Agreements on Contract Manufacturing of Drugs (2020 Edition),” which are intended to guide and supervise marketing authorization holders and contract manufacturing enterprises in fulfilling their obligations to ensure drug quality. These guidelines are hereby released and shall take effect from the date of their publication.

　　Hereby announced.

　　National Medical Products Administration

　　September 27, 2020

　　Attachment 1

　 　Guidance on Pharmaceutical Contract Manufacturing Quality Agreements (2020 Edition) 　

　　I. Purpose and Scope

　　To standardize the consignment manufacturing of pharmaceutical products, ensure the quality and safety of such products, and guide and supervise the marketing authorization holder (hereinafter referred to as the “holder”) and the contract manufacturing enterprise (hereinafter referred to as the “contractor”) in fulfilling their obligations to guarantee pharmaceutical quality, this Guidance has been formulated. It does so by establishing a Pharmaceutical Consignment Manufacturing Quality Agreement (hereinafter referred to as the “Quality Agreement”) to implement all quality responsibilities stipulated in applicable pharmaceutical management laws and regulations as well as in the Good Manufacturing Practice for Pharmaceuticals, thereby ensuring that the entire pharmaceutical production process continuously complies with statutory requirements.

　　This guide is intended for use by holders and trustees when entering into quality agreements.

　　II. Legal and Regulatory Basis

　　The Drug Administration Law of the People's Republic of China

　　Vaccine Administration Law of the People's Republic of China

　　Implementation Regulations of the Drug Administration Law of the People's Republic of China

　　Measures for the Administration of Drug Registration

　　Measures for the Supervision and Administration of Pharmaceutical Production

　　Good Manufacturing Practice for Pharmaceutical Products

　　Other pharmaceutical-related laws, regulations, rules, technical specifications, and standards

　　III. Job Requirements

　　(1) Basic Requirements

　　The parties to the quality agreement shall comply with the laws, regulations, and technical standards governing pharmaceutical management, fulfill the rights and obligations stipulated in the “Good Manufacturing Practice for Pharmaceuticals” (hereinafter referred to as GMP), as well as all provisions of the quality agreement, and each party shall bear its corresponding legal responsibilities in accordance with the law.

　　The quality agreement shall specify in detail the respective quality responsibilities of the holder and the contract manufacturer, and stipulate that the holder is legally responsible for the safety, efficacy, and quality controllability of the drug throughout the entire pharmaceutical manufacturing process.

　　The two parties shall establish an effective communication mechanism and designate technical quality contacts in the quality agreement to promptly communicate any issues encountered during the implementation of the quality agreement. In the event of disputes arising from change control, deviations, test results exceeding specifications/trends, or quality complaints, the two parties shall promptly engage in communication and coordination to ensure that such disputes are properly resolved within the bounds of legality, compliance, and manageable risks. The outcomes of these communications shall be documented in writing and retained after being signed and confirmed by both parties.

　　The drafting of the quality agreement should involve the quality management departments and relevant departments of both the holder and the trustee. The technical clauses therein should be drafted by personnel who possess pharmaceutical technology expertise, specialized knowledge in inspection, and familiarity with GMP.

　　The quality agreement shall become effective upon being signed by the legal representatives or enterprise principals of both parties, provided that both parties have reached mutual agreement. (The enterprise principal may delegate authority to the quality officer.)

　　(2) Holder’s Request

　　The marketing authorization holder is legally responsible for the safety, efficacy, and quality control of a drug throughout its entire lifecycle—covering research and development, manufacturing, distribution, and use—and may not delegate to the contract manufacturer any obligations or responsibilities that, by law, can only be fulfilled by the holder itself through a quality agreement.

　　Before signing the quality agreement, the holder shall conduct an assessment of the contractor’s production conditions, technical capabilities, and quality management practices to confirm whether the contractor has the necessary conditions and capabilities for undertaking contract manufacturing, and whether it continuously complies with GMP as well as the quality management requirements for the contracted products. After passing the assessment, the holder shall provide the contractor with the technical and quality documentation related to the contracted pharmaceutical products.

　　During the period of contract manufacturing, the marketing authorization holder shall provide guidance and supervision over the entire process of contract manufacturing, urge the contractor to consistently and stably produce pharmaceutical products that meet the intended use and registration requirements, conduct regular audits of the contractor’s quality management system, and be responsible for the market release of the contracted pharmaceutical products.

　　(3) Requirements of the Trustee

　　The entrusted party shall strictly comply with the quality agreement and ensure that the drugs produced under contract adhere to GMP requirements, are manufactured in accordance with national drug standards as well as the registered standards and production processes approved by the drug regulatory authorities, and is responsible for the release of the contracted drugs for shipment. The names of the drugs, dosage forms, specifications, manufacturing processes, sources of raw and excipient materials, packaging materials and containers that come into direct contact with the drugs, packaging specifications, labels, package inserts, and approval numbers shall be identical to the contents stated in the drug approval documents and registration approvals held by the marketing authorization holder.

　　The trustee shall actively cooperate with the holder in undergoing the audit and implement corrective and preventive measures to address all deficiencies identified during the audit.

　　IV. Specific Requirements

　　(1) Factory Buildings, Facilities, and Equipment

　　The quality agreement shall stipulate that the holder conducts a detailed audit of the contractor’s production conditions and quality management practices. The audit shall cover, but not be limited to:

　　1. Do the production conditions and capabilities, including factory facilities and equipment, meet the requirements of national pharmaceutical standards as well as the drug registration standards and manufacturing processes approved by the drug regulatory authorities?

