FDA Amendments Act of 2007 (P.L. 110-85)
Released: 2010-04-27T00:00:00

Introduction

The Food and Drug Administration Amendments Act (FDAAA; P.L. 110-85 ) was signed into law on September 27, 2007. The law reauthorizes four expiring Food and Drug Administration (FDA) programs and expands the agency's authority to ensure the safety of prescription drugs and biologics, medical devices, and foods. FDAAA represents the most comprehensive FDA legislation since the Food and Drug Administration Modernization Act of 1997 (FDAMA; P.L. 105-115 ).

The primary impetus for the legislation was the renewal of FDA's authority for two key user fee programs that were set to expire at the end of FY2007: the Prescription Drug User Fee Act (PDUFA, last reauthorized in 2002; P.L. 107-188 ), and the Medical Device User Fee and Modernization Act (MDUFMA, enacted in 2002; P.L. 107-250 ). The law also reauthorizes two other expiring authorities, which are related to pediatric pharmaceuticals: the Best Pharmaceuticals for Children Act (BPCA, last reauthorized in 2002; P.L. 107-109 ), and the Pediatric Research Equity Act (PREA, enacted in 2002; P.L. 108-155 ).

In addition to the reauthorizations, FDAAA contains several other FDA-related provisions. These include provisions designed to enhance drug safety, spark the development of pediatric medical devices, expand the types of trials and the substance of information in clinical trial databases, create a new nonprofit entity to assist FDA with its mission, improve food safety, and affect a number of other areas related to public health. Several of FDAAA's provisions contain the authorization to appropriate funding; these are listed in Appendix A . Many create additional responsibilities with deadlines for federal agency personnel; see Appendix B . In addition, several of the authorities have sunset dates in 2012 or early 2013; see Appendix C .

FDAAA's impact on FDA is important to two ongoing policy discussions. One discussion centers around the possibility of additional legislation to refine or restructure the agency's regulatory role. Understanding current law, as amended by FDAAA, is a good starting point for any such discussion. The second discussion is that of medical products in the health care system. The agency plays a critical role in bringing medical products to market, which is described below. In performing that role, as refined by FDAAA, FDA's regulation of medical products affects their quality, availability, and cost within the health care system.

Food and Drug Administration Basics

The FDA, an agency within the Department of Health and Human Services (HHS), regulates the safety of most human foods, all animal feeds, and certain other products such as cosmetics. The agency also regulates the safety and effectiveness of human drugs, biologics (e.g., vaccines), medical devices, and animal drugs. Those products regulated for effectiveness must be reviewed and approved by FDA before they can be placed in commerce, a process called premarket approval . (FDA is tasked with postmarket surveillance for these products as well.) Products regulated only for safety may enter commerce with little FDA oversight, though the agency may inspect production facilities and require that certain good manufacturing practices be carried out. FDA has the statutory authority to withdraw from commerce any product it regulates that it determines to be unsafe.

Media coverage of issues related to the safety of food (e.g., spinach), drugs (e.g., Vioxx), and medical devices (e.g., cardiac stents) has brought congressional attention to FDA's performance and the funding it has available to carry out its statutory responsibilities. For those products requiring premarket approval, a central issue for Congress is how best to balance the need for the agency to help speed the products it regulates to market if they are safe and effective, and correct them, or keep them from entering or staying on the market, if they are not. For human foods, animal feeds, and other products not requiring premarket approval, key issues relate to FDA's ability to assure product safety and protect public health by preventing health threats from occurring, or by identifying and responding to problems quickly.

Legislative Background: S. 1082 and H.R. 2900

Prior to the introduction of H.R. 3580 , the bill enacted as FDAAA, each chamber of Congress had passed its own version of comprehensive FDA reauthorization and reform legislation. These were the Food and Drug Administration Revitalization Act ( S. 1082 ), and the Food and Drug Administration Amendments Act of 2007 ( H.R. 2900 ). While most of the bills' provisions were similar, S. 1082 contained some provisions that were not present in H.R. 2900 on the topics of food safety, prescription drug importation, and domestic pet turtle market access. Of those, only the food safety provisions were adopted in FDAAA. See Table 1 for a listing of major topics covered in each bill.

Report Roadmap

The remaining sections of this report contain descriptions of the key FDA programs addressed in FDAAA. FDAAA includes eleven titles, each of which is discussed below in its own section of this report. Each section introduces the topic, surveys the ways in which new provisions changed the law, provides links to relevant CRS reports, and presents a detailed table comparing FDAAA-enacted provisions to any existing previous law. The one exception is Title X, Food Safety, which is described briefly in this report, but addressed in more detail in a separate CRS report. In the text and tables, the Commissioner means the FDA Commissioner, and the Secretary means the HHS Secretary. The report uses several other acronyms as well, all of which are spelled out at their first point of use and in Appendix D .

For clarity, the tables comparing FDAAA with previous law have the following attributes. Table provisions are cited to their location in FDAAA. Where applicable, cites are also included for the Federal Food, Drug, and Cosmetic Act (FFDCA), the Public Health Service Act (PHSA), and the United States Code (USC). The USC citations vary in specificity to match the citations listed in FDAAA. When table text extends across previous and current law fields, this indicates one of two things. If an FDAAA cite is present, FDAAA is reauthorizing or restating portions of provisions identical to those of the prior law. If no FDAAA cite is present, a preexisting law interacts with and is fundamental to interpreting FDAAA, but has not been amended by it.

Title I. Prescription Drug User Fee Amendments of 2007

Title I of FDAAA, the Prescription Drug User Fee Amendments of 2007 (referred to as PDUFA IV), provides a five-year extension of FDA's authority to collect user fees from manufacturers of drug and biological products and expands the authorized uses of fee revenue. User fee revenue has provided an increasing proportion of FDA funding since PDUFA was first enacted in 1992. In FY1994, the first year FDA noted PDUFA revenue use in its budget justification documents, the fees contributed 9.7% of the human drug program's budget. At the time of FDAAA's passage, the FY2007 budget showed that PDUFA fees made up 44.7% of the agency's human drug program budget.

In the years leading to PDUFA's enactment in 1992, FDA, consumers, and manufacturers all sought to shorten the time between a manufacturer's submission of an application and the agency's decision on whether to approve the product. FDA lacked the funding for staff to review those products quickly. With PDUFA, Congress gave FDA a revenue source to supplement direct appropriations. Congress also structured PDUFA to restrict the use of collected funds to new product review, and established a mechanism for agency-industry collaboration to create performance goals that set targets, primarily for review times.

PDUFA has had a range of effects. New application review times decreased from 29 months in 1987 to 17 months in 1994. PDUFA's restriction of the use of fee revenue to premarket review created what many saw as an imbalance between resources available to premarket and postmarket activities. In its 1997 and 2002 reauthorizations, Congress gave FDA limited authority to use some of the fees for postmarket safety activities.

