Highlights of Drug and Biologic Related Provisions of 21st Century Cures (Part Two)

December 15, 2016By Michelle L. Butler & James E. Valentine

As we previously reported, the President signed into the law the 21st Century Cures Act (Act) on December 13, 2016 (find the full text here). This post is part two of a two-part post that summarizes the relevant provisions related to development of drugs and biologics. Part one of this summary (covering Subtitles A-D of Title III of the Act) can be found here.

In addition, Hyman, Phelps & McNamara, P.C.’s summary of Subtitle F of Title III of the Act pertaining to medical device development provisions can be found here. We expect to publish additional posts, including a post summarizing the combination product provision and a post summarizing relevant health care provisions.

Here is a summary of Subtitles E, G-I of Title III of the Act pertaining to drug development.


Subtitle E—Antimicrobial Innovation And Stewardship

Sec. 3041. Antimicrobial resistance monitoring.

Section 3041 amends the Public Health Service Act (PHS Act) to require HHS to encourage reporting on aggregate antimicrobial drug use and antimicrobial resistance to antimicrobial drugs and implementation of antimicrobial stewardship program by the DoD, VA, and the Indian Health Service. The section also directs HHS to provide technical assistance to the DoD and VA as appropriate and upon request.

The section requires HHS to publish a report on antimicrobial resistance in humans and use of antimicrobial drugs, including qualified infectious disease products under section 506(h) of the Federal Food, Drug, and Cosmetic Act (FDC Act). The report is required within one year of the date of enactment of the Act. In addition, HHS is directed to disseminate, as appropriate, guidance and educational materials related to development and implementation of evidence-based antimicrobial stewardship programs or practices at health care facilities.

The section requires HHS to work with State and local public health departments on programs related to antimicrobial resistance.

To fulfill the purposes of this section, HHS is directed to provide a mechanism for facilities to report data related to their antimicrobial stewardship activities.

Sec. 3042. Limited population pathway.

Section 3042 amends the FDC Act to allow FDA to approve an antibacterial or antifungal drug, along or in combination with other drugs, 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 NDA or BLA approval/licensure are met; and
  • FDA receives a written request from the sponsor to approve the drug as a limited population drug.

FDA then must make its determination of safety and effectiveness of the drug to reflect the benefit-risk profile of the drug in the intended limited population, considering the severity, rarity, or prevalence of the infection and the available or lack of alternative treatment. FDA may approve the drug even though there is a lack of evidence to fully establish a favorable benefit-risk profile in a broader patient population.

A drug approved under this section is subject to the following requirements:

  • Labeling and advertising of the drug must contain the statement “Limited Population” in a prominent manner;
  • Inclusion of the statement “This drug is indicated for use in a limited and specific population of patients” in the prescribing information; and
  • Submission to FDA copies of all promotional materials at least 30 days prior to dissemination of the materials.

These postapproval requirements can be removed if a broader indication for the drug is approved under an NDA or BLA.

The section also requires FDA to issue draft guidance describing criteria, processes, and other considerations for demonstrating safety and effectiveness of limited population antibacterial and antifungal drugs. FDA has 18 months to issue the draft guidance document, and another 18 months after the public comment period on the draft guidance ends, to issue a final guidance. However, FDA may still approve antibacterial and antifungal drugs under this section prior to issuing such guidance.

The section requires FDA to provide prompt advice to the sponsor of a drug seeking approval under this section.

In addition, FDA must report to Congress at least every other year the number of requests for approval and the number of approvals of drugs under this section. No later than December 2021, GAO must also provide Congress a report on the coordination of activities of the Antimicrobial Resistance Task Force and the approval pathway under this section.

Sec. 3043. Prescribing authority.

Section 3043 specifies that nothing in Subtitle E of the Act restricts the prescribing of antimicrobial drugs and other products, including qualified infectious disease products, by health care professionals, or otherwise limits the practice of health care.

Sec. 3044. Susceptibility test interpretive criteria for microorganisms; antimicrobial susceptibility testing devices.