　　2. Has the entrusted party determined, based on factors such as the characteristics of the commissioned pharmaceutical products, the manufacturing processes, and the intended use, the feasibility of shared use of facilities, production equipment, and premises for multiple products, and does it have a corresponding report? The risk assessment report for co-production of multiple products must be reviewed and approved by the marketing authorization holder.

　　(2) Materials and Products

　　The quality agreement shall stipulate that the holder is responsible for selecting, managing, and auditing material suppliers. Such suppliers must comply with the Good Manufacturing Practice standards established by the National Medical Products Administration as well as the relevant requirements for associated review and approval processes. The holder shall provide the list of qualified suppliers to the entrusted party; after the entrusted party has reviewed and approved these suppliers, they will be included in the entrusted party’s list of qualified suppliers and used for verification and acceptance upon the entrusted party’s entry into the facility.

　　The quality agreement shall clearly stipulate that the holder or the contract manufacturer is responsible for procuring materials. The holder may, as needed, entrust the contract manufacturer with material procurement, provided that such arrangement is explicitly agreed upon in the quality agreement.

　　The quality agreement shall clearly stipulate that the holder or the entrusted party is responsible for the acceptance, sampling, retention of samples, testing, and release of materials. After completion of testing and release, each party shall transfer a copy or other form of the test report and the material release review form to the other party. Whether the other party needs to conduct additional testing based on the assessment of product quality control shall be specified in the quality agreement.

　　The quality agreement shall clearly stipulate that the entrusted party is responsible for inspecting finished products and must ensure that all finished products undergo full inspection. Upon completion of the inspection, the inspection report shall be submitted to the holder in the form of a copy or other appropriate means.

　　The quality agreement and the documentation of both parties’ quality management systems shall clearly specify how to ensure that warehouse management complies with the relevant requirements, including accurate and error-free labeling information, as well as protective measures taken to prevent confusion, errors, contamination, and cross-contamination.

　　The quality agreement shall clearly define the responsibilities of both parties regarding the transportation and storage of materials and products, as well as the measures for maintaining proper storage conditions. It shall also specify the respective duties of each party to ensure that the quality of materials and products remains controllable throughout the transportation process.

　　(3) Confirmation and Verification

　　The quality agreement shall stipulate that process validation for the product may only be carried out after the contractor has completed the necessary qualification and verification activities—including those related to facility infrastructure, equipment, and utility systems—and has achieved the expected results. The contractor’s process validation and cleaning validation plans and reports must be reviewed and approved by both parties.

　　(4) Document Management

　　To ensure that the contract manufacturer can fully understand the product’s manufacturing processes, quality characteristics, and other relevant aspects, and thereby consistently and reliably produce products that meet the intended purpose, the quality agreement shall stipulate that the holder must provide the contract manufacturer with all necessary technical documentation, including but not limited to the following documents (if these documents are photocopies, they must be stamped with the holder’s official seal on each page or along the spine):

　　1. Drug Registration Certificate;

　　2. Manufacturing processes, quality standards, instructions for use, and labels approved by the drug regulatory authority;

　　3. Quality standards and inspection standard operating procedures for raw materials, excipients, packaging materials, intermediates, and finished products when submitting drug registration applications;

　　4. Internal control quality standards for enterprises;

　　5. Drafts of drug instructions and packaging labels filed with the provincial drug regulatory authorities;

　　6. Product toxicity data and other relevant documentation related to cleaning validation.

　　The entrusted party shall, based on the documentation provided by the holder and taking into account the enterprise’s existing production technology conditions and quality management practices, prepare the corresponding technical documents for contract manufacturing. These documents must be reviewed and approved by both parties. The technical documents shall include, but are not limited to: quality standards for raw materials, excipients, packaging materials, intermediates, and finished products; production process specifications for the product; blank batch production records, batch packaging records, and batch inspection records, among others.

　　The quality agreement shall clearly stipulate that both the holder and the contract manufacturer shall, in accordance with GMP requirements, retain all production and quality documents and records directly related to the contracted products. Both parties shall establish a GMP documentation system covering the entire process for the contracted products, which will be used for comprehensive control throughout actual production, thereby preventing issues such as overlapping or unclear responsibilities and omissions in the documentation system that could compromise the effective implementation of GMP across the entire process.

　　The quality agreement should clearly specify how to ensure that all records and documents are readily accessible and searchable at any time in compliance with GMP requirements, as well as how document copies should be made under controlled procedures.

　　(5) Production Management

　　The quality agreement or the entrusted party's quality management system documentation shall specify the methods for determining the production date, batch number, and expiration date of the entrusted products.

　　The holder shall provide guidance and supervision throughout the entire process of commissioned production, ensuring that the contract manufacturer is able to produce products that meet the registered standards in accordance with the registered manufacturing processes, and minimizing any deviations from the process specifications and operating procedures as much as possible.

　　The trustee must develop specific Standard Operating Procedures for rework, reprocessing, and recycling activities related to the entrusted products. These documents must be reviewed and approved by both parties. In practice, the trustee shall notify the holder in advance and obtain written approval before commencing any such activities.

　　(6) Quality Control and Quality Assurance

　　1. Quality Control Laboratory Management

　　(1) Sampling

　　The quality agreement shall clearly specify that the holder or the entrusted party is responsible for sampling raw materials, excipients, packaging materials, intermediate products, and finished products.