During 2004 discussions in preparation for PDUFA IV, several safety problems with aggressively marketed drugs—such as Vioxx—received wide publicity. This heightened the ongoing concern over the balance of attention between premarket review and postapproval safety monitoring. FDAAA reflects that increased focus on postapproval drug safety throughout, but especially in this title, described below, and in Title IX (Enhanced Authorities Regarding Postmarket Safety of Drugs), discussed later in this report.

Title I of FDAAA addresses types of fees, authorized fee revenue, authorized uses of fees, new fees for the advisory review of direct-to-consumer television advertisements, reauthorization and report requirements, and effective dates, as summarized in the following material.

Types of Fees. FDAAA reauthorizes the assessment, collection, and use of three types of fees from manufacturers of drugs and biological products. These are application fees, establishment fees, and product fees.

Authorized Fee Revenue. FDAAA establishes fee revenues, for each fiscal year, of $392,783,000, with various adjustments for inflation, workload, rent and rent-related expenses, and final-year adjustments. Congress added to that base amount fee revenues for drug safety totaling $225 million over the five-year reauthorization.

Authorized Uses of Fees. The new law expands the list of postmarket safety activities for which the fees could be used. These include developing and using adverse-event data-collection systems, including information technology systems; developing and using improved analytical tools to assess potential safety problems, including access to external data bases; and implementing and enforcing new FFDCA requirements relating to postapproval studies and clinical trials, labeling changes, risk evaluation and mitigation strategies, and adverse event reports and postmarket safety activities.

FDAAA also removes the calendar and time limitations on postapproval activities. When Congress first allowed PDUFA revenue use on postmarket activities in 2002, it set a three-year limit from the time of a drug's approval.

New Fees for Advisory Review of Advertisements. FDAAA creates a new user fee to support FDA's advisory review of prescription-drug television advertising. The program calls for a manufacturer to pay a fee if it voluntarily submits an advertisement for pre-dissemination review. The review is to be advisory. The law authorizes FDA to assess fees only on manufacturers that request such reviews. It further directs that if the Secretary has not received at least $11.25 million in fees by 120 days after enactment, the DTC advisory review user fee program shall not commence and all collected fees shall be refunded.

Reauthorization and Report Requirements. FDAAA codifies certain core elements of the prescription drug user fee program that, although included in PDUFA I, II, and III, were never placed into the FFDCA. One is the requirement for annual performance and fiscal reports to Congress. The others relate to the Secretary's interaction and communication with various stakeholders. These include public hearings regarding the Secretary's negotiations with industry regarding performance goals; and the requirement that the Secretary, in preparation for the next PDUFA reauthorization, consult with congressional committees, scientific and academic experts, health-care professionals, representatives of patient and consumer advocacy groups, and the regulated industry to develop recommendations for PDUFA V, including goals and plans for meeting the goals.

Effective Dates. The amendments in this title took effect on October 1, 2007. Authority to assess, collect, and use drug fees ceases to be effective October 1, 2012. The reporting requirements cease to be effective January 31, 2013.

Title II. Medical Device User Fee Amendments of 2007

Title II of FDAAA, the Medical Device User Fee Amendments of 2007 (MDUFA 2007), reauthorizes FDA's authority to collect user fees from medical device manufacturers, and makes certain other amendments to the regulation of devices. Congress initially gave the agency the authority to collect such fees in 2002, with the Medical Device User Fee and Modernization Act (MDUFMA; P.L. 107-250 ). MDUFMA established user fees for premarket applications (PMAs), premarket notifications (510(k)s), and other types of requests to market medical devices. The 2002 law incorporated, by reference, performance goals for many types of premarket device reviews. It also enabled third-parties to conduct establishment inspections, and added new regulatory requirements for reprocessed single-use devices.

In FY2007, when FDAAA was enacted, medical device user fees generated $35,202,000. This represents an increase of 144.7% over the amount first collected in FY2003. In FY2007, devices user fees comprised 9.0% of the agency's user fee revenue, and 1.8% of its total budget.

FDA's authority to collect medical device user fees was due to expire on October 1, 2007. Congress reauthorizes the authority in MDUFA 2007, Subtitle A. In Subtitle B, it amends some aspects of the regulation of medical devices. The details of each of these are discussed below.

Subtitle A. Fees Related to Medical Devices

Subtitle A of MDUFA 2007 reauthorizes FDA's expiring authority to collect user fees through October 1, 2012, and makes certain other changes to MDUFMA. The primary change is that MDUFA 2007 adds three new types of user fees (annual establishment fees, registration fees, and 30-day fees). The first two are to be paid regularly by establishments with devices on the market, generating a predictable base of device user fee income for FDA. MDUFMA had only enabled the collection of fees for applications related to FDA's approval or clearance of a product, which the agency had noted made the agency's user fee income difficult to predict. This was because the number of applications could vary from year to year. The agency asserted that, by contrast, fees paid annually would result in a revenue stream that was more reliable. This move toward a more predictable funding stream mirrors the approach taken by PDUFA for drugs and biological products.

MDUFA 2007 lowers the amounts of fees paid by device manufacturers for FY2008, and then includes a subsequent annual increase in fee amounts through FY2012. Despite the FY2008 decrease in the amounts of individual fee amounts, the total fee revenue generated will increase from FY2007 levels; revenue lost in reduced fee amounts will be offset by revenue generated by new types of fees.

MDUFA 2007 changes some provisions relevant to specific types of fees. Both MDUFMA and MDUFA 2007 generally establish fee amounts for various types of activities by setting them as a proportion of the cost of submitting a PMA. The amount charged for a PMA is therefore also called the base fee . MDUFA 2007 strikes a provision that had required the Secretary to adjust the premarket notification fee amount annually in a unique way, instead it sets it, like other fees, as a percentage of the base fee amount. For a different fee, the FDAAA-created establishment fee, the law gives the Secretary the authority to increase the fee amount in FY2010 if too few manufacturers have paid it.

MDUFA 2007 changes the law regarding reduced fees paid by small businesses in several ways. Under MDUFMA, entities qualifying as small businesses had certain fees waived and paid others at a reduced rate. MDUFA 2007 further reduces the fee amounts small businesses pay, removes a provision that the assets of partners and parent firms be considered in small business qualification, and enables foreign firms to qualify as small businesses.

Regarding modular applications, those submitted to FDA in separate pieces, MDUFA 2007 for the first time also affords the possibility of refunds for applications withdrawn at different points.

MDUFA 2007 extends a trigger requirement beyond FY2007 indefinitely. The trigger, which is designed to ensure that user fees supplement rather than supplant direct appropriations, requires that there be a certain amount of medical device-related direct appropriations in order for the Secretary to assess medical device user fees and be expected to meet performance goals.

MDUFA 2007 amends a provision regarding the collection of fees in excess of the amount authorized. The previous law required that if fees collected for a fiscal year exceed the authorized appropriation, the excess would be subtracted from the subsequent year's authorization. By contrast, MDUFA 2007 allows excess fees to be carried over to cover shortfalls over the course of several years.

