New Congress, New Challenges in the Year Ahead

Democrats are back on top in Congress and are mapping a broad agenda for change. Prescription drug pricing, medical product safety, and access to needed treatments are high on the priority list. Manufacturers will be in the hot seat answering questions about patent practices, high-risk products, and why drugs cost less in other countries than in the United States. The real challenge, however, will be to gain approval of a bill to reauthorize the Prescription Drug User Fee Act (PDUFA) before the program expires on Sept. 30, 2007. Such legislation also would renew user fees for medical devices and continue the pediatric drug exclusivity program.

Jill Wechsler

Reaching agreement on these must-pass measures in a short time frame will require industry to negotiate with some highly critical Congressional leaders. Reps. John Dingell of Michigan and Henry Waxman of California, both key players in shaping the original user fee program 15 years ago, will be orchestrating the debate. Dingell now chairs the House Energy and Commerce Committee, which oversees the US Food and Drug Administration and multiple healthcare issues. Waxman is the senior Democrat on that panel and also will be investigating industry practices and FDA programs as chairman of the House Government Reform Committee.

The more narrowly divided Senate will adopt a more collaborative approach, making it easier for industry to gain a hearing on PDUFA and other important issues. Senate Health, Education, Labor, and Pensions (HELP) Committee Chairman Sen. Ted Kennedy (D-MA) has cosponsored drug-safety legislation with ranking minority member Mike Enzi (R-WY), and the two plan to work together on PDUFA reauthorization and related measures.

In Washington This Month

FDA officials and industry representatives have been discussing user-fee issues and options for several months to present an agreed-on user-fee plan to Congress to shape the debate. The PDUFA proposal includes requested fees, timelines for application processing, and the range of FDA activities that fees will support. The new five-year agreement is expected to boost user fees considerably to generate about $400 million in payments, with the cost of filing a new drug application (NDA) jumping over the $1-million mark. Added fees have been proposed to support more timely review of manufacturer advertising and marketing materials, as well as a significant expansion in FDA postmarketing safety oversight. But efforts by Congress to tap fees to fund additional FDA activities tangential to application review will set off a sharp debate over just how much of government activities should be supported by industry fees.

Adding on

With Democrats and Republicans unlikely to agree on many legislative proposals this year, both sides will regard any PDUFA bill as a ready vehicle for confronting a broad range of healthcare issues. Measures to enhance drug safety, to speed generic drugs to market, and to expand drug importing are all likely to be hung on the PDUFA Christmas tree. There may even be a move to give FDA authority to regulate tobacco, an issue that has gained broad support on Capitol Hill.

"All these issues will be in play," acknowledges Jim Greenwood, president of the Biotechnology Industry Organization (BIO) and formerly a leading Republican on the House Energy and Commerce Committee. Industry's task is to identify a working majority in the House and Senate that can "deal with these issues responsibly," Greenwood says. With PDUFA, "we can't play veto games."

Focus on safety

A top priority for Congress is to enact drug-safety legislation. Kennedy and Enzi have developed a bipartisan measure that retains FDA's current oversight structure instead of establishing an independent drug-safety office. The legislation backs most other popular proposals: stronger controls on the use of high-risk therapies, a more powerful drug-safety oversight board to resolve disputes, curbs on drug advertising, broader posting of clinical trial results, and penalties for failure to complete postapproval studies. Enzi and Kennedy held a hearing on the proposal in November 2006 to jump-start deliberations on this high-profile issue.

At the same time, Scott Gottlieb, then FDA deputy commissioner, gave a speech mapping out the agency's preferred approach to improving drug safety. Gottlieb emphasized the need for better information about safety problems, more analytical tools to evaluate safety signals, and improved FDA communication about potential safety problems. He encouraged tapping user fees to provide more resources for drug-safety oversight but cautioned that over-reliance on risk-management plans could be burdensome for health professionals who have to implement them.

