Watchdog And Innovator: Modernizing The FDA-Industry Relationship

As each medical advance introduces a new regulatory challenge, FDA’s need for reinvention is as constant as industry’s need for innovation. If the agency is going to help sponsors bring breakthrough medicines to market, it must rethink its role as both watchdog and regulatory innovator.

• Industry and FDA often appear adversarial, but their relationship is in fact symbiotic.
• To improve its own performance and the potential value of the products it reviews, FDA must embrace certain controversial ideas, including adoption of comparative effectiveness research and use of post-market data to speed drug approvals.
• FDA can further smooth drugs’ regulatory paths by expanding the use of techniques that have helped add certainty for oncology and rare disease therapies.
• Expediting the approval pathway for companion diagnostics and further encouraging the use of biomarkers will cement FDA’s global leadership role and encourage growth in emerging fields.

While the biopharmaceutical industry has embarked on a new age of accountability and personalization in medicine, Commissioner Margaret Hamburg, MD, and her predecessor, Andrew von Eschenbach, MD, have charged the Food and Drug Administration (FDA) with advancing regulatory science and innovation. Industry and FDA agree that to deliver innovative therapies, regulatory approval and drug development processes must keep pace with advances in biomedical research, medical technology, and health care delivery. Industry should view FDA not only as its chief regulator, but also as a partner in product development. In turn, the agency should strive to balance its dual role as protector (watchdog) and promoter (innovator) of public health.

The public dialogue addressing the effectiveness of the medical product approval process might suggest an adversarial relationship between industry and FDA. A 2011 National Venture Capital Association MedIC Coalition report stated that FDA regulatory challenges are driving biomedical investment away from the US. In another report, the Biotechnology Industry Organization (BIO) called for “game-changing strategies,” including updating FDA’s mission to “incorporate modern scientific tools, standards, and approaches.” Yet PricewaterhouseCoopers has found in periodic industry surveys that the relationship has improved during the past decade. A recent Elsevier Business Intelligence survey of life sciences venture capitalists confirms this thawing. (See (Also see "No Obvious Prescription For Biopharma Investors" - Scrip, 13 Sep, 2012.).)

Traditionally, industry has seen its responsibility as developing innovative products that improve health outcomes, while providing FDA the information it needs to make a decision on safety and efficacy. FDA has focused on reviewing applications within a reasonable period to give the public access to life-saving and -enhancing treatments without exposing patients to harm. PwC’s most recent survey exploring the relationship between industry and FDA (Improving America’s Health V) found that neither thoroughly takes advantage of opportunities for collaboration during the product development process.

Patient demands put further stress on the relationship. Patients simultaneously expect quick access to novel and potentially life-saving products from industry and assurance from FDA that they will not suffer harm from those innovations. Finding the right balance to meet these sometimes conflicting expectations presents a challenge for FDA.

Numbers Point To Innovation Deficit

FDA has acknowledged that timely review of the safety and effectiveness of new drugs and biologics is central to its mission to protect and promote the public health. Venture capitalists and industry advocates say that product review times have slowed and the approval process has become more costly and unpredictable as the balance has tilted toward protecting public safety.

In response, FDA has pointed to its record, saying that it has ensured the safety and effectiveness of new therapies while approving innovative drugs earlier and faster than anywhere else in the world, including the European Union. As evidence, in a report on FY 2011 approvals, FDA cites its successes in approving cancer therapies and drugs for rare (orphan) diseases.

A 2012 study by the Tufts Center for Drug Development confirmed that FDA approved cancer drugs faster than its European counterparts from 2000 to 2011. A separate Yale University School of Medicine study found that the pace of cancer drug approvals was faster in the US than in Europe or Canada.

Although the speed of approving priority drugs has improved in recent years, the overall number of new molecular entity (NME) approvals has fallen short. It can be argued that the quality of NMEs serves as a better gauge of innovation than the quantity. But the numbers do provide an important benchmark.

Some place responsibility for the innovation deficit squarely in the hands of the regulator. A closer look at the data indicates that accountability lies also with industry and the scientific community. A declining number of new drug applications (NDAs) and biological license applications (BLAs) undoubtedly has contributed to the downward trend in product approvals.

