FDA uncovers ‘significant’ data integrity concerns at Indian CRO

The US Food and Drug Administration (FDA) has notified sponsors of new and generic drug applications that in vitro bioequivalence (BE) studies conducted by Raptim Research, an Indian contract research organization (CRO), may have been falsified and that studies conducted by the firm that are necessary to support approval must be repeated.

FDA notified ANDA sponsors that they must repeat the BE studies at an acceptable alternate study site and respond to the agency within 30 days to address the deficiency caused by the inclusion of BE studies conducted by Raptim.

This conclusion was drawn after multiple surveillance and for-cause inspections of ANDAs, which included Raptim data from its site in Navi Mumbai, India, between 2019 and 2023. As a result, a general correspondence letter was issued on August 6, 2024. The letter raised "significant concerns" about the company's studies, including the potential for data falsification.

The company’s response failed to adequately address the data integrity concerns, leading FDA to issue an untitled letter on 27 March.

FDA said in the untitled letter that the firm appeared to generate results from reusing samples from a single donor and then “recorded these results as if they came from different skin donors in a separate study.”

For example, “FDA identified multiple subject skin donor replicates with nearly identical results” between different studies. FDA’s general correspondence letter raised concerns that the study data appear falsified in that to produce results from in vitro permeation studies conducted at the facility.

It added that the firms “in vitro study conduct resulted in the submission of false information to FDA regarding the measurement of the bioavailability of a drug product or the demonstration that a drug product is bioequivalent to a reference listed drug.”

FDA said it is also changing the therapeutic equivalence rating in its Approved Drug Product with Therapeutic Equivalence Evaluations (Orange Book) for any approved ANDA that relied on bioequivalence data from Raptim to BX, which indicates that data reviewed by the agency are insufficient to determine therapeutic equivalence of the generic product to its brand-name product.

A drug with a BX rating can be prescribed but is not recommended as automatically substitutable at the pharmacy for the brand-name drug.

According to an August 2023 market report on India’s domestic CRO sector conducted by the country’s Department of Pharmaceuticals, Raptim has secured approval for BCS-based biowaiver studies for FDA-approved versions of cevimeline, amitriptyline, and doxepin; EU-approved studies for varenicline; and for buspirone in Canada.

FDA

FDA uncovers ‘significant’ data integrity concerns at Indian CRO

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