Original Title: Notice from the Shandong Provincial Drug Administration on the Issuance of the "Implementation Rules for Market Authorization Holders of Contract-Manufactured Drugs in Shandong Province to Fulfil Their Primary Responsibilities"

Chapter I General Provisions

Article 1: To further implement the primary responsibility for drug quality and safety of marketing authorization holders for outsourced production (hereinafter referred to as “B Certificate Holders”) and to ensure drug quality and safety throughout the entire lifecycle, these Implementation Rules are formulated in accordance with the “Drug Administration Law of the People’s Republic of China,” the “Measures for the Administration of Drug Registration,” the “Measures for the Supervision and Administration of Drug Production,” the “Provisions on the Supervision and Administration of Marketing Authorization Holders’ Implementation of Primary Responsibility for Drug Quality and Safety” (hereinafter referred to as the “Provisions”), the “Announcement of the National Medical Products Administration on Strengthening the Supervision and Administration of Outsourced Production by Marketing Authorization Holders” (hereinafter referred to as the “Announcement”),the "Guidelines for On-site Inspections of Contract Manufacturing by Drug Marketing Authorization Holders" (hereinafter referred to as the "Inspection Guidelines"), and other relevant provisions, these Implementation Rules are hereby formulated.

Article 2 These Implementation Rules apply to the conduct of B Certificate holders within Shandong Province in fulfilling their primary responsibility for drug quality and safety in accordance with the law, as well as the supervision and administration thereof.

Article 3 B-license holders shall possess the capabilities in quality management, risk prevention and control, and liability compensation necessary to ensure the safety, efficacy, and controllable quality of drugs, and shall bear primary responsibility for the quality and safety of drugs throughout their entire life cycle in accordance with the law. B-license holders shall strengthen management over entities entrusted to carry out drug manufacturing, distribution, pharmacovigilance, and other activities, ensuring that such entrusted entities fulfill their quality assurance obligations in accordance with the agreement and bear corresponding legal responsibilities.

Article 4: B License holders shall allocate sufficient resources and personnel based on the specific products under contract manufacturing, strengthen training for key personnel, and conduct regular audits of contract manufacturers to ensure that the contract manufacturing process and drug quality consistently meet statutory requirements.

Article 5: The B Certificate holder and the contract manufacturer shall strengthen communication and cooperation, and establish and improve communication mechanisms to ensure the effective integration of both parties’ quality management systems. In the event of disputes regarding change control, deviations, test results exceeding limits or trends, quality complaints, or adverse drug reactions, both parties shall promptly engage in communication and consultation to ensure proper resolution within the scope of legality, compliance, and controllable risk, and jointly safeguard drug quality and safety.In the event of drug quality abnormalities, both parties shall immediately control risks, investigate causes, implement comprehensive corrective actions, and adopt effective risk control measures.

Chapter II: Requirements for Fulfilling Primary Responsibilities

Article 6 The B License Holder shall strictly implement the requirements of laws and regulations related to drug management, establish a quality management system covering the entire process of drug research, development, production, distribution, and use, and continuously improve it; establish drug quality objectives to ensure that the drugs produced meet their intended use and registration requirements.

Article 7 The B Certificate holder shall obtain a "Drug Manufacturing License" and drug approval documents in accordance with the law, and may only market and sell drugs after passing the GMP compliance inspection as required. In the event of changes to the registered address (business premises), legal representative, enterprise head, quality manager, quality authorization holder, or production manager, the holder shall strictly follow the requirements for drug manufacturing license registration to process the changes.

After obtaining a Drug Manufacturing License, the License Holder shall not arbitrarily alter or lower the standards and conditions approved by the drug regulatory authorities during the licensing inspection. When the volume of products released for market increases, the enterprise shall strengthen infrastructure, allocate sufficient personnel, enhance information management, and improve quality management standards to ensure compliance with quality management requirements for products released for market.

