The Comprehensive Affairs Department of NMPA Solicits Public Comments on “Reference Template for Quality Agreement on Drug Consignment Production (Draft for Comments)”

1. Definition

"Audit": refers to the inspection and evaluation of the production quality management system of the trustee by the holder.

"Batch": a certain amount of raw materials, packaging materials or finished products produced through one or more processing processes with expected uniform quality and characteristics. In order to complete certain production operation steps, it may be necessary to divide a batch of products into several sub-batches and finally merge them into a uniform batch. In the case of continuous production, the batch must correspond to a certain number of products with expected uniform characteristics in production. The batch can be a fixed number or the amount of products produced in a fixed time period.

"Batch record": all documents and records used to record the production, quality inspection and release review of each batch of drugs, which can trace all historical information related to the quality of the finished product.

2. Purpose

Clearly define the various quality responsibilities of the holder and the trustee to implement the laws and regulations on drug management and the drug production quality management specifications, and ensure that the entrusted production behavior continues to comply with the requirements of drug laws and regulations and technical specifications.

3. Basic information

3.1 Contact information

Please refer to Appendix 2 Contact information for information such as the contact information of the holder and the trustee.

3.2 Responsibilities

The holder and the trustee shall perform the relevant obligations stipulated in the "Regulations on the Supervision and Administration of Drug Production" and the "Good Manufacturing Practice for Drugs", and each shall assume corresponding responsibilities. For details on the division of responsibilities, please refer to Annex 3.

The parties to the agreement shall comply with all applicable laws, regulations and technical specifications, establish a good communication mechanism, and ensure the safety, effectiveness and quality control of the entrusted production of drugs. For specific requirements, please refer to the provisions of this Agreement.

3.3 Registration information and technical documents

The holder shall transfer the registration information and technical documents related to product production to the trustee before the production process validation, and if necessary, shall send personnel to train the trustee. When the relevant registration information changes, the holder shall inform the trustee within X working days from the date when the relevant registration information is approved for change.

The trustee shall keep confidential all the registration information and technical documents of the products involved in this agreement, and establish the corresponding quality system and quality documents in accordance with the requirements of the laws, regulations and technical specifications for drug management. The key quality documents such as product process procedures, quality standards, batch records, etc. involved in this agreement shall be reviewed and approved by both the holder and the trustee.

4. Compliance with laws and regulations

The holder and the trustee shall comply with the following laws and regulations to ensure that the entire process of entrusted production continues to meet the statutory requirements:

"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"

"Drug Registration Management Measures"

"Drug Production Supervision and Management Measures"

"Drug Production Quality Management Standards"

Other applicable laws, regulations and technical specifications

Product quality standards

The holder and the trustee shall promptly notify each other in writing of any known changes in current laws and regulations that may affect the quality of drug production and the responsibilities of both parties. The relevant contents of this agreement shall be revised in accordance with the requirements of laws and regulations.

5. Production and supply

5.1 Plant facilities and equipment

The trustee shall ensure that the plant facilities, equipment, computer systems, etc. related to the production and inspection of the product are in good condition and have been confirmed, and the production process, cleaning procedures, analytical methods, etc. have passed relevant verification. For changes that may affect the safety, effectiveness and quality control of the product, if re-verification is required after evaluation by both parties, the trustee shall conduct re-verification activities. The trustee shall determine the feasibility of sharing the factory, production facilities and equipment for multiple products based on the characteristics, process and intended use of the entrusted drugs, and shall have a corresponding report. The risk assessment report on co-production of products shall be reviewed and approved by the holder.

5.2 Materials

The holder shall select, manage and review the material suppliers, and the suppliers shall comply with the quality management specifications formulated by the State Drug Administration and the relevant requirements for related review and approval. The holder shall provide the qualified supplier catalog to the trustee, and after the trustee's review and approval, it shall be included in the trustee's qualified supplier catalog for the trustee's inspection and acceptance when entering the factory. The holder and the trustee shall agree on the material purchaser in advance. X is responsible for the procurement of materials used in product production, and shall be responsible for supplier management and material quality assurance. It shall establish relevant procedures for material receipt, inspection, release and storage in accordance with relevant laws and regulations, and receive, inspect, retain samples, release and store materials in accordance with the procedures.

The trustee shall list the materials and qualified supplier catalog required for the production of the product involved in this agreement in the production process specifications of the product. Materials not in the catalog shall not be used for contract production. If it is necessary to add qualified suppliers to the list and change material suppliers, the holder must be notified in writing and the relevant supplementary agreement must be signed.

5.3 Production process

The trustee shall, in accordance with this agreement, draft the production process procedures, blank batch records and other relevant quality documents of the product based on the registered prescription, production process and quality standards, and shall be reviewed and approved by both the holder and the trustee.

The trustee shall perform production operations in accordance with the production process procedures and record them in a timely and truthful manner.

When any deviation from the approved process procedures occurs, the entrusted pharmaceutical manufacturer shall conduct deviation investigation and handling in accordance with the "Deviation Management" of this agreement.

When the production process of the product needs to be changed, both parties shall manage it in accordance with the "Change Control" of this agreement.

The entrusted pharmaceutical manufacturer shall make batch records according to the approved production and carry out production activities in an environment that meets the corresponding production conditions.

5.4 Product batch number preparation

The trustee shall formulate a product batch number preparation procedure, and the principles for batch number preparation are defined in Appendix 1.

5.5 Production date and validity period

The trustee shall formulate the management procedures for the production date, validity period or re-inspection period of the products. The definition and form of the production date and validity period of the products involved in this agreement are shown in Appendix 1.

5.6 Production, inspection and equipment records

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

Each batch of products shall have batch production records, batch packaging records and batch inspection records (including intermediate product testing and QC inspection records before product release).

The trustee shall keep all records related to product production in accordance with the "Document Management" requirements of this agreement.

5.7 Rework, reprocessing and recycling

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

If the trustee needs to rework, reprocess or recycle the products involved in this agreement, it shall inform the holder in advance and obtain its written approval before production operations can be carried out.

The Trustee shall record all rework, reprocessing and recycling activities and keep them as part of the batch record.

5.8 Production Site Supervision

For the production process of the products covered by this Agreement, the Holder shall guide and supervise the production activities of the Trustee.

Specific news link: The General Department of the State Drug Administration publicly solicits opinions on the "Reference Template for Quality Agreements for Drug Manufacturing (Draft for Comments)"