The 21st Century Cures Act (Division A of P.L. 114-255)
Congressional research reportDec 23, 2016
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The 21st Century Cures Act (Division A of
P.L. 114-255)
Amanda K. Sarata, Coordinator
Specialist in Health Policy
Updated December 23, 2016
Congressional Research Service
7-....
www.crs.gov
R44720
The 21st Century Cures Act (Division A of P.L. 114-255)
Summary
The 21st Century Cures Act (P.L. 114-255) was signed into law on December 13, 2016, by
President Barack Obama. On November 30, 2016, the House passed the House amendment to the
Senate amendment to H.R. 34, the 21st Century Cures Act, on a vote of 392 to 26. The bill was
then sent to the Senate where it was considered and passed, with only minor technical
modification, on December 7, 2016, on a vote of 94 to 5.
The law consists of three divisions:
Division A—21st Century Cures Act;
Division B—Helping Families in Mental Health Crisis; and
Division C—Increasing Choice, Access, and Quality in Health Care for
Americans.
CRS has published a series of reports on this law, one on each Division. This is the report for
Division A of the law.
This report provides a brief summary of each provision of the 21st Century Cures Act (Division A
of P.L. 114-255), by title, subtitle, and section. The Division includes five titles, as follows: (1)
Innovation projects and state responses to opioid abuse; (2) Discovery; (3) Development; (4)
Delivery; and (5) Savings.
Title I provides funding for biomedical research, including the Precision Medicine Initiative
(PMI) and the Cancer Moonshot Initiative, for the opioid crisis response, and for the Food and
Drug Administration (FDA) to support certain new activities authorized by the law.
Title II, consisting of seven subtitles, requires or authorizes a number of activities to support
biomedical research, including the reauthorization of the National Institutes of Health (NIH) and
the reform of that agency through numerous administrative, reporting, and data access provisions.
The Title includes provisions that support young investigators funded by NIH; pediatric research;
collaborative research such as research on neurological disease; and precision medicine efforts,
and specifically the PMI.
Title III, consisting of ten subtitles, focuses on modifying the drug and device approval pathways
at the FDA to support innovation, and specifically includes provisions that support patientfocused drug development and streamlined and clarified pathways to approval for drugs,
combination products, antimicrobials, Orphan drugs, drugs for rare disease, and regenerative
therapies. This Title also contains provisions making modifications to the medical device
approval pathway and reforms to the FDA’s hiring process. Finally, it addresses FDA’s regulation
of medical countermeasure and vaccine development.
Title IV focuses on health care delivery, and includes provisions that together address the federal
policies to promote the adoption and use of electronic health record (EHR) technology, as well as
a handful of Medicare delivery provisions addressing telehealth services in Medicare, site-ofservice price transparency for certain Medicare services, Local Coverage Determinations (LCDs)
under Medicare, and a technology and pharmaceutical ombudsman for Medicare.
Title V provides savings for the Division, and includes Medicare and Medicaid savings; Patient
Protection and Affordable Care Act (ACA, P.L. 111-148, as amended) savings, including
Prevention and Public Health Fund (PPHF) and territory funding; and savings from the Strategic
Petroleum Reserve (SPR) drawdown.
Congressional Research Service
The 21st Century Cures Act (Division A of P.L. 114-255)
Contents
Introduction ..................................................................................................................................... 1
Title I-Innovation Projects and State Responses to Opioid Abuse .................................................. 2
Section 1001. NIH Innovation Projects .............................................................................. 2
Section 1002. FDA Innovation Projects .............................................................................. 5
Section 1003. Account for the State Response to the Opioid Abuse Crisis ........................ 6
Title II- Discovery ........................................................................................................................... 7
Subtitle A- National Institutes of Health Reauthorization......................................................... 7
Section 2001. National Institutes of Health Reauthorization .............................................. 7
Section 2002. Eureka Prize Competitions........................................................................... 7
Subtitle B- Advancing Precision Medicine ............................................................................... 8
Sections 2011-2014. Precision Medicine Establishment and Data Protections .................. 9
Subtitle C- Supporting Young Emerging Scientists .................................................................. 9
Section 2021. Investing in the Next Generation of Researchers. ........................................ 9
Section 2022. Improvement of Loan Repayment Program. .............................................. 10
Subtitle D- National Institutes of Health Planning and Administration ...................................11
Section 2031. National Institutes of Health Strategic Plan ................................................11
Section 2032. Triennial Reports ........................................................................................ 12
Section 2033. Increasing Accountability at the National Institutes of Health .................. 12
Section 2034. Reducing Administrative Burden for Researchers ..................................... 13
Section 2035. Exemption of the National Institutes of Health from the Paperwork
Reduction Act Requirements. ........................................................................................ 14
Section 2036. High-Risk, High-Reward Research............................................................ 15
Section 2037. National Center for Advancing Translational Sciences. ............................ 16
Section 2038. Collaboration and Coordination to Enhance Research .............................. 17
Section 2039. Enhancing the Rigor and Reproducibility of Scientific Research .............. 18
Section 2040. Improving Medical Rehabilitation Research at the National
Institutes of Health ......................................................................................................... 19
Section 2041.Task Force on Research Specific to Pregnant Women and Lactating
Women ........................................................................................................................... 19
Section 2042. Streamlining National Institutes of Health Reporting Requirements ......... 19
Section 2043. Reimbursement for Research Substances and Living Organisms .............. 20
Section 2044. Sense of the Congress on Increased Inclusion of Underrepresented
Populations in Clinical Trials ......................................................................................... 20
Subtitle E- Advancement of the National Institutes of Health Research and Data
Access .................................................................................................................................. 21
Sections 2051. Technical Updates to Clinical Trials Database ......................................... 21
Section 2052. Compliance Activities Reports................................................................... 21
Section 2053. Updates to Policies to Improve Data .......................................................... 22
Section 2054. Consultation ............................................................................................... 22
Subtitle F- Facilitating Collaborative Research ...................................................................... 23
Section 2061. National Neurological Conditions Surveillance System ............................ 23
Section 2062. Tick-Borne Diseases .................................................................................. 23
Section 2063. Accessing, Sharing, and Using Health Data for Research Purposes .......... 24
Subtitle G- Promoting Pediatric Research .............................................................................. 25
Section 2071. National Pediatric Research Network ........................................................ 25
Section 2072. Global Pediatric Clinical Study Network ................................................... 25
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The 21st Century Cures Act (Division A of P.L. 114-255)
Title III-Development .................................................................................................................... 26
Subtitle A-Patient Focused Drug Development ...................................................................... 26
Sections 3001-3004. Patient Experience Data, Patient-Focused Drug
Development Guidance, Streamlining Patient Input, Report on Patient
Experience Drug Development ...................................................................................... 26
Subtitle B-Advancing New Drug Therapies ........................................................................... 27
Section 3011. Qualification of Drug Development Tools ................................................. 27
Section 3012. Targeted Drugs for Rare Diseases .............................................................. 29
Section 3013. Reauthorization of Program to Encourage Treatments for Rare
Pediatric Diseases .......................................................................................................... 30
Section 3014. GAO Study of Priority Review Voucher Programs ................................... 31
Section 3015. Amendments to the Orphan Drug Grants ................................................... 31
Section 3016. Grants for Studying Continuous Drug Manufacturing ............................... 32
Subtitle C-Modern Trial Design and Evidence Development ................................................. 33
Section 3021. Novel Clinical Trial Designs ...................................................................... 33
Section 3022. Real World Evidence.................................................................................. 33
Sections 3023-3024. Protection of Human Research Subjects, Informed Consent
Waiver or Alteration for Clinical Investigations ............................................................ 34
Subtitle D-Patient Access to Therapies and Information ........................................................ 36
Section 3031. Summary Level Review ............................................................................. 36
Section 3032. Expanded Access Policy ............................................................................ 37
Sections 3033-3036. Regenerative Therapies ................................................................... 38
Section 3037. Health Care Economic Information ........................................................... 39
Section 3038. Combination Product Innovation ............................................................... 40
Subtitle E-Antimicrobial Innovation and Stewardship ........................................................... 42
Section 3041. Antibacterial Resistance Monitoring. ......................................................... 42
Section 3042. Limited Population Pathway. ..................................................................... 43
Section 3043. Prescribing Authority. ................................................................................ 44
Section 3044. Susceptibility Test Interpretive Criteria for Microorganisms;
Antimicrobial Susceptibility Testing Devices................................................................ 44
Subtitle F-Medical Device Innovations................................................................................... 45
Section 3051. Breakthrough Devices ................................................................................ 45
Section 3052. Humanitarian Device Exemption ............................................................... 48
Section 3053. Recognition of Standards ........................................................................... 48
Section 3054. Certain Class I and Class II Devices .......................................................... 50
Section 3055. Classification Panels .................................................................................. 51
Section 3056. Institutional Review Board Flexibility ....................................................... 52
Section 3057. CLIA Waiver Improvements ...................................................................... 53
Section 3058. Least Burdensome Device Review ............................................................ 54
Section 3059. Cleaning Instructions and Validation Data ................................................. 55
Section 3060. Clarifying Medical Software Regulation ................................................... 56
Subtitle G-Improving Scientific Expertise and Outreach at FDA ........................................... 58
Section 3071. Silvio O. Conte Senior Biomedical Research and Biomedical
Product Assessment Service .......................................................................................... 58
Section 3072. Hiring Authority for Scientific, Technical, and Professional
Personnel........................................................................................................................ 59
Section 3073. Establishment of Food and Drug Administration Intercenter
Institutes ......................................................................................................................... 59
Section 3074. Scientific Engagement ............................................................................... 60
Section 3075. Drug Surveillance ...................................................................................... 61
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The 21st Century Cures Act (Division A of P.L. 114-255)
Section 3076. Reagan-Udall Foundation for the Food and Drug Administration ............. 62
Subtitle H-Medical Countermeasures Innovation ................................................................... 62
Sections 3081-3085. Medical Countermeasures Innovation ............................................. 63
Section 3086. Encouraging Treatment for Agents that Present a National Security
Threat ............................................................................................................................. 64
Section 3087. Paperwork Reduction Act Waiver During a Public Health
Emergency ..................................................................................................................... 65
Section 3088. Clarifying FDA Emergency Use Authorization ......................................... 65
Subtitle I-Vaccine Access, Certainty, and Innovation ............................................................. 66
Sections 3091-3093. Predictable Review Timelines of Vaccines by the ACIP,
Review of Processes and Consistency of ACIP Recommendations, Encouraging
Vaccine Innovation ........................................................................................................ 67
Title IV- Delivery .......................................................................................................................... 67
Sections 4001-4008. Policies to Promote the Adoption and Use of EHR
Technology .................................................................................................................... 70
Section 4009. Improving Medicare Local Coverage Determinations ............................... 72
Section 4010. Medicare Pharmaceutical and Technology Ombudsman ........................... 73
Section 4011. Medicare Site-of-Service Price Transparency ............................................ 73
Section 4012. Telehealth Services in Medicare ................................................................ 74
Title V-Savings .............................................................................................................................. 75
Section 5001. Savings in the Medicare Improvement Fund ............................................. 75
Section 5002. Medicaid Reimbursement to States for Durable Medical Equipment ........ 75
Section 5003. Penalties for Violations of Grants, Contracts, and Other
Agreements .................................................................................................................... 75
Section 5004. Reducing Overpayments of Infusion Drugs ............................................... 78
Section 5005. Increasing Oversight of Termination of Medicaid Providers ..................... 79
Section 5006. Requiring Publication of Fee-for-Service Provider Directory ................... 81
Section 5007. Fairness in Medicaid Supplemental Needs Trusts ..................................... 82
Section 5008. Eliminating Federal Financial Participation with Respect to
Expenditures under Medicaid for Agents Used for Cosmetic Purposes or Hair
Growth ........................................................................................................................... 83
Section 5009. Amendment to the Prevention and Public Health Fund ............................. 83
Section 5010. Strategic Petroleum Reserve Drawdown ................................................... 84
Section 5011. Rescission of Portion of ACA Territory Funding ....................................... 84
Section 5012. Medicare Coverage of Home Infusion Therapy ......................................... 85
Tables
Table 1. CRS Experts List ............................................................................................................... 2
Appendixes
Appendix. List of Acronyms ......................................................................................................... 88
Contacts
Author Contact Information .......................................................................................................... 92
Congressional Research Service
The 21st Century Cures Act (Division A of P.L. 114-255)
Introduction
The 21st Century Cures Act (P.L. 114-255) was signed into law on December 13, 2016, by
President Barack Obama. On November 30, 2016, the House passed the House amendment to the
Senate amendment to H.R. 34, the 21st Century Cures Act, on a vote of 392 to 26. The bill was
then sent to the Senate where it was considered and passed, with only minor technical
modification, on December 7, 2016, on a vote of 94 to 5.1
The law consists of three divisions:
Division A—21st Century Cures Act;
Division B—Helping Families in Mental Health Crisis; and
Division C—Increasing Choice, Access, and Quality in Health Care for
Americans.
CRS has published a series of reports on this law, one on each Division. This is the report for
Division A of the law.2
Division A of the law provides funding for biomedical research—including the Precision
Medicine Initiative (PMI) and the Cancer Moonshot Initiative—and for the opioid crisis response;
modifies Food and Drug Administration (FDA) pathways for the approval of regulated medical
products; and makes a number of reforms to the National Institutes of Health (NIH). Division A
of the law also includes and builds on provisions from both the previously passed House bill,
H.R. 6 (The 21st Century Cures Act, passed in July 2015), and a package of Senate medical
innovation bills that were considered in the early part of 2016.
As noted, both the House and the Senate considered previous legislation to support medical
innovation, primarily through reforms to the NIH and changes to the drug, biologic and device
approval pathways at the FDA. On February 3, 2015, Senators Lamar Alexander and Patty
Murray, chairman and ranking Member of the Committee on Health, Education, Labor and
Pensions, announced the start of a bipartisan initiative to "examine the process for getting safe
treatments, devices and cures to patients and the roles of the [FDA] and the [NIH] in that
process."1 This initiative culminated in a package of 19 bipartisan bills that were reported out of
the Senate Health, Labor, Education, and Pensions (HELP) Committee in a series of three
executive sessions held on February 9, 2016; March 9, 2016; and April 6, 2016. One of these 19
bills, The Adding Zika Virus to the FDA Priority Review Voucher Program Act (S. 2512),
subsequently was passed by both chambers and signed into law on April 19, 2016 (P.L. 114-146).
The Senate's medical innovation package was that chamber's companion effort to the House's 21st
Century Cures initiative, which resulted in the House passage of H.R. 6, the initial version of the
21st Century Cures Act, on July 10, 2015, on a vote of 344 to 77. H.R. 6 was the result of a series
of hearings and roundtable meetings hosted by the House Energy and Commerce Committee
dating back to spring 2014. The hearings and roundtables focused on a broad range of topics,
including modernizing clinical trials, incorporating patient perspectives into medical research and
1
The Congressional Budget Office's (CBO) score of H.R. 34 (Rules Committee Print 114-67, as amended by
Amendment Number 5) is available at https://www.cbo.gov/sites/default/files/114th-congress-20152016/costestimate/H.R.34amendment5.pdf.
2 For information on Division B, see CRS Report R44718, The Helping Families in Mental Health Crisis Reform Act of
2016 (Division B of P.L. 114-255), coordinated by Erin Bagalman.