Ensuring quality

Drug-safety problems often arise from inadequate quality control in manufacturing, a topic that FDA will continue to address through its "Pharmaceutical CGMPs for the 21st Century" initiative. Since FDA concluded the initial phase of the project in Sept. 2004, an internal Council on Pharmaceutical Quality has headed up agency efforts to adopt a more risk-based approach to good manufacturing practices (GMP) inspections, manufacturing supplements, assessing chemistry, manufacturing, and controls (CMC) data, and overseeing manufacturing quality systems.

FDA published a final guidance in Sept. 2006 describing ways manufacturers can establish quality systems for ensuring compliance with GMPs. The guidance avoids imposing new requirements, emphasizing instead its voluntary approach to a more risk-based quality-assurance process. This guidance eventually will be modified to reflect standards for quality drug manufacturing developed by the International Conference on Harmonization (ICH). FDA supports this more global approach to promoting regulatory flexibility based on demonstration of quality-control systems that mitigate risks associated with pharmaceutical development and production. This and other initiatives will be discussed at a workshop in late February to review progress and to update industry on these quality initiatives.

At the same time, FDA and other federal agencies are taking steps to enforce quality standards and compliance with FDA rules, a topic that congressional panels will be revisiting in coming months. The US Department of Health and Human Services Office of the Inspector General (OIG) is reviewing how well drug manufacturers take requested corrective actions following plant inspections that uncover GMP deficiencies. And, the growing volume of drugs and medical devices from overseas has raised concerns about whether FDA can ensure that foreign manufacturers observe its quality and compliance policies. The OIG plans to review actions taken by FDA when it finds serious deficiencies at foreign plants to ensure that foreign firms comply with enforcement actions.

Curbing counterfeiters

Concerns that unsafe drugs could threaten public health are driving efforts to halt drug counterfeiting and protect the prescription-drug supply chain. Several members of Congress back legislation to stiffen penalties for drug counterfeiters, and FDA is ramping up investigations of these operators.

In addition, FDA seeks to implement its long-delayed rule that requires certain wholesalers to maintain pedigrees on the drugs they distribute. The agency issued a guidance in November clarifying how the fairly complex tracking program should work. Manufacturers and authorized distributors of record (ADRs) do not have to keep pedigrees, but FDA is encouraging all parties in the supply chain to do so. Another FDA guidance explains that agency investigators will focus enforcement efforts on those drugs most likely to be counterfeited such as very expensive, high-volume, and critical medicines. Small distributors, however, claim that the pedigree requirement will force them out of business and have gone to court to block the program.

Meanwhile, FDA is continuing its campaign against drug counterfeiting. At a meeting on electronic track-and-trace technology, FDA Commissioner Andrew von Eschenbach noted that any anticounterfeiting effort requires a multi-layer approach, including initiatives to ensure product and packaging integrity, increased penalties for counterfeiters, and support from state officials, in addition to pedigrees and tracking.

Von Eschenbach also discussed the need for more cooperation among drug regulatory agencies to battle fake drugs at a Nov. 2006 international summit in Washington. Directors of medical-products agencies from 20 countries attended the summit. And, the World Health Organization has launched a new drive to halt the surge in drug counterfeiting, which is particularly rampant in developing nations.

Going electronic

E-pedigree systems are just one example of how more-effective electronic information systems can address drug safety and other regulatory challenges. FDA is pursuing a number of e-data initiatives to streamline the drug-approval process, better assess adverse events, and make it easier for patients and health professionals to obtain current information on approved medicines. A new Bioinformatics Board headed by deputy commissioner Janet Woodcock is overseeing the development of data and technology standards to automate the communication of important information. One priority is to overhaul the agency's adverse-event reporting system. The group also is establishing a standard computerized medical vocabulary and an electronic system for listing drug products and manufacturing sites.

In December 2006, FDA held a public hearing on the feasibility of requiring drug manufacturers to submit regulatory documents electronically. Such a mandate would apply initially to applications to conduct clinical trials and to gain approval for new drugs, biologics, and generic drugs. Eventually it would extend to adverse event reports, postapproval amendments, and other applications. FDA acknowledges that it would need to improve its own capability for collecting information electronically but anticipates that e-data systems would facilitate access to important drug information for both internal and external assessment.