Section 3044 amends the FDC Act to clarify FDA’s authority to update susceptibility test interpretive criteria for antimicrobial drugs (i.e., to determine how much of a drug to use and which infections a drug is useful in treating) when necessary for public health, due to, among other things, the constant evolution of microorganisms that leads to the development of resistance to drugs. Unique management of such drugs is necessary to delay or prevent the development of further resistance. The section requires FDA to identify appropriate susceptibility test interpretive criteria for such drugs at the time of approval, if available, or at some later date that they become available. The bases for initial identification of these criteria must be based on available and relevant:

  • Preclinical and clinical data;
  • The relationship of the susceptibility test interpretive criteria to morbidity and mortality associated with the disease or condition for which the drug is used; and
  • Other evidence as appropriate.

The section also requires FDA, within one year of the date of enactment of the Act, to establish and maintain on FDA.gov a dedicated website that contains a list of any appropriate new or updated susceptibility test interpretive criteria standards, including those established by nationally or internationally recognized standards development organizations (referred to as the Interpretive Criteria Website). In addition, FDA must post a list of any interpretive criteria that the Agency has determined to be appropriate regarding legally marketed antimicrobial drugs where:

  • FDA does not recognize, in whole or in part, an interpretive criteria standard from the first list;
  • FDA withdraws recognition of a standard, in whole or in part;
  • FDA approves an NDA or BLA with respect to marketing such a drug for which there are no relevant interpretive criteria included in a standard; and
  • Because the characteristics of such a drug differ from other drugs with the same active ingredient, the interpretive criteria with respect to such drug differ from otherwise applicable interpretive criteria and are determined by FDA to be appropriate for the drug.

FDA must announce the creation of the Interpretive Criteria Website containing this information in the Federal Register. Furthermore, once the Interpretive Criteria Website is established, and every 6 months thereafter, FDA evaluate the lists for new or updated susceptibility test interpretive standards, as well as for approved NDAs and BLAs, and make necessary changes. Each year, FDA must compile all of changes to the lists and publish this information in the Federal Register and provide for public comment.

The section also requires, within one year of the establishment of the Interpretive Criteria Website, a holder of an approved NDA or BLA to remove susceptibility test interpretive criteria, if any, and related information from the approved drug labeling and replace it with a reference to the Interpretive Criteria Website. This can be accomplished through an annual report. Drugs approved after the establishment of the Interpretive Criteria Website must include reference to the website.

In addition, the section creates special conditions for marketing of antimicrobial susceptibility testing devices if those devices meet the following conditions:

  • The device is used to make a determination of susceptibility using susceptibility test interpretive criteria that are either included in a standard recognized by FDA or otherwise listed on the Interpretive Criteria Website;
  • The labeling of such device conveys
    • Information about the in vitro susceptibility of microorganisms, as applicable to antimicrobial drugs,
    • That the safety and efficacy of such drugs in treating clinical infections may or may not have been established in adequate and well-controlled clinical trials for the device to report susceptibility and that the clinical significance of such susceptibility information in those instances is unknown;
    • That the approved labeling for drugs tested using such a device provides the uses for which FDA has approved such drugs; and
    • Any other information FDA finds appropriate to adequately convey the meaning of the data supporting the standards and criteria;
  • The device meets all other requirements to be cleared under section 510(k), classified under section 513(f)(2), or approved under section 515.

The section requires within 2 years of enactment of the Act that FDA submit to Congress a report on the progress of implementing this section.

Subtitle G—Improving Scientific Expertise And Outreach At FDA

Sec. 3071. Silvio O. Conte Senior Biomedical Research and Biomedical Product Assessment Service.

Section 3071 amends the PHS Act to expand the Silvio O. Conte Senior Biomedical Research Service from a maximum of 500 members to 2000 members, which allows the recruitment of additional qualified scientific and technical experts in biomedical research, clinical research evaluation, and biomedical product assessment across HHS. The section also increases the maximum salary of the members to now not exceed the amount of annual compensation of the President (currently $400,000 per year).

The section also directs GAO to study the effectiveness of these reforms on all agencies or departments within HHS that must be provided to Congress as a report within 4 years of the date of enactment of the Act. The GAO study and report must address:

  • Total number of members recruited and retained, and the effect of increasing the number of members;
  • The number of members hired with a doctoral level degree in biomedicine or related field, and the number of members hired with a doctoral or master’s level degree in engineering, bioinformatics, or related emerging field; and
  • The number of members that have been hired by each agency or department within HHS, and how HHS assigns such members.

