FDA User Fees and the Regulation of Drugs, Biologics, and Devices: Comparative Analysis of S. 3187 and H.R. 5651
Released: 2012-06-26T00:00:00

Summary:
UPDATE: On June 18, 2012, the Senate Committee on Health, Education, Labor, and Pensions and the House Committee on Energy and Commerce distributed the text of an agreement that combined provisions of S. 3187 [ES], as passed by the Senate on May 24, 2012, and H.R. 5651 [EH], as passed by the House on May 30, 2012. The full House passed the new version by voice vote under suspension of the rules on June 20, 2012. On June 25, 2012, the Senate voted for cloture to limit debate on that bill, S. 3187 [EAH], the Food and Drug Administration Safety and Innovation Act of 2012 [hereinafter referred to as "the agreement"]. The Senate is expected to vote on the agreement sometime the week of June 25, 2012. For information on selected features of the agreement, see the Introduction of this report.
The Senate Committee on Health, Education, Labor, and Pensions and the House Committee on Energy and Commerce have worked for more than a year developing Food and Drug Administration (FDA)-related legislation, versions of which both chambers passed in the last week of May 2012. S. 3187 (the Food and Drug Administration Safety and Innovation Act) and H.R. 5651 (the Food and Drug Administration Reform Act of 2012) each include provisions that would affect the regulation of human drugs, biological products, and medical devices, along with several agency-wide administrative or miscellaneous items. Majority and minority committee leaders have expressed the desire to get a completed bill to the President before July 4, 2012.
The impetus to the timing of these bills is that current authority for FDA to collect fees under the Prescription Drug User Fee Amendments (PDUFA) of 2007 and the Medical Device User Fee Amendments (MDUFA) of 2007 will expire on October 1, 2012, unless reauthorizing legislation is enacted before then. Member statements at committee hearings indicated no opposition to reauthorization and very little comment about changes to the current user fee programs. Because Members of Congress generally consider the user fee reauthorizations to be must-pass legislation—for example, the user fee revenue accounts for more than half of the agency's human drug program budget—they have used these bills as vehicles for numerous additional measures.
The introduction to this report highlights selected features of S. 3187 [EAH], the agreement, relative to S. 3187 [ES] and H.R. 5651 [EH]. The remainder of this report provides, in a series of 14 tables, comparisons of the provisions in S. 3187 [ES] and H.R. 5651 [EH], presented generally in the order in which they appear in the Senate bill, the first to be reported by committee. Each table addresses a broad topic (e.g., human device regulation) and is preceded by narrative discussing the policy and legislative context of the table's provisions.

subsections: section_title: Introduction
paragraphs: The Senate and the House have each passed bills whose provisions would affect a broad range of Food and Drug Administration (FDA) activities regarding drugs, biological products, and medical devices: S. 3187 , the Food and Drug Administration Safety and Innovation Act, passed on May 24, 2012; and H.R. 5651 , the Food and Drug Administration Reform Act of 2012, passed on May 30, 2012. The timing of these bills coincides with the October 1, 2012 expiration of FDA's authority under current law to collect fees under the Prescription Drug User Fee Amendments (PDUFA) of 2007 and the Medical Device User Fee Amendments (MDUFA) of 2007. Because revenue from those fees supports over 2,000 full-time equivalent FDA positions and accounts for more than half of the agency's drug and device review resources, Members of Congress have referred to the user fee reauthorizations as generally uncontroversial, must-pass legislation. The Senate Committee on Health, Education, Labor, and Pensions and the House Committee on Energy and Commerce have, in addition to developing legislation that would reauthorize the drug and device user fees, crafted additional titles that would create new user fee authority for generic drugs and biosimilar biological products, permanently authorize programs to encourage or require studies of drugs for pediatric use, medical device regulation, drug regulation, and several areas, such as advisory committee conflict of interest, that cut across FDA product areas. Congress had also made user fee authorizing legislation in 2007 a vehicle for addressing other FDA-related issues.
