On May 24, to further strengthen the supervision and management of Marketing Authorization Holders (MAHs) engaged in contract manufacturing, the National Medical Products Administration (NMPA) published the “Notice on Strengthening the Supervision and Management of Marketing Authorization Holders Engaging in Contract Manufacturing (Draft for Comments)” on its official website, seeking public feedback.

The main content of this draft is divided into four parts: “Strict Management of Permits for Contract Manufacturing,” “Strengthening Quality Management for Contract Manufacturing,” “Strengthening Inspection and Supervision of MAHs Engaging in Contract Manufacturing,” and “Other Matters.” It consists of 17 articles, with the public comment period ending on June 23.

1. Implementing Principal Responsibility | Authorization Does Not Relinquish Responsibility

According to the Drug Administration Law, a Marketing Authorization Holder refers to an enterprise or pharmaceutical research institution that holds a drug registration certificate. Since the implementation of the MAH system in China in 2015, MAHs have been allowed to be separate from manufacturing enterprises, enabling MAHs to choose between manufacturing drugs themselves or engaging contract manufacturing organizations. This initiative encourages R&D entities to focus resources on drug development and innovation, optimizes resource allocation, and curbs low-level, repetitive industry construction. Since then, the number of MAHs engaging in contract manufacturing, particularly those relying solely on contract manufacturing, has surged significantly.

However, regardless of the manufacturing approach, the MAH bears primary responsibility for the safety, efficacy, and quality controllability of the drug throughout its entire lifecycle.

It is reported that to fully implement the principal responsibility of MAHs for drug quality and safety, the NMPA formulated and implemented the “Regulations on the Supervision and Management of the Implementation of Drug Quality and Safety Principal Responsibility by Marketing Authorization Holders,” which took effect on March 1 of this year. Building upon this, the NMPA also formulated the “Notice on Strengthening the Supervision and Management of Marketing Authorization Holders Engaging in Contract Manufacturing (Draft for Comments)” (hereinafter referred to as the “Draft”) and the “On-Site Inspection Guidelines for Marketing Authorization Holders Engaging in Contract Manufacturing” (hereinafter referred to as the “Inspection Guidelines”) to further tighten permit management for contract manufacturing, strengthen quality management, urge MAHs to fulfill their responsibilities diligently, and ensure drug quality and safety throughout the lifecycle.

For those intending to engage in contract manufacturing and applying for a Drug Manufacturing License (referred to as Type B License) or applying for changes to the permitted scope of a Type B License, this Draft requires that provincial-level drug regulatory authorities strictly review application materials in accordance with the “Measures for the Supervision and Administration of Drug Manufacturing” (Order No. 28 of the State Administration for Market Regulation) and the “Announcement of the National Medical Products Administration on Implementing the Newly Revised Measures for the Supervision and Administration of Drug Manufacturing” (Announcement No. 47 of 2020). This includes a strict review of the notification of GMP compliance inspection issued by the provincial-level drug regulatory authority where the contract manufacturer is located, along with the consent for contract manufacturing. Based on risk assessment, the provincial-level drug regulatory authority where the contract manufacturer is located may issue a GMP compliance inspection notification based on inspection results for the same dosage form or the same production line.

For products intended for registration but not yet granted marketing authorization, the Draft requires provincial-level drug regulatory authorities to guide applicants through prior communication. Applicants should complete the pharmaceutical, pharmacological/toxicological, and clinical trial studies required to support drug registration, finalize quality standards, complete process validation at commercial scale, and be prepared for drug registration inspection and testing before applying for the issuance of a Drug Manufacturing License or an extension of the manufacturing scope. If the product fails to obtain marketing authorization, the provincial-level drug regulatory authority shall revoke the Drug Manufacturing License or reduce the relevant manufacturing scope in accordance with the law.

2. Encouraging Improvement of Quality Management Systems | Promoting High-Quality Innovation

To further implement the principal responsibility of MAHs, the Draft stipulates that MAHs must establish management departments with clearly defined responsibilities, equip themselves with managerial personnel commensurate with the scale of drug production and distribution, and establish a quality management system covering the entire drug production process as required. MAHs of traditional Chinese medicine injections and multi-component biochemical drugs must possess their own manufacturing capabilities. MAHs of biologics (excluding vaccines and blood products) are encouraged to possess their own manufacturing capabilities. If production capacity is insufficient and additional contract manufacturing sites are needed, the procedures stipulated in the “Measures for the Management of Post-Marketing Changes of Drugs” must be strictly followed.

The Draft proposes that MAHs should continuously improve their quality management systems and enhance quality management throughout the entire process. MAHs of multi-component biochemical drugs are encouraged to establish their own raw material bases and strengthen process control over raw materials of human or animal origin. Manufacturers of traditional Chinese medicine injections are encouraged to use Chinese medicinal materials that comply with the requirements of the Good Agricultural Practice for Chinese Medicinal Materials (GAP) to ensure the quality, safety, and stable supply of raw materials.

Regarding cross-provincial contract manufacturing and changes involving cross-provincial transfer of MAHs, the Draft specifies that the provincial-level drug regulatory authority where the original MAH is located shall, within 30 working days after the transfer is completed, compile the results data from all historical change filings and reports related to the product and upload them to the national drug regulatory data sharing platform, associating them with the drug product file. This will enable the provincial-level drug regulatory authority in the receiving location to access and use the information, ensuring supervision is based on the most current approved information.

The Draft also requires that provincial-level drug regulatory authorities conduct inspections and supervision in accordance with the “Regulations on MAH Management,” the “Inspection Key Points,” etc. It mandates that provincial-level drug regulatory authorities carry out a comprehensive special inspection covering all MAHs engaged in contract manufacturing this year. It further details cross-provincial regulatory responsibilities and emphasizes enhancing information connectivity and sharing in supervision.

The concurrently released draft of the “Inspection Guidelines” primarily includes three sections: “Institution and Personnel,” “Quality Management System,” and “MAH Management of Contract Manufacturing.” The main content of the “Inspection Guidelines” was formed by extracting and summarizing requirements related to MAH contract manufacturing from existing regulations such as the “Regulations on MAH Management,” the “Good Manufacturing Practice for Drugs,” and the “Guidelines for Quality Agreements for Drug Contract Manufacturing (2020 Edition).” It outlines key aspects that need to be verified during on-site inspections of contract manufacturing activities.