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ICH: Q5A(R2) Guideline on Viral Safety of Biotechnology Products adopted

ICH: Q5A(R2) Guideline on Viral Safety of Biotechnology Products adopted

The Assembly of the International Council for Harmonisation (ICH) has adopted the revised Q5A(R2) Guideline on the Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin. The guideline describes a general approach to testing and assessing the viral safety of those products and sets out the data that should be submitted in marketing authorisation applications and registration packages. These products include biotherapeutics and biological products derived from characterised cell cultures of human or animal origin (mammals, birds, insects). The term "virus" used therein does not include non-conventionally transmissible pathogens, such as mammalian prion-associated pathogens.

This document applies to:

  • Products produced from in vitro cell culture using recombinant DNA technologies such as interferons, monoclonal antibodies, and recombinant subunit vaccines.
  • Products derived from hybridoma cells grown in vivo as ascites: special considerations apply for these products.
    Annex 1 contains additional information on testing cells propagated in vivo.
  • Certain genetically engineered viral vectors and viral vector-derived products, which can undergo virus clearance without a negative impact on the product. These products may include viral vectors produced using transient transfection or from a stable cell line, or by infection using a recombinant virus. It also includes viral vector-derived recombinant proteins, for example, baculovirus-expressed Virus-like Particles (VLPs), protein subunits, and nanoparticle-based vaccines and therapeutics.
  • Adeno-associated virus (AAV) gene therapy vectors that depend on helper viruses such as baculovirus, herpes simplex virus, or adenovirus for their production.
    Specific guidance on genetically engineered viral vectors and viral vector-derived products is provided in Annex 7.

Excluded from the scope are:

  • Inactivated viral vaccines and live attenuated viral vaccines containing self-replicating agents.

The guideline provides three additional recommendations on the established and complementary approaches to control the potential viral contamination of biotechnology products:

  • Selecting and testing cell lines and other raw materials, including media components, for the absence of undesirable infectious viruses
  • Assessing the capacity of the production process to clear infectious viruses
  • Testing the product at appropriate steps of production.

The document has reached Step 4 of the ICH process, is now considered harmonised, and represents the current state of science and technology. This was announced following the ICH meeting in Prague on 31 October 2023. The draft guideline was first presented in September 2022 (we reported). After implementation, it will subsequently be published on the ICH website.


ICH: Press Release: ICH Assembly Meeting, Prague, Czech Republic, October/November 2023