MDUFA 2007 amends a provision describing how FDA may use the device fees it collects. The new provision in theory could have enabled fees to be expended on postmarket activites, but does not appear, in practice, to have done so. It states that fees will be dedicated toward expediting the process for the review of device applications and for assuring the safety and effectiveness of devices, as set forth in a letter from the Secretary to relevant congressional committees ("Commitment Letter"). It is conceivable that assuring the safety and effectiveness of devices could be interpreted to encompass postmarket surveillance, however the Commitment Letter does not list surveillance and enforcement activities. In addition, MDUFA 2007 maintains two separate MDUFMA provisions that articulate and generally limit the expenditure of user fee funds to premarket activities.

MDUFA 2007 requires the Secretary to continue to file annual performance and fiscal reports through FY2012, and writes these report requirements into the FFDCA. The law also requires that the performance report include information on previous cohorts for which the Secretary had not given a complete response.

In FDA's development of its performance goal recommendations to the Congress, MDUFA 2007 maintains MDUFMA's requirements that the agency consult with an array of groups, and take specified steps to invite public input. Unlike the previous law, MDUFA 2007 specifies that the recommendations be revised upon consideration of public comments, requires the recommendations' transmittal to Congress, and writes the performance goal-related requirements into the FFDCA.

Separate from the user fee authorizations, MDUFA 2007 authorizes the appropriation of specific sums from FY2008 through FY2012 for the review of postmarket safety information on medical devices. MDUFMA made similar authorizations, though no funds were appropriated.

MDUFA 2007 became effective on October 1, 2007.

Subtitle B. Amendments Regarding Regulation of Medical Devices

Subtitle B of MDUFA 2007 makes various changes to the regulation of medical devices. It extends from FY2007 through FY2012 the authority to have third parties review premarket notifications.

Producers of devices that are marketed in the United States are required to register annually with FDA. MDUFA 2007 restricts the period within which device producers must register with the Secretary. It also reduces from twice to once per year the requirement that those who register with the Secretary provide a list of devices on which they perform specific functions (e.g., the manufacture, preparation, propagation, compounding or processing of a device).

MDUFA 2007 amends electronic registration regulations to require electronic filing as a default, and without necessitating rulemaking by the Secretary as would have previously been required.

MDUFA 2007 amends two portions of the FFDCA's provisions regarding records and reports on devices . First, it adds a requirement that the Secretary promulgate regulations establishing a unique identification system for medical devices. Second, it modifies the reporting requirements for devices linked to serious injuries or deaths.

MDUFA 2007 revises the requirements for inspections by accredited third parties in three ways. First, it reduces administrative requirements associated with qualifying for the program. Second, it expands participation in the program. Third, it permits device companies to voluntarily submit to FDA reports by third parties assessing conformance with appropriate international quality systems standards, such as those set by the International Standards Organization. FDA is to consider the information in these reports in setting its inspection priorities.

MDUFA 2007 requires the Comptroller General to conduct two studies, and the FDA to conduct one. The Comptroller General is required to conduct one study on the appropriate use of the process under FFDCA 510(k) (premarket notification) to determine whether a device is safe and effective. It is required to conduct a second study on nosocomial (hospital-acquired) infections associated with medical devices. The FDA is required to conduct a study on whether the relationship between indoor tanning device use and the development of skin damage warrants a label change for the devices.

Title III. Pediatric Medical Device Safety and Improvement Act of 2007

Title III of FDAAA is the Pediatric Medical Device Safety and Improvement Act of 2007 (PMDSIA). PMDSIA was enacted based upon reports of a critical need for pediatric medical devices that help diagnose and treat diseases and conditions affecting children. Apparently, developing medical devices for children is less profitable and more problematic than developing them for adults. Fewer children need medical devices than adults, and children have physical attributes (e.g., size, biochemistry, growth rates), activities, and environmental influences that are different from those of adults.

In order to encourage the development of the pediatric devices, PMDSIA creates some new reporting requirements related to certain pediatric devices, offers several types of incentives to manufacturers to create pediatric medical devices, and gives FDA the authority to require postmarket studies of approved pediatric devices to ensure their continued efficacy and safety.

PMDSIA creates a set of reporting requirements for applications made under FFDCA 515 and 520(m). Section 515 governs PMAs to market class III devices (these require FDA's highest level of safety controls). Section 520(m) governs humanitarian device exemptions (HDEs). An HDE allows a manufacturer with a device aimed at a U.S. patient population of less than 4,000 to market the product without having to demonstrate its effectiveness (only its safety), and to have certain application fees waived. The exemption from proving effectiveness is designed to encourage manufacturers to develop medical devices for these small markets, assisting patients with rare diseases and conditions who might otherwise not be served. PMDSIA creates requirements for both types of applications, inserting a new section, 515A, into the medical device approval regulations.

Section 515A requires those requesting approval to market a device under 515 and 520(m) to include, if readily available, a description of any pediatric subpopulation with the disease or condition that the devices is intended to treat, and the number of affected pediatric patients. Section 515A also allows the Secretary to conclude that adult data can be used to support a reasonable assurance of effectiveness in pediatric subpopulations, as appropriate. The section also requires the Secretary to report annually to relevant congressional committees, specified information about pediatric devices approved in the preceding year.

PMDSIA creates one set of incentives for manufacturers to create pediatric medical devices by making some modifications directly to the HDE. Primarily, PMDSIA exempts some specified manufacturers of pediatric devices from the general HDE prohibition on selling a device for an amount that exceeds its costs of research and development, fabrication, and distribution. The exemption extends only to specified requests submitted on or before October 1, 2012. PMDSIA gives the Secretary specified pricing-exemption related enforcement and inspection authorities, and creates reporting requirements for adverse events related to devices that qualify for the pricing exemption. The law also requires the Comptroller General to submit a report to relevant congressional committees on the impact of the pricing exemption.

Regarding funding for research on pediatric medical devices, the PMDSIA requires the Secretary to establish a demonstration project to promote pediatric device development. The law authorizes $6 million per year for FY2008 through FY2012 to support the demonstration grants and related activities. The law also requires the National Institutes of Health (NIH) Director to designate a contact point to help pediatric medical device developers locate funding. In addition, it requires the Secretary to submit a plan for expanding pediatric medical device research and development to relevant congressional committees.

Finally, the PMDSIA incorporates certain postmarket surveillance measures related to pediatric medical devices. It expands the conditions under which the Secretary may require postmarket studies as a condition of approval for class II or III devices to include devices expected to have significant use in pediatric subpopulations. These studies may exceed the general 36-month limitation in duration if necessary to assess the impact of the device on pediatric populations' growth and development. The PMDSIA also includes a related dispute resolution provision, entitling a manufacturer to request a review, during which the device may not be deemed misbranded except as necessary to protect public health.

