Over-the-counter drug monograph reform the topic of subcommittee hearing

Under proposed legislation, “Over-the-Counter Monograph Safety, Innovation, and Reform Act of 2017,” the over-the-counter (OTC) monograph process would be modernized to streamline rule-making and cut down on FDA resources, while being funded through the establishment of a user fee program. In a hearing before the House Committee on Energy and Commerce’s subcommittee on health on September 13, 2017 regarding the discussion draft, witnesses from the industry and the FDA voiced their support, as well as real world examples and reasoning, for the proposed changes.

Monographs and current process

Unless the FDA has approved a new drug application, the only way an OTC drug can be marketed is if it conforms to a monograph—a standard set of specifications established by the FDA for each therapeutic category of product—and is thus considered generally recognized as safe and effective (GRASE). A monograph is created through a three-step public rulemaking process via the Federal Register and a public comment period. It requires the convening of advisory review panels, publishing of an advanced notice of proposed rulemaking (ANPRM) with a comment period, review by the FDA, publishing a tentative final monograph (TFM), and later finalization of the monograph and subsequent amendments and updates. The FDA has around 88 rulemakings in 26 therapeutic categories covering over 100,000 OTC drug products, and there are 800 active ingredients for over 1,400 uses that the FDA oversees. There are no user fees associated with monograph products currently, and a small staff oversees the OTC program as well as attending to other current mandates. The rulemaking process spans many years and the industry waits for a decade or more for finalized monographs, for example, the ANPRM for external analgesic products was published in 1979 and the monograph has still not been finalized.

Legislation

Since 2014, the FDA has examined monograph reform and the possible creation of a user fee program. The discussion draft includes proposes the following changes: (1) authorizing of the OTC Monograph User Fee Program; transition of OTC monographs from a rulemaking process to an administrative order procedures; (2) expediting administrative order procedures for OTC monograph drugs that pose an imminent hazard to public health or are associated with serious adverse events; (3) providing for a procedure to account for minor changes; (4) providing for a two-year exclusivity period for certain OTC innovative changes; and (5) clarifying how sunscreens would be reviewed.

Stakeholder witnesses

 Witnesses from across the industry presented statements before the subcommittee. They touched not only on the problems with the current process and their support of the proposals, but also their support in the industry supplementing the government’s efforts with the user fee program.

  • Bridgette L. Jones, MD, FAAP, representing the American Academy of Pediatrics (AAP), raised an example of how long it takes to get a monograph changed. Over a decade ago, in response to a petition to the FDA, an FDA advisory committee voted unanimously “that it was no longer appropriate for adult data on cough and cold products to be extrapolated to establish efficacy of the drugs in children under 12 . . . [and that] cough and cold drugs not be used in children under 6 years of age.” Currently, not even draft changes have been made to the monograph. She also noted that it is appropriate that the monograph be amended to provide dosing instructions for children under two years of age and that “if the monograph process worked better, surely this change would have happened years ago.”
  • Scott Melville, President and CEO of Consumer Healthcare Products Association (CHPA), notes the value that OTC medicines bring to the health of Americans and to the U.S. health care system and stresses that it’s important that the oversight process “is one that is efficient, transparent, and accommodating to innovation.” He also notes that his industry “is willing to supplement government resources with a modest user fee program.”
  • Kirsten Moore, Project Director, Health Care Products, The Pew Charitable Trusts, gave examples of the “unnecessary delay incorporated into a multi-step rulemaking system, which compromises FDA’s ability to respond swiftly to address new safety information and protect consumers” and urged Congress to pass the legislation as soon as possible.
  • Michael Werner, Partner, Holland & Knight, on behalf of the Public Access to SunScreens (PASS) Coalition, and Gil Roth, President, Pharma & Biopharma Outsourcing Association, also spoke in support of the OTC legislation.
  • Janet Woodcock, MD, Director for the Center for Drug Evaluation and Research (CDER) with the FDA confirmed the troubles with the current process and the present staffing levels raised by the other stakeholders. Her agency, as well as the other organizations, offered to continue to work with Congress to make the OTC reforms a reality.

FDA user fees reauthorized by House vote

In a bipartisan action, the House of Representatives today passed H.R. 2430, the FDA Reauthorization Act (FDARA) of 2017, by voice vote. FDARA reauthorizes the FDA’s user fee programs for prescription drug, medical device, generic drug, and biosimilar biological products. The current user fee programs are set to expire in September 2017 and account for almost a quarter of the FDA’s funding.