This report provides a legislative analysis of the provisions in S. 3187 and H.R. 5651 , including brief summaries of relevant provisions in current law, mostly the Federal Food, Drug, and Cosmetic Act (FFDCA). Current law descriptions generally relate only to provisions that the bills would change; the current law column, therefore, does not always provide a complete description of the relevant law. Material is grouped by broad topics and presented in the general order of sections in the Senate bill, the first to be reported out of committee. The report begins each topic with a discussion of the overall issue to set the policy or legislative context of the bills' provisions and then uses a table to present the comparison of the bills and current law.
In Tables 1 through 4, which describe the legislative language for four user fee programs, the Senate and House descriptions are merged in one column because of their substantive similarity (the few differences are noted). Tables 3, 4, and 11 address new provisions and do not, therefore, have current law columns. The remaining tables have three columns: current law, S. 3187 , and H.R. 5651 . In each table, the rows generally follow the order of provisions in the Senate bill, with comparable House provisions, if any, described in the relevant Senate rows. House provisions without comparable Senate provisions are then presented in the order they appear in the House bill.
The following grid lists the tables that follow in this report; it also lists the section numbers of S. 3187 (as passed) and H.R. 5651 (as passed) covered in each table.
This report is one in a suite of CRS products that provide detailed background and analysis of FDA-related issues. For further information on many of the issues that Members and panelists raised in the committee hearings leading up to these bills (including drug approval, development incentives, device regulation, pediatric drugs, and user fees), see the CRS website (the Medical Product Regulation listings at http://www.crs.gov/pages/subissue.aspx?cliid=2678 ) or contact [author name scrubbed], Specialist in Drug Safety and Effectiveness, or one of the other authors of this report.
section_title: User Fee Acts
paragraphs: Titles I through IV of both the Senate and House bills would authorize FDA to collect user fees and direct the revenue to fund specified activities relating to prescription drugs, medical devices, generic drugs, and biosimilar biological products. The first two are reauthorizations of current programs; the second two would authorize new user fee programs.
With the Prescription Drug User Fee Act in 1992, Congress authorized FDA to collect user fees from the manufacturers of brand-name prescription drugs and biological products and to use the revenue for specified activities. PDUFA became possible when FDA, industry, and Congress agreed on two concepts: (1) performance goals —FDA would commit to performance goals it would negotiate with industry that set target completion times for various review processes; and (2) use of fees —the revenue from prescription drug user fees would be used only for activities to support the review of human drug applications and would supplement—rather than replace—funding that Congress appropriated to FDA. The added resources from user fees allowed FDA to increase staff to review what was then a backlog of new drug applications and to reduce application review times. Over the years, Congress has added similar authority regarding medical devices and animal drugs. User fees make up 35% of the FY2012 FDA budget. Their contribution to FDA's human drug program is larger at 51%.
Following the precedent set by PDUFA, all the user fee programs addressed in this legislation include both (1) legislation and (2) performance goals agreements developed with representatives of the regulated industry in consultation with representatives of patients and advocates, academic and science experts, and congressional committees.
subsections: section_title: Prescription Drug User Fee Reauthorization5
paragraphs: FDA may use the revenue from PDUFA fees to support "the process for the review of human drug applications." With each reauthorization of PDUFA, Congress has expanded the range of activities included in that phrase. The prescription drug user fee program covers new drugs whose sponsors are the first to apply for marketing approval (excluding, therefore, generic drugs) and new biological products (excluding, therefore, the new category of biosimilar biological projects).
Material in Table 1 refers to changes that S. 3187 (as passed) and H.R. 5651 (as passed) would make to current law. Unless otherwise noted, the PDUFA provisions in S. 3187 , H.R. 5651 , and the HHS-proposed legislative language are substantively the same. For a more complete description of current law and discussion of issues relating to the Prescription Drug User Fee Act, see CRS Report R42366, Prescription Drug User Fee Act (PDUFA): Issues for Reauthorization (PDUFA V) in 2012 , by [author name scrubbed].
section_title: Medical Device User Fee Reauthorization7
paragraphs: Congress gave FDA the authority to collect fees from the medical device industry in 2002. User fees and direct appropriations from Congress fund review of medical devices by the FDA. Medical devices are a wide range of products that are used to diagnose, treat, monitor, or prevent a disease or condition in a patient. For many medical devices, FDA approval or clearance must be obtained prior to marketing in the United States. The purpose of user fees is to support the FDA's medical device premarket review program and to help reduce the time it takes the agency to review and make decisions on marketing applications. The user fee law provides revenue for FDA; in conjunction, the agency negotiates with industry to set performance goals for the premarket review of medical devices. The medical device user fee program was modeled after PDUFA program.
