HHS OIG Announces FY 2008 Work Plan; 9 New FDA Studies Identified, Including Clinical Trial Oversight and Off-Label Promotion

The Department of Health and Human Services’ (“DHHS”) Office of Inspector General (“OIG”) recently announced its Fiscal Year 2008 Work Plan.  The OIG Work Plan, issued annually, sets forth various projects to be addressed during the coming fiscal year by the Office of Counsel to the Inspector General, the Office of Audit Services, the Office of Evaluation and Inspections, and the Office of Investigations.  The various factors OIG takes into account to identify the areas most worthy of attention in the fiscal year include:

• Requirements for OIG reviews, as set forth in laws, regulations, or other directives;
• Requests made or concerns raised by Congress and DHHS management;
• Significant management and performance challenges facing DHHS; 
• Work performed by DHHS and other organizations; and
• Actions to implement OIG recommendations from previous reviews.

The 2008 Work Plan includes 12 planned studies involving FDA policy – 9 of which are new, and 3 of which are a continuation from the Fiscal Year 2007 Work Plan.  The summary below is taken from OIG’s description of the planned and continued studies.  The 2007 Work Plan led to the publication of various reports, including the September 2007 OIG report on FDA’s clinical trial oversight.

New Studies

Implementation of Pandemic Influenza Preparedness Strategic Plan – OIG will review FDA’s implementation of its Pandemic Influenza Preparedness Strategic Plan.  The plan focuses on accelerating development, production, and regulatory reviews of vaccines, antivirals, and diagnostic devices for an effective national response.  OIG will determine whether FDA is meeting the timeframes it has established for deliverables in the plan.

Food and Drug Administration’s Implementation of Select Agent Regulations – OIG will review FDA’s implementation of select agent Federal regulations at its laboratories.  This effort continues our previous work at university, State, and private laboratories, which generated recommendations aimed at strengthening control of select agents. Pursuant to 42 CFR Part 73, OIG will assess compliance with select agent Federal regulations regarding security plans, accountability for select agents, and access to select agents.

Oversight of Off-Label Drug Promotion – OIG will assess FDA’s oversight and review of allowable off-label drug promotion and enforcement. Pursuant to provisions of the Food, Drug, and Cosmetic Act at 21 U.S.C. §§ 331 and 355, among others, FDA has the authority to regulate the labeling and promotion of drugs and to restrict off-label marketing.

Submission of Electronic Drug Labels – OIG will review FDA’s oversight of drug manufacturers’ compliance with the requirement to electronically submit to FDA complete and accurate drug labels for currently marketed prescription drugs.  In December 2003, FDA published final regulations (21 CFR §§ 314.50(l), 314.94(d), 601.14(b), and 314.81(b), respectively) requiring drug manufacturers to ectronically submit to FDA specific labeling content for new drug applications, abbreviated new drug applications, certain biologics license applications, and annual reports.  In November 2005, drug manufacturers were required to begin electronic submission of prescribing and product information for prescription drug labels in a structured product-labeling format.  The format is intended to give health care providers accurate, up-to-date drug information using standardized medical terminology in a readable, accessible format. OIG will examine the accuracy and completeness of electronic labels submitted to FDA and identify any factors that contribute to inaccurate or missing information.

Adverse Event Reporting for Medical Devices – OIG will review FDA’s adverse-event-reporting system for medical devices. Medical device manufacturers are required under 21 CFR Part 803 to report deaths, serious injuries, and device malfunctions to FDA within 30 calendar days or within 5 working days if the event requires remedial action to prevent substantial harm to the public.  Device reporting is a key part of FDA’s oversight of new medical devices, providing an early warning of problems with devices after they reach the market.  OIG will evaluate the extent to which FDA ensures compliance with adverse-event-reporting requirements and the way in which FDA uses medical device adverse event reports to identify and address safety concerns.

Oversight of Research Misconduct by Clinical Investigators – OIG will review FDA’s oversight and discipline of clinical investigators found to have engaged in research misconduct. Regulations at 21 CFR Part 312 provide FDA with authority to oversee and discipline clinical investigators for research misconduct. OIG will review FDA’s progress in implementing recommendations made by OIG during a 2000 review. OIG recommended at the time that FDA develop internal guidance on the thresholds that violations must meet to justify disqualifying a clinical investigator from receiving investigational products for use in clinical trials.