These efforts build on FDA's requirement that pharmaceutical companies file drug-labeling information electronically, beginning with newly approved drugs and those filing efficacy supplements. The rule also revises the content and format of the package insert to provide the most important information about prescription drugs up front where it can be better understood and more easily accessed by health professionals as well as patients. These data are establishing an electronic prescribing information database, operated by the National Library of Medicine and readily available to the health community.

Spurring innovation

A main fear of FDA officials and industry executives is that mandates for more safety data and curbs on uses of approved medicines could slow drug development and approval. The decline in innovative new therapies coming to market prompted FDA to launch its Critical Path initiative two years ago and to release its Critical Path Opportunities List in early 2006. Since then, the agency has been encouraging the formation of consortia and cooperative projects that can yield new tools for evaluating test therapies, for streamlining clinical trials, and for modernizing manufacturing methods, equipment and facilities.

These activities support the development of personalized medicine based on pharmacogenomics data able to identify those individuals most likely to respond to a medicine or to experience serious side effects. Although this represents a major departure from the blockbuster-drug development model, targeted therapy has been championed by FDA and federal health officials, and manufacturers are recognizing that new drugs for broad patient populations now may be hard to identify.

Pharmaceutical companies are joining the shift to personalized medicine by supporting new consortia and other efforts to identify and validate new biomarkers and develop new diagnostics and screening tests to identify certain enzymes and receptors linked to response. FDA is encouraging broader use of pharmacogenomics data by offering manufacturers early informal advice about how to analyze and submit genomic data that facilitate regulatory review. Scientists from FDA, industry, and academia seek to develop standards and best practices for submitting and validating such information and gene-expression measurements in microarrays.

Developing countermeasures

The national campaign to build defenses against terrorist events and emerging health threats is spurring innovation in vaccines and new countermeasures for anthrax, plague, radiation emergencies, and dangerous viruses and infectious diseases. FDA plays a central role in ensuring the quality and safety of these new therapies, as well as vaccines and treatments for seasonal and pandemic influenza. Congress recently approved legislation to expand funding for private research on new treatments, which should spur new research efforts. OIG investigators are examining FDA's progress in assessing and inspecting vaccine-manufacturing processes; in developing and assessing new vaccine-production technologies; and in monitoring the safety and effectiveness of pandemic vaccines through improved information and reporting systems.

More on Medicare

Campaigning Democrats called for lower drug prices and improved access to needed treatments and now are weighing options to deliver on these promises. A top priority for new House Speaker Nancy Pelosi (D-CA) is to repeal Medicare's "noninterference" clause so that the government can negotiate for lower drug prices directly with pharmaceutical companies instead of leaving that task to private prescription-drug plans.

Such a change will not be easy. Democrats could push through a straight repeal measure, but that would not necessarily alter the program under a Republican administration that believes private drug plans can negotiate prices better than bureaucrats. An alternative is to establish a separate government-run drug plan that would compete with all the private insurers, but this, too, would be difficult to implement. Industry fears that a move by the federal government to negotiate drug prices for all Medicare beneficiaries will lead to a national formulary with set prices for the government program and ultimately the broader market. Reformers like to point to the low drug prices enjoyed by the Veterans Administration (VA), but usually fail to note that the VA has a smaller formulary than most Medicare drug plans and serves a relatively small patient population. Even so, repeal was a favorite Democratic campaign slogan and one the new leaders will try hard to fulfill as they gear up for the bigger presidential election campaign in two years.

Pharmaceutical and biotechnology companies may be more enthusiastic about Pelosi's promise to expand federal support for embryonic stem-cell research. Increased funding for biomedical research, however, won't do much good if added regulation and price controls dry up financial investment in the biotechnology industry, points out Greenwood of BIO. "We need to persuade the new leadership that when they're making speeches on stem-cell research, they have to make sure that biotechnology companies will be there to develop the promised new cures," Greenwood comments. "We need to protect the biotechnology goose laying the golden eggs."

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