![]() Lastly, carbon content is variable (but mostly negligible) from resin to resin compared to proteins.įor removing resin residues, the most commonly used solutions are sodium hydroxide (NaOH) and sodium chloride (NaCl), or even hot water for injection (WFI). The chemical compatibility allows resins to be stored in caustic solutions, which can be beneficial due to their antimicrobial properties. Also, proteins in general degrade in the presence of caustic solutions while most resins have good chemical compatibility. As a general rule, the longer and more complex a molecule is, the harder it is to clean. For example, the resin size may be more than 3000 times larger than a protein. Residues from a chromatography resin are different from a protein in multiple ways. Most cleaning validation approaches are centered around removing either protein or process impurities from surfaces, and not on the resin residue itself. All these items must also be free from resin residues prior to use on the next product batch. Other equipment that may have indirect contact with the resin are the slurry and packing tanks, and smaller parts such as hoses and valves. After cleaning, the resins may be placed in another vessel for short or long-term storage. While the resin packing is typically dedicated to one product, the chromatography column system may be employed for multiple products. Cleaning of the resin residue itself specifically from process equipment surfaces has not been widely addressed. Regeneration of resin as described above has been well documented. Many times, the regenerating solution is used to store the cleaned resin for a prolonged time when not in use either in the column or in a separate storage vessel (7). Other publications show that resins are effectively cleaned and sanitized with acidic solutions such as benzyl alcohol (8). Caustic solutions have also been effective at inactivating most viruses, bacteria, yeasts, fungi, and endotoxins and can be easily detected, removed, and disposed of. ![]() Caustic solutions at concentrations between 0.1–2 M were reported to be effective at regenerating most types of resins (6–7). Once impurities bind irreversibly, accumulating over time and consequently deteriorating the chromatography process performance, the resin needs to be regenerated to restore process performance and to minimize the risk of carryover (5). Regeneration may be done after every loading cycle or after a few loading cycles. The process consists of removing residual proteins and impurities from the resin while inside the column. Regenerating or “cleaning” the resin is necessary for this purpose. For that reason, biopharmaceutical manufacturers reuse chromatography resins multiple times to make them affordable for inclusion in downstream processes (3–4). The decision to reuse or dispose of resins is primarily driven by a cost analysis (1–2). ![]() They can be either disposed of or cleaned to an acceptable level to render them suitable for use in subsequent cycles. Regenerating resinsĬhromatography resins are typically dedicated to a single product. These particles can be physically or chemically modified to provide specificity to grab or repel molecules within mixtures. The stationary phase in liquid chromatography uses fine, solid beads referred to as resins that are packed and held in a column by meshes. Liquid chromatography is used for separating materials in biopharmaceutical production, primarily for purifying proteins by separating product and impurities. ![]()
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