# Senate Medical Innovation Bills: Overview and Comparison with the 21st Century Cures Act (H.R. 6) > Briefs, arguments, decisions, and more. URL: https://www.frixlaw.com/law-library/documents/crs%3AR44502 ## Record - **Collection:** Congressional research report - **Document type:** CRS Report - **Published:** May 17, 2016 - **Citation:** R44502 ## Text Senate Medical Innovation Bills Senate Medical Innovation Bills: Overview and Comparison with the 21st Century Cures Act (H.R. 6) C. Stephen Redhead, Coordinator Specialist in Health Policy Amanda K. Sarata, Coordinator Specialist in Health Policy Judith A. Johnson Specialist in Biomedical Policy Agata Dabrowska Analyst in Health Policy Frank Gottron Specialist in Science and Technology Policy Sarah A. Lister Specialist in Public Health and Epidemiology Elayne J. Heisler Specialist in Health Services May 17, 2016 Congressional Research Service 7-.... www.crs.gov R44502 Senate Medical Innovation Bills Summary Both the House and the Senate are considering legislation to support medical innovation, primarily through reforms to the National Institutes of Health (NIH) and changes to the drug, biologic, and device approval pathways at the Food and Drug Administration (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.” 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. The Senate’s medical innovation package is that chamber’s companion effort to the House’s 21st Century Cures initiative, which culminated in the House passage of H.R. 6, the 21st Century Cures Act, on July 10, 2015, on a vote of 344 to 77. H.R. 6 is the result of a series of hearings and roundtable meetings hosted by the House Energy and Commerce Committee dating back to spring 2014. While consisting of many different provisions, H.R. 6 is 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 for each of the bills in the Senate medical innovation package (1) background on the issue, or issues, addressed by the bill, including a summary of relevant current law; (2) a summary of the bill’s provisions; and (3) where applicable, identification of comparable provisions in H.R. 6 that address the same topic. For a summary of all the provisions in H.R. 6, as passed by the House, including an explanation of how the bill would change current law, see CRS Report R44071, H.R. 6: The 21st Century Cures Act. Congressional Research Service Senate Medical Innovation Bills Contents Introduction ..................................................................................................................................... 1 Report Roadmap........................................................................................................................ 2 The FDA Device Accountability Act of 2015 (S. 1622) .................................................................. 2 Use of Nonlocal Institutional Review Boards for Review of Investigational Device Exemptions and [Humanitarian] Device Exemptions (§2) .................................................... 2 Issue Background ................................................................................................................ 2 Senate Legislation ............................................................................................................... 3 Comparable Provisions in the 21st Century Cures Act (H.R. 6) .......................................... 3 CLIA Waiver Study Design Guidance for In Vitro Diagnostics (§3) ........................................ 3 Issue Background ................................................................................................................ 3 Senate Legislation ............................................................................................................... 4 Comparable Provisions in the 21st Century Cures Act ........................................................ 4 Ensuring Least Burdensome Means of Evaluating Devices (§4) .............................................. 4 Issue Background ................................................................................................................ 4 Senate Legislation ............................................................................................................... 6 Comparable Provisions in the 21st Century Cures Act (H.R. 6) .......................................... 6 Preventing Superbugs and Protecting Patients Act (S. 2503) .......................................................... 7 Issue Background ................................................................................................................ 7 Senate Legislation ............................................................................................................... 8 Comparable Provisions in the 21st Century Cures Act ........................................................ 8 The Advancing Breakthrough Medical Devices for Patients Act of 2016 (S. 1077) ....................... 8 Issue Background ................................................................................................................ 8 Senate Legislation ............................................................................................................. 10 Comparable Provisions in the 21st Century Cures Act (H.R. 6) .........................................11 Advancing Hope Act of 2016 (S. 1878) .........................................................................................11 Issue Background ...............................................................................................................11 Senate Legislation ..............................................................................................................11 Comparable Provisions in the 21st Century Cures Act ...................................................... 12 Advancing Targeted Therapies for Rare Diseases Act of 2016 (S. 2030) ..................................... 13 Issue Background .............................................................................................................. 13 Senate Legislation ............................................................................................................. 13 Comparable Provisions in the 21st Century Cures Act ...................................................... 14 Patient-Focused Impact Assessment Act of 2016 (S. 1597) .......................................................... 14 Issue Background .............................................................................................................. 14 Senate Legislation ............................................................................................................. 14 Comparable Provisions in the 21st Century Cures Act ...................................................... 15 Promise for Antibiotics and Therapeutics for Health Act (S. 185) ................................................ 15 Issue Background .................................................................................................................... 15 Antibacterial Resistance Monitoring (§2) ............................................................................... 16 Senate Legislation ............................................................................................................. 16 Comparable Provisions in the 21st Century Cures Act ...................................................... 16 Limited Population Pathway for Antibacterial Drugs & Prescribing Authority (§§3-4)......... 16 Senate Legislation ............................................................................................................. 16 Comparable Provisions in the 21st Century Cures Act ...................................................... 17 Congressional Research Service Senate Medical Innovation Bills Advancing Precision Medicine Act of 2016 (S. 2713) .................................................................. 18 Issue Background .............................................................................................................. 18 Senate Legislation ............................................................................................................. 20 Comparable Provisions in the 21st Century Cures Act ...................................................... 20 The Combination Products Innovation Act of 2016 (S. 1767) ...................................................... 21 Issue Background .............................................................................................................. 21 Senate Bill ......................................................................................................................... 21 Comparable Provisions in the 21st Century Cures Act ...................................................... 23 Health Software: The Medical Electronic Data Technology Enhancement for Consumers’ Health Act (S. 1101) ................................................................................................................... 23 Issue Background .............................................................................................................. 23 Senate Legislation ............................................................................................................. 24 Comparable Provisions in the 21st Century Cures Act ...................................................... 25 Interoperability: Improving Health Information Technology Act (S. 2511) .................................. 25 Issue Background .............................................................................................................. 25 Senate Legislation ............................................................................................................. 28 Comparable Provisions in the 21st Century Cures Act ...................................................... 29 The Medical Countermeasures Innovation Act of 2015 (S. 2055) ................................................ 30 Medical Countermeasures (§§2-6) .......................................................................................... 30 Issue Background .............................................................................................................. 30 Senate Legislation ............................................................................................................. 30 Comparable Provisions in the 21st Century Cures Act ...................................................... 32 Priority Review to Encourage Treatments for Agents that Present National Security Threats (§§7-8)..................................................................................................................... 32 Issue Background .............................................................................................................. 32 Senate Legislation ............................................................................................................. 32 Comparable Provisions in the 21st Century Cures Act ...................................................... 32 Next Generation Researchers Act (S. 2014) .................................................................................. 33 Issue Background .............................................................................................................. 33 Senate Legislation ............................................................................................................. 33 Comparable Provisions in the 21st Century Cures Act ...................................................... 34 Advancing NIH Strategic Planning and Representation in Medical Research Act (S. 2745) .......................................................................................................................................... 35 NIH Strategic Plan (§2) ........................................................................................................... 35 Issue Background .............................................................................................................. 35 Senate Legislation ............................................................................................................. 36 Comparable Provisions in the 21st Century Cures Act (H.R. 6) ........................................ 36 Inclusion of Women and Minorities in Research (§§3-9) ....................................................... 36 Issue Background .............................................................................................................. 36 Senate Legislation ............................................................................................................. 37 Comparable Provisions in the 21st Century Cures Act (H.R. 6) ........................................ 38 Promoting Biomedical Research and Public Health for Patients Act (S. 2742) ............................ 38 Reducing and Streamlining Administrative Burden at NIH (§2, 3, 5, and 10) ....................... 38 Issue Background .............................................................................................................. 39 Senate Legislation ............................................................................................................. 39 Comparable Provisions in the 21st Century Cures Act (H.R. 6) ........................................ 41 Reimbursement for Research Substances and Living Organisms (§4) ................................... 41 Congressional Research Service Senate Medical Innovation Bills Issue Background .............................................................................................................. 