Title IV. Pediatric Research Equity Act of 2007

FDA has approved for adult use many products never tested in children. Yet clinicians often prescribe them for children believing that the safety and effectiveness demonstrated with adults would hold for younger patients. However, this off-label prescribing can result in children receiving products that do not work for them, or receiving too much or too little of a potentially useful drug. Studies show that, depending on the maturation and development of a child's organs and other factors, some drugs vary in how long they stay in the body, affecting their usefulness. Some side effects are unique to children or children of specific ages, including effects on growth and development.

Recognizing the obstacles (which could be economic, ethical, legal, or mechanical) that make manufacturers reluctant to conduct research to address these questions, FDA and Congress developed two approaches to facilitate pediatric research. FDAAA continues both programs. The first, the Pediatric Research Equity Act (FDAAA Title IV, discussed in this section) is a mandatory program that requires pediatric assessments as part of every new application regarding a new ingredient, indication, dosage form, dosing regimen, or route of administration. The second, the Best Pharmaceuticals for Children Act (FDAAA Title V, discussed in the following section of this report) is voluntary, offering a six-month marketing exclusivity for a product in return for pediatric studies.

In 1998, FDA published the Pediatric Rule, which mandated that manufacturers submit pediatric testing data, referred to as a pediatric assessment , at the time of all new drug applications. In 2002, a federal court declared the rule invalid, holding that FDA lacked the statutory authority to promulgate it. Congress gave FDA that authority with the enactment of the Pediatric Research Equity Act of 2003 (PREA; P.L. 108-155 ). PREA requirements cover all drug and biological product applications or supplements to applications concerning a new active ingredient, new indication, new dosage form, new dosing regiment, or new route of administration. The Act includes provisions for deferrals and waivers. PREA also authorizes the Secretary to require the sponsor of an already approved and marketed drug or biological product to submit a pediatric assessment based on criteria described in the law.

The Pediatric Research Equity Act of 2007, Title IV of FDAAA, reauthorizes PREA, amending it to strengthen standards for required tests, explanation of deferrals, labeling, and publicly accessible information. PREA now requires the Secretary to establish an internal committee, composed of FDA employees with specified expertise, to participate in the review of pediatric plans and assessments, deferrals, and waivers. The law requires the Secretary to track assessments and labeling changes and to make that information publicly accessible; establishes a dispute resolution procedure, which allows the Commissioner, after specified steps, to deem a drug to be misbranded if a manufacturer refuses to make a requested labeling change; and includes review and reporting reporting requirements for adverse events.

PREA requires reports from both the Institute of Medicine (IOM) and the Government Accountability Office (GAO). It also continues to link the program's authorization to the five-year authority FDAAA provides to the pediatric exclusivity program. (See discussion of FDAAA Title V in the next section of this report.)

Title V. Best Pharmaceuticals for Children Act of 2007

Title V of FDAAA reauthorizes and changes legislation first passed in 1997. As part of the FDA Modernization Act of 1997 ( P.L. 105-115 ), Congress provided drug manufacturers with a financial incentive to conduct pediatric use studies on their patented products. The "Pediatric Studies of Drugs" provision provided that if a manufacturer complied with a written FDA request for a specific pediatric study, FDA would add six months to its market exclusivity for that product. This tool is the second approach that FDA and Congress have taken to encouraging pediatric drug research, the other, required pediatric assessments of new products, is discussed in the preceding section of this report regarding FDAAA Title IV.

In 2002, the Best Pharmaceuticals for Children Act (BPCA 2002; P.L. 107-109 ) reauthorized the exclusivity provisions for another five years. It also added provisions to encourage pediatric research of products that were no longer covered by patent or other marketing exclusivity agreements, to which pediatric exclusivity was not relevant. It required the Secretary to list those off-patent products for which pediatric studies are needed to assess safety and effectiveness. It also established an off-patent research fund at NIH (PHSA 409I) and authorized appropriations of $200 million for FY2002 and such sums as are necessary for each of the five years until the provisions were set to sunset on October 1, 2007.

For on-patent drugs whose manufacturers declined FDA's written requests for studies (and, therefore, exclusivity), BPCA 2002 amended FFDCA 505A to allow FDA to refer drugs needing pediatric studies to the Foundation for the NIH (FNIH, PHSA 499), creating a second program of FDA-NIH collaboration.

Other provisions in the 2002 BPCA included giving priority status to pediatric supplemental applications; the establishment of an FDA Office of Pediatric Therapeutics (OPT); the definition of pediatric age groups to include neonates; and a direction to the Secretary to contract with the IOM for a review of regulations, federally prepared or supported reports, and federally supported evidence-based research, all relating to clinical research involving children. The IOM report to Congress was also to include recommendations on best practices relating to research involving children.

Title V of FDAAA again reauthorizes the pediatric exclusivity program, amending FFDCA 505A to sunset on October 1, 2012. It also encourages research on off-patent products, strengthens the requirements for labeling changes based on the results of pediatric use studies, and provides for the reporting of adverse events.

FDAAA authorizes the Secretary to grant additional marketing exclusivity, for both new drugs and drugs already on the market, only after a sponsor has completed and reported on the studies that the Secretary has requested in writing, including appropriate formulations of the drug for each age group of interest, and after any appropriate labeling changes are approved, all within the agreed upon time frames. An applicant who turns down a request on the grounds that developing appropriate pediatric formulations of the drug is not possible must provide evidence to support that claim.

The new law requires that the sponsor propose pediatric labeling resulting from the studies. For a product studied under this section, the labeling must include study results and the Secretary's determination whether those results demonstrate the drug's safety and effectiveness (if the results do or do not indicate safety and effectiveness, or if they are inconclusive). The product sponsor must disseminate labeling change information to health care providers, and the Commissioner must report to the Secretary on the review of all adverse event reports and recommendations on actions in response. Other provisions of the law set time frames for the actions it requires.

Public notice requirements are expanded beyond the current notice of an exclusivity decision to include copies of the written request. The Secretary must also publicly identify any drug with a developed pediatric formulation that studies had demonstrated to be safe and effective for children that an applicant has not introduced onto the market within one year.

A new dispute resolution process includes referral to the Pediatric Advisory Committee. The internal review committee, which FDAAA Title IV requires the Secretary to establish, must review all written requests. The Secretary, with that committee, must track all pediatric studies and labeling changes according to specified questions.

Other provisions require applicants to submit, along with the report of requested studies, all postmarket adverse event reports regarding that drug; refine study scope to allow the Secretary to include preclinical studies; and except from exclusivity any drug with another exclusivity that is to expire in less than nine months.

FDAAA amends PHSA Section 409I (as discussed earlier), which required that the Secretary, through the NIH Director and in consultation with the Commissioner and pediatric research experts, list approved drugs for which pediatric studies are needed to assess safety and effectiveness. It changes the specifications from an annual list of approved drugs to a list, revised every three years, of priority study needs in pediatric therapeutics, including drugs or indications.

