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New legislation, government programs aim to bolster drug discovery and reduce regulatory hurdles.
Amidst the clamor to curb the cost and time of drug development and thus speed more new products to patients, policymakers are devising "pro-innovative" approaches for testing and regulating medical products. Some of these proposals may be included in the user-fee legislation moving forward on Capitol Hill, along with provisions to ensure drug safety and help FDA contend with an increasingly global marketplace. In addition, several Obama administration initiatives offer support for biomedical innovation as part of broader economic and regulatory programs.
After a year of discussion about doing more to translate biomedical discoveries into effective therapies, National Institutes of Health (NIH) Director Francis Collins is moving forward with his collaborative effort to "repurpose" old drugs sitting on manufacturers' shelves. US Health and Human Services (HHS) Secretary Kathleen Sebelius joined Collins and three leading pharmaceutical companies last month to announce a pilot program to uncover new uses for abandoned compounds.
The new National Center for Advancing Translational Sciences (NCATS) is linking up with Pfizer, AstraZeneca, and Eli Lilly to support independent studies on about 20 drugs that the companies previously developed but never brought to market. NIH will provide $20 million in grants next year to fund promising research proposals, along with templates for agreements on dealing with intellectual property. The manufacturers will provide researchers with the compounds and relevant data, while retaining rights to their products, Collins explained. Researchers from academia, nonprofits, and biotech companies will be able to publish study results and negotiate licenses on new discoveries. The research agreement templates are key to speeding up negotiations among all parties and making the program work. NIH intentionally ruled out seeking additional uses for approved drugs, as those raise more complex IP issues.
NIH is soliciting comments on the templates and plans to publish the list of compounds available for research in a few months in an effort to award initial grants by spring 2013. Manufacturers view the NIH program as a way to extend the kinds of arrangements they already have with individual research institutes, including AstraZeneca's partnership with the United Kingdom's Medical Research Program. The selected compounds have been tested for safety in early clinical trials, but lacked sufficiently robust results to support larger studies. The hope is that these abandoned products will do better with new targets and new indications.
Public–private partnerships to repurpose approved drugs is one item in the national "Bioeconomy Blueprint" from the White House Office of Science and Technology Policy (OSTP), which maps out opportunities to promote economic growth and improve public health through biotech innovation. This grab-bag of ideas also cites research to support pluripotent cell technology and collaborations to validate promising drug targets and develop standards that can improve protein manufacturing processes. The report calls for FDA to use its vast repository of clinical-drug safety and efficacy data to speed drug development and envisions harnessing biology as a manufacturing platform for rapid production of new high-value materials, medicines, devices, and fuels.
New drug development also may benefit from a number of measures before Congress that aim to speed up regulatory review and eliminate hurdles to market approval. These measures have been proposed as additions to legislation reauthorizing the Prescription Drug User Fee Act (PDUFA) and several other new and old FDA user-fee programs; there's pressure to get the bill done before the end of June.
The basic PDUFA agreement negotiated by FDA and industry last year includes provisions encouraging research on new treatments for rare diseases and identifying new biomarkers and research tools able to streamline clinical studies. FDA would approve more applications in the first review cycle through greater interaction with sponsors during the review process. An important, but less noticed, item sets the stage for manufacturers to file applications for new drugs and biologics in a common, electronic format within five years.
In addition to the agreed-on PDUFA plan, a host of additional legislative "enhancements" to the bill aim to make the regulatory process more efficient and predictable. The Senate Health, Education, Labor, and Pensions Committee approved its Food and Drug Safety and Innovation Act (FDASIA) in April, but acknowledged that it still needs to resolve several issues related to innovation and supply-chain security before the bill comes up for vote by the full Senate. The House negotiated a similar but slightly different measure a few weeks later. Debate continues over incentives for manufacturers to develop new antibiotics and added leverage for FDA to use priority review and fast-track approval strategies to speed new treatments to market. Industry also would like more flexibility for scientific experts with ties to industry to serve on FDA advisory committees. Both manufacturers and patient advocates want to expand FDA's use of the accelerated-approval process, and the agency agrees to some extent.
