RAPS is closely monitoring developments in the Coronavirus (COVID-19) outbreak. See our public safety page for the latest updates.

Regulatory Focus™ > News Articles > 2020 > 3 > FDA Closes Zolgensma Data Manipulation Case Without Any Regulatory Action

FDA Closes Zolgensma Data Manipulation Case Without Any Regulatory Action

Posted 31 March 2020 | By Zachary Brennan 

FDA Closes Zolgensma Data Manipulation Case Without Any Regulatory Action

The US Food and Drug Administration’s (FDA) Center for Biologics Evaluation and Research on Tuesday said it has completed its review of Novartis’s data manipulation linked to its spinal muscular atrophy gene therapy Zolgensma (onasemnogene abeparvovec-xioi) and will not take regulatory action.

Paul Richards, acting chief of CBER’s consumer affairs branch, told Focus: “FDA has completed its review of the inspection, the evidence collected, and the firm’s responses and corrective actions to the inspectional observations, and the agency has classified the inspection as Voluntary Action Indicated (VAI).  Classifying an inspection as VAI means that objectionable conditions were found and documented but the objectionable conditions observed during the inspection do not meet the threshold for regulatory action.”

Although FDA said the manipulated data did not impact the safety or efficacy of Zolgensma, which could remain on the market, Novartis knew of the manipulated data before it won approval and only informed FDA of the situation afterward.

CBER Director Peter Marks previously warned that the company could be subject to civil or criminal penalties.
But this case and FDA’s handling of the repercussions may set a precedent for other companies that might discover manipulated data, not inform FDA until after a product is approved, and expect to not be held responsible by FDA.

Richards added via email: “FDA takes data integrity very seriously, and expects data submitted in support of a marketing application to be reliable and accurate. Data integrity is a critical component of a company’s quality system and should be maintained throughout the product’s lifecycle. Safety and effectiveness of biological products, including gene therapies, cannot be assured when data have been altered, either unintentionally or intentionally.” 

He also said data integrity issues are “commonly the result of inadequate controls and procedures to assure complete, consistent and accurate data,” and less frequently, “data integrity issues are the result of deceptive practices.”

The manipulation first came to light for FDA last June (Zolgensma was approved 24 May 2019), and according to a memo from Wilson Bryan, director of FDA’s Office of Tissues and Advanced Therapies, Novartis was aware of the data manipulation as early as 14 March 2019. While Bryan said the therapy would have ultimately been approved, he noted that its approval would have been delayed beyond its goal date of 31 May 2019 had the agency been aware of the data manipulation sooner.

Regulatory Focus newsletters

All the biggest regulatory news and happenings.