With the exception of 2002, the 23 NME applications submitted to FDA’s Center for Drug Evaluation and Research (CDER) during 2010 represent the lowest number in 15 years. The number climbed back up to 29 in 2011 and to 22 through September 2012, but it’s too early to conclude that an upward trend is emerging. (See (Also see "New Molecular Entities Approved In 2012" - Pink Sheet, 1 Oct, 2012.).) Exhibit 1 compares the number of applications submitted to the number of approvals.

Product innovation has slowed at a difficult time for the industry, when patents are expiring, generics are acquiring market share, government and private payors are demanding more value for money, and investors are shying away from biotech and medical device start-ups. Although regulators are not directly responsible for the pace of new drug development, regulatory policies can influence whether it is economically feasible to develop new products.

Exhibit 1

New Molecular Entity Applications And Approvals, CDER

Calendar Year	Applications Filed	Drugs Approved
2004	32	36
2005	38	20
2006	26	22
2007	35	18
2008	34	24
2009	37	26
2010	23	21
2011	29	30

Includes NDAs and BLAs

FDA

More than 60% of industry respondents to the Improving America’s Health V survey said FDA had changed its position on at least one of their reviews during the past two years. Almost half said FDA staff changes had resulted in a break of continuity of at least one of their reviews. Such difficulty heightens the uncertainty of approval, and venture capitalists say that it discourages investors.

“At a time when the center of gravity of many industries, such as automobiles and computers, has been shifting to Asia, biomedical innovation is one field where the United States continues to be especially strong on the global stage,” says Fred Hassan, a managing director and partner at Warburg Pincus, an active investor in health care companies. “The FDA’s role in this biomedical ecosystem is critical to protect the US’ preeminence, so the FDA has a bigger calling beyond its day-to-day activities.” Hassan is also chairman of the board at Bausch & Lomb, incoming chairman at Avon Products, and former CEO of Schering-Plough.

“At a time when the center of gravity of many industries, such as automobiles and computers, has been shifting to Asia, biomedical innovation is one field where the United States continues to be especially strong on the global stage. The FDA’s role in this biomedical ecosystem is critical to protect the US’ preeminence, so the FDA has a bigger calling beyond its day-to-day activities.” - Fred Hassan, Warburg Pincus

FDA Can Build On Existing Models For Success

FDA, acutely aware of commentary from industry and venture capitalists, has made a commitment to promote biomedical innovation, releasing several reports outlining its efforts during 2010 and 2011. Its innovation initiatives have roots in the 2004 launch of its Critical Path Initiative, which attempts to bridge the translational gap between basic scientific research and the development process. In 2010, FDA reported that it would begin to align Critical Path with its Advancing Regulatory Science Initiative, a move that could bring more attention to the program.

Some models for collaborative innovation have grown from Critical Path, and FDA has launched other programs that could serve as blueprints for the change required to balance its role in the US innovation ecosystem as both watchdog and innovator. These models have succeeded, in part, through collaboration with industry, academia, and other government agencies. (See Exhibit 2.)

Exhibit 2

Public-Private Partnerships For Innovation

C-Path (Formally known as the Critical Path Institute)	An independent, nonprofit organization, which serves as an impartial facilitator of collaborative efforts among scientists from government, academia, patient advocacy organizations, and the private sector to support FDA’s regulatory science initiatives.
C-Path Predictive Safety Testing Consortium (PSTC)	A collaboration that resulted in the development of seven new biomarkers that signal kidney injury. The project involved 16 global companies and regulatory scientists from FDA, European Medicines Agency, and Japanese Pharmaceuticals and Medical Devices Agency.
C-Path Coalition Against Major Diseases	A coalition that developed the world’s largest, standardized database of Alzheimer’s clinical trial results gathered from 11 industry-sponsored trials, the first database of combined clinical trials to be shared openly by pharmaceutical companies and made available to qualified researchers around the world. Its purpose is to help promote earlier diagnosis, more effective measurements of disease progression, and more efficient trial designs.
Development of AIDS therapies and avian flu vaccines	FDA, academia, other agencies, and the industry worked together to develop treatments and vaccines and bring them to market.
Sentinel	This adverse event monitoring system had its roots in a public-private consortium, the Observational Medications Outcomes Partnership (OMOP), funded by the Foundation for the National Institutes of Health. The partnership is conducting a multiyear initiative to research methods to analyze health care databases to identify and evaluate safety and benefit issues of drugs already on the market. OMOP draws on the expertise and resources of the pharmaceutical industry, academic institutions, nonprofit organizations, FDA, and other federal agencies.
Accelerated approval pathways	FDA’s Orphan Drug Program encourages development of treatments for diseases that affect 200,000 or fewer through a longer period of exclusivity, an accelerated approval process, and incentives for pediatric drug development.