If a drug marketing authorization application is not approved, the applicant shall apply for the cancellation of the drug manufacturing license or for a reduction in the corresponding scope of production within six months. After a drug manufacturing license is approved, if a drug marketing authorization application remains unfiled for an extended period and the facilities, equipment, personnel, etc., clearly fail to meet the requirements for the drug manufacturing license and registration, the above requirements shall apply.

Article 8 Holders of a Class B License shall establish a management organization with clearly defined responsibilities that is commensurate with the drugs they hold, and shall appoint a sufficient number of management and operational personnel appropriate to the scale of drug production and operations, to ensure that the actual quality management needs regarding the types, quantities, and production batches of the held drug products are met.

Holders of a Class B License shall establish an independent quality management department, clearly defining its responsibilities to perform quality management throughout the entire process, participate in all quality-related activities, and review all documents related to quality management.

Article 9 The legal representative and the enterprise head shall bear overall responsibility for drug quality. The enterprise head shall implement the primary responsibility for full-process quality management in accordance with the requirements of the Regulations, the Announcement, and the Inspection Guidelines.

The enterprise head shall possess work experience in the pharmaceutical field, be familiar with laws, regulations, and rules related to drug management, and possess a strong sense of legal compliance, responsibility, quality, and risk awareness. The enterprise head shall regularly review measures for implementing primary responsibility for quality management and faithfully perform their duties.

Article 10 Key personnel, including the enterprise head, production head, quality head, and quality authorized person, shall be full-time employees holding a Class B Certificate and shall meet the requirements of relevant quality management standards. The quality head and production head shall not hold both positions concurrently. The qualifications and duty requirements for key personnel shall be implemented in accordance with the Regulations. Key personnel shall not fall under any circumstances prohibited by laws and regulations related to pharmaceuticals from engaging in pharmaceutical production and business operations.

For the contract manufacturing of sterile pharmaceuticals, the production manager, quality manager, and quality authorized person of the License B holder shall each have at least 5 years of practical experience in pharmaceutical production and quality management, including at least 3 years of practical experience in the production and quality management of sterile pharmaceuticals. For the contract manufacturing of traditional Chinese medicine injections and multi-component biochemical pharmaceuticals, the production manager, quality manager, and quality authorized person of the License B holder shall have at least 3 years of practical experience in the production and quality management of similar dosage forms.

A License B holder may designate multiple Qualified Persons based on the characteristics of the commissioned production varieties, production scale, number of contract manufacturers, and other actual circumstances, with clearly defined responsibilities covering the release duties for all marketed products. In cases of temporary delegation of authority, the delegated personnel shall meet the relevant qualifications for Qualified Persons, be approved by the enterprise’s legal representative or responsible person, and have the scope, matters, and duration of the delegation specified in writing; the original Qualified Person shall continue to bear corresponding responsibilities.

Article 11: License holders are encouraged to establish their own quality control laboratories to conduct testing. Personnel, equipment, and facilities shall be commensurate with the nature of the product and the scale of production to ensure that all required testing items are completed in accordance with regulations. When outsourcing testing to contract manufacturers, on-site assessments of the contract manufacturer’s personnel, equipment, facilities, and quality management practices shall be conducted to confirm their capability to perform the contracted testing.The holder of a Certificate B shall supervise the entire process of the commissioned testing. When commissioning the production of biological products, traditional Chinese medicine injections, or multi-component biochemical drugs, the holder shall, in accordance with regulations, select a portion of batches annually for comparison of test results to confirm that the commissioned manufacturer’s testing capabilities meet product requirements.

In principle, the B Certificate holder or the contract manufacturer shall not further delegate testing to a third party; however, for specific testing items involving specialized testing equipment that is costly to use and used infrequently, the B Certificate holder may commission a qualified third-party testing institution to conduct the testing. The B Certificate holder shall review the qualifications and capabilities of the third-party testing institution, enter into a testing delegation agreement with it, and report to the regional inspection branch.