Financial Disclosure Requirements for Clinical Investigators – OIG will review the disclosure to FDA of financial interests of clinical investigators, as required by 21 CFR § 54, associated with drug, device, and biologic applications.  Financial conflicts of interest create a potential for bias that may negatively impact the integrity of the data as well as human subject protection.  OIG will determine the nature of financial interests disclosed by clinical investigators, the extent to which applicants monitor their clinical investigators for financial interests, and the extent to which FDA oversees the process.

Oversight of Food Safety Operations – OIG will review FDA’s oversight and operations related to three broad areas: imported foods, imported pet food and feed products, and recall procedures for human food and pet food. In the area of imported foods, OIG will determine the extent of FDA’s enforcement authorities; whether and how it determines that foreign countries’ food safety standards and inspections meet U.S. food safety requirements (or that their food products exported to the United States are in compliance with requirements), whether and how it determines that foreign measures are equivalent to U.S. food safety measures, and how frequently FDA evaluates companies that export food products to the United States. In area of the area of imported pet food and feed products, OIG will determine the extent of FDA’s enforcement authorities, including whether it requires imported pet food and feed to be produced under the same safety standards as those under which pet food and feed are produced in the United States. OIG will also determine whether FDA samples imported pet food and feed for chemicals and microbial pathogens. If FDA is not sampling food and feed products, OIG will determine why. In the area of human food and pet food recall procedures, OIG will determine the extent of FDA’s enforcement authorities, identify FDA procedures to implement those authorities, determine whether and how FDA is carrying out the activities called for in its procedures, and determine whether FDA conducted tests for melamine in human food immediately after melamine was found in pet food.  These various reviews are being conducted in response to a congressional request.

Food Facility Inspections – OIG will review FDA’s food facility inspection process and its methods for determining which facilities will be inspected. FDA monitors the safety of domestic food primarily through inspections of farms, warehouses, manufacturers, packers, and other types of food establishments. Section 702(a) of the Food, Drug, and Cosmetic Act authorizes FDA to conduct inspections to enforce the provisions of that statute and other applicable laws. Under this authority, FDA carries out surveillance inspections to gauge overall industry compliance with manufacturing practices and compliance inspections based on known or suspected problems with specific manufacturers. FDA’s district officers, with guidance from FDA headquarters, determine the number, type, and specific firms to be inspected. OIG will identify trends in the types of FDA facility inspections and their effectiveness in protecting the food supply.

Continued Studies

Generic Drug Approval Process – OIG will review FDA’s timeframes for reviewing original generic drug applications and identify factors that affect the timely review of these applications. FDA is required by 21 CFR § 314.100 to approve or disapprove applications for generic drugs within 180 days of submission. As of 2006, the agency had a backlog of approximately 1,000 generic drug applications, one-third of which had exceeded the 180-day statutory time limit. OIG will assess average application review times and identify factors contributing to the backlog.

Management of Information Technology Projects – OIG will review the adequacy of management and contracting practices of the Office of Information Technology (OIT) within FDA’s Center for Drug Evaluation and Research.  Requirements found in the Federal Acquisition Regulation (FAR), specifically parts 5-16 and 39, govern FDA’s contracting practices. OIG will review a sample of FDA information technology contracts, including those for the Adverse Event Reporting System II, and determine the adequacy and effectiveness of OIT’s acquisition management processes.  Our review will also focus on contractor selection and oversight.

Traceability in the United States Food Supply Chain – OIG will review FDA’s ability to trace food products back through the U.S. food supply chain.  The food traceability model, known as “one-up, one back,” is incorporated in regulations that FDA has issued to implement section 306 of the Public Health Security and Bioterrorism Preparedness and Response Act of 2002 (the Bioterrorism Act) and is intended to help FDA respond to a deliberate attack on the Nation’s food supply or other public health emergency involving food. The Bioterrorism Act and FDA’s regulation at 21 CFR Part 1, Subpart J, require persons that manufacture, process, pack, hold, transport, distribute, receive, or import food under FDA’s jurisdiction to maintain records that identify the immediate previous sources and immediate subsequent recipients of food that they receive or release. Compliance with this requirement will enable FDA to trace back through the supply chain any food FDA believes may pose a serious health threat and to trace forward through the food chain to alert facilities of potentially contaminated food. OIG will assess selected food facilities’ implementation of Federal requirements to maintain records that FDA may access if it has a reasonable belief that the food may present a threat of serious adverse health consequences or death to humans or animals.