SOURCE: FDA

Despite pockets of success, industry perception is that FDA is not keeping up with rapidly advancing technology. Only 8% of those surveyed for Improving America’s Health V (results at: http://www.pwc.com/us/en/health-industries/publications/improving-americas-health-v.jhtml) feel that FDA is doing enough to advance personalized medicine, and the majority agree FDA should increase biomarker development funding. More than half of respondents think that FDA lacks the capability to implement the Critical Path Initiative to bring innovative, high-demand therapies to market quickly. Expansion and strengthening of existing innovative models, such as the Orphan Drug Program, could instill more confidence in FDA’s ability to keep pace with science. The Orphan Drug Program’s encouragement of breakthrough technologies through a fast-track approval process encourages investors, who see a clearer path to market in these products.

The Pharmaceutical Research and Manufacturers of America report that during the decade prior to enactment of the Orphan Drug Act in 1983, FDA approved fewer than a dozen drugs for orphan conditions. Since the law’s enactment, more than 350 have reached the market, and more than 450 are in late-stage development.

Cancer is often the target of drugs approved under the program. FDA has approved more novel drugs for cancer more quickly and enabled these drugs to come to market sooner than has its European counterpart, the European Medicines Agency (EMA). Of 23 new cancer drugs approved by both FDA and EMA FY 2003–2010, FDA approved 21 first; all reached the US market first. Apparently, the model for evaluating this class of drugs is working. If it were to become the business-as-usual model for FDA, it could serve as an impetus for innovation.

FDA Resource Efficiency Essential To Its Mission

The operating budget for FDA grew approximately 174% from 2001 to 2010. Congress allocated $2.497 billion for FY 2012, short of the $2.7 billion President Obama had proposed. These figures do not include user fees paid to FDA by industry.

Since 1992, Prescription Drug User Fee Act (PDUFA) fees have generated significant additional funding for the agency. In 2002, the Medical Device User Fee and Modernization Act (MDUFMA) authorized user fees for medical device applications as well.

On July 9, 2012, President Obama signed the Food and Drug Administration Safety and Innovation Act, authorizing the fifth iteration of PDUFA (covering FY 2013–2017). This act renewed fees for medical device applications and added generics and biosimilars to the mix. Collectively, the fees that pharmaceutical, medical device, and generics manufacturers will pay during the period covered by this legislation will amount to approximately $6.4 billion.

Industry is unsure of its return on investment in FDA through user fees. In the Improving America’s Health V survey, 48% of industry respondents did not believe that user fees accelerate the review process. The same percentage thought that the purpose and application of user fees lack transparency.

FDA Pledges To Advance Regulatory Science And Innovation

FDA clearly stated its vision in its “Strategic Priorities 2011–2015” report: “FDA is dedicated to world-class excellence as a science-based regulatory agency with a public health mission. We aim to provide effective and innovative leadership – both domestically and internationally – to protect health, prevent illness, prolong life, and promote wellness.”

Yet it is unclear whether FDA has the resources it needs to achieve this vision. Without the highest level of expertise in new sciences, such as genomics and regenerative medicine, FDA’s ability to evaluate and predict product performance could become increasingly limited, and the path to market and beyond uncertain and problematic.

FDA has acknowledged that regulatory science must evolve along with medical science. With the release of its “Driving Biomedical Innovation” report in October 2011, FDA positioned itself not only as a regulator, but also as “a public health agency facilitating the development of new, innovative products to meet the needs of patients and the American public.”

