FDA Revamps to Meet New Challenges

Pressure to spur development of new medical products, deal with an increasingly global pharmaceutical supply chain, and accomplish more tasks with tighter budgets is prompting visible changes at FDA. Commissioner Margaret Hamburg took a broad look at the agency's long-established administrative structure following the departure of Deputy Commissioner Joshua Sharfstein at the beginning of the year, with an eye to meeting expanded regulatory assignments.

Jill Wechsler

In recent years, Congress has called on the agency to regulate food quality more closely and to monitor tobacco marketing, while continuing to ensure the safety, quality, and efficacy of medical products. The result is a top-level reorganization that shifts daily management and decision-making to others, permitting the commissioner to focus more on crucial scientific and policy issues.

TOP DEPUTIES

Most notable is the designation of a cadre of top deputies to oversee important agency functions (see Figure 1). Of particular importance to pharmaceutical and biotech manufacturers, a new deputy commissioner for medical products and tobacco, Stephen Spielberg, now coordinates the activities of FDA centers for drugs, biologics, medical devices, and tobacco products. Spielberg also will oversee a cluster of programs that affect all medical units, including offices for orphan drugs, pediatric therapeutics, combination products, and good clinical practices.

Figure 1: FDA organizational chart after recent restructuring by Commissioner Hamburg, as of November 2011 (www.fda.gov).

Another new deputy commissioner for global regulatory operations and policy, Deborah Autor, will manage FDA's Office of International Programs and the Office of Regulatory Affairs, which runs the agency's far-flung field force. This force includes FDA foreign offices, which have been established around the world to support oversight of an expanding volume of food and medical products imported into the United States. Autor is quite familiar with supply-chain vulnerabilities and difficulties related to surging imports. She previously headed the Office of Compliance (OC) within the Center for Drug Evaluation and Research (CDER), which also has been overhauled.

The explosion in foreign production of FDA-regulated products requires more collaboration and information exchange with established regulatory counterparts, according to Autor. "We can never get enough resources to cover all those facilities," she told the PDA–FDA Joint Regulatory Conference in September 2011. Autor also seeks to level the playing field between US-based and foreign manufacturers by gaining authority to block drugs from US markets if their producers limit or refuse FDA inspection or fail to comply with US quality standards. Autor anticipates further assessment of these approaches in a consensus study by the Institute of Medicine (IOM) on the global public-health risks from substandard, falsified, and counterfeit medical products.

These two new deputies join the head of FDA's Office of Foods, Michael Taylor, who oversees the Center for Food Safety and Applied Nutrition and the Center for Veterinary Medicine. An FDA veteran, Taylor has the daunting task of implementing recent food safety legislation without the resources and personnel necessary to inspect more food facilities and to expand oversight as required.

Chief Scientist Jesse Goodman continues to lead important regulatory science initiatives. Goodman's office oversees the National Center for Toxicological Research, counterterrorism and threats, and professional development and integrity for FDA professionals. Special offices for women's health and for minority health fall under Goodman's purview, but also report to Hamburg.

Counselor to the Commissioner John Taylor, who served as Hamburg's temporary deputy commissioner for much of this past year, returns to his advisory role, but with specific staff responsibilities. He will manage policy and planning functions, legislative relations, and external affairs, which includes FDA's press office and liaison with the healthcare community.

Hamburg also is establishing a high-level office of operations with a chief operating officer to head the agency's increasingly complex administrative functions. These functions include information technology, finance, facility management, and budget formulation.

The aim of these organizational changes, Hamburg explained in a July 2011 announcement, is to establish a more effective management structure for an agency that now has 12,000 employees (1600 of which reside in the Commissioner's office) and is responsible for regulating more than 20% of US consumer products. The new structure reduces the number of officials reporting directly to the commissioner, while emphasizing the importance of innovation and science and the effect of globalization on FDA and regulated entities.

These changes also aim to address various criticisms of FDA's regulatory posture. Manufacturers claim that an overly-cautious approach to potential safety issues generates unreasonable requirements that keep innovative and effective products from patients, explained consultant Steve Grossman at the October FDA Inspections Summit sponsored by FDA Week. Patient and disease groups, particularly those involved with rare conditions, echo these concerns and are pushing for FDA to revise risk calculations so that promising therapies can reach the market without delay.

Yet, consumer representatives and some members of Congress continue to voice concerns about product safety. Demands for more extensive testing of new drugs both prior to approval and after coming to market led to provisions in the 2007 FDA Amendments Act (FDAAA) that added greatly to FDA's oversight responsibilities for new drugs and biologics. Now, some legislators want to modify certain FDAAA requirements, particularly those for Risk Evaluation and Mitigation Strategies (REMs) and conflict-of- interest rules.

