INVESTIGATING GENERICS: Hundreds Of Drugs Remain On The Market After Fraudulent Trials

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<p>Hundreds of FDA-approved drugs on the market may have been approved based on fraudulent data. This is according to a <a href="https://www.fda.gov/drugs/drug-safety-and-availability/notification-pharmaceutical-companies-clinical-and-bioanalytical-studies-conducted-synapse-labs-pvt">notice</a> from the U.S. Food and Drug Administration (FDA) to drug manufacturers in June 2024. The announcement explained that studies conducted by<a href="http://www.synapselabs.com/"> Synapse Labs</a> Pvt. Ltd, a contract research organization (CRO) in India hired by many U.S. pharmaceutical companies, will need to be redone to confirm the safety and efficacy of the affected medications.</p>
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<p>The FDA did not identify the potentially problematic medications or pull them from the shelves. MedShadow’s president and founder <a href="https://medshadow.org/suzanne-b-robotti/">Suzanne Robotti</a> says, “If the data used to approve these generics might be tainted, then the FDA should require the drugs to be withdrawn until their safety and efficacy can be confirmed.”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 was a member of the FDA Drug Safety and Risk Management Committee from 2017-2024. </p>
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<p>While the FDA has kept the full list of impacted drugs under wraps, a <a href="https://www.bloomberg.com/news/articles/2024-07-09/generic-viagra-cialis-lipitor-safety-in-question-after-fda-finds-false-data">Bloomberg investigation</a> 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. </p>
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<p>Here’s what happened, and what you need to know.</p>
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<h2 class="wp-block-heading">What is a Contract Research Organization?</h2>
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<p>A <a href="https://www.cancer.gov/publications/dictionaries/cancer-terms/def/contract-research-organization">contract research organization</a> (CRO) is a company hired by pharmaceutical manufacturers to conduct studies on drugs. Some CROs specialize in running and managing clinical trials. These studies are <a href="https://grants.nih.gov/policy-and-compliance/policy-topics/clinical-trials/definition#:~:text=Clinical%20Trial%20Stewardship.-,NIH%20Definition%20of%20a%20Clinical%20Trial,related%20biomedical%20or%20behavioral%20outcomes">performed</a> with human participants to assess the long-term safety and efficacy of new, brand-name drugs before they can be approved. <a href="https://www.fda.gov/drugs/development-approval-process-drugs#:~:text=Developed%20and%20Approved.-,FDA%20Approval:%20What%20it%20means,result%20of%20chance%20or%20bias">Clinical trials</a> are required by the FDA to demonstrate that the benefits of a new drug outweigh its risks. </p>
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<p>Others focus on <a href="https://www.merckmanuals.com/home/drugs/brand-name-and-generic-medications/bioequivalence-and-interchangeability-of-generic-medications">bioequivalence studies</a>. 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.</p>
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<p>According to the company’s website, Synapse Labs Pvt. Ltd 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.</p>
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<h2 class="wp-block-heading">How was the Fraud Detected? </h2>
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<p>The Synapse fraud was first identified in Europe. The Spanish regulator <a href="https://www.ema.europa.eu/en/documents/referral/synapse-article-31-referral-assessment-report_en.pdf">brought the issue</a> to the attention of the European Medicines Agency (EMA)—Europe’s equivalent to the U.S. FDA—in June 2023, at which point the EMA initiated an investigation.</p>
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<p>Six months later, the <a href="https://www.ema.europa.eu/en/documents/referral/synapse-article-31-referral-synapse-labs-pvt-ltd-ema-recommends-suspension-medicines-over-flawed-studies_en.pdf">EMA recommended</a> that nearly 400 drugs be suspended until the studies demonstrating their safety and efficacy could be redone.</p>
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<p>Following the EMA’s recommendation, the FDA began its own investigation. In several <a href="https://www.fda.gov/media/179326/download?attachment">letters to Synapse</a> 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.<sup>4 </sup></p>
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<p>“Fraudulent data in medical research is a big problem and leads us down the wrong path,” says <a href="https://chfm.ufl.edu/profile/mainous-arch/">Arch Mainous III</a>, PhD, a professor and vice chair for research in the department of Community Health and Family Medicine at the University of Florida. “It could have serious implications for patients whose physicians are making ‘evidence-based decisions’ based on fraudulent evidence.”</p>
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<h2 class="wp-block-heading">Are Medications Tested by Synapse Labs Safe?</h2>
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<p>Patients can report suspected side effects of drugs after they’ve been approved to the <a href="https://www.fda.gov/drugs/surveillance/questions-and-answers-fdas-adverse-event-reporting-system-faers">FDA’s Adverse Event Reporting System (FAERS)</a>. 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 <a href="https://www.fda.gov/drugs/questions-and-answers-fdas-adverse-event-reporting-system-faers/january-march-2021-potential-signals-serious-risksnew-safety-information-identified-fda-adverse">identified several reports</a> of excessive menstrual bleeding from patients taking blood thinners such as Eliquis (apixaban) and <a href="https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/202155Orig1s039,s040lbl.pdf">updated</a> the <a href="https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=202155">label</a> to reflect the risk of this possible side effect.</p>
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<p>So far, the FDA says it has not found any indications on the FAERS database that drugs currently on the market that were tested by Synapse are dangerous. </p>
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<h2 class="wp-block-heading">What Will Happen to Drugs Tested by Synapse Labs?</h2>
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<p>The FDA has asked manufacturers to <a href="https://www.fda.gov/drugs/drug-safety-and-availability/notification-pharmaceutical-companies-clinical-and-bioanalytical-studies-conducted-synapse-labs-pvt">submit their plans</a> to the FDA by July 18, 2024 (30 days from the notice) to either withdraw the drug or redo the studies. 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.</p>
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<h2 class="wp-block-heading">What Can I Do to Ensure My Medications are Safe?</h2>
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<p>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. </p>
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<p>You can <a href="https://www.accessdata.fda.gov/scripts/cder/ob/index.cfm?resetfields=1">search the Orange Book</a> database for any generic medications you’re taking to confirm their bioequivalence status. 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 may make their own generic version of a brand-name drug, and only some use Synapse to do their bioequivalence testing. For example, if you search atorvastatin calcium, in the Orange Book, you’ll find nearly 92 results, four of which have the BX label.</p>
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<p>If a medication you take has a BX status, talk to your healthcare provider or pharmacist about whether another option might be better for you. Keep in mind a “BX” label does not necessarily mean that the drug was tested by Synapse. The status could have been changed for a variety of reasons.</p>
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<p>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.</p>
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