 Table 2 refers to changes in current law that would be made by Sections 202 and 203 of S. 3187 (as passed), and Sections 202 and 203 of H.R. 5651 (as passed). The language in these sections of the two bills is virtually identical. For a more complete description of the MDUFA program see CRS Report R42508, The FDA Medical Device User Fee Program , by [author name scrubbed].
section_title: Generic Drug User Fee Authorization9
paragraphs: Material in Table 3 refers to the legislation that would authorize the collection and use of generic drug user fees. The Generic Drug User Fee Amendments (GDUFA) titles in S. 3187 (as passed) and H.R. 5651 (as passed) would create new FFDCA sections 744A, B, C and are patterned after PDUFA, which was first enacted in 1992 and reauthorized in five-year increments. GDUFA would become effective October 1, 2012, or upon enactment, and would sunset on October 1, 2017. Unless otherwise noted, the GDUFA provisions in S. 3187 , H.R. 5651 , and the HHS-proposed legislative language are substantively the same.
Integral to the operation of the generic drug user program are the performance goals stated in the FDA-industry agreement that the HHS Secretary submitted to Congress along with proposed legislative language. For a description of that agreement and a discussion of issues relating the proposed Generic Drug User Fee Amendments of 2012, see CRS Report R42540, Proposed FDA User Fee Acts: Generic Drug User Fee Amendments of 2012 (GDUFA) and Biosimilar User Fee Act of 2012 (BSUFA) , by [author name scrubbed] and [author name scrubbed].
section_title: Biosimilar User Fee Authorization10
paragraphs: A biosimilar is a biological product that is highly similar to a brand-name (innovator) biological product made by a pharmaceutical or biotechnology company. A biological product, or biologic, is a preparation, such as a drug or a vaccine, that is made from living organisms. In contrast to the relatively simple structure and manufacture of chemical drugs, biosimilars, with their more complex nature and method of manufacture, will not be identical to the brand-name product, but may instead be shown to be highly similar.
The biotechnology industry began developing its first biologics for use as human therapeutic agents in the late 1970s and early 1980s. Biotechnology products are expected to become a larger share of the drugs sold by the pharmaceutical industry to U.S. consumers. However, with no parallel to the generic alternatives for chemical drugs, the cost of therapeutic biologics is often prohibitively high for individual patients.
Biological products are, in general, regulated—licensed for marketing—under the Public Health Service Act (PHSA), and chemical drugs are regulated—approved for marketing—under the Federal Food, Drug, and Cosmetic Act (FFDCA). The Drug Price Competition and Patent Term Restoration Act of 1984 ( P.L. 98-417 ), often referred to as the Hatch-Waxman Act, provided a mechanism for the approval of generic drugs under the FFDCA but not under the PHSA.
The Biologics Price Competition and Innovation Act of 2009 (BPCIA), enacted as Title VII of the Patient Protection and Affordable Care Act (ACA; P.L. 111-148 ), established a new regulatory authority within the FDA by creating a licensure pathway for biosimilars analogous to that which allowed for the approval of generic chemical drugs via the Hatch-Waxman Act. Under the new pathway, a biosimilar may be approved by demonstrating that it is highly similar to a biological product that is already allowed on the market by FDA. The BPCIA also authorized FDA to collect associated user fees.
The proposed Biosimilar User Fee Act (BSUFA) would require the collection of six types of fees from industry. Fee amounts would be based on inflation-adjusted PDUFA fee amounts for each fiscal year. Because there are no currently marketed biosimilar biological products, the proposal includes fees for products in the development phase to generate fee revenue for the new program and to enable companies to have meetings with FDA in the early development of biosimilar biological products. A company may chose to discontinue participation in the biosimilar biological product development program but must pay a reactivation fee to resume further product development with FDA.
