What To Learn From US FDA Warning Letters and Their Impact on Pharmacovigilance Operations

Pharmacovigilance Review
December 2016
Author: Mitchell Gandelman, Sciformix Corporation

Drug safety and pharmacovigilance (PV) are paramount to the development of new drugs and the continued use of approved medications. PV remains a complex series of activities that must be well planned and coordinated as well as operational in all countries where the drug is used. Continual monitoring initiated by companies with both internal and external audits becomes essential to ensure appropriate PV. In addition to company-directed audits, regulatory agencies also inspect PV activities to ensure compliance with regulations. In this review, US Food and Drug Administration (FDA) Warning Letters (WLs) to pharmaceutical companies regarding post-marketing PV are discussed in an attempt to understand and learn from the failures identified, and, thus, continually improve the quality of PV globally.

The inspections carried out by the FDA can result in the FDA issuing WLs to persons or organisations for violations of regulatory significance, and these WLs may lead to serious consequences. FDA WLs are characteristically informal and advisory; the ultimate aim of a WL is to establish voluntary compliance with the law and provide prior notice. WLs are issued for violations of regulatory significance and can lead to enforcement actions if not adequately corrected; however, a WL does not commit the FDA to take action. On the other hand, the FDA can take action without prior issuance of WLs. Corrective, preventive or promised actions by the company do not preclude the FDA from issuing a WL. Thus, receiving a WL is a cause for real concern to companies, as the identified violations can lead to significant enforcement actions by the government negatively affecting public relations and future regulatory interactions 1,2.


  1. Food and Drug Administration. Regulatory Procedures Manual. 4-1 – Warning Letters. Silver Spring, MD, USA: FDA. Available at: http://www.fda.gov/iceci/compliancemanuals/regulatoryproceduresmanual/ucm176870.htm
  2. Frestedt J. Warning Letters Reference Guide, 2016 Edition. Needham, MA, USA: Barnett International.

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