　　(2) Inspection

　　If the quality agreement stipulates that the inspection of raw materials, excipients, packaging materials, and intermediate products shall be carried out by the contract manufacturer, the contract manufacturer shall perform validation, transfer, or verification of the corresponding testing methodologies. The validation, transfer, or verification plans and reports shall be reviewed and approved by the holder. Finished products must be fully inspected by the contract manufacturer in accordance with the methods approved during registration.

　　(3) Out-of-Specification (OOS) Results and Out-of-Trend (OOT) Results

　　The quality agreement shall stipulate that any inspection results—whether exceeding specified limits or showing trends beyond acceptable ranges—that are detected by either party during inspections related to the contracted manufacturing products shall be handled in accordance with their respective procedures, and the other party shall be notified immediately. During the handling process, all documented records generated shall be provided to the other party in the form of photocopies or other appropriate means, so that the parties can analyze and address any product quality issues.

　　(4) Sample retention

　　The quality agreement shall clearly specify that the holder or the contract manufacturer is responsible for retaining samples. The storage conditions and quantities of retained samples must comply with GMP requirements. The location for sample retention and the responsibilities for its management shall be clearly defined. Any retained samples of finished products and materials (including raw materials, excipients, and packaging materials that come into direct contact with the drug) prepared by the contract manufacturer—including the methods for sample retention and the quantities to be sampled—must be reviewed and approved by the holder.

　　2. Release of materials and products

　　The agreement shall clearly stipulate that the marketing authorization holder must appoint a quality authorized person responsible for the final release of products for market launch. The marketing authorization holder may not delegate the responsibility for product release for market launch to a contract manufacturer. The contract manufacturer shall be responsible for the release of products upon shipment from the factory.

　　The release of materials may be authorized by the holder to the quality management department of the entrusted party, or it may be stipulated in the quality agreement.

　　3. Continuous Stability Study

　　The quality agreement shall clearly stipulate that the holder or the contract manufacturer is responsible for ongoing stability studies. When the contract manufacturer is responsible, the ongoing stability study plan and reports must be reviewed and approved by both parties.

　　The stability study data and evaluation results generated by either party shall be promptly communicated to the other party. The evaluation should include a comparison and analysis of the data with those from historical batches (including registered submission batches and batches produced by other contractors, etc.), so as to promptly identify any adverse trends in stability.

　　4. Change Control

　　As the responsible party, the marketing authorization holder shall, in accordance with the regulations of the National Medical Products Administration, comprehensively assess and verify the impact of the proposed changes on the safety, efficacy, and quality control of the drug. Both the marketing authorization holder and the contract manufacturer shall carry out the changes in compliance with applicable pharmaceutical management laws, regulations, rules, and technical standards. Any party making changes that could potentially affect the quality of the drug shall promptly notify the other party in writing.

　　The quality agreement shall stipulate that both parties must establish change control procedures and clearly define the corresponding work measures to be taken when changes occur. It shall also specify that the risk level associated with changes to contracted manufacturing products shall be assessed and determined by the holder, and the contractor must obtain the holder’s review and approval before implementing any such changes.

　　5. Deviation Handling

　　The quality agreement shall stipulate that any deviations occurring during the trustee’s activities in production quality management shall be handled in accordance with the deviation handling procedures.

　　The entrusted party shall assess the impact of all deviations related to the products manufactured under contract on the product’s safety, efficacy, and quality control. Based on the nature, scope, and degree of impact of each deviation on product quality, the party may implement categorized management and report the proposed corrective and preventive measures to the holder. The deviation handling report must be reviewed and approved by the holder.

　　6. Corrective and preventive measures.

　　The quality agreement shall specify that any issues identified—such as deviations, out-of-specification test results, complaints, changes, and findings from product quality review analyses—related to the contracted manufacturing of products must be investigated, and necessary corrective and preventive measures must be implemented. The depth and form of the investigation shall be commensurate with the risk level. Corrective and preventive measures shall be reviewed and approved by the holder.

　　7. Supplier evaluation and approval

　　The quality agreement shall stipulate that the holder conducts quality audits of all suppliers of materials used in production and establishes a file of qualified suppliers. The entrusted party shall maintain a directory of qualified suppliers and, if necessary, may participate in the quality audit process.

　　8. Product Quality Review and Analysis

　　The quality agreement shall clearly stipulate that the holder or the entrusted party shall conduct product quality review and analysis in accordance with GMP requirements, and the analysis report shall be reviewed and approved by the holder.

　　(7) Complaints and Adverse Reaction Reports

　　The quality agreement shall clearly stipulate that the marketing authorization holder shall establish a pharmacovigilance system and carry out pharmacovigilance activities in accordance with applicable requirements. Both the marketing authorization holder and the contract manufacturer shall regularly monitor the quality, efficacy, and adverse reactions of their pharmaceutical products. If any suspected adverse reactions are identified, they shall promptly report them as required. The marketing authorization holder shall be responsible for handling quality complaints, while the contract manufacturer shall provide assistance and cooperation. Upon receiving a complaint, the contract manufacturer shall promptly notify the marketing authorization holder.

　　(8) Contract Manufacturing and Contract Testing

　　The quality agreement shall stipulate that the entrusted party may not subcontract the production of the product to other enterprises.