41 Senate Legislation ............................................................................................................. 41 Comparable Provisions in the 21st Century Cures Act (H.R. 6) ........................................ 41 National Vaccine Injury Compensation Program (§6) ............................................................ 42 Issue Background .............................................................................................................. 42 Senate Legislation ............................................................................................................. 42 Comparable Provisions in the 21st Century Cures Act (H.R. 6) ........................................ 42 Vaccine Meetings; Report on Vaccine Innovation (§7) ........................................................... 42 Issue Background .............................................................................................................. 42 Senate Legislation ............................................................................................................. 43 Comparable Provisions in the 21st Century Cures Act (H.R. 6) ........................................ 43 Clinical Trials Database (§§8-9) ............................................................................................. 43 Issue Background .............................................................................................................. 43 Senate Legislation ............................................................................................................. 44 Comparable Provisions in the 21st Century Cures Act (H.R. 6) ........................................ 44 National Center for Advancing Translational Sciences (§11) ................................................. 45 Issue Background .............................................................................................................. 45 Senate Legislation ............................................................................................................. 45 Comparable Provisions in the 21st Century Cures Act (H.R. 6) ........................................ 46 Enhancing the Stature and Visibility of Medical Rehabilitation Research at the NIH Act (S. 800) ....................................................................................................................................... 46 Issue Background .............................................................................................................. 46 Senate Legislation ............................................................................................................. 46 Comparable Provisions in the 21st Century Cures Act ...................................................... 47 Advancing Research for Neurological Diseases Act of 2016 (S. 849) .......................................... 47 Issue Background .............................................................................................................. 47 Senate Legislation ............................................................................................................. 47 Comparable Provisions in the 21st Century Cures Act ...................................................... 47 FDA and NIH Workforce Authorities Modernization Act (S. 2700) ............................................. 48 Silvio O. Conte Senior Biomedical Research Service (§2) ..................................................... 48 Issue Background .............................................................................................................. 48 Senate Legislation ............................................................................................................. 48 Comparable Provisions in the 21st Century Cures Act ...................................................... 48 Hiring Authority for Scientific, Technical, and Professional Personnel (§3) .......................... 49 Issue Background .............................................................................................................. 49 Senate Legislation ............................................................................................................. 49 Comparable Provisions in the 21st Century Cures Act ...................................................... 49 Establishment of Food and Drug Administration Intercenter Institutes (§4) .......................... 50 Issue Background .............................................................................................................. 50 Senate Legislation ............................................................................................................. 50 Comparable Provisions in the 21st Century Cures Act ...................................................... 51 Scientific Meetings (§5) .......................................................................................................... 51 Issue Background .............................................................................................................. 51 Senate Legislation ............................................................................................................. 51 Comparable Provisions in the 21st Century Cures Act (H.R. 6) ........................................ 51 Reagan-Udall Foundation for the Food and Drug Administration (§6) .................................. 52 Issue Background .............................................................................................................. 52 Senate Legislation ............................................................................................................. 52 Comparable Provisions in the 21st Century Cures Act ...................................................... 52 Congressional Research Service Senate Medical Innovation Bills NIH Research Information Collection Exempted from Paperwork Reduction Act (§7) ......... 53 Issue Background .............................................................................................................. 53 Senate Legislation ............................................................................................................. 53 Comparable Provisions in the 21st Century Cures Act (H.R. 6) ........................................ 53 Studies (§8) ............................................................................................................................. 53 Issue Background .............................................................................................................. 53 Senate Legislation ............................................................................................................. 54 Comparable Provisions in the 21st Century Cures Act ...................................................... 54 Summary Level Review (§9) .................................................................................................. 54 Issue Background .............................................................................................................. 54 Senate Legislation ............................................................................................................. 55 Comparable Provisions in the 21st Century Cures Act ...................................................... 55 Drug Surveillance (§10) .......................................................................................................... 56 Issue Background .............................................................................................................. 56 Senate Legislation ............................................................................................................. 56 Comparable Provisions in the 21st Century Cures Act ...................................................... 57 Biological Product Innovation (§11) ....................................................................................... 57 Issue Background .............................................................................................................. 57 Senate Legislation ............................................................................................................. 57 Comparable Provisions in 21st Century Cures Act (H.R. 6) ............................................. 57 Expanded Access Policy (§12) ................................................................................................ 57 Issue Background .............................................................................................................. 57 Senate Legislation ............................................................................................................. 58 Comparable Provisions in the 21st Century Cures Act ...................................................... 58 Finalizing Draft Guidance on Expanded Access (§13) ........................................................... 58 Issue Background .............................................................................................................. 58 Senate Legislation ............................................................................................................. 59 Comparable Provisions in the 21st Century Cures Act ...................................................... 59 Amendments to the Orphan Drug Act (§14) ........................................................................... 59 Issue Background .............................................................................................................. 59 Senate Legislation ............................................................................................................. 60 Comparable Provisions in the 21st Century Cures Act ...................................................... 60 Standards for Regenerative Medicine and Advanced Therapies (§15) ................................... 60 Issue Background .............................................................................................................. 60 Senate Legislation ............................................................................................................. 60 Comparable Provisions in 21st Century Cures Act (H.R. 6) ............................................. 61 Good Guidance Practices (§16)............................................................................................... 61 Issue Background .............................................................................................................. 61 Senate Legislation ............................................................................................................. 61 Comparable Provisions in the 21st Century Cures Act ...................................................... 62 Paperwork Reduction Act Waiver during a Public Health Emergency (§17) ......................... 62 Issue Background .............................................................................................................. 62 Senate Legislation ............................................................................................................. 63 Comparable Provisions in the 21st Century Cures Act ...................................................... 63 Contacts Author Contact Information .......................................................................................................... 63 Congressional Research Service Senate Medical Innovation Bills Introduction Both the House and the Senate are considering legislation to support medical innovation, primarily through reforms to the National Institutes of Health (NIH) and changes to the drug, biologic and device approval pathways at the Food and Drug Administration (FDA). Both NIH and FDA are agencies within the Department of Health and Human Services (HHS). 