At the April annual meeting of the Food and Drug Law Institute (FDLI), FDA Commissioner Margaret Hamburg voiced support for legislative language that would provide "clarity to industry and the public" on the use of accelerated approval for "a wide variety of diseases and conditions, including rare diseases." Hamburg also backed proposals to codify the concept of "breakthrough drugs"—that is, products that elicit such a dramatic response in early clinical trials that they warrant market approval based on limited clinical evidence.
Yet, Hamburg doesn't want overly proscriptive legislation. She said nothing about appointing an FDA "chief innovation officer" with authority to ensure that reviewers accept data from unconventional clinical research programs previously okayed by the agency. FDA also opposes industry's proposal to expand the agency's mission statement from "promoting the public health" to include "spurring economic growth." Agency officials say it's impossible to calculate how approval or rejection of a new drug or medical device would affect jobs and growth, as one sponsor might gain from approval, but a competitor could lose.
Hamburg expressed concern that the strong "anti-government and anti-regulation sentiment" expressed in some legislative proposals could "lower FDA's high public health standards that have served patients, consumers, industry, and the public health for so long, and so well." High standards for safety and efficacy, she said, "will ensure that innovations actually help patients," and that they receive coverage from third-party payers.
FDA moved to highlight its increased commitment to drug safety over the last five years in a report from the Center for Drug Evaluation and Research (CDER) on "Advances in FDA's Safety Program for Marketed Drugs." CDER now spends equal resources on postmarket oversight as on premarket approval, reported Director Janet Woodcock, and new authorities provided by the FDA Amendments Act of 2007 have enabled the agency to require more than 385 postmarket drug safety studies, to mandate 65 new safety labeling changes, and to initiate 64 risk evaluation and mitigation strategies (REMS) since 2008.
However, a report from the Institute of Medicine on "Ethical and Scientific Issues in Studying the Safety of Approved Drugs" calls for FDA to do more to monitor and disclose safety issues involving marketed medicines. The expert panel, which launched this study in 2010 to help FDA prevent future Vioxx-type safety crises, advised the agency to create a comprehensive, publicly available document that would map drug risks and safety concerns throughout the product lifecycle. CDER officials dismissed that idea, noting that developing such a Benefit and Risk Assessment and Management Plan, or BRAMP, for every approved drug would be "challenging" given the agency's limited resources and probably would require lengthy new rulemaking.
What FDA would like to see in the PDUFA legislation is enhanced authority to ensure the safety and quality of drugs and active ingredients now imported from all over the world, as described in its new report on "Global Engagement" and last year's "Pathway to Global Product Safety and Quality." These documents note FDA's increased overseas presence through its network of international offices, as well as efforts to strengthen regulatory agencies in other countries, to collaborate on science-based standards, to share knowledge and inspection resources, and to develop a range of joint surveillance and preparedness activities.
At the FDLI meeting, Hamburg cited several legislative provisions that would enable the agency to deal with rising global drug production: make it easier for FDA to share confidential information with trusted regulatory authorities; enable FDA to refuse admission and to destroy unsafe drug imports; require manufacturers to report to FDA threats to the supply chain; and require a "robust" system to track and trace drugs throughout the supply chain.
The proposed generic-drug user-fee program, she noted, will help by supporting more frequent inspections of foreign manufacturers of active ingredient and drug products. There seems to be agreement that manufacturers should report earlier to FDA about looming shortage situations. But industry appears wary of legislation that sets stiff penalties for a host of reporting and disclosure requirements. Manufacturers don't want to invest millions in a system able to track drugs down to individual vials. The debate continues.
Jill Wechsler is Pharmaceutical Technology's Washington editor, 7715 Rocton Ave., Chevy Chase, MD 20815, tel. 301.656.4634, firstname.lastname@example.org.