The proposed legislative language would allow for the waiver of the biosimilar biological product application fee for the first such application from a small business. A "small business" is as an entity with fewer than 500 employees, including affiliates, that does not have a drug product that has been approved under a human drug or biosimilar biological application and introduced or delivered for introduction into commerce. The biosimilars user fee authority would cease to be effective October 1, 2017. For further information, see CRS Report R42540, Proposed FDA User Fee Acts: Generic Drug User Fee Amendments of 2012 (GDUFA) and Biosimilar User Fee Act of 2012 (BSUFA) , by [author name scrubbed] and [author name scrubbed].
 Table 4 refers to changes that would be made by sections 402 and 403 of S. 3187 (as passed) and sections 402 and 403 of H.R. 5651 (as passed); the language in the two bills is identical and differs from the HHS proposal in only minor technical details. These changes would add new sections 744G, 744H and 744I to the FFDCA.
section_title: Pediatric Medical Products13
paragraphs: Drug manufacturers may be reluctant to test drugs and medical devices in children because of economic, ethical, legal, and other obstacles. Market forces alone do not provide sufficient incentives to overcome these obstacles. The Best Pharmaceuticals for Children Act (BPCA, P.L. 107-109 ) and the Pediatric Research Equity Act (PREA, P.L. 108-155 ) offer drug manufacturers financial and regulatory incentives to test their products for use in children. The Pediatric Medical Device Safety and Improvement Act of 2007 (PMDSIA, P.L. 110-85) creates reporting requirements for pediatric medical devices, incentives for manufacturers to create pediatric medical devices, and gives the FDA the authority to require postmarket studies of approved pediatric devices to ensure their continued efficacy and safety.
BPCA and PREA, passed by Congress in 2002 and 2003 and subsequently reauthorized in 2007, represent Congress' attempt to address the need for pediatric testing. BPCA created an incentive (extended market exclusivity) for manufacturers to conduct studies on pediatric use, and PREA created a requirement for manufacturers to test the safety and effectiveness of their products in pediatric populations. BPCA sunsets on October 1, 2012, and current law authorizes PREA only as long as BPCA is in effect.
Extended marketing exclusivity may be an attractive incentive to a manufacturer with a product that is being sold under patent or other types of exclusivity protections. BPCA also includes provisions to refer pediatric studies of off-patent products, which no longer have market exclusivity, to the National Institutes of Health (NIH), and manufacturer-declined studies of on-patent products to the Foundation for the NIH (FNIH).
BPCA and PREA studies result in information on new dosing, new indications of use, new safety information, and new data on effectiveness that inform labeling changes for pediatric dosing, warnings, and instructions on how to prepare formulations for pediatric populations. Although BPCA and PREA were developed separately, they are usually discussed in tandem. Their 2007 reauthorizations were paired in both committee hearings and legislative vehicle.
Both S. 3187 and H.R. 2516 would permanently authorize BPCA and PREA. They each would also amend or add provisions in current law. Provisions in these bills are compared with each other and to current law in Table 5 .
section_title: Human Medical Device Regulation16
paragraphs: Medical devices include a wide range of products that are used to diagnose, treat, monitor, or prevent a disease or condition in a patient. Medical devices are broadly integrated into health care, and include simple devices, such as tongue depressors, as well as more complex devices, such as implantable hips. The extent of FDA authority to regulate whether a device may be marketed in the United States and how it is monitored afterward varies across types of devices.
In order to determine the applicability of premarket requirements (i.e., clearance or approval before marketing) for a given device, FDA classifies the device based on the risk to the patient: (1) low-risk devices are Class I; (2) moderate-risk are Class II; and (3) high-risk are Class III. Low-risk medical devices (Class I) and a very small number of moderate-risk medical devices (Class II) are exempt from premarket review. In general, for moderate-risk and high-risk medical devices, there are two pathways that manufacturers can use to bring such devices to market with FDA's permission: (1) premarket approval (PMA) and (2) premarket notification submission (also known as a 510(k) submission, after the section in the FFDCA that authorized this type of notification). According to a 2009 GAO report, of the more than 50,000 devices that were listed by manufacturers with FDA from FY2003 through FY2007, about 67% were exempt from premarket review; the remainder entered the market via the 510(k) process (31%), the PMA process (1%) or via other means, such as humanitarian use devices.
