FDA Inspection Response and the “15-Minute Rule” (Revised Edition)

Latest Trends in FDA Inspections

In recent years, FDA inspections have been significantly intensified. In fiscal year 2025, 694 more inspections were conducted compared to the previous fiscal year. This demonstrates that the FDA has markedly strengthened its inspection and enforcement activities. Inspections are now being conducted more frequently, with greater scrutiny, larger inspection teams, and longer inspection durations.

In June 2025, the FDA launched an internal AI system called “Elsa.” This system analyzes FDA internal data including adverse event reports, anomalies in compliance data, Form 483 observations, and historical inspection outcomes to determine inspection priorities for high-risk facilities. Facilities with unresolved inconsistencies or corrective and preventive actions (CAPAs) may be flagged earlier and more frequently, resulting in more focused enforcement.

Risk-Based Inspection Approach

Since 2004, the FDA has adopted a risk-based inspection approach. Through this approach, inspection frequency has decreased for companies exporting products to the United States that do not pose high risks. However, companies that import raw materials from high-risk regions such as China and India, or those manufacturing high-risk products such as sterile drugs or narrow therapeutic index drugs, face an increased likelihood of inspection.

The Food Safety Modernization Act (FSMA) mandates that high-risk facilities must be inspected at least once every three years, and non-high-risk facilities at least once every five years. Additionally, the Food and Drug Omnibus Reform Act of 2022 (FDORA) requires annual inspections of infant formula manufacturing facilities.

Selection of Products for Inspection

Products subject to FDA inspection are not limited to those exported to the United States. This is because the FDA is interested in the “attitude” and overall quality management system of the company. Since it is assumed that companies will have adequately prepared for inspection of U.S. export products after receiving inspection notification, inspectors may also examine other products to evaluate the company’s true quality management capabilities.

Inspection Notice Period and Duration

For domestic U.S. companies, inspections are generally conducted without prior notice. In the worst case, notification may come as little as one day in advance. Inspections may continue for several weeks with thorough investigation.

On the other hand, for companies outside the United States, inspection notification has traditionally been provided several months in advance, with the inspection period typically lasting 4-5 days. However, on May 6, 2025, the FDA announced an expansion of unannounced inspections at foreign manufacturing facilities. This new inspection strategy aims to ensure that foreign manufacturers receive the same level of oversight and regulatory scrutiny as domestic companies. It seeks to eliminate the “double standard” between foreign and domestic facilities and expose non-compliance that might otherwise be concealed during pre-announced inspections.

Consequences of Refusing Inspection

Companies exporting pharmaceuticals or medical devices to the United States cannot refuse FDA inspections. Refusing an FDA inspection or failing an inspection may result in import detention by U.S. Customs authorities.

The Food and Drug Administration Safety and Innovation Act (FDASIA) of 2012 added Section 501(j) to the Federal Food, Drug, and Cosmetic Act (FD&C Act). This provision deems drugs adulterated if they have been “manufactured, processed, packed, or held in any factory, warehouse, or establishment and the owner, operator, or agent of such factory, warehouse, or establishment delays, denies, or limits an inspection, or refuses to permit entry or inspection.” Subsequently, the FDA Reauthorization Act of 2017 (FDARA) expanded this provision to include medical devices.

Basic Principles of Inspection Response

The most important aspect of FDA inspection is honesty and transparency. Documents that were not created at the appropriate time should not be created after the fact. Companies must respond as they are, honestly. Creating documents after inspection or falsifying records constitutes a serious regulatory violation and may lead to more severe penalties.

Practical Implementation of the “15-Minute Rule”

What is the 15-Minute Rule?

During inspections, requested documents and records must be presented to inspectors promptly. The so-called “15-minute rule” refers to an industry best practice stating that “appropriate materials must be presented within 15 minutes in response to an inspector’s request.” While this is not formally codified as an official FDA rule, it is widely recognized in the industry and serves as an important guideline for inspection preparation.