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regulatory processes, precision/personalized medicine, digital health care, and more. While it
consisted of many different provisions, H.R. 6 was primarily focused on efforts to increase
strategic investments in medical research at NIH and change some aspects of how the FDA
executes its regulatory oversight mission with regard to the review and approval of new drugs,
biologics, and medical devices.
This report provides a brief summary of each provision of the 21st Century Cures Act (Division A
of P.L. 114-255), by title, subtitle, and section.3 The Division includes five titles, as follows: (1)
Innovation projects and state responses to opioid abuse; (2) Discovery; (3) Development; (4)
Delivery; and (5) Savings. Most provision summaries include a brief background of current law
in addition to a description of the new provision of law. Throughout the report, clarity takes
priority over consistency. For example, some summaries are more detailed than others where such
detail is necessary to highlight important changes. A list of acronyms used throughout this report
can be found in Appendix of this report.
Table 1. CRS Experts List
Erin Bagalman
Opioid epidemic funding
Cliff Binder
Medicaid, Fraud and abuse
Kirsten J. Colello
Medicaid supplemental needs trusts
Agata Dabrowska
FDA drug regulation
Susannah Gopalan
Telehealth in Medicare
Frank Gottron
Medical countermeasures innovation
Jim Hahn
Medicare Part B, Site-of-service price transparency
Elayne J. Heisler
Health care workforce and education
Judith Johnson
National Institutes of Health, FDA medical device and biologics regulation
Sarah A. Lister
Antimicrobial and vaccine development, Collaborative research, PPHF
Annie Mach
ACA territory funding
Paulette Morgan
Durable Medical Equipment
Robert Pirog
Strategic Petroleum Reserve drawdown
C. Stephen Redhead
Data privacy, Health Information Technology, Regulation of medical software
Amanda Sarata
Precision medicine, Clinical laboratory regulation
Title I-Innovation Projects and State Responses to
Opioid Abuse
Section 1001. NIH Innovation Projects
The National Institutes of Health (NIH) is the lead federal agency charged with performing and
supporting biomedical and behavioral research. It also has major roles in training biomedical
3 Three sections are excluded from this report due to their technical, non-substantive nature: Section 1004 (Budgetary
treatment), Section 3101 (Technical corrections), and Section 3102 (Completed studies).
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researchers and disseminating health information. Congress doubled the NIH budget from $13.65
billion to $27.1 billion in the five-year period from FY1998 to FY2003; during that period,
annual increases in the 14%-15% range were the norm. Since then, increases from regular
appropriations have been between 1.0% and 3.2% each year.4 The growth rate of the NIH budget
has been at or below the rate of inflation, which for biomedical research in FY2015 is estimated
to be 2.2%.5 NIH funding in FY2015 was 22% lower than the FY2003 level, the peak of the
doubling period in constant 2012 dollars.6
A recent analysis of U.S. expenditures on biomedical research found that “U.S. government
research funding declined from 57% (2004) to 50% (2012) of the global total, as did that of U.S.
companies (50% to 41%), with the total U.S. (public plus private) share of global research
funding declining from 57% to 44%. Asia, particularly China, tripled investment from $2.6
billion (2004) to $9.7 billion (2012) preferentially for education and personnel.”7 The United
States continues to be the top supporter of both public and industry medical research. 8 However,
some Members of Congress and many in the biomedical research community have expressed
concern over the rapidly increasing investments being made by other countries in this area of
research.
Many of those who are concerned about the U.S. global position in biomedical research
investment have made frequent calls for increased support for research at NIH. However, another
recent analysis of U.S. biomedical research funding cautioned that the past pattern of rapid
doubling of the NIH budget followed by slowdowns in federal funding “created an unsustainable
hypercompetitive system that is discouraging even the most outstanding prospective students
from entering our profession—and making it difficult for seasoned investigators to produce their
best work.”9 Rather than short-term infusions of cash that disappear, the authors recommend that
greater emphasis be placed on the predictable and stable growth of federal funds for the research
enterprise.10 In responding to questions raised by Senator Elizabeth Warren during a May 5, 2015,
Senate hearing, NIH Director Francis Collins agreed that continued NIH budget increases—
ranging from 3.7% annually to inflation plus 4% or 5%—would be preferred to a temporary
larger investment that disappears.11
4 For further information, see CRS Report R43341, NIH Funding: FY1994-FY2017, by Judith A. Johnson.
5 The Biomedical Research and Development Price Index (BRDPI) is developed each year for NIH by the Bureau of
Economic Analysis of the Department of Commerce. It reflects the increase in prices of the resources needed to
conduct biomedical research—including personnel services, supplies, equipment—and indicates how much the NIH
budget must change to maintain purchasing power. See http://officeofbudget.od.nih.gov/gbiPriceIndexes.html.
6 For further information, see CRS Report R43341, NIH Funding: FY1994-FY2017, by Judith A. Johnson.
7 Hamilton Moses, David H. M. Matheson, Sarah Cairns-Smith, et al., “The Anatomy of Medical Research: U.S. and
International Comparisons,” Journal of the American Medical Association, vol. 313, no. 2 (January 13, 2015), pp. 174189.
8 Overall medical research funding in the United States was $117.2 billion in 2011. See Figure 8 on page 181 in
Hamilton Moses, David H. M. Matheson, Sarah Cairns-Smith, et al., “The Anatomy of Medical Research: U.S. and
International Comparisons,” Journal of the American Medical Association, vol. 313, no. 2 (January 13, 2015).
9 Bruce Alberts, Marc W. Kirschner, Shirley Tilghman, and Harold Varmus, “Rescuing U.S. biomedical research from
its systemic flaws,” Proceedings of the National Academy of Sciences, vol. 111, no. 16 (April 22, 2014), pp. 57735777.
10 Ibid., p. 5775.
11 U.S. Congress, Senate Committee on Health, Education, Labor, and Pensions, Continuing America’s Leadership:
Realizing the Promise of Precision Medicine for Patients, 114th Cong., 1st sess., May 5, 2015.
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The Advisory Committee to the Director of NIH, authorized under PHSA Section 222, provides
“advice on matters pertinent to NIH mission responsibilities in the conduct and support of
biomedical research.”12
Provision
Section 1001 establishes the “NIH Innovation Account” in the Treasury, to which specified
amounts are transferred for each of FY2017 through FY2026. Such amounts from the account are
authorized to be appropriated to the NIH Director for the purpose of carrying out the NIH
Innovation Projects. Amounts appropriated from this account are available until expended.
Specifically, the provision authorizes appropriations to support
the Precision Medicine Initiative, specified amounts for FY2017 through
FY2026, total not to exceed $1.455 billion;
the Brain Research through Advancing Innovative Neurotechnologies Initiative
(BRAIN Initiative), specified amounts for FY2017 through FY2026, total not to
exceed $1.511 billion;
cancer research, specified amounts for FY2017 through FY2023, total not to
exceed $1.8 billion; and
regenerative medicine using adult stem cells, specified amounts for FY2017
through FY2020 that total $30 million; no funds are to be appropriated for this
activity after FY2020. This research is to be undertaken in coordination with the
FDA.
Within six months of enactment, the NIH Director must submit to the specified congressional
committees a work plan including the proposed allocation of funds authorized to be appropriated
for each year, FY2017 through FY2026, for the NIH Innovation Projects. Prior to submitting the
work plan, the NIH Director must seek recommendations on the allocations of funds and the
contents of the proposed work plan from the Advisory Committee to the Director of NIH. The
work plan must include recommendations from this Advisory Committee, the amount of money
to be obligated or expended in each fiscal year for each NIH Innovation Project, a description and
justification of each such project, and a description of how each such project supports the
strategic research priorities identified in the NIH Strategic Plan.
Not later than October 1 of each year, FY2018 through FY2027, the Director of NIH must submit
to the specified congressional committees a report including the amount of money obligated or
expended in the prior fiscal year for each NIH Innovation Project, a description of any such
project using funds provided by this section, and whether such projects are advancing the
strategic research priorities identified in the NIH Strategic Plan. The specified House and Senate
committees may request an update on the allocation of funding under this section or the
description of the NIH Innovation Projects, which the NIH Director must provide in the form of
additional reports or testimony.
Section 1001 specifies that these funds may be used only for NIH Innovation fund projects
(notwithstanding any transfer authority in any appropriations act).
The section also specifies that amounts in the account are not available until appropriated in
subsequent appropriations acts. Notably, the amounts subsequently appropriated (i.e., the budget
authority and the resulting outlays) for FY2017 through FY2026, up to the amounts transferred,
are to be subtracted from any cost estimates provided for purposes of budget controls. Effectively,
12 NIH, Advisory Committee to the Director, Charter, at http://acd.od.nih.gov/charter.htm.
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the appropriations from the account will not be counted against any spending limits, such as the
statutory discretionary spending limits; that is, the amounts appropriated from the account will be
considered outside those limits for FY2017 through FY2026.
Section 1001 sunsets on September 30, 2026.
Section 1002. FDA Innovation Projects
The Food and Drug Administration (FDA) regulates the safety of foods (including dietary
supplements), cosmetics, and radiation-emitting products; the safety and effectiveness of drugs,
biologics (e.g., vaccines), and medical devices; and public health aspects of tobacco products.
FDA’s budget (i.e., its total program level) has two funding streams: annual appropriations (i.e.,
discretionary budget authority, or BA) and industry user fees. In FDA’s annual appropriations,
Congress sets both the total amount of appropriated funds and the total amount of user fees that
the agency is authorized to collect and obligate for that fiscal year. Appropriated funds are largely
for the Salaries and Expenses account, with a much smaller amount for the Buildings and
Facilities account. The different user fees contribute only to the Salaries and Expenses account.
Between FY2012 and FY2016, FDA’s total program level increased from $3.832 billion to
$4.745 billion. Although congressionally appropriated funding increased by 9% over that time
period, user fee revenue increased more than 50%. In FY2016, user fees accounted for 42% of
FDA’s total program level.13
The Science Board to the FDA is an advisory committee that provides “advice to the
Commissioner and other appropriate officials on specific complex scientific and technical issues
important to FDA and its mission, including emerging issues within the scientific community.”
Among other things, the Science Board is also tasked with providing, where requested, “expert
review of Agency sponsored intramural and extramural scientific research programs.”
Provision
Section 1002 establishes the “FDA Innovation Account,” to which a total of $500 million is
authorized to be transferred over a nine-year period (FY2017-FY2025).14 It specifies that amounts
in the account are not available until appropriated in subsequent appropriations acts and that once
made available, these amounts are available until expended. The amounts from the account are
authorized to be appropriated to the FDA Commissioner for the purpose of carrying out the FDA
Innovation Projects specified as activities under subtitles A through F of Title III (e.g., Subtitle
A—Patient Focused Drug Development, Subtitle B—Advancing New Drug Therapies, Subtitle
F—Medical Device Innovations), as well as Section 3073 of this Act establishing FDA
Intercenter Institutes; these activities are described later in this report.
The amounts subsequently appropriated (i.e., the budget authority and the resulting outlays) for
FY2017 through FY2025, up to the amounts transferred, are to be subtracted from any cost
estimates provided for purposes of budget controls. Effectively, the appropriations from the
account will not be counted against any spending limits, such as the statutory discretionary
13 CRS Report R44576, The Food and Drug Administration (FDA) Budget: Fact Sheet, by Agata Dabrowska and Susan
Thaul.
14 For each of fiscal years 2017 through 2025, the following amounts are authorized to be transferred to the FDA
Innovation Account: $20 million in FY2017; $60 million in FY2018; $70 million in FY2019; $75 million in FY2020;
$70 million in FY2021; $50 million in FY2022; $50 million in FY2023; $50 million in FY2024; $55million in
FY2025.
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spending limits; that is, the amounts appropriated from the account will be considered outside
those limits for FY2017 through FY2025.
Within six months of enactment, the FDA Commissioner is required to submit to the specified
congressional committees a work plan including the proposed allocation of funds authorized to be
appropriated for each fiscal year (FY2017 through FY2025) for the FDA Innovation Projects.
Prior to submitting the work plan, the FDA Commissioner must seek recommendations on the
allocations of funds and the contents of the proposed work plan from the Science Board. The
work plan must include recommendations from the Science Board, the amount of money to be
obligated or expended in each fiscal year for each FDA Innovation Project, and a description and
justification of each such project.
Section 1002 requires the FDA Commissioner, not later than October 1 of each fiscal year 2018
through 2026, to submit to the specified congressional committees a report including the amount
of money to be obligated or expended in each fiscal year for each FDA Innovation Project, a
description of any such project using funds provided by this section, and how the activities are
advancing public health. The specified House and Senate committees may request an update on
the allocation of funding under this section or the description of the FDA Innovation Projects,
which the FDA Commissioner must provide in the form of additional reports or testimony.
Section 1002 specifies that these funds may be used only for FDA Innovation fund projects
(notwithstanding any transfer authority in any appropriations act).
Section 1002 sunsets on September 30, 2025.
Section 1003. Account for the State Response to the Opioid Abuse Crisis
The Substance Abuse and Mental Health Services Administration (SAMHSA) administers block
grants authorized by PHSA Title XIX and numerous other grants authorized by PHSA Title V, as
well as other activities. Each state that receives a block grant from SAMHSA is required to
submit to the HHS Secretary a report about block grant funds received in the preceding fiscal
year—including the purposes for which funds were expended, the state’s activities under the
block grant, and the recipients of block grant funds.
Provision
Section 1003 establishes the “Account for the State Response to the Opioid Abuse Crisis” in the
Treasury, to which $500 million is transferred for each of FY2017 and FY2018. Such amounts
from the account are authorized to be appropriated to the HHS Secretary for use as grants to
support state responses to opioid abuse. Specifically, the provision authorizes appropriations to
support two categories of grants to states: (1) grants “for the purpose of addressing the opioid
abuse crisis” and (2) grants for activities that supplement opioid-related activities undertaken by
the state agency that administers the substance abuse block grant.
Section 1003 requires that such funds (1) shall not be used for any other purpose (notwithstanding
any transfer authority in any appropriations act) and (2) shall be subject to the same requirements
as SAMHSA’s substance abuse prevention and treatment programs under PHSA Titles V and
XIX. It further requires a state receiving such a grant to include specified information about the
use of the grant in the report already required in connection with the block grants.
The amounts in the account are not available until appropriated in subsequent appropriations acts.
Notably, the amounts subsequently appropriated (i.e., the budget authority and the resulting
outlays) for FY2017 and FY2018, up to the amounts transferred, are to be subtracted from any
cost estimates provided for purposes of budget controls. Effectively, the appropriations from the
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account will not be counted against any spending limits, such as the statutory discretionary
spending limits; that is, the amounts appropriated from the account will be considered outside
those limits for FY2017 and FY2018.
