The FDA’s Office of Scientific Investigations has issued a warning letter to Paris-based AB Science, a pharmaceutical company that targets cancer and other diseases with high unmet medical need, for compromising the safety of study participants by failing to properly monitor its clinical trials and ensure investigators follow protocol requirements.
An FDA inspection found that AB Science’s monitoring practices were inadequate to detect that investigators failed to report five serious adverse events (SAEs) within the 24-hour timeframe specified in the study protocol; in two instances, the SAEs weren’t reported for at least three years and one wasn’t reported at all. In addition, investigators failed to perform protocol-required laboratory tests designed to identify potential side effects that could put study volunteers at risk.
Violations also included missing timeframes included in the Investigational New Drug (IND) application for writing and approving monitoring reports—in some instances, reports weren’t completed at all—and failing to submit numerous lab results required by the protocol to the data management team.
The FDA violations detailed in the warning letter involved pancreatic cancer and gastrointestinal stromal tumor (GIST) studies conducted by AB Science primarily between 2009 and 2013.
AB Science did not respond to requests from CenterWatch Weekly for comment. In a statement posted July 14 on its website, AB Science said the company already has replied to the FDA warning letter and also has implemented “appropriate corrective and preventative actions” in response to the deviations. In addition, the company said it’s upgrading its quality assurance system to ensure compliance with Good Clinical Practice (GCP) requirements.
“AB Science has been inspected more than a dozen times in the past by numerous health authorities and always responded satisfactorily,” the statement said.
FDA spokesperson Stephen King said he is unable to comment on whether the agency will take further regulatory action against AB Science since the compliance matter remains open.
“What we can say is that our focus is on whether the conditions we observe on inspection pose risks to patient health and safety, or to the safety, efficacy and quality of the drug products,” he said. “Our warning letters give notice to sponsors of the types of problems we observe on inspection in order to provide the sponsors the opportunity to take voluntary corrective actions.”
The warning letter was issued June 16 based on violations identified during an FDA inspection of AB Science—which has a U.S. office in Chatham, N.J.—last September. When the inspection ended, AB Science was told to address the deficiencies and establish procedures that would prevent similar violations in the future.
AB Science, which acknowledged that its monitoring activities were inadequate in a written statement to the FDA, submitted a corrective action plan to the agency in October that provided for new monitoring strategies and team training practices. While the FDA did not comment on the relevance of the action plan presented by AB Science, the warning letter said the company didn’t adequately address ways to measure effectiveness of the plan or ensure compliance with regulations going forward.
AB Science’s statement said the company has responded to the FDA on these two action items.
The FDA’s crackdown on AB Science’s insufficient monitoring practices comes during a renewed discussion in the clinical research community about the importance of restoring integrity and trust in the enterprise following the sentencing of ex-Iowa State scientist Dong-Pyou Han for falsifying HIV research data.
Bioethics expert Arthur Caplan, Ph.D., the founding director of the Division of Medical Ethics in NYU Langone Medical Center’s Department of Population Health, said the FDA’s warning to AB Science, while unrelated to the HIV research misconduct, sends a serious message to the industry about the need to take clinical trial monitoring and adverse events reporting seriously.
“Monitoring for adverse events is the strongest moral obligation a company doing research has. It is protecting subjects against harm,” he said. “If they can’t do it, won’t do it or are indifferent about it, they should not be doing research on human subjects.”
AB Science, which already has registered its lead drug masitinib in Europe and the U.S. to treat cancer in dogs, currently is running 11 phase III studies with the compound in humans for a number of oncology indications, as well as for inflammatory and central nervous system diseases.
This isn’t the first time that the FDA has voiced concerns about AB Science’s practices. Last year, the agency issued a warning letter to the company for marketing its Kinavet-CA1 canine drug, conditionally approved to treat mast cell tumors in dogs, for off-label uses, including atopic dermatitis in dogs and asthma in cats. The FDA also cited AB Science for omitting important warning information in marketing materials about how the drug could affect humans in case of consumption.
Email comments to Karyn Korieth at firstname.lastname@example.org.
This article was reprinted from Volume 19, Issue 29, of CWWeekly, a leading clinical research industry newsletter providing expanded analysis on breaking news, study leads, trial results and more. Subscribe »