Alnylam Pharmaceuticals, Inc. – FDA EIR, Apr 25, 2018

An FDA inspection of Alnylam Pharmaceuticals in Cambridge, MA, was conducted from April 2 to April 25, 2018. This high-priority sponsor inspection, performed under Compliance Program 7348.810 for investigational drug patisiran-LNP (ALN-TTR02), revealed three significant observations documented on an FDA Form 483.

Firstly, Alnylam's electronic record systems, including those used by a primary endpoint vendor, did not meet regulatory requirements for validation, data retention, audit trails, or electronic signatures (21 CFR Part 11). Issues included the use of non-compliant Excel spreadsheets and an electronic data capture system where reasons for data changes were not recoverable.

Secondly, the company failed in its sponsor responsibilities (21 CFR 312.53) to ensure proper study conduct and investigator qualification. This was evidenced by persistent non-compliance at multiple clinical sites (81, 91, 61), including untrained personnel obtaining informed consent, incomplete adverse event documentation, and significant gaps in source data. Critical monitoring plans (for the CRO, primary endpoint vendor, and safety) were not finalized prior to initial subject screening, and the electronic data capture system was implemented late without a contingency plan. Additionally, the sponsor did not adequately address identified non-compliance issues by monitors.

Finally, Alnylam failed to submit a required statement to the FDA detailing the transfer of regulatory obligations to its contract research organization. Alnylam management acknowledged these findings and committed to submitting a written response to the FDA within 15 business days.