　　The quality agreement shall stipulate that any commissioned testing involving raw materials, excipients, packaging materials, intermediate products, and finished products must comply with applicable pharmaceutical laws and regulations as well as GMP requirements. When the contract manufacturer entrusts testing items to a third party, such delegation shall be subject to review and approval by the marketing authorization holder.

　　(9) Product Shipment and Recall

　　The quality agreement shall specify the particular carrier to be used for shipment. If third-party transportation is involved, such arrangements must comply with GMP requirements as well as relevant laws, regulations, and normative documents, and must be approved by the holder. The holder shall be responsible for the product quality throughout the entire shipping process.

　　The marketing authorization holder shall establish a drug recall system and develop procedures for managing drug recalls. When a drug recall becomes necessary, the marketing authorization holder shall be responsible for carrying out the recall, and the contract manufacturer shall cooperate accordingly.

　　(10) Self-inspection

　　The quality agreement shall stipulate that any defects related to the contracted products identified during self-inspection activities, as well as the corrective and preventive measures taken, shall be promptly reported to the holder by the contractor.

　　(11) Other

　　1. The quality agreement shall specify detailed corporate information of both parties, including: company name, drug manufacturing license number, unified social credit code, registered address (business premises), production address and workshop or production line, postal code, and other relevant details.

　　2. The quality agreement shall specify detailed information on the key personnel of both parties, including: the name, position, contact telephone number, and email address of the legal representative, enterprise head, production manager, quality manager, and quality authorization person, to facilitate communication and exchange between the two parties.

　　3. The quality agreement shall clearly stipulate that the holder is responsible for submitting annual reports, as required, on the pharmaceutical product’s manufacturing and sales, post-marketing studies, risk management, and other relevant matters. The holder shall also be responsible for establishing and implementing a drug traceability system and for reporting production stoppages of shortage drugs. The entrusted party shall provide assistance and cooperation.

　　4. The marketing authorization holder and the contract manufacturer must at least sign a consignment agreement and a quality agreement. The consignment agreement is a commercial agreement under which the marketing authorization holder entrusts the contract manufacturer with the production of pharmaceutical products, clearly defining the respective rights and obligations of both parties. The quality agreement is a comprehensive arrangement among all parties involved in the contractual manufacturing relationship for pharmaceutical products, specifying how the products are to be manufactured in compliance with GMP requirements. It focuses on meeting regulatory and legal requirements as well as the supervisory demands of regulatory authorities, and must ensure that both parties can effectively fulfill their obligations regarding pharmaceutical quality assurance. The quality agreement is not a commercial agreement and typically does not include general commercial terms such as confidentiality, pricing and costs, delivery terms, limitation of liability, or compensation for damages.

　　5. The quality agreement shall include a version and change history, with a summary of the content of each previous change.

　　Appendix 2

　　Drug Contract Manufacturing Quality Agreement Template

　　(2020 Edition)

　　This template is designed to serve as a blueprint for the quality agreement on pharmaceutical contract manufacturing to be signed between the marketing authorization holder and the contracted manufacturer. The marketing authorization holder and the contracted manufacturer should make appropriate adjustments based on their specific circumstances to ensure that the entire pharmaceutical manufacturing process continuously complies with statutory requirements.

　　Marketing Authorization Holder (hereinafter referred to as the Holder): xxx

　　Drug Production License Number: xxx

　　Unified Social Credit Code: xxx

　　Address (business premises): xxx

　　Postal code: xxx

　　Contract manufacturing enterprise for pharmaceutical products (hereinafter referred to as the contractor): xxx

　　Drug Production License Number: xxx

　　Unified Social Credit Code: xxx

　　Address (business premises): xxx

　　Production address and production workshop or production line: xxx

　　Postal code: xxx

　　The holder and the trustee (hereinafter referred to as “the Parties”) are willing to comply with this Quality Agreement and fulfill all agreed-upon activities, responsibilities, and obligations.

　　1 Definition

　　Audit: Refers to the holder’s inspection and evaluation of the trustee’s production quality management system.

　　Batch: A defined quantity of finished products produced through one or more processing steps and possessing expected uniform quality and characteristics. To complete certain production operations, it may be necessary to divide a batch into several sub-batches, which are then combined to form a homogeneous batch. In continuous production, a batch must correspond to a specific quantity of products that exhibit the expected uniform characteristics throughout the production process; the batch size can be either a fixed quantity or the amount of product manufactured within a fixed time period.

　　Batch Records: Documents and records used to chronicle all activities related to the production, quality inspection, and release review of each batch of pharmaceutical products, enabling traceability of all historical information pertinent to the quality of the finished product.

　　2 Purpose

　　Clearly define the quality responsibilities of both the holder and the trustee in implementing the provisions of pharmaceutical management laws, regulations, rules, and Good Manufacturing Practice for Pharmaceuticals, ensuring that the commissioned manufacturing activities continuously comply with the requirements of pharmaceutical laws, regulations, rules, and technical standards.

　　3 Basic Information

　　3.1 Product Information

　　Information on contract-manufactured products is provided in Appendix 1.

　　3.2 Contact Information

　　The contact information for the holder and the trustee is provided in Appendix 2.

　　3.3 Responsibilities

　　The holder and the trustee shall fulfill the relevant obligations stipulated by the laws, regulations, and rules on pharmaceutical management as well as the Good Manufacturing Practice for Pharmaceuticals, and each shall bear its respective responsibilities. The list of responsibilities is provided in Appendix 3.

