FDA Commissioner Margaret Hamburg testified at the Senate Health, Education, Labor and Pensions (HELP) Committee, addressing timeliness of drug and device review, drug shortages and the supply chain, compounding implementation, and opioid abuse. Hamburg spoke to the accomplishments of the FDA Safety and Innovation Act (FDASIA) and Drug Quality and Security Act (DQSA).
Food and Drug Administration Safety and Innovation Act
User Fee Program Implementation
FDASIA includes the reauthorization of the Prescription Drug User Fee Act (PDUFA V) and the Medical Device User Fee Act (MDUFA III). PDUFA was passed in 1992 in order to speed up the FDA’s drug approval process.
Both User Fee Acts allow the FDA to collect substantial fees from pharmaceutical manufacturers to fund the regulatory review of new medicines. According to Hamburg, PDUFA V addressed many top priorities by industry and the FDA. These enhancements were “funded by a modest 6 percent increase in PDUFA user fees.” Under MDUFA III, FDA is authorized to collect user fees that will total approximately $595 million over five years. “In exchange for the additional user fees, FDA committed to meet much-enhanced performance goals for the device review process,” Hamburg noted.
“Coming at a time of continuing budget restraints, this steady source of funding is essential to support and maintain FDA’s staff of experts who review the thousands of product submissions we receive every year, and do so in a timely and thoughtful manner,” Hamburg states. “Over the years, our user fee programs have ensured predictable, consistent, and streamlined premarket programs for industry and have helped speed patient access to safe and effective new products.”
Generic Drug User Fee Amendments of 2012
The Generic Drug User Fee Amendments of 2012 (GDUFA), created to build on the success of PDUFA, is designed to speed access to safe and effective generic drugs to the public and reduce costs to industry. The law requires industry to pay user fees to supplement the costs of reviewing generic drug applications and inspecting facilities. To date, the backlog of pre-GDUFA applications has been reduced by approximately 40 percent. FDA also “facilitated development of the most comprehensive list of generic drug industry participants,”
Biosimilars User Fee Act
The Biologics Price Competition and Innovation Act, enacted as part of the Affordable Care Act, established a new abbreviated approval pathway for biological products shown to be “biosimilar to” or “interchangeable with” an FDA-licensed biological product. Approved biosimilars are expected to be less expensive than the reference products, providing clinicians and their patients access to more affordable treatments that are biosimilar or interchangeable.
Hamburg noted that because “there are currently no FDA-approved biosimilar biological products…the BsUFA program includes fees for products that are in the development phase to generate fee revenue in the near-term and to enable sponsors to have meetings with FDA early in the development of biosimilar biological product candidates.” In March 2013, FDA published draft guidance for industry entitled “Formal Meetings Between the FDA and Biosimilar Biological Product Sponsors or Applicants.”
The FDASIA also includes (1) a provision to encourage the development of antibacterial drugs; (2) a “powerful tool to facilitate the development and review of ‘breakthrough therapies,'” requiring FDA to expedite the review of a drug if “it may offer substantial improvement…for patients with serious or life-threatening diseases;” (3) provisions intended to improve the safety and effectiveness of pediatric drugs and devices; and (4) provisions to encourage development of treatment for rare diseases.
According to Wolters Kluwer, approximately $56 million in 2013 user fee funds are now unavailable to the FDA due to the sequestration. . For example, the small 6 percent increase in PDUFA user fees was essentially canceled out by the amount sequestered.
Patient Engagement
In addition to the reimplementation of user fees, the FDASIA also includes provisions intended to enhance patient engagement with FDA through the Patient-Focused Drug Development Program. FDA developed the program to obtain the patient perspective on certain disease areas during the five year period of PDUFA V.
The FDA held a two-day public workshop in September 2013 to engage and solicit information on patient preference from stakeholders, including patients, health care providers, industry, and academic leaders, and also “recently completed an obesity pilot study that has developed new tools that can be used to measure patient preferences.”
