In order to further strengthen supervision and administration of contract manufacturing of marketed drugs, clarify the obligations and responsibilities of all parties, and urge the marketing authorization holders (hereinafter referred to as MAHs) for marketed drugs under contract manufacturing and contract manufacturers to jointly fulfill the main responsibility of ensuring drug quality and safety, the relevant matters concerning strengthening supervision and administration of drug contract manufacturing are hereby announced in accordance with the Drug Administration Law of the People's Republic of China and the Provisions for the Supervision and Administration of Drug Manufacturing.

I. Strengthening the responsibility of contract manufacturers

(I) Contract manufacturers shall establish and improve a quality management system and ensure its continuous and effective operation, strictly comply with Good Manufacturing Practice for Drugs (hereinafter referred to as drug GMP), and, on the basis of adequate technical transfer research, organize manufacturing in accordance with national drug standards and the prescriptions and manufacturing processes approved by the drug regulatory authorities, and earnestly fulfill the obligations and responsibilities agreed upon in the contract manufacturing agreement and quality agreement.

(II) Contract manufacturers shall possess organizational structures, personnel, premises, and equipment matching the products under contract manufacturing, have corresponding quality assurance capabilities and risk management abilities, and ensure that the manufacturing process continuously complies with laws and regulations.

(III) Contract manufacturers shall establish an evaluation mechanism for MAHs and the products under contract manufacturing. Before accepting contract manufacturing, the contract manufacturers shall conduct a comprehensive evaluation of the MAHs and the proposed products under contract manufacturing, focusing on the MAH's qualifications, quality management capabilities, as well as the risk factors of the proposed products under contract manufacturing, the feasibility of accepting technical transfer, and the feasibility of co-line production. Only after passing the evaluation may the parties sign the contract manufacturing agreement and quality agreement. For drug contract manufacturing between enterprises implementing a unified quality management system within the same group, the evaluation contents such as the qualifications and quality management capabilities of MAHs, may be simplified.

Contract manufacturers shall prioritize cooperation with MAHs that possess independent research and development management capabilities and master of key process technologies of the contracted products. The MAHs shall actively cooperate with the comprehensive evaluation conducted by the contract manufacturers and provide true and valid materials for the contract manufacturers' evaluation.

(IV) Both contract parties shall strengthen risk identification, communication, analysis, evaluation, and handling during the technical transfer process, provide technical training to relevant personnel, and carry out technical transfer work in accordance with relevant laws, regulations, and technical guidelines, ensuring adequate technical transfer research and the consistency of product quality before and after the transfer. During the technical transfer, if both contract parties find that the technical transfer is difficult to accomplish due to software and hardware conditions, production management, quality management, etc., or that risks to drug manufacturing quality may arise, they shall immediately communicate and take measures to control the risks; if the risks are difficult to control effectively, they shall terminate the cooperation. For products where R&D is outsourced to a third party, the MAHs shall coordinate for enhanced collaboration between the third party engaged in R&D and the contract manufacturer to jointly complete the technical transfer work.

During the technical transfer, contract manufacturers shall undertake the following tasks:

(1) Assign a person in charge responsible for technical transfer liaison, establish a technical transfer working group, and clarify the responsibilities of the person in charge and members of the working group;

(2) Establish and improve the technical transfer management system, review the feasibility of technical transfer plans developed by relevant parties, and implement the plan requirements;

(3) Conduct qualification or validation of facilities and equipment, cleaning methods, analytical methods, manufacturing processes, and other related work in accordance with laws and regulations, as well as co-line production risk assessments;

(4) Cooperate with the MAHs to summarize and analyze technical transfer data and records, and review the technical transfer report to ensure that the records and data of the technical transfer process are true, accurate, complete, and traceable;

(5) Formulate technical documents, such as manufacturing process procedures and blank batch records, based on the results of qualification or validation and co-line production risk assessment, combined with the MAH's technical transfer documents and technical transfer outcomes, and submit such documents to the MAH for review and approval.

