How Can Cell Culture Conditions Affect Biologic Product Quality?
By Trisha Gladd, Editor, Life Science Connect
When it comes to the development of new biotherapeutics, particularly glycoproteins and other post-translationally modified proteins, it is important that such modifications do not alter the activity, pharmacokinetics, or stability of a protein nor provoke immunogenicity in the patient. By understanding what factors can change a protein, as well as the steps to detect and analyze those changes, the risk of doing so is reduced and the efficacy and safety of the drug is preserved.
On Wednesday, March 11th, Michiel E. Ultee, PhD, Ulteemit BioConsulting, will be presenting a webinar with Richard Easton, PhD, team leader at SGS Life Science Services, titled Implications of Cell Culture Conditions on Biologic Product Quality. The key learning objectives for the webinar are to “analyze factors that affect changes to drug products during bioreactor operations, review regulatory considerations, and understand glycan analysis methods.” Dr. Ultee says he and Dr. Easton will be drilling down in the area of glycosylation, the carbohydrate that is added on to many proteins as part of their complete development.
For his part, Ultee will discuss the different types of proteins, the complexity, the various types of cell lines that are used in biopharmaceuticals to produce each type of protein, as well as some depth on the subject of glycoproteins and glycosylation. “I plan to cover which type of cell you should use and then the particular clone you're going to use to produce the protein,” he explains. “I’ll then discuss the cell culture effects, specifically the choice of media that these cells grow in, the additional nutrients or feeds that are given to the cells, and the conditions of the bioreactor—how the bioreactor itself is run and under what conditions of pH, oxygenation, temperature and other parameters. All of these conditions can affect the secondary structures on the protein.” Dr. Easton will finish the webinar by covering analytical techniques for the determination of carbohydrate structures on proteins, specifically mass spectrometry and chromatographic techniques and how they are used to determine the structure and composition of the different carbohydrate structures.
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| Michiel E. Ultee, PhD, Ulteemit BioConsulting |
Why Does Industry Need to Understand The Implications Of Cell Culture Conditions?
Ultee says it’s important to cover this topic for a number of reasons. “First, there is an expectation from the FDA and the European regulatory authorities that the protein will be fully characterized, which means not just the amino acids but also the carbohydrates and other post-translational modifications,” he explains. “They require those types of analysis. If you'd have a slightly different composition every time you run the bioreactor, then you're going to have inconsistent processing and they're going to be concerned about that, because you may not produce a consistent drug.”
Moreover, a more complete understanding of protein structure and how to control it has become industry practice to produce more consistent, quality products. Biosimilars present an even greater challenge. “For anyone developing a biosimilar or biogenetic of a protein, these secondary structures on the protein must be very similar to what the innovator drug is.” For example, if you're developing a biosimilar to Humira, you'll have to match that carbohydrate profile fairly closely. In order to do that, he says there has to be control of the choice of cells, the way the cells are grown, and the analyses done along the way, in order to ensure consistent production.
“It’s important people understand that therapeutic proteins are inherently complex, much more so than small-molecule drugs. The pharmaceutical industry is shifting towards biologics, but there’re still a lot small molecule drugs, which are defined by a precise chemical structure,” notes Ultee. “Any given protein is really a collection of closely related family members, and you have to be able to characterize how that distribution is within the family.”
A live webcast of the webinar will take place on Wednesday, March 11th at 11 AM ET and will then be replayed on Wednesday, March 18th at 3 PM CET. Attendees can register for free at www.biopharminternational.com/efficacy