The Definition of a Biologic Product

What is a biologic? According to the US Food and Drug Administration the FDA defines a biologic as ‘any product that is derived from natural sources that is produced using biotechnology methods and other cutting-edge technologies’. Biologic products can be composed of proteins, sugars, nucleic acids, or combinations of these to produce drugs as vaccines, blood and blood derived product, allergenics, somatic cells, gene therapy, monoclonal antibodies, antibody drug conjugates, tissues, and recombinant therapeutic proteins to name a few.

Unlike chemically synthesized drugs that can be highly characterized for structure and purity, biologic drugs are typically complex mixtures that are difficult to fully characterize, owing to their production from natural sources where variability is more difficult to control than in synthetic reactions. Accordingly, a biologic product is characterized in part by the manufacturing process and starting materials, such as a proprietary cell line and a manufacturing process in the case of a mammalian or microbial derived biologic product. Additionally, routine analytical testing and characterization analysis is performed on biologic products to as great an extent as possible to create a fingerprint of product characteristics that can always be used to positively identify the product. Ultimately the combination of analytical testing, analytical characterization, starting materials and the manufacturing process all lend a hand in defining a biologic product.

Another hallmark of a biologic product is that highly complex manufacturing processes are typically used to express and purify the product. In biologic manufacturing there are usually three important headings for manufacturing which can be modified depending on the specific type of biologic: upstream production, product harvest and recovery, and downstream purification. For upstream production, this typically involves the production of the biologic product of interest to a high concentration. In culture-based processes, this would involve growing a live culture of cells or microorganisms to a high density and then promoting the cells to produce the biologic of interest. During product harvest and recovery, the focus of the process is on crude separation of the product from its complex upstream ‘soup’, which is highly dependent on how the product is expressed. Once product is crudely isolated from the culture, it then goes through highly selective purification processes using targeted column chromatography, filtration, charged membranes and tangential flow filtration to achieve a product that is of high purity and quality. The combination of these processes to produce biologics, which are typically run in one long sequence, can take weeks to complete in a GMP manufacturing environment.

Finally, most biologics are typically thermally labile, meaning they are sensitive to over exposure to higher temperatures, owing to the fact they are naturally derived from biological sources and retain an inherently natural structure that is usually an important factor in maintaining product efficacy. Due to this, biologic products are either stored in cold (2-80C), frozen (-10 to -200C), ultra-frozen (≤ -600C) or lyophilized (freeze-dried) format for long-term storage, with the final chosen storage condition almost always derived from empirical product stability data.

If you need help from a Bioprocess Consultant with the development and manufacturing of your biologic, please call us at Bio-Processing Alliance (BPAI) to arrange a meeting with our Biologics Consulting experts. Our wealth of experience in the expression, purification and GMP manufacturing of biologic products for human clinical and commercial use can help you advance your important program forward quickly and effectively.

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