[03/28/2025] FDA has identified significant data integrity and study conduct concerns with bioequivalence studies conducted by Raptim Research Pvt. Ltd., a contract research organization (CRO) based in Navi Mumbai, India.
Information for sponsors
The agency has notified sponsors of new drug applications (NDAs) and abbreviated new drug applications (ANDAs) that in vitro studies conducted by Raptim are not acceptable, and when those studies are essential for approval, they must be repeated at study sites that do not have data integrity concerns.
Applications with in vivo studies conducted by Raptim will be handled on a case-by-case basis during the course of a standard submission review. Study concerns can be addressed by the applicants with appropriate steps, which may include providing additional information to justify how the data from the studies can still be relied upon, re-analyzing the study samples and re-conducting statistical analysis to demonstrate bioequivalence, or conducting a new study. Sponsors may contact the relevant FDA review division in the Office of Generic Drugs or the Office of New Drugs for further information or clarification.
Information for patients
FDA reviews postmarket safety reports for approved drugs and is continuing to investigate reports for drugs that relied on studies conducted by Raptim for approval. The agency has not identified any information to indicate that drugs approved based on studies conducted by Raptim are not safe or effective.
FDA remains vigilant and will take action to protect patients as appropriate. Patients should talk to their doctor about the medicines they take before discontinuing use, because sometimes stopping a drug can be dangerous.
Information for health care professionals
FDA is changing the therapeutic equivalence rating to “BX” for certain approved and marketed generic drugs that relied on bioequivalence data from Raptim until repeat studies are submitted and determined to be adequate.
A “BX” rating indicates data reviewed by the agency are insufficient to determine therapeutic equivalence (substitutability) of the generic product to its brand-name product. A drug with a “BX” rating is still approved and can be prescribed but is not recommended as automatically substitutable at the pharmacy (or by a pharmacist) for the brand-name drug.
FDA actions
FDA is committed to protecting the health of the American public by holding approved products to high standards of quality, safety, and efficacy.
FDA conducted multiple surveillance and for-cause inspections related to ANDAs containing data from Raptim between 2019 and 2023. FDA issued a general correspondence letter on August 6, 2024, informing Raptim of FDA’s significant concerns regarding studies conducted at its site, including concerns of potential data falsification. Raptim responded on October 17, 2024, but did not adequately address FDA’s data integrity concerns. The agency conducted a thorough analysis of information provided in Raptim’s response and participated in a meeting with Raptim in February 2025. FDA concluded that Raptim created and caused the submission of falsified in vitro data to FDA. FDA issued an untitled letter on March 27, 2025, informing Raptim that certain studies conducted at its site are not acceptable because of data integrity and study conduct concerns.
Additional information
Questions and Answers Regarding Data Integrity Violations at Raptim
FDA is asking companies with approved abbreviated new drug applications (ANDAs) and New Drug Applications (NDAs) that relied upon in vitro studies conducted at Raptim to respond within 30 days with their plans to either:
- re-conduct these studies at study sites that do not have data integrity concerns in order to submit a supplement within the next year, or
- voluntarily request withdrawal of approval of the affected ANDA or NDA.
FDA has restrictions on what it can legally disclose because it is confidential information whether a particular drug applicant uses a particular contract research organization for studies it submits. However, if you are concerned about whether a generic drug you are taking has a “BX” rating, you can:
- Go to the Orange Book and type in the name of your drug.
- In the list that comes up, look for the name of the manufacturer that appears on the bottle. Then look for the row with that drug and manufacturer and find the code in the column “TE Code.”
- If the code is “BX,” you may wish to consult with your health care provider about continued use of the drug. The code BX is assigned to specific drug products for which the data that have been reviewed by the agency are insufficient to determine therapeutic equivalence, as outlined by the Orange Book Preface. Many drugs have a “BX” rating for reasons unrelated to this action, but the drugs affected by this action have, as noted, had their ratings changed to “BX.”
FDA has notified Raptim that it is the company’s responsibility to develop, implement, and execute corrective and preventive actions that are sufficient to ensure violations do not occur in future studies. For FDA to rely upon data generated by Raptim in future applications, the company will need to address these system-wide failures and ensure the company maintains compliance with FDA regulations.
FDA has reviewed all drugs affected by this action and is working with the other manufacturers of these drugs to help ensure adequate supply is available. Supply of these drugs is currently meeting demand and projected demand; FDA will continue to monitor supply.