(V) Contract manufacturers shall establish relevant risk prevention and control systems, and cooperate with MAHs to carry out quality management activities, such as risk assessment, validation, communication, review, and the implementation of related risk control measures. During the contract manufacturing of marketed products, the contract manufacturers shall, based on the product type, process characteristics and production status, cooperate with the MAHs in conducting quarterly risk assessment and annual product quality review analysis. Any deviation shall be promptly recorded, handled, and the MAHs shall be promptly notified of such deviation; if any quality risk or compliance risk is identified, effective risk control measures shall be taken jointly with the MAHs; in case of major quality risks or compliance risks, manufacturing shall be immediately suspended. Contract manufacturers shall establish relevant systems and cooperate with the MAHs in pharmacovigilance activities.

For the contract manufacturing of high-risk products such as sterile drugs, MAHs shall assign personnel to supervise validation activities by on-site inspections at least once a year, including sterilization process validation and aseptic process simulation tests; the contract manufacturers shall provide access to relevant sites and areas, provide relevant records, and actively cooperate with MAHs in the relevant work.

(VI) Both contract parties shall ensure the effective connection of quality management systems and strengthen the management of drug manufacturing, inspection records and data. Contract manufacturers shall designate a person responsible for connecting with the quality management system of MAHs and clarify their responsibilities; the quality agreement shall specify that MAHs have the right to consult the management systems, operating procedures, documents and records related to the contract manufacturing activities, and to inspect the sites related to the contract manufacturing activities, to ensure that the contract manufacturing complies with laws, regulations, technical specifications, and the quality management requirements of MAHs.

(VII) Contract manufacturers and MAHs shall establish a quality information communication procedure, formulate a list of communication items in accordance with the risk management principle (at least including deviations, changes, out-of-specification/out-of-trend results, qualification and validation, retention samples and stability studies, pharmacovigilance, inspection status by drug regulatory authorities, adverse credit records, etc.), and clarify the communication personnel and responsibilities, communication methods and relevant timeframes to ensure smooth, timely, and effective communication.

(VIII) Contract manufacturers shall strengthen co-line production risk management in accordance with the Guidelines for Quality Risk Management in Co-line Drug Manufacturing and other provisions. When co-line production conditions change (such as the addition of commercially manufactured drugs, addition of non-commercial products, changes in prescriptions and manufacturing processes, changes in facilities and equipment, or other major changes, etc.), the contract manufacturers shall form clear and definite co-line production risk assessment conclusions, take effective risk control measures based on the assessment conclusions, and promptly notify the MAHs of all co-line production products of the risk assessment conclusions and the risk control measures adopted; business information that is legally protected may be excluded from such notifications. Contract manufacturers shall carefully study the feedback from MAHs, take corresponding measures, and reach an agreement with MAHs. For potential risks, contract manufacturers shall take corrective and preventive measures approved by MAHs.

Contract manufacturers shall reasonably determine the number of products to be accepted for contract manufacturing and the production plan in light of the designed production capacity of the production line, co-line production risk assessment, cleaning validation, production management, material and finished product management, etc., to ensure that the production capacity is always within a reasonable range.

(IX) Contract manufacturers shall establish a change control system in accordance with the relevant provisions on drug change management and drug GMP requirements, and diligently conduct change research and control.

Relevant changes involving the products under contract manufacturing shall not be implemented without the approval of MAHs. The contract manufacturer shall cooperate with MAHs to jointly conduct change-related research, determine the category of changes, and assist MAHs in completing applications for approval, filing, or reporting in accordance with the law. Where both contract parties fail to reach consensus on the category of changes, change management shall be conducted in accordance with the higher category. If contract manufacturers or MAHs conclude through assessment that implemented changes pose quality risks, they shall promptly take corresponding measures to ensure the elimination of risks.

