Congress and Obama Seek to Bolster Drug Safety

Contaminated peanut butter, syringes filled with tainted heparin, drugs from India with fraudulent laboratory tests, and other manufacturing and quality-control crises are spurring efforts to overhaul US Food and Drug Administration programs and policies. In February 2009, President Barack Obama criticized FDA's inability to catch contaminated products and urged a "complete review of FDA operations." The Government Accountability Office (GAO) put FDA on its federal agency "high-risk" list in January 2009, citing a need to improve its data on manufacturing facilities and to conduct more foreign inspections.

Jill Wechsler

Instead of just blasting the agency, though, the Obama administration is providing added resources to enhance FDA's oversight of product safety. Congress finally approved legislation in March 2009 to appropriate funding for the government's 2009 fiscal year, which began in October 2008. The bill gives FDA more than $2 billion in appropriated funds, a $325 million increase over 2008. After adding in user fees, the agency will have a record $2.6 billion budget. The Alliance for a Stronger FDA cheered this "important down payment" to meet pressing agency needs. Whether FDA's budget continues to increase remains to be seen as the Obama administration rolls out details of its FY 2010 budget.

The FY 2009 budget includes $413 million for drugs and $184 million for biologics. User fees add $500 million to provide a total of $1 billion for drug oversight. That includes $41 million set aside for the Office of Generic Drugs, $16 million to support the agency's Critical Path Initiative, and $6.6 million to enhance the review of direct-to-consumer drug advertising.

Congress wants to keep a close watch on how FDA uses these significant funding increases to enhance food and medical product safety and has requested detailed quarterly reports on new hires, inspections, and technology acquisitions. The legislators expect a significant increase in foreign and domestic facility inspections, expansion of laboratory infrastructure, upgrades in agency information technology, and improved electronic screening of imports based on integrated risk-based information systems. Congressional leaders also urge active initiatives to prevent product contamination, including conducting compliance audits of food producers and foreign drug facilities to gain a better understanding of risks and how to address them.

Global oversight

FDA is slated to receive even more resources to boost foreign drug inspections under the FDA Globalization Act of 2009 (HR 759), a priority initiative for Rep. John Dingell (D-MI). Main cosponsors include Rep. Frank Pallone (D-NJ), head of the House Energy and Commerce Committee (E&C) Health subcommittee, and Rep. Bart Stupak (D-CO), chair of the E&C Oversight subcommittee, who has been investigating FDA import and inspection failings for several years. Pallone plans to hold hearings on the legislation and move it through committee simultaneously with health-reform measures.

In Washington This Month

The Globalization Act would authorize FDA to inspect foreign drug manufacturers every two years, block questionable imports, and crack down on those who fail to comply. Regulatory parity is sought to ensure that lax oversight and fewer overseas inspections are not a reason for manufacturers to shift operations from the US to Asia. All registered manufacturers and importers, including generic drugmakers, will have to pay new user fees to support the broader oversight program, and manufacturers will ensure the integrity of product supply chains through ePedigrees. Current law requires FDA to inspect drug manufacturers every two years, but the agency has never had sufficient resources to do so. The legislation aims to avoid that dilemma by establishing a detailed process for FDA to calculate fees every year to meet program costs.

FDA also would gain the power to recall, destroy, or detain unsafe, adulterated, or misbranded goods. The bill includes added authority to subpoena records and to impose criminal penalties for drug counterfeiting, a power long advocated by pharmaceutical and legal authorities. To support a larger inspection program, FDA is instructed to establish a dedicated cadre of inspectors for foreign food and medical product facilities. FDA officials, moreover, are prohibited from closing down field laboratories or district offices without making a case for such changes in a reorganization plan that would be reviewed by GAO and submitted to Congress.

Of particular interest to pharmaceutical companies is new language specifying that even rigorous FDA policies and programs do not override state laws. This provision reflects Democratic opposition to FDA preemption of state liability laws that are more stringent than federal standards. The measure may be less important, however, in the wake of the recent Supreme Court ruling in the widely watched Wyeth v. Levine case. Last month, the Justices rejected Wyeth's (Madison, NJ) claim that FDA approval of a drug and its labeling overrides state laws and agreed with the plaintiff that FDA decisions are not the last word in drug regulation. The provision in the Globalization Act supports this principle and clearly opens the door for state prosecutors and plaintiffs' attorneys to bring actions against companies that run afoul of state rules, even if they comply with FDA regulations.

The revised Globalization Act does address several concerns that FDA and manufacturers raised about an earlier proposal. Instead of requiring country-of-origin labeling for every ingredient in a product, FDA would gain a year to develop rules for providing this information to the public. That review process may permit alternative methods for providing useful patient information about the sources of drug components, possibly through websites or other sources.

The legislation further encourages FDA and industry to adopt risk-based approaches for ensuring the quality and safety of imported pharmaceuticals and active ingredients. FDA would gain flexibility to schedule inspections based on the risk of a specific product and compliance history of the company, which could reduce inspections from every two to four years at firms that present a strong record of compliance with good manufacturing practices (GMPs).

Pipeline protection

An important section of the Dingell bill addresses ways to secure drug-manufacturing pipelines, an FDA initiative that has been mired in controversy for some 20 years. The agency has been working with industry since 1988 to develop policies and standards for ePedigrees on ingredient sources and all parties involved in drug manufacturing, distribution, packaging, and dispensing. Objections from small wholesalers, repackagers, and pharmacists, however, have blocked agreement, ultimately through a lawsuit challenging FDA's ePedigree rules.

