Hundreds of FDA-approved drugs on the market may have been approved based on fraudulent trials. This is according to a notice from the U.S. Food and Drug Administration (FDA) to drug manufacturers in June 2024 saying that Synapse Labs, a contract research organization (CRO) in India hired by many of the U.S. pharmaceutical companies, had falsified data.1 The announcement explained that studies conducted by Synapse Labs will need to be redone to confirm the safety and efficacy of the medications impacted.
The FDA did not identify the potentially problematic medications or pull them from the shelves. MedShadow founder Suzanne Robotti says, “If the data used to approve these generics might be tainted, then the FDA should require the drugs to be withdrawn until their safety and efficacy can be confirmed.” Robotti has been a member of the FDA Drug Safety and Risk Management Committee for the past seven years.
In response to an email from Robotti, Mary Kremzner, PharmD, MPH, Director of the Division of Drug Information at the FDA wrote on October 7, 2024, “Although we are unable to disclose which specific drug applications are affected, FDA is aware of 39 application (35 ANDAs and 4 NDAs) impacted by the data integrity violations at Synapse. This number includes pending applications, tentatively approved, and approved applications.”
ANDA stands for Abbreviated New Drug Application. These are the applications companies send to the FDA to get a generic drug on the market in the U.S. NDA stands for New Drug Application, the type of application a company sends the agency in hopes of getting a new brand name drug approved for the market.
While the FDA has kept the full list of impacted drugs under wraps, a Bloomberg Investigation found that some commonly used generic medications — including atorvastatin (the generic form of Lipitor) and sildenafil (the generic form of Viagra) — were among those involved in the fraudulent trials.2
Here’s what happened and what you need to know.
What is a Contract Research Organization?
A contract research organization (CRO) is a company hired by pharmaceutical manufacturers to conduct studies on drugs.3 Some CROs specialize in running and managing clinical trials. These studies are performed with human patients to assess the long-term safety and efficacy of new, brand-name drugs before they can be approved. Clinical trials are required by the FDA to demonstrate that the benefits of a new drug outweigh its risks.
Others focus on bioequivalence studies. For these, the company is tasked with showing that a newly developed generic drug is chemically equivalent to a drug that has already been deemed safe and effective by the FDA. Bioequivalence studies are all that’s required because clinical trials are not necessary for generic drug approval.
Synapse Labs provides both types of services, suggesting they conduct studies for both brand name and generic drugs, but as of right now, only the generic drugs are under investigation.
How was the Fraud Detected?
The Synapse fraud was first identified in Europe. Spanish regulators brought the issue to the attention of the European Medicines Agency (EMA)—Europe’s equivalent to the U.S. FDA—about a year ago, in July 2023, at which point the EMA initiated an investigation.
Six months later, the EMA recommended that nearly 400 drugs be suspended until the studies demonstrating their safety and efficacy could be redone.
Following the EMA’s recommendation, the FDA began its own investigation. In several letters to Synapse sent between February and June of 2024, the FDA reported uncovering a number of troubling signs of fraud: study participants with nearly identical data, abnormal distribution trends, and data that appeared to have been replaced and reanalyzed. These observations and other anomalies suggested that data had been falsified.4
“Fraudulent data in medical research is a big problem and leads us down the wrong path,” says Arch Mainous III, PhD, a professor of Health Services Research, Management and Policy at the University of Florida. “It could have serious implications for patients whose physicians are making ‘evidence-based decisions’ based on fraudulent evidence.”
Are Medications Tested by Synapse Labs Safe?
Patients can report suspected side effects of drugs after they’ve been approved to the FDA’s Adverse Event Reporting System (FAERS).5 The agency monitors this database for clusters of any unexpected side effects. If such a cluster occurs, this triggers an investigation to see if the reported symptoms are likely to have been caused by the medication, and if any action needs to be taken. In some cases, the drug’s label may need to be updated; in more extreme situations, the drug could be pulled from the market. For example, in 2021, the FDA identified several reports of excessive menstrual bleeding from patients taking blood thinners such as Eliquis (apixaban) and updated the label to reflect the risk of this possible side effect.6
An FDA spokesperson told Med Shadow in an email, “FDA continues to investigate postmarketing safety reports for marketing applications of drugs that relied on bioavailability/bioequivalence studies conducted by Synapse for approval. To date, FDA has not identified reports that raise signals of new serious safety risks with these products.”
What Will Happen to Drugs Tested by Synapse Labs?
The FDA has asked manufacturers to submit their plans to the FDA by July 18, 2024 (30 days from the notice) to either withdraw the drug or redo the studies.7 For now, the agency says that it can’t divulge which companies used Synapse to test their drugs—which CROs a company works with is confidential. The drugs affected will remain available while the companies conduct the new studies.
“There are legal restrictions on what the FDA can disclose regarding a particular drug applicant’s confidential information, such as whether that applicant uses a particular contract research organization for certain studies it submits,” The FDA spokesperson wrote.
What Can I Do to Ensure My Medications are Safe?
There are some steps you can take to see if any medications you take were impacted. For generic drugs, the FDA has updated the therapeutic equivalent (TE) status in an online database called the Orange Book. Any impacted drugs will now be categorized as “BX,” which means that there is insufficient data to consider the medication equivalent to the existing brand-name drug. A “BX” label does not stop the manufacturer or pharmacies from selling the drug, but it does stop pharmacies from automatically offering it as an alternative to a brand name.
You can search the Orange Book database for any generic medications you’re taking to confirm their bioequivalence status.8 To do this, you’ll need your pill bottle so you can check not just the ingredient but the name of the applicant holder or manufacturer. Many different manufacturers make their own generic version of a brand name drug, and only some used Synapse to do their bioequivalence testing. For example, if you search atorvastatin, in the Orange Book, you’ll find nearly 187 results, eight of which have the BX label.
“Patients should not make changes to their treatment except in consultation with their health care professional. If a patient is taking any products with a therapeutic equivalence rating of “BX” and has concerns, they should contact the prescribing health care provider to discuss whether or not a different drug would be more appropriate.,” the FDA spokesperson wrote. Keep in mind a “BX” label does not necessarily mean that Synapse tested the drug. The status could have been changed for a variety of reasons.
So far, the investigation is focused on generic drugs, and there does not seem to be any way to tell if a brand-name drug was tested by Synapse.
