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Developing the right comparability and analytical assays is critical to successful interactions with regulatory agencies. That’s the advice of Christiane Niederlaender, PhD, vice president of technical and expert in chemistry, manufacturing, and controls (CMC), at clinical research organization Parexel.
Niederlaender, who gave a talk about regulatory considerations for advanced therapy (ATMP) manufacturing at the Bioprocessing Summit Europe in March, says it’s essential that companies get their analytics right for their product to be accepted.
“There’s overwhelming similarities between the EU and the United States in terms of ATMPs, but there are also nuances,” she says. “In terms of general take-home messages, with characterization, we now know more about what you need to do for different cells, but we also know the hazards of having inadequate analytical approaches.”
In one case, Niederlaender explains, a company went through several rounds of revisions by the FDA. Although on the surface this was about the clinical paperwork, it was obvious that the results of their potency assay were unclear.
“It’s a great case study of how, although it’s difficult to get the analytics right, if you don’t, it can prevent your product from succeeding,” she continues. Another challenge is ensuring continuity in your analytical approach. “Continuity is the backbone of comparability. If you’re making changes that cause your assays to become completely different, it’s hard to maintain that continuity of results and ensure your results remain comparable over time.”
Setting quality attributes early in development
To overcome this, Niederlaender suggests thoroughly understanding your product and setting quality attributes early in development. “If you set specifications that are relevant and understand the mechanism of action, you can reflect that in the potency assays,” she points out and recommends that process developers organize the collection of CMC data early in development and carefully profile their product.
“You should know the key attributes you need from your new medicine. They don’t change over time and, if you’re logical about it, you can identify the critical issues and gather process and batch data to build a continuous picture right from early development,” she notes.
Finally, Niederlaender recommends creating a roadmap of interactions with the regulator and, at each stage, getting a second pair of eyes to consider what analytics are needed.
“Sometimes, you can ask the right questions, but in the wrong way, and then you don’t get a meaningful answer—it’s far better to do a proper gap analysis and then you can go about things a different way,” she advises.