If the Secretary determines there is a need for pediatric information for a drug for which pediatric studies have not been completed, the Secretary must either issue a proposal to award a grant to conduct such studies, if funds are available through FNIH, or refer the drug for inclusion on the list established under PHSA Section 409I. FDAAA also requires reports from the IOM and the GAO.

The provisions in Title V of FDAAA make up the following two tables: the first addressing amendments to FFDCA, the second relating to PHSA.

Title VI. Reagan-Udall Foundation

The Reagan-Udall Foundation for the FDA

Title VI of FDAAA adds new FFDCA Sections 770, 771, and 772 requiring the establishment of the Reagan-Udall Foundation for the Food and Drug Administration (the Foundation), a nonprofit corporation to advance FDA's mission regarding product development, innovation, and safety. The initial Board of Directors (the Commissioner, and the directors of NIH, CDC, and AHRQ) is to select the appointed members from a National Academy of Sciences-provided candidate list and then resign from the board. The ongoing board is to include representatives from industry, academic research organizations, government agencies, patient or consumer advocacy organizations, and health care providers.

FDAAA directs the Foundation to establish goals and priorities relating to unmet needs and then coordinate with federal programs, and award grants, contracts, and other agreements with public and private individuals and entities to advance those goals. Title VI directs the Commissioner to transfer between $500,000 and $1,250,000 to the Foundation from FDA appropriations each year.

Office of the Chief Scientist

FDAAA added a new FFDCA Section 910 that requires the Secretary to establish an Office of the Chief Scientist within the FDA Office of the Commissioner. Among the duties of the Secretary-appointed Chief Scientist would be to oversee, coordinate, and ensure quality and regulatory focus of FDA's intramural research programs.

Critical Path Public-Private Partnerships

A new FFDCA Section 566 authorizes the Secretary, through the Commissioner, to enter into collaborative agreements (Critical Path Public-Private Partnerships) with eligible educational or tax-exempt organizations to implement the FDA Critical Path Initiative. The agreements are to develop innovative, collaborative projects in research, education, and outreach for the purpose of fostering medical product innovation, enabling the acceleration of medical product development, and enhancing medical product safety.

The provision specifies the expertise and experience required of a partner entity. It requires the Secretary to submit an annual report to the authorizing congressional committees, and authorizes to be appropriated $5 million for FY2008 and such sums as may be necessary for each of FY2009 through FY2012.

Title VII. Conflicts of Interest

Title VII of FDAAA, Conflicts of Interest , contains provisions that revise FDA's approach to advisory committee members' conflicts of interest. FDA uses advisory committees to provide the agency with independent advice from outside experts on issues related to human and veterinary drugs, biological products, medical devices, and food. Advisory committees make recommendations to FDA, which FDA may or may not follow. To be credible and useful, many say that FDA must eliminate or reduce conflicts of interest in its committees. However, others note that the most expert members in the field are often those involved directly or indirectly in the activities about which FDA is seeking advice, creating the potential for such conflicts. In 2006 and 2007, the media reported that FDA advisory committees are biased in favor of drug approval, and that many committee members have conflicts of interest.

Prior to the passage of FDAAA, the law generally required that committee members be free from conflicts of interest, but allowed for exceptions to that rule under specific circumstances. A conflict of interest might have required a potential committee member to disclose the conflict, refrain from voting, and/or not participate in a committee, depending on the nature of the conflict. The law was articulated primarily in three locations: (1) the Federal Advisory Committee Act (5 USC Appendix; FACA); (2) the FDA advisory committee policy (21 USC 355(n)), which applied only to trials of drugs and biologics—not devices; and (3) a law governing special government employees—such as advisory committee members—Acts Affecting Personal Financial Interest (18 USC 208).

FDAAA inserts a new provision into Chapter VII, Subchapter A, of the FFDCA, effective October 1, 2007. The provision changes both the process of recruiting advisory committee members, as well as some circumstances under which and processes by which conflict-of-interest waivers may be granted. The new provisions repeal 21USC 355(n), but move much of its substance to a new location; the effect is that the requirements previously only applicable to drug and biologic advisory committees apply to committees providing advice on all types of products that FDA regulates.

FDAAA defines an advisory committee as a FACA-covered entity that provides the Secretary with advice and recommendations regarding activities of the FDA, and defines financial interest as defined under 18 USC 208(a). This definition covers activities such as a person's or their family members' current or future employment, trusteeship, or directorship. On its face, it does not apply to activities such as stock ownership, former employment, or receipt of a grant or contract, although FDA's regulations do require disclosure of these types of activities.

FDAAA requires advisory committee member recruitment mechanisms to be focused on reaching experts from areas such as academia, medical research institutions, and public interest and consumer groups. It also discourages the number of permissible exceptions to the financial conflict rules, such as the use of waivers or written certifications.

FDAAA requires advisory committee members' full financial disclosure prior to a meeting on a related matter. It precludes participation by a member with a conflict of interest unless exempted by the Office of Government Ethics. The Act also allows a waiver of the voting restriction if necessary to provide the committee with essential expertise.

FDAAA restricts the percentage of committees' membership that may consist of people who have received one of three types of exceptions to the financial conflict prohibitions: (1) waivers granted by the Secretary under newly created FDAAA provisions, (2) written determinations under 18 USC 208(b)(1), and (3) written certifications under 208(b)(3). The Secretary is required to determine the number and proportion of advisory members who received exceptions in FY2007. For FY2008 through FY2012, the Secretary must reduce the proportion of excepted members by an additional 5% per year from the FY2007 number. This limitation does not apply to financial interest exemptions made under 18 USC 208(b)(2).

FDAAA requires public disclosures for conflict-of-interest determinations, certifications, and waivers (but not 208(b)(2) exemptions), except for those exempted from disclosure under the Freedom of Information Act of 1974 (5 USC 522). It requires the Secretary to submit annual reports regarding advisory committee membership and conflict-of-interest waivers. It also requires the Secretary to review and update FDA conflict-of-interest guidance not less than once every five years.

Title VIII. Clinical Trial Databases

Title VIII of FDAAA, Clinical Trial Databases , expands requirements for the registration of clinical trials, and adds requirements for the publication of their results. The text of the title was arrived at after extensive discussions, which required an understanding of the nature of scientific inquiry and medical product development.

Scientific inquiry is, at its best, an objective exercise in which results are not pre-ordained, and all valid findings are published. Medical product development depends upon traditional scientific methods, and product sponsors are typically business enterprises. Prior to marketing, product sponsors are required to demonstrate the safety and effectiveness of their products, typically through clinical trials. However, both sponsors and medical journals may be reluctant to publish the results of trials that fail to show that products perform better than a placebo, or that raise too many safety concerns. In 2004, Congress and others raised questions about the safety and effectiveness of several FDA-approved products (e.g., antidepressants, anti-inflammatory drugs, and cardiac stents) about which unfavorable trial results had not been publicly disclosed. The issue of public access to all trial results, regardless of their findings, then gained significant traction.