Title II- Discovery
Subtitle A- National Institutes of Health Reauthorization
Section 2001. National Institutes of Health Reauthorization
NIH derives its statutory authority from the Public Health Service Act of 1944 (PHSA), as
amended.15 PHSA Section 301 grants the HHS Secretary broad permanent authority to conduct
and sponsor research.16 In addition, PHSA Title IV, “National Research Institutes,” authorizes in
greater detail various activities, functions, and responsibilities of the NIH Director and the
institutes and centers.17 The last major NIH reauthorization was the NIH Reform Act of 2006
(P.L. 109-482). The NIH Reform Act, in PHSA Section 402A, authorized total funding levels for
NIH appropriations for FY2007 ($30,331,309,000), FY2008 ($32,831,309,000), and such sums
as necessary for FY2009. Overall NIH authorization expired at the end of FY2009 and has not
been extended by Congress. Annual appropriations, together with Section 301 of the PHSA, have
provided authority for NIH programs to continue from FY2009 to the present.
Provision
Section 2001 amends PHSA Section 402A, to authorize appropriations for NIH in FY2018
($34,851,000,000), FY2019 ($35,585,871,000), and FY2020 ($36,472,442,775).
Section 2002. Eureka Prize Competitions
Section 105 of the America COMPETES Reauthorization Act of 2010 (P.L. 111-358) provides
federal agencies with broad authority to carry out programs designed to stimulate innovation
through prize competitions.18 Before passage of P.L. 111-358, only certain federal agencies had
the authority to initiate prize competitions. The White House Office of Science and Technology
Policy (OSTP) publishes annual reports on the implementation of Section 105 as required by P.L.
111-358.19 Currently a number of federal government agencies, including NIH, sponsor
challenges or prize competitions in science and medical research. A current list of such challenges
is available on the Challenge.gov website.20 A search of the website on December 8, 2016,
resulted in 15 competitions conducted by NIH or one of the NIH ICs. Examples of research topics
covered in the various challenges include breast cancer genetics, antimicrobial resistance, and
drug abuse and addiction research.
15 42 U.S.C. §§201-300mm-61.
16 42 U.S.C. §241.
17 42 U.S.C. §§281-290b.
18 For more information, see CRS Report R43880, The America COMPETES Acts: An Overview, by Heather B.
Gonzalez.
19 Office of Science and Technology Policy, “Implementation of Federal Prize Authority: Fiscal Year 2015 Progress
Report,” August 2016, at https://www.whitehouse.gov/sites/default/files/fy2015_competes_prizes_report.pdf.
20 https://www.challenge.gov/list/.
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Provision
Section 2002 requires the NIH Director, under authorities in 15 U.S.C. §3719, to support prize
competitions for one or both of the following goals: (1) identifying and funding areas of
biomedical science that could realize significant advancements through a prize competition and
(2) improving health outcomes, particularly with respect to human diseases and conditions such
as those that are serious and represent a significant disease burden in the United States. With
regard to the second goal, the prize competition may also target human diseases and conditions
where public and private investment in research is disproportionately small relative to federal
government expenditures for prevention and treatment activities and those diseases and
conditions with potential for a significant return on investment. The section requires the NIH
Director to collect information on the effect of prize competition innovations on advancing
biomedical science or improving health outcomes and the effect of the innovations on federal
expenditures. This information must be included in the NIH triennial report, required in PHSA
Section 403.
Subtitle B- Advancing Precision Medicine
Precision medicine is a relatively new term for what has traditionally been called personalized
medicine, the idea of providing health care to individuals based on specific patient characteristics.
On February 25, 2016, the White House hosted a Precision Medicine Initiative (PMI) Summit to
mark the one-year anniversary of the initiative’s launch, first announced in the 2015 State of the
Union address. In the first year, the PMI’s three key entities—National Institutes of Health (NIH),
Food and Drug Administration (FDA), and the Office of the National Coordinator for Health
Information Technology (ONC)—began work in this area. The FY2017 President’s budget
requests a total of $309 million for the PMI: $4 million to FDA, $5 million to ONC, and the
remaining $300 million to NIH.
Precision medicine research efforts rely on the collection of large amounts of health and other
data; therefore, access to this data may be a concern in the context of this type of research. The
sharing of genetic and genomic data among private individuals, researchers, and the federal
government has, at times, prompted concerns that the information, if collected or retained by a
federal executive branch agency, could be subject to public release pursuant to the Freedom of
Information Act (FOIA). FOIA, however, specifies nine categories of information that may be
exempted from the rule of disclosure, allowing agencies to withhold applicable records.
Exemption 3 allows agencies to withhold applicable records if the data are specifically exempted
from disclosure by a statute other than FOIA, if that statute meets criteria laid out in FOIA. These
types of Exemption 3 statutes are often referred to as b(3) exemptions because they are authorized
in 5 U.S.C. §552(b)(3).
As a mechanism for addressing compelled disclosure of research data, NIH currently issues
Certificates of Confidentiality pursuant to PHSA Section 301(d) (42 U.S.C. §241(d)) at the
request of an investigator. A Certificate of Confidentiality protects investigators from being
compelled to disclose information that would identify research subjects in any civil, criminal,
administrative, legislative, or other proceeding. In this way, having a Certificate of
Confidentiality can help promote participation in research by adding an additional layer of
privacy protection.
At the other end of the spectrum, the sharing of research data—specifically, genomic data
generated by NIH-funded research—has also received attention in the context of precision
medicine. NIH has established a comprehensive policy for the sharing of genomic data that
“applies to all NIH-funded research that generates large-scale human or non-human genomic data
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as well as the use of these data for subsequent research.” This policy requires investigators to
outline their data-sharing plans as part of their funding applications; if investigators fail to submit
the required data, NIH may withhold funding.
Sections 2011-2014. Precision Medicine Establishment and Data Protections
Provisions
Title II, Subtitle B, has four sections (Sections 2011-2014) that together aim to support precision
medicine by (1) codifying the PMI; (2) requiring issuance of Certificates of Confidentiality to
investigators of federally funded research; (3) protecting identifiable, sensitive information from
release under FOIA; and (4) requiring the sharing of NIH-supported research data in certain
circumstances.
Section 2011 codifies the President’s Precision Medicine Initiative (PMI) in a new PHSA Section
498E, by encouraging the HHS Secretary to establish and carry out the PMI, and by allowing
specified components and authorities in the carrying out of the PMI as well as identifying
requirements of the initiative, including, for example, complying with existing law and regulation
regarding human research subjects protections. It also requires, not later than one year after
enactment, the HHS Secretary to submit a report to Congress on relevant data access policies and
procedures, and consultation with experts in the development of those policies.
Section 2012 amends PHSA Section 301(d) to require the HHS Secretary to issue a Certificate of
Confidentiality to research investigators of research funded wholly or in part by the federal
government in which sensitive, identifiable information is collected to protect the privacy of
research participants. The section prohibits the individual with the certificate from disclosing
sensitive information about the research participants, with certain exceptions, as specified, and
would make this type of information immune from the legal process. In addition, the section
requires that these protections exist in perpetuity and that the HHS Secretary must minimize the
burden to researchers of compliance with this section, and must coordinate across involved HHS
entities. The requirements of this section become effective 180 days after the date of enactment of
the act.
Section 2013 amends PHSA Section 301 to allow the HHS Secretary to exempt from disclosure
under FOIA exemption (b)(3) specified biomedical information that identifies an individual or
that has an associated risk that the information may be reidentified. The HHS Secretary is
required to make each such exemption available in writing and to the public, upon request.
However, this does not limit individual research participants access to their own data.
Section 2014 amends PHSA Section 402(b) to allow the HHS Secretary to require recipients of
NIH grants or agreements to share data generated from such NIH grants or agreements in a
manner consistent with all applicable federal law regarding human subject protections, propriety
interests, confidential commercial information, and intellectual property.
Subtitle C- Supporting Young Emerging Scientists
Section 2021. Investing in the Next Generation of Researchers.
Congress has had a long-standing interest in developing the future biomedical research
workforce. Recent concerns have focused on ways to reduce the time between when young
investigators complete their training and when they receive their first independent NIH research
grant (i.e., achieve research independence). NIH has created a number of initiatives to shorten this
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time, in part to better retain young investigators in biomedical research. The Departments of
Labor, Health and Human Services, and Education, and Related Agencies Appropriations Act,
2016 (P.L. 114-113, Division H), instructed the NIH Director to enter into a contract with the
National Academy of Sciences (NAS) to conduct a comprehensive study of the policies affecting
the next generation of researchers in the United States.
Provision
Section 2021 amends Part A of Title IV of the PHSA by adding a new Section 404M, which
establishes the Next Generation of Researchers Initiative (the Initiative) within the office of the
NIH Director. The Initiative requires the NIH Director to coordinate all NIH policies and
programs focused on promoting and providing opportunities for new researchers and for
promoting earlier research independence. Among other things, the NIH Director would have to
coordinate with relevant agencies, professional associations, and academic institutions to improve
and update information on the biomedical workforce to inform training, recruitment, and
retention programs of biomedical researchers. In establishing the Initiative, the NIH Director is
required to consider recommendations made by NAS in its study on the next generation of
researchers. Not later than two years after completion of the NAS study, the NIH Director would
be required to submit a report to specified congressional committees regarding any actions taken
by NIH with respect to the NAS recommendations.
Section 2022. Improvement of Loan Repayment Program.
NIH funds seven loan repayment programs for researchers. Three of these are intramural
programs that provide educational loan repayment benefits to researchers in exchange for
undertaking research while employed by NIH. Intramural loan repayment programs support
researchers from disadvantaged backgrounds, those who are investigating AIDS, and those
undertaking general research (including general research by physicians during their fellowship
training). Four of these programs help extramural researchers repay their educational loans. These
funds are awarded competitively to researchers who are employed by a qualifying educational
institution. Specific programs are available to extramural researchers investigating health
disparities, undertaking contraception and infertility research, engaging in clinical research, and
examining pediatric-related topics. Researchers may receive up to $35,000 per year in loan
repayment benefits under each of these programs. Under current law, appropriations for loan
repayments remain available until the end of the second fiscal year after they are appropriated.
Provision
Section 2022 renames PHSA Section 487A “Intramural Loan Repayment Program” and
consolidates existing NIH intramural loan repayment programs. Specifically, it (1) transfers the
authority to administer these program from the HHS Secretary to the NIH Director; (2) increases
annual loan repayment amounts from a maximum of $35,000 to a maximum of $50,000; and (3)
provides loan repayment benefits for individuals who conduct research in areas of emerging
scientific or workforce needs, in addition to individuals who conduct research on AIDS, and
clinical researchers from disadvantaged backgrounds. In addition, Section 2022 authorizes the
NIH Director to amend the categories eligible for intramural loan repayment as scientific and
workforce priorities change. Finally, the section prohibits the NIH Director from entering into a
loan repayment contract with individuals unless they have substantial amounts of educational
loans relative to income as determined by the NIH Director and permits amounts appropriated for
new loan repayment contracts to remain available until the end of the second fiscal year after they
are appropriated.
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Section 2022 similarly amends the NIH’s extramural loan repayment program. Specifically, it (1)
retitles PHSA 487B “Extramural Loan Repayment Program,” (2) transfers authority for the
program from the HHS Secretary to the NIH Director, (3) increases loan repayment amounts to a
maximum of $50,000 per year, (4) prohibits the NIH Director from entering into a loan
repayment contract with individuals unless they have substantial amounts of educational loans
relative to income as determined by the NIH Director, and (5) permits amounts appropriated for
new loan repayment contracts to remain available until the end of the second fiscal year after they
are appropriated. In addition, Section 2022 retains authorization for current topics eligible for
extramural loan repayment (contraception and infertility, pediatric research, minority health
disparities, clinical research, and clinical research conducted by individuals from disadvantaged
backgrounds). The section makes extramural researchers who are conducting research in an area
of emerging scientific or workforce need eligible for loan repayment benefits, and it authorizes
the NIH Director to amend the categories eligible for extramural loan repayment as scientific and
workforce priorities change.
Finally, Section 2022 repeals existing authorizations for NIH loan repayment programs in PHSA
Sections 464z, 487C, 487E, and 487F. It requires a GAO report, not later than 18 months after
enactment, that (1) reports on NIH efforts to attract, retain, and develop emerging scientists,
including underrepresented individuals in the sciences; (2) reports on the research areas where
individuals are receiving increased loan repayment amounts; and (3) analyzes the impact of
changes included in this act on addressing workforce shortages.
Subtitle D- National Institutes of Health Planning and
Administration
Section 2031. National Institutes of Health Strategic Plan
PHSA Section 402(b)(5) specifies that the NIH Director “shall ensure that scientifically based
strategic planning is implemented in support of research priorities as determined by the agencies
of the National Institutes of Health.” Current law does not direct NIH Institutes and Centers (ICs)
to coordinate or collaborate in the development of IC strategic plans. NIH provides access to
many of its strategic plans on the agency’s website.21 The NIH Reform Act of 2006 (P.L. 109482) enhanced the authority of the NIH Director’s Office to perform strategic planning and
provided for trans-NIH initiatives by enacting the Common Fund into law and requiring strategic
planning for the fund. The Common Fund is part of the Office of the Director and is intended to
support research in emerging areas of scientific opportunity, public health challenges, and
knowledge gaps that might benefit from collaboration between two or more ICs.
Provision
Section 2031 amends PHSA Section 402 by adding a new subsection (m), which describes a
strategic plan for NIH. Within two years of enactment, and once every six years thereafter, the
NIH Director, in consultation with the IC Directors, must develop and submit to the appropriate
committees of Congress, and post on the NIH website, a six-year NIH Strategic Plan. The NIH
Strategic Plan is expected to provide direction to the biomedical research investments made by
NIH, facilitate IC collaboration, leverage scientific opportunity, and advance biomedicine.
The NIH Strategic Plan must identify research priorities, such as advancement of treatment, cure
and prevention of health conditions, emerging scientific opportunities, and rising public health
21 See for example http://report.nih.gov/strategicplans/#tab2.
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challenges. The research strategy must address the disease burden in the United States, including
rare diseases, and the many factors that contribute to health disparities. Other elements to be
included in the NIH Strategic Plan are (1) coordination of research among the ICs; (2) priorities
for funding research through the Common Fund; (3) training the biomedical workforce; and (4)
collaboration with other agencies and departments. The individual IC strategic plans are required
to be prepared regularly, to be informed by the NIH Strategic Plan, and to have a common
template. The NIH Director must consult with the IC directors, researchers, patient advocacy
groups, and industry leaders when developing the strategic plan.
Section 2032. Triennial Reports
PHSA Title IV establishes numerous reporting requirements for the NIH Director related to the
activities of the agency. Specifically, PHSA Section 403(a) requires the NIH Director to submit to
Congress biennially a report on NIH activities. Among other things, the report must include an
assessment of the state of biomedical and behavioral research, and details of all the research
activities conducted or supported by the ICs of NIH.
Provision
Section 2032 amends PHSA Section 403(a) by replacing the biennial reporting requirement of the
NIH Director with a triennial requirement. The section adds new, and clarifies existing, reporting
requirements, including a description of intra-NIH activities and funding made available for
conducting and supporting research that involves collaboration between an IC and one or more
other ICs.
Section 2033. Increasing Accountability at the National Institutes of Health
PHSA Section 405 specifies that the National Cancer Institute Director is appointed by the
President and the Directors of the other NIH Institutes are appointed by the HHS Secretary. Each
NIH Institute Director reports directly to the NIH Director.