　　The parties to the quality agreement shall comply with all applicable laws, regulations, and technical standards pertaining to pharmaceutical products, establish a sound communication mechanism, and ensure that the safety, efficacy, and quality of the contracted pharmaceutical products are controllable. Specific requirements are set forth in the various provisions of this quality agreement.

　　3.4 Registration Materials and Technical Documents

　　The holder shall transfer the product-related registration data and technical documents to the entrusted party prior to the validation of the manufacturing process. If necessary, the holder shall also dispatch personnel to provide training to the entrusted party. When any relevant registration information is changed, the holder shall notify the entrusted party within X days from the date on which the relevant registration information is approved for amendment.

　　The trustee shall maintain the confidentiality of all registration data and technical documents related to the products covered by this Quality Agreement, and shall establish a corresponding quality system and quality documentation in accordance with the requirements of pharmaceutical management laws, regulations, and technical standards. With regard to key quality documents covered by this Quality Agreement—such as process specifications, quality standards, and batch records—their approval by both parties is required.

　　4 Legal and Regulatory Basis

　　Both parties shall comply with the "Drug Administration Law of the People's Republic of China," the "Vaccine Administration Law of the People's Republic of China," the "Implementation Regulations of the Drug Administration Law of the People's Republic of China," the "Measures for Drug Registration Management," the "Measures for Drug Production Supervision and Administration," the "Good Manufacturing Practice for Pharmaceutical Products," as well as other laws, regulations, rules, technical specifications, and standard requirements related to pharmaceuticals.

　　The holder and the trustee shall promptly notify each other in writing of any known changes to applicable laws and regulations that could potentially affect the quality of the manufactured pharmaceutical products and the respective responsibilities of both parties. Where such changes involve matters covered by this Quality Agreement, the agreement shall be revised in accordance with applicable legal and regulatory requirements.

　　5 personnel

　　According to GMP requirements, the contract manufacturer shall ensure that relevant personnel have undergone training and their qualifications have been confirmed.

　　6. Factory Buildings, Facilities, and Equipment

　　The entrusted party shall ensure that the facilities, equipment, computer systems, and other resources related to the production and inspection of the product are in good condition and have all been duly validated. Moreover, the production processes, cleaning methods, analytical methods, and other relevant procedures must have undergone appropriate validation. In the event of any changes that could potentially affect the safety, efficacy, or quality control of the product and that, following assessment by both parties, require revalidation, the entrusted party shall carry out the necessary revalidation activities. The entrusted party shall determine, based on factors such as the characteristics of the drug being manufactured under contract, the manufacturing process, and the intended use, the feasibility of shared use of facilities, production equipment, and resources among multiple products, and shall prepare a corresponding report. The risk assessment report for co-production of multiple products shall be reviewed and approved by the marketing authorization holder.

　　7 Materials and Products

　　7.1 Materials

　　The marketing authorization holder is responsible for selecting, managing, and auditing material suppliers. Suppliers must comply with the quality management standards established by the National Medical Products Administration as well as the relevant requirements for associated review and approval processes. The marketing authorization holder shall provide the list of qualified suppliers to the entrusted party. After the entrusted party has reviewed and approved these suppliers, they will be included in the entrusted party’s list of qualified suppliers and used for verification and acceptance upon the entrusted party’s entry into the facility.

　　The holder and the trustee shall agree in advance on the supplier of materials. The holder or the trustee shall be responsible for procuring the materials used in product manufacturing and shall assume responsibility for supplier management and quality assurance of the materials. The parties to the quality agreement shall establish, in accordance with applicable laws and regulations, procedures for the receipt, inspection, sample retention, release, and storage of materials, and shall carry out the receipt, inspection, sample retention, release, and storage of materials in compliance with these procedures.

　　Materials not listed in this directory may not be used for contract manufacturing. If the holder needs to add qualified suppliers to the directory or change material suppliers, it shall sign a supplementary agreement with the contract manufacturer.

　　7.2 Rework, Reprocessing, and Recycling

　　The trustee shall develop written management procedures for rework, reprocessing, and recycling, which shall be reviewed and approved by both parties.

　　If the trustee needs to perform rework, reprocessing, or recycling activities on the products covered by this quality agreement, it shall notify the holder in advance and obtain its written approval before commencing any production operations.

　　The entrusted party shall record all rework, reprocessing, and recycling activities and retain them as part of the batch records.

　　8 Confirmation and Verification

　　8.1 System of the Validation Plan

　　The entrusted party shall develop a relevant validation plan before product production.

　　8.2 Confirmation of Factory Facilities and Equipment

　　The trustee is responsible for confirming and performing preventive maintenance and repairs on the relevant facilities, equipment, and computer systems used in product manufacturing and inspection, ensuring that they are always maintained in a validated state. The trustee is also responsible for conducting regular calibration of instruments and meters to ensure their use within their valid calibration period.

　　8.3 Validation of Process and Analytical Methods

　　The entrusted party shall conduct process validation for the product. After the initial process validation is successfully completed, ongoing process verification shall be carried out. In the event of any abnormal conditions being detected, such conditions shall be handled in accordance with the “Deviation and OOS Management” provisions of this Quality Agreement. The process validation plan and report shall be reviewed and approved by both parties to the Quality Agreement.