Sec. 3072. Hiring authority for scientific, technical, and professional personnel.

Section 3072 amends the FDC Act by allowing FDA to appoint scientific, technical, or professional positions that support the development, review, and regulation of medical products within the competitive service. In addition, the section provides that such appointments may have a maximum salary to now not exceed the amount of annual compensation of the President (currently $400,000 per year).

The section requires FDA to provide to Congress, within 18 months of the date of enactment of the Act, a report on workforce planning that examines FDA’s need for qualified individuals for scientific, technical, or professional positions. The report must address:

  • An analysis of workforce needs at FDA and the strategic plan for addressing such needs, including through use of this section; and
  • A recruitment and retention plan for hiring qualified candidates.

In addition, GAO is directed to conduct a study of the ability of FDA to hire, train, and retain qualified scientific, technical, and professional staff, not including contractors, needed to fulfill its missions. The GAO study and report must address:

  • Information about the progress of FDA in recruiting and retaining qualified scientific, technical, and professional staff outstanding in he field of biomedical research, clinical research evaluation, and biomedical product assessment;
  • Any critical staffing needs at the FDA, and any barriers to hiring, training, and retaining qualified staff;
  • An examination of FDA recruitment and retention strategies; and
  • Recommendations for potential improvements that would address FDA staffing needs.

The GAO report must be sent to Congress by January 1, 2022.

Sec. 3073. Establishment of Food and Drug Administration Intercenter Institutes.

Section 3073 amends the FDC Act to require FDA to establish one or more “Intercenter Institutes” within FDA for a major disease area or area. Such Intercenter Institute is directed to develop and implement processes for coordination of activities, as applicable to the disease area(s), among CDER, CBER, and CDRH, including:

  • Coordination of staff from Centers with diverse product expertise in the specific diseases;
  • Streamlining, as appropriate, the review of medical products for specific diseases;
  • Promotion of scientific programs within the Centers;
  • Development of programs and strategies to recruit, train, and provide continuing education opportunities for the personnel of the Centers;
  • Enhancement of interactions of the Centers with patients, sponsors, and the external biomedical community; and
  • Facilitation of collaborative relationships of the Centers with other HHS agencies.

FDA must establish at least one Intercenter Institute within one year of the date of enactment of the Act, and must provide for a period of public comment during the time that each institute is being implemented. The section also allows for FDA to terminate any institute with 60 days public notice. FDA has already established an “Oncology Center of Excellence” that largely mirrors the structure and activities of an Intercenter Institute; it is unclear if the Agency will attempt to satisfy the requirement to establish an Intercenter Institute by converting it the Oncology Center of Excellence to an “Oncology Intercenter Institute” under the process set out in this section.

Sec. 3074. Scientific engagement.

Section 3074 establishes that scientific meetings that are attended by HHS professionals for whom attendance is directly related to their professional duties and the mission of HHS (a) are not considered conferences for the purposes of complying with Federal reporting requirements contained in annual appropriations Acts and (b) are not considered conferences for purposes of a restriction contained in an annual appropriations Act or any other regulation restricting travel to such a meeting.

The section requires each operating division of HHS to post an annual report on scientific meeting attendance and related travel spending for each fiscal year no later than 90 days after the end of the fiscal year.

Sec. 3075. Drug surveillance.

Section 3075 amends the FDC Act to make targeted revisions to FDA’s drug surveillance program. FDA will have more flexibility related to existing requirements that it screen the Adverse Event Reporting System database and evaluate its REMS program. The section also directs FDA to make publicly available best practices for drug safety surveillance using the Adverse Event Reporting System and criteria for public posting of adverse event signals.

Sec. 3076. Reagan-Udall Foundation for the Food and Drug Administration.