Once a device is on the market, FDA has authority to carry out certain activities to monitor their safety and effectiveness. The extent of the agency's postmarket authority is tied to characteristics of the device. Manufacturer requirements include areas such as labeling, postmarket surveillance, device tracking, and adverse event reporting.
Provisions in the House and Senate passed bills both would make modifications to various aspects of premarket and postmarket device regulation. Premarket modifications include those intended to: (1) streamline the de novo 510(k) for novel devices; (2) affect the efficiency, transparency, and data requirements of the 510(k) and PMA processes; and (3) alter or make clarifications to certain types of exempt devices, for example, custom devices and humanitarian use devices. With respect to postmarket regulation, provisions focus on expanding active postmarket surveillance; altering requirements related to postmarket studies for devices; and strengthening both device recall and tracking capabilities through a recall program and the unique device identifier system. Miscellaneous reforms include those aimed at increasing transparency of FDA's approval and clearance decisions and processes for issuing industry guidance documents; improving health information technology for the agency; and harmonizing device regulation with FDA's international counterparts. Medical device related provisions are presented in Table 6 , in the order in which they appear in the Senate bill.
section_title: Human Drug Regulation
paragraphs: A key FDA responsibility is to regulate the safety and effectiveness of drugs sold in the United States. FDA divides that responsibility into two phases: preapproval (premarket) and postapproval (postmarket). FDA reviews manufacturers' applications to market drugs in the United States; a drug may not be sold unless it has FDA approval. The agency continues its oversight of drug safety and effectiveness as long as the drug is on the market. For an overview of FDA's responsibility in many of these areas, see CRS Report R41983, How FDA Approves Drugs and Regulates Their Safety and Effectiveness , by [author name scrubbed].
Beginning with the Food and Drugs Act of 1906, Congress has incrementally refined and expanded FDA's responsibilities regarding drug approval and regulation. Members of the 112 th Congress have suggested that FDA take additional efforts across the lifespan of its drug products. Provisions that either the Senate or House have passed cluster around encouraging product development, expediting application and review processes, attending to product integrity, preventing and mitigating drug shortages, and regulating medical gases. This report continues with each of those clusters, in the order they appear in the Senate bill. The drug regulation section ends with a cluster of individual provisions that, although labeled miscellaneous, each target an area of congressional concern and potential FDA responsibility.
subsections: section_title: Pharmaceutical Supply Chain19
paragraphs: FDA's earliest authorities, in 1906, concerned product integrity: Did the label accurately indicate the powdered and liquid ingredients in a bottle of elixir? Changes in the law reflected the mid-century pharmaceutical industry with mostly domestic factories. As drug production has shifted to a global chain of manufacturers, processers, packagers, importers, and distributors, FDA leadership, among others, has suggested that the agency's statutory tools do not match its responsibilities. The agency, manufacturers, wholesalers, pharmacists, and consumers have suggested solutions to Congress. Some of those are formed as provisions in the Senate- and House-passed bills, as described in Table 7 . Members continue discussions about chain-of-custody documentation, track-and-trace technologies and requirements, and anti-counterfeiting technology and enforcement tools, attempting to find an effective and feasible mix that covers domestic and foreign facilities.
section_title: Incentives for Anti-Infective Drugs21
paragraphs: The treatment of infectious diseases often depends on the availability of anti-infective drugs. Approved drugs can become ineffective if infectious organisms develop resistance to them. However, development of new anti-infective drugs is not always attractive to sponsors; the drugs are often used short-term and/or in small numbers of patients, compared with so-called "blockbuster" drugs. In addition, some drug companies cite unique regulatory challenges in the approval of anti-infective drugs.
S. 3187 and H.R. 5651 propose to offer incentives for the development of certain new anti-infective drugs by providing an extended period of exclusivity, i.e., a period in which the new drug may be marketed without generic competition. The bills stipulate the types of new anti-infective drugs that would qualify for incentives. These provisions, summarized and compared in Table 8 , are modified from the freestanding Generating Antibiotic Incentives Now Act of 2011 (GAIN Act), S. 1734 / H.R. 2182 .