In April 2017, the House Energy and Commerce Committee, along with the Senate Health, Education, Labor and Pensions (HELP) Committee, released a discussion draft of the Food and Drug Administration (FDA) Reauthorization Act of 2017, reauthorizing the FDA’s user fee agreements (see Discussion draft of FDA user fee amendments is on the table, Health Law Daily, April 18, 2017). The draft followed a series of hearings examining the four individual user fee programs – the Generic Drug User Fee Amendments (GDUFA) and the Biosimilar User Fee Act (BsUFA), the Prescription Drug User Fee Act (PDUFA), and the Medical Device User Fee Amendments (MDUFA) (see HELP Committee hears ardent support for next round of user fee agreements, Health Law Daily, April 4, 2017 Committee holds optimistic hearing on medical device fees, Health Law Daily, March 29, 2017; PDUFA VI reauthorization would aid 21st Century Cures Act implementation, Health Law Daily, March 23, 2017; and User fee program reauthorizations necessary for product development, Health Law Daily, March 3, 2017).

FDARA is currently before the Senate (see HELP committee advances FDA user fee agreements to Senate floor, Health Law Daily, May 12, 2017).

Energy and Commerce committee unanimously approves FDA reauthorization

The House Energy and Commerce Committee voted unanimously—54 to zero—to approve H.R. 2430, the Food and Drug Administration Reauthorization Act of 2017 (FDARA), after a markup on June 7, 2017. The bill would reauthorize the FDA’s user fee programs for prescription drug, medical device, generic drug, and biosimilar biological products. Without the reauthorization, the use fee programs will expire at the end of September, 2017.

The FDARA would renew the FDA’s authority to collect user fees from the makers of prescription brand drugs, medical devices, generic drugs, and biosimilars. The fees account for more than one-fourth of the agency’s funding (see HELP committee advances FDA user fee agreements to Senate floor, May 12, 2017).

The bill passed the committee with six amendments, offered by: Chairman Greg Walden (R-Ore), Rep. Ryan Costello (R-Pa), Rep. Scott Peters (D-Calif), Rep. Mimi Walters (R-Calif), and Rep. Jan Schakowsky (D-Ill). Rep. Schakowsky offered two amendments. The amendments are designed to further the development of generic therapies, update approval and quality reporting requirements for medical devices, allow for risk-based classification of accessories, foster the development of medical device safety surveillance pilots, and encourage steps to lower the cost of prescription drugs.

PDUFA VI reauthorization would aid 21st Century Cures Act implementation

Since 1992, the Prescription Drug User Fee Act (PDUFA) has authorized the FDA to collect user fees from biopharmaceutical manufacturers to supplement Congressional appropriations. Revenues from these fees are used on activities related to the review and regulation of new drug products. In exchange for these fees, the FDA commits to meeting certain performance goals, such as reviewing applications within specified timeframes. The FDA’s ability to collect these fees must be reauthorized every five years. Each five-year reauthorization sets a total amount of fee revenue for the first year and provides a formula for annual adjustments to that total based on inflation and workload changes.

On March 22, 2017, the House Energy and Commerce Committee’s Subcommittee on Health held a hearing to examining the PDUFA program. PDUFA, as reauthorized by the Food and Drug Administration Safety and Innovation Act of 2012 (FDASIA) (P.L. 112-144), expires in September 2017, and must be reauthorized for the fiscal years 2018 to 2022.

This will be the sixth reauthorization of PDUFA. The proposed agreement (PDUFA VI), builds upon process improvements enacted pursuant to FDASIA, including enhanced support for the Breakthrough Therapy Program. Further, it would aid in the implementation of several key provisions in the 21st Century Cures Act and further streamline the development and review of innovative new drugs for patients. The FDA estimates that the fees negotiated in PDUFA VI will average approximately $1 billion per year.

At the hearing, the following individuals testified on how the program has been implemented to date and presented recommendations pertaining to its reauthorization:

Allen

In his testimony, Allen pointed out that: “Prior to the initial user-fee authorizations, patients in other parts of the world were gaining access to new medicines faster than Americans, with only about 10 percent of new treatments reaching U.S. patients first.” That paradigm has largely been reversed, according to Allen. “Between 2003 and 2016, 73 new cancer drugs were approved by both the FDA and EMA [European Medicines Agency]. Of those drugs, 97 percent (71 of 73) were available in the U.S. before Europe. Furthermore, the FDA approved new cancer drugs on average nearly 6 months faster than the EMA.”

Allen also stated that PDUFA VI:

  • Advances the role of patients and their experiences;
  • supports the continued success of the Breakthrough Therapy Designation, a designation that may be given to a drug intended to treat a serious illness for which preliminary clinical evidence indicates a substantial improvement over any existing interventions. To date, 170 Breakthrough Therapy Designations have been granted, leading to 79 indications approved by the FDA using this process;
  • promotes qualifications and the use of drug development tools;
  • enhances the use of real-world evidence in regulatory decision-making; and
  • effectively communicated scientific advances.