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 remaining 18 bills that comprise the Senate’s medical innovation legislative effort include the following:                   S. 1878, The Advancing Hope Act of 2015; S. 1622, The FDA Device Accountability Act of 2015; S. 2503, Preventing Superbugs and Protecting Patients Act; S. 2030, The Advancing Targeted Therapies for Rare Diseases Act of 2015; S. 2014, Next Generation Researchers Act; S. 800, The Enhancing the Stature and Visibility of Medical Rehabilitation Research at NIH Act; S. 849, Advancing Research for Neurological Diseases Act of 2015; S. 2511, Improving Health Information Technology Act; S. 1077, The Advancing Breakthrough Medical Devices for Patients Act of 2015; S. 1101, The Medical Electronic Data Technology Enhancement for Consumers Health Act; S. 2055, The Medical Countermeasures Innovation Act of 2015; S. 1767, The Combination Products Innovation Act of 2015; S. 1597, Patient Focused Impact Assessment Act of 2015; S. 185, Promise for Antibiotics and Therapeutics for Health Act; S. 2713, Advancing Precision Medicine Act of 2016; S. 2745, Advancing NIH Strategic Planning and Representation in Medical Research Act; S. 2742, Promoting Biomedical Research and Public Health for Patients Act; and S. 2700, FDA and NIH Workforce Authorities Modernization Act. 1 Senate Health, Education, Labor, and Pensions Committee, February 3, 2015, at http://www.help.senate.gov/chair/ newsroom/press/alexander-murray-announce-initiative-to-examine-drug-device-development-and-review-process. Congressional Research Service 1 Senate Medical Innovation Bills The Senate’s medical innovation package is that chamber’s companion effort to the House’s 21st Century Cures initiative, which culminated in the House passage of H.R. 6, the 21st Century Cures Act, on July 10, 2015, on a vote of 344 to 77. H.R. 6 is 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 regulatory processes, precision/personalized medicine, digital health care, and more. While consisting of many different provisions, H.R. 6 is 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. Report Roadmap This report provides for each of the 18 bills in the Senate medical innovation package: (1) background on the issue, or issues, addressed by the bill including a summary of relevant current law; (2) a summary of the bill’s provisions; and (3) where applicable, identification of comparable provisions in H.R. 6 that address the same topic. In some cases, the House and Senate legislation address the same topic in an entirely different way. In other cases, the House and Senate legislation address the topic in a similar way but with key substantive differences. In a few instances, the language in the House and Senate bills is substantively identical. For a summary of all the provisions in H.R. 6, as passed by the House, including an explanation of how the bill would change current law, see CRS Report R44071, H.R. 6: The 21st Century Cures Act. The FDA Device Accountability Act of 2015 (S. 1622) Use of Nonlocal Institutional Review Boards for Review of Investigational Device Exemptions and [Humanitarian]2 Device Exemptions (§2) Issue Background The HHS Human Subject Regulations are a core set of federal standards for protecting human subjects in HHS-sponsored research.3 These regulations are commonly referred to as the Common Rule because the same requirements have been adopted by many other federal departments and agencies, which apply the regulations to the research they fund. Under the Common Rule, research protocols must be approved by an Institutional Review Board (IRB) to ensure that the rights and welfare of research subjects are protected.4 2 Senate provision uses the word “Human.” 3 45 C.F.R. Part 46, Subpart A. 4 45 C.F.R. §46.109. Congressional Research Service 2 Senate Medical Innovation Bills FDA has issued its own set of Human Subject Regulations, which are similar, but not identical, to the Common Rule.5 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. All clinical evaluations of investigational devices (unless exempt) must have an investigational device exemption (IDE) before the clinical study is initiated.6 An IDE allows an unapproved device (most commonly an invasive or life-sustaining device) to be used in a clinical study to collect the data required to support a premarket approval (PMA) submission.7 The IDE permits a device to be shipped lawfully for investigation of the device without requiring that the manufacturer comply with other requirements of the Federal Food, Drug, and Cosmetic Act (FFDCA), such as registration and listing. Devices approved by FDA via the humanitarian device exemption (HDE) are for diagnosing or treating diseases or conditions that affect fewer than 4,000 individuals in the United States each year. An HDE application is similar to a PMA, but it is exempt from the effectiveness requirements. Such devices may be used in a facility only after a local IRB has approved their use in that facility, except in certain emergency situations.8 Senate Legislation The provision would amend Section 520(g) of the FFDCA, regarding IDEs, and Section 520(m) of the FFDCA, regarding HDEs, by removing the word “local” in all references to local IRBs, including in the stipulation that an approved humanitarian use device may be used in a facility only after a local IRB has approved such use, except in certain emergency situations. Comparable Provisions in the 21st Century Cures Act (H.R. 6) The use of non-local IRBs for review of IDEs and HDEs provision in H.R. 6 (i.e., Title II, Subtitle O, Section 2262) is comparable to S. 1622. The House provision would also require the Secretary, within 12 months of enactment, to revise or issue regulations or guidance, as necessary, to carry out these amendments. CLIA Waiver Study Design Guidance for In Vitro Diagnostics (§3) Issue Background The Clinical Laboratory Improvement Amendments (CLIA) of 1988 provide the Centers for Medicare & Medicaid Services (CMS) with authority to regulate clinical laboratories to ensure the accuracy of test results, given that these results drive clinical decisionmaking.9 CLIA requires laboratories to receive certification before they are allowed to carry out clinical laboratory testing on a human sample. CLIA certification is based on the level of complexity of testing that a laboratory is performing, graded as low, moderate, or high. FDA is responsible for categorizing clinical laboratory tests according to their level of complexity.10 Laboratories that perform only 5 21 C.F.R. Parts 50, 56, 312, and 812. 6 See 21 C.F.R. §812. Devices are exempt from IDE requirements when testing is noninvasive, does not require invasive sampling, does not introduce energy into a subject, and is not stand-alone (i.e., is not used for diagnosis without confirmation by other methods or medically established procedures). See 21 C.F.R. §812.2(c)(3). 7 FDA, Device Advice: Investigational Device Exemption (IDE), July 9, 2009, http://www.fda.gov/MedicalDevices/ DeviceRegulationandGuidance/HowtoMarketYourDevice/InvestigationalDeviceExemptionIDE/default.htm. 8 FFDCA §520(m)(4). 9 PHSA §353; 42 U.S.C. §263a. 10 See FDA, “CLIA Categorizations,” http://www.fda.gov/medicaldevices/deviceregulationandguidance/ Congressional Research Service 3 Senate Medical Innovation Bills low-complexity tests (called waived tests) receive a certificate of waiver (COW) from CMS. Conversely, only laboratories certified to do so may perform moderate- and high-complexity tests. FDA determines whether a test is waived (i.e., low-complexity) or not based on information submitted about the test by the manufacturer, and FDA has issued guidance to support the manufacturer’s submission of this information.11 Under current law, waived tests are those “that have been approved by FDA for home use or that, as determined by the Secretary, are simple laboratory examinations and procedures that have an insignificant risk of an erroneous result.”12 The guidance recommends ways to demonstrate that a test is both “simple” and has “an insignificant risk of an erroneous result.” Demonstrating the latter includes showing that a test’s accuracy is comparable to a method whose accuracy has already been established and documented. (Section V of the guidance document addresses approaches to demonstrating accuracy.) Senate Legislation S. 1622 Section 3 would require the Secretary, not later than one year after enactment, to publish draft guidance that revises Section V of the current guidance, including providing clarification on the appropriate use of comparable performance between a waived and moderately complex laboratory user to demonstrate accuracy. Not later than one year after the comment period for the draft guidance closes, the Secretary would be required to publish final revised guidance. Comparable Provisions in the 21st Century Cures Act Section 2228 of H.R. 6 (Title I, Subtitle M) is substantively identical to the Senate legislation. Ensuring Least Burdensome Means of Evaluating Devices (§4) Issue Background Section 205 of the Food and Drug Administration Modernization Act of 1997 (FDAMA, P.L. 105-115) amended Section 513 of the Federal Food, Drug, and Cosmetic Act (FFDCA), adding two provisions commonly referred to as the “Least Burdensome Provisions.” The two provisions stipulate that FDA consider the “least burdensome” data or information “necessary” to demonstrate a reasonable assurance of device effectiveness in a premarket approval (PMA) application or substantial equivalence to predicate devices with differing technological characteristics in certain 510(k) notifications. The two provisions are as follows: Section 513(a)(3)(D)(ii) Any clinical data, including one or more well-controlled investigations, specified in writing by the Secretary for demonstrating a reasonable assurance of device effectiveness shall be specified as a result of a determination by the Secretary that such data are necessary to establish device effectiveness. The Secretary shall consider, in consultation with the applicant, the least burdensome appropriate means of ivdregulatoryassistance/ucm393229.htm. 11 FDA, “Guidance for Industry and FDA Staff: Recommendations for Clinical Laboratory Improvement Amendments of 1988 (CLIA) Waiver Applications for Manufacturers of In Vitro Diagnostic Devices,” Center for Devices and Radiological Health, January 30, 2008, http://www.fda.gov/downloads/MedicalDevices/ DeviceRegulationandGuidance/GuidanceDocuments/ucm070890.pdf. 12 PHSA §353(d)(3), “Requirements for Certificate of Waiver”; 42 U.S.C. §263a(d)(3). Congressional Research Service 4 Senate Medical Innovation Bills evaluating device effectiveness that would have a reasonable likelihood of resulting in approval. Section 513(i)(1)(D) Whenever the Secretary requests information to demonstrate that devices with differing technological characteristics are substantially equivalent, the Secretary shall only request information that is necessary to making substantial equivalence determinations. In making such requests, the Secretary shall consider the least burdensome means of demonstrating substantial equivalence and request information accordingly. FDA published final guidance on the least burdensome provisions on October 4, 2002.13 Under the guidance, FDA may allow the use of non-clinical data—such as laboratory and/or animal testing—in place of clinical data for the approval of PMA devices in certain circumstances, such as “devices or modifications of approved devices for which scientifically valid information is available in the public domain.”14 When clinical data are needed, FDA allows manufacturers to consider study designs to shorten the length of the study. Such study designs include the use of “surrogate endpoints and statistical methods, such as Bayesian analyses,” and study designs other than the gold standard—the randomized controlled trial.15 Although FDA allows for substitution of laboratory data in certain circumstances, the absence of problems in laboratory testing may not always predict what happens to a device over time in the human body, where forces that cannot be replicated in laboratory testing act upon the device. For example, “the malfunction of [Medtronic and St. Jude Medical] implantable cardioverter-defibrillator leads, which resulted in a widespread recall, and the hazards posed by particles shed from [DePuy] metal-on-metal hip replacements were not predictable based on engineering insights or in vitro studies.”16 The 2002 FDA guidance states, “[r]eliance on postmarket controls (e.g., ... postmarket surveillance, and the Medical Device Reporting requirements) should be considered as a mechanism to reduce the premarket burden for 510(k)s and PMAs, while still ensuring the safety 13 FDA, The Least Burdensome Provisions of the FDA Modernization Act of 1997: Concept and Principles; Final Guidance for FDA and Industry, October 4, 2002, http://www.fda.gov/RegulatoryInformation/Guidances/ ucm085994.htm. 14 Ibid. 15 Ibid. In a randomized controlled trial (RCT), participants are randomly assigned to two or more groups. One group receives the intervention (the new treatment), while the control group receives current therapy or a placebo. Randomization ensures that any patient characteristics that might affect the outcome will be roughly equal across each group in the study. Any difference in outcomes between the groups is then likely due to the intervention. The RCT is often called the gold standard of evidence for a clinical trial. A surrogate end point may not be a reliable predictor of actual patient benefit. It is a laboratory measurement, such as blood pressure or cholesterol level, used as a substitute for a clinically meaningful end point that measures directly how a patient feels, functions, or survives. The use of Bayesian analyses allows studies to be combined in order to reduce the sample size needed for the experimental and/or control device. 