Among other differences between the bills, the Senate bill limits eligible products to those that would be used to treat serious or life-threatening infections, while the House bill would offer such incentives to any type of anti-infective drug that would otherwise qualify. Members of Congress disagree on which approach would be more effective in spurring the development of new drugs to treat serious infections.
section_title: Expedited Drug Development and Review Processes23
paragraphs: Before a drug may be sold in the United States, the Food and Drug Administration (FDA) must approve an application from its manufacturer. The progression to drug approval begins before FDA involvement with, first, basic scientists work in the laboratory and with animals, and, second, a drug or biotechnology company develops a prototype drug. That company must seek and receive FDA approval, by way of an investigational new drug (IND) application, to test the product with human subjects. Those tests, called clinical trials, are carried out sequentially in Phase I, II, and III studies, which involve increasing numbers of subjects. The manufacturer then compiles the resulting data and analysis in a new drug application (NDA). FDA reviews the NDA with three major concerns: (1) safety and effectiveness in the drug's proposed use; (2) appropriateness of the proposed labeling; and (3) adequacy of manufacturing methods to assure the drug's identify, strength, quality, and identity. The Federal Food, Drug, and Cosmetic Act (FFDCA) and associated regulations detail the requirements at each step. Not all reviews and applications follow the standard procedures.
In certain circumstances, FDA regularly uses three formal mechanisms to expedite the development and review process. For a drug for a serious or life-threatening condition, accelerated approval and animal efficacy approval processes—provided for in regulations—change what is needed in an application when a drug or biological product may provide a meaningful therapeutic benefit over existing treatments. A fast track product designation —provided for in law—affects the timing and smoothness of the application process for a drug with the potential to address an unmet medical need. Priority review —based in FDA procedures—affects the timing of the review, not the process leading to submission of an application, when FDA determines a drug would address an unmet need.
Provisions in S. 3187 and H.R. 5651 would amend the FFDCA to "help expedite the development and availability to patients of treatments for serious or life-threatening diseases or conditions while maintaining safety and effectiveness standards." They would do so by combining elements of the regulatory accelerated approval process and the statutory fast track product designation, and creating a new designation— breakthrough therapy —for a drug whose preliminary clinical data suggest a possible substantial improvement over existing therapies. Table 9 describes the Senate and House provisions arrayed generally in relation to current law. Although the provisions all are meant to bring needed drugs to consumers sooner than they would get there otherwise, they focus on different elements of the overall process. One element is the product. Some provisions identify characteristics of the drug, the patient group, or the disease that would make a drug eligible for a designation: a fast track product or a breakthrough therapy. A second element is the interaction between FDA and the drug developer or manufacturer. Some provisions would create administrative processes that could make the development go more smoothly. A third element is the criteria used in assessing evidence of safety and effectiveness. Some provisions would allow different uses of surrogate outcome measures or look to newer scientific methods and tools to better predict clinical benefits. Both bills also include reporting, guidance, and evaluation provisions.
section_title: Drug Shortages30
paragraphs: Since 2005, FDA, clinicians, pharmacists, and patients have noted more frequent drug shortages—when the local or nationwide supply of a particular dosage is inadequate to meet demand. Recent shortages have clustered around generic sterile injectable drugs used during surgery or hospital care, although shortages have affected brand-name products and oral tablets for a wide range of diseases and conditions.
Immediate causes of shortages include: (1) manufacturing quality problems (such as contaminants); (2) interruption in supply of ingredients; (3) unanticipated increase in demand (e.g., the unavailability of another product for the same condition, recent attention to an off-label use, or approval of an additional indication or user population); (4) business decisions by individual firms (e.g., to cut back on the number of facilities dedicated to a particular drug, or to shut down during renovation); and (5) unanticipated weather, accident, or other event. Less clear is why the rate of shortages (or public awareness of them) is increasing now.