Article 12 When entrusting the conduct of production, distribution, pharmacovigilance, or other related work, a委托 agreement and a quality agreement shall be signed with the entrusted party. The quality systems of the B Certificate holder and the entrusted party shall be closely integrated, jointly constituting a quality management system covering the entire life cycle of the drug.When outsourcing the storage or transportation of drugs, the B Certificate holder shall assess the contractor’s quality assurance and risk management capabilities, enter into outsourcing and quality agreements with the contractor in accordance with relevant regulations, and periodically review the contractor’s storage and transportation management practices to ensure that the storage and transportation processes comply with the Good Distribution Practice (GDP) and the storage conditions required for the drugs.

Article 13 The B License holder shall provide guidance and supervision throughout the entire contract manufacturing process to ensure that the contract manufacturer can produce drugs that meet the registered standards in accordance with the registered manufacturing process. Obligations and responsibilities that are legally required to be fulfilled by the B License holder shall not be transferred through a quality agreement.

Article 14 The B Certificate holder shall establish a training management system in accordance with requirements, formulate training programs or plans, and conduct pre-employment and continuing training for personnel involved in the entire drug lifecycle. The content shall include theory and practice, laws and regulations, job responsibilities, and operational skills. When conducting contract manufacturing, the B Certificate holder shall ensure that the personnel of the contract manufacturer can consistently meet the requirements for the production of the product.

Key personnel of the License B holder shall be proficient in pharmaceutical laws, regulations, and relevant document requirements; familiar with the quality attributes, process characteristics, and risk profiles of the drugs they hold; and shall continuously strengthen training to enhance their professional competence and ability to perform duties. They shall undergo personal competency assessments through the training examination system as required, accept on-site assessments and spot checks conducted during supervisory inspections and risk communication activities organized by regulatory authorities, and periodically evaluate the effectiveness of training.

Article 15 The B Certificate holder shall fulfill its responsibility for drug release, establish drug release procedures, review the release procedures established by the contract manufacturer, clarify the drug release standards, and strictly review the drug test results, release documents, key production records, and deviation control status provided by the drug manufacturer upon release.They shall verify that the drug manufacturing process complies with GMP and the approved manufacturing process, that raw materials, excipients, and packaging materials meet statutory requirements, and that test results comply with national drug standards. If all requirements are met, the product may be released for marketing only after being signed off by the Quality Authorized Person. When a decision is made not to release the product for marketing, the Certificate B holder shall immediately notify the contract manufacturer.

If, after drug release, risks are identified—such as non-compliance with national drug standards or the production process requirements approved by drug regulatory authorities—both the principal and the contract manufacturer shall promptly implement corresponding risk control measures.

Article 16: The B Certificate holder shall establish a post-marketing change control system in accordance with requirements, formulate internal change classification principles, a list of change items, work procedures, and risk management requirements, and implement them diligently; based on product characteristics, the B Certificate holder shall collaborate with the contract manufacturer to conduct relevant research, assessments, and necessary validation, determine the change management category, and implement the change after approval or filing, or include it in the annual report.

The B Certificate holder shall strictly formulate product manufacturing specifications in accordance with the information approved during the regulatory review and registration process, and strengthen change management. Any inconsistencies between the drug’s production site, formulation, manufacturing process, production equipment, quality standards, and other factors and the product’s manufacturing process information sheet or registration application materials shall be classified as change items. The risk level of changes related to contract-manufactured products shall be assessed and determined by the B Certificate holder, and the contract manufacturer shall obtain review and approval from the B Certificate holder prior to implementing such changes.

Article 17. The B Certificate holder shall prepare an annual report based on a summary of the previous year’s drug production, sales, post-marketing research, and risk management activities, while also including information on shared production lines for commissioned products, quality disputes between the parties, and any adverse information regarding the contract manufacturer.The annual drug report must be approved by the enterprise’s legal representative or the person in charge of the enterprise (or their authorized representative in writing) and submitted within the prescribed time limit to ensure that the information in the annual drug report is true, accurate, complete, and traceable, and complies with laws, regulations, and relevant provisions.

Major or moderate changes shall not be split into minor changes and submitted via the annual report to circumvent the approval or filing process.

