On April 6, 2016, the Senate Committee on Health, Education, Labor and Pensions (HELP) voted to approve five bills on biomedical research, drug development, and President Obama’s Precision Medicine Initiative. Together they represent the third and final tranche of the Senate’s Innovation for Healthy Americans initiative, which was initially conceived as a single bill, but now consists of a package of 19 separate bills. The package is the companion effort to the House’s July 2015 passage of H.R. 6, the 21st Century Cures Act.
The remaining bills are now headed to the Senate floor as a package, where HELP Committee Chairman Lamar Alexander (R-TN) and Ranking Member Patty Murray (D-WA) will look to resolve a dispute over mandatory funding for the National Institutes of Health (NIH). The 21st Century Cures Act passed the House with a provision granting US$8.8 billion in mandatory funding to the NIH, which Senate Democrats support and would like to see in the final Senate package, but Senate Republicans are interested in more targeted funding for NIH.
Bills approved at the April 6 markup focus on streamlining FDA review of combination products (S. 1767), the Precision Medicine Initiative and NIH research (S. 2713), combatting antibiotic resistance (S. 185), FDA and NIH workforce issues (S. 2700), NIH research on minority groups and health disparities (S. 2745), and streamlining NIH administrative processes (S. 2742).
The HELP Committee previously approved legislation on February 9 on medical records compliance (S. 2511), concerns about infection control (S. 2503), treatment of rare diseases (S. 2030), approvals of medical devices (S. 1622), added surveillance on neurological diseases (S. 849), and encouragement for rehabilitation research (S. 800), and young researchers (S. 2014).
In March, the HELP Committee reported out legislation on renewing the addition of rare pediatric diseases to a priority review process (S. 1878), adding Zika vaccine eligibility (S. 2512), and expedited reviews of medical devices (S. 1077), plus measures addressing FDA’s regulation of medical software (S. 1101), FDA’s assessment of patient engagement on new drugs (S. 1597), and the development of medical countermeasures against bioterrorism (S. 2055). S. 2512, adding Zika to the Priority Review Voucher Program Act, passed the Senate on March 17, was approved by a voice vote in the House on April 12, and enacted on April 19.
As this legislation progressed in the Senate, on April 26 the House Appropriations Committee reported H.R. 5054, the Agriculture, Rural Development, Food and Drug Administration, and Related Agencies Appropriations Act of 2017. The bill, if approved by the Senate and the President, includes legislative language restricting FDA from (1) requiring electronic (rather than paper) distribution of drug labeling information to healthcare professionals; (2) permitting research in which a human embryo is intentionally created or modified to include a heritable genetic modification; and (3) implementing a 2013 proposed rule on updating generic drug labels.
The Appropriations bill also includes several non-binding policy riders that urge the FDA to do the following: (1) collaborate with industry on adaptive clinical trials for antibiotics; (2) finalize guidance on drug compounding; (3) engage with patient groups to educate about biosimilars; (4) use intermediate clinical endpoints to approve treatments for rare diseases such as Duchenne muscular dystrophy; (5) redirect funds from combatting the Ebola virus to combatting the Zika virus; (6) send a report to Congress on the FDA-CMS parallel review pilot; (7) suspend its work on a final guidance on laboratory-developed tests and work with Congress on a legislative alternative; (8) improve consistency of inspections of medical device facilities; (9) convene a working group of stakeholders to inform policy on the appropriate scope of scientific and medical information that can be shared with physicians, insurers, and researchers; (10) issue guidance on the use of surrogate endpoints for regenerative medicine products; and (11) approve medication-assisted treatments for opioid addiction and over-the-counter naloxone.
Overview of the Senate Innovation for Healthy Americans Legislative Package
This Advisory summarizes key provisions of the Senate package that were not included in the House-passed bill.
House Energy and Commerce Committee Chairman Fred Upton (R-6th-MI) and Ranking Member Diana DeGette (D-1st-CO) have praised the Senate’s efforts and anticipate naming conferees for a conference committee, assuming passage of the Senate package.
The provisions of the Senate package include:
S. 2700, FDA and NIH Workforce Authorities Modernization Act (S.2700), sponsored by Senators Alexander (R-TN), and Murray (D-WA)
Sec. 4. Establishment of FDA Intercenter Institutes. This provision would require FDA to establish one or more Intercenter Institutes for a major disease area. The Institute must develop processes for coordinating activities across CBER, CDER, and CDRH, including coordinating expertise of staff, streamlining review processes to the extent permissible under current law, and enhance interactions with patients, sponsors, and the biomedical community. FDA must provide a period for public comment on the Institute and must establish at least one Institute within one year of enactment.