Prior to the enactment of FDAAA, clinical trial registration was required at the outset of certain clinical trials testing drugs to treat life-threatening diseases or conditions. This requirement was criticized because it did not mandate the registration of a broader range of trials, because it contained no enforcement mechanism, and because it did not require the posting of trial results. Title VIII of FDAAA contains provisions related to all three criticisms.

FDAAA's provisions apply to trials involving not only drugs, but also devices and biologics. The Act includes requirements pertaining to most clinical trials beyond Phase I. In general, FDAAA requires that specified information be submitted by the trial's responsible party (RP; usually the trial sponsor), to the NIH Director. Following submission, the NIH Director is to make the information publicly available via the Internet, with specified exceptions. Enforcement mechanisms are provided for noncompliant RPs. For the purpose of carrying out the clinical trials database provisions, FDAAA authorizes $10,000,000 for each fiscal year. Further details of the way that FDAAA amends current law are discussed below, in subsections entitled Registry; Results; Coordination, Compliance, and Enforcement; and Other Items.

Registry

FDAAA requires the expansion of the existing data bank (clinicaltrials.gov, which is hosted by the National Library of Medicine) to include the registration of applicable drug, device, and biologics trials as described above. Submissions for the registry are to include four types of material: descriptive information about the trial, recruitment information for potential subjects, trial location and contact information, and administrative data, such as protocol identification numbers. The information required by FDAAA includes and expands upon that required under previous law, as well as elements of the World Health Organization's International Clinical Trials Registry Platform registration data set. The Secretary may modify these requirements by regulation.

In making the information public, the NIH Director is to ensure that it is searchable in a number of specified ways. The Director is also to ensure that the registry is easily used by the public, and that entries may be easily compared.

FDAAA generally requires the RP to submit information to the NIH Director within 21 days after the first patient is enrolled in the trial. This requirement is similar to the one that existed previously. The NIH Director is required to post information about drug and biologics trials not later than 30 days after the information is submitted by the RP. In contrast, for device trials, information is to be posted not earlier than the date of FDA approval or clearance, and not later than 30 days after approval or clearance.

The RP for an applicable clinical trial is required to submit updates to the NIH Director to reflect changes to registry information. The Director is to make the update information publicly available and generally ensure that previously submitted information remains accessible.

Results

Previous law allowed for the inclusion of results information with the consent of the trial sponsor, but did not require it. FDAAA requires the Secretary, acting through the NIH Director, to expand the registry to include results of applicable clinical trials and to ensure that the results are made publicly available via the Internet. Three categories of results information are to be added according to the following timeframe. First, beginning 90 days after FDAAA enactment, the Secretary is to ensure that the registry contains links to specified existing results . Second, within one year after FDAAA enactment, the Secretary, acting through the NIH Director, is to expand the registry to include specified basic results . Third, within three years after FDAAA enactment, the Secretary is to add information to create an expanded registry and results data bank by rulemaking.

The first type of results to be made available in the registry, existing results , consists of links to existing FDA and NIH documentation. These results must be posted for clinical trials that form the primary basis of an efficacy claim or are conducted after product approval or clearance. Links to this information are to be posted not earlier than 30 days after the approval or clearance of the product, or not later than 30 days after the information becomes publicly available.

The second type of results to be made available in the registry, basic results , consists of demographic, outcome, and scientific point of contact information, as well as agreements that restrict the principal investigator (PI) to publicly discuss or publish results. These results must be submitted for products that FDA has approved, licensed, or cleared. The RP is to submit basic results information to the Secretary within one year following the earlier of the estimated or actual completion date of the trial, with certain exceptions.

The third type of results information, expanded registry and results , is to be submitted to and made available in the registry pursuant to rulemaking. Rulemaking is to occur within three years of FDAAA enactment. Rulemaking is to require the submission of clinical trial information for approved or cleared products, and is to determine whether results information for unapproved products should be included as well. The expanded registry and results database is to include basic results, as well as: (1) a non-technical summary of results; (2) a technical summary of results; (3) protocol information; and (4) such other categories the Secretary determines are appropriate.

FDAAA directs the Secretary to promulgate a second set of regulations regarding adverse event reporting. Not later than 18 months after FDAAA enactment, the Secretary is to determine the best method for including appropriate information on serious and frequent adverse events in the registry and results database. If the Secretary fails to take action within 24 months after FDAAA enactment, the Secretary must include specified adverse-event related elements in the registry and results database. As amended by P.L. 110-316 , FDAAA's adverse event reporting requirements apply to drugs, biologics, and medical devices. The House passed a measure that would expand it to devices as well.

An RP may voluntarily submit information about trials that are not required for submission if the RP has made submissions for all required trials. If necessary to protect public health, the Secretary may require the submission of additional registry and results information.

Coordination, Compliance, and Enforcement

The former registry law did not contain any specific compliance or enforcement measures. By contrast, FDAAA contains four sets of enforcement and compliance requirements, and specifies civil penalties for noncompliance. One set attaches to federal grant funding. A second set of compliance requirements must be met when submitting a drug, biological product, or device submission to the FDA. A third set of FDAAA requirements specifies that clinical trial information submitted by the RP must be truthful and not misleading in any particular. Under a fourth set of requirements, the NIH Director is to include a notification in the database if an RP fails to submit required clinical trials registry or results information.

Previous law did not specify penalties or enforcement mechanisms related to registry requirements. Previous law contained general mechanisms for enforcing compliance with FDA requirements that may have been applicable, but which FDA never used for registry requirement violations. FDAAA amends the prohibited acts section of the FFDCA, to clarify that the clinical trial databases provisions are enforceable. FDAAA also amends the FFDCA's civil monetary penalty provisions, articulating those for noncompliance with the clinical trial database requirements.

Other Items

FDAAA contains a few additional provisions pertaining to informed consent, state clinical trial databases, and FFDCA violations. It requires the Secretary to update investigational new drug regulations so that informed consent includes a statement that clinical trial information has been or will be submitted for inclusion in the registry databank. Previous law contained informed consent requirements, but none specific to the registry.

The Act prohibits any state or political subdivision from requiring the registration of clinical trials or their results in a database. It also specifies that the fact of submission of off-label use clinical trial information, if in compliance with revised registry and results database requirements, is not to be construed as evidence of a new intended use. In addition, the availability of compliant database submissions is not to be considered as labeling, adulteration, or misbranding under the FFDCA.

Title IX. Enhanced Authorities Regarding Postmarket Safety of Drugs

Title IX of FDAAA gives the FDA new authorities to ensure drug safety and effectiveness. These build on decades of incremental additions to FDA's regulatory scope and its ability to identify drug safety problems and to correct or minimize them.

