Jill Wechsler

There was much back-slapping and high-fives on Capitol Hill in late June, as leading legislators reached across party lines to quickly approve the Food and Drug Administration Safety and Innovation Act (FDASIA). The bill (S. 3187), which President Obama signed into law last month, enables FDA to collect some $6 billion in fees over the next five years from pharmaceutical and medical device companies. It's much cleaner than the 2007 user-fee measure, which set so many requirements on FDA that it slowed drug approvals for a year.

Now the real work begins, as FDA moves to implement new policies and prepare a host of required guidances and reports. As with most 300-page bills, FDASIA has something for everyone: patient advocates gained incentives for developing critical medicines; providers applauded policies to curb drug shortages; and FDA and industry cheered renewal of user fees that will keep the agency going for another five years.

Accepting risk

On the "spurring innovation" side, this fifth version of the Prescription Drug User Fee Act (PDUFAV) offers assistance for sponsors and greater transparency in the application review process. An important theme is that FDA and pharma should consider patient willingness to accept risk in product development and regulation. Patient advocates played a prominent role in pressing for faster FDA approval of certain new treatments.

Specific provisions provide expedited review of fast-track products and clarification of evidence and endpoints to support accelerated approval of drugs for serious or life-threatening conditions. Grants for developing orphan products will continue, and revised conflict-of-interest rules will make it easier to bring in "knowledgeable experts" to serve on advisory committees, especially those dealing with rare diseases.

Infectious disease experts won incentives for developing new antibiotics: an added five years exclusivity will apply to specific "qualified infectious disease products," which FDA has to define and list. Other provisions stabilized programs that encourage development of new formulations and expanded labels for pediatric treatments, and a new pilot will test whether an offer of priority review vouchers, which can be redeemed for a speedy FDA review of another product, will accelerate development of new therapies for rare childhood diseases.

A less-noticed but important provision requires electronic submission of applications for drugs and biologics, once FDA establishes policies and standards for doing so. Here, FDA and the legislators take the unusual step of making agency guidance mandatory, a strategy that seeks to move this policy forward without a lengthy rulemaking process. And the final bill aims to reduce duplicative clinical studies by encouraging FDA to accept foreign clinical trial data that supports new drug applications.

FDASIA also allows manufacturers to make minor modifications in Risk Evaluation and Mitigation Strategy (REMS) programs. Generic drug makers lost out in their campaign to prevent brand companies from using REMS to block access to products needed to test and develop new generic competitors, an issue that could affect biosimilar development down the road. However, other changes in generic exclusivity policy and procedures for handling citizens' petitions promise to accelerate consumer access to generics.

Some Senators sought to add restrictions on the prescribing and sale of opioid painkillers to rein in the rampant abuse of these products, but ran into strong objections from pharmacists. Instead, FDA will hold a public meeting on this thorny topic. That could address whether FDA's long-awaited REMS for extended-release opioids, which was released last month, does enough to control abuse, in that it fails to require prescribers to meet certain educational requirements.

Supply chain security

As the analysts and lawyers continue to pore over the fine print of the legislation, the Monday-morning quarterbacks questioned whether Congress should have taken more time to resolve contentious issues, notably requirements for a national track-and-trace system for prescription drugs. Here, policymakers were stalemated by industry's insistence that tracking apply only to production lots—and not individual vials and bottles, as FDA demanded. Manufacturers consequently still face multiple state tracking requirements, starting with a California law that goes into effect in 2015.

Even so, the final law contains a wealth of provisions designed to help FDA detect and block adulterated medical products. All drug manufacturers and foreign suppliers have to register with FDA using a unique facility identifier. Importers must meet numerous requirements and file registration information electronically. FDA may block imports from manufacturers that deny access to inspectors and may detain —and even destroy—adulterated products at the border, instead of having to send them back to the shipper. Manufacturers have to notify FDA if a drug may be stolen or counterfeited, and intentional adulteration for economic gain carries stiff penalties, including jail time.

Supreme Court Shapes Sales

To curb critical drug shortages, the law extends reporting requirements for manufacturers anticipating short supply situations and gives FDA clear leeway to expedite inspections and application reviews to help mitigate or prevent a shortage. The Drug Enforcement Administration has to provide timely approvals or denials of requests to increase quotas of controlled substances when needed to address a drug shortage. There will be an FDA annual report on its success in stopping shortages, along with a drug shortage list that will help patients and providers stay informed about supply problems. And a new HHS task force will examine ways to enhance the federal response to shortages and create a strategic plan to address these problems.

Regulating apps

FDASIA even addresses how FDA may—or may not—regulate medical applications for smartphones and other computer devices, a hot issue for software developers, manufacturers, and health authorities. The final bill stops short of prohibiting FDA from finalizing a draft guidance issued last year that proposed agency regulation of software that links to a device such as an MRI or infusion pump—but not low-risk apps such as calorie counters. Even so, FDA officials are expected to hold off on issuing new guidance until a working group required by FDASIA quickly (in 18 months) develops a strategy for an "appropriate, risk-based regulatory framework" on health IT "that promotes innovation, protects patient safety and avoids regulatory duplication." FDA will consult with the National Coordinator for Health Information Technology and the Federal Communications Commission and include manufacturers, payers, venture capitalists, IT vendors, patients, providers, and others in the working group.

The compromise measure reflects concerns of software and medical device companies that FDA will over-regulate this budding industry, squashing innovation and promising health technology in the process. Some 40,000 medical apps have been developed, some by pharma companies looking to enhance patient use of treatments for diabetes and other medical conditions and to help manage clinical trials. A firm recently sought and gained FDA approval for an app that displays radiological images, and some IT firms support FDA regulation to gain more predictability in market requirements, despite the cost and time of compliance.

With so many provisions, it's not surprising that FDASIA does not please everyone. Some consumer advocates warn that more accelerated approvals may expose patients to unsafe therapies. Infectious disease experts wanted provisions to ensure appropriate use of antibiotics. FDA will consider these and other perspectives in developing a communications plan on risks and benefits of medical products and in assessing the gains provided by new PDUFA V review program for new drugs and biologics.

Jill Wechsler is Pharmaceutical Executive's Washington correspondent. She can be reached at jwechsler@advanstar.com