This report shows that FDA recognizes its strong influence over the stakeholders in the medical product development ecosystem. FDA says that it “has an important role to play in shaping the future of medical breakthroughs by bringing stakeholders together to identify and overcome the challenges of product development and assessment.”

Although it has already taken steps in this direction, FDA could make greater use of its influential position to partner with health industries (payor, provider, pharma), academia, consumer and patient organizations, and NIH in development of new therapies to improve health outcomes. Closer collaboration could change the tendency of industry and agency to approach each other only when necessary, moving concerned parties toward an environment of total product life-cycle management, in which researchers engage FDA early and often in the product development process and over a product’s life.

The past effort on the part of both FDA and industry has not been sufficient to sustain the level of collaboration required to advance the development of today’s new breed of pharmaceuticals and medical technologies. Both parties could improve their efforts to collaborate on solutions to filling the innovation deficit. For example, the Improving America’s Health V survey revealed that the industry is not consistent in scheduling presubmission and end-of-phase meetings with FDA, and FDA does not always encourage these meetings. The new user-fee agreement calls for even more meetings. These will not improve the product approval process unless both parties fully participate, but each side has strong reasons to try to make them work: industry wants to get a return for the increased user fees it is paying, and FDA wants to show that the longer review clock it requested will indeed result in more first-cycle approvals.

Exhibit 3

FDA’s Plans For Innovation

Rebuild FDA’s small business outreach services.

Build the infrastructure to drive and support personalized medicine.

Create a rapid drug development pathway for targeted therapies.

Harness the potential of data mining and information sharing, while maintaining strong privacy protections.

Increase consistency and transparency in the medical device review process.

Train the next generation of innovators.

Streamline and reform regulations.

FDA, “Driving Biomedical Innovation,” October 2011

The Centre for Innovation in Regulatory Science (CIRS) could provide an example of collaboration among the various stakeholders in medical product development. The organization encourages the international pharmaceutical industry, regulatory authorities, and academia to come together to debate and develop regulatory policy. Twenty-two companies from the United States, Japan, and Europe and 25 regulatory bodies from around the world, including FDA, are members. CIRS conducts international workshops and surveys, analyzes data from leading pharmaceutical companies and regulatory agencies, and produces publications. CIRS tracks regulatory review processes in two databases: the Regulatory Review Times Database and the Regulatory Agency Benchmarking Database.

Perhaps FDA could develop this type of neutral ground to allow its stakeholders to come together to share concerns and solutions. This would provide a safe harbor for representatives from the agency and multiple companies within the biopharmaceutical industry for precompetitive collaboration. Ten leading biopharmaceutical companies have recently taken a step in this direction, forming [TransCelerate BioPharma Inc.], a nonprofit organization to speed the development of new medicines. They will combine resources to identify and solve common drug development challenges to improve the quality of clinical studies and bring new medicines to patients faster. (See (Also see "Major Pharmas To Collaborate In Non-Profit Initiative To Resolve Clinical Development Hurdles" - Pink Sheet, 19 Sep, 2012.).)

Some FDA initiatives already moving toward greater collaboration with internal and external stakeholders could be strengthened. Those outlined in Exhibit 4 could form the basis of larger initiatives.

Exhibit 4

FDA Collaborative Innovation Initiatives

Science and Innovation Strategic Advisory Council	Helps set and discuss major cross-cutting scientific priorities for the agency; proposes and evaluates programs and partnerships; meets twice a year; comprises FDA’s chief scientist and key senior leadership from the Office of the Commissioner, FDA centers, and the Office of Regulatory Affairs.
Science Board	Provides advice to the commissioner, chief scientist, and FDA centers on FDA’s scientific programs; addresses complex scientific and technical issues within the agency, industry, and academia; periodically reviews and informs the scientific strategic plan and regulatory science priorities proposed by the Science and Innovation Strategic Advisory Council and the chief scientist.
FDA-NIH Joint Leadership Council	Collaboration to help speed the translation of research into medical products and therapies; NIH is awarding $9.4 million over three years to support four research projects in regulatory science, and FDA is contributing approximately $950,000; funded projects will attempt to inform scientists and regulatory reviewers about medical product safety and improve the evaluation and availability of new medical products. Examples of funded projects: research on nanoparticles for drug delivery, a heart-lung model to test the safety and efficacy of drugs, innovative clinical trial design, and a novel strategy to predict eye irritation.

