This column has recently reported on some of these hot topics, including state sunshine (aggregate spend) laws (March 2011), clinical investigator oversight (May 2011), and the regulatory pathway for biosimilars (June 2011). Although the preceding list of top issues in 2011 is by no means comprehensive, it illustrates the diversity of issues and challenges confronting government and industry. The following spotlights a few of the topics trending in 2011.
User fees collected from industry provide increased Resources to help cover part of FDA costs of reviewing marketing applications, enabling the agency to reduce review times and improve the efficiency of the review process. User fees for prescription drug and biological products are currently authorized under the Prescription Drug User Fee Amendments of 2007 (PDUFA IV). PDUFA IV authorizes FDA to collect three types of user fees — application, product, and establishment fees — from applicants who submit certain new drug or biological product applications or supplements. Because PDUFA IV will expire at the end of September 2012, FDA began negotiations with regulated industry on PDUFA reauthorization (PDUFA V).
Reauthorization discussions began in 2010 with public input, followed by separate discussions with stakeholders and industry, which were completed in May. Among some of the proposed changes for PDUFA V are enhanced communication initiatives for early product development, mid- and late-cycle review meetings, revised risk-benefit assessments, and more FDA review staff. FDA expects to publish proposed PDUFA V recommendations in the fall for public comment, with final review and clearance by administration officials by the end of the year, in time for transmission of the recommendations to Congress in January 2012.
In addition to preparing PDUFA V recommendations, FDA is trying to complete negotiations and recommendations for a new generic drug user fee program. The agency is also in the early stages of establishing a biosimilar user fee program, having published a proposal in May for industry and stakeholder consideration.
Promotion and Advertising
FDA’s Division of Drug Marketing, Advertising, and Communications (DDMAC) is responsible for assuring that prescription drug promotion and advertising is truthful, balanced and accurately communicated. Although expectations for 2011 were that DDMAC would match or surpass its 2010 pace in issuing warning and untitled letters, the number of enforcement letters are down by over 60% for January to mid-June 2011 compared to the same period in 2010.
Of the dozen enforcement letters issued through mid-June 2011, four were the result of FDA’s “Bad Ad” program, launched in May 2010 to encourage healthcare professionals to recognize and report suspected misleading drug promotion. The year-end report for the program highlighted the program’s success, including 328 reports — three times the average rate of reports received in previous years — from healthcare professionals, consumers, and regulated industry of potentially untruthful or misleading promotion. FDAs plans to expand the “Bad Ad” program in the future, building on healthcare professionals’ heightened awareness and understanding of misleading drug promotion.
Guidelines for prescription drug advertising via social media were eagerly anticipated in the first quarter of 2011. Long after FDA’s public hearing on social media in November 2009, social media guidance remains to be seen. At the end of April, FDA published a notice seeking comments on a series of studies designed to test different ways of presenting benefit and risk information in direct-to-consumer prescription drug websites. Although a separate initiative, FDA’s notice stated that the studies will complement qualitative research planned for social media issues, thus signaling that social media guidance is unlikely in the near future.
Although DDMAC’s enforcement activities appear to have waned in 2011, other enforcement activities based on prescription drug marketing are growing at a rapid rate. Through joint efforts of the Department of Justice (DOJ), Office of the Inspector General of the Department of Health and Human Services, U.S. Attorneys’ Offices, and FDA, government investigations and prosecutions of companies and individuals based on unlawful prescription drug marketing continue unabated in 2011. The joint effort is part of the Health Care Fraud Prevention and Enforcement Action Team initiative, launched in 2009.
Cases against pharmaceutical manufacturers represent a significant component of the DOJ’s healthcare fraud caseload for 2011. In fact, the DOJ has increased the number of agents and attorneys dedicated to investigating health care fraud in 2011. In the Civil Division, the majority of cases under the False Claims Act are healthcare cases, with an increasing number initiated by private relators (“qui tam” plaintiffs). The DOJ is also closely monitoring possible violations of the Foreign Corrupt Practices Act committed by pharmaceutical companies conducting business in other countries. With the benefit of increased resources and funding, government anti-fraud actions based on the unlawful promotion and advertising of prescription drugs will continue to grow in 2011 — and beyond.
Patient Medication Information
In February, FDA published draft guidance regarding the distribution requirements of Medication Guides and when a Medication Guide is required as part of a REMS. The guidance was issued to address confusion among drug companies and healthcare professionals about when a Medication Guide should be provided to a patient. In addition, the guidance communicated the agency’s new position that Medication Guides will be approved under the FDA’s labeling regulations, and occasionally as part of a REMS, depending on the risks associated with the product. This position alters the FDA’s past policy of considering any Medication Guide to be part of a REMS.
The focus on Medication Guides appears to be part of a larger effort focused on providing clear and adequate labeling appropriate for patients. With the issuance of the draft guidance, FDA explained that industry should expect further changes to Medication Guides. Specifically, FDA is currently working on and developing more useful patient medication information (PMI) that may ultimately replace Medication Guides. The goal of uniform PMI is to correct the current problem of uncoordinated and sometimes conflicting written prescription drug information received by patients in varying formats, including consumer medication information, patient package inserts and Medication Guides. Last August, FDA held a public hearing to obtain input on a new framework for and development of PMI. In December, FDA announced a study to examine three PMI prototypes, including bubbles of information, boxed columns of information, and a format modeled after over-the-counter “Drug Facts” labeling. Although study results are not expected until next year, the recent guidance reflects the agency’s continued commitment to developing PMI, leading to a possible change in current policy and regulations.
Oversight of Clinical Investigators
In 2011, FDA has continued to focus its attention on ensuring the integrity of clinical trials and resulting data by improving regulations and guidance governing the conduct of clinical investigators. This column reported on FDA’s proposed rule to amend regulations governing the disqualification of clinical investigators (see Contract Pharma May 2011, Oversight of Clinical Investigators). Since then, FDA has published draft guidance governing financial disclosures required of clinical investigators. FDA regulations require persons who submit a marketing application for a drug or biological product to provide certain information concerning the compensation and financial interests and arrangements of any clinical investigator conducting clinical studies used to support the safety or efficacy of a product for purposes of approval. The guidance addresses issues raised by OIG and industry, and is intended to assist clinical investigators, industry and agency staff in interpreting and complying with current FDA regulations governing financial disclosures by clinical investigators. When finalized, the guidance will supersede the 2001 FDA guidance on the same topic.
In June, FDA issued draft guidance to articulate principles for determining whether an FDA-regulated product contains nanomaterials or otherwise involves the use of nanotechnology. The guidance is admittedly only a first step toward providing greater regulatory clarity on FDA’s approach to nanotechnology. It is overdue following a July 2007 report by FDA’s Nanotechnology Task Force, but comes on the heels of principles for regulating nanotechnology and nanomaterials issued jointly by the Office of Science and Technology Policy, Office of Management and Budget, and the United States Trade Representative. In the future, and in connection with its Nanotechnology Task Force, the agency plans to issue more specific guidance tailored to particular products or classes of products involving nanotechnology or nanomaterials.
The number and variety of legal and regulatory questions and issues involving prescription drugs and biological products continues to grow. Although some issues are more significant than others, current regulatory and policy agendas suggest that the next half of 2011 promises to keep up the pace.
Heather D. Bañuelos is counsel in the Washington, D.C. office of Hunton & Williams LLP in the firm’s Food and Drug Practice. She can be reached at firstname.lastname@example.org.