A few weeks after finishing negotiations with FDA over a PDUFA V deal that seeks to tweak drug oversight with changes to the review process, BIO now plans to propose sweeping changes to the U.S. regulatory system.

This week the biotech trade association will call for the creation of a provisional approval pathway, mandates for FDA to promote medical innovation, and a complete restructuring of the agency's relationships with Congress and the White House.

BIO's FDA innovation agenda is coupled with proposals for congressional action to bolster capital formation (see "Talking Capital in the Capitol," A14).

Although it is separate from the PDUFA deal, BIO's package of regulatory innovation proposals is certain to provide food for thought for congressional committees that are just starting to consider legislation that could accompany the reauthorization of user fees.

Underscoring the connection between regulatory innovation and PDUFA, a member of BIO's board of directors will present the organization's recommendations at a July 7 House Energy and Commerce Committee hearing about PDUFA. The committee, which has jurisdiction over FDA, has also invited the National Venture Capital Association to testify about recommendations developed by its Medical Innovation and Competitiveness Coalition (MedIC).

MedIC includes life science VCs and their portfolio companies.

Separately, patient and consumer groups are lobbying Congress with ideas for changing the way medical products are regulated. Some of the patient proposals have been incorporated into the National Health Council's Modernizing Our Drug & Diagnostics Evaluation and Regulatory Network (MODDERN) Cures Act (see BioCentury, Monday, May 30).

BIO plans to first release concept papers describing its ideas for revitalizing the U.S. biotech industry, and then seek congressional champions to introduce comprehensive legislation in both houses of Congress, BIO President and CEO Jim Greenwood told BioCentury.

Getting progressive

Several of BIO's and NVCA's highest impact proposals, including creation of a progressive approval pathway, could be accomplished without congressional intervention, but BIO has concluded public debate and legislation are needed to provide an impetus for action.

Progressive or conditional approval has been discussed at FDA and among regulatory experts for years. The idea is to move away from a binary approval decision to a gradual easing of new drugs onto the market for defined patient populations, with restrictions on use modulated based on real-world data.

Conditional approval was at the heart of proposals for regulatory innovation presented in BioCentury's 2010 Back to School report (see BioCentury, Sept. 13, 2010).

On the June 12 broadcast of BioCentury This Week, BioCentury's public affairs television program, FDA Commissioner Margaret Hamburg said she has discussed the possibility of creating a progressive approval pathway with Janet Woodcock, director of the agency's Center for Drug Evaluation and Research (CDER).

Hamburg has been briefed on BIO's proposals, Greenwood said.

Under BIO's version of progressive approval, FDA would allow sponsors to market therapies for unmet medical needs that provide significant advances to standard of care, or for targeted therapies, based on solid safety data and evidence that such a therapy is "more likely than not to provide favorable benefit-risk to its intended patient population," according to briefing slides BIO presented to patient groups last week.

This could mean allowing drugs on the market after Phase II trials and while Phase III trials were under way, Sara Radcliff, EVP for health at BIO, told BioCentury.

products approved under the progressive pathway could be restricted using FDA's authority to impose REMS that limit which patients and physicians can receive or prescribe a drug, and with requirements for postmarket registries.

Rather than propose a new pathway, NVCA is calling for FDA to "expand its use of the accelerated approval pathway for new drugs." It thinks "Congress should make clear that the agency has the authority and the public mandate to behave flexibly, without a 'one-size-fits-all' standard of evidence, in approving breakthrough drugs for unmet needs where evidence suggests a reasonable likelihood that the benefits outweigh the risks."

NVCA and BIO also want Congress to prod FDA into weighing unmet need more heavily when deciding whether and when products should be approved under existing pathways.

"FDA should update its regulatory standard for balancing the benefits and risks of breakthrough products by emphasizing that the evidence of benefit required of a new product should depend on the level of unmet medical need it addresses and its likely safety risk," NVCA proposes.

On a mission

Both BIO and NVCA want Congress to redefine FDA's mission so the agency is formally charged with advancing medical innovation.

"Congress should amend and strengthen the FDA's statutory mission to include promoting public health through acceleration of access to novel therapies and technologies and require the FDA to routinely assess the impact of its decisions, policies, and priorities on unmet medical needs and medical innovation using agreed upon metrics," according to an NVCA memo outlining MedIC's proposals.

BIO is also calling for a fixed term of office for the FDA commissioner, echoing a recommendation from a 2006 Institute of Medicine report, "The Future of Drug Safety: Promoting and Protecting the Health of the Public."

The commissioner position is "a somewhat thankless job. Job security will help attract the best candidates," Greenwood told BioCentury. A fixed term is also intended to provide some insulation from political pressure.

BIO takes political independence a step further, calling for FDA to be removed from HHS and turned into an independent agency with a head who reports directly to the president, like the Environmental Protection Agency. This would "eliminate a level of bureaucracy," Greenwood said.

BIO is also calling for an external management review board to advise the commissioner.

To bolster FDA's capacity to advance scientific innovation, BIO wants Congress to lift restrictions on funding the Reagan-Udall Foundation. Congress created the foundation in 2007 as a public-private partnership to oversee and fund precompetitive research to advance drug development and regulation. Rep. Rosa DeLauro (D-Conn.) has blocked the funding, saying it is dominated by drug companies.

Another BIO proposal for turning FDA's attention to advancing science and medicine is the creation of a chief innovation officer with "authority to pilot and develop strategies for implementation of promising scientific and regulatory approaches in review divisions."

Both BIO and NVCA also want to improve the advisory committee process.

Conflict-of-interest restrictions have severely restricted the pool of experts who can serve on advisory committees. NVCA is calling for those COI rules to be amended, and to replace restrictions on committee membership with requirements for disclosure of conflicts.

BIO wants Congress to create a chief medical policy officer who would "oversee and improve the FDA advisory committee process." This officer also would have authority to resolve broad medical policy disputes within and across FDA's divisions and centers.

Also, BIO wants Congress to require that advisory committees include a medical or scientific expert appointed by patient organizations.

NVCA thinks the committees should include an "innovation advocate" representing investors and entrepreneurs who finance medical innovation.

Next steps

BIO has created concept papers describing its proposals, and has discussed them with "key members of Congress and their staff," Greenwood told BioCentury. It hopes to have its regulatory and capital formation proposals combined in one bill that would be introduced in the Senate.

Because of the House's different jurisdictional structure, Greenwood envisions two bills in the House, one focusing on FDA, and the other on tax and economic issues.

Greenwood doesn't expect the bills to be enacted, but feels that presenting all of the ideas as a package illustrates the need for comprehensive changes.

BIO's hope is that members of Congress will pick out and champion various elements of its plan and incorporate them into bigger legislative initiatives.


Biotechnology Industry Organization (BIO), Washington, D.C.

Institute of Medicine (IOM), Washington, D.C.

National Venture Capital Association (NVCA), Arlington, Va.

National Health Council, Washington, D.C.

U.S. Food and Drug Administration (FDA), Silver Spring, Md.