Analytical tool designed to accelerate the production of biological products

Two Rutgers engineers who specialize in the process of making drugs derived from living organisms have created an analytical tool they believe will accelerate the discovery and production of biological drugs that are often at the forefront of biomedical research.

In an article on the cover of the American Chemical Society journal, Analytical Chemistry, the researchers provide details of what they call an “automated toolkit” – or, more formally, the N-GLYcanyzer – and its potential for rapidly monitoring drug quality during biologics production, which can range recombinant therapeutic protein vaccines. While most biologics are tested at the end of the manufacturing process for quality and consistency, the Rutgers Toolkit can monitor biologics as they are produced and enable drugs to meet needs. quality compliance from regulatory agencies, such as the U.S. Food and Drug Administration. (FDA).

“This tool allows us to monitor the quality of biologic drugs in near real-time during the biomanufacturing process,” said author Shishir Chundawat, associate professor in the Department of Chemical and Biochemical Engineering at Rutgers School of Engineering. “Continuous monitoring and control of biomanufacturing processes is essential to ensure drug quality. These advanced tools will help the industry save money by avoiding the production of drug batches or batches that deviate from regulatory requirements, ultimately leading to lower healthcare costs for the benefit of patients.

Unlike conventional pharmaceutical drugs made by chemical synthesis, biological drugs are made from cells, proteins or genetic material manipulated by biotechnological techniques or taken directly from humans, animals or microorganisms. Although biologics can offer breakthrough types of treatments, such as monoclonal antibodies to treat COVID-19, they are difficult to manufacture because they are extremely sensitive to changes in the production environment. Bioprocesses are also easily contaminated with microbes and can be spoiled by even slight variations in process conditions such as temperature.

The new tool is an Automated Process Analysis (PAT) technology that uses a software-controlled targeted biomolecule sensor system. It is home to a universal biochemical process active in most living cells called protein N-glycosylation, where proteins modify their surfaces by attaching complex sugar molecules called glycans. The PAT system can quickly track changes in these sugars and can detect when cellular processes go wrong, such as when sugar molecules are not properly attached or incorrect sugars are attached to proteins, which directly impacts the safety and efficacy of the biologic drug.

“Our system will make it possible to produce complex biologicals with molecular-scale precision,” said co-author Aron Gyorgypal, a PhD candidate in Rutgers’ Department of Chemical and Biochemical Engineering who led the study. “Basically, we are able to quickly check the quality of the drug, multiple times during the process, to know for sure that the biologic that is being produced is following the preferred reaction trajectory that meets regulatory and industry expectations for control. quality.

This work was funded by the FDA because of the importance of improving manufacturing processes for biologics and “biosimilars,” namely generic versions of trade-name biologics, Chundawat said. As a result, the details for recreating this PAT system have been made readily available online to facilitate wider adoption by various stakeholders, including the biopharmaceutical industry, as well as drug regulatory agencies.

The researchers tested the robustness of their PAT by tracking the manufacture of trastuzumab, a breast cancer biologic drug, through its 14-day production cycle. Based on the results, they hope that such technology will significantly increase the production of biosimilars.

Federal regulators have been hesitant to allow large-scale production of biosimilars due to quality and safety concerns, Chundawat said. “The FDA will have much more confidence in a drug product that has similar advanced analytical tools used to monitor its manufacturing process,” Chundawat said.

This summer, Gyorgypal received the Oak Ridge Institute for Science and Education (ORISE) fellowship to work at the FDA’s Center for Drug Evaluation and Research (CDER). The ORISE program focuses on a variety of initiatives, including educating the next generation of students/scientists supporting US federal agency missions to strengthen national science education and research initiatives. Gyorgypal will help the FDA evaluate and validate the N-GLYcanyzer analytical toolkit, an effort that could lead to wider adoption of similar PAT tools by the biopharmaceutical industry.

Reference: Gyorgypal A, Chundawat SPS. Integrated process analytical platform for automated monitoring of n-linked glycosylation of monoclonal antibodies. Anal. Chemistry. 2022;94(19):6986-6995. doi:10.1021/acs.analchem.1c05396

This article was republished from the following documents. Note: Material may have been edited for length and content. For more information, please contact the quoted source.