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ICH Q5D Derivation and characterisation of cell substrates used for production of biotechnological/biological products (CPMP/ICH/294/95)

The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) provides guidelines to ensure the quality, safety, and efficacy of pharmaceutical products. ICH Q5D, as outlined in document CPMP/ICH/294/95, addresses the derivation and characterization of cell substrates used for the production of biotechnological and biological products. Below is a detailed elaboration of ICH Q5D:


1. Purpose of ICH Q5D:

ICH Q5D provides guidelines for the establishment of cell substrates used in the production of biotechnological and biological products. The primary goal is to ensure the quality, safety, and consistency of cell substrates to minimize potential risks associated with the final product.

2. Cell Substrate Characterization:

The guideline emphasizes the importance of thorough characterization of the cell substrate. This includes the origin of the cells, their history, and any relevant genetic information. Detailed documentation of the cell line's identity is critical.

3. Cell Line Derivation:

ICH Q5D outlines the principles for deriving cell lines, particularly emphasizing the importance of a clear and documented history of the cells' origin and passage history. Cell lines should be derived using well-documented and controlled processes to ensure their traceability.

4. Genetic Stability:

The guideline highlights the need for assessing and maintaining the genetic stability of cell substrates. Genetic changes or mutations can impact product consistency and safety. Monitoring and documenting the stability of the cell line over time are essential.

5. Evaluation of Tumorigenicity:

Cell substrates should undergo an evaluation for tumorigenic potential. This involves conducting appropriate tests to assess the risk of the cell line forming tumors in vivo. This is especially important for cell lines that have the potential to be tumorigenic.

6. Viral and Microbial Safety:

Ensuring viral and microbial safety is a crucial aspect of cell substrate characterization. The guideline recommends using appropriate testing methods to detect and eliminate potential contaminants, such as viruses or mycoplasma, from the cell substrate.

7. Authentication of Cell Substrates:

Authentication of cell substrates is necessary to confirm their identity and purity. Cell lines should be compared to well-characterized reference cells or other suitable standards to verify their authenticity.

8. Documentation and Records:

Comprehensive documentation is a fundamental requirement. Records detailing the history, characterization, genetic stability, and any relevant safety assessments of the cell substrate must be maintained and made available for regulatory authorities.

9. Regulatory Compliance:

Compliance with ICH Q5D is typically a regulatory requirement when seeking marketing authorization for biotechnological and biological products. Companies must adhere to these guidelines to ensure the quality and safety of their products.

10. Impact on Product Quality:

- The characteristics of the cell substrate directly impact the quality and safety of the final biotechnological or biological product. A well-characterized and stable cell substrate contributes to consistent product quality.


In summary, ICH Q5D provides comprehensive guidance on the derivation and characterization of cell substrates used in the production of biotechnological and biological products. These guidelines aim to ensure the safety and quality of cell substrates and, by extension, the final products. Compliance with these guidelines is essential for obtaining regulatory approval and maintaining product integrity throughout their lifecycle.

Reference 

https://database.ich.org/sites/default/files/Q5D%20Guideline.pdf

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