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Quality Control of Injectable Biologics

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Viral decontamination, that is to remove the virus. We have the viral remove filters. That’s an expensive type of filter. And after that, the biologics need to go through viral decontamination test. And there’s a section for the FDA rules as in Q5A that is specifically dedicated to the viral safety evaluation. And you can look up the references. Pyrogen contamination. Pyrogen is the product of the metabolism of gram-negative bacteria and it is a endotoxin. In the biotechnology laboratory, many recombinant proteins are produced by a gram-negative bacteria. And therefore this product have a tendency or a potential to be contaminated with endotoxins, the pyrogen. And pyrogen cause fever, muscle ache, and shock-like syndromes Pyrogen inactivation of destruction. Now for small molecules is easy.
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You can just knock them out all together with all this procedures. For the therapeuric proteins, we can use ultra filtration, ion exchange chromatography, distillation, active charcoal, or reverse osmosis. Pyrogen test, as in the regular IV injection, you can use the rabbit model. You can use the Limulus Amebocyte Lysate lysate or the LAL test. Or you can use the endotoxin removing gel which is unusual I mean unofficial. Endotoxin removing gel, it is say the jail contains and immobilize ligand. But upon binding with the endotoxin, the ligand would move or would become mobile by gravity chromatography. And the ligand is reusable after endotoxin is washed off. So that’s kind of nice. It is reusable.
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And the removing gel can be used for purification as well as detection. And it can be also used to remove endotoxin in the enzyme cell culture or aqueous buffer. I just want to say very quickly about biosimilar formulation. Argument against generic biologics. Because biological product are process driven, and are very sensitive to changes in formulation and manufacturing process. And that’s why the brand name manufacturer claimed that you can never make a product that is generic to their brand name product. So the best that you can call it as biosimilar. But the processes are changed as a new batch of product is produced because biologics have shorter half-life, so you have to replenish the product from time to time.
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So the original manufacturer is required to demonstrate equivalence of the new batch to the old batch. So in essence, they are making their own biosimilar products. So given time, it will come to terms with the legislation. That is the biosimilar product will be more and more on the market. And nonetheless, the biosimilar products still require comprehensive testing, making the saving a question or questionable.

Biologics exhibit higher molecular weight, complexity in structure, and function that can be affected by changes in the manufacturing process. Initial emphasis on biologics development should be directed to the quality requirements. A variety of excipients constitute the final production of injectable biologics, besides the subtle, process-driving manufacturing operation. Strict quality control is required to ensure quality, efficacy and safety of the biological products. Like the small molecule counterpart, quality control tests must be performed for finished injectable biologics, including Sterility test, Pyrogen test, Clarity test, Leaker test, and Content uniformity test.

Being derived from microbial sources, biologics are more prone to contamination with viruses, mycoplasmas or other microorganisms. Therefore, strict quality control is required to ensure contamination-free quality, efficacy, and safety of biological products. Pyrogen removal can be done by ultra-filtration, ion-exchange chromatography, distillation, active charcoal, or reverse osmosis, followed by pyrogen test. The USP recognizes two pyrogen tests, conducted with rabbits and the Limulus Amebocyte Lysate Viral decontamination is performed by a virus retentive filter under aseptic condition. Biosimilar manufacturing is also briefly reviewed

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Pharmacotherapy: Understanding Biotechnology Products

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