FDA

FDA has committed to support scientific excellence and professional development and increase its efforts to recruit and retain outstanding scientists. If FDA could obtain the resources and cooperation needed to carry out the initiatives outlined in its innovation report, its evolution as innovator could be well under way.

Increased Use Of Biomarkers Critical To Advancing Personalized Medicine

To help reduce the costs and time involved in clinical trials, FDA could expand its efforts to identify, characterize, and qualify biomarkers for regulatory use. With PFUFA V, FDA has taken a step in this direction.

Using biomarkers as inclusion and exclusion criteria could narrow clinical trial populations and reduce the potential for adverse events. These genetic markers could flag individuals who should not use therapies because they would be ineffective and identify those people who would be good candidates for trials.

In August 2011, FDA published guidelines for drugmakers intending to use biomarkers to underpin the development, testing, and approval of new medicines. This step could improve industry’s view of the agency’s effort to advance personalized medicine.

C-Path’s Predictive Safety Testing Consortium (PSTC) has already set a precedent for successful development and use of biomarkers. Co-sponsored by FDA and EMA, PSTC facilitates sharing of information within the industry to develop new tools that provide genetic and phenotypic data for use in drug development. Development of such tools to predict the safety of experimental drugs enables products to reach the market faster and with greater confidence in their safety.

An example of the successful use of biomarkers in clinical testing is the I-SPY 2 trial, developed by the Biomarkers Consortium, a public-private partnership including FDA, NIH, and pharmaceutical companies. This trial uses biomarkers to determine the most appropriate treatment for women with high-risk breast cancer. Using a combination of both biomarkers and adaptive trial design principles, it tests five drugs from three manufacturers as adjuncts to chemotherapy. I-SPY 2 could become a model for the clinical trial of the future. (See (Also see "Solution Development: A Model For Structuring Biotechs And Developing Better Drugs" - In Vivo, 12 Sep, 2012.).)

Most respondents (88%) to the Improving America’s Health V survey agreed that personalized medicine will lead to changes in the industry’s business model. It will steer the life sciences industry away from blockbuster products developed for the masses and toward more targeted therapies. Greater FDA support of biomarker development could help regulatory science keep pace with the advancement of personalized medicine.

Expedited Approval Would Encourage Development Of Companion Diagnostics

Another component of personalized medicine that FDA could do more to encourage – and industry could do more to advance – is the development of companion diagnostics alongside new drugs and biologics. Companion diagnostics complement targeted therapeutics to reduce side effects by identifying patients at increased risk for adverse reactions. They improve efficacy and lower health care costs by more effectively targeting treatments so that patients and insurers do not pay for treatments that might not work.

Researchers can use companion diagnostics to exclude patients from clinical trials and speed the drug development process. Companion diagnostics can strengthen clinical-trial data for drugs under development by focusing on those patients who will benefit most, potentially boosting the odds for marketing approval.

In July 2011, FDA issued draft guidance on companion diagnostics, setting the stage for influencing a culture of innovation. PwC pointed out in its recent “Diagnostics 2011” report, however, that FDA’s document focuses on recommended principles rather than providing detailed guidance on how to design or conduct clinical studies to co-develop a targeted therapeutic and its companion diagnostic.

FDA says the purpose of the guidance is to help manufacturers navigate the approval process more quickly and efficiently. Today the regulatory approval pathways are separate for diagnostics, which must be cleared as medical devices, and drugs. In its guidance, FDA recommends that the development and review of the therapeutic and its companion diagnostic be conducted simultaneously with collaboration among FDA centers to clear both products at the same time. This guidance demonstrates good will by the agency to foster innovation for the industry.

FDA has demonstrated that drugs approved alongside a companion diagnostic often navigate the process more quickly. In August 2011, FDA approved two new cancer therapies alongside a diagnostic. Both were approved before their PDUFA goal. The new regulations and evidence of faster approvals are a good start.

