FDA WARNING_LETTER - Reine Lifescience - November 03, 2017

The FDA inspected Reine Lifescience's drug manufacturing facility in Ankleshwar, Gujurat, India, from October 30 to November 3, 2017, identifying significant deviations from current good manufacturing practice (CGMP) for active pharmaceutical ingredients (API), rendering their API adulterated.

Key violations include: 1. **Failure to validate and verify analytical methods:** Lack of documentation, observed "PD Trial" folder with differing batch data, and inadequate response regarding updated procedures and impact assessment. 2. **Insufficient controls over computerized systems and data integrity:** Disabled audit trails, lack of controls to prevent data deletion/alteration, and administrator access for the quality assurance executive. The response was insufficient regarding interim controls and user privilege definitions. 3. **Failure to adequately validate equipment cleaning procedures:** Release and shipment of API manufactured on multi-product equipment before cleaning validation completion, and an inadequate cleaning validation report that did not evaluate worst-case conditions. The response lacked documentation, rationale, and comprehensive CAPA.

The FDA recommends engaging a qualified CGMP consultant and requires a comprehensive data integrity remediation plan, including an investigation into data inaccuracies, a risk assessment, and a management strategy with a global CAPA plan. The firm was placed on Import Alert 66-40 on March 30, 2018. Failure to correct deviations may result in withheld approvals for new applications and continued refusal of admission of articles into the