SPIELBERG UP FRONT

The challenge for Spielberg, a leading pediatrician and pharmacologist, is to coordinate responses to these issues. His elevated position makes him a ready spokesman for FDA medical-product regulators and gives him authority to make timely policy decisions that otherwise would wait for Hamburg to weigh in. He also will facilitate the development of products that involve multiple agency centers, including combination products, orphan drugs, and pediatric therapies.

Spielberg comes to FDA with 30 years experience in academia and industry. He has served on FDA advisory committees and got to know Hamburg as a member of the advisory Science Board. Before coming to FDA, Spielberg was director of the Center for Personalized Medicine and Therapeutic Innovation at Children's Mercy Hospital in Kansas City, Missouri. Previously, he was dean of Dartmouth Medical School, and prior to that, he held senior research positions at Johnson & Johnson and Merck. While in industry, he chaired a Pharmaceutical Research and Manufacturers of America pediatric task force and was instrumental in promoting the Best Pharmaceuticals for Children Act, which was enacted in 2002 to provide incentives for developing pediatric therapies.

An initial task for Spielberg is to orchestrate reauthorization of the Prescription Drug User Fee Act (PDUFA), along with new fees for generic drugs and biosimilars, by September 2012. Although industry and FDA generally agree on a new five-year PDUFA program, they fear that the legislators will add numerous pet policies to this must-pass legislation.

A related challenge for Spielberg is to help resolve serious disagreements between the medical-device industry and the Center for Devices and Radiological Health (CDRH) over proposals to revise the device-approval process. Safety issues and notable product recalls have prompted efforts to stiffen FDA regulatory and testing requirements, particularly for those products approved under the 510k regulatory procedure. After a lengthy evaluation process, which included public meetings and an IOM report, CDRH officials have proposed changes likely to require additional clinical testing of some devices. Manufacturers are protesting vehemently and urging Congress to support innovation by blocking such action.

"SUPER" CHANGES AT CDER

Parallel to the restructuring of FDA's top management, CDER Director Janet Woodcock has engineered operational changes that also seek to deal with globalization and overcome obstacles to new drug development. Growth in responsibilities and in staff has prompted the elevation of nearly all of CDER's main operating units into "super offices" with broader management structures better able to monitor diverse operations.

In May 2011, Woodcock added the Office of Surveillance and Epidemiology (OSE) to the super-office list, joining the Office of New Drugs, Office of Pharmaceutical Science, and Office of Translational Sciences. OSE Director Gerald Dal Pan gained more support staff for his immediate office, plus for two subordinate offices: the Office of Medication Error Prevention and Risk Management and the Office of Pharmacovigilance and Epidemiology. The various divisions of these larger operators manage CDER's adverse-event reporting system, oversee sponsors' observational studies, prevent medical errors caused by product names, and orchestrate risk-management programs. The move aims to highlight the importance of drug-safety issues and hopefully quiet those who want to shift drug safety out of CDER and into an independent entity.

Next, Woodcock unveiled a new structure for CDER's Office of Compliance, making it another super office with multiple suboffices and divisions. Ilisa Bernstein has been OC acting director since Autor left last summer. While many OC functions remain fairly constant, a new Office of Drug Security, Integrity & Recalls was created to address the challenges of globalization and growing drug counterfeiting and diversion (see the August 2011 Regulatory Beat column, "FDA Maps Strategy to Counter Supply-Chain Threats"). The Office of Manufacturing and Product Quality oversees field inspections and compliance with GMPs. An increasingly visible function is to prevent and mitigate drug shortages related to manufacturing and compliance issues. A larger Office of Scientific Investigations now monitors pharmacovigilance and REMS programs, in addition to the conduct of clinical trials and human subject protection.

More recently, CDER's Office of Medical Policy (OMP) also became a super office. Led by Rachel Sherman, OMP consists of the Office of Prescription Drug Promotion (formerly the Division of Drug Marketing, Advertising, and Communications) and the new Office of Medical Policy Initiatives. This last entity will oversee FDA's Sentinel Initiative for modernizing drug surveillance and adverse event detection; the Clinical Trials Transformation Initiative to modernize trial conduct and oversight; and the Patient Medication Information project which seeks to update FDA policies for communicating risk information to the public. A key task is to support health reform initiatives related to biosimilars and other policy issues.

All the new acronyms are confusing, and critics are skeptical about so many "super" offices within CDER. Woodcock sees these changes as leading to "a high-functioning, policy-driven, risk-based organization" that can "evolve and grow." And with any luck, CDER's new management structure will provide more time for Woodcock to examine drug regulatory operations more broadly and explain its actions and policies to its many constituents.

Organizational charts of the Center for Biologics Evaluation and Research can be found on the FDA website at http://www.fda.gov/AboutFDA/CentersOffices/OrganizationCharts/default.htm.

Jill Wechsler is BioPharm International's Washington editor, Chevy Chase, MD, 301.656.4634, jwechsler@advanstar.com.