Article 18: Holders of Certificate B shall establish a pharmacovigilance system and conduct pharmacovigilance activities in accordance with requirements. They shall regularly assess the quality, efficacy, and adverse reactions of their products; upon identifying suspected adverse reactions, they shall report them promptly in accordance with requirements. Upon receiving complaints regarding product quality, the holder of Certificate B shall collaborate with the contract manufacturer to investigate the complaint; based on the results of the internal investigation, the holder of Certificate B shall take appropriate measures regarding the product involved in the quality complaint.

Where pharmacovigilance-related work is outsourced, the holder shall evaluate and select a contractor possessing the necessary pharmacovigilance conditions and capabilities, enter into a delegation agreement, and conduct regular audits of the contractor to ensure that pharmacovigilance activities continue to meet requirements.

The qualifications and responsibilities of the pharmacovigilance officer shall be implemented in accordance with the "Regulations," ensuring the effective operation and continuous improvement of the pharmacovigilance system and the standardized conduct of pharmacovigilance activities.

Article 19 Holders of Certificate B shall establish relevant management procedures and systems for liability compensation and possess proof of liability compensation capacity or corresponding commercial insurance purchase contracts. Liability compensation capacity shall be commensurate with factors such as the product’s risk level, market scale, and standards for compensation for personal injury.

Article 20. The B License Holder shall establish and implement a drug traceability system, either by building an information-based traceability system in-house or by entrusting a third party to do so as required. The B License Holder shall ensure that the contract manufacturer establishes an information-based traceability management system commensurate with the types and scale of the drugs under contract manufacturing, and shall provide traceability data to the drug regulatory authorities in accordance with regulations.

Article 21. The B Certificate holder is the entity responsible for controlling risks and eliminating potential hazards. It shall establish a drug recall system, formulate drug recall management procedures, and clearly define the division of responsibilities with the contract manufacturer.If a drug has quality issues or other safety hazards, the B Certificate holder shall immediately notify relevant drug distributors and medical institutions to cease sales and use, recall drugs already sold, and, if necessary, immediately instruct the contract manufacturer to halt production; the B Certificate holder shall also report the status of the drug recall and disposal to the regional inspection bureau in a timely manner as required.

Based on the investigation results, the B Certificate holder shall formulate corrective and preventive measures; where such measures involve contract manufacturers, the B Certificate holder shall urge them to complete the measures in a timely manner to ensure that drug quality defects or safety risks are promptly eliminated. Drug manufacturers, drug distributors, and medical institutions shall cooperate to ensure the timely recall of products and effective control of risks.

Article 22 The B Certificate holder shall formulate a post-marketing risk management plan for the drug; requirements may be referenced in the *Shandong Province Guidelines for the Preparation of Post-Marketing Risk Management Plans*. The holder shall proactively conduct post-marketing studies to further confirm the drug’s safety, efficacy, and controllable quality, and strengthen the ongoing management of marketed drugs.

For drugs approved with conditions, corresponding risk management measures shall be implemented, and relevant studies shall be completed in accordance with requirements within the specified timeframe.

Article 23 The B Certificate holder shall formulate a response plan for drug safety incidents and organize training and emergency drills. In the event of a major safety incident related to drug quality, the B Certificate holder shall require the contract manufacturer to immediately take effective measures to address the affected drugs, their raw materials, excipients, packaging materials and containers in direct contact with the drugs, and relevant production lines, and shall immediately report to the Provincial Drug Administration and relevant departments.The B Certificate holder shall carry out risk management in accordance with emergency response requirements to effectively prevent, actively address, promptly control, and eliminate potential risks.

Article 24 The B Certificate holder shall, in conjunction with product risks, regularly organize retrospective analyses of quality management, production management, marketing and use, post-marketing research, and pharmacovigilance monitoring. In principle, risk assessments shall be conducted at least once per quarter to formulate corrective and preventive actions and continuously improve the quality management system.

Article 25. B Certificate holders shall regularly conduct self-inspections or internal audits of the operation of their quality management systems, including supervisory audits of contract manufacturing enterprises. In accordance with the "Measures for the Administration of Risk Self-Inspection Reports of Drug Production and Operation Enterprises in Shandong Province," they shall conduct comprehensive risk self-inspections regarding compliance with laws, regulations, standards, and specifications, and submit reports as required.

