Manufacturers Face Key Policy and Regulatory Challenges

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Pharmaceutical Technology, Pharmaceutical Technology-09-02-2015, Volume 39, Issue 9
Pages: 16–17

Legislation to streamline drug development may get tangled up in user fee negotiations and drug pricing battles.

The later months of 2015 will be important in determining the fate of a number of programs slated to shape drug development and industry health in the years ahead. Legislation to advance biopharmaceutical R&D faces hurdles on Capitol Hill, despite overwhelming House approval in July 2015. Important user fee negotiations between FDA and biopharmaceutical companies have begun, but tight timeframes and competing demands will make it difficult to resolve issues quickly. A mounting backlash against high price tags on important new drugs, moreover, may bolster opposition to initiatives designed to speed new therapies to market.

Moving the 21st Century Cures Act through Congress in 2015 will be tough, as the Senate seeks changes and legislators contend with the usual impasse over the federal budget for fiscal year 2016, as well as debate over the Iran nuclear arms pact and major trade agreements. Next year will be even worse, as the presidential election campaign heats up, coinciding for the first time with the process for re-authorizing user-fee agreements. With a new administration and a new Congress in January 2017, FDA fees and legislation need to be ready for review by both outgoing and incoming officials by the middle of next year.

Prospects for “Cures”
Despite broad enthusiasm for the Cures legislation, the bi-partisan support that moved it through the House may fall apart in the coming months. The measure nearly faltered due to opposition from consumer advocates claiming it would bring more unsafe drugs to market, and from fiscal conservatives opposed to increased mandatory spending for the National Institutes of Health (NIH). But House Energy & Commerce Committee Chairman Fred Upton (R-Mich) and his allies garnered support from hundreds of patient groups, research organizations, medical societies, and biopharmaceutical companies, all eager to increase basic research at NIH and to provide FDA with added resources. These and other stakeholders applauded provisions to more fully incorporate patient experiences in considering a drug’s benefits and risks, expedite new drug approvals through biomarker qualification, streamline clinical trials, encourage sponsors to use data from clinical experience, and provide incentives for developing antibiotics and treatments for rare diseases (1).

The House measure now faces revisions in the Senate, where there is talk of developing a much narrower bill by fall. Some Senate Republicans strongly oppose NIH budget increases, which would erode Democratic support. If the Senate does enact a slimmer bill, it would face difficult conference committee negotiations with the House, and the process could extend well into next year.

Focus on fees
Consequently, many provisions of the Cures legislation may end up in a broad FDA bill to reauthorize user fees for drugs, generic drugs, medical devices, and biosimilars by summer 2017. FDA launched negotiations in June 2015 for revising the Generic Drug User Fee Act (GDUFA II) and in July 2015 for medical devices and for prescription drugs (PDUFA VI). Monthly discussions with industry will begin in September 2015, along with regular meetings for FDA to hear the views of patients, consumers, and health professionals.

The importance of user-fee programs to FDA was evident at the PDUFA meeting with both acting commissioner Stephen Ostroff and deputy commissioner Robert Califf offering comments, along with Center for Drug Evaluation and Research (CDER) Director Janet Woodcock. But fast agreements and leaner authorizing measures won’t be easy to achieve. Generic-drug makers are unhappy with FDA’s slow pace in meeting the goals set by the initial GDUFA program, noting that timeframes for reviewing abbreviated new drug applications (ANDAs) actually have gone up, and there has been little gain in whittling down the massive ANDA backlog. Slow FDA approval of new generic drugs only aggravates shortage situations and delays patient access to important, affordable medicines, industry reps observed at the June 2015 meeting.

Generic-drug firms also complained about rising fees, particularly when FDA had not spent a big chunk of the money it already has collected. Small companies want relief in facility fees, especially companies seeking their first approved product. Manufacturers urged greater transparency and better communication on agency decisions, notably about a stiffer “refuse to accept” policy that permits the agency to reject ANDAs lacking key components.

At the PDUFA public meeting, patient groups and professional organizations offered a range of initiatives meriting user fee support: more biomarker validation, pediatric and neonatal drug development, data transparency initiatives, and greater consistency in review practices by review divisions. A main theme was expanding the use of “real-world” evidence to accelerate drug development. Greg Daniel of the Brookings Institution highlighted strategies for tapping clinical evidence to support agency decisions and to document product safety, while Allan Coukell of the Pew Charitable Trusts emphasized the value of observational data from claims databases.


FDA is expected to seek access to some portion of drug application fees during product development, instead of waiting until filing. Biosimilar sponsors pay a portion of the fee upfront to support CDER’s time and investment in product development meetings, a process that has expanded with the proliferation of breakthrough drugs and other crucial medicines. Currently, only biosimilar sponsors pay a fee to FDA even if no application is filed at the end, points out Gillian Woollett of Avalere Health, a model that FDA would like to extend to other products.



Pricing perils
User-fee negotiations assume a certain number of production facilities and applications for drugs and medical products each year to generate expected fees. But these projections may be tempered by a slowdown in biopharma R&D and sales, as payers and health organizations attack companies for setting unacceptably high prices, as seen with the recent emergence of important new treatments for hepatitis C. Oncologists are livid over soaring prices for new cancer drugs, as seen in a July 2015 editorial in the Mayo Clinic Proceedings signed by 118 physicians that urge action to halt the rising prices (2). The American Society of Clinical Oncology has developed a Cancer Value Framework to relate the value of a drug and its price to clinical benefits and toxicities, a strategy applauded by pharmacy benefit managers.

FDA approval of new PCSK9 inhibitors to manage cholesterol, which could be used by millions of patients, has set off a campaign by payers and insurers to limit indications and prescribing. Praluent (alirocumab), developed by Sanofi and Regeneron Pharmaceuticals, was launched in July 2015 with a $14,600 list price per year--much more than anticipated and way more than currently available cholesterol meds, but with labeling designed to limit use to seriously ill patients. There is much hope for new treatments to prevent Alzheimer’s disease, but already strong pushback against potentially high costs.

The Institute for Clinical and Economic Review (ICER) is developing an assessment of the value of PCSK9 inhibitors as part of its expanded program to provide independent reports on the cost- and comparative-effectiveness and budget impact of new drugs where the value evidence is controversial and where the budget impact may be quite high, as with treatments for cancer, asthma, and diabetes. The escalating focus on drug “value” will be important to policies and programs for biopharma R&D, production, and marketing.

1. Rules Committee Print 114-22 Text Of H.R. 6, 21st Century Cures Act.
2. Mayo Clinic, In Support of a Patient-Driven Initiative and Petition to Lower the High Price of Cancer Drugs, Mayo Clinic Proceedings 90 (8) (August 2015).

Article DetailsPharmaceutical Technology
Vol. 39, No. 9
Pages: 16–17

Citation: When referring to this article, please cite it as J. Wechsler, “Manufacturers Face Key Policy and Regulatory Challenges,” Pharmaceutical Technology39 (9) 2015.