Market concentration and a global supply chain, along with manufacturing capacity constraints, the complex process of drug production, inventory practices, and pricing, act as underlying causes, many believe, of drug shortages. Many of sterile injectable drugs are made by few producers in specialized facilities. For example, when one of two manufacturing facilities goes off-line for any reason, the remaining facility may be able to meet the total demand for a while, but not indefinitely. Patterns of practice in the drug distribution industry, such as just-in-time inventories, leave little back-up capacity from warehouses.
It is not always feasible for other manufacturers to add production capacity to ease a shortage. First, it takes time to construct new facilities. Second, FDA must approve the manufacturing process and recordkeeping along with product specifications. Third, a manufacturer must decide to use the new or existing facility for the drug in shortage rather than for another product that may yield greater profit or better fit within the company's business plan.
FDA has acted within its current authority by asking both sole source and other firms to increase production, exercising flexibility through regulatory discretion (e.g., allowing the importation), expediting review, and communicating with the Drug Enforcement Administration (DEA) about quotas of controlled substances. An Executive Order directed FDA to use all tools to require that manufacturers give advance notice of manufacturing interruptions, to expedite applications, and to work with the Department of Justice (DOJ) to address instances of price gouging, for example, when pharmacies turn to supplies outside their routine distribution channels. FDA and GAO analyses suggested immediate steps to increase notification, increase staffing, develop legislation to require notification, and communicate with the public and within FDA. They suggested longer term steps such as using databases to identify factors that help prevent or mitigate shortages, identifying manufacturing quality issues and having backup plans, using sentinel reports from providers to identify imminent shortages, and encouraging wholesaler transparency. Others have suggested requiring pedigrees and data systems to both track the availability and verify the legitimacy of shipments; and providing incentives to manufacturers. Some have suggested that reimbursement and purchasing policies—for Medicare, Medicaid, other public programs—as well as the interplay of pharmaceutical and medical care billing for injectable oncology drugs may contribute to drug shortages; these possibly reasonable theories have not yet been empirically demonstrated.
Most pending legislation in the 112 th Congress has focused on notification requirements, although at least one Member is developing a plan that could involve Medicare and Medicaid payment policies. The provisions in S. 3187 , as passed in the Senate, focus on expanding the scope of the notification requirements, authorizing expedited inspections and review, and requiring information collection and use, along with studies of the causes and extent of shortages. H.R. 5651 provisions, as passed by the House, focus on notification, a drug shortage list with reasons and estimated duration as determined by the Secretary, coordination with the Attorney General regarding production quotas, and Attorney General actions and report. These provisions are summarized and compared in Table 10 .
section_title: Medical Gas Regulation38
paragraphs: Although medical gases are considered to be prescription drugs under the FFDCA, FDA has exercised regulatory discretion in not requiring new drug applications or imposing user fees on companies. FDA oversees medical gases through current good manufacturing practice (CGMP) regulations (21 CFR parts 210 and 211) and guidance. Medical gas manufacturers sought an approval pathway in law to avoid certain trade and other problems associated with their products being considered "unapproved." Both the Senate and House bills propose a means for the Secretary to approve medical gases that meet requirements through a certification process, which would not confer market exclusivity or require the payment of user fees. The applicable provisions are summarized in Table 11 .
section_title: Miscellaneous Provisions Regarding Human Drug Regulation40
paragraphs: The following additional drug-related provisions are summarized and compared in Table 12 :
Independent assessment of drug approval processes; Drugs for rare diseases; Accessibility of prescription information for the blind and visually impaired; Risk-benefit assessment framework for new drug applications (NDAs); National Academies study on medical innovation inducement; Reauthorization of grants and contracts for development of orphan drugs; Reporting of demographic subgroups in clinical trials data; Reauthorization of exclusivity for single-enantiomer drugs; Prescription drug abuse; Risk evaluation and mitigation strategies (REMS) and drug access for development; Extension of period before forfeiting marketing exclusivity for an ANDA; FDA actions and deadlines on petitions; and Assessment and modification of approved REMS.
section_title: Advisory Committees41
paragraphs: Currently, the Secretary is required to consider potential conflicts of interest in appointing persons to FDA advisory committees. The Secretary must "review the expertise of the individual and the financial disclosure report filed by the individual pursuant to the Ethics in Government Act of 1978 … so as to reduce the likelihood that an appointed individual will later require" one of two written waivers under the criminal financial conflict of interest statute, or a waiver under FDA's conflict of interest waiver provision, in order to serve at advisory committee meetings.