Research supported by NIH is first evaluated by a peer review system.22 Scientists who seek to
compete for NIH research funding must submit detailed applications describing the research they
plan to undertake. NIH considers the applications under a two-tiered system of peer review. First,
the applications are reviewed for scientific and technical merit by committees composed of
nongovernment scientists who are experts in the relevant fields of research. Each application is
thoroughly discussed and given a score representing the average of the scores assigned by the
reviewers. That score becomes the main determinant in whether an applicant will receive funding
from an IC for the research proposal. The funding decisions are fine-tuned by a second level of
peer review in the ICs, when the applications are considered for program relevance by the IC’s
National Advisory Councils or Boards, which are composed of scientific and lay representatives.
Section 202 of the Labor/HHS/ED Appropriations Act, 1993, states at the end of the section that
the payment of compensation to consultants or individual scientists appointed for limited periods
of time is “not to exceed the per diem rate equivalent to the maximum rate payable for seniorlevel positions,” which is “not less than 120% of the minimum rate of basic pay payable for GS–
15 of the General Schedule; and ... not greater than the rate of basic pay payable for level III of
the Executive Schedule.”23
22 Peer review requirements described in PHSA Section 492.
23 P.L. 102-394 and 5 U.S.C. §5376.
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Provision
Section 2033 amends PHSA Section 405 with regard to the appointment and terms of the Director
of the National Cancer Institute and the directors of other NIH ICs. It requires that directors of
ICs be appointed by the HHS Secretary acting through the NIH Director. The Director of the
National Cancer Institute continues to be appointed by the President. It specifies five-year terms
for the IC Directors who are appointed by the HHS Secretary acting through the NIH Director,
and authorizes the NIH Director to remove an IC Director prior to the end of a five-year term if
necessary. It permits the director of an IC to be reappointed at the end of a five-year term, with no
limit to the number of terms served. It requires that, if the office of a director of an IC becomes
vacant before the end of a five-year term, the director appointed to fill the vacancy begin a new
five-year term (as opposed to finishing the five-year term of the previous director). Each current
IC Director is deemed to be appointed for a five-year term as of the date of enactment.
Section 2033 specifies that the compensation limitations in Section 202 of the Labor/HHS/ED
Appropriations Act, 1993, related to time-limited appointments of consultants and individual
scientists, do not apply to directors appointed under this new authority.24
The section adds a new requirement that before a new research grant is made by an IC, the IC
Director will review and approve the award, taking into consideration the mission of the IC, the
scientific priorities identified in the strategic plan, “programs or projects funded by other agencies
on similar research topics and advice by staff and the advisory council or board of such national
research institute or national center.”
Section 2033 also requires the HHS Secretary to submit a report to Congress, not later than two
years following enactment, “on efforts to prevent and eliminate duplicative biomedical research
that is not necessary for scientific purposes.” Among other things, the report must “describe how
the HHS Secretary operationally distinguishes necessary and appropriate scientific replication
from unnecessary duplication, and provide examples of instances where the HHS Secretary has
identified unnecessarily duplicative research and the steps taken to eliminate the unnecessary
duplication.”
Section 2034. Reducing Administrative Burden for Researchers
The Federal Demonstration Partnership (FDP) is “a cooperative initiative among 10 federal
agencies and 119 institutional recipients of federal funds, sponsored by the National Academies,
with a purpose of reducing the administrative burdens associated with federal research grants and
contracts.”25 In 2005 and 2012, FDP conducted surveys of principal investigators of federally
funded projects to determine the impact of federal regulations and requirements on the research
process. In both surveys, researchers reported spending 57% of their time engaged in research and
43% of their time in completing pre- and post-award requirements. “The most commonly
experienced administrative responsibilities included those related to federal project finances,
personnel, and effort reporting. These were also among the most time-consuming responsibilities.
For researchers engaged in projects that required human or animal subjects, the related
Institutional Review Board (IRB) and Institutional Animal Care and Use Committee (IACUC)
24 Ibid.
25 Sandra L. Schneider et al., Federal Demonstration Partnership (FDP) 2012 Faculty Workload Survey: Executive
Summary, April 2014.
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requirements were by far the most time-consuming. Other areas viewed as particularly timeconsuming were those involving clinical trials, subcontracts, and cross-agency differences.”26
Provision
Section 2034 includes a series of requirements that aim to address the administrative burden on
researchers funded by NIH and other federal agencies. First, it directs the HHS Secretary, within
two years of enactment, to lead a review by research funding agencies of all financial conflict-ofinterest regulations and policies and to make revisions to harmonize the policies and reduce the
administrative burden on researchers, as appropriate. It also requires the HHS Secretary to update
this policy and, in doing so, take into account certain specified considerations regarding financial
interest disclosures. Second, it requires the NIH Director to implement measures that aim to
reduce the administrative burdens experienced by primary NIH grant awardees related to
monitoring grant sub-recipients. Third, the HHS Secretary, in consultation with the NIH Director,
is required to evaluate financial expenditure reporting procedures and requirements for NIH
funding recipients and take appropriate action to avoid duplication of effort and minimize burden
to funding recipients.
Fourth, within two years of enactment, the HHS Secretary, in consultation with the NIH Director,
the Secretary of Agriculture, and the FDA Commissioner, must complete a review of regulations
and policies for the care and use of laboratory animals and make appropriate revisions to reduce
administrative burden on investigators. Fifth, the HHS Secretary is required to clarify the
applicability of OMB Uniform Guidance requirements regarding documentation of personnel
expenses for entities receiving HHS grants.
Finally, within one year of enactment, the OMB Director is required to establish a Research
Policy Board, consisting of up to 10 federal and 9 to 12 nonfederal members, as specified, to
provide the NIH Director and other members of the federal government with information on the
effects of regulations related to federal research requirements. The board makes recommendations
on harmonizing regulations and policies to minimize administrative burden across federal
research agencies. Within two years of enactment, and once thereafter, the board must submit a
report to specified offices in OMB, the heads of relevant federal departments and agencies, and
specified House and Senate committees. The report must provide recommendations on scientific
research policy, including regulatory benefits and burdens. The board will sunset on September
30, 2021. The section also requires that GAO, within four years of enactment, conduct an
evaluation of board activities regarding its purpose and responsibilities and submit a report to
Congress.
Section 2035. Exemption of the National Institutes of Health from the
Paperwork Reduction Act Requirements.
The Paperwork Reduction Act (PRA, 44 U.S.C. Chapter 35), enacted in 1980 and amended in
1995, established the Office of Information and Regulatory Affairs (OIRA) in the Office of
Management and Budget (OMB). Congress required that agencies seek OIRA permission before
collecting information from the public. The first of 11 stated purposes was to “minimize the
paperwork burden for individuals ... and other persons resulting from the collection of
26 http://sites.nationalacademies.org/cs/groups/pgasite/documents/webpage/pga_087823.pdf;
http://sites.nationalacademies.org/PGA/fdp/PGA_055749.
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information by and for the Federal Government.”27 The PRA requires that federal agencies
receive clearance from OIRA before requesting most types of information from the public.28 PRA
clearance is required when standardized information is collected from 10 or more respondents
within a 12-month period.29 PRA does not apply to certain types of scientific research, including
collections that are neither sponsored nor conducted by the agency and those that are subject to a
clinical exception.30
Provision
Section 2035 amends PHSA Section 301 by adding a subsection stating that the PRA does not
apply to the collection of information during the conduct of NIH research.
Section 2036. High-Risk, High-Reward Research
Other transaction (OT) authority is a special vehicle used by certain federal agencies for obtaining
or advancing research and development (R&D).31 An OT is not a contract, grant, or cooperative
agreement, and there is no statutory or regulatory definition of “other transaction.” Only those
agencies that have been provided OT authority may engage in other transactions. Generally, OT
authority is created because the government needs to obtain leading-edge R&D from commercial
sources, but some companies (and other entities) are unwilling or unable to comply with the
government’s procurement regulations and certain procurement statutes that govern contracts.
Provision
Section 2036 adds a new PHSA Section 402(n) to allow the NIH Director to approve requests by
IC Directors, or program officers within the Office of the Director, to engage in transactions other
than a contract, grant, or agreement with respect to projects that carry out (1) the Precision
Medicine Initiative, or (2) “research that represents important areas of emerging scientific
opportunities, rising public health challenges, or knowledge gaps that deserve special emphasis
and would benefit from conducting or supporting additional research that involves collaboration
between 2 or more [ICs], or would otherwise benefit from strategic coordination and planning.”32
This provision also requires internal NIH reporting on the use of this authority and requires the
HHS Secretary, through the NIH Director, to submit a report to Congress evaluating the activities
under this new subsection by September 30, 2020.
27 44 U.S.C. §3501.
28 For further information about the PRA, see CRS Report RL30590, Paperwork Reduction Act Reauthorization and
Government Information Management Issues (out of print; available to congressional clients from the author on
request), and CRS Report RL32397, Federal Rulemaking: The Role of the Office of Information and Regulatory
Affairs, coordinated by Maeve P. Carey.
29 See NIH, Office of Science Policy, Genetics, Health and Society, What is the Paperwork Reduction Act?, at
http://osp.od.nih.gov/faq/what-paperwork-reduction-act; and HHS, Frequently Asked Questions About PRA /
Information Collection, at http://www.hhs.gov/ocio/policy/collection/infocollectfaq.html.
30 Cass R. Sunstein, Facilitating Scientific Research by Streamlining the Paperwork Reduction Act Process, Executive
Office of the President, Office of Management and Budget, December 9, 2010, https://www.whitehouse.gov/sites/
default/files/omb/memoranda/2011/m11-07.pdf.
31 For further information, see U.S. Government Accountability Office, DOD Research: Acquiring Research by
Nontraditional Means, GAO/NSIAD-96-11, March 29, 1996, https://www.gpo.gov/fdsys/pkg/GAOREPORTSNSIAD-96-11/pdf/GAOREPORTS-NSIAD-96-11.pdf.
32 PHSA Section 402(b)(7)(A)(i).
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Section 2037. National Center for Advancing Translational Sciences.
Prior to FDA approval, medical products are tested in a clinical trial using human volunteers to
see how the products compare to standard treatments or to no treatment. FDA uses the data from
clinical trials to determine whether to approve a manufacturer’s application for marketing a
medical product. Clinical trials are conducted in three phases.
Phase I trials try to determine dosing, document how a drug is metabolized and excreted,
and identify acute side effects. Usually, a small number of healthy volunteers (between 20
and 80) are used in Phase I trials.
Phase II trials include more participants (about 100-300) who have the disease or condition
that the product potentially could treat. In Phase II trials, researchers seek to gather further
safety data and preliminary evidence of the drug’s beneficial effects (efficacy), and they
develop and refine research methods for future trials with this drug. Sometimes Phase II
clinical trials are divided into Phase IIA (to assess dosing requirements) and Phase IIB
(to study efficacy). If the Phase II trials indicate that the drug may be effective—and the
risks are considered acceptable, given the observed efficacy and the severity of the
disease—the drug moves to Phase III.
In Phase III trials, the drug is studied in a larger number of participants with the disease
(approximately 1,000-3,000). This phase further tests the product’s effectiveness, monitors
side effects and, in some cases, compares the product’s effects to a standard treatment, if
one is already available. As more and more participants are tested over longer periods of
time, the less common side effects are more likely to be revealed.33
Under current law in PHSA Section 479, NIH’s National Center for Advancing Translational
Sciences (NCATS) may develop and provide infrastructure and resources for all phases of clinical
trials research; however, it may support clinical trial activities only through the end of Phase IIA,
with specific exceptions. NCATS may support clinical trial activities through the end of Phase IIB
for treatment of a rare disease or condition if (1) it gives public notice for a period of at least 120
days of NCATS’s intention to support the clinical trial activities in Phase IIB; (2) no public or
private organization provides credible written intent to NCATS that the organization has timely
plans to further the clinical trial activities or conduct clinical trials of a similar nature beyond
Phase IIA; and (3) NCATS ensures that support of the clinical trial activities in Phase IIB will not
increase the federal government’s liability beyond the award value of the center’s support. This
section does not authorize the HHS Secretary to disclose trade secret information or other
privileged or confidential information.
Provision
Section 2037 amends PHSA Section 479 to extend NCATS’s authority to support clinical trial
activities through the end of Phase IIB (instead of Phase IIA) and extends the exception for
treatment of a rare disease or condition through the end of Phase III (instead of Phase IIB).
It adds material to the NCATS annual/biennial report regarding methods and tools developed
since the previous report and whether such methods and tools are being used by the FDA to
support medical product reviews. Under the Cures Act, the next NCATS report, following
enactment, will include a complete list of all such methods and tools developed by research
supported by NCATS.
33 FDA, Inside Clinical Trials: Testing Medical Products in People, What Happens in a Clinical Trial?
http://www.fda.gov/Drugs/ResourcesForYou/Consumers/ucm143531.htm.
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Section 2038. Collaboration and Coordination to Enhance Research
Racial and ethnic minorities traditionally have been underrepresented in clinical trials. For
example, according to a 2011 report from an FDA-sponsored conference, “African Americans
represent 12% of the U.S. population but only 5% of clinical trial participants and Hispanics
make up 16% of the population but only 1% of clinical trial participants.”34 Biological differences
(e.g., genetic differences) may affect how people process or respond to medical products. This
variation could make a treatment less effective or perhaps more toxic for individuals with specific
genotypes. Therefore, it is important to study in clinical trials the safety and effectiveness of
medical products in a broadly representative sample of people who will likely use the products
following FDA approval.
PHSA Section 492B requires the NIH Director to include women and minorities in NIH-funded
clinical research and to conduct or support outreach to recruit minorities and women into clinical
research. Section 492B(d) requires the NIH Director, in consultation with the directors of the
NIH’s Office of Research on Women’s Health and the Office of Research on Minority Health, to
develop guidelines regarding the requirements under Section 492B.35
Provision
Section 2038 amends PHSA Section 402(b), requiring the NIH Director, in assessing research
priorities, to assemble accurate data on study populations in clinical research that specifies the
inclusion of women, members of minority groups, relevant age categories (including pediatric
subgroups), and other demographic variables. The data must be disaggregated by research area,
condition, and disease categories and made publically available on the NIH website. The NIH
Director is required to foster collaboration between the ICs that conduct research on human
subjects, allow for an increase in the number of subjects studied, and utilize a diverse study
population with special consideration of the determinants that contribute to health disparities.
Section 2038 amends PHSA Section 492B to make the biennial report a triennial report and
requires that the report contain specified data on the number of women and members of minority
groups included in clinical research projects conducted during the reporting period.
Section 2038 amends PHSA Section 486 to specify that the coordinating committee for the Office
of Research on Women’s Health will include NIH IC Directors or their senior staff-level
designees.
Section 2038 adds a new PHSA Section 404N, Population Focused Research, which requires the
NIH Director to encourage efforts to improve research related to the health of sexual and gender
minority populations through the increased participation of such groups in clinical research. The
HHS Secretary, in collaboration with the NIH Director and taking into account the
recommendations of the National Academy of Medicine, is required to continue to support
research for the development of appropriate measures related to reporting health information of
sexual and gender minority populations. Within two years of enactment, the HHS Secretary is
required to disseminate and make public such measures.
Section 2038 also amends PHSA Section 464z-3, adding that the National Institute on Minority
Health and Health Disparities Director may foster partnerships between the ICs and may
34 FDA, For Consumers, Clinical Trials Shed Light on Minority Health, at http://www.fda.gov/ForConsumers/
ConsumerUpdates/ucm349063.htm.