Sec. 5. Scientific Meetings. Section 5 would remove barriers in federal budget rules that restrict FDA and NIH scientists’ ability to attend scientific conferences, but would not change rules regarding travel. The provision would require public reporting of an annual report on scientific meeting attendance and travel spending, and detailed descriptions of any meetings with spending over US$30,000.
Sec. 8. Studies. This provision would remove requirements for certain statutorily mandated studies (Report to Congress on the Office of Surveillance and Epidemiology; IOM study of the pediatric studies and exclusivity program; and a Report to Congress on the third party accreditation program for devices)
Sec. 9. Summary Level Review. Section 9 would amend the Federal Food, Drug, and Cosmetic Act to permit FDA to rely upon qualified data summaries of clinical data that demonstrate the safety and effectiveness of a drug to support the approval of a supplemental application for a qualified indication for a drug or biologic. A supplemental application would be eligible for review under this provision if (1) there is existing data available and acceptable to the Secretary demonstrating the safety of the drug and (2) all data used to develop the qualified data summaries are submitted as part of the supplemental application.
Sec. 10. Drug Surveillance. This provision would require FDA to work with scientific experts to develop best practices for drug safety surveillance using the FDA Adverse Event Reporting Systems and criteria for public posting of adverse event signals.
Sec. 11. Biological Product Innovation. This provision would exempt biological products from certain provisions of the Food, Drug, and Cosmetic Act that refer to an official compendium with the objective of preventing delays in the licensure of biosimilar products.
Sec. 15. Standards for Regenerative Medicine and Advanced Therapies. This provision would require the Secretary to work with NIST and stakeholders in regenerative medicine and advanced therapies (defined as cell therapy, gene therapy, gene-modified cell therapy, therapeutic tissue engineering products, human cell and tissue products, and combination products using such therapies) to coordinate and prioritize the development of standards for product development, evaluation and review through regulatory predictability, including manufacturing processes and controls for such therapies. Also, Section 15 would require the Secretary to identify opportunities for the development of laboratory regulatory science research and documentary standards that would help support regenerative medicine. The Secretary would also be required to review relevant regulations and guidelines and update them through a transparent public process.
S. 2713, the Advancing Precision Medicine Act of 2016
Sec. 2. Precision Medicine Initiative. This provision would encourage the Secretary of Health and Human Services to establish a Precision Medicine Initiative to augment efforts to address disease prevention, diagnosis, and treatment. Such an Initiative may include developing a network of scientists, new approaches for addressing scientific, medical, public health, and regulatory science issues; applying genomic technologies to provide data on the molecular basis of disease, collecting information voluntarily provided by a diverse cohort of individuals to better understand health and disease, and other activities. The Secretary would be required to collaborate with agencies within HHS, and to work with the Department of Energy, to identify and address advanced supercomputing needs for the Precision Medicine Initiative.
Sec. 3. Protection of Identifiable, Sensitive Information. This provision would permit the Secretary to exempt from FOIA disclosure biomedical information that is gathered during research if an individual is identified or there is a risk of deducing identity from other information.
Sec. 4. Data Sharing. This provision would permit the Secretary to require recipients of NIH grants or cooperative agreements to share scientific data, to the extent feasible, generated from such NIH grants or cooperative agreements in a manner that is consistent with all applicable federal laws and regulations, including such laws and regulations for the protection of human research participants’ privacy, data security, informed consent, and protected health information; proprietary interests, confidential commercial information, and the intellectual property rights of the funding recipient; and national, homeland, and economic security interests.
Sec. 5. High-Risk, High-Reward Research. Section 5 would permit the Director of NIH to use Other Transactions Authority for projects for high-impact, cutting-edge research that fosters scientific creativity and increases fundamental biological understanding leading to the prevention, diagnosis, or treatment of diseases and disorders. The provision requires an evaluation of the use of the authority and a report to Congress in 2020.
S. 185, Promise for Antibiotics and Therapeutics for Health Act (PATH Act)
Sec. 2. Antibiotic Resistance Monitoring. The PATH Act would encourage the Secretary of Health and Human Services to report information on use of antibacterial drugs, resistance to such drugs, and antibiotic stewardship programs by federal health care facilities. It would require annual public reporting of trends in antibiotic resistance and outreach to/education for State and local health departments and private health care facilities.
Sec. 3. Limited Population Pathway for Anti-Bacterial Drugs. This provision would establish a "limited population pathway" for FDA approval of an antibacterial drug as a limited population drug, if the drug is intended to treat a serious or life-threatening infection in a limited population of patients with unmet needs, the standards for drug approval or biologic licensure are met, and the Secretary receives a written request from the sponsor to approve the drug as a limited population drug.