(X) Where the same contract manufacturer accepts contract manufacturing of drugs with the same generic name from multiple MAHs, or the contract manufacturer itself holds drugs with the same generic name, it shall strictly implement whole-process production management and document management, formulate corresponding process procedures, quality standards, test methods, etc. for finished drug products respectively, and ensure that manufacturing processes are mutually independent and strictly segregated. It shall also strengthen material management, and the management of key materials, intermediate products, and finished drug products shall be mutually independent to avoid confusion and ensure traceability.

Where MAHs entrust multiple contract manufacturers to produce the same drug, MAHs shall ensure that all contract manufacturers manufacture in accordance with the approved manufacturing process. If there are differences in production conditions on the basis of the approved manufacturing process, contract manufacturers shall cooperate with MAHs in conducting comparative analysis, carry out risk assessment on the differences, and formulate corresponding risk prevention and control measures. MAHs shall regularly conduct product quality comparison studies to ensure consistent product quality.

(XI) MAHs and contract manufacturers shall strengthen retention sampling and stability studies. Where MAHs deem it necessary through assessment, both MAHs and contract manufacturers shall conduct retention sampling for relevant materials or conduct retention sampling and continuous stability studies for relevant finished drug products to meet the requirements for drug quality traceability and investigation. For batches of products with such major deviations during manufacturing and the first three batches of products manufactured after the approval and implementation of major changes, both contract parties shall conduct retention sampling and continuous stability studies for the relevant finished drug products. MAHs may conduct retention sampling and stability studies on their own or entrust qualified third-party institutions with such work. Where such work is entrusted to third-party institutions, MAHs shall strengthen the management of such work.

For drug contract manufacturing between enterprises implementing a unified quality management system within the same group, or where contract manufacturers record whole-process manufacturing and test data by means of information technology and can conduct electronic data exchange with MAHs, either MAHs or contract manufacturers may conduct retention sampling and continuous stability studies.

(XII) Contract manufacturers shall establish standard operating procedures for drug release in accordance with laws and regulations, and clarify the standards and conditions for drug release. Drugs that meet the standards, conditions and legal and regulatory requirements may only be released upon the signature of the qualified person. Upon drug release, contract manufacturers shall submit the batch production records, batch test records, deviation investigation records and other relevant records and data related to the products under contract manufacturing to MAHs together. When conducting a marketing release, MAHs shall strictly review the drug quality test results, key production records and deviation control status. When necessary, MAHs shall review the batch production records, batch test records, deviation investigation records and other relevant records and data.

(XIII) Contract manufacturers shall actively cooperate with MAHs in conducting regular on-site audits, and actively cooperate with the provincial drug regulatory authorities where MAHs are located in carrying out extended inspections, and shall not conceal the real situation or provide false materials, and shall promptly rectify the issues identified in the audits or inspections. After MAHs complete the on-site audit of contract manufacturers, MAHs shall promptly prepare an on-site audit report.

(XIV) Contract manufacturers shall preserve whole-process manufacturing and testing data and records in accordance with drug GMP requirements to ensure that the data are true, accurate, complete and traceable. MAHs and contract manufacturers are encouraged to establish an information management system covering the whole process of material management, drug manufacturing and testing, and adopt information-based means to conduct transmission, review, archiving and other work on documents and records of the whole process of drug manufacturing and testing. Where contract manufacturers record whole-process drug manufacturing and testing data by means of information technology and can conduct electronic data exchange with MAHs, in regular audit work, MAHs may use off-site audits to replace some on-site audits.

(XV) MAHs and contract manufacturers shall refine quality management measures in accordance with laws and regulations based on product characteristics and the actual situation of contract manufacturing, update the contract manufacturing agreement and quality agreement in a timely manner to ensure that the agreement contents are consistent with the management systems and document procedures of both contract parties, and strictly perform the obligations and responsibilities agreed in the agreements.