16 Steven N. Goodman and Rita F. Redberg, “Opening the FDA Black Box,” JAMA, vol. 311, no. 4 (January 22, 2014), pp. 361-363. The Medtronic Sprint Fidelis and the St. Jude Medical Riata leads are specific models of cardiac electrodes (thin wires) that connect an implantable cardioverter-defibrillator (ICD) directly to the heart. An ICD monitors heart rhythms and can deliver an electrical shock to restore normal rhythm if life-threatening, irregular heartbeats are detected. The ICD keeps the heart from beating too fast and is surgically implanted in patients who may be at risk of sudden cardiac arrest. Both the Medtronic Sprint Fidelis and the St Jude Medical Riata were recalled because of the potential for wire fracture, causing the ICD to deliver an unnecessary shock or to not operate at all. Deaths and serious injuries were reported in which a fractured Sprint Fidelis or Riata lead may have been a possible or likely contributing factor. As of October 4, 2007, about 268,000 Sprint Fidelis leads had been implanted worldwide, including 172,000 Sprint Fidelis leads implanted in the United States. More than 227,000 Riata leads had been distributed worldwide, and as of 2011, about 79,000 Riata leads remained implanted in U.S. patients. See FDA website at http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm103022.htm and http://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/ucm314930.htm. Congressional Research Service 5 Senate Medical Innovation Bills and effectiveness of the device.”17 However, the FDA’s authority to require postmarket studies of medical devices is limited. A September 2015 GAO study found that of the 392 postmarket surveillance studies ordered by FDA between May 1, 2008, and February 24, 2015, 88% were inactive, 10% were ongoing, and 2% were complete.18 Activities related to implementing the least burdensome provision, including training for staff and advisory panels, are posted on FDA’s website.19 Senate Legislation S. 1622, Section 4, would amend FFDCA Section 513 by adding a new subsection (j), “Training and Oversight of Least Burdensome Requirements.” The Secretary would be required to ensure that each FDA employee involved in the review of premarket submissions, including supervisors, receives training on the “meaning and implementation of the least burdensome requirements” and to periodically assess the implementation of such requirements, including employee training. Under the Senate bill, 18 months after enactment, the FDA ombudsman responsible for device premarket review would be required to conduct an audit of the least burdensome training, including the effectiveness of the training. The audit would be required to include “interviews of persons who are representatives of the industry regarding their experience in the device premarket review process” and a list of the measurement tools used to assess the implementation of the least burdensome requirement. A summary of the audit findings would be required to be submitted to the Senate HELP Committee and the House Energy and Commerce Committee and posted on the FDA website. Regarding PMA applications, S. 1622 would amend FFDCA Section 515(c), adding a new paragraph that would require the Secretary to “consider the least burdensome appropriate means necessary to demonstrate device safety and effectiveness.” It would define the term necessary to mean “the minimum required information that would support a determination by the Secretary that an application provides a reasonable assurance of the safety and effectiveness of the device” and would state that the role of postmarket information must be considered in determining the least burdensome means of demonstrating a reasonable assurance of device safety and effectiveness. In addition, the provision would amend FFDCA Section 517A(a), adding that each substantive summary of the scientific and regulatory rationale for any decision made by FDA’s Center for Devices and Radiological Health (CDRH) regarding the submission or review of a PMA, a 510(k), or an IDE must also include a brief statement on how the least burdensome requirements were considered and applied. Comparable Provisions in the 21st Century Cures Act (H.R. 6) The provision regarding training and oversight in least burdensome appropriate means in H.R. 6 (Title II, Subtitle M, Section 2223) is comparable to S. 1622. Under the House provision, the Secretary would be required to issue draft guidance, no later than 12 months after enactment, that 17 FDA, The Least Burdensome Provisions of the FDA Modernization Act of 1997: Concept and Principles; Final Guidance for FDA and Industry, October 4, 2002, http://www.fda.gov/RegulatoryInformation/Guidances/ ucm085994.htm. 18 GAO, Medical Devices: FDA Ordered Postmarket Studies to Better Understand Safety Issues, and Many Studies Are Ongoing, GAO-15-815, September 2015. 19 FDA, Medical Devices, The Least Burdensome Provisions - Activities Related to Implementation, http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Overview/ MedicalDeviceProvisionsofFDAModernizationAct/ucm136685.htm#7. Congressional Research Service 6 Senate Medical Innovation Bills would update the October 4, 2002, final guidance on the least burdensome provisions. In developing the draft guidance, the Secretary would be required to hold a meeting of stakeholders “to ensure a full record to support the publication of such document.” The House provision amending FFDCA Section 515(c) would not require that postmarket information be considered in determining the least burdensome means of demonstrating a reasonable assurance of device safety and effectiveness. The House provision does not amend FFDCA Section 517A(a) regarding the substantive summary of any decision made by CDRH on the least burdensome requirements. Preventing Superbugs and Protecting Patients Act (S. 2503) Issue Background FFDCA Section 510(k) requires medical device manufacturers to register with the Secretary and, at least 90 days prior to introducing a device intended for human use into interstate commerce, to report to the Secretary (1) the class in which the device is classified and (2) actions taken to comply with applicable device regulatory requirements under FFDCA Sections 514 and 515. This notification requirement is part of the 510(k) premarket approval pathway, a process that is unique to medical devices and if successful results in FDA clearance. Under the 510(k) pathway, the manufacturer must demonstrate that a new device is substantially equivalent to a device already on the market (a predicate device). Substantial equivalence is determined by comparing the performance characteristics of a new device with those of a predicate device; clinical data demonstrating safety and effectiveness are usually not required. Reusable medical devices are those devices that may be reprocessed and used on multiple patients. In March of 2015, FDA released final guidance on the reprocessing of reusable medical devices: Reprocessing Medical Devices in Health Care Settings: Validation Methods and Labeling. This guidance states that, among other things, “(m)anufacturers seeking to bring to market certain reusable devices, such as duodenoscopes, bronchoscopes and endoscopes, should submit to the FDA for review their data validating the effectiveness of their reprocessing methods and instructions.”20 Under Section 604 of the Food and Drug Administration Safety and Innovation Act (FDASIA), the Secretary was required to withdraw draft guidance, issued by FDA in July 2011, entitled “Guidance for Industry and FDA Staff—510(k) Device Modifications: Deciding When to Submit a 510(k) for a Change to an Existing Device,” and leave the prior guidance issued in 1997 in effect. Although patient and consumer groups have generally supported a more rigorous 510(k) notification system, industry had voiced concerns that the 2011 guidance would slow the device regulatory process.21 Section 604 of FDASIA also required a report to House and Senate committees on when a 510(k) notification should be submitted for a modification or change to a legally marketed device. Any new draft guidance (or proposed regulation) on 510(k) device 20 FDA, “Reprocessing Medical Devices in Health Care Settings: Validation Methods and Labeling,” March 15, 2015, http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ UCM253010.pdf. 21 Alexander Gafney, “In a Major Victory for Industry, FDA says Existing 510(k) Guidance to Remain ‘Mostly Unchanged,’” RAPS Regulatory Focus, February 26, 2014, at http://www.raps.org/regulatoryDetail.aspx?id=9982. Congressional Research Service 7 Senate Medical Innovation Bills modification could not be issued before the committees received the report. Final guidance (or regulation) could not be issued until one year after the committees had received the report. This report was completed by FDA in January 2014.22 Senate Legislation S. 2503 would amend FFDCA Section 510 by adding a new subsection (q), “Reusable Medical Devices,” which would require the Secretary, not later than six months after enactment, to identify and publish a list of reusable device types for which reports under Section 510(k) must include (1) instructions for use and (2) validation data regarding cleaning, disinfection, and sterilization. Reports issued after the publication of this list would be required to include instructions for use and validation data, as specified by the Secretary. S. 2503 also would require the Secretary, acting through the FDA Commissioner and not later than one year after the date on which the comment period closes for the draft guidance, to issue final guidance regarding when a notification under 510(k) would have to be submitted for a modification or change to a legally marketed device. Comparable Provisions in the 21st Century Cures Act There are no comparable provisions in H.R. 6. The Advancing Breakthrough Medical Devices for Patients Act of 2016 (S. 1077) Issue Background Under FFDCA Section 515(d)(5), in order to provide for more effective treatment or diagnosis of life-threatening or irreversibly debilitating human diseases or conditions, the Secretary shall provide review priority for devices that represent breakthrough technologies for which no approved alternatives exist, that offer significant advantages over existing approved alternatives, or whose availability is in the best interest of the patients. On April 23, 2014, FDA issued the following draft guidance: Expedited Access for Premarket Approval Medical Devices Intended for Unmet Medical Need for Life Threatening or Irreversibly Debilitating Diseases or Conditions - Draft Guidance for Industry and Food and Drug Administration Staff. As indicated in the title, the FDA draft guidance covered only premarket approval (PMA) medical devices. FDA issued final guidance on April 13, 2015.23 The guidance focuses on balancing risks versus benefits for patients, drafting a Data Development Plan by the medical device sponsor, and collecting postmarket data on a medical device that has received a priority review designation. As described in the FDA guidance, the 22 FDA, Report to Congress, Report on FDA’s Policy to be Proposed Regarding Premarket Notification Requirements for Modifications to Legally Marketed Devices, January 7, 2014, at http://www.fda.gov/downloads/AboutFDA/ CentersOffices/OfficeofMedicalProductsandTobacco/CDRH/CDRHReports/UCM387121.pdf. 23 See http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ UCM393978.pdf. Note that the final FDA Guidance added de novo 510(k) devices. A de novo 510(k), a modified type of 510(k) review pathway, though requiring more data than a traditional 510(k), often requires less information than a PMA application. According to the final guidance, de novo devices “are not eligible for the full scope of the EAP program.” For a definition of EAP, see page 9. Congressional Research Service 8 Senate Medical Innovation Bills expedited review process for a medical device that has received a priority review designation in exchange for lower requirements in the premarket review process, such as less information in the PMA application, relies on the use of surrogate endpoints24 and the collection of postmarket data. According to FDA, the “Expedited Access PMA” (EAP) program features “earlier and more interactive engagement with FDA staff—including the involvement of senior management and a collaboratively developed plan for collecting the scientific and clinical data to support approval— features that, taken together, should provide these patients with earlier access to safe and effective medical devices.”25 FDA intends to withdraw approval for a device if the sponsor fails to adhere to the postmarket requirements, such as data collection, or if the postmarket data prove the device is not safe and effective: As part of the EAP program, FDA intends to impose postmarket requirements, including requiring post-approval studies as a condition of approval for devices subject to a PMA when applicable.26 The extent to which FDA will accept certain data to be collected for an EAP Device in the postmarket setting, rather than premarket, is affected by the Agency’s current authority to mandate completion of post-approval studies and to withdraw PMA approval for marketed devices for which FDA later determines that there is a lack of a showing of reasonable assurance that the device is safe or effective under the conditions of use prescribed, as well as by the current capabilities of FDA’s medical device surveillance system.27 Comments on the April 2014 FDA draft guidance questioned FDA’s ability to enforce postmarket study requirements and urged the agency and Congress “to evaluate whether FDA has sufficient authorities to promptly withdraw product approval if the necessary data are not promptly collected or suggest that the product benefits do not outweigh risks.”28 One media source stated that, regarding the EAP program, FDA “estimates that, at least in the early stages, on average, about six devices a year may qualify for the program, and the [agency] believes it has the resources available to handle that volume.”29 The estimated six devices would represent about 24 The FDA guidance on pages 23-24 describes a surrogate endpoint as follows: “a surrogate endpoint is not itself a measure of clinical benefit, but is used in trials as a substitute which is reasonably likely to predict clinical benefit, based on epidemiologic, therapeutic, pathophysiologic or other scientific evidence. The types of measurements which may be used as a surrogate endpoint are in vitro laboratory or medical imaging measurements, or physical signs (e.g., blood pressure measurements in trials of antihypertensive therapeutics, as a surrogate for clinical endpoints such as stroke, myocardial infarction, or mortality).” 