35 See “NIH Policy and Guidelines on The Inclusion of Women and Minorities as Subjects in Clinical Research,” at
http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.
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encourage the funding of collaborative research to achieve the goals of NIH related to minority
health and health disparities.
Section 2038 requires the NIH Director, within two years of enactment and taking into
consideration the findings of the working group established under Section 2039, to develop
policies for basic research to assess relevant biological variables, including sex, and how
differences between male and female cells, tissues, or animals may be studied and permits the
NIH Director to amend these policies as appropriate. It also requires the NIH Director to (1)
consult with the Office of Research on Women’s Health, the Office of Laboratory Animal
Welfare, and appropriate members of the scientific and academic communities; and (2) conduct
outreach in developing (and updating) policies on the influence of sex as a variable in basic
research, among other requirements. With respect to clinical research involving women and
minorities, the NIH Director must, within one year of enactment, update the guidelines
established under PHSA Section 492B(d) to reflect the science regarding sex differences and
improve adherence to the requirements of Section 492B of the PHSA, among other things.
Section 2038 requires the NIH Director, within six months of enactment, to convene a workshop
of experts on pediatrics and older populations to provide input on appropriate age groups to be
included in research studies. Within six months of the workshop, the NIH Director must
determine if it is necessary to update NIH policies “on the inclusion of relevant age groups in
clinical studies.” The Director is required to make available to the public the findings and
conclusions of the workshop and the updates to policies. The Director must ensure that agerelated data reported in the triennial report are made publicly available on the NIH website.
Section 2039. Enhancing the Rigor and Reproducibility of Scientific Research
Research supported by NIH is evaluated by a peer review system.36 Scientists competing for NIH
funding submit detailed applications describing their research plan. NIH considers the
applications under a two-tiered system of peer review. First, the applications are reviewed for
scientific and technical merit by committees composed of nongovernment scientists who are
experts in the relevant fields of research. Each application is thoroughly discussed and given a
score, which becomes the main determinant in whether an applicant will receive IC funding. A
second level of review occurs in the ICs when the applications are considered for program
relevance by the IC’s National Advisory Councils or Boards, composed of scientific and lay
representatives. The peer review system does not necessarily evaluate the applications for
reproducibility.
Provision
Section 2039 requires the HHS Secretary, acting through the NIH Director, to convene a working
group to make recommendations for a formal policy to enhance the rigor and reproducibility of
NIH-funded scientific research. The working group must consider various specified factors,
including, for example, preclinical and clinical experiment design and methods of statistical
analysis. It also requires the NIH Director, not later than 18 months after enactment, to consider
the recommendations and develop or update policies as appropriate. Finally, the NIH Director
must issue a report to the HHS Secretary and Congress, within two years of enactment, regarding
the recommendations and any subsequent policy changes. This section does not authorize the
HHS Secretary to disclose trade secret information or other privileged or confidential
information.
36 Peer review requirements described in PHSA Section 492.
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Section 2040. Improving Medical Rehabilitation Research at the National
Institutes of Health
PHSA Section 452 established in 1990 the National Center for Medical Rehabilitation Research
(the Center) within the Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD) at NIH to conduct and support research, and disseminate information, on
the rehabilitation of individuals with physical disabilities. It also required the NIH Director to
create a Medical Rehabilitation Coordinating Committee and a National Advisory Board on
Medical Rehabilitation Research.
The section also requires NICHD Director—in collaboration with the Director of the Center, the
Coordinating Committee, and the Advisory Board—as created by this section—to develop, and
periodically revise and update, a comprehensive plan for medical rehabilitation research.
Provision
Section 2040 amends PHSA Section 452 instructing the Director of the Center—in collaboration
with the Director of the Institute, the coordinating committee, and the advisory board—to develop
and, not less than every five years, revise and update a comprehensive plan for medical
rehabilitation research. The research plan must include goals and objectives for such research.
Prior to revising and updating the research plan, the Director of the Center must report to the
coordinating committee and the advisory board on the progress made toward achieving the
research goals and objectives, and provide recommendations for revising and updating the plan.
Within 30 days of revising and updating the plan, the Director of the Center is required to
transmit the plan to the President, and to specified congressional committees.
In addition, Section 2040 requires the HHS Secretary, along with the other federal agencies, to
review their medical rehabilitation research programs and take action to avoid duplication among
those programs through actions such as entering into interagency agreements. Finally, Section
2040 defines medical rehabilitation research as “the science of mechanisms and interventions that
prevent, improve, restore, or replace lost, underdeveloped, or deteriorating function.”
Section 2041.Task Force on Research Specific to Pregnant Women and
Lactating Women
Provision
Within 90 days of enactment, Section 2041 requires the HHS Secretary to establish a Task Force
on Research Specific to Pregnant and Lactating Women. The section specifies the duties,
membership, meeting schedule, and reporting requirements of the task force, which would be
terminated two years after its establishment, with an option for a two-year extension. It requires
the HHS Secretary, not later than two years after enactment, to update regulations and guidance,
as appropriate, regarding the inclusion of pregnant women and lactating women in research. This
section does not authorize the HHS Secretary to disclose trade secret information or other
privileged or confidential information.
Section 2042. Streamlining National Institutes of Health Reporting
Requirements
PHSA Title IV establishes numerous reporting requirements for the NIH Director related to the
activities of the agency. Specifically, PHSA Section 403(a) requires the NIH Director to submit to
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Congress biennially a report on NIH activities. Among other things, the report must include an
assessment of the state of biomedical and behavioral research, and details of all the research
activities conducted or supported by the ICs of NIH.
Provision
Section 2042 modifies or eliminates a number of different NIH reporting requirements. Within
two years of enactment, the heads of each IC must submit to the NIH Director a report on the
amount of funding made available for conducting or supporting research that involves
collaboration between a given IC and at least one other IC. This information will be included in
the triennial report required by Section 403(a), as amended by Section 2032.
It also (1) eliminates an annual reporting requirement regarding the number of experts and
consultants whose services are used by NIH; (2) makes a minor modification to the doctoral
degree reporting requirement; (3) makes a technical correction to a vaccine reporting
requirement; (4) changes the NCATS annual report to a biennial report; (5) eliminates the report
on Centers of Excellence; (6) eliminates the periodic reports on rapid HIV testing; and (7)
eliminates the National Institute on Nursing Research biennial report.
Section 2043. Reimbursement for Research Substances and Living Organisms
PHSA Section 301(a) establishes the general research authorities of the Public Health Service
through the HHS Secretary. Specifically, it requires the HHS Secretary to “conduct in the Service,
and encourage, cooperate with, and render assistance to other appropriate public authorities,
scientific institutions, and scientists in the conduct of, and promote the coordination of, research,
investigations, experiments, demonstrations, and studies relating to the causes, diagnosis,
treatment, control, and prevention of physical and mental diseases and impairments of man.” As
part of these authorities, the HHS Secretary is authorized to make available substances and living
organisms for biomedical and behavioral research.
Provision
Section 2043 amends PHSA Section 301(a) allowing the HHS Secretary, where research
substances and living organisms are made available to researchers through contractors, to direct
the contractors to collect payments for the costs incurred while making these substances and
organisms available. These amounts would be credited to the appropriations accounts that
incurred such costs and would be available until expended.
Section 2044. Sense of the Congress on Increased Inclusion of
Underrepresented Populations in Clinical Trials
PHSA Section 492B requires that the NIH Director ensure that clinical research conducted or
supported by NIH include members of minority groups as subjects. Each IC advisory council
must prepare biennial reports describing the manner in which the IC has complied with this
requirement. The report is submitted to the IC Director and is included in the biennial report
under PHSA Section 403.
Provision
Section 2044 states that it is the sense of Congress that the National Institute on Minority Health
and Health Disparities should include within its strategic plan ways to increase representation of
underrepresented populations in clinical trials.
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Subtitle E- Advancement of the National Institutes of Health
Research and Data Access
Sections 2051. Technical Updates to Clinical Trials Database
Sponsors of clinical trials for drugs, biologics, and devices regulated by the FDA are required to
submit registration and summary results information to ClinicalTrials.gov, the clinical trial
registry and results data bank operated by NIH’s National Library of Medicine (NLM) pursuant
to PHSA Section 402 subsections(i)-(j). Subparagraph 402(j)(2)(B) requires the NIH Director to
ensure that the public may, in addition to keyword searching, search the entries in the data bank
by various specified criteria, including the disease or condition being studied, the name of the
drug or device under investigation, and the location of the clinical trial. The NIH Director is
instructed to add search categories as deemed necessary and to ensure that the data bank is easy to
use, and that its entries are easily compared.
Under PHSA Section 402(j), those responsible for specified clinical trials of FDA-regulated
products have been required to submit registration information to ClinicalTrials.gov since
December 2007, submit summary results information for clinical trials of approved products
since September 2008, and submit adverse events information since September 2009. The section
also required the HHS Secretary, by rulemaking, to expand the requirements for submission of
summary results information, and authorized the HHS Secretary to use rulemaking to make other
changes in the requirements for submission of registration and results information. In November
2014, HHS published a proposed rule to clarify and expand requirements for the submission of
clinical trial registration and results information to ClinicalTrials.gov. The comment period was
extended until March 23, 2015; about 900 comments were received. The final rule was published
on September 21, 2016, and is expected take effect on January 18, 2017.37
Provision
Section 2051 amends PHSA Section 402(j)(2)(D), regarding posting of data, by adding new
language requiring the NIH Director to inform responsible parties of the option to request that
information for a medical device clinical trial be publically posted prior to the date of clearance or
approval. Section 2051 adds language that defines “combination product” for purposes of this
database.
Section 2052. Compliance Activities Reports
PHSA Section 402(i)-(j) delineates the requirements for the clinical trials database but currently
does not require the submission of a report to Congress.
Provision
Section 2052 requires the HHS Secretary, acting through the NIH Director and in collaboration
with the FDA Commissioner, to submit to Congress, not later than two years after enactment, a
report that “describes education and outreach, guidance, enforcement, and other activities
undertaken to encourage compliance with Section 402(j) of the PHSA” (i.e., with submission to
the clinical trials database).
37 NIH provides information on selected events, policies, and laws related to the development and expansion of Clinical
Trials.gov at https://clinicaltrials.gov/ct2/about-site/history.
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This section also requires the HHS Secretary, acting through the NIH Director and in
collaboration with the FDA Commissioner, to submit to Congress a report on registered clinical
trials, as specified, including activities undertaken by the HHS Secretary to educate responsible
persons about compliance with the requirements in Section 402(j). The HHS Secretary must
submit an initial report not later than two years after the compliance date of the final rule
implementing Section 402(j) of the PHSA. Two follow-up reports are required, which include
information on actions taken to enforce compliance with the ClinicalTrials.gov reporting
requirements.
Section 2053. Updates to Policies to Improve Data
PHSA Section 492B requires the NIH Director to include women and minorities in NIH-funded
clinical research and to conduct or support outreach to recruit minorities and women into clinical
research. Section 492B(c) requires the NIH Director to “ensure that the trial is designed and
carried out in a manner sufficient to provide for a valid analysis of whether the variables being
studied in the trial affect women or members of minority groups, as the case may be, differently
than other subjects in the trial.”
Provision
Section 2053 amends PHSA Section 492B(c), adding that the NIH Director must consider
whether grant award recipients conducting research related to the inclusion of women and
minority populations in clinical research have complied with the reporting requirements of
ClinicalTrials.gov. The NIH Director must also take such compliance into consideration when
awarding any future grants to such an entity. The Director of NIH must encourage the reporting of
results to ClinicalTrial.gov “through any additional means determined appropriate by the
Director.”
Section 2054. Consultation
PHSA Section 402(i)-(j) requires that the HHS Secretary consult with FDA, NIH, and the Centers
for Disease Control and Prevention (CDC) prior to establishing the “data bank of information on
clinical trials for drugs for serious or life-threatening diseases and conditions.” In addition, it
requires that the HHS Secretary consult with experts in risk communication to ensure that posted
information regarding the database is not misleading to patients or the lay public. The HHS
Secretary must also consult with other federal agencies to ensure that clinical trial information is
submitted to the database.
Provision
Section 2054 requires, within 90 days of enactment, the HHS Secretary to consult with relevant
federal agencies, including FDA, the Office of the National Coordinator for Health Information
Technology, and NIH, as well as other stakeholders (including patients, researchers, physicians,
industry representatives, and developers of health information technology), to receive
recommendations to improve ClinicalTrials.gov, including improvements in usability,
functionality, and search capability.
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Subtitle F- Facilitating Collaborative Research
Section 2061. National Neurological Conditions Surveillance System
The PHSA does not explicitly authorize or require surveillance of neurological diseases in
general, although the HHS Secretary may conduct such activities under general authorities in
PHSA Title III. Surveillance is explicitly authorized for certain specified neurological disorders
(e.g., amyotrophic lateral sclerosis and autism spectrum disorder).38
Provision
Section 2061 adds a new PHSA Section 399S-1, which requires the HHS Secretary, through the
CDC Director and in consultation with specified parties, to establish a National Neurological
Conditions Surveillance System by enhancing and expanding relevant surveillance infrastructure
and activities. The system may include a registry. In establishing the system, the HHS Secretary is
required to collect and manage information in order to facilitate research and, as is practicable, to
include information on incidence and prevalence, demographics, risk factors, and diagnostic and
progression markers.39 Additional data elements may include the natural history, prevention,
detection, management, and treatment approaches for the diseases, and the development of
outcome measures. The HHS Secretary initially may address a limited number of neurological
diseases.
The section also authorizes the HHS Secretary to award grants, contracts, or cooperative
agreements with public or private nonprofit entities to implement this provision. The HHS
Secretary must make information and analysis obtained from the system available to other federal
health agencies and state and local agencies, and, as appropriate and subject to federal privacy
laws, to researchers and the public. Within one year of the establishment of a system under this
section and biennially thereafter, the HHS Secretary must provide to Congress and the public an
interim report on such system. A report on implementation of this section is due to Congress four
years after enactment. The section authorizes to be appropriated $5 million for each of fiscal
years 2018 through 2022 to carry out activities under this section.
Section 2062. Tick-Borne Diseases
The HHS Secretary is given broad authority to conduct research related to disease under Title III
of the PHSA. Specifically, the HHS Secretary is required to conduct research, investigations,
experiments, demonstrations, and studies relating to the causes, diagnosis, treatment, control, and
prevention of disease.40 The act does not explicitly address tick-borne diseases, but HHS agencies
do carry out research and public health activities on tick-borne diseases under the Secretary’s
general authority.
38 PHSA Section 399S; 42 U.S.C. §280g-7 and PHSA Section 399AA; 42 U.S.C. §280i.
39 A disease marker is a substance or other measurable parameter that can be used to identify the presence or severity
of a health condition. A progression marker is one that could indicate worsening or improvement in the condition over
time.
40 PHSA Section 301 et seq.; 42 U.S.C. §241 et seq.
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Provision
Section 2062 requires the HHS Secretary to continue to conduct or support epidemiological,
basic, translational, and clinical research related to vector-borne diseases, including tick-borne
diseases. It also requires the HHS Secretary to ensure that the triennial report of the NIH Director
to Congress41 includes information on NIH activities with respect to tick-borne diseases.