II. Strengthening supervision and administration of contract manufacturing

(XVI) Where a contract manufacturer intends to apply for the issuance of a Drug Manufacturing License for contract manufacturing (hereinafter referred to as Class C License) or for a change of licensing items of the Class C License, all provincial drug regulatory authorities shall conduct strict examination in accordance with the Provisions for the Supervision and Administration of Drug Manufacturing (State Administration for Market Regulation, SAMR Decree No. 28), the Announcement of the National Medical Products Administration on the Issues Pertaining to Implementation of the Newly Revised Provisions for the Supervision and Administration of Drug Manufacturing (No. 47, 2020), the Announcement of the National Medical Products Administration on Strengthening the Regulation of Drug Marketing Authorization Holders' Contract Manufacturing (No. 132, 2023) and other requirements, as well as the requirements of this Announcement. Only applications that comply with the provisions shall be approved for the issuance of a Class C License or have relevant changes approved.

(XVII) Where sterile drugs are intended to be manufactured under contract, in principle, either the MAH or the contract manufacturer shall have at least three years of commercial manufacturing experience in sterile drugs of the same dosage form.

Contract manufacturing of sterile drugs may also be carried out if either the MAH or the contract manufacturer has at least three years of R&D or manufacturing experience in sterile drugs of the same dosage form under any of the following circumstances:

1. The drugs are innovative drugs, improved new drugs, national shortage drugs, national clinically essential and easy-to-short-supplied drugs, drugs with clinical urgent needs, drugs with urgent needs for response to public health emergencies, drugs for rare diseases, as well as overseas-manufactured drugs already marketed domestically that are transferred to domestic manufacturing;

2. Sterile drugs manufactured under contract between enterprises implementing a unified quality management system within the same group;

3. Contract manufacturers that record whole-process data of material management, drug manufacturing and testing by means of information technology and are capable of electronic data exchange with MAHs;

4. Contract manufacturers that have primarily participated in the R&D and clinical trial drug manufacturing of the sterile drugs intended to be manufactured under contract.

For the intended contract manufacturing of sterile drugs, the head of production, head of quality, and qualified person of the contract manufacturer shall each have at least five years of practical experience in drug manufacturing and quality management, including at least three years of practical experience in sterile drug manufacturing and quality management. For the intended contract manufacturing of traditional Chinese medicine injections and multi-component biochemical drugs, the head of production, head of quality, and qualified person of the contract manufacturer shall also have at least three years of practical experience in the manufacturing and quality management of the same type of drug products.

(XVIII) For products for which no commercial-scale batches have been marketed and released within the re-registration cycle, if MAHs intend to carry out contract manufacturing, they shall first resume manufacturing in accordance with the relevant requirements for resumption of manufacturing of long-term discontinued drugs as specified in the Re-registration Application Procedures for Domestically Manufactured Drugs of the National Medical Products Administration. MAHs may resume manufacturing by means of contract manufacturing for national shortage drugs, national clinically essential and easy-to-short-supplied drugs, drugs that have passed the generic drug quality and efficacy consistency evaluation, and drugs that were manufactured under contract before discontinuation.

Where a relevant production line has been idle for a long time (more than three years for sterile production lines, more than five years for other types of production lines) and intends to resume manufacturing, drug manufacturers shall conduct qualification and validation before resuming production, and apply to the provincial drug regulatory authority at their locality for drug GMP compliance inspection. The products inspected may be those held by the enterprise or manufactured under contract, and contract manufacturing may be accepted only after passing the inspection.

(XIX) Where both contract parties are located in the same provincial administrative region and intend to handle relevant licensing items for entrusted or contract manufacturing, the provincial drug regulatory authority may handle the relevant licensing items for the Drug Manufacturing License for Contract Manufacturing (hereinafter referred to as Class B License) and the Class C License simultaneously without issuing a Written Opinion on Drug Contract Manufacturing.

