FDA Office of Inspections and Investigations: Organization and Inspection Operations

On October 1, 2024, the U.S. Food and Drug Administration (FDA) implemented a large-scale reorganization involving approximately 8,000 employees, transforming the former Office of Regulatory Affairs (ORA) into the newly established Office of Inspections and Investigations (OII). This organizational reform aimed to establish a system specialized in inspection, investigation, and import operations, and to strengthen collaboration across the FDA. OII serves as the frontline organization for FDA’s inspection activities and conducts inspections of regulated products and manufacturing facilities as its primary mission.

This reorganization represents the single largest organizational transformation in the agency’s recent history and was initiated in response to the 2022 infant formula crisis. Based on an evaluation by the Reagan-Udall Foundation, an independent nonprofit organization, the FDA determined that organizational dysfunction and siloed departments had contributed to the problem. The reorganization proposal was completed in December 2023, approved by the Secretary of Health and Human Services on March 5, 2024, officially took effect on May 13, 2024, and was fully implemented on October 1, 2024.

Mission and Responsibilities

OII’s primary mission is to protect public health through inspections. OII ensures the safety of FDA-regulated products by conducting inspections of regulated products and manufacturers and reviewing products proposed for import into the United States. OII investigators literally function as the FDA’s “eyes and ears,” conducting on-site regulatory oversight through domestic and international networks. The name change is intended to more clearly convey the organization’s role as the frontline of the FDA, providing real-time insights and science-based evidence necessary to ensure the safety and quality of products Americans depend on.

The specific scope of responsibilities includes the following:

Inspection Activities: Conducting systematic and rigorous inspections of regulated products and manufacturing facilities

Investigation Operations: Conducting thorough investigations when violations of laws and regulations are suspected

Import Control: Reviewing and inspecting regulated products imported into the United States (processing over 20 million entries annually)

Collaborative Activities: Building cooperative inspection systems with state, local, tribal, territorial, and foreign regulatory authorities

Emergency Response: Responding to emergencies and natural disasters related to FDA-regulated products and facilities (excluding foodborne outbreaks, which are managed by the Human Foods Program)

An important aspect of the reorganization is that compliance functions have been transferred to each product center (Center for Drug Evaluation and Research [CDER], Center for Devices and Radiological Health [CDRH], Center for Biologics Evaluation and Research [CBER], Center for Veterinary Medicine [CVM], etc.), and OII has been reorganized as a pure inspection enforcement agency. Approximately 1,500 ORA staff members were reassigned to product centers to work directly on inspections and investigations. This alignment eliminates duplication and brings investigators closer to center program staff, which is particularly effective when the FDA needs to respond to and evaluate ongoing violative inspections.

Organizational Structure

OII is divided into multiple specialized departments (Inspectorates), each responsible for specific product categories. By specializing inspection functions by product category, the organization has established an efficient oversight system. Major divisions include the following:

Office of Medical Device and Radiological Health Inspectorate (OMDRHI): Responsible for inspections of medical devices, radiation products, and mammography facilities. Led by Office Director Anne Reid and Deputy Office Director Rhonda Mecl, it consists of six divisions: four domestic divisions (West, South, Northeast, and Midwest), a Division of Global Operations, and a Division of Mammography and Radiological Health Inspectorate.

Office of Human Food Inspectorate (OHFI): Responsible for oversight of food manufacturing facilities. Divided into two divisions: one covering 26 eastern states and another covering 24 western states and overseas territories.

Office of Animal Food Inspectorate (OAFI): Conducts inspections of animal feed and related products

Office of Human and Animal Drug Inspectorate (OHADI): Responsible for inspections of pharmaceutical manufacturing facilities

Office of Biologics Inspectorate (OBI): Conducts inspections of biological product facilities including vaccines, blood products, and cell and gene therapy products

Office of Bioresearch Monitoring Inspectorate (OBMI): Responsible for auditing clinical trial sites and non-clinical study facilities. Divided into four regional divisions covering the Northeast (Connecticut, New York, etc.), South (Florida, Georgia, etc.), Midwest (Texas, Illinois, etc.), and West (California, Hawaii, etc.).

Office of Import Operations (OIO): Responsible for reviewing imported products. Oversees five regional import districts and is deployed at major ports (New York, Los Angeles, etc.) and border inspection stations (three locations on the Mexican border, etc.).

Office of Criminal Investigations (OCI): Conducts investigations of criminal cases related to FDA-regulated products. This organization continues virtually unchanged after the reorganization and continues criminal investigation activities for all FDA-regulated products.

