We have previously discussed the issues surrounding animal-derived products for research and why animal origin-free (AOF) alternatives are preferred [Blog - why animal origin free?]. These include the potential for cross-contamination with other bioactive proteins or contaminants, which can introduce unwanted variability. When considering proteins used for the development of cell therapy, further assurance of purity and consistency is paramount, particularly due to the potential risk of harm through the application of an improperly manufactured product.
FDA guidance [1] recommends that animal-origin-free products are used for the manufacture of cell and gene therapy products wherever possible. Regulatory submissions must include assurances of the safety and quality of materials used in manufacturing.
How are animal products used in cell therapy?
Cell and gene therapy protocols are complex and multi-step. Protocols may include the ex vivo expansion of patient-derived or donor cells, gene editing, cell banking - all processes that may require the use of animal derived reagents or substrates. Examples of human- and animal-derived materials may include blood products, antibodies produced in animal cells, and growth factors and cytokines produced in human, mammalian or insect cell lines.
What are the risks?
FDA guidance warns:
“The use of human- and animal-derived materials at any point in the manufacturing process can affect the safety, potency, purity, and stability of the final product.” - Considerations for the Use of Human-and Animal-Derived Materials in the Manufacture of Cell and Gene Therapy and Tissue-Engineered Medical Products.
Introduction of adventitious agents
The use of human and animal derived materials during cell therapy product manufacturing introduces safety concerns over the increased risk of infectious disease transmission. Infectious agents such as viruses, parasites, bacteria, mycoplasma and transmissible spongiform encephalopathies (TSEs) may be inadvertently introduced into the product. In a research context, this can increase variability and lead to poor data quality, ultimately wasting time and resource. However, in the manufacture of cell and gene therapy products, such contamination can pose a serious risk to patient safety.
Material lot-to-lot consistency
Human and animal derived materials can contribute to product variability by affecting the reproducibility of the manufacturing process or the quality of the final product. For example, fetal calf serum varies significantly between batches and is highly variable depending on factors such as fetal age, geographic location, and time of collection following the mother’s slaughter [2]. This can lead to differences in cell growth rate, phenotype, or differentiation potential. Growth factors and cytokines produced in animal cells can also vary in composition and bioactivity from lot-to-lot due to changes in mammalian host cells. In cell therapy product manufacture, variability in cell growth, differentiation, and phenotype directly translates into variability in the final product administered to patients.
Material identity, potency and purity
In addition to the potential safety concerns caused by the possible introduction of adventitious agents, other impurities from human- or animal-derived products can cause safety or reproducibility issues. Recombinant human or animal proteins, such as growth factors and antibodies, may contain impurities or contaminants originating from the expression system. Particularly problematic is the risk of cross-contamination with similar endogenous growth factors and cytokines, which may activate unintended signaling pathways and cellular responses [3]. Uncontrolled levels of impurities and contaminants between lots introduce variability in cell and gene therapy product manufacturing. Read more in our blog – Unexpected consequences: growth factor cross-contamination in mammalian and E. coli expressed growth factors
Regulatory guidance on the use of human- and animal-derived materials in cell and gene therapy
FDA guidance includes recommendations for the development of cell and gene therapy (CGT) and tissue-engineered medical products (TEMPs) that are manufactured using human- and animal-derived materials. Key considerations include donor screening and testing, adventitious agent detection, risk assessment, and materials management.
The FDA recommends the use of materials that are free from human- or animal-derived proteins (e.g., tissue culture media without human or animal components, recombinant proteins) wherever possible. These alternatives may have fewer safety risks and offer greater consistency in their composition, thus avoiding donor-to-donor variability, and reducing the unpredictability of how such proteins affect cellular or tissue growth and properties.
Why use Qkine animal origin-free cell therapy grade growth factors and cytokines?
Qkine has launched a range of high-purity, animal origin-free growth factors and cytokines under the Cell Therapy Grade label, offering a high-quality, value-driven alternative to other suppliers’ GMP-grade recombinant proteins. As the term ‘GMP-grade’ can be ambiguous, Qkine has developed its Cell Therapy Grade range with clearly defined quality assurance criteria and comprehensive documentation.
Qkine Cell Therapy Grade proteins are manufactured in an ISO 9001:2015-certified facility, in accordance with ISO 20399:2022 standards, and with GMP-compliant processes, making them suitable for use in cell and gene therapy development.