Section 3076 amends the FDC act to amend the governance of the Board of Directors in the following ways:

  • Allows the Board of Directors of the Reagan-Udall Foundation, through amendments to the bylaws, to provide for more than 14 voting members on the Board of Directors and provides procedures for appointing such Directors;
  • Clarifies that a Special Government Employee is not considered an “employee of the Federal Government” for purposes of being allowed to serve on the Board;
  • Provides for staggered terms of Directors; and
  • Eliminates the restriction that the Executive Director’s compensation may not exceed that of the FDA Commissioner.

The section also amends how funds received from entities other than the U.S. Treasuring (e.g., from private entities) must be managed with regard to accounting practices.

Subtitle H—Medical Countermeasures Innovation

Sec. 3081. Medical countermeasure guidelines.

Section 3081 amends the PHS Act to require HHS to ensure timely and accurate recommended utilization guidelines for qualified countermeasures, qualified pandemic and epidemic products, and security countermeasures, including for such products in the Strategic National Stockpile.

The section also requires HHS, no later than March 1 of each year in which HHS determines that the amount of funds available for procurement of security countermeasures (i.e., in the BioShield Special Reserve Fund) is less than $1.5 billion, to submit to Congress a report detailing the amount of such funds available for procurement and the impact of such amount on:

  • Meeting security countermeasure needs; and
  • The annual Public Health Emergency Medical Countermeasures Enterprise and Strategy Implementation Plan.

Sec. 3082. Clarifying BARDA contracting authority.

Section 3082 amends the PHS Act to direct Biomedical Advanced Research and Development Authority (BARDA) to carry out programs funded by the special reserve fund (e.g., for procurement of security countermeasures), specifically including the execution of procurement contracts, grants, and cooperative agreements.

Sec. 3083. Countermeasure budget plan.

Section 3083 amends the PHS Act to direct HHS to develop a five-year budget plan based on medical countermeasures priorities, including addressing novel or emerging infectious diseases and the efforts to development medical countermeasures for such threats. Finally, the section specifies that the plan must be provided to Congress no later than March 15 of each year and must be made publicly available.

Sec. 3084. Medical countermeasures innovation.

Section 3084 amends the PHS Act to direct BARDA to enter an agreement with an independent, nonprofit entity (a Medical Countermeasures Innovation Partner) to:

  • Foster and accelerate development and innovation of medical countermeasures and technologies that may assist advanced research and development of qualified countermeasures, including using strategic venture capital practices;
  • Promote the development of new and promising technologies that address urgent medical countermeasure needs, as identified by HHS;
  • Address unmet public health needs relating directly to medical countermeasure requirements; and
  • Provide expert consultation and advice to foster viable medical countermeasure innovators.

Under the agreement, BARDA must provide direction to the partner, including by communicating the medical countermeasure needs, requirements, and problems to be addressed. The section requires that BARDA provide Congress quarterly reports from the partner on the progress being made toward meeting the needs set out in the agreement. In addition, the section directs GAO within 4 years of the date of enactment of the Act to conduct an independent evaluation and report to Congress on the activities conducted under this section. This section sunsets after September 30, 2022.

Sec. 3085. Streamlining Project BioShield procurement.

Section 3085 amends the PHS Act to remove certain steps from the BioShield Special Reserve Fund, which is intended to reflect current execution of the fund. The section also requires HHS to notify Congress of each decision to make special reserve funds for procurement of a security countermeasure. Finally, the section makes available payments from the special reserve fund to a vendor for procurement of a security countermeasure.

Sec. 3086. Encouraging treatments for agents that present a national security threat.

Section 3086 amends the FDC Act to establish a priority review voucher program for a “material treatment medical countermeasure application,” which is

  • A human drug application intended for use:
    • To prevent, or treat harm from a biological, chemical, radiological, or nuclear agent identified as a material threat; or
    • To mitigate, prevent, or treat harm from a condition that may result in adverse health consequences or death and may be caused by administering a drug or biological product against such agent;
  • Determined by FDA to be eligible for priority review;
  • Approved after the date of enactment of the Act, and
  • For a human drug, no active ingredient of which has been approved under section 505(b)(1) of the FDC Act or section 351(a) of the PHS Act.

The section specifies that a priority review voucher is to be awarded for such an application upon approval by FDA. It also allows for the sponsor that receives the priority review voucher to transfer the voucher (and subsequently be transferred) prior to its use.

