FDA to Withdraw Generic Drug After Company Repeatedly Fails to Resubmit Bioequivalence Data

Regulatory NewsRegulatory News | 25 October 2019 |  By 

After the US Food and Drug Administration (FDA) discovered an abbreviated new drug application (ANDA) relied on data from a disreputable contract researcher, and after repeated attempts over five years to get the company to resubmit new data, the agency on Friday proposed to withdraw the approval for Cipla subsidiary InvaGen Pharmaceuticals’ trandolapril tablets.

“The basis for the proposal is that the holder of the ANDA has repeatedly failed to submit the required data to support a finding of bioequivalence for this ANDA,” FDA said, noting the company can request a hearing.

FDA first approved the InvaGen trandolapril tablets in 2007, but the ANDA was supported by bioanalytical analysis conducted by Houston-based contract research organization Cetero Research. And that analysis was conducted during a five-year window when FDA inspections raised significant concerns about the validity of the site’s reported results. Due to what FDA found to be the “widespread falsification” of data by Cetero, the agency called on any sponsors using the site to redo certain studies.

In 2011, FDA sent a letter to InvaGen explaining that it needed to conduct new bioequivalence studies or re-assay the samples from the original bioequivalence study for this particular ANDA and submit them within six months. But InvaGen did not respond to the letter.

In August 2016, FDA sent another letter to InvaGen requesting that, within 30 calendar days, InvaGen either supplement the ANDA with the requested bioequivalence data or voluntarily seek withdrawal of the ANDA. InvaGen responded a month later and said it needed a nine-month extension to conduct the new studies and submit them.

But in April 2017, FDA sent another letter to InvaGen denying the nine-month extension because InvaGen had already had a significant amount of time to provide the requested data.

InvaGen again did not respond to FDA’s letter, and two months later in the June 2017 Cumulative Supplement to the 37th Edition of the Orange Book, the ANDA for InvaGen Pharmaceuticals’ trandolapril tablets was moved to the discontinued section of the Orange Book.

"In the absence of information showing bioequivalence between the generic drug at issue and the RLD [reference listed drug], there is no basis for concluding that the Agency’s finding of safety and efficacy supporting approval of the RLD can be used as a basis to support approval of the generic drug," FDA said.

Federal Register


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Tags: ANDA, Cetero, CRO, FDA, InvaGen

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