FDA Warns Sanofi For Failing To Report Side Effects
8 CommentsBy Ed Silverman // February 22nd, 2011 // 10:42 am
You read it here first. In a harsh warning letter, the FDA has reprimanded Sanofi-Aventis for failing to meet regulatory deadlines for reporting serious side effects with many of its drugs, including the Lovenox blood thinner, the Multaq heart drug and the Allegra D allergy pill, and also did not report post-marketing studies or completed, unpublished clinical trials in NDA annual reports. The seven-page missive, which was dated January 28, comes after the agency reviewed Sanofi paperwork last May. And a separate letter dated February 9 notes that a Sanofi plant in Germany has problems with contamination.
When it came to reporting adverse events, however, some reporting delays stretched back as far as 2007 - there was a delay of 896 days in reporting side effects associated with the Glyburide diabetes med. Other delays were not quite as lengthy - Sanofi waited only 30 days to report adverse events concerning its Amaryl diabetes drug. But even 30 days is too long. Here’s why…
Federal law requires that adverse drug reports that are both serious and unexpected must be filed with the FDA within 15 calendar days of initial receipt. Overall, the FDA counted 185 initial 15-day reports were submitted late between January 1, 2009 and March 31, 2010. There were also 127 follow-up, or post-marketing adverse event, reports that were submitted late during the same period.
The FDA then writes that Sanofi’s standard operating procedure for gathering reports “fails to provide written adverse drug experience definitions required to assess and evaluate adverse drug experiences” for submitting individual safety reports, including those required to be reported within 15 days. And the “Adverse Event Reporting Form” used by call center contractors for noting adverse reports do not correctly identify adverse outcomes required to determine the seriousness of an adverse event.
How could this happen? As Pfizer did last June when confronted with the same problem, Sanofi blamed computer problems, according to the FDA letter. The agency, however, continues to identify issues, such as a lack of training for the support, incomplete SOPs and work instructions, and inaccurate recordkeeping of older adverse events. And the system “does not display accurate clock dates on MedWatch forms for cases which were initially entered…” As they say, timing is everything.
To cope, Sanofi previously wrote the FDA that the Accenture consulting firm was retained to resolve the computer problems. But the FDA wants to see results. “To date, however, we have not received any response from you indicating that you or your contractor has evaluated or determines the root cause of these issues, or taken steps to resolve them or re-validate your computer system to correct deficiencies,” the agency writes (read the letter here).
Meanwhile, the agency was also incensed that Sanofi failed to include all other postmarketing studies in NDA annual reports for three drugs - Apidra, Eloxatin and Ketek - and did not include summaries of completed, unpublished clinical trials. The drugmaker had previously told the FDA that, in March 2008, it would start including foreign clinical trials in its database for NDA annual reports.
“Yet, information obtained during the inspection…indicates that your firm has still failed to report on the status of certain foreign postmarketing clinical trials or studies. Moreover, we are troubled that your firm did not disclose to FDA, until the 2010 inspection, that it did not report on foreign trial or studies prior to 2008,” the FDA letter states. The agency then writes that the “corrective and preventive action plan and the revised NDA annual reports…are still inadequate.”
The February 9 letter takes Sanofi to task for failing to maintain Good Manufacturing Practices at its facility in Frankfurt, where the drugmaker failed to identify the organisms recovered from a sterility test for the Apidra insulin treatment and “failed to keep written procedures designed to prevent microbiological contamination of drug products purporting to be sterile.” Last September, for instance, personnel “involved in the cleaning operations and aseptic connections during filling, were observed demonstrating incorrect aseptic techniques to prevent product contamination” (read the letter here).
In response to warning letter about adverse events, a Sanofi spokesman sends us this statement: “Patient safety is our highest priority at sanofi-aventis U.S. and we are committed to the ongoing comprehensive understanding and communication of the safety of our products. We work globally to collect, evaluate, and process all adverse events received and report them to the FDA and other regulatory authorities throughout the world within rigid timelines. We acknowledge the FDA’s observations and accept that we can and must strengthen procedures and systems for reporting. Sanofi-Aventis is already working to address these observations and will continue to work with the FDA to ensure compliance with all reporting requirements.”
industry insider
Don’t start believing that SA flaks will be burning the midnight oil. Just as an example, Abbott started receiving similar warning letters almost a full decade before Meridia was pulled from the market.