Article 26. B Certificate holders shall ensure the production and supply of drugs in accordance with regulations, and shall promptly collect, compile, and analyze information on drug supply and demand. For drugs listed on the national list of shortage drugs subject to production suspension reporting, if production is planned to be suspended, the B Certificate holder shall report to the Provincial Bureau six months prior to the planned suspension; in the event of an unplanned suspension, the B Certificate holder shall report to the Provincial Bureau within three days. If necessary, a report shall be submitted to the national drug regulatory authority.

Chapter III Quality Management System

Article 27 When outsourcing production, the License B holder shall assess the contract manufacturer’s production conditions, technical capabilities, quality management, and corporate creditworthiness. In accordance with the principles of “quality first” and “compliance as the top priority,” the License B holder shall confirm that the contract manufacturer possesses the necessary conditions and capabilities for contract manufacturing, and is capable of continuously complying with Good Manufacturing Practice (GMP) for pharmaceuticals and meeting the production quality management requirements for the outsourced drug. License B holders are encouraged to select pharmaceutical manufacturers that facilitate enhanced drug quality management and risk prevention and control for contract manufacturing.

Article 28 The B Certificate holder and the contract manufacturer shall establish a documentation system covering the entire process and establish a sound communication mechanism between the two parties to ensure effective integration of their respective quality systems. This is to prevent issues such as overlapping or unclear responsibilities and omissions in the documentation system that could compromise the integrity and traceability of information throughout the entire process.

The Licensee shall provide the contract manufacturer with necessary technical data in accordance with the *Guidelines for Quality Agreements on Contract Manufacturing of Drugs*. Should any changes occur in relevant registration information, the Licensee shall promptly notify the contract manufacturer and, if necessary, provide training to the contract manufacturer. The Licensee shall review and approve relevant documents and records prepared by the contract manufacturer and retain production quality documents and records directly related to the contract-manufactured products as required.

Article 29: If the contract manufacturer falls under any of the following circumstances, the License B holder shall consider terminating the contract manufacturing arrangement or replacing the contract manufacturer:

(1) The contract manufacturer has been investigated and penalized for serious violations of laws or regulations;

(2) A major drug quality and safety incident has occurred;

(3) The quality system fails to operate normally, and records and data regarding drug production process control and quality control are found to be inaccurate;

(4) High-risk products are manufactured on shared production lines, and effective risk control measures have not been promptly implemented for identified risks, rendering product quality unguaranteed;

(5) Refusal to cooperate in matters such as change management, deviation management, recalls, and complaint handling;

(6) The entity has a record of serious legal violations or breaches of trust;

(7) Multiple batches of products fail random inspections;

(8) Other circumstances warranting the termination of contract manufacturing.

The B Certificate holder shall ensure, through contractual agreements or other means, that after the termination of contract manufacturing activities, the handover of technical documentation between the contracting parties, the management of retained samples, and stability studies continue to be carried out in accordance with laws, regulations, and contractual requirements.

Article 30. The B Certificate holder shall conduct at least one audit of the contract manufacturer annually. The type and frequency of audits for contract manufacturing enterprises shall be determined based on the product, dosage form, and production status, taking into account drug safety risk alerts as well as the results of previous inspections, testing, adverse reaction monitoring, and complaints and reports.

For special product categories (such as high-risk products including biological products, traditional Chinese medicine injections, multi-component biochemical drugs, and sterile drugs, as well as key products such as pediatric medications), the audit frequency shall be appropriately increased based on risk management principles, with no fewer than two audits per year. Upon discovering serious quality and safety risks or similar circumstances, the B Certificate holder shall immediately conduct a targeted audit of the contract manufacturer.

Article 31. The B Certificate holder shall provide guidance and supervision over the manufacturing process of the commissioned drug, ensuring production is conducted in accordance with national drug standards and the approved formulation and process, and that the contract manufacturing process consistently complies with GMP requirements.