25 See http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm394294.htm. 26 21 C.F.R. 814.82 states: “FDA may impose post-approval requirements in a PMA approval order or by regulation at the time of approval of the PMA or by regulation subsequent to approval.” In addition, under §522 of the FD&C Act and FDA’s implementing regulations at 21 C.F.R. Part 822, FDA may order postmarket surveillance for certain Class III devices. 27 FDA, Expedited Access for Premarket Approval and De Novo Medical Devices Intended for Unmet Medical Need for Life Threatening or Irreversibly Debilitating Diseases or Conditions, Guidance for Industry and Food and Drug Administration Staff, April 13, 2015, pp. 8-9, http://www.fda.gov/downloads/MedicalDevices/ DeviceRegulationandGuidance/GuidanceDocuments/UCM393978.pdf. Regarding de novo 510(k) devices, the final FDA Guidance on page 9 also stated the following: “FDA would not offer a greater ability to collect postmarket benefit-risk data otherwise typically collected premarket for a de novo request (as we may for a PMA device) because once a de novo request is granted, the product can serve as a predicate for a device that need only demonstrate substantial equivalence for a 510(k) clearance. This would be problematic if we granted a de novo for a device that subsequently was shown not to be safe or effective based on required postmarket data collection.” 28 See http://www.pewtrusts.org/en/about/news-room/news/2014/07/22/pew-comments-to-fda. 29 David Filmore, “Leap ahead with EAP? FDA proposes new expedited PMA pathway,” The Gray Sheet, vol. 40, no. Congressional Research Service 9 Senate Medical Innovation Bills 15% of FDA’s total PMA applications in one year. Other comments on the FDA draft guidance questioned whether FDA has sufficient resources to dedicate to the EAP program.30 Senate Legislation S. 1077 would add a new Section 515B, “Priority Review for Breakthrough Devices,” to Chapter V of the FFDCA. The new section would require the Secretary to establish a program to provide priority review for devices that (1) provide more effective diagnosis or treatment of a lifethreatening or irreversibly debilitating condition; and (2) represent breakthrough technologies for which no approved alternatives exist, offer significant advantages over existing alternatives, or the availability of which is in the best interest of patients. The section would allow requests for priority review from device sponsors of PMA medical devices and one other type of regulatory decision involving a medical device.31 The section would require the Secretary in 60 days to determine whether the request for priority review would be granted. Such requests would be evaluated by a team of experienced FDA staff and senior managers. All determinations—either approval or denial of priority review—would require a “substantive summary of the scientific and regulatory rationale” for the determination, pursuant to FFDCA Section 517A. If the Secretary approves a priority review designation for a device, the Secretary would not be able to withdraw the designation because another “breakthrough” device was subsequently cleared or approved, thereby resulting in the specified criteria (i.e., no approved alternatives exist, offer significant advantages over existing approved or cleared alternatives, or the availability of which is in the best interest of patients) no longer being met. Each priority review device would be assigned a team of staff, “including a team leader with appropriate subject matter expertise and experience.” Senior FDA personnel would oversee each team to facilitate the efficient development and review of the device. Among other things, the Secretary would be required to “provide for interactive communication with the device sponsor during the review process,” and expedite “the Secretary’s review of manufacturing and quality systems compliance.” The Secretary would be required to “disclose to the sponsor, not less than 5 business days in advance the topics of any consultation concerning the sponsor’s device that the Secretary intends to undertake with external experts or an advisory committee and provide the sponsor an opportunity to recommend such external experts.” The Secretary would be allowed to, as appropriate, “coordinate with the sponsor regarding early agreement on a data development plan.” The Secretary would also be able to ensure that clinical trial design is as efficient as practicable and would be able to facilitate “expedited and efficient development and review of the device through utilization of timely postmarket data collection” with regard to PMA applications. Agreements on clinical protocols would be considered binding, but may be subject to change under certain circumstances. The provision specifies that both the agreement and subsequent changes to the clinical protocol must be agreed to in writing. The Secretary would be required to issue, not later than one year after enactment, guidance on the implementation of the new Section 515B of the FFDCA. In addition, the Secretary would be required to issue a report, on January 1, 2017, to the Senate Health, Education, Labor and Pensions Committee and the House Energy and Commerce Committee describing the program 17 (April 28, 2014), pp. 1, 5-6. 30 See http://center4research.org/public-policy/testimony-briefings-statements/comments-on-expedited-access-forpremarket-approval-medical-devices/. 31 A petition for classification under FFDCA §513(f)(2). Congressional Research Service 10 Senate Medical Innovation Bills added under new FFDCA Section 515B, including recommendations to strengthen the program and better meet patient needs in a timely manner. Comparable Provisions in the 21st Century Cures Act (H.R. 6) The provision in H.R. 6 regarding priority review for breakthrough devices (Title II, Subtitle L, Sections 2201) is comparable to S. 1077. Importantly, the House provision would allow priority review requests from device sponsors of both 510(k) devices and PMA medical devices, and one other type of regulatory decision involving a medical device.32 The House provision would allow denied priority review requests to be reconsidered if reconsideration is requested within 30 days of the denial and other specified criteria are met. The House provision does not specify the number of business days in which FDA would “disclose to the sponsor, in advance the topics of any consultation concerning the sponsor’s device that [FDA] intends to undertake with external experts or an advisory committee and provide the sponsor an opportunity to recommend such external experts.” The House provision adds specific details regarding efficient clinical trial design, such as “the adoption of shorter or smaller clinical trials, application of surrogate endpoints, and use of adaptive trial designs and Bayesian statistics.” The House provision does not specify that the agreement on clinical protocols and any subsequent changes must be agreed to in writing. The House provision does not specify a deadline on the requirement for FDA guidance on Section 515B of the FFDCA, nor does it require a report by FDA on the program added under FFDCA Section 515B. Advancing Hope Act of 2016 (S. 1878) Issue Background 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. FDASIA terminated the authority to award such vouchers one year after the 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. 114-113). Senate Legislation S. 1878 would amend 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.” This 32 A petition for classification under FFDCA §513(f)(2). Congressional Research Service 11 Senate Medical Innovation Bills legislation also would amend the definition of a “rare pediatric disease product application” to mean a human drug application, as specified, that is approved after the enactment of S. 1878. S. 1878 would amend FFDCA Section 529(b)(4) by adding 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 Secretary of such intent upon submission of the rare pediatric disease product application. It would also extend eligibility for a rare pediatric disease priority review voucher, to a sponsor of a rare pediatric disease product application, unapproved as of the date of enactment of S. 1878, that submitted the application at least 90 days after the enactment of the Prescription Drug User Fee Amendments of 2012 and on or before the date of enactment of S. 1878. The bill would extend the authority to award such priority review vouchers until September 30, 2022. A new drug application or a biologics license application submitted to FDA after the enactment of S. 1878 and before September 30, 2022, would remain eligible to receive a priority review voucher even if approval comes after September 30, 2022, provided the application is approved before September 30, 2027, and is designated as a drug for a rare pediatric disease. This section also would prohibit a sponsor of a rare pediatric disease product application from receiving more than one priority review voucher issued under S. 1878 for the same product application. S. 1878 also would require that GAO study the voucher program and report to the Senate Committee on Health, Education, Labor, and Pensions and the House Committee on Energy and Commerce, 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. Comparable Provisions in the 21st Century Cures Act H.R. 6 contains a comparable provision (Section 2152, Reauthorization of Rare Pediatric Disease Priority Review Voucher Incentive Program), which would extend the authority to award rare pediatric disease priority review vouchers until December 31, 2018. A new drug application or a biologics license application submitted to FDA after the enactment of H.R. 6 and before December 31, 2018, would remain eligible to receive a priority review voucher even if approval comes after December 31, 2018. Similar to S. 1878, the House provision also would amend the definition of “rare pediatric disease” 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.” Unlike the Senate bill, the House provision would add to the list of characteristics of a pediatric rare disease product application that the product not have received a tropical disease priority review voucher.33 Like S. 1878, the House provision also would require that GAO study the voucher program and report to the House Committee on Energy and Commerce and the Senate Committee on Health, Education, Labor, and Pensions, by December 31, 2017, 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. 33 FFDCA §524. Priority review to encourage treatments for tropical diseases. Congressional Research Service 12 Senate Medical Innovation Bills Advancing Targeted Therapies for Rare Diseases Act of 2016 (S. 2030) Issue Background 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 genetic mutations that cause the disease. 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),34 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. 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. Senate Legislation S. 2030, the Advancing Targeted Therapies for Rare Diseases Act of 2015, would add a new Section 529A “Targeted Drugs for Rare Diseases” to Subchapter B of chapter V of the FFDCA, 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.” This legislation would authorize the Secretary to allow 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), for a drug that incorporates or utilizes the same or similar genetically targeted technology or for a variant protein-targeted drug.35 S. 2030 would define genetically targeted drugs, genetically targeted technology, and variant protein-targeted drugs. New Section 529A should not be construed to limit the Secretary’s product approval authorities, or to entitle 34 FFDCA §526, “Designation of Drugs for Rare Diseases or Conditions”; 21 U.S.C. §360bb. 35 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/. Congressional Research Service 13 Senate Medical Innovation Bills sponsors to obtain information in another sponsor’s application without permission of the other sponsor. Comparable Provisions in the 21st Century Cures Act The comparable provision in the House bill (H.R. 6, Title II, Subtitle C, Section 2041, “Precision Medicine Guidance and Other Programs of Food and Drug Administration”) would add a new Subchapter J, Precision Medicine, to Chapter V of the FFDCA; this subchapter would include a new Section 592, “Precision medicine regarding orphan-drug and expedited-approval programs.” For a precision drug or biological product application where the product is for the treatment of a serious or life-threatening disease or condition and has been designated as an orphan drug under FFDCA Section 526 as a drug for a rare disease or condition, the new FFDCA Section 592 would allow the Secretary to do two things. First, as with the Senate bill, the Secretary would be allowed to rely on information about a drug or biological product that has been previously submitted, either by the same or a different sponsor (with permission), in approval of an application. This may be for either a new product, or for a different indication for an existing product. Second, in contrast to the Senate bill, it would allow the Secretary to consider the application for expedited review programs, including accelerated approval. Similar to S. 2030, new Section 592 should not be construed to limit the Secretary’s product approval authorities, or to entitle sponsors to obtain information in another sponsor’s application without permission of the other sponsor. Patient-Focused Impact Assessment Act of 2016 (S. 1597) Issue Background FDASIA (P.L. 112-144) expanded FDA’s authorities and strengthened the agency’s ability to safeguard and advance public health. 