The section also requires the HHS Secretary to establish a working group to review the status of
research on tick-borne diseases and relevant federal activities, and to report on such activities and
any recommended changes every two years. The section provides requirements related to the
working group’s membership, responsibilities, meeting frequency, and reporting. The working
group is subject to the Federal Advisory Committee Act (FACA), and will terminate six years
after enactment.
Section 2063. Accessing, Sharing, and Using Health Data for Research
Purposes
The Health Information Portability and Accountability Act (HIPAA) privacy rule describes the
circumstances under which HIPAA-covered entities such as health plans and health care
providers are permitted to use or disclose individually identifiable health information (i.e.,
protected health information, or PHI) without an individual’s written authorization.42 In general,
covered entities may use or disclose PHI for the purposes of treatment, payment, and other
routine health care operations with few restrictions.43
The disclosure of PHI to researchers generally requires an individual’s authorization unless an
Institutional Review Board (or equivalent Privacy Board) waives the authorization.44 A covered
entity may, however, allow researchers access to PHI to prepare a research protocol, provided the
PHI is not removed from the covered entity. The privacy rule traditionally has required
authorizations to be study-specific; authorizations for future research were prohibited. In a
January 2013 final rule, HHS permitted authorizations for future research if a sufficiently clear
description of the future research is provided.45
Provision
Section 2063 instructs the HHS Secretary, within one year of enactment, to issue guidance
clarifying some of the privacy rule’s restrictions on researchers’ access to PHI. First, the HHS
Secretary is required to clarify that the rule’s provision prohibiting researchers from removing
PHI during preparation of a research protocol permits remote access to PHI by researchers,
provided appropriate security and privacy safeguards are in place and the PHI is not copied or
retained by the researchers. Second, the Secretary is required to clarify the circumstances under
which a HIPAA authorization to use or disclose PHI for future research contains sufficient
information; for example, the authorization (1) sufficiently describes the purposes such that it
would be reasonable for an individual to expect that the PHI could be used or disclosed for future
41 This report is required under PHSA Section 403, 42 U.S.C. §283, as amended by this act.
42 The HIPAA privacy rule is codified at 45 C.F.R. Part 164, Subpart E.
43 45 C.F.R. §164.506.
44 45 C.F.R. §164.512(i)(1)(i).
45 Department of Health and Human Services, Office of the Secretary, “Modifications to the HIPAA Privacy, Security,
Enforcement, and Breach Notification Rules Under the Health Information Technology for Economic and Clinical
Health Act and the Genetic Information Nondiscrimination Act; Other Modifications to the HIPAA Rules; Final Rule,”
78 Federal Register 5566, 5611, January 25, 2013.
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research; (2) states that the authorization will either expire at a specified time or will remain valid
unless revoked by the individual; and (3) provides revocation instructions to the individual.
Finally, Section 2063 requires the HHS Secretary, within one year of enactment, to convene a
working group to study the uses and disclosures of PHI for research purposes. The working group
must include various specified federal and nonfederal members, and must report to the HHS
Secretary within one year of its establishment with recommendations on whether the uses and
disclosures for research purposes should be modified, as specified. The HHS Secretary must
submit the report to Congress and make it publicly available, at which time the working group
shall terminate.
Subtitle G- Promoting Pediatric Research
Section 2071. National Pediatric Research Network
In 2013, PHSA Section 409D(d) established the NIH Pediatric Research Network “in order to
more effectively support pediatric research and optimize the use of Federal resources.”46
Provision
Section 2071 amends PHSA Section 409(D)(d) to (1) eliminate language telling the NIH Director
to consult with the Director of the Eunice Kennedy Shriver National Institute of Child Health and
Human Development but (2) retains language telling the NIH Director to collaborate with the ICs
that carry out pediatric research, (3) amends language to require the NIH Director (it had
previously been permitted) to award funding to support the pediatric research consortia, and (4)
require that support for the pediatric research consortia not exceed five years.
Section 2072. Global Pediatric Clinical Study Network
Provision
Section 2072 expresses the sense of Congress that (1) NIH should encourage a global pediatric
clinical study network through funding to support new and early stage investigators; (2) the HHS
Secretary should engage with clinical investigators and international authorities, including those
in the European Union, during the formation of the network to encourage their participation; and
(3) the HHS Secretary should continue to encourage and facilitate the network after it is
established.
46 Section 409D(d) was added to the PHS Act by P.L. 113-55, the Prematurity Research Expansion and Education for
Mothers who deliver Infants Early Reauthorization Act, or the PREEMIE Reauthorization Act, which was signed into
law on November 27, 2013.
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Title III-Development47
Subtitle A-Patient Focused Drug Development
The Food and Drug Administration Safety and Innovation Act (FDASIA; P.L. 112-144) expanded
FDA’s authorities and strengthened the agency’s ability to safeguard and advance public health.48
FDASIA added a new FFDCA Section 569C “Patient Participation in Medical Product
Discussion,” facilitating increased involvement of patients earlier in the regulatory process for
medical product review. Section 569C directs the HHS Secretary to
develop and implement strategies to solicit the views of patients during the medical product
development process and consider the perspectives of patients during regulatory
discussions by (1) fostering participation of a patient representative who may serve as a
special government employee in appropriate agency meetings with medical product
sponsors and investigators; and (2) exploring means to provide for identification of patient
representatives who do not have any, or have minimal, financial interests in the medical
products industry.
Sections 3001-3004. Patient Experience Data, Patient-Focused Drug
Development Guidance, Streamlining Patient Input, Report on Patient
Experience Drug Development
Provisions
Section 3001 amends FFDCA Section 569C by adding a new subsection (b), “Statement of
Patient Experience,” requiring the HHS Secretary, upon approval of a new drug application
(NDA), to make public any patient experience data and related information submitted and
reviewed as part of the application. “Data and information” refers to patient experience data,
information on patient-focused drug development tools, and other relevant information, as
determined by the HHS Secretary. “Patient experience data” is defined as
(1) data that are collected by any persons (including patients, family members and
caregivers of patients, patient advocacy organizations, disease research foundations,
researchers, and drug manufacturers); and (2) are intended to provide information about
patients’ experiences with a disease or condition, including—(A) the impact of such
disease or condition, or a related therapy, on patients’ lives; and (B) patient preferences
with respect to treatment of such disease or condition.
Section 3002 requires the HHS Secretary, acting through the FDA Commissioner, to develop a
plan to issue draft and final guidance, over a period of five years, regarding the collection of
patient experience data and the use of such data in drug development. This section specifies the
contents of the guidance documents (e.g., methods that could be used to collect and submit
patient experience data, and methodologies, standards, and technologies that could be used to
collect and analyze clinical data for regulatory decisionmaking).
Section 3003 exempts FDA from the Paperwork Reduction Act clearance process when
requesting patient experience data under sections 3001 and 3002 of the 21st Century Cures Act.
47 Subtitle J, “Technical Corrections,” is not summarized in this report.
48 FDA, The Food and Drug Administration Safety and Innovation Act (FDASIA) Section 1137: Patient Participation
in Medical Product Discussions Report on Stakeholder Views, February 19, 2016; see http://www.fda.gov/downloads/
ForPatients/About/UCM486859.pdf.
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Section 3004 requires the HHS Secretary, acting through the FDA Commissioner, to publish on
the FDA website, no later than June 1 of 2021, 2026, and 2031, a report “assessing the use of
patient experience data in regulatory decision-making, in particular with respect to the review of
patient experience data and information on patient-focused drug development tools....”
Subtitle B-Advancing New Drug Therapies
Section 3011. Qualification of Drug Development Tools
Lengthy clinical trials have been found to contribute to the high cost of drug development. In
clinical settings where the disease course is long and an extended period of time would be
required to measure the intended clinical benefit of a drug, surrogate endpoints—based on the
measurement of biomarkers—may be used to determine the clinical benefit of a product, rather
than clinical endpoints. Surrogate endpoints “enable smaller, faster, and thus cheaper clinical
trials. In addition, pharmaceutical companies argue that using surrogates means that fewer
patients are exposed during testing, and beneficial new medications reach the market faster. The
main disadvantage of these endpoints is that favorable effects on surrogates do not automatically
translate into benefits to health.”49 A number of drugs have been approved on the basis of
surrogate endpoint data and, after adoption into medical practice, have been shown to be harmful
through clinical trials or other subsequent analysis.50 The FDA uses surrogate endpoints in about
half of new drug approvals.51
The Institute of Medicine defines a clinical endpoint as “a characteristic or variable that reflects
how a patient [or consumer] feels, functions, or survives. Death is one example of a clinical
endpoint.”52 IOM defines “surrogate endpoint” in the following way:
a biomarker that is intended to substitute for a clinical endpoint. A surrogate endpoint is
expected to predict clinical benefit (or harm or lack of benefit or harm) based on
epidemiologic, therapeutic, pathophysiologic, or other scientific evidence. For example,
blood pressure has served as a surrogate endpoint for morbidity and mortality due to
cardiovascular disease in trials of several classes of antihypertensive drugs. A surrogate
endpoint represents a special use of a biomarker, in which the biomarker substitutes for a
clinical endpoint.53
FDASIA (P.L. 112-144) amended FFDCA Section 506 (on fast track products) by adding the
following: “The HHS Secretary shall ... establish a program to encourage the development of
surrogate and clinical endpoints, including biomarkers, and other scientific methods and tools that
can assist the HHS Secretary in determining whether the evidence submitted in an application is
reasonably likely to predict clinical benefit for serious or life-threatening conditions for which
significant unmet medical needs exist.”54
49 Staffan Svensson, David B. Menkes, and Joel Lexchin, "Surrogate Outcomes in Clinical Trials—A Cautionary Tale,"
JAMA Internal Medicine, vol. 173, no. 8 (April 22, 2013), pp. 611-612.
50 Staffan Svensson, David B. Menkes, and Joel Lexchin, “Surrogate Outcomes in Clinical Trials—A Cautionary Tale,”
JAMA Internal Medicine, vol. 173, no. 8 (April 22, 2013), Supplementary Online eTable.
51 Jerry Avorn and Aaron S. Kesselheim, “The 21st Century Cures Act—Will It Take Us Back in Time?,” The New
England Journal of Medicine, June 3, 2015, http://www.nejm.org/doi/full/10.1056/NEJMp1506964.
52 IOM, Perspectives on Biomarker and Surrogate Endpoint Evaluation: Discussion Forum Summary, January 18,
2011, p.6.
53 Ibid.
54 FFDCA §506(d)(2).
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Provision
Section 3011 adds a new FFDCA Section 507, “Qualification of Drug Development Tools,”
which requires the HHS Secretary to establish a process for the qualification of drug development
tools. A drug development tool is defined to include (1) a biomarker; (2) a clinical outcome
assessment; and (3) any other method, material, or measure that the HHS Secretary determines
aids drug development and regulatory review.
Under new FFDCA Section 507, the HHS Secretary is allowed to accept a qualification
submission based on factors that include its scientific merit, and the HHS Secretary is allowed to
prioritize review of a qualification submission based on factors including, for example, the
severity, rarity, or prevalence of the disease being targeted or the availability or lack of an
alternative treatment. The HHS Secretary is allowed, through grants or other specified
mechanisms, to consult with biomedical research consortia and may consider their
recommendations in review of the qualification submission. “Biomedical research consortia” is
defined as collaborative groups that may take the form of public-private partnerships and may
include, among others, government agencies, institutions of higher education, patient advocacy
groups, industry representatives, clinical and scientific experts, and other relevant individuals.
The HHS Secretary is required to carry out a full review of the qualification package and to
determine if the drug development tool at issue is qualified for its proposed context of use.
A qualified drug development tool is allowed to be used to obtain approval or licensure of a drug
or biologic or to support a product’s investigational use. The HHS Secretary is allowed to rescind
or modify the granted qualification if he or she determines the drug development tool is not
appropriate for the proposed context; if the HHS Secretary does this, the requestor would be
granted a meeting, upon request, with the HHS Secretary to discuss the basis of the decision.
New FFDCA Section 507 requires the HHS Secretary to make public on the FDA website, and
update at least biannually, information about the qualification submissions, the HHS Secretary’s
determinations in response to the submissions, and any subsequent modifications to the HHS
Secretary’s determinations, among others. It also specifies that nothing in this section is to be
construed to allow the HHS Secretary to release any information contained in an application for
approval or licensure of a drug or biologic that is confidential commercial or trade secret
information; in addition, nothing in the section is allowed to be construed as altering the standards
of evidence for approval or licensure of a drug or biologic or to limit the Secretary’s authority to
approve or license such products.
The section also requires the HHS Secretary, not later than three years after enactment, to publish
draft guidance to implement new FFDCA Section 507, in consultation with the biomedical
research consortia and other interested parties through a collaborative public process. The
guidance is required to, for example, provide “a conceptual framework describing appropriate
standards and scientific approaches to support the development of biomarkers.” The HHS
Secretary is required to issue final guidance not later than six months after the comment period
for the draft guidance closes. To inform the guidance, the HHS Secretary is required, in
consultation with the biomedical research consortia, to develop a taxonomy for the classification
of biomarkers for use in drug development. The HHS Secretary is required to make this publicly
available not later than two years after enactment and to finalize the taxonomy not later than one
year after the public comment period closes.
The section requires the HHS Secretary, not later than two years after enactment, to convene a
public meeting regarding the qualification process under new FFDCA Section 507. The HHS
Secretary is also required to publish a report on FDA’s website, not later than five years after
enactment, to include specified information.
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Section 3012. Targeted Drugs for Rare Diseases
Precision medicine is a relatively new term for what has traditionally been called personalized
medicine (or targeted medicine), the idea of providing health care to individuals based on specific
patient characteristics. This approach relies on companion diagnostics to target drugs and
biological products to specific subsets of patients. Rare diseases often have genetic origins, and
advances in medicine have resulted in the development of new treatments that work by targeting
the genetic mutations that cause these diseases. It is inherently difficult to develop drugs for rare
diseases because of the small patient population available to conduct clinical trials, so targeted
therapies are generally first developed for patients with the most frequent disease-causing
mutations. However, to provide therapies for the full spectrum of certain genetic rare diseases,
additional targeted therapies would need to be developed.
Targeted therapies, because they may be treating small subsets of patients, sometimes qualify as
“orphan drugs.” Such drugs are called orphan drugs because firms may lack the financial
incentives to sponsor products to treat small patient populations. Orphan drugs receive their
designation pursuant to FFDCA Section 526(a),55 a designation that was created by the Orphan
Drug Act (P.L. 97-414) to encourage firms to develop pharmaceuticals to treat rare diseases and
conditions by providing an extended period of market exclusivity. FFDCA Section 526(a) defines
“rare disease or condition” as any disease or condition that affects fewer than 200,000 persons in
the United States, or affects more than 200,000 persons in the United States and for which there is
no reasonable expectation that the cost of developing and making the drug available in the United
States will be recovered from U.S. sales.
Provision
Section 3012 adds a new FFDCA Section 529A “Targeted Drugs for Rare Diseases,” with the
purpose of facilitating the “development, review, and approval of genetically targeted drugs and
variant protein targeted drugs to address an unmet medical need in one or more patient subgroups,
including subgroups of patients with different mutations of a gene, with respect to rare diseases or
conditions that are serious or life-threatening; and maximize the use of scientific tools or
methods, including surrogate endpoints and other biomarkers, for such purposes.”