For biological products, traditional Chinese medicine (TCM) injections, and multi-component biochemical drugs, on-site guidance and supervision must be conducted at the contract manufacturer’s premises as required; on-site supervision for other product categories is encouraged based on risk assessment. Personnel stationed at the contract manufacturer’s premises shall possess practical experience in production and quality management within the relevant field and be familiar with the product’s manufacturing processes and quality control requirements. The job responsibilities of such personnel and relevant requirements regarding sampling and testing by the License B holder shall be clearly specified in the quality agreement.

For the contract manufacturing of biological products, TCM injections, and multi-component biochemical drugs, the B Certificate holder shall continuously improve the level of quality management throughout the entire process, and relevant work shall be carried out in accordance with the requirements of the "Announcement."

Article 32 The B Certificate holder shall, based on factors such as the characteristics, manufacturing processes, and intended use of the contract-manufactured drug, confirm that the contract manufacturer’s production conditions and capabilities—including premises, facilities, and equipment—meet the requirements for contract manufacturing; supervise the contract manufacturer in maintaining premises, facilities, and equipment according to schedule; and conduct necessary validation and verification in conjunction with the contract-manufactured drug.

Article 33 For shared-line production, both parties shall conduct an assessment in accordance with the *Guidance on Quality Risk Management for Shared-Line Production of Drugs* to determine the feasibility of sharing production facilities, equipment, and premises across multiple products, establish feasible contamination control measures, and identify risks of contamination and cross-contamination.The B Certificate holder shall periodically inspect the contract manufacturer’s implementation of contamination control measures, establish necessary testing items based on the risk assessment, and conduct testing to ensure the quality and safety of the drug. The B Certificate holder shall review and approve the risk assessment report for shared-line production.

The B Certificate holder bears primary responsibility for the feasibility and controllability of shared-line production for the products it holds, reviews and approves the contract manufacturer’s shared-line production risk assessment report, and periodically reviews the risk control measures for shared-line production to ensure effective control of contamination and cross-contamination risks. If either party makes changes that may affect the quality of the contract-manufactured drug, it shall promptly notify the other party in writing; the B Certificate holder shall conduct a comprehensive assessment and review and approve the change application and report in accordance with established procedures.

Article 34. The B Certificate holder shall fulfill primary responsibility for the management of materials (raw and auxiliary materials, pharmaceutical packaging materials), including the selection, management, and audit of material suppliers, and shall establish qualified supplier records. Where necessary, the contract manufacturer may participate in the quality audit process.

The B Certificate holder shall establish principles for tiered material management and on-site audit requirements based on risk assessment. Through evaluation, the B Certificate holder shall determine the audit entity, method, content, and frequency; in principle, the on-site audit cycle for critical materials shall not exceed three years.

The B Certificate holder shall strengthen supervision of the contract manufacturer’s material management activities to ensure the contract manufacturer fulfills the obligations specified in the agreement; if the contract manufacturer discovers any abnormalities during the material management process, it shall promptly report them to the B Certificate holder.

Article 35 The B Certificate holder shall establish management systems for product rework, reprocessing, and recycling activities. Relevant documents established for the contracted product shall be reviewed and approved by both parties, and the B Certificate holder shall supervise these activities.

Article 36. The B Certificate holder shall confirm that the contract manufacturer may proceed with product process validation only after completing the necessary qualification and validation (including facilities, equipment, and utility systems); the protocols and reports for process validation and cleaning validation shall be approved by both parties.

Article 37. The B Certificate holder shall clarify the responsibilities for testing raw materials and intermediate products through a quality agreement. When relevant testing is performed by the contract manufacturer, the B Certificate holder shall ensure that the contract manufacturer conducts method validation, transfer, or confirmation; the protocols and reports shall be reviewed and approved by the B Certificate holder. If either party discovers that test results exceed limits or deviate from trends, they shall immediately notify the other party, and both parties shall jointly analyze and address the product quality issue.