36 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 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. Senate Legislation S. 1597 would amend FFDCA Section 569C by adding a new subsection (b), “Statement of Patient Experience,” which would require the Secretary, upon approval of a new drug application, 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 36 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. Congressional Research Service 14 Senate Medical Innovation Bills patient-focused drug development tools, and other relevant information, as determined by the Secretary. In addition, S. 1597 would require the 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 describes the content of those required guidance documents and defines, for the purposes of this section, “patient experience data” as 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 are intended to provide information about patients’ experiences with a disease or condition, including the impact of such disease or condition, or a related therapy, on patients’ lives; and patient preferences with respect to treatment of such disease or condition. Finally, S. 1597 would require the Secretary, acting through the FDA Commissioner, to publish, no later than June 1, 2021, 2026, and 2031, on the FDA website, a report “assessing the trends of the Food and Drug Administration with respect to the review of patient experience data and information on patient-focused drug development tools as part of approved applications.” Comparable Provisions in the 21st Century Cures Act H.R. 6 also contains a provision related to patient experience data (Title II, Subtitle A, Section 2001, “Development and Use of Patient Experience Data to Enhance Structured Risk-Benefit Assessment Framework”). However, the House provision is quite different from the Senate bill. H.R. 6 would amend FFDCA Section 505 by deleting a clause from Section 505(d) and adding new subsections (x) and (y). The new 505(x) would restate the deleted 505(d) requirement for the Secretary to “implement a structured risk-benefit assessment framework in the new drug approval process.” The new 505(y) would require the Secretary to “establish and implement processes under which” entities “seeking to develop patient experience data” could submit ideas and data to the Secretary and the Secretary could request materials from those entities, which could include the manufacturer and nonmanufacturer groups. This provision would define “patient experience data” as data collected by patients, parents, caregivers, patient advocacy organizations, disease research foundations, medical researchers, research sponsors, or other parties determined appropriate by the Secretary that is intended to facilitate or enhance the Secretary’s riskbenefit assessments, including information about the impact of a disease or a therapy on patients’ lives. The new subsection would also require the Secretary to issue implementation guidance after holding several methodological workshops and a public meeting. Promise for Antibiotics and Therapeutics for Health Act (S. 185) Issue Background According to the Centers for Disease Control and Prevention (CDC), each year in the United States, at least 2 million people become infected with bacteria that are resistant to antibiotics, and Congressional Research Service 15 Senate Medical Innovation Bills at least 23,000 of them die from these infections.37 Antibiotics are intended for short-term use, making the development of new ones potentially less attractive to drug developers. Addressing barriers to antibiotic drug approval may help counter this problem. One such proposal is the socalled Limited Population Antibacterial Drug (LPAD) approval pathway for new antibacterial drugs.38 Such a pathway would involve smaller clinical trials in a limited population of patients that have serious or life-threatening infections and unmet medical needs due to the lack of an effective approved antibiotic. This streamlined approach would result in more uncertainty about potential risks posed by the product, and therefore a greater need for post-market scrutiny.39 Antibacterial Resistance Monitoring (§2) Senate Legislation Section 2 would amend PHSA Section 319E to require the HHS Secretary to (1) encourage and assist in reporting of antibacterial drug use, drug resistance, and antibiotic stewardship programs 40 in health care facilities of the Indian Health Service, Department of Veterans Affairs (VA), and Department of Defense (DOD); (2) report annually on antibacterial drug resistance trends, stewardship programs, and other matters; (3) provide guidance and other informational materials about antibiotic stewardship for residential and ambulatory health care facilities; (4) assist states with their antibacterial resistance prevention activities; and (5) establish a mechanism for facilities to report antibiotic stewardship activities and drug resistance, including for drugs approved under the LPAD pathway established in the Act. Comparable Provisions in the 21st Century Cures Act Section 2121, subsection (g) would add a new subsection 317U to the PHSA requiring the HHS Secretary to establish a monitoring system for the use of antibacterial and antifungal drugs, including products approved under the LPAD pathway, as well as changes in bacterial and fungal resistance to drugs. The Secretary would be required to make summaries of data from this system publicly available. Limited Population Pathway for Antibacterial Drugs & Prescribing Authority (§§3-4) Senate Legislation Section 3 would create new FFDCA Section 506(g), “Limited population pathway for antibacterial drugs.” This review pathway would allow the Secretary to approve an antibacterial 37 Centers for Disease Control and Prevention (CDC), “Antibiotic Resistance Threats in the United States, 2013,” http://www.cdc.gov/drugresistance/threat-report-2013/. 38 Note that this is a proposed pathway and that FDA does not currently have the authority to review and approve new antibacterial drugs using the LPAD pathway. See for example Allan Coukell, “To Fight Antimicrobial Resistance, Allow FDA to Approve New Drugs for Limited Populations,” Health Affairs Blog, April 5, 2016, http://healthaffairs.org/blog/. 39 Ibid. See also President’s Council of Advisors on Science and Technology (PCAST), Report to the President on Combating Antibiotic Resistance, “Goal 4.2. Drug approval based on clinical trials in limited patient populations,” September 2014, pp. 32 ff., https://www.whitehouse.gov/administration/eop/ostp/pcast. 40 Antibiotic stewardship refers to policies and programs of antibiotic use intended to optimize health benefits while minimizing the risk of development of drug resistance. For more information see CDC, “Core Elements of Hospital Antibiotic Stewardship Programs,” http://www.cdc.gov/getsmart/healthcare/implementation/core-elements.html. Congressional Research Service 16 Senate Medical Innovation Bills drug as an LPAD drug if certain conditions are met: (1) if the drug is intended to treat a serious or life-threatening infection in a limited population of patients with unmet needs; (2) the standards for new drug application approval are met; and (3) the Secretary receives a written request from the sponsor to approve the drug as an LPAD drug. This review pathway would include the following elements:     It would require that the Secretary’s determination of the safety and efficacy of a limited population antibacterial drug “reflect[s] the benefit-risk profile of the drug in the intended limited population.” Products approved using this pathway must carry prominent labeling noting the intended use for a limited and specific population of patients. Sponsors must submit promotional materials to FDA for review 30 days prior to dissemination. Sponsors may pursue this pathway concurrently with other specified streamlined approval pathways, as applicable. Section 3 would require the Secretary to issue within 18 months of enactment guidance “describing criteria, processes, and other general considerations for demonstrating the safety and effectiveness of limited population antibacterial drugs.” It would also require the Secretary to provide advice to the sponsor regarding the approval of an LPAD drug. If an LPAD drug obtains approval for a broader indication, this legislation would allow the Secretary to remove any postmarketing conditions (e.g., labeling requirements). Section 3 would require the Secretary to report to Congress at least every two years on the number of requests for approval and the number of approvals of LPAD drugs. It also would require GAO to report on the coordination of monitoring activities required by S. 185, and the extent to which this limited pathway has streamlined premarket approval for such antibacterial drugs for limited populations, among other things. Section 4 states that S. 185 should not be construed to alter current prescribing or other medical practices. Comparable Provisions in the 21st Century Cures Act The House bill contains a comparable provision (Title II, Subtitle G, Section 2121, “Approval of Certain Drugs for Use in a Limited Population of Patients”). The House provision would add a new FFDCA subsection 505(z), “Approval of certain antimicrobial and antifungal drugs for use in a limited population of patients.” This would be an expedited review pathway for certain antibacterial and antifungal drugs (including biologics) intended for use in limited, defined populations of patients that have severe, life-threatening infections for which current treatment options may be limited or absent, and for which the benefits of a product could outweigh harms that would not be acceptable in broader population use. Some elements of the review pathway proposed in the House bill are comparable to those in the Senate bill, for example:   The Secretary could consider limited data sets and non-clinical data as substantial evidence of safety and effectiveness, recognizing the smaller populations available for study of an LPAD drug, and the different balance of benefit versus harm in these populations. Products approved using this pathway must carry prominent labeling noting the intended use for a limited and specific population of patients. Congressional Research Service 17 Senate Medical Innovation Bills     Sponsors must submit promotional materials to FDA for review 30 days prior to dissemination. Sponsors may pursue this pathway concurrently with other specified streamlined approval pathways, as applicable. FDA would be required to issue draft implementation guidance within 18 months of enactment. This provision should not be construed to alter current prescribing or other medical practices (such as off-label prescribing). Other elements of the review pathway were found only in the House provision, for example:   Upon a sponsor’s request, FDA may enter into written agreement with the sponsor to define the process and data needed to review the limited population use application. The process could not proceed without such written agreement. The process must adhere to existing goals and procedures agreed upon by sponsors and FDA in the Prescription Drug User Fee Amendments of 2012 (P.L. 112-144, Title I). In addition, the House provision would require the Secretary to conduct and publish an assessment of the program within 48 months of enactment, and to seek public input. It also would allow the Secretary to expand the limited population use pathway if deemed beneficial by the assessment above. Advancing Precision Medicine Act of 2016 (S. 2713) Issue Background 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. Currently, medical care is generally provided in a “trial and error” manner, with treatment adjusted based on real-time patient response. Precision medicine would tailor medical treatment to individual patients, thus aiming to improve health outcomes and save health care costs. 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. The mission of the PMI is “(t)o enable a new era of medicine through research, technology, and policies that empower patients, researchers, and providers to work together toward development of individualized care.”41 In the first year, the PMI’s three key agencies— 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. For More Information CRS Insight IN10227, The Precision Medicine Initiative, by Amanda K. Sarata and Judith A. Johnson. 41 Executive Office of the President, “The Precision Medicine Initiative,” https://www.whitehouse.gov/precision- medicine. Congressional Research Service 18 Senate Medical Innovation Bills Precision medicine research efforts rely on the CRS Report R44026, Genomic Data and Privacy: collection of large amounts of health data; Background and Relevant Law, coordinated by Amanda K. Sarata. 