Section 3012 allows the HHS Secretary to permit the sponsor of a new drug application for a
genetically targeted drug or a variant protein-targeted drug to rely on data and information that
has been previously developed and submitted, either by the same or a different sponsor (with
permission), as part of an approved application that incorporates or uses the same or similar
genetically targeted technology or for a variant protein-targeted drug.56 It defines genetically
targeted drugs, genetically targeted technology, and variant protein targeted drugs. New FFDCA
Section 529A is not to be construed to limit the HHS Secretary’s product approval authorities, or
to entitle sponsors to obtain information in another sponsor’s application without permission of
the other sponsor.
55 FFDCA §526, “Designation of Drugs for Rare Diseases or Conditions”; 21 U.S.C. §360bb.
56 An example of a variant protein-targeted drug is Gleevec (imatinib), which is used to treat leukemia and other kinds
of cancer. It targets at least one variant form of a tyrosine kinase enzyme (an enzyme is a protein) called BCR-Abl
tyrosine kinase (chromosol translocation); see http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1907317/.
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Section 3013. Reauthorization of Program to Encourage Treatments for Rare
Pediatric Diseases
FDASIA (P.L. 112-144) added a new FFDCA Section 529, creating the pediatric priority review
voucher program. This voucher program, funded by user fees, provides a transferable voucher,
under specified conditions, to a sponsor of an approved new drug or biological product for a rare
pediatric disease to be used for the priority review of another application. The term “rare pediatric
disease” refers to a disease that affects (1) individuals aged from birth to 18 years, and (2) fewer
than 200,000 persons in the United States, or affects more than 200,000 persons in the United
States and for which there is no reasonable expectation that the cost of developing and making the
drug available in the United States will be recovered from U.S. sales. For example, in 2014,
BioMarin was awarded a rare pediatric disease priority review voucher for the drug Vimizim
(elosulfase alfa) —a treatment for a rare congenital enzyme disorder.57 BioMarin sold the voucher
to Sanofi and Regeneron for $67.5 million, and it was then used to speed the approval of Praluent
(alirocumab) injection, a cholesterol-lowering treatment.58
FDASIA terminated the authority to award such vouchers one year after the HHS Secretary
awards the third-priority voucher and required the GAO, beginning on the date of the third
voucher award, to study and then report on the effectiveness of the voucher program in the
development of products that prevent or treat rare pediatric diseases. FDA awarded the third
voucher in March 2015, triggering the March 2016 sunset of this authority. This authority was
extended until September 30, 2016, by the Consolidated Appropriations Act of 2016 (P.L. 114113).
The Advancing Hope Act of 2016 (P.L. 114-229), reported as part of the package of Senate
medical innovation bills, was signed into law on September 30, 2016.59 The law temporarily
extended the program’s authority through December 31, 2016. It also amended the definition of
“rare pediatric disease” in FFDCA Section 529(a) by adding the following words in italics: “The
disease is a serious or life-threatening disease in which the serious or life-threatening
manifestations primarily affect individuals aged from birth to 18 years, including age groups
often called neonates, infants, children, and adolescents.” It also added the requirement that the
sponsor of a rare pediatric disease product application that intends to request a voucher for a rare
pediatric disease product notify the HHS Secretary of such intent upon submission of the rare
pediatric disease product application. In addition, the law required that GAO study the voucher
program and report to Congress, by January 31, 2022, on the program’s effectiveness as an
incentive for developing drugs that treat or prevent rare pediatric diseases and that would not
otherwise have been developed.
57 FDA News Release, “FDA approves Vimizim to treat rare congenital enzyme disorder,” February 14, 2014, see
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm386008.htm.
58 RAPS, “First Pediatric Priority Review Voucher Goes up for Sale, Fetching $67M,” July 31, 2014, see
http://www.raps.org/Regulatory-Focus/News/2014/07/31/19905/First-Pediatric-Priority-Review-Voucher-Goes-up-forSale-Fetching-67M/#sthash.RsUDF53u.dpuf. See also “Drug Makers Buy Pricey Vouchers to Speed Products to
Market,” http://www.wsj.com/articles/drug-firms-buy-pricey-vouchers-to-speed-products-to-market-1445333403.
59 H.R. 6, Section 2152, Reauthorization of Rare Pediatric Disease Priority Review Voucher Incentive Program, also
contained a comparable provision. For additional information, see CRS Report R44502, Senate Medical Innovation
Bills: Overview and Comparison with the 21st Century Cures Act (H.R. 6), coordinated by C. Stephen Redhead and
Amanda K. Sarata.
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Provision
Section 3013 extends the authority to award such priority review vouchers until September 30,
2020. A new drug application or a biologics license application submitted to FDA after the
enactment of the 21st Century Cures Act for a product designated as a rare pediatric disease drug
before September 30, 2020, remains eligible to receive a priority review voucher, provided it is
approved by September 30, 2022. This provision also removes the requirement that GAO study
the pediatric priority review program under FFDCA Section 529.
Section 3014. GAO Study of Priority Review Voucher Programs
Under the Prescription Drug User Fee Act (PDUFA) of 1992, FDA agreed to specific goals for
improving the drug review time and created a two-tiered system of review times: Standard
Review and Priority Review. Compared with the amount of time standard review generally takes
(approximately 10 months), a priority review designation means FDA’s goal is to take action on
an application within 6 months.60 An application for a drug may receive priority review
designation if it is for a drug that treats a serious condition and, if approved, would provide a
significant improvement in safety or effectiveness.
An application may also receive priority review if it is the subject of a priority review voucher.
Currently, FDA has two authorized priority review voucher programs (the rare pediatric disease
priority review program, and the tropical disease priority review program), funded by user fees,
which provide a transferable voucher, under specified conditions, to a sponsor of an approved
new drug or biological product to be used for the priority review of another application. The
purpose of the priority review drug voucher programs is to incentivize development of new
treatment for diseases that may otherwise not attract development interest from companies due to
either cost or lack of market opportunities. Section 3086 of this bill creates a third priority review
voucher program to encourage the development of drugs and vaccines for agents that present a
threat to national security.
Provision
Section 3014 requires the Comptroller General to conduct a study addressing the effectiveness
and impact of three FDA priority review voucher programs: (1) the neglected tropical disease
priority review voucher program, (2) the rare pediatric disease priority review voucher program,
and (3) the priority review voucher program for drugs and vaccines to treat agents that present a
national security threat. It requires the Comptroller General to submit a report to Congress with
specified contents (including drug indications, value of the voucher, resources used for drug
review under these programs, and consideration of program improvements) by January 31, 2020.
The Comptroller is directed to conduct the study and issue the specified reports in a way that does
not compromise national security.
Section 3015. Amendments to the Orphan Drug Grants
The Orphan Drug Act of 1983 (P.L. 97-414) was signed into law to incentivize development of
drugs to treat rare diseases, each of which affects fewer than 200,000 individuals in the United
States. Since the law’s passage, FDA has approved over 400 new orphan drugs and biological
products.61 Incentives for sponsors of orphan drugs include seven years of market exclusivity, tax
60 FDA, Priority Review, http://www.fda.gov/ForPatients/Approvals/Fast/ucm405405.htm.
61 FDA, Office of Orphan Products Development, see http://www.fda.gov/AboutFDA/CentersOffices/
OfficeofMedicalProductsandTobacco/OfficeofScienceandHealthCoordination/ucm2018190.htm.
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credits for clinical trial expenses, user fee waivers, and eligibility for federal grants to cover costs
of qualified clinical testing expenses.
The FFDCA contains provisions to grant market exclusivity for statutorily defined time periods
(in months or years) to the holder of an approved drug application for a product that is, for
example, a drug used in the treatment of a rare disease or condition, the first generic version of a
drug to come to market, certain pediatric uses of approved drugs, and new qualified infectious
disease products. During the period of exclusivity, FDA does not grant marketing approval to
another manufacturer’s product.
Section 5 of the Orphan Drug Act (21 U.S.C. 360ee) allows the HHS Secretary to make grants
and enter into contracts with certain entities to assist in “defraying the costs of qualified clinical
testing expenses incurred in connection with the development of drugs for rare diseases and
conditions.” Section 5 defines “qualified testing” as human clinical testing
(i) which is carried out under an exemption for a drug for a rare disease or condition under
section 505(i) of the Federal Food, Drug, and Cosmetic Act (or regulations issued under
such section); (ii) which occurs after the date such drug is designated under section 526 of
such Act and before the date on which an application with respect to such drug is submitted
under section 505(b) or under section 351 of the Public Health Service Act; and (B)
preclinical testing involving a drug is designated under section 526 of such Act and before
the date on which an application with respect to such drug is submitted under section 505(b)
or under section 351 of the Public Health Service Act.
Provision
Section 3015 amends Section 5 of the Orphan Drug Act (21 U.S.C. 360ee) to broaden the use of
grants made by the HHS Secretary to assist in “defraying the costs of developing drugs for rare
diseases or conditions” to include “prospectively planned and designed observational studies and
other analyses conducted to assist in the understanding of the natural history of a rare disease or
condition and in the development of a therapy.”
Section 3016. Grants for Studying Continuous Drug Manufacturing
In March 2015 congressional testimony, the then FDA Commissioner spoke of new
manufacturing technologies that could eventually “lower costs, limit drug shortages, and reduce
supply chain vulnerabilities.”62 Continuous manufacturing, for example, could produce a drug in
a “continuous stream” rather than in a “series of sequential and discrete” operations. She noted
the need for “academic research in this area and expanding opportunities for collaboration,
possibly through public-private partnerships or consortia.”
Provision
Section 3016 allows the HHS Secretary to “award grants to institutions of higher education and
nonprofit organizations for the purpose of studying and recommending improvements to the
process of continuous manufacturing of drugs and biological products and similar innovative
monitoring and control techniques.”
62 Statement of Margaret A. Hamburg, M.D., Commissioner of Food and Drugs, Food and Drug Administration,
Department of Health and Human Services, before the Committee on Health, Education, Labor and Pensions, United
States Senate, March 10, 2015, http://www.fda.gov/newsevents/testimony/ucm437481.htm.
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Subtitle C-Modern Trial Design and Evidence Development
Section 3021. Novel Clinical Trial Designs
The traditional approach to clinical trials for drugs has focused on a design planned in advance
that includes specific treatments and doses and durations, specified decision rules for
patient/subject assignment to treatment groups, and prespecified statistical analysis to test a
prespecified qualitative and quantitative hypothesis. Because the analytic plan is set in advance, it
does not lend itself to unintentional (or intentional) bias as data are reviewed. A researcher may
feel strongly about a hypothesis and hope that the results will confirm an idea, but he or she must
carry out the analysis so the results can be understood and replicated by others. A drawback to
trials with this kind of static design is that they tend to take a long time and cannot adapt to new
information learned during the trial. In recent years, some clinical and methodological researchers
have looked to adaptive trial designs and statistical analyses using techniques (such as Bayesian
statistics) that can provide mid-course feedback. Because a mistaken finding of effectiveness or
safety could put a dangerous drug on the market or delay the approval of a useful drug, FDA has
acted cautiously in accepting alternative trial designs. In 2010, FDA published draft guidance on
the use of adaptive trial design.63
Provision
Section 3021 requires the HHS Secretary to conduct a public meeting and issue guidance to assist
sponsors in “incorporating complex adaptive and other novel trial designs into proposed clinical
protocols and applications for new drugs” under FFDCA Section 505 and biological products
under PHSA Section 351. Such guidance must address, for example, the use of complex adaptive
and other novel trial designs, including how such trials “help to satisfy the substantial evidence
standard” under FFDCA Section 505(d), and the types of quantitative and qualitative information
that should be submitted for review. Prior to updating or issuing guidance, the HHS Secretary is
required to consult with stakeholders through a public meeting. Not later than 18 months after the
date of the public meeting, the HHS Secretary, acting through the FDA Commissioner, must
update or issue draft guidance, and final guidance not later than one year after the close of the
public comment period on the draft.
Section 3022. Real World Evidence
To approve a new drug for marketing in the United States, FDA reviews the sponsor’s new drug
application (NDA) to assess, among other things, whether the drug is safe and effective for its
intended purpose. FFDCA Section 505(d) refers to “substantial evidence,” which it defines as
evidence consisting of adequate and well-controlled investigations, including clinical
investigations, by experts qualified by scientific training and experience to evaluate the
effectiveness of the drug involved, on the basis of which it could fairly and responsibly be
concluded by such experts that the drug will have the effect it purports or is represented to
have under the conditions of use prescribed, recommended, or suggested in the labeling or
proposed labeling thereof. If the Secretary determines, based on relevant science, that data
from one adequate and well-controlled clinical investigation and confirmatory evidence
(obtained prior to or after such investigation) are sufficient to establish effectiveness, the
Secretary may consider such data and evidence to constitute substantial evidence for
63 FDA, “DRAFT Guidance for Industry: Adaptive Design Clinical Trials for Drugs and Biologics,” Center for Drug
Evaluation and Research and Center for Biologics Evaluation and Research, February 2010, http://www.fda.gov/
RegulatoryInformation/Guidances/default.htm.
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purposes of the preceding sentence. The Secretary shall implement a structured risk-benefit
assessment framework in the new drug approval process to facilitate the balanced
consideration of benefits and risks, a consistent and systematic approach to the discussion
and regulatory decisionmaking, and the communication of the benefits and risks of new
drugs. Nothing in the preceding sentence shall alter the criteria for evaluating an
application for premarket approval of a drug.
The associated rule (21 C.F.R. 314.126) describes characteristics of “adequate and well-controlled
studies,” which include a statement of objectives, an analytic plan, a control group, quantification
of treatment duration and timing, and method of sample size determination. The study design
would lead to the identification of appropriate research subjects and include methods to minimize
bias in the assignment of subjects to treatment groups as well as in data analysis.
These characteristics basically describe a controlled (often randomized) clinical trial. The rule,
however, places these characteristics in the context of having “been developed over a period of
years and are recognized by the scientific community as the essentials of an adequate and wellcontrolled clinical investigation.” The rule states that FDA should “consider” these characteristics
in its determination of effectiveness claims.
Provision
Section 3022 adds a new FFDCA Section 505F, “Utilizing Real World Evidence,” requiring the
HHS Secretary to “establish a program to evaluate the potential use of real world evidence to help
to support the approval of a new indication for a drug approved under Section 505(c) and to help
support or satisfy postapproval study requirements.” The provision defines “real world evidence”
as “data regarding the usage, or the potential benefits or risks, of a drug derived from sources
other than randomized clinical trials.”
Section 3022 requires the HHS Secretary to establish a draft framework for implementing the
program to include specified content (e.g., sources of real world evidence such as ongoing safety
surveillance, observational studies, claims, and patient-centered outcomes research activities). It
also requires the HHS Secretary, in developing the framework, to consult with interested parties,
which could be done via a public-private partnership or a contract, grant, or other appropriate
arrangement. The HHS Secretary is required to use the new “program to evaluate the potential
use of real world evidence” to inform the development of guidance for industry. This section is
not to be construed to alter the standards of evidence for approval of drugs or biologics, including
the substantial evidence standard, or to alter “the Secretary’s authority to require postapproval
studies or clinical trials, or the standards of evidence under which studies or trials are evaluated.”