The Secretary’s determination of safety and effectiveness of a limited population antibacterial drug must reflect the benefit-risk profile of the drug in the intended limited population, taking into account the severity, rarity, or prevalence of the infection the drug is intended to treat and the availability or lack of alternative treatment in such limited population. Such drug could be approved under this subsection notwithstanding a lack of evidence to fully establish a favorable benefit-risk profile in a population that is broader than the intended limited population.
The labeling and advertising for the product would be required to contain the statement "Limited Population" in a prominent manner, and the prescribing information for the drug would be required to include the statement "This drug is indicated for use in a limited and specific population of patients." Drug sponsors would need to submit copies of all promotional materials to FDA at least 30 days prior to disseminating them. Drugs approved for a limited population may also seek designation or approval under other authorities.
The PATH Act would also require the Secretary to draft guidance on the criteria and processes for demonstrating the safety and effectiveness of limited population antibacterial drugs and publish final guidance within 18 months of the close of the comment period on the draft guidance. Under this framework, the Secretary may approve drugs for a limited population prior to issuing such guidance. If the Secretary approves a broader indication for the drug, the postmarketing requirements with regard to labeling and review of promotional materials may be removed.
The bill includes a rule of construction that nothing in this subsection alters the authority of the Secretary to approve drugs and biologics, including the standards of evidence and applicable conditions for approval, standards of approval, or authority to monitor drugs.
A report to Congress every 2 years and a GAO report by the end of 2021 would also be required.
Sec. 4. Prescribing Authority. The PATH Act includes a rule of construction stating that it does not restrict the prescribing of antibacterial drugs or other products by health care professionals or to "limit the practice of health care."
S. 2745, Advancing NIH Strategic Planning and Representation in Medical Research Act
Sec. 2. NIH Strategic Plan. This provision would require the NIH Director and Directors of the NIH research institutes and centers to develop an NIH Strategic Plan within 2 years of enactment and every 6 years thereafter. The plan would provide direction to the biomedical research investments made by the NIH, facilitate collaboration across the institutes and centers to leverage scientific opportunity, and advance biomedicine. The Director would consider disease burden in the US, rare diseases and conditions, biological and social determinants of health that contribute to health disparities, and include strategic priorities for use of the Common Fund.
Sec. 3. Collaboration to Enhance Diversity in Clinical Research. This provision would require the NIH Director to collect additional data to assess research priorities including scientific opportunity, public health burden, and study populations of clinical research that include women, minority groups, and other demographic groups. The data must be disaggregated by research area, condition, and disease categories.
Sec. 4. Promoting Inclusion in Clinical Research. NIH centers and institutes would be required to consult at least once per year with the Director of the National Institute on Minority Health and Health Disparities and the Director of the Office of Research on Women's Health when developing strategic plans. The provision also clarifies an existing requirement that NIH-funded clinical research studies include appropriate subgroup analyses showing the impact on women. Starting one year after enactment, applicants for new grants for clinical research studies, and for extensions of existing grants, would be required to submit those analyses to the clinicaltrials.gov database, and the Director of NIH would consider compliance with this requirement in awarding future grants.
Sec. 5. Research Related to Sexual and Gender Minority Populations. The NIH Director would be required to encourage research on the health of sexual and gender minority populations, facilitate the development of valid methodologies for such research, support research on measures for reporting health information about sexual and gender minorities, and publicly report measures within two years, taking into account recommendations by the National Academy of Medicine.
Sec. 6. Improving Coordination Related to Minority Health and Health Disparities. The NIH Director would encourage funding of collaborative research projects that are related to minority health and health disparities.
Sec. 7. Enhancing the Rigor and Reproducibility of Scientific Research. The Secretary would be required to, within one year, convene a working group and develop recommendations for a formal policy to enhance rigor and reproducibility of NIH-funded research. The plan must consider preclinical experimental design, including analysis of sex as a biological variable; analyses of data stratified by measures of health disparities; statistical methodologies; and data and information sharing. The Director of NIH would be required to update policies within 18 months, and submit a report to the Secretary and Congress within 2 years.
Sec. 8. Task Force on Research Specific to Pregnant and Lactating Women. This provision would establish, within 90 days of enactment, a Task Force on Research Specific to Pregnant and Lactating Women that includes the Directors of CDC, NIH, FDA, and other federal entities with responsibility for women’s and children’s health. The Task Force would also include representatives from relevant medical societies, nonprofit organizations, and industry with expertise on pregnant or lactating women or children. The Task Force would be required to report to the Secretary and Congress within 18 months on ways to address gaps in knowledge about safe and effective therapies for pregnant and lactating women, and make recommendations to improve development of such therapies. No later than 2 years following enactment, the Secretary must update applicable regulations and guidance on the inclusion of pregnant and lactating women in clinical research, considering any recommendations of the Task Force.
For a side-by-side comparison of the Senate package and the House-passed 21st Century Cures Act, please click here.