Office of Field Operations and Response: Provides enterprise inspectorate support and manages emergency response. A Division of Tobacco Inspectorate is established within this office.

Other Divisions Responsible for Cross-Cutting Functions: These include the Office of Management, Office of Business Informatics and Solutions Management, and Office of Training, Education and Development.

Field Office Network

The 2024 reorganization transformed the organization from the traditional district office system to a vertically integrated organization specialized by product category. As a result, different offices may be responsible for food and pharmaceuticals in the same region. Each Inspectorate has its own regional structure and provides specialized expertise in its respective product areas.

OII’s major offices are located as follows:

Headquarters: Silver Spring, Maryland

Northeast Region: Boston, New York, Philadelphia, Baltimore

Midwest Region: Chicago, Kansas City, Minneapolis, Detroit

South Region: Atlanta, Dallas, Miami, Nashville

West Region: Los Angeles, San Francisco, Seattle, Denver

Overseas Territories: San Juan (Puerto Rico), Hagåtña (Guam)

Characteristic features of the OII field office network include that each office oversees multiple states and is organized by specialty area (food/pharmaceuticals/medical devices/biologics). Offices are strategically deployed at major ports and border inspection stations for import surveillance, and multiple bioresearch specialized divisions are established for clinical trial auditing.

Foreign Inspection Activities

OII conducts inspections not only within the United States but also at manufacturing facilities around the world through a global inspection network. The FDA’s foreign inspection program began in 1955 with inspections of European antibiotic manufacturing companies and now covers a wide range of product categories including pharmaceuticals, medical devices, and foods.

As of September 2024, 58% of facilities supplying drugs to the FDA are located overseas, with India and China accounting for approximately 40% of all foreign facilities. The FDA focuses oversight on manufacturing facilities in these high-risk regions.

Qualifications and Selection Criteria for Foreign Investigators

Investigators selected from OII play an important role in inspecting foreign manufacturing facilities. Selection criteria for investigators include the following:

Foreign Language Capability: Priority placement for Chinese and Hindi speakers

Expertise: Experts with deep knowledge of domestic and foreign regulatory requirements

Independence: Ability to make sound decisions with minimal supervision

Cultural Adaptability: Maturity and patience to perform duties diplomatically when faced with unfamiliar environments and language barriers, consideration for religious practices and customs

Experience Collaborating with Local Regulatory Authorities: Work experience in international regulatory environments

Staffing of Foreign Offices and Challenges

The FDA has established foreign offices in India and China but faces challenges in staffing. As of November 2021, there was one vacancy out of six positions in the India office and four vacancies out of nine positions in the China office, but as of June 2024, four out of seven positions in the India office and seven out of nine positions in the China office were vacant, indicating a deteriorating situation.

Reasons for the difficulty in recruiting investigators include extensive travel requirements (25-75% of work time), lower salaries compared to private industry (former investigators can earn more than twice the compensation in private companies), and intensified competition with the private sector.

Inspection Performance and Trends

Inspection Volume Trends Before and After the Pandemic

The COVID-19 pandemic had a significant impact on the FDA’s inspection capacity. In March 2020, the FDA largely paused domestic and foreign drug inspections, and regular international visits did not resume until 2022.

Inspection Volume Trends:

• Fiscal Year 2019 (Pre-pandemic): Over 1,300 drug quality assurance inspections
• Fiscal Years 2020-2021: Significant decrease in inspections
• Fiscal Year 2023: 1,065 drug inspections (444 domestic, 621 foreign) – 36% below pre-pandemic levels
• Fiscal Year 2024: 989 drug quality assurance inspections – still below pre-pandemic levels

In Fiscal Year 2024, over 62% of inspections were conducted at foreign facilities, representing an all-time high proportion. Inspections in India and China increased notably, with 34% of facilities listed in the Site Catalog in India and 28% in China being inspected.

The number of inspections of drug and medical device manufacturing facilities in China increased dramatically from 61 in Fiscal Year 2023 to over 227 in Fiscal Year 2024.

Inspection Backlog

As of May 2024, approximately 2,000 pharmaceutical manufacturing firms had not been inspected by FDA staff since before the pandemic. This backlog includes over 340 plants in India and China, which are major sources of drug ingredients for the United States.

In 2024, the FDA published a plan to address the pandemic-era inspection backlog in response to recommendations from the Government Accountability Office (GAO). The plan outlines a risk-based strategy to prioritize overdue inspections and mitigate gaps in oversight.

