Impact of U.S. FDA Warning Letters in Europe: Practical Considerations for Industry

Today’s global pharmaceutical supply chain is highly interconnected and action taken by one regulator may have a global impact. This blog explores why European manufacturers and marketing authorization holders should pay attention to U.S. Food and Drug Administration (FDA) Warning Letters sent to their key suppliers — including active substance manufacturers, finished product manufacturers, or quality control laboratories — as they may materially affect authorization holders in Europe. In light of a new approach announced by the UK Medicines and Healthcare Products Regulatory Agency, we consider the European authorities’ approach to FDA Warning Letters and the potential impact for industry.

The U.S. Food and Drug Administration (FDA) may issue Warning Letters to regulated manufacturers when it identifies significant violations of federal requirements. As FDA notes, “Warning Letters are issued to achieve voluntary compliance and to establish prior notice.”¹  The agency takes the position that Warning Letters are issued only for violations of regulatory significance that would lead to enforcement action if they are not remedied. Regulators worldwide watch FDA Warning Letters as sources of insight into compliance issues.

1. MHRA’s Evolving Approach to FDA Warning Letters

Until recently, the UK Medicines and Healthcare Products Regulatory Agency (MHRA) Inspection Action Group (IAG) and Defective Medicines Report Centre (DMRC) took a proactive stance on notifying UK companies affected by FDA Warning Letters. They would “regularly receive US FDA Warning Letters (including Official Action Indicated and import ban letters) and contact UK licence holders who may be implicated,” for instance, where a contract manufacturer or active pharmaceutical ingredient (API) supplier in receipt of an FDA Warning Letter was supplying products to a company in the UK.

In August 2025, however, the MHRA announced a revised approach: The agency will not routinely notify marketing authorization holders (MAHs) in the UK about FDA Warning Letters involving their third-party manufacturers. Instead, MHRA has highlighted the responsibility of all manufacturers, wholesale license holders, and API registrants to monitor FDA Warning Letters as part of their supplier qualification and oversight programs.

In practice, MHRA expects companies to have robust procedures, such as detailed technical/quality agreements with suppliers, to ensure they learn of regulatory action as a matter of course. The onus is now on industry to “review and risk assess US FDA Warning Letters” and determine whether any action is needed on their part, mirroring the approach generally taken in the EU (see below).

The change of approach by MHRA is seen as a move to free up MHRA’s resources rather than a signal that that the monitoring of foreign regulatory action is becoming less important. Notably, if a company’s own risk assessment of an FDA Warning Letter reveals a potential impact on UK product quality or patient safety, the company should notify the MHRA. In addition, the MHRA retains the discretion to intervene or escalate matters on its own motion through the IAG, which is responsible for recommending and implementing regulatory action for breaches aross all good practices and the DMRC, which provides an emergency assessment and communication system in regard to allegedly defective medicines.

2. EU Handling of FDA Warning Letters

In the EU, an FDA Warning Letter generally does not trigger an automatic notification from authorities to the affected EU manufacturing or marketing authorization holder. Instead, license holders are expected to monitor foreign regulatory activities relevant to their activities, including FDA enforcement actions and advisory actions such as Warning Letters relating to their contractors. EU authorization holders are required to proactively evaluate any impact using the principles of quality risk management and, depending on the outcome of the risk assessment, take appropriate action. The evaluation includes notifying the European Medicines Agency (EMA) or the national authorities in case the risk assessment reveals a potential impact on product quality or patient safety, and it includes assessing whether the situation may lead to abnormal disruption in supply due to a contractor compliance situation, in which case relevant notifications should be made to the competent authorities. Action may also include performing a for-cause audit or delisting the contractor from the approved contractor list.

European authorities may also intervene directly through coordinated action in case of serious good manufacturing practice (GMP) noncompliance (issues where regulatory action is considered necessary to remove a potential risk to public health). Such process may start with information originating from third-country authorities or international organizations, including FDA Warning Letters. For centrally authorized medicines, the EMA leads the oversight and coordinates any EU-wide response. For nationally authorized products, the relevant competent authorities lead the risk assessment and actions but work closely with the other member states’ authorities to ensure a unified approach. Immediate actions may include issuing rapid alerts throughout the EU, recalling affected batches from the market, or prohibiting further supply of products from the implicated site. If warranted, authorities can issue an official GMP noncompliance statement, effectively barring the site from supplying the EU.

A notable development is that beginning October 1, 2025, the EMA may accept inspection findings by the FDA for inspections conducted outside of the U.S. under the EU-U.S. mutual recognition agreement (MRA) on GMP. This may be done voluntarily and on a case-by-case basis. Practically, this means that marketing authorization applications or variation applications may be able to rely on FDA inspections, thereby postponing the EU inspection that would normally be required during the assessments (see Q&A on impact of EU-USA MRA on marketing authorization applications and relevant variations). Applicants are encouraged to proactively contact the relevant regulatory authorities to discuss the need and timing of any potential inspections. With respect to the FDA inspection findings, an EMA Q&A indicates that to rely on the mutual recognition, the outcome of the FDA inspection should not be classified as “Official Action Indicated.”

3. Practical Considerations

For global authorization holders, the interconnectivity of the global supply chain carries important implications. The MHRA’s shift in approach is an important reminder to pharmaceutical and biopharmaceutical companies that proactive compliance monitoring and strong internal protocols are critical to remain complaint.

Key takeaways:

• Monitor FDA and other regulators’ inspections of contractors. Companies should establish a routine process to identify FDA Warning Letters and other global regulatory actions that involve their contractors. Companies cannot rely on regulators to inform them; both the MHRA and EMA expect companies to keep apprised as part of supplier oversight.
• Ensure robust contracts and technical agreements. Include clauses in agreements with contractors that require prompt notification when the contractor is inspected and prompt notification of the outcome of such inspection as well as prompt notification of communications by agencies such as FDA regarding site classification or the receipt of a Warning Letter or untitled letter. FDA typically discloses Warning Letters publicly, but the timing for publication can be delayed.
• Maintain robust internal escalation protocols. Companies should have clear, documented procedures for action if a contractor is implicated in an FDA Warning Letter, GMP noncompliance report, or similar regulatory action. Typically, the quality assurance unit would promptly initiate a risk assessment of any potential impact on the company’s activities. Based on the outcome, the company can determine appropriate actions, ranging from enhanced testing of incoming materials to qualifying alternative suppliers.

FDA Warning Letters can have a global impact, with real implications for EU and UK authorization holders. Regulators on both sides of the Atlantic share information, and they increasingly expect companies to closely monitor regulatory developments that may affect their supply chains. Vigilance over global regulatory actions, robust supplier oversight, and well-prepared internal processes are essential to prevent a warning overseas from becoming a crisis at home.

The Sidley Global Life Sciences team continues to monitor these developments closely. We are available to assist companies in anticipating and managing the EU and UK regulatory implications of FDA Warning Letters and related compliance issues.

¹FDA Regulatory Procedures Manual at 4-1-1.