Durst DST Regulation Group noted that on July 12, 2024, the Food and Drug Review and Inspection Center of the State Drug Administration (hereinafter referred to as CFDI) issued opinions on soliciting "Guidelines for On-site Inspection of Cell Therapy Products" and feedback through electronic E-mail before July 29, 2024. This is also the second inspection guide on specific drugs issued by CFDI in conjunction with the Special Drug Inspection Center of the State Food and Drug Administration, following the "Guidelines for the Inspection of Radioactive Drug Production" (draft for comments "issued on July 10. The following is the relevant content of the announcement:

The full text is divided into four chapters, namely:

1. Purpose

To guide the inspectors to inspect the production site of cell therapy products, and formulate this guide according to the "good manufacturing practice (revised in 2010)" and the appendix, combined with the actual production quality management of cell therapy products in China at the present stage. Inspectors can refer to the requirements of this guide, the enterprise's production and quality management inspection, combined with the actual site and risk-based, evaluation of its production and quality management situation.

2. scope of application

The cell therapy products mentioned in this guide refer to human-derived live cell products prepared through appropriate in vitro operations (such as isolation, culture, amplification, genetic modification, etc.) approved for the market according to the drug, including after or without genetic modification Cells, such as autologous or allogeneic immune cells, stem cells, tissue cells or cell lines and other products; excluding blood components for blood transfusion, existing

Proposed hematopoietic stem cells, germ-related cells, tissues composed of cells, organoid products, and the like for transplantation.

This guideline covers the on-site inspection of cell therapy products, including the whole process from the transportation, reception, product production and inspection of donor materials to the release, storage and transportation of finished products, as well as the production, inspection and release of genetically modified vectors directly used in the production of cell products or other materials that give cells specific functions.

3. Regulatory Basis

v "the People's Republic of China Drug Administration Law"

v the People's Republic of China Biosecurity Act

v Regulations on Biosafety Management of Pathogenic Microbiology Laboratories

v Measures for the Supervision and Administration of Drug Production

v Measures for the Administration of Drug Registration

v Pharmacopoeia of the People's Republic of China (2020 Edition)

v Measures for the Administration of Drug Inspection (Trial)

v Requirements for Drug Records and Data Management (Trial)

v Pharmaceutical Manufacturing Quality Management Regulations and Appendix

v Guidelines for Quality Management of Cell Therapy Products (Trial)

v Announcement of the State Food and Drug Administration on Strengthening the Supervision and Administration of Production Entrusted by Drug Marketing License Holders (No. 132 of 2023)

v Notice of the General Department of the State Food and Drug Administration on the issuance of the guidelines for the on-site inspection of the production entrusted by the holders of the drug marketing license (CFDA [2023] No. 81)

v General Requirements for Laboratory Biosafety (GB 19489)

v Technical Code for Building of Biosafety Laboratory (GB 50346)

v Regulations on Manufacturing and Verification Approved by Drug Administration

4. inspection points

General (I) requirements

(II) Quality Management

1. Risk management

2. Data Reliability Management

3. Management review

4. Institutions and personnel

5. Validation and Verification

6. Product Release

7. Change Management

8. Deviation Management

9. Material supplier management

10. Product Quality Review

11. Complaint, Return and Recall Management

12. Management of commissioned production and outsourcing activities

13. Self-inspection

(III) plant and facilities

1. Plant facilities

2. Equipment

(IV) materials and products

1. Materials

2. Products

(V) production management

1. Overview of varieties

2. Production process and control

3. The production of genetically modified vectors or other materials that give cells specific functions directly used in the production of cell products

4. Sterility assurance, anti-contamination and cross-contamination, anti-error confusion

5. Aseptic process simulation

6. Process Validation

(VI) Quality Control

1. Laboratory Facilities and Environment

2. Instrument and equipment management

3. Inspection and sample retention

4. Bacteria, cells and standard substances for inspection

5. Inspection sample management

6. Inspection process management

7. Stability investigation

8. Commissioned inspection

9. Validation of analytical methods

(VII) packaging and labeling

1. Packaging containers and labels

2. Product packaging production management

(VIII) product traceability system

1. Overview

2. Traceability of the whole process of cell therapy products

3. Management of product traceability system

(IX) donor materials and medical institution management

1. Donor materials

2. Management of medical institutions