　　8.4 Cleaning Validation

　　The entrusted party shall conduct cleaning validation on production equipment and utensils that come into direct contact with pharmaceutical products to prevent contamination and cross-contamination. The methods used for cleaning validation shall be validated or confirmed, and the protocols and reports shall be reviewed and approved by both parties to the quality agreement.

　　9 File Management

　　9.1 Production Process

　　The entrusted party shall, in accordance with this Quality Agreement, prepare the production process procedures, blank batch records, and other relevant quality documents for the contracted products based on the manufacturing processes and quality standards approved by the drug regulatory authorities, as well as the technical documentation provided by the holder, and such documents shall be reviewed and approved by both parties.

　　The entrusted party shall perform production operations in accordance with the manufacturing process specifications and keep timely and accurate records.

　　When any deviation from the approved process specifications occurs, the contractor shall conduct and handle the deviation investigation in accordance with the “Deviation and OOS Management” section of this Quality Agreement.

　　When changes are required in the product’s manufacturing process, both parties shall manage them in accordance with the “Change Control” provisions of this Quality Agreement.

　　The entrusted party shall organize production in accordance with the approved manufacturing process specifications under the applicable conditions and maintain records as required.

　　9.2 Production, Inspection, and Equipment Records

　　The trustee shall establish records for the production and inspection equipment involved in this quality agreement, including but not limited to equipment status, batch information of all products/materials used, equipment operating conditions, and operational parameters.

　　Each batch of products shall be accompanied by batch production records, batch packaging records, and batch inspection records (including intermediate product testing records and QC inspection records prior to product release).

　　The trustee shall, in accordance with the “Document Management” requirements of this Quality Agreement, retain all records related to product manufacturing.

　　9.3 Batch Production Records

　　The entrusted party shall establish a management procedure for batch production records and prepare batch production records for products based on the approved process specifications. The batch production records shall include all production steps of the product. Any changes to batch records shall be managed in accordance with the “Change Control” provisions of this Quality Agreement.

　　The entrusted party shall completely record all production processes in accordance with batch records and GMP requirements.

　　9.4 Document Management

　　The entrusted party shall properly preserve all relevant documents and records pertaining to the production, inspection, and shipment of the products covered by this Quality Agreement. Such records shall be retained for at least X years after the product’s expiration date, with documents to be kept permanently. Documents related to regulatory inspections of the products covered by this Quality Agreement shall be retained for at least X years. The holder has the right to obtain and retain the inspection reports for the entrusted products.

　　Within X months prior to the expiration of the retention period for all document materials, the trustee shall consult the holder in writing regarding the disposition of the relevant documents and, in accordance with the holder’s instructions, proceed with the destruction or transfer of such documents.

　　Documents that shall be approved in writing by the holder include, but are not limited to: process specifications, batch production records, material, intermediate product, and product quality standards, process validation plans and reports, analytical method validation plans and reports, product complaint investigation reports, deviation investigation reports that may affect product quality, safety, or compliance with laws and regulations, documentation on changes that may affect product quality, safety, or compliance with laws and regulations, annual reports on product quality review and analysis, annual reports on material quality review and analysis, supplier files, and so forth.

　　10 Production Management

　　10.1 Product Batch Number Compilation

　　The trustee shall establish procedures and principles for the assignment of product batch numbers.

　　10.2 Production Date and Expiration Date

　　The trustee shall establish procedures and principles for managing the production date and expiration date of the product.

　　10.3 Production Site Supervision

　　With regard to the manufacturing process of the products covered by this quality agreement, the holder shall provide guidance and supervision over the contractor’s production activities.

　　11 Quality Control and Quality Assurance

　　11.1 Quality Control Laboratory Management

　　11.1.1 Sampling

　　The party responsible under the quality agreement shall develop standard operating procedures for sampling materials, intermediate products, and finished products, and shall carry out sampling in accordance with these procedures. The sampling shall be representative.

　　11.1.2 Inspection

　　The entrusted party shall establish management procedures for laboratory control to ensure that all testing activities are conducted under conditions that comply with GMP requirements.

　　The entrusted party shall conduct inspections in accordance with the quality standards for materials and products approved by the drug regulatory authority. Finished products must undergo full-scale testing according to the methods approved during registration. All quality standards covered by this Quality Agreement shall be reviewed and approved by the holder.

　　The entrusted party shall, in accordance with relevant regulations, develop a validation (transfer or confirmation) plan for analytical methods applicable to raw materials, excipients, packaging materials, intermediates, and finished products, and upon completion of the work, prepare a validation report. The validation plan and validation report must be approved by the holder before being used for the official inspection of manufactured products.

　　11.1.2.1 Materials

　　The party responsible under the quality agreement shall ensure that all materials used in production comply with the approved quality standards, and only materials that have passed inspection and been released may be used in product manufacturing. If there are any changes to the quality standards, both parties shall manage such changes in accordance with the “Change Control” provisions of this quality agreement.

　　11.1.2.2 Intermediate products

　　The entrusted party shall perform and document all intermediate product inspections in accordance with the approved quality standards.

　　11.1.2.3 Product

　　If a product fails to meet the approved quality standards upon inspection, it shall be handled in accordance with the “Deviation and OOS Management” section of this Quality Agreement.

　　11.1.3 Sample Retention

　　The party responsible under the quality agreement shall retain samples of materials and products in accordance with GMP requirements. The retained samples shall be stored under the registered and approved storage conditions for at least one year beyond the expiration date of the drug. Materials shall be stored under the specified conditions for at least two years after the product has been released. Proper records shall be maintained for the retained samples.