Allen cautioned, however, that “proposed cuts to biomedical research will put the brakes on the engine of discovery, abandon progress on new tools to enhance product evaluation, impede opportunities for new businesses in the biotech sector, and most perilously, jeopardize the development of new medicines for patients desperate for progress.”

Pritchett

In supporting PDUFA VI reauthorization, Pritchett stated: “For nearly twenty-five years, PDUFA has provided much needed resources to the FDA’s human drug review program that has resulted in greater certainty and predictability for patients who depend on safe and effective innovative medicines.” Pritchett also noted the following benefits under PDUFA:

  • The FDA has approved over 1,500 new drugs and biologics since 1992, including treatments for cancer, cardiovascular, neurological, infectious and rare diseases.
  • The number of new medicines being approved on their first review cycle is at a historic high, including approvals for new medicines to treat rare diseases.
  • Review times for drug applications have dropped by nearly 55 percent.
  • The median approval time for standard applications has decreased from 22.1 months in 1993 to an estimated 10 months in 2015.
  • The median approval time for priority applications has similarly decreased from 13.2 months in 1993 to an estimated 7.9 months in 2014.

Pritchett concluded: “At a time when the U.S medical innovation ecosystem is facing severe strains and increased global competition, it is imperative that the FDA is equipped to help us deliver the next generation of new treatments and cures to meet patients’ unmet medical needs. PDUFA VI will help the FDA ensure that patients receive effective and lifesaving drugs, while maintaining the United States’ global leadership in biomedical innovation.”

Holcombe

Holcombe’s testimony cautioned Congress on the cost of the program: “Since 2002, the PDUFA program has grown at an average of 11 percent per year; this is unsustainable moving into the future. Changes are needed that address the fee collection structure to increase efficiency and reduce administrative burdens for both FDA and companies.”

Holcombe believes that the proposed PDUFA VI agreement would address these concerns by:

  • limiting the carryover balance levels, thus reducing possible over-collection of fees and the need for complicated administrative mechanisms to deal with such over-collections;
  • eliminating supplement fees, which will further simplify fee collections;
  • replacing the current product and manufacturing fees with a new program fee that will constitute 80 percent of the annual fee collections; and
  • reducing the percentage that application fees contribute to the total from the current 33 percent to 20 percent, thus mitigating the overall impact of this difficult-to-predict revenue source.

Holcombe also pointed out the benefits of important overlaps between provisions in the 21st Century Cures Act and the proposed PDUFA VI agreement. She offered the following examples of overlap:

  • The 21st Century Cures Act and PDUFA VI are complementary, in terms of ensuring that FDA (1) has and uses effectively an efficient process for qualifying biomarkers; (2) publishes guidance to help applicants for biomarker qualification understand the taxonomy and data standards; (3) makes public a list of qualified biomarkers and pending applications; and (4) engages external experts in biomarker qualification.
  • Patient-focused drug development. Guidance development, public meetings, development of methods and standards for collecting information and data, and use of patient perception and experience information in the FDA regulatory decision about the benefits and risks of a drug are all elements of both 21st Century Cures and the PDUFA VI agreement.
  • Real-world evidence. The 21st Century Cures Act provides helpful context for the work under PDUFA VI, and provisions of the two that differ are easily harmonized.
  • Innovative trial design. While the 21st Century Cures Act focuses on adaptive trials and Bayesian approaches, PDUFA VI takes a broader approach, opening its pilot program to other trial designs while also highlighting adaptive trials and Bayesian approaches.

Holcombe concluded by indicating the Biotechnology Innovation Organization strongly supports and applauds the enactment of 21st Century Cures, and it strongly supports the PDUFA VI proposed agreement.

Woodcock

At the hearing, Subcommittee Vice Chairman Brett Guthrie (R-Ky) asked Woodcock for an update on the FDA’s Oncology Center of Excellence, a key component of 21st Century Cures and a committee-supported initiative. Woodcock elaborated on the center’s structure and the important work it will be doing.

With regards to PDUFA VI, Woodcock noted: “The PDUFA VI reauthorization proposal . . . was submitted to Congress in December under the previous Administration, and reflects a different approach to the federal budget.” She also stated: “Center to PDUFA VI, and its largest single investment component, are plans to elevate patient voices in developing new drugs to treat their diseases. The agreement shares the committee’s goals reflected in the 21st Century Cures Act – and the highest priority of our stakeholders – to leverage essential patient input and insights to fight disease.”