The FDA’s official guidance “Circumstances that Constitute Delaying, Denying, Limiting, or Refusing an Inspection” explicitly states that delays in producing records may be considered obstruction of inspection. Facilities must be prepared to provide requested documentation in a timely manner. Delays in producing records, especially without reasonable explanation, can be considered an attempt to obstruct the inspection.

Practical Response

To achieve this, the following measures are essential:

Pre-Inspection Preparation

• Adequate document organization: Organize all records logically and ensure rapid access
• Document management system development: Build a system that can efficiently search both electronic and paper records
• Index creation: Prepare indices or reference files indicating the location of important documents
• Rehearsal implementation: Conduct mock inspections to verify the document presentation process

Response During Inspection If presenting materials will take more than 15 minutes, the “inspection coordinator” should take the following steps:

1. Clearly explain the reason for the delay (e.g., compilation of large volumes of records is necessary, translation is required, retrieval from off-site storage is needed)
2. Explain specifically when materials can be presented (e.g., by 3:00 PM today, by 10:00 AM tomorrow)
3. Politely request to move on to the next question
4. Ensure materials are presented by the promised time

Reasonable Reasons for Delay Delays may be considered reasonable in the following circumstances:

• When compilation or preparation of large volumes of records is necessary
• When translation from a foreign language to English is required
• When records must be retrieved from off-site archives
• When data extraction from electronic record systems requires time

However, even in these cases, efforts to minimize delay as much as possible are required.

FDA Guidance: Delaying, Denying, Limiting, or Refusing an Inspection

The FDA issued the guidance “Circumstances that Constitute Delaying, Denying, Limiting, or Refusing a Drug Inspection” in October 2014. Subsequently, a draft revised version was issued in December 2022, and the final revised version was issued in June 2024. This revision expanded the scope to include medical devices.

This guidance defines the actions, inactions, and circumstances that the FDA considers to constitute delaying, denying, or limiting inspection, or refusing to permit entry or inspection. Specifically, they are classified into the following categories:

Delay of Inspections

• Delays in scheduling pre-announced inspections
• Delays during inspection (such as restricting access to facilities or manufacturing processes)
• Delays in producing records

Denial of Inspection

• Refusing FDA investigators’ entry to facilities
• Acts that prevent completion of inspection
• Statements or physical actions intended to mislead, deceive, or impede inspectors

Limiting of Inspection

• Restricting access to facilities or manufacturing processes
• Impeding or resisting photography
• Restricting access to or copying of records
• Restricting sample collection

Refusal to Permit Entry or Inspection

• Active or passive behaviors that do not allow entry to facilities or specific areas
• Inaction that fails to take measures necessary to permit inspection

Response to Form 483

If Form FDA 483 (Inspectional Observations) is received after inspection, responding within 15 business days is recommended. This deadline is not merely for submitting a response, but for demonstrating commitment to quality and compliance through the thoroughness of the response.

Effective Form 483 responses should include the following elements:

• Specific responses to each observation
• Results of root cause analysis
• Corrective and preventive action (CAPA) plans
• Implementation schedule
• Verification methods for effectiveness

For Medical Device Manufacturers: QMSR Compliance

For medical device manufacturers, February 2, 2026 is a critical date. On this day, the FDA’s new Quality Management System Regulation (QMSR) will take effect. The QMSR revises the former Quality System Regulation (QSR, 21 CFR Part 820) to harmonize internationally with ISO 13485:2016.

Key Changes in the QMSR

Harmonization with International Standards The QMSR incorporates by reference ISO 13485:2016 (Medical devices – Quality management systems – Requirements for regulatory purposes) and Chapter 3 of ISO 9000:2015 (Quality management systems – Fundamentals and vocabulary).

Terminology Changes The traditional terms Device Master Record (DMR), Device History Record (DHR), and Design History File (DHF) are unified as the Medical Device File (MDF) in accordance with ISO 13485.

Integration of Risk Management Risk management is integrated throughout the quality management system, requiring a risk-based approach in all processes, not just in design validation.

Changes in Inspection Methods The FDA is developing a new inspection process aligned with QMSR requirements. A new inspection program to replace the traditional Quality System Inspection Technique (QSIT) is scheduled to be implemented from February 2, 2026. The FDA will now inspect management reviews, quality audits, and supplier audit reports, removing previous exemptions.