　　11.2 Release of Materials and Products

　　Material Release: The party responsible as stipulated in the quality agreement shall be responsible for releasing materials, ensuring that all materials used in production meet the approved quality standards and have passed inspection.

　　Product Release for Shipment: The entrusted party shall establish appropriate organizational structures, management systems, and quality control measures such as sampling and inspection. Before releasing products for shipment, the entrusted party must complete all necessary inspections and confirm that the products meet the required quality standards. The quality authorized representative of the entrusted party is responsible for reviewing batch production records and batch inspection records, and making the decision on whether to release the products for shipment. If a decision is made not to release the products for shipment, the entrusted party shall immediately notify the holder. After products have been released for shipment, if the entrusted party identifies any risk that the products do not comply with national pharmaceutical standards or the manufacturing process requirements approved by the drug regulatory authority, it shall immediately notify the holder.

　　Product Release for Market Launch: The marketing authorization holder shall establish procedures for the release of pharmaceutical products for market launch and assign a Qualified Person for Quality to conduct a comprehensive review of products released by the contract manufacturer in accordance with these procedures. Such review shall not only verify whether the test results comply with national pharmaceutical standards but also confirm that the drug manufacturing process adheres to GMP requirements, that the approved production processes have been followed, and that raw materials, excipients, and packaging materials meet statutory requirements. After the contract manufacturer completes the production release, it shall submit batch production records and batch inspection records to the marketing authorization holder for final review, upon which the holder will make the decision on whether to release the product for market launch. In the event that the holder decides not to release the product for market launch, it shall immediately notify the contract manufacturer.

　　11.3 Continuous Stability Study

　　The party responsible under the quality agreement shall conduct stability studies on materials, intermediate products, and finished products. When OOS or OOT results are observed in stability study samples, both parties shall immediately communicate and launch an investigation, and handle the OOS according to the “Deviation and OOS Management” provisions of this quality agreement.

　　11.4 Change Control

　　The marketing authorization holder is the entity responsible for making changes and shall, in accordance with the regulations of the National Medical Products Administration, conduct a comprehensive assessment and verification of the impact of such changes on the safety, efficacy, and quality control of the drug. Both the marketing authorization holder and the contract manufacturer shall manage these changes in compliance with applicable pharmaceutical laws, regulations, rules, and relevant technical guidance principles.

　　Both parties shall establish a change control procedure to clearly define the operational measures to be taken when changes occur that may affect product safety, efficacy, quality controllability, or regulatory compliance, and ensure smooth coordination and cooperation in their respective roles. When the entrusted party initiates a change, it shall notify the holder X days in advance. The degree of risk associated with the proposed change shall be assessed and determined by the holder, and the change must be reviewed and approved by the holder before implementation. When the holder initiates a change, it shall provide written notice to the entrusted party X days in advance, requesting the latter to conduct an assessment and carry out the change.

　　The holder shall conduct thorough research and validation, and implement or report the change only after obtaining the required approval and filing as stipulated, ensuring that the drug can continue to be produced consistently and stably with the same quality as before the change was implemented.

　　11.5 Deviation and OOS Management

　　Both parties shall establish deviation and Out-of-Specification (OOS) management procedures in accordance with GMP requirements. For any deviations or OOS incidents occurring during the production, inspection, storage, shipment, stability studies, and other activities related to the products covered by this Quality Agreement, the Contract Manufacturer shall record, investigate, and retain such incidents in compliance with the standard operating procedures. The investigation must assess the impact of the deviation or OOS on the product’s safety, efficacy, and quality control. The root cause must be identified, and effective corrective and preventive measures must be implemented. The Contract Manufacturer shall submit all deviation reports to the Holder for review and assessment.

　　For minor deviations that do not affect the safety, efficacy, or quality control of the product, the entrusted party shall document, investigate, evaluate, and track such deviations. At the time of product release, the holder shall review all deviations.

　　For deviations and Out-of-Specification (OOS) results that may affect the safety, efficacy, and quality control of the product, the entrusted party shall notify the holder in writing within X days and complete the investigation within X days from the date on which the deviation or OOS occurred, submitting the investigation report to the holder for review and approval.

　　11.6 Product Quality Review and Analysis

　　The party responsible under the quality agreement shall conduct an annual product quality review and analysis of the drugs manufactured under contract, and shall complete the report within X days after the end of the specified review period, submitting it for written approval by the holder.

　　11.7 Complaints and Adverse Reactions

　　When receiving complaints about product quality, the holder shall, together with the entrusted party, investigate the product complaints. The entrusted party shall cooperate fully and complete a self-inspection report within X days, which shall then be submitted to the holder for approval. Based on the findings of the self-inspection, the holder shall take appropriate corrective measures regarding products involved in quality complaints. For quality defects caused by the production process, the entrusted party shall develop effective corrective and preventive measures, which shall be reviewed and approved by the holder.

　　When the trustee collects quality complaint risks related to other products that may involve the entrusted product, the trustee shall promptly notify the holder of the relevant information, organize an investigation, establish appropriate corrective and preventive measures, and submit these measures for review and approval by the holder in accordance with the relevant change management procedures.