Where both contract parties are not located in the same provincial administrative region and intend to handle relevant licensing items for contract manufacturing:

(1) For those that have not yet obtained a Drug Manufacturing License, or need to add a manufacturing address and manufacturing scope, the contract manufacturer shall apply to the provincial drug regulatory authority at its locality for the issuance of the Class C License or a change of licensing items in accordance with the Announcement of the National Medical Products Administration on the Issues Pertaining to Implementation of the Newly Revised Provisions for the Supervision and Administration of Drug Manufacturing (No. 47, 2020) and other requirements. For applications that meet the requirements, the provincial drug regulatory authority at the locality of the contract manufacturer shall go through the procedures for issuing the Class C License or changing licensing items, and simultaneously issue a Written Opinion on Drug Contract Manufacturing based on the results of the drug GMP compliance inspection or license inspection.

(2) For those that already hold a Drug Manufacturing License with the corresponding manufacturing address and manufacturing scope, the contract manufacturer shall submit application materials to the provincial drug regulatory authority at its locality; the provincial drug regulatory authority at the locality of the contract manufacturer shall conduct strict review of the application materials, issue a Written Opinion on Drug Contract Manufacturing based on the results of drug GMP compliance inspection or license inspection, and carry out inspection as required if necessary.

After contract manufacturers obtain the Written Opinion on Drug Contract Manufacturing, MAHs shall apply to the provincial drug regulatory authority in their localities for the Class B License within 12 months. The provincial drug regulatory authority at the locality of MAHs shall conduct a strict review of the application materials submitted by MAHs, carry out on-site inspection of the applicant in accordance with provisions, and issue the Class B License or approve relevant changes if the provisions are met. After MAHs complete the licensing items for the Class B License, contract manufacturers shall, within 60 working days, submit an application to the provincial drug regulatory authority at their locality to record the relevant changes, such as the enterprise names of both contract parties, product names, and approval numbers, in the duplicate of the Drug Manufacturing License.

(XX) Relevant licensing items for contract manufacturing shall be handled in accordance with the provisions on changing manufacturing addresses or manufacturing scopes as stipulated in Article 16 of the Provisions for the Supervision and Administration of Drug Manufacturing, and no separate validity period shall be set. When the Drug Manufacturing Licenses of MAHs and contract manufacturers are renewed upon expiration, the provincial drug regulatory authority at the locality of contract manufacturers does not need to issue the Written Opinion on Drug Contract Manufacturing again.

Where the marketing authorization fails to be approved, the required manufacturing conditions are not met, or the contract activities are terminated due to agreement provisions or other factors, MAHs and contract manufacturers shall, within six months after the termination of contract activities, voluntarily apply to the provincial drug regulatory authorities at their respective localities for cancellation or reduction of the corresponding contract or contract manufacturing scope.

(XXI) The provincial drug regulatory authorities at the localities of contract manufacturers shall carry out targeted inspections of contract manufacturers based on risk, focusing on the operation of the quality management systems of contract manufacturers. Those whose quality management systems fail to operate continuously and effectively or that are suspected of violations of laws and regulations shall be investigated and handled in a timely manner in accordance with laws and regulations. Inspections of contract manufacturers may be carried out simultaneously with routine inspections, license inspections, as well as extended inspections conducted by the provincial drug regulatory authorities at the localities of MAHs.

All provincial drug regulatory authorities shall carry out quality sampling and testing of contract-manufactured products based on risk. The provincial drug regulatory authorities at the localities of MAHs may carry out sampling and testing in the manufacturing, circulation (including internet drug trading) and use stages, or request the provincial drug regulatory authorities at the localities of contract manufacturers to carry out sampling and/or testing in the manufacturing stage.