Inspection Classifications and Violation Rates

FDA inspections are classified into the following three categories:

NAI (No Action Indicated): No compliance issues found

VAI (Voluntary Action Indicated): Minor violations present but can be addressed through voluntary improvements

OAI (Official Action Indicated): Significant violations present and regulatory or administrative actions are recommended

According to Fiscal Year 2023 data, inspection classification trends are as follows:

Worldwide: 93% of all facilities in the CDER Site Catalog received NAI or VAI classifications in their most recent inspection

Foreign Facilities: Foreign facilities are more than twice as likely to have compliance issues identified compared to domestic facilities

India: Indian manufacturers had the highest rate of serious Current Good Manufacturing Practice (CGMP) violations at 13% of inspected facilities

Pre-announced Inspections: In Fiscal Year 2023, approximately 90% of FDA’s foreign inspections were pre-announced. This contrasts with inspections at U.S. domestic facilities, which are typically conducted unannounced.

This practice of providing advance notice has raised concerns about the effectiveness of foreign inspections in identifying genuine compliance issues. However, despite advance notice, FDA investigators have continued to uncover serious deficiencies abroad, including instances of document destruction during inspections.

Congressional Concerns Regarding Inspection Result Variability

The U.S. House Energy and Commerce Committee conducted an analysis of FDA inspection outcomes in India and China from January 2014 to April 2024 (limited to investigators who conducted 10 or more inspections). This analysis revealed tremendous variation in inspection outcomes.

Some FDA inspectors found compliance issues during all or almost all of their inspections, while other inspectors rarely reported a single compliance issue. Two inspectors never found a single compliance issue over the course of a combined 24 inspections in India. Another inspector found zero compliance issues in 20 out of 23 inspections (85%) in China while finding compliance issues with almost half of domestic inspections during the same period.

In contrast, 16 FDA inspectors, with over 325 inspections collectively in India, found compliance issues during every inspection they conducted. As a measure of what a pattern of rigorous inspections should look like, the Committee reviewed the inspection outcomes for three FDA inspectors with professional reputations for thoroughness who also had at least 10 inspections in China or India during the studied time period. These expert inspectors reported finding no compliance issues during inspections in China at a rate of only 6.7 to 11.4 percent and at a rate of zero to 9.5 percent in India.

The Committee expressed concern that these findings suggest vast differences in the skill, thoroughness, and competence of FDA inspectors.

Unannounced Inspection Pilot Program

In response to these concerns, the FDA is expanding unannounced inspections in India and China. As of May 2024, the FDA had initiated 114 pilot inspections in India (94 of which were unannounced) and 28 in China (16 of which were unannounced). The FDA plans to complete approximately 250 unannounced inspections and approximately 250 pre-announced inspections, totaling approximately 500 pilot inspections across both countries.

On May 6, 2025, the FDA announced that it will expand the use of unannounced inspections at foreign manufacturing facilities producing foods, essential medicines, and other medical products for U.S. consumers and patients. This announcement came one day after the White House issued an Executive Order instructing the FDA to provide regulatory relief to promote domestic production of critical medicines and improve the FDA’s risk-based inspection regime to enhance routine inspections of foreign facilities. This expansion will build upon the FDA’s existing Foreign Unannounced Inspection Pilot Program in India and China, with the aim of ensuring that foreign facilities will receive the same level of regulatory oversight and scrutiny as domestic facilities.

Reasons for Conducting Inspections

Inspections are primarily planned for the following reasons:

New Application-Related: Inspections of suppliers related to New Drug Applications (NDAs), Abbreviated New Drug Applications (ANDAs), and Biologics License Applications (BLAs)

Past Violation History: Follow-up investigations of companies that have previously received GMP violations or warning letters

Risk-Based Selection: Facilities selected considering factors such as production volume, process complexity, and product criticality

Post-Market Surveillance: Inspections of companies with product recalls or adverse event reports

Routine Surveillance Inspections: Inspections conducted periodically based on risk

Inspection Approach

OII’s operations focus on rigorous and transparent inspections and investigations based on scientific evidence. OII’s operating principle is to “conduct rigorous, transparent, and science-based inspections and investigations, providing real-time evidence and insights necessary for fact-based regulatory decisions to protect public health.”