Article 38. The B Certificate holder shall ensure that the storage conditions and quantities of retained samples comply with GMP requirements and shall maintain records in accordance with regulations. In particular, when the contract manufacturer retains samples of finished products or raw materials (including the retention methods and sample quantities), such retention must be reviewed and approved by the holder. For any abnormalities discovered during the sample retention process, the B Certificate holder shall organize an investigation and implement risk control measures.

Article 39. The B Certificate holder shall not delegate the product release for market authorization to the contract manufacturer. The contract manufacturer is responsible for the product’s release from the factory. The responsibilities for raw material release shall be clearly defined in the quality agreement to ensure that raw material release complies with requirements.

Article 40 Both parties shall clarify responsibilities regarding the transportation of materials and products to prevent mix-ups, errors, contamination, and cross-contamination, and ensure that the transportation process complies with the "Measures for the Supervision and Administration of the Quality of Drug Distribution and Use." For products with special storage and transportation requirements, ensure that they remain under the specified storage conditions throughout the entire process and maintain monitoring records in accordance with regulations.

Article 41 Both parties shall clarify responsibilities for ongoing stability studies to ensure their implementation in accordance with the agreement, and encourage increasing the number of stability study batches based on product characteristics. Where the contract manufacturer is responsible for ongoing stability studies, the stability study protocol and report shall be reviewed and approved by both parties; the License B holder is encouraged to conduct on-site supervision of the testing process for stability study samples.

Article 42. The B Certificate holder shall establish a deviation management procedure that complies with legal and regulatory requirements. For deviations related to contract-manufactured products that occur during production quality management activities, the B Certificate holder shall ensure that the contract manufacturer handles them in accordance with the deviation handling procedure.

The B Certificate holder shall investigate issues identified in relation to the contract-manufactured product, including deviations, out-of-specification test results, complaints, changes, and product quality retrospective analyses, take necessary corrective and preventive actions, and ensure their effective implementation.

Article 43. The B Certificate holder shall ensure that product quality retrospective analyses are completed in accordance with the requirements of the agreement to confirm the stability and reliability of the process, as well as the applicability of current quality standards for raw and auxiliary materials and finished products; promptly identify adverse trends; and determine the direction for product and process improvements.

Article 44. The B Certificate holder shall specify in the quality agreement that the contract manufacturer must promptly report to the B Certificate holder any defects related to the contract product discovered during self-inspection activities, as well as the corrective and preventive actions taken.

Article 45 If the contract manufacturer develops a poor credit record during the contract manufacturing period, the B Certificate holder shall promptly conduct an audit and report the audit findings to the regional inspection branch. At the same time, the B Certificate holder shall dispatch personnel to the site to manage the contract manufacturing process and ensure that the production process continues to comply with pharmaceutical GMP and regulatory requirements.

Chapter IV Other Provisions

Article 46. The B Certificate holder and the contract manufacturer shall cooperate with the drug regulatory authorities in their supervision and inspection of the entity and in sampling and testing, and shall cooperate with extended inspections of relevant parties. They shall not refuse or evade supervision and inspection or sampling and testing, nor shall they forge, destroy, or conceal relevant evidence materials, or tamper with sealed or impounded items without authorization.

Article 47. The B Certificate holder shall organize the rectification of deficiencies identified during supervisory inspections and shall urge the contract manufacturer to complete the rectification of its own deficiencies. The B Certificate holder shall review and confirm the rectification measures related to the quality management of the contract-manufactured drug and, where such deficiencies affect the quality of a batch of products, shall propose recommendations for the disposition of that batch.

Article 48. The B Certificate holder and its key personnel shall bear corresponding legal liability in accordance with the law for non-clinical studies, clinical trials, production and operation, post-marketing studies, adverse reaction monitoring, reporting, and handling of medicinal products.

Chapter V Supplementary Provisions

Article 49 Blood products, narcotic drugs, psychotropic substances, toxic drugs for medical use, and drug-related precursor chemicals shall not be entrusted for production in accordance with the law; where there are special provisions for vaccines and other products, such provisions shall prevail.

These Implementation Rules shall come into effect on July 1, 2024.