Drug Shortages and the Supply Chain
“Preventing drug shortages has been, and continues to be, a top priority for FDA,” Hamburg notes, and FDA has “increased substantially the resources [they] devote to drug shortages and expanded [their] work to prevent them.” The address noted that FDA helped prevent 170 shortages in 2013, 282 shortages in 2012, and 195 shortages in 2011. “[T]he number of new drug shortages declined significantly in 2012 to 117 and fell even further to 44 in 2013.
Title VII of FDASIA strengthens drug safety in an “increasingly global drug supply chain in which nearly 40 percent of finished drugs and 80 percent of APIs are imported.” Title VII allows FDA to protect the global drug supply chain by: (1) increasing FDA’s ability to collect and analyze data to enable risk-informed decision-making, (2) advancing risk-based approaches to facility inspection, (3) partnering with foreign regulatory authorities, and (4) driving safety and quality throughout the supply chain through strengthened enforcement tools.
Unique Device Identifier System
Hamburg also discussed the FDA’s Unique Device Identifier (UDI) System, aimed at providing a “consistent, standardized” way to identify medical devices. The FDA hopes the system “will provide improved visibility as devices move through the distribution chain, enhancing the ability to quickly and efficiently identify marketed devices when recalled and improve the accuracy and specificity of adverse event reports; it will also offer a clear way of documenting device use in electronic health records and clinical information systems.”
Drug Quality and Security Act
The Drug Quality and Security Act (DQSA) was passed on November 27, 2013, and seeks to oversee the compounding of drugs and make them safer, and outlines steps to identify and trace certain prescription drugs as they are distributed in the United States.
At the Senate health committee hearing, U.S. Senator Lamar Alexander (R-Tenn) stated with approval: “It has been a little over 100 days since the president signed the Drug Quality and Security Act, and in that time 30 facilities have registered as outsourcing facilities nationwide—they’ve done that voluntarily–and these 30 facilities all have done this without receiving guidance on the requirements they’ll have to meet for the sterile drugs they make. So that’s a good sign, and I believe that once we have more clarity, the number of outsourcing facilities will go up significantly.”
In terms of security, Hamburg outlined steps to build an electronic, interoperable system to identify and trace prescription drugs as they are distributed in the US. The development of the system will be phased over ten years with additional requirements that include: placing unique product identifiers on individual drug packages and providing product and transaction information at each sale with lot level information, in paper or electronic format. Ten years after enactment, the system will facilitate the exchange of information at the individual package level about where a drug has been in the supply chain. The new system will:
- Enable verification of the legitimacy of the drug product identifier down to the package level;
- Enhance detection and notification of illegitimate product in the drug supply chain; and
- Facilitate more efficient recalls of drug products.
This system will enhance FDA’s ability to help protect consumers from exposure to drugs that may be counterfeit, stolen, contaminated, or otherwise harmful.
Opioids
During the Senate meeting, Hamburg said opioid abuse is a “serious public health threat,” although it is important that patients with legitimate needs be able to access needed treatments and that “hydrocodone is an important [drug] for treating legitimate pain,” she said. She noted a “serious addiction threat” and said “prescriber practice is a serious component.”
Chairman Tom Harkin (D-IA) pressed Hamburg about the FDA’s approval of Zohydro, a single-entity hydrocodone product, pointing to an advisory panel’s recommendation against approval. Dr. Hamburg said the only available product also contained acetaminophen and cited concerns on liver toxicity, adding that Zohydro was “unique as a single hydrocodone product without that risk.” However, according to many opponents, this makes the drug easier to abuse. Some have called for a non-crushable, abuse resistant opioid formulation (Washington Post). Hamburg stated the agency “recognizes [Zohydro] is a powerful drug” and that it “serves an important niche for pain therapy,” while FDA also “understands the broader context of opioid misuse and weighs carefully risks and benefits.”