This inspection-centered approach includes the following principles:

Evidence-Based Decision Making: Collecting and evaluating evidence obtained through thorough inspections

Global Inspection Network: Comprehensive product oversight through domestic and foreign inspections and investigations

Scientific Inspection Methods: Application of inspection protocols based on the latest scientific knowledge

Transparent Inspection Process: Ensuring transparency in the inspection process and results

Accountability: Fulfilling responsibilities as individuals, teams, and organizations involved in inspections

Utilization of Alternative Inspection Tools

During the pandemic, the FDA relied on tools such as record requests, virtual site evaluations, and foreign regulator reports to maintain regulatory oversight. The Consolidated Appropriations Act of 2023 included a provision for the FDA to conduct additional work on developing its foreign drug inspection program and explore further use of alternative inspection tools.

The FDA and other agencies have considered broader reforms to supplement traditional inspections. In one pilot program, the U.S. Department of Defense partnered with a private laboratory to test prescription drugs for contaminants, an approach common in Europe. Experts have also proposed incentivizing U.S. pharmacy chains and distributors to source products only from high-quality manufacturers, thereby extending quality assurance responsibilities throughout the supply chain.

Impact on Industry

The establishment of OII has significant implications for regulated companies. It is important for companies to understand OII’s specific functions and responsibilities and to understand how engagement with this new organization differs from the former ORA structure.

Key Changes Companies Must Address

Identifying New Contact Points: With staff reassignments and establishment of new roles, it is necessary to identify new contact points within the FDA. OII serves as the contact point for inspections, while compliance issues are handled by the responsible departments in each product center.

Changes in Compliance Expectations: With changes to the FDA’s structure, it is necessary to respond to new or modified compliance expectations. Speedier resolutions of alleged violations identified during inspections are expected. Since product specialists will be more involved in reviewing issues and evaluating corrective actions proposed by companies, companies must be prepared for faster resolution.

Updating Internal Procedures: It is necessary to update internal protocols to align with these changes.

Possibility of More Efficient and Frequent Inspections: With ORA staff reassigned to focus more directly on inspections and investigations, FDA-regulated companies might experience more efficient and possibly more frequent inspections.

Best Practices for Company Response

The following best practices are recommended for companies to effectively respond to OII’s new inspection environment:

Strengthening Inspection Preparedness: Prepare a system that can respond to inspections at all times in anticipation of increased unannounced inspections

Establishing Document Management Systems: Establish electronic record management systems to enable rapid provision of documents during inspections

Multilingual Support: Ensure documentation in English and inspection response capabilities at international manufacturing facilities

Real-Time Communication Systems: Establish rapid communication lines with OII and related product centers

Continuous Training: Continue GMP education for staff and ensure understanding of the latest regulatory requirements

Inspection Process and Procedures

Inspection Notice and Receipt of Establishment Inspection Reports (EIR)

With the reorganization, some changes have occurred in the inspection process. After an inspection, one copy of the Establishment Inspection Report (EIR) is provided to the top management official or designated representative of the inspected firm in accordance with the criteria and instructions in Field Management Directive 145. When conditions are met, the EIR is transmitted electronically from department-specific email addresses for each product category. The EIR is password-protected, and the password is issued in a separate email.

For medical device-related inspections, the following department-specific contact addresses have been established:

• Division 1 (West): OII-DEVICES-West-FMD145@fda.hhs.gov
• Division 2 (South): OII-DEVICES-South-FMD145@fda.hhs.gov
• Division 3 (Northeast): OII-Devices-Northeast-FMD145@fda.hhs.gov
• Division 4 (Midwest): OII-Devices-Midwest-FMD145@fda.hhs.gov

Responding to FDA Form 483 Observations

If deficiencies are discovered during an inspection, investigators record observations on FDA Form 483. Companies must respond in writing to these observations. After the reorganization, the procedures for responding to Form 483 remain essentially unchanged, although responses may need to be sent to the compliance departments of the appropriate product centers as well.

Staffing and Organizational Culture Challenges

Continuing Challenge of Inspector Shortage

As of June 2024, the FDA had 225 vacancies in its inspection workforce, approximately four times the pre-COVID number. Factors contributing to the shortfall include:

Extensive Travel Requirements: Travel up to 50% of work time

Non-Competitive Salaries: Lower starting salaries compared to industry roles

Increased Competition from the Private Sector: Former inspectors can earn more than double their FDA salary in private companies

Recent Reductions in Force: Recent reductions in force at the FDA eliminated a number of positions and further strained inspection capacity

Investigator Attrition and Retention

From the start of Fiscal Year 2022 to June 2024, ORA hired 105 new investigators into the general pool of approximately 230 authorized investigators but lost 105. Of these 105 drug investigator losses, 61% left for other FDA positions including other positions in ORA, 29% left the FDA, and 10% retired. The turnover rate for ORA investigators in the general pool was more than twice as high as the ORA-wide turnover rate in Fiscal Years 2022 and 2023.

