Following an inspection earlier this year that yielded a Form 483, Indian generics juggernaut Alembic Pharmaceuticals has received a harsher reprimand from the U.S. FDA, though not for the sorts of manufacturing infractions that typically land copycat medicine makers in the agency’s crosshairs.
The warning letter posted to the FDA’s website this week—which follows an early March inspection of the Alembic Research Centre Bioequivalence facility in the Indian city of Vadodara—comes down to a singular concern: The company failed to properly obtain informed consent for an in vivo bioequivalence study at the site, which revolves around an unnamed investigational drug.
Alembic did not immediately respond to Fierce Pharma’s request for comment on the write-up or respond to questions about the identity of the redacted product.
To score approval for their abbreviated new drug applications (ANDAs), generics makers typically must demonstrate that their proposed copy is bioequivalent to its reference product. In guidance issued (PDF) to generic drugmakers earlier this year, the FDA clarified that the focus of most bioequivalence studies falls on “the release of the drug substance from the drug product into the systemic circulation.”
The FDA alleges in its letter that Alembic “failed to seek informed consent” for its bioequivalence study “under circumstances that provided the prospective subject or representative with sufficient opportunity or information to consider whether to participate and that minimized the possibility of undue influence.”
The agency’s concern comes back to Alembic’s informed consent form (ICF), in which Alembic asserted, per the FDA, that “‘This study is a clinical research project, but no part of it is of an experimental nature.”
That phrasing “may lead individuals to mistaken conclusions about whether the study is a ‘clinical investigation’” as defined under FDA regulations, the agency added.
Alembic previously received the lesser reprimand of a Form 483 in the wake of the inspection by the FDA’s Bioresearch Monitoring Program in March. In a response submitted to the regulator later that month, Alembic explained its rationale behind the ICF, which it credited to the “firm’s understanding of, among other things, the nature and purpose of bioequivalence studies,” according to the FDA.
Still, the FDA suggested that the “inconsistencies” in Alembic’s form made it tricky for prospective study participants to make an informed decision.
Additionally, the FDA noted that certain corrective pledges by Alembic around the inclusion of a clinical investigation definition in its consent form procedure and the removal of the suspect language remain “inadequate” because the company hasn’t offered enough detail about how it will fulfill its duty as a clinical investigator to ensure compliance with the FDA’s informed consent regulations.
Upon receipt of the letter, dated July 10, a 15-day countdown kicked off, during which Alembic can address the concerns in the FDA write-up.
As a major manufacturer of generic drugs, which make up the bulk of U.S. prescriptions, Alembic is no stranger to FDA scrutiny. The company has initiated U.S. recalls in recent years tied to nitrosamine impurities in generic antidepressants and subpar impurity testing results for more than 80,000 bottles of a bacterial eye infection treatment.
The manufacturer was also hit with a Form 483 at an oncology injectables formulation facility in the Indian state of Gujarat some four years back.