A New Regulatory Path For Regenerative Medicine?

FDA could help advance the development of breakthrough innovations by creating a separate regulatory pathway, guidance, and standards for products based on regenerative medicine, which often involve complex biologic and device combinations. They represent the confluence of clinical medicine, engineering, and science. FDA could reduce the difficulty of bringing such products to market by establishing a separate approval pathway for them staffed with dedicated, highly trained reviewers. FDA already has established a fellowship program to extend and enhance its ability to regulate regenerative medicine products effectively and to permit the agency to participate in product development.

FDA Could Clarify Its Role In Comparative Effectiveness Research

Comparative effectiveness research weighs the benefits of a product against similar treatments already on the market. If a study were to find that an older, already approved product works better than a newer, more expensive one, payors would be less likely to reimburse for the latter. Making this type of data available to developers earlier during the development process would enable them to abandon costly products that offer only incremental improvement and would be unlikely to beat what is already on the market. On the other hand, comparative effectiveness data could speed more beneficial products through the development process.

Although comparative effectiveness focuses on clinical outcomes, a determination of economic value plays a part. Evaluating for cost effectiveness is not a new concept. In the UK, the National Institute for Health and Clinical Excellence (NICE) provides guidance to the National Health Service (NHS) not only to ensure quality, but also value for money.

In the US, FDA already requires some drugs to be studied against similar drugs that are on the market, notably asking for a superiority trial for Effient (prasugrel) over clopidogrel. In addition, a growing number of payors already conduct economic evaluations of new treatments and refuse to reimburse for products that they do not believe carry sufficient evidence of economic and clinical value.

The Patient Protection and Affordable Care Act created the Patient-Centered Outcomes Research Institute (PCORI) to fund and prioritize comparative effectiveness research. PCORI announced funding of $30 million over two years for 50 pilot projects and said it would award $120 million during 2012 for innovative projects that effectively incorporate patients and stakeholders in research teams and address the areas of focus of PCORI’s National Priorities and Research Agenda.

In addition to funding, data are a vital component of comparative effectiveness research. FDA recognizes that researchers could benefit from its vast repository of clinical data on the safety, effectiveness, and performance of drugs, biologics, and devices. The agency awarded funds in October 2010 to a Johns Hopkins University-led research team to advance patient-centered outcomes research by using its immense stores of data.

FDA subsequently stated in its five-year plan 2011–2015 that its Partnerships in Comparative Effectiveness Science (PACES) initiative “will facilitate the development of PCOR [patient centered outcomes research], which will allow FDA to better understand which interventions are most effective for patients under specific circumstances – a key part of the FDA’s public health mission.” The plan further stated that the “standardization of FDA data, coupled with a better understanding of clinical interventions, has the potential to ultimately transform the regulatory review and decision-making process.”

Industry might not agree that comparative effectiveness should be part of FDA’s role. A majority of the Improving America’s Health V survey respondents (68%) said FDA should not have the authority to approve or deny a drug based on its economic or clinical value (in addition to the agency's traditional responsibility for assessing quality, safety, and efficacy).

Over time, the industry might see some benefit in cooperating with FDA on comparative effectiveness initiatives. Payor demand for proof of value will only grow stronger in coming years. Rather than leave the setting of standards solely up to regulators, industry could work with the agency and offer outcomes data to assist in their development.

Broader Use Of Post-Market Surveillance To Accelerate A Drug’s Market Entry

FDA uses risk evaluation and mitigation strategies (REMS) to allow certain high-demand, high-risk drugs to enter the market with predefined safety controls to mitigate adverse effects. REMS allow patients to gain early access to some drugs that otherwise would not gain approval. The program has worked well for a limited number of products. However, consideration should be given to an adaptive regulatory system that allows conditional approval of a broader range of products.

Broadening the use of post-market surveillance through an adaptive regulatory system could serve two purposes: 1) provide more real-world scenarios for how patients might use drugs in concert with other therapies, taking into consideration rates of medication compliance, and 2) make drugs available earlier to treat patients with life-threatening conditions (live licensing). While this type of conditional approval carries inherent risk, the potential for truly understanding the profile of a product may outweigh the harm.