A key reason for the high turnover is that some positions require travel ranging from 25% to 75% of the time. Other issues cited include compensation, training, workload, and work-life balance.

Organizational Culture Transformation

The reorganization represents a “huge culture change” affecting approximately 3,586 employees in OII (reduced from over 5,000 in the former ORA), according to Michael Rogers, Associate Commissioner for Regulatory Affairs (now Associate Commissioner for Inspections and Investigations). This transformation includes adapting to new roles, establishing new reporting lines, and closer collaboration with product centers.

To ensure a smooth transition, the FDA recognizes that there might be an initial period of adjustment as employees relocate and work with new methods, but believes that the transition will go smoothly if implemented during 2024.

Warning Letter and Enforcement Action Trends

In Fiscal Year 2024, the FDA issued 105 warning letters for quality issues, the highest number in five years. Warning letters are formal notices for companies to correct serious GMP violations or other regulatory violations. Companies that receive warning letters typically must submit a corrective action plan to the FDA within 15 business days.

Regarding Import Alerts, among all facilities that were issued Import Alerts, 39% were located in China and 13% were located in India, significantly higher than the 10% average for other regions. This reflects ongoing quality control challenges and regulatory compliance issues in these regions.

Future Outlook and Continuing Challenges

Technological Innovation and Digital Transformation

The FDA continues to modernize the inspection process. The use of digital tools, expansion of remote records reviews, and prioritization of inspection targets through data analysis are being advanced. As part of the reorganization, the Office of Business Informatics and Solutions Management was established within OII to be responsible for improving information systems and data management.

Furthermore, the newly established Office of Enterprise Transformation within the Office of the Commissioner focuses on key information technology transformation projects across the FDA and drives high-priority, cross-cutting business process improvement efforts.

Strengthening Risk-Based Approaches

The FDA continues to improve its risk-based inspection strategy. This includes prioritizing facilities considering factors such as production volume, process complexity, past compliance history, and product criticality. Drug Amount Report data for Fiscal Year 2024 is used to support this prioritization process.

Expanding International Cooperation

The FDA continues to expand cooperation with foreign regulatory authorities. Through Mutual Recognition Agreements (MRAs) and confidential information sharing arrangements, the FDA can leverage inspection results from other countries’ regulatory authorities to allocate its own inspection resources more efficiently.

Continuing Challenges

Despite the reorganization, several challenges remain:

Coordination Associated with Separation of Compliance Functions: Effective collaboration between OII and compliance departments in each product center is critical. In the initial stages, it is necessary to adapt to new reporting lines and decision-making processes.

Securing and Retaining Inspection Personnel: The inspector shortage problem has not been resolved and requires continued efforts to recruit and retain talent.

Post-Pandemic Inspection Backlog: The FDA needs to continue to increase inspection capacity to address the backlog of approximately 2,000 pharmaceutical manufacturing facilities that have not been inspected since the pandemic.

Budgetary Constraints: The FDA’s inspection program is subject to federal budget constraints and congressional funding allocation decisions. Because foreign inspections are more costly than domestic inspections, budgetary challenges directly impact inspection capacity.

Conclusion

The FDA Office of Inspections and Investigations is the core of the inspection system in the U.S. regulatory framework and serves as the frontline organization for public health protection. As its name indicates, inspections and investigations are positioned as the most important elements of its operations. The reorganization on October 1, 2024, represents the single largest transformation in the FDA’s history, affecting approximately 8,000 employees.

The creation of OII has strengthened the FDA’s international inspection capability and improved oversight of high-risk regions, particularly China and India. By specializing inspection functions by product category and strengthening collaboration with product centers, more efficient and effective regulatory oversight has become possible.

However, challenges remain to be overcome, including inspector shortages, post-pandemic inspection backlogs, and coordination challenges associated with the separation of compliance functions. The FDA continues to modernize its inspection program through the expansion of unannounced inspections at foreign facilities, utilization of alternative inspection tools, and continuous improvement of risk-based approaches.

Companies dealing with international medical device and pharmaceutical supply chains must continuously monitor OII’s new organizational structure and operating policies and adapt to the changing regulatory environment. Through its core functions of thorough inspections, meticulous investigations, and strict import control, OII will continue to ensure the safety, effectiveness, and quality of FDA-regulated products. Companies must be prepared for more frequent and efficient inspections, speedier resolution of violations, and deeper involvement of product specialists. With proper preparation and a commitment to continuous compliance, companies can succeed in OII’s new inspection environment.