Since the 1938 passage of the FFDCA, the manufacturer of a new drug has had to demonstrate to FDA the product's safety before the agency would approve it for marketing in the United States. In 1962, the Harris-Kefauver Amendments to the FFDCA added product effectiveness to the premarket requirements. FDA cannot assert that any drug is completely safe. Instead, it considers whether, given the available information, the drug is safe enough when used correctly by the types of individuals and for the diseases or conditions for which it was tested. FDA and others must remain alert to new information as those drugs are used more widely because, until a very large number of individuals have taken a drug, a rare adverse effect may not occur or a very common condition may not be recognized as drug-associated.

Prior to FDAAA, the law allowed FDA to require a postmarket study as a condition of its initial approval of a marketing application, but did not authorize FDA to add such requirements after approval. The law did not allow FDA to require that manufacturers submit drug advertising material for review or approval before dissemination. Neither did it provide for civil penalties, authorizing only the revocation of approval or licensing (or the threat of revocation) to compel manufacturers to change labeling or advertising.

Subtitle A. Postmarket Studies and Surveillance

Subtitle A includes various provisions regarding postmarket studies and surveillance of human drugs. Its provisions do not apply to veterinary drugs.

Postapproval Studies and Clinical Trials

FDAAA authorizes the Secretary, under specified conditions after a drug is on the market, to require a study or a clinical trial. The Secretary may determine the need for such a study or trial based on newly acquired information. To require a postapproval study or trial, the Secretary must determine that (1) other reports or surveillance would not be adequate, and (2) the study or trial would assess a known serious risk or signals of serious risk, or identify a serious risk. The law directs the Secretary regarding dispute resolution procedures.

Labeling Changes

FDAAA authorizes the Secretary, upon learning of new relevant safety information, to require a labeling change. It also creates procedures, including time limits, for notification, review, dispute resolution, and violation, regarding labeling change requirements.

Risk Evaluation and Mitigation Strategies

FDAAA authorizes the Secretary to require, under specified conditions, a risk evaluation and mitigation strategy (REMS) at the time of a new application, after initial approval or licensing when a new indication or other change is introduced, or when the Secretary becomes aware of new information and determines a REMS is necessary. Any approved REMS must include a timetable of assessments.

The Secretary may include requirements regarding instructions to patients and clinicians, and restrictions on distribution or use (and a system to monitor their implementation). The law allows a waiver from REMS restrictions on distribution or use for certain medical countermeasures in the time of a declared public health emergency, and creates a mechanism to assure access to a drug with a REMS for off-label use for a serious or life-threatening disease or condition.

FDA practice has long included most of the elements that a REMS may include. FDAAA gives FDA, through the REMS process, the authority for structured follow-through, dispute resolution, and enforcement. These include required reviews of approved REMS at specified times initially and then as the Secretary determines; detailed procedures for the review of both proposed REMS and required or voluntary assessments or modifications; establishment of a Drug Safety Oversight Board; and evaluation of whether the various REMS elements assure safe use of a drug, and whether they limit patient access or place an undue burden on the health care system.

Enforcement

FDAAA expands the definition of misbranding to include the failure to comply with certain requirements regarding REMS, postmarket studies and clinical trials, and labeling. It establishes civil monetary penalties for violations of those requirements. The maximum for one violation is $250,000, up to $1 million for all violations within one adjudication proceeding. The law describes escalating penalties, based on continuing violations and efforts at correction, up to $10 million in a single proceeding.

Television Advertising

FDAAA creates a new FFDCA Section 503B to authorize the Secretary to require submission of a television advertisement to the Secretary for review before its dissemination. Based on this review , during which the Secretary may consider the impact the drug might have on specific population groups (such as older and younger individuals, or racial and ethnic minorities), the Secretary may recommend, but not require, changes in the ad. The law authorizes the Secretary to require that an ad include certain disclosures without which the Secretary determines that the ad would be false or misleading. These disclosures concern information about a serious risk listed in a drug's labeling, and the date of a drug's approval.

An amendment to the FFDCA requires that television and radio ads present the required information on side effects and contraindications in a clear, conspicuous, and neutral manner (Section 502(n)).

A new FFDCA Section 303(g) establishes civil penalties for the dissemination of a false or misleading direct-to-consumer (DTC) advertisement. The amount is limited to $250,000 for the first violation in any three-year period, and to $500,000 for each subsequent violation in that period.

FDAAA requires a study by the FDA Advisory Committee on Risk Communication and a report to Congress from the Secretary regarding DTC advertising and its communication of health information and its effect on information access and health disparities among population subsets.

Active Surveillance and Assessment

FDAAA directs the Secretary to collaborate with public, academic, and private entities to develop a postmarket risk identification and analysis system using electronic databases. Detailed provisions require the Secretary to protect individually identifiable health information; consult the Drug Safety and Risk Management Advisory Committee; communicate with key stakeholders; coordinate with other drug safety data sources; and report to Congress. FDAAA authorizes the appropriation of $25 million for each of FY2008 through FY2012 in addition to funds available under PDUFA for these activities.

Information Dissemination

Various sections of Title IX of FDAAA, in addition to those described above, address the provision of health information. One required report to Congress must address how best to communicate risks and benefits to the public, including the use of REMS and whether to use a unique symbol in the labeling of a new drug or indication. Any published DTC prescription drug advertisement must include a statement encouraging the reporting of negative side effects to FDA, along with a 1-800 number and website address. The Secretary must submit a report to Congress after studying whether the statement in printed advertisements is appropriate for television advertisements.

Funding

FDAAA authorizes increased appropriations to support components of the drug safety provisions. For the surveillance and assessment activities, the Secretary may use $25 million of PDUFA fees each year to carry out those activities. For REMS and other drug safety activities in this title, the new law increases the revenue authorized under PDUFA by an additional $225 million over the period FY2008 through FY2012, and designates its use for drug safety activities.

Subtitle B. Other Provisions to Ensure Drug Safety and Surveillance

The provisions in Subtitle B of FDAAA Title IX address topics related to drug safety. The first section requires the Secretary to issue guidance for the conduct of clinical trials of antibiotic drugs ; and convene a public meeting regarding orphan antibiotic products. A few sections address the physical security of drug products, such as requiring the Secretary to develop standards and technology to protect the drug supply chain against counterfeit and damaged drugs.

Other sections address communication with the public, expert committees, and others, about agency actions and plans. The Secretary must develop and maintain an Internet Web site with extensive drug safety information, and publish a list of all authorized generic drugs . The Secretary must provide public access to action packages for product approval or licensure, including certain reviews; and establish an Advisory Committee on Risk Communication . The Secretary must refer an application for a new active ingredient to an FDA advisory committee or include in the action letter reasons for not doing so. FDAAA requires that the Secretary report on FDA's implementation of its plan to respond to recommendations in the IOM 2006 report The Future of Drug Safety .