　　The marketing authorization holder shall establish a pharmacovigilance system and carry out pharmacovigilance activities in accordance with applicable requirements. Both the marketing authorization holder and the contract manufacturer shall regularly assess the quality, efficacy, and adverse reactions of their pharmaceutical products. If any suspected adverse reactions are identified, they shall promptly report them as required. The marketing authorization holder is responsible for handling quality complaints, and the contract manufacturer shall provide assistance and cooperation. Upon receiving a complaint, the contract manufacturer shall promptly notify the marketing authorization holder.

　　12 Product Storage, Shipment, and Recall

　　12.1 Product Storage

　　The entrusted party shall effectively monitor and maintain the storage conditions for materials and products, store production materials, intermediate products, and finished products in accordance with the designated storage conditions, and ensure compliance with GMP requirements.

　　12.2 Shipment

　　After the product is released for marketing by the holder, it shall be transported to the location designated by the holder in accordance with the contractual agreements. During the storage and shipment of the product, the entrusted party shall take necessary measures to ensure that there is no risk of confusion, error, contamination, or cross-contamination, and to ensure that the product complies with GMP requirements throughout the storage and transportation process. The entrusted party shall also take necessary measures to guarantee the integrity of the product packaging.

　　12.3 Recall

　　The holder is responsible for the product recall and shall decide whether to recall the relevant batch of products. The entrusted party shall provide the necessary information and cooperate fully with the recall efforts.

　　If the trustee has reasonable grounds to believe that relevant batches of products covered by this quality agreement should be recalled, it shall submit its views and reasons in writing to the holder.

　　13 On-site audit

　　The holder shall conduct on-site audits of the trustee’s production conditions, technical capabilities, and quality management practices to ensure that the trustee possesses the necessary production conditions and quality management capabilities for the products covered by this quality agreement. After the trustee’s qualifications have been confirmed and approved, the holder shall conduct on-site audits of the trustee at least once per year; for vaccine trustees, such audits shall be conducted quarterly, while for trustees handling other high-risk products, audits shall be conducted every six months. In cases where serious quality or safety risks are identified or other necessary circumstances arise, the holder shall immediately carry out a cause-based audit of the trustee. The trustee shall actively cooperate with the holder in conducting these on-site audits.

　　During the review process, the holder shall comply with the trustee’s systems, procedures, and requirements for security and confidentiality.

　　Any deficiencies identified by the holder during the on-site audit shall be actively addressed by the entrusted party, which shall develop a corrective action plan, clearly define corrective and preventive measures, and submit the plan to the holder for review and approval within X days following the completion of the audit. After the corrective actions are completed, the holder shall conduct an audit and confirmation within X days.

　　14 Compliance Support

　　When the holder needs to obtain product-related documentation for purposes such as inspections by drug regulatory authorities or product registration submissions, the entrusted party shall cooperate in providing the relevant materials, including but not limited to product research data, analytical method validation reports, and process validation reports.

　　The holder is responsible for preparing and submitting annual reports as required, covering aspects such as pharmaceutical production and sales, post-marketing studies, and risk management. The holder is also responsible for establishing and implementing a drug traceability system and for reporting the suspension of production of shortage drugs. The entrusted party shall provide assistance and cooperation.

　　15 Regulatory Supervision and Inspection

　　If the trustee or holder receives notice from the regulatory authority of an inspection and supervision of the relevant product or site, it shall promptly inform the holder within X days and submit a written report on the inspection findings to the holder within X days after the completion of the inspection and supervision.

　　When the holder is subject to supervision and inspection by the drug regulatory authority and is required to provide documentation related to contract manufacturing, the contract manufacturer shall cooperate and provide such information. When on-site inspections are necessary, the contract manufacturer shall also extend its cooperation.

　　During the supervision and inspection process, if necessary, one party shall actively assist the other party in undergoing the supervision and inspection.

　　16 Dispute Resolution for Quality

　　In the event of a quality dispute arising from the contract manufacturing of related products, both parties shall resolve the issue in accordance with applicable pharmaceutical laws, regulations, and rules, GMP requirements, and the terms of the quality agreement.

　　16.1 Both parties shall communicate directly to confirm the actual circumstances of the incident.

　　16.2 The trustee shall conduct an investigation and prepare a comprehensive investigation report. The investigation report shall provide a detailed account of the incident, including the sequence of events, the root causes, the findings of the investigation, and relevant evidence. The investigation report shall be submitted to the holder for review and approval. Both parties shall negotiate and resolve the issue based on the investigation report.

　　16.3 If a quality dispute cannot be resolved through negotiation, both parties shall select a third party to conduct an assessment and make a determination, and then agree on a resolution based on the results of the third-party assessment and determination.

　　16.4 The holder is responsible for the final disposition of products manufactured under contract.

　　16.5 Other circumstances.

　　17 deadline

　　This quality agreement shall take effect from the date of signing and remain in force throughout the duration of the contract manufacturing.

　　If both parties cease contract manufacturing, this quality agreement shall be retained for at least one year after the expiration date of the last batch of drugs released for marketing.

　　If either party needs to modify the contents of this Quality Agreement, both parties shall reach a mutual agreement and re-sign the agreement. The previous version of the Quality Agreement shall automatically become invalid upon the entry into force of the new version.

　　18 Change History

Date	Version	Change Overview

19 signatures

Holder

Draftsperson	Reviewer	Approver
Signature	Signature	Signature
Position	Position	Position
Date	Date	Date

 

Trustee

Draftsperson	Reviewer	Approver
Signature	Signature	Signature
Position	Position	Position
Date	Date	Date