The section also provides specific requirements regarding notice of use of the priority review voucher: at least 90 days notice to FDA prior to submission of the application, which serves as a legally binding commitment to pay the user fee. A sponsor may transfer the voucher after such notice is given, provided that the application has not yet been submitted.

Furthermore, the section requires FDA to publish notice in the Federal Register and on FDA.gov within 30 days of (a) issuing a voucher under this section and (b) approving a drug that used a voucher issued under this section. The section limits the eligibility of applications from receiving more than one priority review voucher under the various voucher programs. The awarding of vouchers under this section sunsets after October 1, 2023.

Sec. 3087. Paperwork Reduction Act waiver during a public health emergency.

Section 3087 amends the PHS Act by allowing HHS to make a determination that waives voluntary collection of information from the Paperwork Reduction Act requirements during the period of a public health emergency or the period of time necessary to determine if a disease or disorder will become a public health emergency, or for a reasonable period of time during the immediate postresponse review regarding the public health emergency. If HHS determines that a waiver is necessary, it must promptly post on the HHS website a brief justification for the waiver, the anticipated timeframe, and the HHS agencies and offices that the waiver applies to; this must be updated, as applicable.

Sec. 3088. Clarifying Food and Drug Administration emergency use authorization.

Section 3088 amends the FDC Act to explicitly allow for emergency use authorizations for animal drugs.

Subtitle I—Vaccine Access, Certainty, And Innovation

Sec. 3091. Predictable review timelines of vaccines by the Advisory Committee on Immunization Practices.

Section 3091 directs the Advisory Committee on Immunization Practices, as appropriate, upon licensure of any vaccine or any new indication for a vaccine, to consider the use of the vaccine at its next regularly scheduled meeting. If the Advisory Committee does not make a recommendation regarding use of the vaccine, it must provide an update on the status of its review.

The section also directs the Advisory Committee to make recommendations with respect to use of certain vaccines in a timely manner, including those that are designated as Breakthrough Therapies or could be used in a public health emergency.

Sec. 3092. Review of processes and consistency of Advisory Committee on Immunization Practices recommendations.

Section 3092 requires the Centers for Disease Control and Prevention (CDC) to conduct a review, with input from vaccine stakeholders, of the processes used by the Advisory Committee on Immunization Practices in formulating and issuing recommendations pertaining to vaccines, including with respect to consistency. Such review must include an assessment of:

  • The criteria used to evaluate vaccines, including any areas for which flexibility is necessary and the reason for it;
  • The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to the review and analysis of scientific and economic data, include the scientific basis; and
  • The extent to which the processes used by the work groups of the Advisory Committee are consistent among such groups, including the reasons for any variation.

The section requires CDC within 18 months after the date of enactment of the Act to provide Congress a report on the results of the review, including any recommendations on improving consistency of the processes.

Sec. 3093. Encouraging vaccine innovation.

Section 3093 directs CDC to ensure that its staff within the Office of Infectious Diseases coordinate with respect to public health needs, epidemiology, and program planning and implementation considerations related to immunizations, including with regard to meeting with stakeholders.

Specifically, the section requires HHS, in collaboration with NIH, CDC, FDA, and BARDA, and in consultation with the DoD, VA, and stakeholders, to submit to Congress and post on the HHS website a report on ways to promote innovation in the development of vaccines that minimize the burden of infectious diseases. The report must include:

  • The current status of vaccine development;
  • Consideration of the optimal process to determine which vaccines would be beneficial to public health and how information on such vaccines is disseminated to key stakeholders;
  • Examination and identification of whether obstacles exist that inhibit the development of beneficial vaccines; and
  • Recommendations about how best to remove any obstacles in order to promote and incentivize vaccine innovation and development.

The section also amends the PHS Act to require HHS to revise the Vaccine Injury Table as part of the vaccine injury compensation program to include vaccines recommended by CDC for routine administration in pregnant women. The section further amends the PHS Act, for purposes of petitions for compensation for vaccine-related injury or death, to explicitly include both a woman who received a covered vaccine while pregnant and any child who was in utero at the time such woman received the vaccine.

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