Industry is open to such a live-licensing approach to drug and device approvals. More respondents to the Improving America’s Health V survey agreed than disagreed that FDA’s all-or-nothing approach to drug approval should be replaced with this type of limited-launch, living-license process. This process would be based on gradual accumulation of data over time and conditional incremental approvals beginning with evidence from smaller populations. With each incremental increase in evidence of safety, efficacy, and value, FDA would extend the license to cover more patients, different indications, or different formulations. An incremental approach could help advance more personalized treatments tailored to specific patient populations.

FDA Could Reassess Operational And Talent Management

Like the industry it regulates, FDA continuously strives to improve internal processes and use its resources more effectively and efficiently. Recent initiatives have included upgrading information technology and providing new training opportunities for staff. In keeping with this effort, FDA could consider the following improvements:

1.Share resources, such as expertise in metabolic pathways, across the centers of FDA (CDER, Center for Biologics Evaluation and Research [CBER], Center for Devices and Radiological Health [CDRH]). This approach could identify and load-balance overtaxed areas within FDA to ease bottlenecks within the approval and oversight processes. Further, cross-trained teams of shared subject matter experts could allow FDA to engage and guide drug and device developers earlier in the approval process.

2.Develop strategies and incentives to hire and retain talent with technical and managerial expertise that aligns with recent developments in science and industry.

3.Create an operation and vision akin to those of a commercial organization, continuously refining strategy and operational processes to meet the demands of a changing health care system.

In the commercial world, a board of directors establishes and manages a company’s vision, leadership, and strategic plan. An FDA board of directors could serve in an advisory, stewardship, and advocacy capacity.

FDA could follow the carrot-and-stick approach that the Centers for Medicare and Medicaid Services (CMS) uses to encourage physicians to implement record-management systems. In return for reduced user fees, FDA could require drug manufacturers to follow standardized and regulated submission guidelines for product approval that clearly define what is expected and required of submitters up front. Just as CMS will punish noncompliant physicians with lower reimbursement rates, companies that do not conform to standard product submission processes, and therefore cost FDA more in terms of resources, would pay higher user fees.

An Opportunity For Reinvention

For more than 100 years, FDA has been recognized and praised as the gold standard of regulation throughout the world. The agency has recently renewed its commitment to keep pace with rapid expansion of scientific knowledge and the biopharmaceutical industry’s growing complexity. FDA has the opportunity to become recognized as more than an approval body – to be perceived as an authority in scientific, technological, and regulatory fields. Innovation and scientific rigor should be top of mind when people think of FDA.

Supporting the new collaborative, outcomes-driven paradigm emerging in health care to rethink interactions among regulators, the biopharmaceutical industry, and the broader health care spectrum, FDA could set the agenda for high-value health care delivery and work closely with industry, patients, payors, and providers to achieve it. The biopharmaceutical industry should consider FDA not as an adversary, but as a partner in developing pioneering medicines and devices that help people worldwide have longer and higher-quality lives. Industry would need to engage FDA early in the development process, seeking advice and counsel, sharing data and results to keep the regulator involved at strategic points along the path to market approval and beyond, and extending collaboration into post-market monitoring and product readjustment.

This partnership also requires industry to work with FDA to bring critical programs and issues to the forefront of the political discussion. FDA operates within boundaries set by Congress. Legislation that would grant more authority and resources to FDA in development of programs aligning to new science, such as regenerative medicine, and new tools, such as comparative effectiveness, will not be forthcoming without industry support.

With more constructive input from industry, greater authority from Congress, and a regulatory process more in tune with rapidly advancing medical science, the agency could reinvent itself as the R&D innovation leader, guiding industry and the broader health care system along the path of personalized medicine. Only in doing so can FDA spur health industries, academia, and government to reinvigorate medical product development and improve America’s and the world’s health.

Michael Mentesana ([email protected]) is Pharmaceuticals and Life Sciences US R&D Advisory Services Co-Leader, PricewaterhouseCoopers LLP. PWC Pharmaceuticals and Life Sciences manager Joseph Markmann contributed to this feature.