The Secretary must also screen weekly the Adverse Event Reporting System database and report quarterly regarding new safety information or potential signals of a serious risk; report on procedures for addressing ongoing postmarket safety issues identified by the Office of Surveillance and Epidemiology; and annually review the backlog of postmarket safety commitments, report to Congress, and set relevant dates.

Finally, FDAAA prohibits the use in food of certain drugs or biological products, and prohibits the Secretary from delaying the review of generic drug applications on the basis of certain citizen petitions . P.L. 110-316 amended the FDAAA provision, adding the requirement that consideration of petitions be separate and apart from review and approval of any application.

Title X. Food Safety

Title X of FDAAA, entitled Food Safety, contains provisions designed to enhance FDA's authority and responsibilities to ensure the safety of the food supply. These were added to FDAAA after several widely reported outbreaks of food-borne illness that affected hundreds of individuals. In response, many members of Congress expressed concern about both domestic and imported food products and whether the current food safety system is adequate for handling the current globalized food supply.

As enacted, FDAAA requires the Secretary to establish processing and ingredient standards, update labeling requirements for pet food, and establish an early warning and surveillance system to identify adulteration and outbreaks of illness associated with pet food. The Secretary is to work with states to improve the safety of produce and strengthen state food safety programs. The Act requires the creation of a registry for reportable information on foods (including human and animal products) with safety problems that allows for the identification of the supply chain of the reportable food. Alerts are to be issued for such foods, with records maintained and available for inspection. Additional provisions require attention to aquaculture and seafood inspection, environmental risks associated with genetically engineered seafood products, imported foods, pesticide monitoring and ginseng dietary supplements.

Title XI. Other Provisions

Title XI of FDAAA, entitled Other Provisions , contains provisions relating to a number of topics. It is divided into two subtitles. Subtitle A—In General covers a range of topics: FDA employee publications, tropical disease treatments, genetic tests, NIH, and severability of FDAAA. Subtitle B—Antibiotic Access and Innovation focuses solely on that issue. Both are discussed below.

Subtitle A. In General

The first topic addressed in Subtitle A is agency clearance of employee scientific publications. The Secretary is required to establish and make publicly available clear written policies to implement the publication provisions. For FDA officers or employees who are directed by policy to obtain agency review or clearance prior to their work's publication or presentation, FDAAA provides a timeline for such review or clearance. Nothing in the policy is to be construed as affecting any restrictions on publication or presentation provided by other law.

The second topic addressed in Subtitle A is the introduction of a priority review voucher as an incentive to develop medical products that treat tropical diseases. Qualifying diseases are those listed in the law, and any other infectious disease the Secretary designates by regulation. Diseases designated by regulation must disproportionately affect poor and marginalized populations, and must have treatments with no significant market in developed nations. The FDAAA provision adds a new use to the older FDA priority review mechanism. Rather than (or in addition to) providing the possible financial benefit of priority review to a sponsor for its tropical disease product application, FDAAA directs FDA to reward that sponsor for developing that product by giving it a priority review voucher that it can use for any one proposed subsequent product that would not otherwise qualify for priority review. The new provision further alters FDA's priority review mechanism by allowing the tropical disease product sponsor to transfer the voucher, including by sale, to another entity. The Secretary is to establish a user fee program and set the fee amounts for sponsors of human drug applications that are the subject of a priority review voucher.

The third topic addressed is the regulation of genetic testing. FDAAA requires that, if the specified Secretary's Advisory Committee does not complete and submit its report and recommendations regarding regulation and oversight of genetic testing to the Secretary by July 2008, the Secretary is to enter into a contract with the IOM to conduct a study and issue a report on the topic.

The fourth topic consists of technical amendments to sections of the PHSA (42 USC 201 et seq.), making five changes. Though the section is titled "NIH Technical Amendments," the first provision does not apply to NIH, but is rather a correction to P.L. 109-417 , the Pandemic and All-Hazards Preparedness Act, and applies to the hospital preparedness program administered by the HHS Assistant Secretary for Preparedness and Response. The provision amends PHSA Section 319C-2 to make appropriate reference to the applicable funding formula for hospital preparedness and surge capacity grants. The second provision adds minority health disparities to the types of data that the NIH Director is to assemble to assess research priorities. The third provision adds postdoctoral training funded through research grants to the list of research activities that the NIH Director is required to catalog in a biennial report to Congress. The fourth provision designates PHSA 403C (relating to the drug diethylstilbestrol) as 403D. The fifth provision specifies that each institution that receives an NIH award for training graduate students under its subchapter (PHSA, Title IV, Part A) need only report to NIH information regarding postdoctoral training funded through research grants, and not each degree-granting program at the institution. It further indicates that leaves of absence are to be subtracted when calculating the average time between graduate study and receipt of a doctoral degree.

The fifth topic addressed is severability. It directs that if any provision of FDAAA is found to be unconstitutional, the remainder of the Act shall remain in effect.

Subtitle B. Antibiotic Access and Innovation

FDAAA addresses antibiotic access and innovation by amending both the FFDCA and the PHSA. It also requires a GAO report assessing the effect of these provisions.

Under separate sections of the FFDCA, FDA both regulates antibiotics and provides incentives for the development of orphan drugs. FDAAA links those approaches by amending the Orphan Drug Act to require the Commissioner to consider (including convening a public meeting) which serious and life-threatening infectious diseases might be designated as rare diseases. If appropriate, the Secretary, by issuing new guidance, could designate product development activities for those diseases as qualifying for grants and contracts under the Orphan Drug Act. FDAAA also extends the Secretary's authority to issue grants and contracts for orphan drug development, and authorizes the appropriation of $30 million for each of FY2008 through FY2012.

FDAAA also adds a new subsection to FFDCA that allows a sponsor to consider as the same active ingredient a specific kind of chemical variant (a non-racemic drug) of an ingredient in an approved (racemic) drug. In addition, a separate provision of the law amends the PHSA to require the Secretary, through the Commissioner, to make publicly available clinically susceptible concentrations of bacteria (amounts that characterize the level of bacterial susceptibility and resistance to a drug).

Appendix A. Authorized Appropriations

Appendix B. Action Items with Deadlines for Government Officials

The following chart contains a listing of FDAAA action items with deadlines for government officials. It is broken down by FDAAA title. Within each title, action items are listed by deadline. More detailed information regarding each of the items in the chart is available in the section of this report that corresponds to the title in which it is listed.

The following notes may be helpful to the reader. First, the chart includes federal agency personnel deadlines with specific dates only. It does not list deadlines for action by non-governmental personnel, though FDAAA includes many of these. Neither does it list required actions for federal agency personnel that have no specific deadlines, though FDAAA contains many of these as well. Second, for user ease, the title of the person required to take action is bolded. Third, for items that require action at regular intervals (such as annual reports), only the initial item is listed by date. The requirement for recurrence is specified in the text.

Appendix C. Authorities with Sunset Dates

Appendix D. Alphabetical List of Acronyms