FDA: Drug firms using 24/7 production need more viral safety data

The US FDA has urged protein therapeutics makers using continuous manufacturing to take steps to keep products virus free.

The regulator made the suggestion in a recent concept paper along with more general advice on how industry can use 24/7 production to manufacture protein drugs more efficiently.

Viral contamination is an issue for all biopharmaceuticals made in processes that use mammalian cell lines. The cells contain sequences that can produce potentially harmful virus-like particles that must be removed from the finished product.

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In batch mode drug manufacturing the methods for removing these virus-like particles are well established.

Safety studies

Viral safety processes for continuous-mode biopharmaceutical manufacturing processes are less well defined according to the FDA, which suggested industry review the limited number of studies available when developing removal strategies.

“Continuous manufacturing is still a novel concept for therapeutic proteins, and there are few published studies dedicated to ensuring that such therapeutics are not contaminated due to viruses.

“Studies such as these provide both internal and external stakeholders with insights into understanding potential viral safety concerns and potential methods used for manufacturing developmental studies.”

The agency also said it is making effort to support additional research on the viral safety of continuous processes.

“As the submission of regulatory applications with continuous manufacturing elements increases, FDA subject matter expertise and tangible publicly available examples is critical for successful implementation of continuous manufacturing paradigms and is supportive of the Emerging Technology Program and other evaluations.”

Solutions

The FDA also said that drug firms using continuous processes to make drugs will need to invest in new technologies or adapt existing systems and methods to ensure products are virus free.

“CDER researchers found three process steps to be key for promoting viral clearance during CM [continuous manufacturing] operations: capture chromatography, viral inactivation, and viral filtration.

“For these steps CM involves either a new technological change to the equipment or an adaptation from an inherently static step to a dynamic step with extended processing times.”