Under the criminal financial conflict of interest statute, advisory committee members (whether they are special or regular government employees) are prohibited from participating "personally and substantially … through decision, approval, disapproval, recommendation, the rendering of advice … or otherwise" if they have a financial interest. Advisory committee members are also prohibited from participating if any of the following have a financial interest: the member's spouse; minor child; general partner; organization in which the member serves as an officer, director, trustee, general partner or employee; or any person or organization with whom he is negotiating or has any arrangement concerning prospective employment.
However, the criminal financial conflict of interest statute has several waiver provisions. The first of two specifically referenced in FFDCA Sec. 712 allows for a waiver if the advisory committee member fully discloses the financial interest and the official who appoints the member makes a written determination, in advance, that the financial "interest is not so substantial as to be deemed likely to affect the integrity of the services which the Government may expect from such officer or employee." The second wavier allows the official responsible for the advisory committee member's appointment, after reviewing the financial disclosure report, to make a written certification "that the need for the individual's services outweighs the potential for a conflict of interest created by the financial interest involved."
The FFDCA has its own, additional prohibition and waiver for conflicts of interest. Under the current FFDCA Sec. 712(c)(2)(A), any member of an advisory committee would be prohibited from participating in any "particular matter" in an advisory committee meeting in which such member, or an immediate family member of such member, has a "financial interest that could be affected by the advice given to the Secretary with respect to such matter." The HHS Secretary retains the right to grant a waiver to any member of such advisory panel to participate in "a particular matter considered in a committee meeting," either as a voting or non-voting member of the advisory committee, when the Secretary determines that "it is necessary to afford the advisory committee essential expertise."
Provisions in S. 3187 and H.R. 5651 regarding advisory committee conflicts of interest are summarized and compared with current law and with each other in Table 13 .
section_title: Administrative Reforms and Miscellaneous Topics52
paragraphs: A number of additional provisions in the two bills are summarized and compared in Table 14 . These provisions are:
Reauthorization of the Critical Path Public-Private Partnerships; Guidance regarding Internet promotion of medical products; Electronic submission of applications; Tanning bed labeling; Global clinical trials; Regulatory science; Information technology; Reporting requirements for medical products covered by user fee agreements; Strategic integrated management plan for FDA workforce; Patient participation in medical product discussions; Nanomaterials in FDA-regulated products; GAO report regarding online pharmacies; Medication and device errors; Statutory Pay-As-You-Go statement; Communicating drug information, including to underrepresented subgroups; Report on small businesses; Whistleblower protection, U.S. Public Health Service; Clinical trial registration; Compliance date for over-the-counter sunscreen products; Changes to the Controlled Substances Act (CSA); and Prescription drug monitoring programs.
section_title: Next Steps
paragraphs: The Senate voted 96-1 to pass S. 3187 on May 24, 2012. The House voted 387-5 to pass H.R. 5651 on May 30, 2012. PDUFA and MDUFA sunset on October 1, 2012 and committee bipartisan leadership has been committed to completing the reauthorizations before FDA would have to initiate lay-off notification procedures that would disrupt drug and device application review and postmarket safety activities. FDA-focused newsletters and the national media report that "ping-pong" negotiations, rather than a formal conference committee, are underway between House and Senate staff and Members to resolve the differences between the bills.
Despite a successful bipartisan effort to build a core set of drug and device provisions that could join, but not derail, must-pass user fee provisions, there remain complex issues that Members of Congress will likely pursue after a final bill is passed out of S. 3187 and H.R. 5651 . These include changing the premarket approval and clearance procedures for medical devices, further developing a supply chain system that meets global demands, and looking at whether federal health program drug payment policies influence drug shortages. Whether Congress needs a must-pass vehicle, next facing FDA in 2017, to achieve these legislative changes remains to be seen.
subsections: section_title: Appendix. Acronyms