Sections 3023-3024. Protection of Human Research Subjects, Informed Consent
Waiver or Alteration for Clinical Investigations
Provisions
The HHS Human Subject Regulations are a core set of federal standards for protecting human
subjects in HHS-sponsored research.64 These regulations are commonly referred to as the
“Common Rule” because the same requirements have been adopted by many non-HHS federal
departments and agencies, who apply the regulations to the research they fund. Under the
Common Rule, research protocols must be approved by an Institutional Review Board (IRB) to
64 45 C.F.R. Part 46, Subpart A.
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ensure that the rights and welfare of the research subjects are protected.65 The rule lists several
criteria for IRB approval, including the requirement that researchers obtain the informed consent
of their research subjects.66 In addition, it sets out the types of information that must be provided
to prospective research subjects during the informed consent process, including an explanation of
the purpose of the research, a description of the research procedures, and a description of the risks
and benefits of the research.67 An IRB may decide to waive the informed consent requirement if it
determines that (1) the research poses no more than minimal risk to the subjects, (2) the waiver
will not adversely affect the rights and welfare of the subjects, and (3) the research is not
practicable without a waiver.68
HHS has promulgated additional protections for certain vulnerable populations involved in
research. Those groups include pregnant women, human fetuses, and neonates; prisoners; and
children.69
FDA has issued its own set of Human Subject Regulations, which are similar, but not identical, to
the Common Rule.70 FDA applies these regulations to all the research it regulates, including
clinical trials of new drugs and medical devices, regardless of the source of funding for the
research. Humanitarian use devices, which are currently approved by FDA for diagnosing or
treating diseases or conditions that affect fewer than 4,00071 individuals in the United States each
year, may be used in a facility only after a local IRB has approved their use in that facility, except
in certain emergency situations.72
In July 2011, HHS published an advance notice of proposed rulemaking (ANPRM) requesting
public comment on a broad range of amendments to the Common Rule, with the goal of
“enhancing the effectiveness of the research oversight system by improving the protections for
human subjects while also reducing burdens, delays, and ambiguity for investigators and human
subjects.”73 HHS sought comments on such changes as refining the current risk-based regulatory
framework, coordinating IRB review of multisite studies, and harmonizing the regulations and
guidance of different agencies. Last fall, HHS and 15 other federal departments and agencies
jointly released a proposed rule to amend the Common Rule.74 A final rule has not yet been
published.
Provisions
Section 3023 requires the HHS Secretary, to the extent possible, to harmonize differences
between the HHS Human Subject Regulations and the FDA Human Subject Regulations. The
HHS Secretary is required to modify the HHS and FDA regulations and associated rules for
vulnerable populations to reduce regulatory duplications and unnecessary delays; accommodate
multisite and cooperative research projects; incorporate local consideration, community values,
65 45 C.F.R. §46.109.
66 45 C.F.R. §46.111(a)(4).
67 45 C.F.R. §46.116(a).
68 45 C.F.R. §46.116(d).
69 45 C.F.R. Part 46, Subparts B (pregnant women, fetuses, neonates), C (prisoners), and D (children).
70 21 C.F.R. Parts 50, 56, 312, and 812.
71 Section 3052 of this act changed “fewer than 4,000” to “not more than 8,000.”
72 FFDCA §520(m)(4).
73 Department of Health and Human Services, Food and Drug Administration, “Human Subject Research Protections:
Enhancing Protections for Research Subjects and Reducing Burden, Delay, and Ambiguity for Investigators,” 76
Federal Register 44512, July 25, 2011.
74 80 Federal Register 53931, September 8, 2015.
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and mechanisms to protect vulnerable populations; and to ensure that human research that is
subject to the HHS regulations or to the FDA regulations may use joint or shared IRB review, an
independent IRB, or some other IRB arrangement to avoid duplication of effort.
Within three years of enactment, the HHS Secretary, in consultation with specified stakeholders,
is required to issue regulations or guidance as necessary to implement the harmonization required
under this section. The HHS Secretary is further required to submit, within two years of
enactment, a report to Congress on the progress made toward completing such harmonization.
Section 3024 amends FFDCA Section 520(g) (“Exemption for Devices for Investigational Use”)
to allow the HHS Secretary, subject to such conditions as he may prescribe, to waive the informed
consent requirement for individuals participating in the clinical trial of a medical device if the
trial poses no more than minimal risk to the participants and includes appropriate safeguards to
protect their rights, safety, and welfare.
Section 3024 also amends FFDCA Section 505(i) (regarding the investigational use of drugs) to
modify the existing requirement for informed consent as a condition of the HHS Secretary
granting an exemption to allow manufacturers, or sponsors of investigations, to not require
certification of informed consent for individuals participating in the clinical trial of a drug if it is
not feasible, if it is contrary to the best interest of human beings, or if the trial poses no more than
minimal risk to the participants and includes appropriate safeguards to protect their rights,
safety, and welfare (new language in italics).
Subtitle D-Patient Access to Therapies and Information
Section 3031. Summary Level Review
FFDCA Section 505 and accompanying regulations provide the framework for FDA’s approval of
a sponsor’s new drug application (NDA). For a drug whose active ingredient has never been
FDA-approved, the law requires the sponsor to submit an NDA that includes data to provide
evidence of the drug’s safety and effectiveness for its intended use, information about the
manufacturing process, and the drug labeling. Once a product has an approved NDA, FDA
requires that the manufacturer submit a supplemental NDA each time the manufacturer wants to
change the labeling, the manufacturing process, or the dosing, or when it wants to add a new
indication (a new intended use) of the drug. Regulations at 21 C.F.R. Sections 314.50 and 314.54
describe the required contents of those applications. Regarding clinical data, the regulations direct
the applicant to submit, in addition to descriptions and analysis of controlled and uncontrolled
clinical studies,
(iv) A description and analysis of any other data or information relevant to an evaluation
of the safety and effectiveness of the drug product obtained or otherwise received by the
applicant from any source, foreign or domestic, including information derived from clinical
investigations, including controlled and uncontrolled studies of uses of the drug other than
those proposed in the application, commercial marketing experience, reports in the
scientific literature, and unpublished scientific papers. (21 C.F.R. 314.50(d)(5)(iv))
The clinical data submission must also include an “integrated summary of the data demonstrating
substantial evidence of effectiveness for the claimed indications.”75
75 21 C.F.R. §314.50(d)(5)(v).
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Provision
Section 3031 amends FFDCA Section 505(c) and PHSA Section 351(a)(2) to permit the HHS
Secretary to rely upon “qualified data summaries” to support the approval of a supplemental NDA
submitted by the sponsor of an approved drug seeking to add a new “qualified” indication to the
approval. A “qualified indication” is one “for a drug that the HHS Secretary determines to be
appropriate for summary level review.” This provision adds that such supplemental application is
eligible only if data demonstrating the safety of the drug are available and acceptable to the HHS
Secretary, and all data used to develop the qualified data summaries are submitted as part of the
supplemental NDA. It requires the HHS Secretary to post on the FDA website, and update
annually, the number of applications reviewed solely based on a qualified data summary, and the
average time for completion of reviews using and not using the review flexibility, among other
specified information. This section defines qualified data summary as a “summary of clinical data
that demonstrates the safety and effectiveness of a drug with respect to a qualified indication.”
Section 3032. Expanded Access Policy
FDA regulates the U.S. sale of drugs and biological products, basing approval or licensure on
evidence of the safety and effectiveness for a product’s intended uses. Without that approval or
licensure, a manufacturer may not distribute the product except for use in the clinical trials that
will provide evidence to determine that product’s safety and effectiveness. Under certain
circumstances, however, FDA may permit the sponsor to provide an unapproved or unlicensed
product to patients outside that standard regulatory framework. One such mechanism is expanded
access to investigational drugs, commonly referred to as “compassionate use.”76
If excluded from a clinical trial because of enrollment limitations, a person, acting through a
physician, may request access to an investigational new drug outside of the trial. FDA may grant
expanded access to a patient with a serious disease or condition for which there is no comparable
or satisfactory alternative therapy, if, among other requirements, probable risk to the patient from
the drug is less than the probable risk from the disease; if there is sufficient evidence of safety and
effectiveness to support the drug’s use for this person; and if providing access “will not interfere
with the ... clinical investigations to support marketing approval.”77 The widespread use of
expanded access is limited by an important factor: whether the manufacturer agrees to provide the
drug, which—because it is not FDA-approved—cannot be obtained otherwise. FDA does not
have the authority to compel a manufacturer to participate. Manufacturers may consider several
factors in deciding whether to provide an investigational drug, such as available supply, perceived
liability risk, limited staff and facility resources, and need for data to assess safety and
effectiveness. Although FDA reports the number of investigational drug requests it receives,
manufacturers do not.
Provision
Section 3032 adds a new FFDCA Section 561A, “Expanded Access Policy Required for
Investigational Drugs,” to require a manufacturer or distributor of an investigational drug to be
used for a serious disease or condition to make its policies on evaluating and responding to
compassionate use requests publicly available. Required elements of the policy include contact
information for the manufacturer or distributor of the drug, request procedures, “the general
76 CRS Report R44134, Access to Unapproved Drugs: FDA Policies on Compassionate Use and Emergency Use
Authorization, by Susan Thaul.
77 FFDCA §561(b).
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criteria the manufacturer or distributor will use to evaluate such requests for individual patients,
and for responses to such requests,” anticipated time to acknowledge request receipts, and a
hyperlink or other reference to the clinical trial record containing information about expanded
access to the drug. The new section states that posting of policy would not guarantee patients
access to an investigational drug. The provision also allows a manufacturer or distributor to revise
its policy at any time. Section 3032 becomes effective on the later of the date that is 60 days after
the enactment of the 21st Century Cures Act or “the first initiation of a phase 2 or phase 3 study ...
with respect to such investigational drug.”
Sections 3033-3036. Regenerative Therapies
Regenerative medicine is defined by NIH as “the process of creating living, functional tissues to
repair or replace tissue or organ function lost due to age, disease, damage, or congenital
defects.”78 The regulation of cells or tissues intended for implantation or infusion into a human
patient is the responsibility of the FDA Center for Biologics Evaluation and Research (CBER).
FDA refers to such cells as HCT/Ps, which stands for human cells, tissues, and cellular and
tissue-based products. Stem cells are one example of HCT/P. CBER held a public workshop on
standards development for cellular therapies and regenerative medicine products in March 2014.
Provisions
Section 3033 adds a paragraph (g) to FFDCA Section 506 to require the HHS Secretary, at the
request of the sponsor of a drug, to facilitate an “efficient development program for, and expedite
review of” a drug that qualifies as a regenerative advanced therapy. To be eligible for such
designation, the drug must (1) be a regenerative medicine therapy, (2) be intended to treat,
modify, reverse, or cure a serious or life-threatening disease or condition, and (3) have
preliminary clinical evidence indicating that the drug has the potential to address unmet medical
needs for such a disease or condition. This designation may be requested with or after submission
of an investigational new drug (IND) application. An application regarding a regenerative
medicine therapy is eligible for priority review and for accelerated approval in addition to “early
interactions [with FDA] to discuss any potential surrogate or intermediate endpoint.” The term
“regenerative medicine therapy” includes cell therapy, therapeutic tissue engineering products,
human cell and tissue products, and combination products using any such therapies or products,
except for those regulated under PHSA Section 361 and 21 C.F.R. 1271. This section specifies the
procedure through which the sponsor of a drug could request such designation, how the HHS
Secretary would respond to the request, and postapproval requirements. This section is not to be
construed to alter the authority of the HHS Secretary to approve drugs and license biologics
pursuant to the FFDCA and PHSA Section 351, respectively, including standards of evidence, or
to alter the requirement of postapproval studies.
Section 3034 requires the HHS Secretary, acting through the FDA Commissioner, to issue draft
guidance within one year of enactment of the 21st Century Cures Act, and final guidance not later
than 12 months after the close of the public comment period on the draft guidance, “clarifying
how, in the context of regenerative advanced therapies, the HHS Secretary will evaluate devices
used in the recovery, isolation, or delivery of regenerative advanced therapies,” as specified.
Section 3035 requires that before March 1 of each calendar year, with respect to the previous
calendar year, the HHS Secretary submit a report to Congress on (1) the number and type of
78 FDA, Public Workshop: Synergizing Efforts in Standards Development for Cellular Therapies and Regenerative
Medicine Products, March 31, 2014. Agenda, transcript, presentation slides at
http://www.fda.gov/biologicsbloodvaccines/newsevents/workshopsmeetingsconferences/ucm364114.htm.
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applications for regenerative advanced therapies filed, approved or licensed, withdrawn, or
denied, and (2) the number of such applications or therapies that were granted accelerated
approval or priority review.
Section 3036 amends the FFDCA by adding a new Section 506G, “Standards for Regenerative
Medicine and Regenerative Advanced Therapies.” This section requires the HHS Secretary, in
consultation with the National Institute of Standards and Technology (NIST) and specified
stakeholders, to facilitate an effort toward the development of standards for regenerative medicine
and advanced therapies through a transparent public process to support, such as “through
regulatory predictability, the development, evaluation, and review of” such therapies. It also
requires the HHS Secretary to review and update relevant regulations and guidance, as
appropriate.
This section further requires the Office of Combination Products (OCP) to help coordinate timely
review of combination products across relevant agency centers and to ensure that persons are
designated in each primary agency center as points of contact for the sponsors of combination
products. It specifies additional duties for OCP related to communication, and facilitating
meetings between the agency and the sponsors. It requires the HHS Secretary, not later than four
years after enactment and after a public comment period, to issue final guidance on the
combination product review process, as specified, and adds reporting requirements to the annual
report to Congress on the activities of OCP, as specified.
It amends FFDCA Section 520(h)(4) to prohibit the use of information contained in an application
for premarket approval of a class III device from being used in an application for premarket
approval of a combination product that contains an approved drug constituent, unless the
applicant provides a patent certification and notifies the holder of the approved application and
patent owner that the patent is invalid or will not be infringed upon.
It also requires the HHS Secretary to identify, not later than 18 months after enactment, types of
combination products and manufacturing processes that the HHS Secretary proposes may adopt
different good manufacturing processes or streamlined mechanisms. This list is to be published in
the Federal Register, finalized after public comment, and updated as needed.
Section 3037. Health Care Economic Information
Under FFDCA Section 502, a drug or device is deemed to be misbranded if, among other things,
its labeling is false or misleading. Section 502(a) specifies that health care economic information
provided in the course of selecting drugs for managed care or other similar organizations, by a
formulary committee or similar entity, is not to be considered false or misleading if the
information “directly relates” to a use of the drug as approved under FFDCA Section 505 or
licensed under PHSA Section 351(a); the information must also be based on competent and
reliable scientific evidence. Information that helps substantiate the health care economic
information presented in accordance with this section must be made available to the HHS
Secretary upon request. Health care economic information is defined to mean “any analysis that
identifies, measures, or compares the economic consequences, including the costs of the
represented health outcomes, of the use of a drug to the use of another drug, to another health care
intervention, or to no intervention.”
Health care providers generally may prescribe a drug for an unapproved use when they judge that
it is medically appropriate for their patient (often called “off-label” use).79 Drug companies,
79 FDA, “Understanding Unapproved Use o
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