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 §301(d) of the Public Health Service Act (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. This requirement can help promote participation in research by adding an additional layer of privacy protection. In contrast to compelled disclosure of research data by FOIA request, sharing of genomic data generated by NIH-funded research is a priority of NIH. The agency 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 as well as the use of these data for subsequent research.”42 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. Precision medicine research will often be considered to be highly innovative, risky, and potentially high-reward, and will also often require close partnerships with private industry. The NIH Common Fund, within the Office of the NIH Director, supports the High-Risk, High-Reward Research Program. This program has “four unique funding opportunities for exceptionally creative scientists who propose highly innovative approaches to major challenges in biomedical research.”43 These awards are intended “to encourage creative, outside-the-box thinkers to pursue exciting and innovative ideas about biomedical research.” Other transaction (OT) authority is a special vehicle used by certain federal agencies for obtaining or advancing research and development (R&D). 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. 42 National Institutes of Health, “National Institutes of Health Genomic Data Sharing Policy,” http://gds.nih.gov/PDF/NIH_GDS_Policy.pdf, p. 1. 43 NIH, Office of Strategic Coordination, The Common Fund, High-Risk Research, at https://commonfund.nih.gov/highrisk/index. Congressional Research Service 19 Senate Medical Innovation Bills Senate Legislation S. 2713, the Advancing Precision Medicine Act of 2016, has five provisions that together would 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; (4) requiring the sharing of NIH-supported research data in certain circumstances; and (5) supporting high-risk, high-reward research. Specifically, the provisions would support precision medicine in the following ways:      Codify the President’s Precision Medicine Initiative (PMI) by encouraging the 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 (§2). Amend PHSA Section 301(d) to require the Secretary to issue a Certificate of Confidentiality to research investigators of federally funded research in which sensitive, identifiable information is collected to protect the privacy of research participants. The provision would prohibit 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 (§3). Amend PHSA Section 301 to allow the 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 Secretary would be required to make each such exemption available in writing and to the public, upon request (§4). Amend PHSA Section 402(b) to allow the 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 (§5). Add a new PHSA Section 402(m) to allow the NIH Director to approve requests by institute and center directors to engage in transactions other than a contract, grant, or agreement with respect to projects for high-impact, cutting-edge research, as specified. This provision would require the Secretary to submit a report to Congress evaluating the activities under this new subsection by September 30, 2020 (§6). Comparable Provisions in the 21st Century Cures Act Title II, Subtitle C, Section 2041, of H.R. 6 addresses precision medicine but is not comparable to S. 2713 in its approach. This section would require the Secretary, not later than 18 months after enactment, to issue and periodically update guidance to help sponsors develop a precision drug or biological product. It would also, for a precision drug or biological product application where the product is for the treatment of a serious or life-threatening disease or condition and has been designated as an orphan drug, allow the Secretary to consider the application for expedited review programs and to rely on previously submitted information about the drug or biological product (for more information, see S. 2030, the Advancing Targeted Therapies for Rare Diseases Act of 2015). In addition, Section 1028 of H.R. 6 (Title I, Subtitle B) addresses high-risk, high-reward research, and has a similar focus as the Senate bill provision; however, it would not establish OT authority, nor would it require a report to Congress. This section would require the NIH institute directors to Congressional Research Service 20 Senate Medical Innovation Bills establish programs to conduct or support projects that pursue innovative approaches to major contemporary challenges in biomedical research and to set aside a specific percentage of funding for such projects. The Senate bill would not require the allocation of a certain percentage of funding for this research. The Combination Products Innovation Act of 2016 (S. 1767) Issue Background FDA regulatory authority over medical product safety and effectiveness covers drugs, biological products, and medical devices. The agency generally divides responsibilities for the review of marketing applications in its product-centered offices. The Center for Drug Evaluation and Research (CDER) reviews new drug applications for approval, the Center for Biologics Evaluation and Research reviews biologics license applications for licensure, and the Center for Devices and Radiological Health (CDRH) reviews premarket approval applications for approval and 510(k) notifications for clearance. In 2002, Congress directed FDA to establish an Office of Combination Products (OCP) to facilitate the timely review and regulation of drug-device, drug-biologic, and device-biologic combination products, pursuant to the requirements in FFDCA Section 503. Both drugs and devices are defined in the FFDCA as products intended to diagnose, prevent, or treat disease, or otherwise affect the structure or any function of the body. Unlike a drug, however, a device “does not achieve its primary intended purposes through chemical action within or on the body ... and is not dependent upon being metabolized for the achievement of its primary intended purposes.” OCP is required to determine the primary mode of action of a combination product and regulate it based on that determination. Generally, OCP treats a drug-device combination product as a drug unless the manufacturer can prove that it satisfies the device exclusionary clause; i.e., the product does not rely on chemical action to achieve its primary intended purpose. A manufacturer whose product is assigned to CDER will have a higher standard of evidence, a potentially higher requirement for supporting data, a higher user fee, and probably a longer premarket review time period than a manufacturer whose product is assigned to CDRH. Senate Bill S. 1767 would amend Section 503(g) of the FFDCA to require the Secretary to assign a primary center for the regulation of combination products and to conduct premarket review of these products under a single application whenever appropriate, among other things. The bill would require the Secretary to determine the primary mode of action for a combination product— defined as the single mode of action expected to make the greatest contribution to the overall intended therapeutic effects of the product—in order to determine how best to review the product. The Secretary would not be permitted to determine that the primary mode of action is that of a drug or biologic solely because the combination product has any chemical action within or on the body. If the sponsor of a combination product disagreed with the Secretary’s determination and requested an explanation, the Secretary would be required to provide a substantive scientific rationale for the determination. In addition, the sponsor would be able to propose and, subject to Congressional Research Service 21 Senate Medical Innovation Bills an agreement with the Secretary, conduct additional studies to establish the relevance of any chemical action in the product’s primary mode of action. At any time following the Secretary’s determination of the product’s primary mode of action, the sponsor would be permitted to submit a proposed combination product review plan, as specified. The Secretary would be required to provide a written response to the sponsor indicating whether the plan was accepted, accepted in part, or denied. The bill would allow the sponsor, if the plan were to be denied, to request a meeting with the Secretary to discuss the information and requirements necessary to make the plan acceptable. A denied plan would be allowed to be resubmitted. With respect to an accepted plan, in whole or part, the Secretary would be required to accept the plan if the Secretary determines the data to be collected are appropriate for premarket approval; in addition, a plan, in whole or in part, that has been accepted would be required to remain in effect except with written agreement of the Secretary and the sponsor or pursuant to a decision by the reviewing primary agency center director that a relevant scientific issue had been identified since acceptance of the plan. If such a decision were to be issued, the Secretary would be required to provide written notice to the sponsor as well as an opportunity for a meeting. For premarket review of a combination product that includes an approved constituent component (e.g., a drug or device), the Secretary would be allowed to require that a sponsor submit only that information that is necessary to determine the safety of the combination product, including any incremental risks or benefits posed by the product, taking into account any prior findings for the approved constituent parts. For premarket review of a combination product that contains an approved drug constituent, the applicant would be permitted to rely upon investigational studies not conducted by the applicant and for which the applicant has not obtained a right of reference.44 In relying upon these studies, the applicant would be required to certify any patents that claim the approved drug or claim use of the approved drug.45 The applicant would also be required to give notice to the holder of the approved application and patent owner that the patent is invalid or will not be infringed upon. The approval of an application containing such certification would be required to be made effective as specified in FFDCA Section 503(c)(3), among other requirements. Notwithstanding any other provision of Section 503(g)(5), an application for a combination product that contains an approved drug constituent would be considered a 505(b)(2) application.46 The bill would not prohibit a sponsor from submitting separate applications for the constituent parts of a combination product, unless the Secretary determines that a single application is necessary. The bill would further require 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. The bill would specify additional duties for OCP related to communication; facilitating meetings between the agency and the sponsors; and dispute resolution. The bill would require the Secretary, not later than four years after enactment, to issue final guidance on the combination product review process, as specified, 44 Right of reference means “the authority to rely upon, and otherwise use, an investigation for the purpose of obtaining approval of an application, including the ability to make available the underlying raw data from the investigation for FDA audit, if necessary.” 21 C.F.R. 314.3. 45 Such patent information is generally published in the Orange Book when the application is approved. 46 A 505(b)(2) application is one for which one or more of the investigations relied upon by the applicant for approval "were not conducted by or for the applicant and for which the applicant has not obtained a right of reference or use from the person by or for whom the investigations were conducted.” FFDCA §505(b)(2)). Congressional Research Service 22 Senate Medical Innovation Bills and would add reporting requirements to the annual report to Congress on the activities of OCP as specified. The bill would amend 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. The bill would also require the Secretary to identify, not later than 18 months after enactment, types of combination products that the Secretary proposes may adopt different good manufacturing practices. This list would be required to be published in the Federal Register and updated as needed. Comparable Provisions in the 21st Century Cures Act Section 2181 of H.R. 6 addresses the issue of combination products, but would take a different approach than the Senate legislation. The H.R. 6 section would amend FFDCA Section 503(g)(4)(C) to require that the Secretary “issue final guidance that describes the responsibilities of each agency center regarding its review of combination products.” Health Software: The Medical Electronic Data Technology Enhancement for Consumers’ Health Act (S. 1101) Issue Background Increasingly, health care facilities are using computer systems for routine administrative and financial transactions (e.g., patient scheduling, claims processing) and for capturing and exchanging clinical information (e.g., electronic health records). One area that is undergoing especially rapid growth and innovation is mobile health. This term refers to the use of portable devices, such as smartphones and tablets, for medical purposes. Users interface with mobile devices through the use of software applications (“apps”). The number of health-related mobile apps being developed, downloaded, and used is increasing at an almost exponential rate. Some apps simply access stored medical information, while others capture and input patient data into an electronic health record (EHR). Many apps now provide clinical decision support (CDS) using algorithms that use clinical information to generate customized (i.e., patient-specific) diagnosis and treatment recommendations. Regulators are particularly interested in mobile apps that could pose a risk to patients if they malfunction. These include apps used to display and transfer data from a patient monitor; apps that control an existing device; and apps that transform a mobile platform into a medical device (e.g., an app that allows patients to use their smartphone to record electrocardiograms using a lead that connects to the phone). Congressional Research Service 23 Senate Medical Innovation Bills Under the FFDCA, the FDA has regulatory authority over software that meets the statutory definition of a medical device and is “intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease.”47 FDA released a nonbinding guidance document on mobile medical apps in September 2013, in which it stated its intention to focus on the functionality of the mobile health product, not the mobile platform itself.48 Thus, the agency does not plan to regulate smartphone or tablet manufacturers. FDA further stated its intention to adopt a risk-based approach by applying its regulatory oversight to “only those mobile apps that are medical devices and whose functionality could pose a risk to patient safety if the mobile app were to not function as intended.” In February 2015, FDA released updated guidance on its risk-based approach to regulating mobile medical apps.49 The agency provided examples of mobile apps that do not meet the statutory definition of a medical device and so are not subject to its regulatory authority. They include apps used to automate general office operations in health care settings. The agency then gave examples of mobile apps that may meet the definition of a medical device but for which the agency intends to exercise enforcement discretion—meaning that it does not intend to apply regulatory oversight—because the apps pose minimal risk to the public. This category includes mobile apps that help asthmatics track inhaler usage and asthma episodes; apps that give patients a portal into their own EHR; and apps intended for individuals to log, track, or make decisions related to general wellness (e.g., Fitbit). Finally, FDA provided examples of mobile apps that are the focus of the agency’s regulatory oversight. These apps meet the definition of a medical device, and they pose a significant risk to patient safety if they do not function as intended. Examples include apps that connect to an existing device for the purpose of controlling its operation, function, or energy source; apps that are used in active patient monitoring or analyzing patient-specific medical device data from a connected device; and apps that transform a mobile platform into a regulated medical device. The updated guidance did not address regulation of CDS software. That topic remains under consideration. Senate Legislation S. 1101, the Medical Electronic Data Technology Enhancement for Consumers’ Health (MEDTECH) Act, would exclude certain types of health software from the FFDCA definition of medical device, including products that provide a variety of administrative and health management functions; electronic health record technology that creates, stores, transfers, and displays patient information; and software that interprets and analyzes patient data to help make clinical diagnosis or treatment decisions (including CDS tools). In general, this would preclude FDA from regulating these products as medical devices. However, S. 1101 creates an exception allowing FDA to exercise regulatory authority if the agency determines that the use of the software “would be reasonably likely to have serious adverse health consequences” based on four specified criteria. One of the criteria is the likelihood and severity of patient harm if the software were not to perform as intended. The exception would 47 FFDCA §201(h), 21 U.S.C. §321(h). 48 Food and Drug Administration, Mobile Medical Applications: Guidance for Industry and Food and Drug Administration Staff, September 25, 2013. 49 Food and Drug Administration, Mobile Medical Applications: Guidance for Industry and Food and Drug Administration Staff, February 9, 2015, http://www.fda.gov/downloads/MedicalDevices/UCM263366.pdf. Congressional Research Service 24 Senate Medical Innovation Bills apply to EHR systems (and other software that simply creates, stores, transfers, and displays data), as well as CDS and other analytic tools. This risk-based approach broadly reflects the agency’s current guidance on regulating mobile medical apps. Comparable Provisions in the 21st Century Cures Act The health software provisions in H.R. 6, Sections 2241-2243, are similar to those in S. 1101. Like the Senate bill, H.R. 6 would exclude various types of software applications from FDA’s regulatory oversight. Excluded applications include products that provide administrative and health management functions; software that creates, stores, transfers, and displays patient information; and analytic tools that provide both general health information and patient-specific information (i.e., CDS). The House bill also would establish a risk-based exception allowing FDA to exert regulatory authority. However, H.R. 6 would create a narrower exception for CDS software that the agency determines “poses a significant risk to patient safety” based on the same four criteria specified in S. 1101. Interoperability: Improving Health Information Technology Act (S. 2511) Issue Background The Health Information Technology for Economic and Clinical Health (HITECH) Act of 2009 authorized Medicare and Medicaid incentive payments to acute-care hospitals and physicians who attest to being meaningful users of certified electronic health record (EHR) technology.50 The law instructed the Secretary to make the measures of meaningful use more stringent over time, which CMS has done in stages. Stage 1 of meaningful use requires eligible hospitals and physicians to use EHR technology to meet a series of meaningful use objectives that generally involve capturing and storing structured patient data (e.g., vital signs, medications, lab test results). Providers must use EHR technology that has been tested and certified as having the capability to perform these functions. Testing and certification entities are authorized by the HHS Office of the National Coordinator for Health Information Technology (ONC). Stage 2 of meaningful use requires eligible hospitals and physicians to use their EHR technology to perform more advanced functions, such as giving patients access to their electronic health information and exchanging patient data during transitions of care (e.g., a hospital discharge to a rehabilitation facility, or a physician referral). Beginning in 2015, hospitals and physicians that are not meaningful EHR users are subject to a Medicare payment adjustment (i.e., penalty) unless they qualify for a hardship exception. CMS published a final rule in October 2015 modifying the meaningful use Stage 2 objectives and establishing the objectives for Stage 3, which hospitals and physicians must meet by 2018.51 The agency made significant changes to the meaningful use program in response to the concerns of 50 P.L. 111-5, Division B, Title IV; 123 Stat. 467. 51 Centers for Medicare & Medicaid Services, “Medicare and Medicaid Programs; Electronic Health Record Incentive Program - Stage 3 and Modifications to Meaningful Use in 2015 Through 2017; Final Rule,” 80 Federal Register 62761, October 16, 2015. Congressional Research Service 25 Senate Medical Innovation Bills health care providers about the challenges and burdens they face in making EHR technology work. For example, CMS eliminated several clinical documentation objectives, and instead focused on a few objectives that capture more advanced uses of the technology (e.g., CDS, health information exchange). CMS also published an accompanying final rule (the 2015 Edition final rule) that expands the certification program.52 In addition to certifying the next generation of EHR technology that hospitals and physicians need to achieve meaningful use Stage 3, the program will be able to certify health information technology (HIT) products with a different combination of capabilities and functionalities that meet the needs of other types of health care providers and settings that are not eligible to participate in the EHR incentive program. The 2015 Edition final rule for the certification program established new transparency requirements for HIT developers. It also seeks to improve interoperability, for example, by requiring certified HIT products to adopt new and updated vocabulary and content standards for structured health information, including a common clinical data set composed of standardized data elements, and by improving the testing of the ability of HIT systems to transmit, receive, and use standardized clinical documents. ONC released a national interoperability roadmap in October 2015—developed over an 18-month period with input from numerous stakeholders—to coordinate efforts around achieving HIT interoperability.53 ONC expects the roadmap to evolve in partnership with the public and private sectors as technology and policy dictate. The roadmap establishes interoperability goals for the next 10 years, with 2017 set as the deadline for individuals and health care providers along the care continuum to be able to send, receive, find, and use core clinical data. The roadmap discusses the payment and regulatory drivers for promoting interoperability, as well as the central policy and technical components of a fully interoperable nationwide health information infrastructure. A key challenge is overcoming legal and governance barriers to trusted information exchange by getting stakeholders to agree to and follow a common set of standards, services, policies, and practices that facilitate exchange and use of electronic health information without limiting competition. Medicare Access and CHIP Reauthorization Act of 2015 (MACRA)54 MACRA declared it a national objective to achieve widespread interoperability of certified EHR technology by the end of 2018. The law defines interoperability as the ability of health information systems to not only exchange clinical information but to also use the information based on common standards in order to improve care and patient outcomes. In addition, MACRA instructed the Secretary, within one year of enactment, to submit a report to Congress on ways to help health care providers compare and select certified EHR technology, such as through surveying EHR users and vendors and making such information publicly available. 52 Office of the National Coordinator for Health Information Technology, “2015 Edition Health Information Technology (Health IT) Certification Criteria, 2015 Edition Base Electronic Health Record (EHR) Definition, and ONC Health IT Certification Program Modifications; Final Rule,” 80 Federal Register 62601, October 16, 2015. 53 Office of the National Coordinator for Health Information Technology, Connecting Health and Care for the Nation: A Shared Nationwide Interoperability Roadmap, Final Version 1.0, October 2015, https://www.healthit.gov/sites/ default/files/hie-interoperability/nationwide-interoperability-roadmap-final-version-1.0.pdf. 54 P.L. 114-10, §106(b), 129 Stat. 138. Congressional Research Service 26 Senate Medical Innovation Bills Finally, MACRA required the Secretary, in consultation with stakeholders, to establish interoperability metrics to measure progress toward achieving the national objective of widespread interoperability of certified EHR technology by July 1, 2016. If that objective is not met by December 31, 2018, the Secretary will have until December 31, 2019, to submit a report to Congress identifying the barriers to widespread interoperability and providing recommendations for achieving it. Information Blocking ONC released a report to Congress on health information blocking in April 2015.55 The report defined information blocking as knowingly and unreasonably interfering with the exchange or use of electronic health information, and examined the nature and extent of the practice based on available evidence. It also detailed the actions that ONC is taking, in coordination with other federal agencies, to address information blocking. Finally, the report identified gaps in authority that limit the ability of ONC and other federal agencies to effectively target, deter, and remedy such conduct. MACRA requires eligible hospitals and physicians, beginning April 2016, to indicate through meaningful use attestation (or some other process specified by the Secretary) that they have not knowingly and willfully taken any action to limit or restrict the interoperability of their certified EHR technology. Patient Access The Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule gives individuals the right of access to inspect, obtain a copy of, and transmit to a third party a copy of their health information.56 One of the meaningful use objectives that must be met by hospitals and physicians using certified EHR technology is to provide individuals with the ability to view, download, and transmit (VDT) their electronic health information. As part of meeting that objective, the 2015 Edition final rule for the certification program requires [Text truncated at 120,000 characters. The full text is on the page linked above.] --- Source: Frix Law Library, https://www.frixlaw.com/law-library/documents/crs%3AR44502. Public record. Not legal advice.