Reality
WOW….now there’s a shocker!!!! SA not following their own SOPs, policies, quidelines, compliance documentation? Where is the benefit in “out-sourcing” this and who is or should be held accountable within the company? As stuff rolls downhill……why does it never run up?
Reality
…….and what Board Member would actually use any “excuse”, specifically that it is the computer’s fault. Are you serious?
laura
This news make me disgusted and frustrated and discouraged and angry, but mostly it makes me sad.
You see, it was five years ago today that my mother passed away after reacting to Seprafilm, a class 3 medical device that is manufactured by Genzyme, the company that Sanofi Aventis is in the process of buying. And, she really didn’t just “pass away”. She lived the last month of her life in the most intense of intensive care, with concrete intestines, breathing through a ventilator and in total agony. If one were to describe the way that they don’t want to pass, her passing would be one that they would describe.
My mom had been an active, healthy woman. Her surgery had been routine, one that many women undergo frequently. She didn’t ask for Seprafilm, it was used after a second thought for a secondary condition that hadn’t been identified prior to the surgery.
I’m not even sure why Seprafilm is considered a Class 3 medical device, or a medical device at all, for that matter. It’s a membrane that is used to prevent adhesions. Unlike most medical devices, that are hardware, it dissolves into the body, in most cases, never to be seen again. In all too many cases, however, the patient reacts to the hyaluronic acid that it is made from and is left with severe, if not catastrophic consequences. And yet, for some reason, there are absolutely no hyaluronic acid allergy warnings on Seprafilm’s labeling. Other products made from the same source of hyaluronic acid have warnings on their labels, but, according to Genzyme and the FDA, Seprafilm is absolutely safe.
Nonetheless, Seprafilm has the classification that every company would pay to have their product receive, “CLASS 3 MEDICAL DEVICE” or, in other words, “TOTALLY IMMUNE FROM LIABILITY”. Class 3 medical devices have the unique privilege of facing no legal consequences. They do have to undergo clinical trials in order to be approved but, once they’re approved by the FDA, anything that happens after the approval, or in some cases in the clinical trial process if the FDA doesn’t catch it, is essentially free of legal consequence.
Genzyme never reported my mother’s death to the FDA, a report that would have raised a red flag concerning the safety of their very profitable product. I’m left to wonder, how many other deaths they didn’t report in order to fly under the FDA radar.
And I’m sitting here, five years to the day, after the death of my mother at the hands of Genzyme, reading that the company that is buying them is not reporting side effects to the FDA.
Five years ago, today, I was sure that the government did everything it could to protect us. I knew that if a product was approved by the FDA, it was safe. And, above all, I was certain that, regardless of how powerful medical device companies are, a person’s right to stand before a court of law and state their case would never be taken away from them.
But that was then, and this is now. Now I know that my mother died a horrible death and the company that killed her is accountable to no one. And I know that the company that is buying them will make no changes, they’re doing exactly what Genzyme did. And I know that it doesn’t matter to them whether or not they report adverse events because they don’t have to. But, mostly, I know that I miss my mom.
RockDoc
The buck stops in the office of Sanofi’s Chief Medical Officer.
Jenifer Pinto
Its really sad to note that an organization of such a huge regard is so non-compliant. Blaming late submissions on system failures is certainly NOT-DONE!!
Dianne
Laura, the suffering your mom was made to endure and the pain your family will always have breaks my heart. There is significant guilt to go around: the manufacturer, the FDA, the doctor, the main-stream media, our legal system. The guilty don’t bare any of the burden. Who gets hurt are the innocent victims and their loved ones.
laura
Thank you, Dianne. I know that you totally understand what my family has gone through. Until you experience what we’ve experienced, it is hard to understand or believe that medical device preemption, as in “no chance of holding a company accountable, we don’t care if you have a legitimate claim, it’s not going to happen, period, exclamation point, the end.”, is the law of the land in the United States. (In Michigan’s case, it’s even more unbelievable, both drugs and medical devices are preempted.) And because of that, companies can treat the reporting of adverse events and deaths with a wink and a nod.
Corporations are entities, not human beings. They base they’re decisions upon the bottom line, not their conscience. If the reporting of an adverse event or death will affect the bottom line, there is a good chance it won’t get reported. And so, for the FDA to base their regulatory actions upon the good will of drug and medical device corporations is beyond naive, it’s sheer stupidity.