(XXII) All provincial drug regulatory authorities shall, in accordance with the principle of territorial regulation, strengthen the assessment of the performance of key personnel of both drug contract enterprises in the approval of drug contract manufacturing licenses and regular regulation. Based on the assessment and inspection results, they may take measures such as interviews, warnings, and rectification within a specified time limit. If the key personnel are found to have inadequate job performance capabilities, risk control measures such as suspension of manufacturing and sales may be further taken if necessary.

(XXIII) All provincial drug regulatory authorities shall make use of platforms such as drug safety credit files and the national drug sampling and testing information system to properly transmit the supervision and inspection information and quality sampling and testing information of cross-provincial contract-manufactured products, establish a smoothly operating coordinated regulation mechanism, and form an effective regulation closed loop.

(XXIV) Where drug regulatory authorities find that MAHs or contract manufacturers have provided false personnel resumes, false data, records, on-site assessment reports, etc., in the application for manufacturing licenses, they shall handle the matter in accordance with Article 123 of the Drug Administration Law and other provisions.

Where contract manufacturers, during contract manufacturing, commit acts such as manufacturing counterfeit or substandard drugs, fabricating manufacturing and testing records, failing to release drugs in accordance with laws and regulations, failing to manufacture in accordance with the manufacturing process provided by MAHs, or failing to comply with drug GMP in contract manufacturing activities, they shall bear corresponding legal liabilities in accordance with the law, and the provincial drug regulatory authority at the locality of contract manufacturers shall handle the matter in accordance with Articles 116, 117, 124, 126, and 127 of the Drug Administration Law.

The provincial drug regulatory authority at the locality of contract manufacturers shall promptly notify the provincial drug regulatory authority at the locality of MAHs of the above-mentioned violations and the investigation and handling results.

III. Other matters

(XXV) All provincial drug regulatory authorities shall strengthen policy publicity and implementation, and urge MAHs and contract manufacturers to conduct comprehensive self-inspections in accordance with the requirements of this Announcement. Where the contract manufacturing situation is inconsistent with the requirements of this Announcement, both contract parties shall conduct consultations, formulate a rectification plan, and, in principle, complete rectification within one year after the issuance of this Announcement. If the rectification period of individual items does need to exceed one year, the reasons and completion time limit shall be clearly defined. Provincial drug regulatory authorities shall urge MAHs and contract manufacturers to complete rectification within a time limit; if those failing to complete rectification within the time limit shall have their contract manufacturing activities suspended in accordance with the law, or their relevant manufacturing scopes reduced, until their Drug Manufacturing Licenses are revoked in accordance with the law.

(XXVI) For innovative drugs, improved new drugs, national shortage drugs, national clinically essential and easy-to-short-supplied drugs, drugs with clinical urgent needs, drugs with urgent needs for response to public health emergencies, drugs for rare diseases, as well as overseas-manufactured drugs already marketed domestically that are transferred to domestic manufacturing, support shall be given to expanding production capacity or accelerating drug marketing progress by means of contract manufacturing.

(XXVII) For newly established contract manufacturers and production lines where newly added contract-manufactured products involve selected drugs in national centralized procurement or high-risk drugs, they are encouraged to be equipped with production and quality information management systems such as Manufacturing Execution System (MES), Laboratory Information Management System (LIMS), Document Management System (DMS) and Warehouse Management System (WMS), to continuously improve and perfect the quality management system.

The development of high-level and professional Contract Development and Manufacturing Organizations (CDMOs) that have participated in R&D, achieved product commercialization, and possess the corresponding production capacity, is encouraged, and support shall be given to their acceptance of contract manufacturing; relevant enterprises are supported to accept supervision and inspection by WHO-Listed Authorities (WLA).

(XXVIII) This Announcement shall come into force as of the date of issuance. Drug manufacturing license applications and drug registration applications already accepted before the issuance of this Announcement shall be handled in accordance with the original requirements. Unless otherwise stipulated by laws, regulations, rules, and the National Medical Products Administration.

National Medical Products Administration of the People's Republic of China

December 30, 2025