Actions for Preparation

• Gap analysis: Identify differences between the current quality management system and QMSR requirements
• Develop action plan: Create and implement a plan to address identified differences
• Staff training: Train personnel on QMSR requirements and changes
• Internal audit: Conduct a comprehensive internal audit against QMSR requirements before February 2, 2026
• Documentation: Document audit results, non-conformities, and areas for improvement in CAPAs or related documents

Note: Even with ISO 13485:2016 certification, FDA inspections are not exempted. Manufacturers must modify their quality management systems to comply with QMSR requirements.

Best Practices for Inspection Preparation

Organizational Structure Development

• Formation of inspection response team and clarification of roles
• Designation of inspection coordinator
• Establishment of back room (war room)

Document Management

• Development of document management system
• Preparation of shadow binders (copies for inspection)
• Ensuring consistency between electronic and paper records

Personnel Development

• Regular implementation of mock inspections
• Inspection response training
• Training in methods for answering questions

Continuous Improvement

• Analysis of past inspection results
• Understanding of industry trends
• Continuous improvement of quality systems

Conclusion

FDA inspections are an unavoidable and important process for pharmaceutical and medical device companies. From 2025 to 2026, the FDA is significantly strengthening its inspection activities, with many changes underway including utilization of AI technology, expansion of unannounced inspections, and implementation of the new QMSR.

Companies are required to take the following responses to address these changes:

• Inspection response based on honesty and transparency
• Construction of a document management system enabling rapid document presentation (with the 15-minute rule in mind)
• Appropriate and prompt response to Form 483
• Implementation of continuous quality improvement activities
• For medical device companies, completion of QMSR compliance by February 2, 2026

Most importantly, maintaining high quality standards on a daily basis and practicing continuous improvement is essential. Inspections should be viewed as an opportunity to confirm the soundness of a company’s quality management system and should be approached proactively.

Comparison Table: Key Regulatory Changes

Aspect	Prior to 2025	Current (2025-2026)
Domestic Inspections (US)	Generally unannounced	Remain unannounced, increased frequency
Foreign Inspections	Pre-announced (several months)	Transitioning to unannounced (announced May 2025)
Inspection Selection	Risk-based	Risk-based + AI-driven (Elsa system, launched June 2025)
Food Safety High-Risk	Every 3 years	Every 3 years (FSMA mandate)
Food Safety Non-High-Risk	Every 5 years	Every 5 years (FSMA mandate)
Infant Formula	Periodic	Annual (FDORA 2022 mandate)
Medical Device QMS	QSR (21 CFR Part 820)	QMSR (incorporating ISO 13485:2016) effective Feb 2, 2026
Medical Device Inspection	QSIT methodology	New inspection program aligned with QMSR from Feb 2, 2026
Document Production	Timely manner expected	15-minute rule (industry best practice)
Inspection Obstruction Guidance	2014 guidance (drugs only)	2024 guidance (drugs and devices)

Timeline of Recent Regulatory Developments

Date	Event
2004	FDA adopts risk-based inspection approach
2011	FSMA signed into law, mandating inspection frequencies
2012	FDASIA adds Section 501(j) to FD&C Act (drugs)
October 2014	FDA issues guidance on delaying/denying drug inspections
2017	FDARA extends Section 501(j) to devices
2022	FDORA mandates annual infant formula inspections
December 2022	Draft revised guidance on inspection obstruction
January 31, 2024	QMSR Final Rule issued
June 2024	Final guidance on delaying/denying drug or device inspections
May 6, 2025	FDA announces expansion of unannounced foreign inspections
June 2025	FDA launches “Elsa” AI system for inspection prioritization
Fiscal Year 2025	694 more inspections than FY 2024
February 2, 2026	QMSR takes effect

This revised column incorporates the latest regulatory requirements, recent developments in FDA inspection practices, and emerging trends as of January 2026. It maintains the original intent and key messages while updating outdated information and adding critical new developments such as the QMSR transition, AI-driven inspection selection, and the expansion of unannounced foreign inspections.