OIG Plans to Focus on How FDA Inspects Generic Manufacturers and Enforces Postmarketing and Clinical Trial Transparency Requirements; Will Also Look Into the Early Experiences With DSCSA
The Department of Health and Human Services Office of Inspector General recently released its 2015 Work Plan. OIG’s annual Work Plan summarizes new and ongoing reviews and activities that OIG plans to pursue regarding HHS agency programs, with particular focus on Medicare and Medicaid reimbursement and program integrity. We summarized the Work Plan on Monday, but here we focus on OIG’s review plan regarding the Food and Drug Administration (FDA).
OIG states that their review of FDA activities will focus on a few issues:
(1) Inspections of generic drug manufacturer facilities.
OIG states that they want to determine the extent to which FDA conducts inspections of generic drug manufacturers. “We will also describe the results of such inspections and the enforcement actions taken by FDA in response to shortcomings or deficiencies,” the report states.
OIG initially included this prong in their 2014 Work Plan as well. While OIG is not in charge of the actual inspections, it is reasonable to assume FDA may step up its enforcement activities in light of the new, added oversight.
OIG notes that FDA typically inspects drug manufacturing facilities before generic drug approval and conducts routine inspections of foreign and domestic manufacturers to monitor compliance with good manufacturing practices.
(2) FDA’s oversight of postmarketing studies of approved drugs
The 2007 Food and Drug Administration Amendments Act (FDAAA) specifically provides FDA with authority to require drug manufacturers to conduct postmarket safety studies and clinical trials to assess possible serious risks associated with the drugs. Once FDA notifies a drug sponsor of the need for a postmarketing study or clinical trial, the company is required to provide a timetable for completion, including study milestones, and periodic status reports on progress toward completion of the PMRs. If a company fails to comply with the timetable, FDA is authorized to take enforcement action against the company, unless the company can demonstrate good cause for the failures.
In their 2015 Plan, OIG states that they will determine the extent to which FDA requires postmarketing studies and clinical trials for new drug applications. Furthermore, OIG will assess how FDA monitors postmarketing requirements and “takes enforcement action against applicants that do not comply with them.”
Currently, FDA states that their enforcement actions may include issuing a Warning Letter and assessing civil monetary penalties. A company that violates postmarketing study requirements may be subject to civil monetary penalties of up to $250,000 per violation, with the possibility of additional monetary penalties if the violation continues uncorrected. In addition, if a company violates postmarketing study requirements, its product may be deemed misbranded.
Currently, FDA’s list of Warning Letters shows the last post-marketing violation letter went to Shionogi, Inc., for failing to complete a clinical trial for the dosage of its painkiller Rybix. Shionogi had written to FDA that it would not complete the study because the costs of the postmarketing requirement “were not commercially justified based on the sales potential for Rybix.”
It will be interesting to follow any enforcement actions related to postmarketing requirements in the coming year.
(3) Review of information exchange in the drug supply chain
OIG states that they will put a priority on reviewing the early experience of drug supply chain "trading partners" in complying with the Drug Supply Chain Security Act (DSCSA). They plan to discuss the implementation with drug manufacturers, wholesale distributors, and dispensers.
The DSCSA seeks to minimize contaminated medicine or fake products making their way to pharmacy somewhere along the supply chain. The Act facilitates the “track and trace” of certain pharmaceuticals through the distribution chain by requiring manufacturers, repackagers, wholesale distributors, and dispensers to exchange certain information when engaging in transactions. Required product information includes the proprietary name of the drug, the strength and dose, the National Drug Code number, the container size, date of transaction, and several other identifiers. This requirement goes into effect on January 1, 2015, for manufacturers, repackagers, and wholesale distributors, and on July 1, 2015, for dispensers.
(4) Drug sponsors’ compliance with clinical trial reporting requirements
In 2007, Congress passed the FDAAA (42 U.S.C. § 282(j)) which mandated that certain clinical trials be registered and their results be reported in ClinicalTrials.gov, a clinical trial registry and results database.
“These reporting requirements are an important tool that enhances FDA’s ability to assess and monitor a drug’s safety and efficacy,” states OIG.
“We will determine the extent to which clinical trials comply with the reporting requirements set forth by the FDAAA and the way in which FDA is ensuring that these requirements are met.”
It will be interesting to follow FDA's proactive response to OIG's 2015 Work Plan, as well as the reports that OIG issues following their inspection.