The situation has become even more confusing and costly as states have enacted diverse pedigree reporting and tracking policies, and major retailers have established electronic identifier requirements for pharmaceutical products. Industry has supported numerous track-and-trace pilots and now is pressing for uniform rules for ensuring the integrity of drug supply chains throughout the world.

The Globalization Act would tackle this thorny issue by requiring manufacturers to maintain records about all processors, distributors, and shippers that handle a drug product through its preparation, compounding, processing, distribution, shipping, importing, and warehousing. This information would be available electronically. Repackagers would be exempt from the pedigree program, however, and it will be a challenge to decide which party is responsible for which information.

Legislative alternatives

All the headlines about food and drug safety failures are generating additional legislative proposals in the House and Senate. Rep. Rosa DeLauro (D-CT), chairman of the House Appropriations Committee that oversees FDA's budget, recently reintroduced a bill to separate food regulation from medical-product approvals by creating a separate Food Safety Administration. DeLauro believes that such a transformation of the regulatory system is needed to give food safety the attention it requires.

Several leading Senators support a food safety bill, which may be more agreeable to food companies. The FDA Food Safety Modernization Act, sponsored by Senate majority whip Richard Durbin (D-IL), proposes more targeted user fees for domestic and foreign food operators to support increased inspections, while also giving FDA more power to monitor food quality and recall noncompliant products. The Durbin bill reflects concerns of some members of Congress that the massive shift of food and pharmaceutical production to Asia and other regions not only exposes Americans to low-quality and adulterated products, but also may leave the US vulnerable to supply-chain interruptions during a pandemic or other emergency. Sen. Sherrod Brown (D-OH) is examining the shift of drug production overseas and its impact on drug safety, prices, and US jobs. Specialty-chemical manufacturers in the US have complained that lax FDA inspection of foreign drug producers encourages foreign outsourcing and that comparable regulation of domestic and foreign manufacturers is needed to establish a level playing field in the world pharmaceutical market.

Ironically, legislation to increase FDA inspections of foreign drugmakers may reopen the drug importing window. A group of leading Senators has proposed a bill that allows nationwide reimportation of prescription drugs, claiming the program would save $50 billion over 10 years. All the imports would have to come from FDA-approved manufacturing plants in Canada, the European Union, Australia, New Zealand, and Japan—a policy that anticipates more frequent inspections and a drug-pedigree system.

FDA initiatives

While Congress weighs these options, FDA is issuing guidance and launching programs to bolster oversight of foreign manufacturers and provide pipeline security. FDA, the European Medicines Agency, and Australia's Therapeutic Goods Agency recently launched an 18-month pilot project to collaborate on GMP inspections of API manufacturers. The aim is to reduce the foreign-inspection burden on each agency and to avoid redundant oversight efforts. At the beginning of this year, FDA also joined six federal agencies involved with food, drugs, consumer products, transportation, and trade in issuing a governmentwide policy for ensuring good importer practices. A joint draft guidance recommends ways for importers to prevent or detect hazards or contamination through a product's life cycle.

FDA's "Beyond our Borders" program is expanding into more regions after opening three offices in China a year ago and establishing a formal presence in Brussels. FDA opened an office in Costa Rica, in January 2009, that focuses on food imports. Other outposts are planned for Mexico, South America, and the Middle East. Most recently, FDA launched operations in New Delhi and Mumbai, India, to provide technical advice and inspect facilities, primarily of drug manufacturers that export products to the US.

A new FDA Voluntary Secure Supply Chain pilot program will offer expedited entry to products from drug manufacturers able to demonstrate control over product quality from time of manufacture through entry into the US. The two-year initiative will start with 100 manufacturers seeking expedited treatment for a maximum of five products each. FDA hopes the pilot will demonstrate ways to prevent import of contaminated or counterfeit drugs and will allow the agency to focus its oversight and enforcement efforts on high-risk products and operations.

Another initiative supports supply-chain security by establishing a standardized numerical identifier (SNI) for drug and biologic products, as required by the FDA Amendments Act of 2007 (FDAAA) and reiterated in the proposed Globalization Act. A guidance document issued in January 2009 proposes that manufacturers use a product's national drug code plus a unique eight-digit serial number for identifying drug packages. Manufacturers and repackagers are not required to use SNIs, but those that do should follow the FDA standard. FDA considers this policy key to developing track-and-trace systems and plans further proposals on identifiers for pallets and cases, as well as standards for product authentication and validation.

Another proposal aims to speed up FDA admissibility decisions on drug imports at ports of entry. The agency is querying manufacturers about the feasibility of providing electronic information on product code, country of production, manufacturer, and ultimate consignee to facilitate decisions about which products should be approved and where further review is needed.

Manufacturer responsibility

A common thread in these FDA and Congressional initiatives is that manufacturers ultimately are responsible for the quality and safety of the food and drugs they produce or import into the US. Even with more inspections and tighter border controls, FDA officials acknowledge that it's impossible to detect every product failure or substandard process. Increased foreign sourcing of ingredients creates ever more complex supply chains and added difficulties in protecting against product contamination, diversion, and counterfeiting.

At a conference on pharmaceutical supply chain challenges cosponsored by FDA and the Parenteral Drug Association in September 2008, manufacturers stressed the need for a uniform, universal drug-pedigree system that documents product sourcing. FDAAA gave FDA power that may help it address the legal issues that have stymied regulatory action in this area. Additional legislation may further support policy and program development. Manufacturers want standards that support supply-chain security and global harmonization of policies for ensuring product quality through the supply chain.

For more on this topic, see the online exclusive "Downpayment on Health Reform"

Jill Wechsler is Pharmaceutical Technology's Washington editor, 7715 Rocton Ave., Chevy Chase, MD 20815, tel. 301.656.4634, jwechsler@advanstar.com