Unlike foetal bovine serum (FBS), which is the most used cell culture supplement, human platelet lysate (hPL) products are described as research, clinical, or good manufacturing practices (GMP) grade. Raw materials (also known as ancillary materials), which are used to make therapeutic products are graded by manufacturers to highlight their compliance with regulatory specifications. These specifications ensure the material’s purity, traceability, and safety for the intended use. Regulatory authorities, such as the Food and Drug Administration (FDA) and European Medicines Agency (EMA), play a crucial role in defining and enforcing these grades to meet the exact requirements for each industry and application. Therefore, hPL production is a highly controlled and transparent process that advances cell culture applications in a human-relevant and ethical manner.
Research grade hPL
Research-grade materials are used for basic research, which is not intended for human use. Their regulatory requirements are less stringent compared to clinical or GMP-grade materials. Consequently, research-grade materials are cheaper to produce and can be produced in any research facility or institution.
Research-grade hPL serves as a xeno-free supplement to support in-vitro propagation and maintenance of various human cell types for cell culture. Safety and sterility are ensured in these products during the production process.1 These products often require the addition of an anti-coagulant (heparin) during cell culture to prevent jelling, which is caused by residual platelet debris.
Clinical Grade hPL
Clinical grade refers to materials that are suitable for direct therapeutic use in humans. These materials are approved as drugs by relevant regulatory bodies and are tested for their safety and efficacy for human use.
Clinical grade hPL supports the propagation and maintenance of various human cell types for regenerative medicine and cell therapy. While safety and sterility are assured during the production process, these products also undergo gamma-irradiation to reduce the risk of potential pathogen contamination. Clinical grade hPL is produced in facilities that implement quality management systems, where quality control is performed using validated protocols. These products are usually fibrinogen-depleted and do not require the addition of anti-coagulants for cell culture.
GMP grade hPL
Of the three grades, the GMP grade is the highest standard that guarantees the product’s purity, traceability, and safety for commercial distribution. Adherance to GMP guidelines ensures that the quality of the product is not affected during production and transport. Production facilities need to be upgraded to adhere to current GMP guidelines.
Effects of gamma-irradiation
Both clinical and GMP-grade products are gamma-irradiated to and ensure the highest level of safety in clinical applications. However, gamma-irradiation can also damage growth factors and reduce the cell-culture performance of hPL. Studies indicate that at a dose of 45 kGy, growth factors are significantly decreased.2 Therefore, lower doses (25–35 kGy) are used to ensure pathogen reduction without affecting growth factors.3
Comparing hPL grades to FBS
FBS is not graded according to routine practice, which is otherwise used to describe raw materials used in biomedical research. Its suppliers often indicate its geographical origin. Geographical origin, which affects the diet of the dame, contributes to the variability observed in FBS composition, affecting the reproducibility of cell culture experiments. As FBS is a byproduct of the beef and dairy industry, there is no legal requirement to ensure transparency regarding the process of harvesting and reporting of volumes. In 1994, 30,000 litres of New Zealand FBS were sold globally, but only 15,000 litres of high-quality FBS were reported to be collected. 4 The full scale of such discrepancies remain unknown.
In 2013, a severe case of fraudulent blending with adult bovine serum albumin, received a lot of attention and highlighted the lack of transparency involved in the production of FBS. Although the International serum industry association (ISIA) has developed a traceability scheme that provide a degree of quality assurance for FBS products, the system only allows the user to challenge its origin but does not provide any further information. Even though some FBS products are gamma-irradiated, its non-human origin possess too high a risk for clinical and therapeutic applications. This has prevented the advancement of regenerative medicine and biotherapeutics as well as reduced the translatability of cell culture research to the clinical.
References:
- Bieback, K., Fernández‐Muñoz, B., Pati, S., & Schäfer, R. (2019). Gaps in the knowledge of human platelet lysate as a cell culture supplement for cell therapy: a joint publication from the AABB and the International Society for Cell & Gene Therapy. Cytotherapy, 21(9), 911–924. https://doi.org/10.1016/j.jcyt.2019.06.006 ↩︎
- Razani, E., Aghayan, H. R., Alavi-Moghadam, S., Yari, F., Gharehbaghian, A., & Sharifi, Z. (2022). A comparative study of pathogen inactivation technologies in human platelet lysate and its optimal efficiency in human placenta-derived stem cells culture. Journal of Virological Methods, 302, 114478. https://doi.org/10.1016/j.jviromet.2022.114478 ↩︎
- Huang, C., Liang, F., Lin, Y. C., Chen, Y., Tseng, R., & Huang, M. (2019). Gamma irradiation of human platelet lysate: validation of efficacy for pathogen reduction and assessment of impacts on hpl performance. Cytotherapy, 21(5), S82–S83. https://doi.org/10.1016/j.jcyt.2019.03.498 ↩︎
- Gstraunthaler, G., Lindl, T., & Van Der Valk, J. (2014). A severe case of fraudulent blending of fetal bovine serum strengthens the case for serum-free cell and tissue culture applications. Alternatives to Laboratory Animals, 42(3), 207–209. https://doi.org/10.1177/026119291404200308 ↩︎
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