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Guideline on development and manufacture of lentiviral vectors (CHMP/BWP/2458/03)

The guideline with the reference number "CHMP/BWP/2458/03" pertains to the "Guideline on Development and Manufacture of Lentiviral Vectors." This guideline was developed by the Committee for Medicinal Products for Human Use (CHMP) and the Biotechnology Working Party (BWP) of the European Medicines Agency (EMA). It provides recommendations and regulatory guidance for the development and manufacture of lentiviral vectors, which are widely used in gene therapy and cell therapy applications. Here's an overview of the key points covered in this guideline:


1. Introduction:

The guideline begins with an introduction highlighting the increasing importance of lentiviral vectors in advanced therapies and the need for guidance on their development and manufacture.

2. Scope:

It defines the scope of the guideline, which covers the development and manufacture of lentiviral vectors intended for use in gene therapy and cell therapy products for human use.

3. Quality and Characterization:

The guideline emphasizes the importance of establishing a robust quality control and characterization process for lentiviral vectors. It includes recommendations for the identification, testing, and characterization of vectors.

4. Vector Design and Construction:

Recommendations are provided for the design and construction of lentiviral vectors. This includes considerations for the viral backbone, regulatory elements, and transgene expression cassettes.

5. Production Process:


The guideline outlines principles for the production process, including vector production methods, cell substrate selection, and cultivation conditions.

6. Testing and Release:

It discusses the testing requirements for lentiviral vectors to ensure their safety, potency, and quality. This includes analytical methods, identity testing, and in-process controls.

7. Safety:

Safety considerations are highlighted, including the importance of minimizing the risk of replication-competent lentivirus (RCL) contamination and ensuring vector purity.

8. Documentation and Regulatory Submission:

The guideline provides guidance on the documentation required for regulatory submissions related to lentiviral vectors.

9. Clinical Trials:

It emphasizes the importance of comprehensive preclinical testing and risk assessment before initiating clinical trials involving lentiviral vectors.

10. Interaction with Regulatory Authorities:

- The guideline encourages early and ongoing interaction with regulatory authorities to address questions and ensure compliance with regulatory requirements.

11. Comparability:

- Recommendations are provided for assessing and demonstrating comparability when making changes to the manufacturing process or vector design.

12. Stability Testing:

- The guideline discusses the stability testing requirements for lentiviral vectors, including storage conditions and shelf-life determination.

13. Traceability and Pharmacovigilance:

- Considerations for traceability and pharmacovigilance are outlined, including the need for monitoring and reporting of adverse events.

14. References:

- The document includes a list of references for further information on lentiviral vector development and manufacturing.

This guideline is essential for ensuring the quality, safety, and consistency of lentiviral vectors used in advanced therapy medicinal products. It provides a regulatory framework to guide developers and manufacturers through the process of bringing these vectors to clinical use while meeting stringent regulatory requirements. Developers and manufacturers in the field of gene therapy and cell therapy should consult this guideline for detailed guidance on lentiviral vector development and manufacture. Please note that specific requirements and recommendations may evolve, so it's important to consult the most up-to-date version of the guideline on the EMA's official website or through regulatory authorities

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